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Introduction: Vitamin D insufficiency is common in patients who receive hemodialysis yet there is no clear guidance regarding surveillance or treatment. We hypothesized that increasing 25(OH)D3 levels is associated with lower phosphate, parathyroid hormone (PTH) and alkaline phosphatase (ALP)., Methods: Baseline 25(OH)D3 level was measured in all patients receiving in-centre hemodialysis in June, 2017. Laboratory parameters were measured every 6 (phosphate, calcium) or 12 weeks (25(OH)D3, PTH, ALP) until February, 2021. In September, 2018 a treatment algorithm of 50,000 IU weekly until sufficient, followed by 50,000 IU monthly was suggested. Generalized linear mixed regression models including linear spline effects, a log link function, and random effects were used to examine the impact of increasing 25(OH)D3 levels on calcium, phosphate, ALP and PTH., Results: Of 697 participants, 15% and 57% had vitamin D deficiency (25(OH)D3 < 25 nmol/L) and insufficiency (between 25 and 74 nmol/L). Incorporating up to 7272 observations, increasing 25(OH)D3 was associated with significantly decreasing PTH for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment. In an interaction model, the negative slope between 25(OH)D3 and PTH remained significant beyond 75 nmol/L in the absence of calcitriol. Increasing 25(OH)D3 was associated with significantly decreasing phosphate for 25(OH)D3 levels between 25 and 75nmol/L regardless of vitamin D treatment, and below 25 nmol/L in values of untreated patients. Calcium increased across the spectrum of 25(OH)D3 regardless of vitamin D treatment. 0.2% of 25(OH)D3 levels exceeded 250 nmol/L and 2.1% of calcium levels exceeded the normal range., Conclusions: Vitamin D treatment in a real-world setting was safe and associated with lower PTH levels. Whether improved biochemical markers translate to a reduction in., (S. Karger AG, Basel.)

Objectives: This study's aims were to describe the outcomes of patients with diabetes presenting with their first ED visit for hyperglycemia, and to identify predictors of recurrent ED visits for hyperglycemia., Methods: Using linked databases, we conducted a population-based cohort study of adult and pediatric patients with types 1 and 2 diabetes presenting with a first ED visit for hyperglycemia from April 2010 to March 2020 in Ontario, Canada. We determined the proportion of patients with a recurrent ED visit for hyperglycemia within 30 days of the index visit. Using multivariable regression analysis, we examined clinical and socioeconomic predictors for recurrent visits., Results: There were 779,632 patients with a first ED visit for hyperglycemia. Mean (SD) age was 64.3 (15.2) years; 47.7% were female. 11.0% had a recurrent visit for hyperglycemia within 30 days. Statistically significant predictors of a recurrent visit included: male sex, type 1 diabetes, regions with fewer visible minority groups and with less education or employment, higher hemoglobin A1C, more family physician or internist visits within the past year, being rostered to a family physician, previous ED visits in the past year, ED or hospitalization within the previous 14 days, access to homecare services, and previous hyperglycemia encounters in the past 5 years. Alcoholism and depression or anxiety were positive predictors for the 18-65 age group., Conclusions: This population-level study identifies predictors of recurrent ED visits for hyperglycemia, including male sex, type 1 diabetes, regions with fewer visible minority groups and with less education or employment, higher hemoglobin A1C, higher previous healthcare system utilization (ED visits and hospitalization) for hyperglycemia, being rostered to a family physician, and access to homecare services. Knowledge of these predictors may be used to develop targeted interventions to improve patient outcomes and reduce healthcare system costs., (© 2024. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Objective: People living with diabetes mellitus (DM) and chronic kidney disease can have difficulty attending multiple appointments to receive DM care. We developed and studied the utility of a DM outreach program to offer in the hemodialysis (HD) unit., Methods: We conducted a quality improvement project in a satellite HD unit in London, Ontario, Canada, between August 1, 2019, and July 31, 2022. We assessed for baseline gaps in DM care among those with DM, performed root-cause analysis with key stakeholders to identify critical drivers of gaps, and conceptualized a certified diabetes educator-led outreach program to offer in the HD unit. We aimed to improve DM self-monitoring, hypo- and hyperglycemia, and DM-related screening. We used run and control charts to track outcome measures over time and modified our outreach program iteratively., Results: Fifty-eight persons with DM receiving HD participated in our program. Support spanned multiple waves of the COVID-19 pandemic. With 4 tests of change, we observed improvement in DM self-monitoring with a modest decline in self-reported hyperglycemia. There were no adverse consequences, and satisfaction with our program was high., Conclusions: Although we did not meet all measures of success during the pandemic, outreach DM support in the HD unit appeared to improve self-monitoring and self-reported hyperglycemia. Similar programs could be modified and implemented in other centres., (Copyright © 2023 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the relationship between household food insecurity and healthcare costs in children living in Ontario, Canada., Methods: We conducted a cross-sectional, population-based study using four cycles of the Canadian Community Health Survey (2007-2008, 2009-2010, 2011-2012, 2013-2014) linked with administrative health databases (ICES). We included Ontario children aged 1-17 years with a measure of household food insecurity (Household Food Security Survey Module) over the previous 12 months. Our primary outcome was the direct public-payer healthcare costs per child over the same time period (in Canadian dollars, standardized to year 2020). We used gamma-log-transformed generalized estimating equations accounting for the clustering of children to examine this relationship, and adjusted models for important sociodemographic covariates. As a secondary outcome, we examined healthcare usage of specific services and associated costs (e.g. visits to hospitals, surgeries)., Results: We found that adjusted healthcare costs were higher in children from food-insecure than from food-secure households ($676.79 [95% CI: $535.26, $855.74] vs. $563.98 [$457.00, $695.99], p = 0.047). Compared with children living in food-secure households, those in insecure households more often accessed hospitals, emergency departments, day surgeries, and home care, and used prescription medications. Children from food-secure households had higher usage of non-physician healthcare (e.g. optometry) and family physician rostering services., Conclusion: Even after adjusting for measurable social determinants of health, household food insecurity was associated with higher public-payer health services costs and utilization among children and youth. Efforts to mitigate food insecurity could lessen child healthcare needs, as well as associated costs to our healthcare systems., (© 2023. The Author(s) under exclusive license to The Canadian Public Health Association.)

Background: Current diabetic ketoacidosis (DKA) treatment guidelines recommend using normal saline (NS); however, NS may delay DKA resolution by causing more hyperchloremic metabolic acidosis compared with balanced crystalloids. This study's objective was to determine the feasibility of a future multicentred randomised controlled trial (RCT) comparing intravenous Ringer's lactate (RL) with NS in managing ED patients with DKA., Methods: We conducted a parallel-arm, triple-blind, pilot RCT of adults (≥18 years) with DKA at a Canadian academic tertiary care ED. The primary feasibility outcome was recruitment rate (target ≥41.3% of eligible participants over the 1-year study period); the primary efficacy outcome was time elapsed from ED presentation to DKA resolution. The superiority margin for a clinically significant difference was chosen to be a 40% time reduction to DKA resolution. We also assessed the need to break allocation concealment and loss to follow-up. Patients with clinical suspicion for DKA were screened for inclusion and enrolled patients were randomised 1:1 to receive RL or NS. Patients, clinicians and outcome assessors were blinded to allocation., Results: We enrolled 52 (25 RL, 27 NS) of 60 eligible patients (86.7%), exceeding our target recruitment rate. There were more patients in the NS group with type 1 diabetes, and more patients in the RL group had an admission co-diagnosis in addition to DKA. For the 44 participants with confirmed laboratory evidence of resolution, median (IQR) time to DKA resolution for RL versus NS was 15.7 (10.4-18.8) and 12.7 (7.9-19.2) hours, respectively. There were no cases where blinding was broken, and there was no loss to follow-up., Conclusions: This pilot trial demonstrated our protocol's feasibility by exceeding our target recruitment rate. Our results may be used to inform future multicentre trials to compare the safety and efficacy of RL and NS in managing DKA in the ED., Trial Registration Number: NCT04926740., Competing Interests: Competing interests: Outside of this study, KKC has received a research award sponsored in part by AstraZeneca. She has attended conferences sponsored by Merck. She has received honoraria for delivering certified medical education from Sutherland Global Services Canada ULC, the Canadian Medical and Surgical Knowledge Translation Group and the CPD Network. There are no other conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Denosumab can improve bone health in advanced kidney disease (CKD) but is associated with hypocalcemia. We created a clinical care pathway focused on the safe provision of denosumab in advanced CKD that reduced the risk of hypocalcemia by 37% at our hospital. Similar pathways could be adopted and tested in other centers., Purpose: There is an increased risk of hypocalcemia with denosumab in advanced chronic kidney disease (CKD). We aimed to reduce the proportion of patients with advanced CKD who experienced denosumab-induced hypocalcemia at our center., Methods: We conducted a quality improvement (QI) project of patients with CKD stage 3b or less (i.e., estimated glomerular filtration rate <45 mL/min/1.73m 2 including dialysis) who were part of the Osteoporosis and Bone Disease Program at St. Joseph's Health Care London (Canada) between December 2020 and January 2023. Our intervention was a clinical care pathway which optimized CKD mineral and bone disorder (CKD-MBD) and 25-hydroxyvitamin levels; provided calcium and vitamin D prophylaxis; promoted multidisciplinary communication between bone and kidney specialists; and carefully monitored calcium post-denosumab injection. Our primary outcome measure was the proportion of patients with hypocalcemia (defined by albumin-corrected serum calcium <1.9mmol/L) at 60 days. Process measures included the appropriate provision of calcium and vitamin D prophylaxis. Balance measures included the development of hypercalcemia and hyperphosphatemia following prophylaxis. We used plan-do-see-act cycles to study four tests of change and presented results using descriptive statistics and run charts., Results: There were 6 patients with advanced CKD treated with denosumab prior to the implementation of our care pathway (March 2015-October 2020; 83% receiving dialysis). At the time of their denosumab injection, 83% were using 500-1000 mg of calcium, and 83% used 1000-2000 IU of vitamin D 3 . Fifty percent developed denosumab-induced hypocalcemia. Following the implementation of our care pathway, 15 patients (40% receiving dialysis) were treated with denosumab. Ninety-three percent received calcium at a daily dose of 350 to 2250 mg and 87% received 1000-2000 IU of vitamin D 3 . Thirteen percent developed denosumab-induced hypocalcemia. There was no hypercalcemia or hyperphosphatemia., Conclusions: A clinical care pathway focused on the safe provision of denosumab in advanced CKD reduced the risk of hypocalcemia in patients treated in our hospital. Similar pathways could be adopted and tested in other centers., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Food insecurity is a serious public health problem and is linked to the mental health of children and adolescents; however, its relationship with mental health service use is unknown. We sought to estimate the association between household food insecurity and contact with health services for mental or substance use disorders among children and adolescents in Ontario, Canada., Methods: We used health administrative data, linked to 5 waves of the Canadian Community Health Survey, to identify children and adolescents (aged 1-17 yr) who had a household response to the Household Food Security Survey Module. We identified contacts with outpatient and acute care services for mental or substance use disorders in the year before survey completion using administrative data. We estimated prevalence ratios for the association between household food insecurity and use of mental health services, adjusting for several confounding factors., Results: The sample included 32 321 children and adolescents, of whom 5216 (16.1%) were living in food-insecure households. Of the total sample, 9.0% had an outpatient contact and 0.6% had an acute care contact for a mental or substance use disorder. Children and adolescents in food-insecure households had a 55% higher prevalence of outpatient contacts (95% confidence interval [CI] 41%-70%), and a 74% higher prevalence of acute care contacts (95% CI 24%-145%) for a mental or substance use disorder, although contacts for substance use disorders were uncommon., Interpretation: Children and adolescents living in a food-insecure household have greater use of health services for mental or substance use disorders than those living in households without food insecurity. Focused efforts to support food-insecure families could improve child and adolescent mental health and reduce strain on the mental health system., Competing Interests: Competing interests: Kelly Anderson reports funding from the Department of Psychiatry Seed Fund Competition, the Petro Canada Young Innovator Award and the Canadian Institutes of Health Research. Kristin Clemens reports honoraria from the CPD Network and the Canadian Medical and Surgical Knowledge Translation Research Group. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Current guidelines for diabetic ketoacidosis (DKA) recommend treatment with normal saline (NS). However, NS, with its high chloride concentrations, may worsen acidosis and contribute to a hyperchloremic metabolic acidosis. Alternatives to NS are balanced crystalloids (e.g. Ringer's Lactate [RL]) which have chloride concentrations similar to human plasma; therefore, treatment with balanced crystalloids may lead to faster DKA resolution. A recent systematic review and meta-analysis by Catahay et al. (2022) demonstrated the need for more blinded, high-quality trials comparing NS versus RL in the treatment of DKA., Methods: We describe a protocol for BRISK-ED (Balanced crystalloids [RInger's lactate] versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department). Our study is a single-centre, triple-blind, pilot randomized controlled trial (RCT) of adults (≥ 18 years) with DKA presenting to an academic tertiary care ED in London, Canada. Patients with clinical suspicion for DKA will be screened and those found to not meet DKA criteria or have euglycemic DKA will be excluded. We will aim to recruit 52 patients with DKA and will randomize them 1:1 to receive intravenous RL or NS. The primary feasibility outcome will be recruitment rate, and the primary efficacy outcome will be time elapsed from ED presentation to DKA resolution. Secondary outcomes include time to insulin infusion discontinuation, intensive care unit admission, in-hospital death, and major adverse kidney events within 30 days, defined as a composite of: i) death, ii) new renal replacement therapy, or iii) final serum creatinine ≥ 200% baseline at the earliest of hospital discharge or 30 days after ED presentation. Patients, clinicians, and outcome assessors will be blinded to allocation group. We will follow an intention-to-treat analysis. Gehan-Wilcoxon, Mann-Whitney U, or chi-square tests will be used to compare groups as appropriate., Discussion: The results of this pilot study will inform the design and feasibility of a full-scale, multicentre RCT to assess fluid choice in adult ED patients with DKA. If proven to demonstrate faster resolution of DKA, administration of balanced crystalloids may replace NS in diabetes treatment guidelines and improve patient and health systems outcomes., Trial Registration: ClinicalTrials.gov, Registration # NCT04926740; Registered June 15, 2021., (© 2023. The Author(s).)

Low bone density is common among those individuals receiving peritoneal dialysis. While cross-sectional studies support an association between low bone mineral density (BMD) and prevalent fracture, relying on bone density alone, particularly at the lumbar spine and in those with high degrees of hyperparathyroidism may underestimate fracture risk. Commonly used risk calculators in the general population have been shown to perform reasonably well in those receiving dialysis although they do not include any risk factors for high turnover bone disease that may play a role in increased fracture risk. The best options for decreasing fracture risk in patients receiving peritoneal dialysis are unclear. The evidence for bisphosphonates is limited to small studies of BMD, and concerns about drug accumulation have limited their use. Denosumab is more commonly used and has some evidence for improvement in BMD but carries with it a high risk of hypocalcaemia requiring rigorous prophylaxis. More research is needed to explore practical methods to identify those at risk of fracture and determine the efficacy of antiresorptive and anabolic therapies to decrease this risk.

Background: The availability and accessibility of patient-centered weight management programs is critical to mitigate the increasing prevalence of obesity in people living with chronic kidney disease (CKD). Little is known about the availability of contemporary programs that can safely and effectively support individuals living with obesity and CKD across North America., Objective: We sought to identify weight management programs specific to those with CKD and explore their safety, affordability, and adaptability to this patient population. We also identified the barriers and facilitators of identified programming including their accessibility to real-world patients (eg, cost, access, support, and time)., Design: Environmental scan of weight management programs., Setting: North America., Patient: People living with CKD., Methods: We identified weight management programs and associated barriers and facilitators, via an Internet-based search of commercial, community-based, and medically supervised weight management programming. We also conducted a gray literature search and contacted weight management experts and program facilitators to explore strategies as well as their barriers and facilitators., Results: We identified 40 weight management programs available to people living with CKD across North America. Programs were commercial (n = 7), community-based (n = 9), and medically supervised (Canada n = 13, U.S n = 8) in origin. Three programs were specifically tailored to CKD (n = 3). In addition to formal programs, we also identified online nutritional resources and guidelines for weight loss in CKD (n = 8), and additional strategies (self-management tools, group orientated programs, moderate energy restrictions in conjunction with exercise and Orlistat) for weight loss from the gray literature (n = 3). Most common barriers were difficulty accessing some of the suggested nutritious food options due to the high cost, lack of support from family, friends and health practitioners, the time commitment required to participate, and the exclusion from weight management programs due to unique dietary needs for the CKD population. Most common facilitators were programs that were patient-centered, evidence-based, and offered both group and individual formats., Limitations: Although our search criteria were broad, it is possible that we did not capture all weight management programs available across North America., Conclusions: This environmental scan has generated a resource list of existing safe and effective programs for or adaptable to people with CKD. This information will inform future efforts to develop and deliver CKD-specific weight management programs to patients living with comorbid disease. Engaging people living with CKD to understand the acceptability of these programs, is an important focus for future research., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background and Aims: Quetiapine is an atypical antipsychotic predominantly metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. We studied the risk of adverse events following coprescription of clarithromycin (a strong CYP3A4 inhibitor) versus azithromycin (not a CYP3A4 inhibitor) in quetiapine users., Materials and Methods: This was a population-based retrospective cohort study from 2004 to 2020 in Ontario, Canada in adult quetiapine users newly co-prescribed clarithromycin ( n  = 16,909) or azithromycin ( n  = 25,267). The primary outcome was the composite of hospital encounters with encephalopathy (defined as a diagnosis of delirium, disorientation, transient alteration of awareness, transient ischemic attack, or unspecified dementia), a fall, or a fracture within 30 days of new coprescription. Secondary outcomes were individual components of the composite outcome, hospital encounter with computed tomography (CT) head scan, and all-cause mortality., Results: Coprescription of clarithromycin versus azithromycin with quetiapine was associated with a higher risk of the primary composite outcome (365 of 16,909 clarithromycin users [2.2%] vs. 309 of 16,929 azithromycin users [1.8%]; absolute risk increase, 0.34% [95% confidence interval, CI, 0.04-0.63]; relative risk [RR], 1.19 [95% CI, 1.02-1.38]). This was primarily driven by an increase in fragility fractures (78 of 16,909 clarithromycin users [0.5%] vs. 45 of 16,923 azithromycin users [0.3%]; absolute risk increase, 0.20% [95% CI, 0.07-0.32]; RR, 1.74 [95% CI, 1.21-2.52]). Hospital encounters with a CT head scan were higher in clarithromycin users (220 of 16,909 [1.3%] vs. 175 of 16,923 azithromycin users [1.0%]; absolute risk increase, 0.27% [95% CI, 0.04-0.50]; RR, 1.26 [95% CI, 1.04-1.54]), but there was no difference in hospital encounters with encephalopathy, falls, or all-cause mortality between macrolide groups., Conclusion: Among adults taking quetiapine, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically greater 30-day risk of a hospital encounter for encephalopathy, falls, or fracture, which was predominantly related to a higher rate of fragility fractures., Competing Interests: Kevin Yau has received speaking honoraria from AstraZeneca unrelated to the current manuscript. Kristin Clemens has received honoraria for delivering certified medical education from the Canadian Medical and Surgical Knowledge Translation Research Group and the CPD Network unrelated to the current manuscript., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Throughout the COVID-19 pandemic, many areas of medicine transitioned to virtual care. For patients with diabetes admitted to hospital, this included diabetes education and insulin teaching. Shifting to a virtual model of insulin teaching created new challenges for inpatient certified diabetes educators (CDE)., Objective: We advanced a quality improvement project to improve the efficiency of safe and effective virtual insulin teaching throughout the COVID-19 pandemic. Our primary aim was to reduce the mean time between CDE referral to successful inpatient insulin teach by 0.5 days., Design, Setting, Participants: We conducted this initiative at two large academic hospitals between April 2020 and September 2021. We included all admitted patients with diabetes who were referred to our CDE for inpatient insulin teaching and education., Intervention: Alongside a multidisciplinary team of project stakeholders, we created and studied a CDE-led, virtual (video conference or telephone) insulin teaching programme. As tests of change, we added a streamlined method to deliver insulin pens to the ward for patient teaching, created a new electronic order set and included patient-care facilitators in the scheduling process., Main Outcome and Measures: Our main outcome measure was the mean time between CDE referral and successful insulin teach-back. Our process measure was the percentage of successful insulin pen deliveries to the ward for teaching. As balance measures, we captured the percentage of patients with a successful insulin teach, the time between insulin teach and hospital discharge, and readmissions to hospital for diabetes-related complications., Results: Our tests of change improved the efficiency of safe and effective virtual insulin teaching by 0.27 days. The virtual model appeared less efficient than usual in-person care., Conclusions: In our centre, virtual insulin teaching supported patients admitted to hospital through the pandemic. Improving the administrative efficiency of virtual models and leveraging key stakeholders remain important for long-term sustainability., 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.)

Aims: Glucagon-like peptide 1 receptor agonists (GLP-1RA) improve glycemic control and promote weight loss in type 2 diabetes (DM2) and obesity. We identified studies describing the metabolic benefits of GLP-1RA in end-staged kidney disease (ESKD) and kidney transplantation., Data Synthesis: We searched for randomized controlled trials (RCTs) and observational studies that investigated the metabolic benefits of GLP-1RA in ESKD and kidney transplantation. We summarized the effect of GLP-1RA on measures of obesity and glycemic control, examined adverse events, and explored adherence with therapy. In small RCTs of patients with DM2 on dialysis, liraglutide for up to 12 weeks lowered HbA1c by 0.8%, reduced time in hyperglycemia by ∼2%, lowered blood glucose by 2 mmol/L and reduced weight by 1-2 kg, compared with placebo. In prospective studies inclusive of ESKD, 12 months of semaglutide reduced HbA1c by 0.8%, and contributed to weight losses of 8 kg. In retrospective cohort studies in DM2 and kidney transplantation, 12 months of GLP-1RA lowered HbA1c by 2%, and fasting glucose by ∼3 mmol/L compared with non-use, and in some reports, weight losses of up to 4 kg were described. Gastrointestinal (GI) side effects were most commonly reported, with hypoglycemia described with GLP-1RA in hemodialysis, particularly in those using insulin., Conclusions: GLP-1RA are growing in popularity in those with DM2 and obesity. In small RCTs and observational cohort studies modest glycemic and weight benefits have been described in ESKD and transplantation, but GI side effects may limit adherence. Larger and longer term studies of GLP-1RA remain important., Competing Interests: Declaration of competing interest KKC has received honoraria for delivering certified medical education from the CPD Network, and the Canadian Medical and Surgical Knowledge Translation Group. TK has received honoraria for speaking engagements from Novo Nordisk Canada, Eli-Lily Canada., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Denosumab can be used in patients with chronic kidney disease (CKD) but has been linked with cases of severe hypocalcemia. The incidence of and risk factors for hypocalcemia after denosumab use are not well established. Using linked health care databases at ICES, we conducted a population-based cohort study of adults >65 years old with a new prescription for denosumab or a bisphosphonate between 2012 and 2020. We assessed incidence of hypocalcemia within 180 days of drug dispensing and stratified results by estimated glomerular filtration rate (eGFR in mL/min/1.73 m 2 ). We used Cox proportional hazards to assess risk factors for hypocalcemia. There were 59,151 and 56,847 new denosumab and oral bisphosphonate users, respectively. Of the denosumab users, 29% had serum calcium measured in the year before their prescription, and one-third had their serum calcium checked within 180 days after their prescription. Mild hypocalcemia (albumin corrected calcium <2.00 mmol/L) occurred in 0.6% (95% confidence interval [CI] 0.6, 0.7) of new denosumab users and severe hypocalcemia (<1.8 mmol/L) in 0.2% (95% CI 0.2, 0.3). In those with an eGFR <15 or receiving maintenance dialysis, the incidence of mild and severe hypocalcemia was 24.1% (95% CI 18.1, 30.7) and 14.9% (95% CI 10.1, 20.7), respectively. In this group, kidney function and baseline serum calcium were strong predictors of hypocalcemia. We did not have information on over-the-counter vitamin D or calcium supplementation. In new bisphosphonate users, the incidence of mild hypocalcemia was 0.3% (95% CI 0.3, 0.3) with an incidence of 4.7% (95% CI 1.5, 10.8) in those with an eGFR <15 or receiving maintenance dialysis. In this large population-based cohort, we found that the overall risk of hypocalcemia with new denosumab use was low but increased substantially in those with eGFR <15 mL/min/1.73 m 2 . Future studies should investigate strategies to mitigate hypocalcemia. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease., Sources of Information: Peer-reviewed clinical trials and observational studies., Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist., Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture., Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Intervention: Ontario's Harmonized Heat Warning and Information System (HWIS) brings harmonized, regional heat warnings and standard heat-health messaging to provincial public health units prior to periods of extreme heat., Research Question: Was implementation of the harmonized HWIS in May 2016 associated with a reduction in emergency department (ED) visits for heat-related illness in urban locations across Ontario, Canada?, Methods: We conducted a population-based interrupted time series analysis from April 30 to September 30, 2012-2018, using administrative health and outdoor temperature data. We used autoregressive integrated moving average models to examine whether ED rates changed following implementation of the harmonized HWIS, adjusted for maximum daily temperature. We also examined whether effects differed in heat-vulnerable groups (≥65 years or <18 years, those with comorbidities, those with a recent history of homelessness), and by heat warning region., Results: Over the study period, heat alerts became more frequent in urban areas (6 events triggered between 2013 and 2015 and 14 events between 2016 and 2018 in Toronto, for example). The mean rate of ED visits was 47.5 per 100,000 Ontarians (range 39.7-60.1) per 2-week study interval, with peaks from June to July each year. ED rates were particularly high in those with a recent history of homelessness (mean rate 337.0 per 100,000). Although rates appeared to decline following implementation of HWIS in some subpopulations, the change was not statistically significant at a population level (rate 0.04, 95% CI: -0.03 to 0.1, p=0.278)., Conclusion: In urban areas across Ontario, ED encounters for heat-related illness may have declined in some subpopulations following HWIS, but the change was not statistically significant. Efforts to continually improve HWIS processes are important given our changing Canadian climate., (© 2022. The Author(s) under exclusive license to The Canadian Public Health Association.)

The primary objective of this review was to synthesize studies assessing the relationships between high temperatures and cardiovascular disease (CVD)-related hospital encounters (i.e., emergency department (ED) visits or hospitalizations) in urban Canada and other comparable populations, and to identify areas for future research. Ovid MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, and Scopus were searched between 6 April and 11 April 2020, and on 21 March 2021, to identify articles examining the relationship between high temperatures and CVD-related hospital encounters. Studies involving patients with pre-existing CVD were also included. English language studies from North America and Europe were included. Twenty-two articles were included in the review. Studies reported an inconsistent association between high temperatures and ischemic heart disease (IHD), heart failure, dysrhythmia, and some cerebrovascular-related hospital encounters. There was consistent evidence that high temperatures may be associated with increased ED visits and hospitalizations related to total CVD, hyper/hypotension, acute myocardial infarction (AMI), and ischemic stroke. Age, sex, and gender appear to modify high temperature-CVD morbidity relationships. Two studies examined the influence of pre-existing CVD on the relationship between high temperatures and morbidity. Pre-existing heart failure, AMI, and total CVD did not appear to affect the relationship, while evidence was inconsistent for pre-existing hypertension. There is inconsistent evidence that high temperatures are associated with CVD-related hospital encounters. Continued research on this topic is needed, particularly in the Canadian context and with a focus on individuals with pre-existing CVD.

Background and Objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been associated with a higher risk of skeletal fractures in some randomized, placebo-controlled trials. Secondary hyperparathyroidism and increased bone turnover (also common in CKD) may contribute to the observed fracture risk. We aimed to determine if SGLT2 inhibitor use associates with a higher risk of fractures compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, which have no known association with fracture risk. We hypothesized that this risk, if present, would be greatest in patients with lower eGFR., Design, Setting, Participants, & Measurements: We conducted a population-based cohort study in Ontario, Canada between 2015 and 2019 using linked provincial administrative data to compare the incidence of fracture between new users of SGLT2 inhibitors and DPP-4 inhibitors. We used inverse probability of treatment weighting on the basis of propensity scores to balance the two groups of older adults (≥66 years of age) on indicators of baseline health. We compared the 180- and 365-day cumulative incidence rates of fracture between groups. Prespecified subgroup analyses were conducted by eGFR category (≥90, 60 to <90, 45 to <60, and 30 to <45 ml/min per 1.73 m 2 ). Weighted hazard ratios were obtained using Cox proportional hazard regression., Results: After weighting, we identified a total of 38,994 new users of a SGLT2 inhibitor and 37,449 new users of a DPP-4 inhibitor and observed a total of 342 fractures at 180 days and 689 fractures at 365 days. The weighted 180- and 365-day risks of a fragility fracture did not significantly differ between new users of a SGLT2 inhibitor versus a DPP-4 inhibitor: weighted hazard ratio, 0.95 (95% confidence interval, 0.79 to 1.13) and weighted hazard ratio, 0.88 (95% confidence interval, 0.88 to 1.00), respectively. There was no observed interaction between fracture risk and eGFR category ( P =0.53)., Conclusions: In this cohort study of older adults, starting a SGLT2 inhibitor versus DPP-4 inhibitor was not associated with a higher risk of skeletal fracture, regardless of eGFR., (Copyright © 2022 by the American Society of Nephrology.)

Background: In-hospital glycaemic management can reduce post-transplant morbidity, but is not always part of transplant care., Objective: We aimed to reduce the mean number of postoperative days in hyperglycaemia (≥2 blood glucose >12 mmol/L in 24 hours) in kidney and liver transplant recipients by 30%. We also aimed to reduce the mean number of days between transplant admission to endocrine consult by 2.0 days., Design, Setting, Participants: We conducted a quality improvement project in liver and kidney transplant recipients admitted to an academic transplant unit in Canada between 1 March 2019 and 1 May 2021., Intervention: We developed a bedside algorithm to monitor post-transplant capillary blood glucose; the algorithm also included thresholds for nursing-initiated inpatient endocrinology consultation., Main Outcome and Measures: We examined outcome (postoperative days in hyperglycaemia, days to inpatient endocrine consultation), process (nursing documentation of postoperative blood sugars) and balancing measures (nursing workload, postoperative days in hypoglycaemia) following implementation of our algorithm. We used Plan-Do-See-Act cycles to study three iterations of our algorithm, and used box plots to present outcomes before and after algorithm implementation., Results: In the pre-intervention period, 21 transplant recipients spent a mean of 4.1 (SD 2.4) postoperative days in hyperglycaemia before endocrine consultation. The mean number of days between hospital admission to endocrine consult was 10.7 (SD 13.0) days.In the post-intervention period, we observed a 62% reduction in postoperative days in hyperglycaemia. The mean number of days between admission and endocrine consult was reduced by 6.3 days (59% reduction)., Conclusions: Implementation of a simple, bedside algorithm for postoperative glucose monitoring and detection of hyperglycaemia in transplant patients, reduced the mean number of postoperative days in hyperglycaemia and time to inpatient endocrine consultation. Our algorithm continues to be used in our academic transplant unit., Competing Interests: Competing interests: Unrelated to this work, KKC has attended conferences sponsored by Merck. She has received honoraria for providing Certified Medical Education talks from Sutherland Global Services Canada, the Canadian Medical and Surgical Knowledge Translation Research Group and the CPD Network. There are no other conflicts to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To examine trends in basal insulin prescribing in older adults with chronic kidney disease (CKD)., Materials and Methods: We conducted a population-based study of adults aged 66 years or older with treated diabetes from 1 January 2010 to 30 September 2020 in Ontario, Canada. We examined prevalent and incident prescriptions for human NPH, Levemir, glargine-100, Basaglar, glargine-300, and degludec insulin over 43 study intervals. We present trends in those with CKD, and in a subgroup, by estimated glomerular filtration rate (eGFR). To provide context for prescribing, we provide demographics, co-morbidities, and the healthcare utilization of included patients., Results: In CKD, use of basal insulin was about 2-fold higher than in the general treated diabetes cohort. Prescriptions for NPH declined over time, while prescriptions for Levemir and glargine-100 increased until 2018 then decreased. Following drug formulary approval (September 2018), prescriptions for glargine-300 and degludec increased substantially. Incident prescriptions for basal insulin in CKD declined over time; however, in those with an eGFR of less than 30 ml/min/1.73m 2 , rates remained stable. In recent years, rates of degludec and glargine-300 have rivalled glargine-100., Conclusions: In an era of new oral and injectable diabetes medications, the use of basal insulin has declined in older adults with CKD. However, in those with more advanced CKD, basal insulin, particularly newer analogues, remain a mainstay treatment., (© 2021 John Wiley & Sons Ltd.)

Background: Patients with diabetes and chronic kidney disease (CKD) have complex diabetes care needs. Diabetes educators can play an important role in their clinical care., Aim: To understand diabetes educators' experience providing diabetes support to patients with CKD and elicit their view on the additional care needs of this population., Methods: We conducted a quantitative online survey of diabetes educators between May 2019 and May 2020. We surveyed English-speaking educators actively practicing in Ontario, Canada for at least 1 year. We recruited them through provincial Diabetes Education Programs and Diabetes Education Section Chairs of Diabetes Canada., Results: We made email contact with 219/233 (94%) Diabetes Education Programs and 11/12 (92%) provincial Diabetes Canada Section Chairs. 122 unique diabetes educators submitted complete surveys (survey participation rate ∼79%). Most worked in community education programs (91%). Almost half were registered nurses (48%), and 39% had practiced for more than 15 years. Respondents noted difficulty helping patients balance complex medical conditions (19%), faced socioeconomic barriers (17%), and struggled to provide dietary advice (16%). One-third were uncertain of how to support those receiving dialysis. Eighty-five percent felt they needed more training and education to care for this high-risk group. When asked about the care needs of patients with CKD, almost all (90%) felt that patients needed more diabetes support in general. Improvement in care coordination was most commonly suggested (38%)., Conclusions: In this study of the diabetes educators' experience treating patients with diabetes and CKD, respondents noted numerous challenges. There may be opportunities to better support both diabetes care professionals, and patients who live with multiple medical comorbidities., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KKC’s Diabetes Canada award was sponsored in part by Astra Zeneca. Outside of the submitted work, she has attended Merck sponsored conferences. She has also received honoraria for delivering Certified Medical Education from Sutherland Global Services Canada ULC and the Canadian Medical and Surgical Knowledge Translation Research Group. SLL has received research grants from NovoNordisk, Sanofi, and Eli Lilly. She has also received personal fees from NovoNordisk, Sanofi and Merck. AM has received honoraria from Abbott, Astra Zeneca, Bayer, BD, Boehringer-Ingelheim, Janssen, Eli Lilly, Merck, NovoNordisk, Roche and Sanofi. She has also participated in Advisory Boards for Abbott, Astra Zeneca, Bayer, BD, Boehringer-Ingelheim, Eli Lilly, and NovoNordisk. TS received a research grant from NovoNordisk. She has also received personal fees from Eli Lilly and Sanofi Canada., (© The Author(s) 2021.)

Introduction: Metformin is the initial oral antihyperglycemic agent (OHA) of choice for most patients with type 2 diabetes (T2D). However, more than one agent is often required for optimal glucose control. As the choice of preferred second OHAs is less well defined, we sought to compare the real-world safety of sulfonylureas to other OHAs as add-on therapy to metformin in patients with T2D., Research Design and Methods: This retrospective cohort study included adults in Manitoba, Canada with T2D from 2006 to 2017. Using a new-user design, we divided patients who started on metformin into two groups: add-on therapy with a sulfonylurea and add-on therapy with a different OHA. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. We calculated propensity scores and applied inverse probability of treatment weights to each individual. We compared groups using Cox proportional hazards regression and explored differences in HRs between pre-2008 (acarbose, meglitinides, and thiazolidinediones) and post-2008 (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose linked transporter-2 inhibitors) OHAs., Results: Our cohort included 32 576 individuals (28 077 metformin plus sulfonylurea and 4499 metformin plus 'other'). Patients newly prescribed a sulfonylurea in the setting of metformin had a higher risk of all-cause mortality (HR 1.44, 95% CI 1.12 to 1.84, p=0.005) and major hypoglycemic episodes (HR 2.78, 95% CI 1.66 to 4.66, p<0.001) than those prescribed an 'other' OHA. No differences in cardiovascular events were observed (HR 0.99, 95% CI 0.81 to 1.22, p=0.92). In subgroup analyses, mortality and cardiovascular event risk was higher in patients prescribed sulfonylureas versus post-2008 OHAs., Conclusions: Sulfonylureas as add-on therapy to metformin are associated with increased risk of all-cause mortality and major hypoglycemic episodes compared with 'other' OHAs. Post hoc analysis suggests newer OHAs may be preferred to sulfonylureas as second-line therapy for glycemic control., Competing Interests: Competing interests: NT has received honoraria or research support from AstraZeneca, Otsuka, and Tricida., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The incidence of severe (S-HTG) and very severe hypertriglyceridemia (VS-HTG) among Canadians is unknown. This study aimed to determine the incidence, characteristics, predictors and care patterns for individuals with VS-HTG., Methods: Using linked administrative healthcare databases, a population-based cohort study of Ontario adults was conducted to determine incidence of new onset S-HTG (serum triglycerides (TG) > 10-20 mmol/L) and VS-HTG (TG > 20 mmol/L) between 2010 and 2015. Socio-demographic and clinical characteristics of those with VS-HTG were compared to those who had no measured TG value > 3 mmol/L. Univariable and multivariable logistic regression were used to determine predictors for VS-HTG. Healthcare patterns were evaluated for 2 years following first incidence of TG > 20 mmol/L., Results: Incidence of S-HTG and VS-HTG in Ontario was 0.16 and 0.027% among 10,766,770 adults ≥18 years and 0.25 and 0.041% among 7,040,865 adults with at least one measured TG, respectively. Predictors of VS-HTG included younger age [odds ratios (OR) 0.64/decade, 95% confidence intervals (CI) 0.62-0.66], male sex (OR 3.83; 95% CI 3.5-4.1), diabetes (OR 5.38; 95% CI 4.93-5.88), hypertension (OR 1.69; 95% CI 1.54-1.86), chronic liver disease (OR 1.71; 95% CI 1.48-1.97), alcohol abuse (OR 2.47; 95% CI 1.90-3.19), obesity (OR 1.49; 95% CI 1.13-1.98), and chronic kidney disease (OR 1.39; 95% CI 1.19-1.63)., Conclusion: The 5-year incidence of S-HTG and VS-HTG in Canadian adults was 1 in 400 and 1 in 2500, respectively. Males, those with diabetes, obese individuals and those with alcohol abuse are at highest risk for VS-HTG and may benefit from increased surveillance., (© 2021. The Author(s).)

People with chronic kidney disease (CKD) are at high risk of bone fractures. In this review, we summarize the complexity of fracture prevention in CKD, describe the usefulness of a medication called denosumab, and review its safety in this population. Our article will help doctors manage brittle bones in CKD and encourage researchers to conduct more studies to improve bone health in CKD., Purpose: Patients with CKD are at increased risk of fragility fractures and associated consequences. We discuss the complexity of fracture prevention in CKD, summarize the efficacy and safety of denosumab, and provide an approach to denosumab-induced hypocalcemia., Methods: Using predefined terms, we searched PubMed, MEDLINE, and Google Scholar for studies on fracture prevention in CKD and the efficacy and safety of denosumab. We included observational studies, randomized controlled trials (RCTs), meta-analyses, evidence-based reviews, and clinical practice guidelines., Results: The diagnosis of osteoporosis and prevention of related fragility fractures is complex in CKD, particularly in those with advanced and end-staged kidney disease (ESKD). Prior to initiating denosumab, it is important to assess for and optimize CKD-mineral and bone disorders (CKD-MBD). In observational studies and small RCTs, denosumab has been shown to improve bone mineral density and reduce bone turnover in CKD, but there have been no studies focused upon its fracture efficacy. Denosumab-induced hypocalcemia has also been reported, which disproportionately impacts those with ESKD. Risk factors for hypocalcemia with denosumab use in CKD include lower baseline serum calcium and 25 hydroxyvitamin D and both low and high bone turnover. Choosing the "right patient" for denosumab, supplementing with calcium and vitamin D, adjusting calcium dialysate, and close clinical monitoring are essential if considering this drug., Conclusion: With optimization of CKD-MBD, calcium and vitamin D supplementation, and close monitoring, denosumab can be considered in CKD. There are however opportunities to better understand its fracture efficacy and safety in an RCT setting., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Background: Childhood food insecurity has been associated with prevalent asthma in cross-sectional studies. Little is known about the relationship between food insecurity and incident asthma., Methods: We used administrative databases linked with the Canadian Community Health Survey, to conduct a retrospective cohort study of children <18 years in Ontario, Canada. Children without a previous diagnosis of asthma who had a household response to the Household Food Security Survey Module (HFSSM) were followed until March 31, 2018 for new asthma diagnoses using a validated administrative coding algorithm. We used multivariable Cox proportional hazard models to examine the association between food insecurity and incident asthma, and adjusted models sequentially for clinical and clinical/socioeconomic risk factors. As additional analyses, we examined associations by HFSSM respondent type, severity of food insecurity, and age of asthma diagnosis. Moreover, we assessed for interaction between food security and child's sex, household smoking status, and maternal asthma on the risk of incident asthma., Results: Among the 27,746 included children, 5.1% lived in food insecure households. Over a median of 8.34 years, the incidence of asthma was 7.33/1000 person-years (PY) among food insecure children and 5.91/1000 PY among food secure children (unadjusted hazard ratio [HR] 1.24, 95% CI 1.00 to 1.54, p = 0.051). In adjusted analyses associations were similar (HR 1.16, 95% CI 0.91 to 1.47, p = 0.24 adjusted for clinical risk factors, HR 1.24, 95% CI 0.97 to 1.60, p = 0.09 adjusted for clinical/socioeconomic factors). Associations did not qualitatively change by HFSSM respondent type, severity of food insecurity, and age of asthma diagnosis. There was no evidence of interaction in our models., Conclusions: Food insecure children have numerous medical and social challenges. However, in this large population-based study, we did not observe that childhood food insecurity was associated with an increased risk of incident asthma when adjusted for important clinical and socioeconomic confounders., Competing Interests: Outside of this work, Kristin Clemens received a research award, sponsored in part by Astra Zeneca. She has attended Merck sponsored conferences. She has received honoraria for delivering Certified Medical Education talks from Sutherland Global Services Canada ULC, the Toronto Ontario Knowledge Translation Working Group Inc, and the Canadian Medical and Surgical Knowledge Translation Research Group. These disclosures do not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other conflicts of interest to disclose.

Background: Older Canadians frequently migrate to warmer destinations for the winter season (snowbirds). Our aim was to examine the prevalence of migration to warmer destinations among Ontarians, and to compare the characteristics and use of health care services of snowbirds to those of older Ontarians who did not migrate for the winter., Methods: We conducted a population-based analysis using health administrative databases from Ontario. We compiled 10 seasonal cohorts (2009/10 to 2018/19) of adults aged 65 or more who filled a travel supply of medications under the Ontario Drug Benefits program (snowbirds) between September and January (snowbird season). We calculated the seasonal prevalence of snowbirds per 100 Ontarians aged 65 or more. We matched each snowbird in the 2018/19 season to 2 nonsnowbirds on age and sex, and compared their characteristics and patterns of use of government-funded health care services., Results: Over the 10-year period, 53 431 to 70 863 Ontarians aged 65 or more were identified as snowbirds (seasonal prevalence 2.6%-3.3%). Compared to nonsnowbirds, snowbirds were more likely to be recent migrants, live in higher-income neighbourhoods, have fewer comorbidities and make more visits to primary care physicians. From January to March 2019, snowbirds accessed government-funded health care services for a median of 0 days (interquartile range [IQR] 0-1 d), compared to 4 days (IQR 2-8 d) among nonsnowbirds., Interpretation: About 3% of older Ontarians migrate to warmer destinations for the winter each season. Since few access health care services in Ontario from January to March, researchers are encouraged to consider the snowbird population and the impact of their absence on evaluations that assume continuous observation., Competing Interests: Competing interests: Kristin Clemens reports a Diabetes Canada Junior Investigator Award sponsored by AstraZeneca, and honoraria for providing accredited continuing medical education talks from Sutherland Global Services Canada ULC and the Canadian Medical & Surgical Knowledge Translation Research Group. She has attended Merck-sponsored conferences. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Background: Air pollution is a known trigger for exacerbations among individuals with asthma, but its role in the development of new-onset asthma is unclear. We compared the rate of new asthma cases in Sarnia, a city with high pollution levels, with the rates in 2 neighbouring regions in southwestern Ontario, Canada., Methods: Using a population-based birth cohort design and linked health administrative data, we compared the hazard of incident asthma among children 0 to 10 years of age between those born in Lambton (Sarnia) and those born in Windsor and London-Middlesex, for the period Apr. 1, 1993, to Mar. 31, 2009. We used Cox proportional hazards models to adjust for year of birth and exposure to air pollutants (nitrogen dioxide, sulphur dioxide [SO 2 ], ozone and small particulate matter [PM 2.5 ]), as well as maternal, geographic and socioeconomic factors., Results: Among 114 427 children, the highest incidence of asthma was in Lambton, followed by Windsor and London-Middlesex (30.3, 24.4 and 19.8 per 1000 person-years, respectively; p < 0.001). Relative to Lambton, the hazard of asthma, adjusted for socioeconomic and perinatal factors, was lower in Windsor (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.67-0.77) and London-Middlesex (HR 0.65, 95% CI 0.61-0.69). Inclusion of air pollutants attenuated this relative difference in both Windsor (HR 0.79, 95% CI 0.62-1.01) and London-Middlesex (HR 0.89, 95% CI 0.64-1.24)., Interpretation: We identified a higher incidence of asthma among children born in Lambton (Sarnia) relative to 2 other regions in southwestern Ontario. Higher levels of air pollution (particularly SO 2 and PM 2.5 ) in this region, as experienced by children in their first year of life, may be contributory., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Aim: To examine the association between childhood food insecurity and incident diabetes., Methods: Using health administrative databases linked to the Canadian Community Health Survey, we conducted a population-based cohort study of children aged <18 years from Ontario, Canada. Children without diabetes who had a household response to the Canadian Community Health Survey Household Food Security Survey Module were followed for a median of 9.5 years for incident diabetes. Multivariable Cox proportional hazards models were used to examine the association between childhood food insecurity and incident diabetes, adjusted sequentially for important clinical and socio-economic risk factors., Results: We included 34 042 children, of whom 5.3% lived in food-insecure households. There were 184 new cases of diabetes, diagnosed at a median age of 16 and 18.5 years in food-secure and food-insecure children, respectively. In unadjusted analysis, childhood food insecurity was associated with an increased risk of incident diabetes (hazard ratio 1.69, 95% CI 1.01 to 2.81). When adjusted for clinical and socio-economic confounders, the relationship was no longer statistically significant (hazard ratio 1.55, 95% CI 0.91 to 2.66, adjusted for clinical confounders; hazard ratio 1.30, 95% CI 0.72 to 2.37, adjusted for clinical/socio-economic confounders). Our results remained robust in sensitivity analyses., Conclusions: Although food-insecure children are a medically and socially vulnerable population, they do not appear to be at increased risk of incident diabetes over a median of 9.5 years., (© 2020 Diabetes UK.)

Urban areas have complex thermal distribution. We examined the association between extreme temperature and mortality in urban Ontario, using two temperature data sources: high-resolution and weather station data. We used distributed lag non-linear Poisson models to examine census division-specific temperature-mortality associations between May and September 2005-2012. We used random-effect multivariate meta-analysis to pool results, adjusted for air pollution and temporal trends, and presented risks at the 99th percentile compared to minimum mortality temperature. As additional analyses, we varied knots, examined associations using different temperature metrics (humidex and minimum temperature), and explored relationships using different referent values (most frequent temperature, 75th percentile of temperature distribution). Weather stations yielded lower temperatures across study months. U-shaped associations between temperature and mortality were observed using both high-resolution and weather station data. Temperature-mortality relationships were not statistically significant; however, weather stations yielded estimates with wider confidence intervals. Similar findings were noted in additional analyses. In urban environmental health studies, high-resolution temperature data is ideal where station observations do not fully capture population exposure or where the magnitude of exposure at a local level is important. If focused upon temperature-mortality associations using time series, either source produces similar temperature-mortality relationships.

Background: Obesity has a significant impact on population health and health care. Administrative databases may be a useful tool to study obesity at a population level. In this work, we aimed to determine the validity of hospital codes for obesity in Ontario, Canada., Methods: Using linked health-care databases (ICES), we conducted a validation study in adults ≥18 years of age who had their height and weight recorded during a hospitalization in southwestern Ontario. We considered a body mass index ≥30 kg/m 2 as our gold standard definition for obesity. We then examined the validity of 2 International Classification of Diseases---10th revision (ICD-10) coding algorithms for obesity (Algorithm 1, ICD-10 E66.X; and Algorithm 2, ICD-10 E65.X-68.X). As additional analyses, we examined the validity of algorithms in different obesity classes (i.e. obese classes 1, 2 and 3), and in patients with diagnosed diabetes and hypertension., Results: There were 34,588 patients included in our study (mean age, 62 years; 47% female). Algorithm 1 performed best, with a sensitivity, specificity, positive predictive value and negative predictive value of 8.8%, 99.8%, 95.4% and 65.1%, respectively. The sensitivity of this algorithm was highest in patients with obesity class 3 (27.4%) and in those with diagnosed diabetes., Conclusions: Hospital codes for obesity have a high positive predictive value and specificity. These codes can be used to build and study cohorts of patients with obesity in administrative database studies. However, given their limited sensitivity, administrative codes provide inaccurate incidence and prevalence estimates., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Glucagon-like peptide-1 receptor agonists and sodium-dependent glucose cotransporter-2 inhibitors have demonstrated clinically significant benefits on glycated hemoglobin, weight, blood pressure and cardiorenal outcomes. The emerging evidence from clinical trials and meta-analyses that assessed the combination of these 2 classes of drugs has been promising. An expert forum that included individuals with expertise in endocrine, cardiology and nephrology issues was held in May 2020 to review the literature on the metabolic and cardiorenal benefits of these 2 classes, independently and in combination, in adults with type 2 diabetes mellitus. Although hard outcome data are not available, the group concluded that the combination of glucagon-like peptide-1 receptor agonists with sodium-dependent glucose cotransporter-2 inhibitors is an emerging option for managing adults with type 2 diabetes as long as cost is not a barrier. Ongoing research may offer further insights on hard cardiorenal outcomes for this therapeutic combination as well as provide direction on the potential of this approach in obesity, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and populations without diabetes., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Patients with diabetes receiving chronic, in-center hemodialysis face healthcare challenges. We examined the prevalence of gaps in their diabetes care, explored regional differences, and determined predictors of care gaps., Methods: We conducted a population-based, retrospective study between January 1, 2016 and January 1, 2018 in Ontario, Canada. We included adults with prevalent diabetes mellitus receiving in-center hemodialysis as of January 1, 2018 and examined the proportion with ( 1 ) insufficient or excessive glycemic monitoring, ( 2 ) suboptimal screening for diabetes-related complications (retinopathy and cardiovascular screening), ( 3 ) hospital encounters for hypo- or hyperglycemia, and ( 4 ) hospital encounters for hypertension in the 2 years prior (January 1, 2016 to January 1, 2018). We then identified patient, provider, and health-system factors associated with more than one care gap and used multivariable logistic regression to determine predictors. Further, we used geographic information systems to explore spatial variation in gaps., Results: There were 4173 patients with diabetes receiving in-center hemodialysis; the mean age was 67 years, 39% were women, and the majority were of lower socioeconomic status. Approximately 42% of patients had more than one diabetes care gap, the most common being suboptimal retinopathy screening (53%). Significant predictors of more than one gap included younger age, female sex, shorter duration of diabetes, dementia, fewer specialist visits, and not seeing a physician for diabetes. There was evidence of spatial variation in care gaps across our region., Conclusions: There are opportunities to improve diabetes care in patients receiving in-center hemodialysis, particularly screening for retinopathy. Focused efforts to bring diabetes support to high-risk individuals might improve their care and outcomes., Competing Interests: K.K. Clemens received a diabetes research award sponsored by AstraZeneca; honoraria for delivering certified continuing medical education talks from the Canadian Medical and Surgical Knowledge Translation Research Group and Sutherland Global Services Canada ULC; and has attended Merck-sponsored conferences. A.X. Garg reports being on the editorial boards of American Journal of Kidney Diseases and Kidney International; receiving research funding from Astellas; serving on the data safety and monitoring board for an investigator-initiated trial program funded by GlaxoSmithKline; and serving as medical lead role to improve access to kidney transplantation and living kidney donation for the Ontario Renal Network (government-funded agency located within Ontario Health). S. Silver reports receiving honoraria from Baxter and Sanofi and serving on the editorial board of the Canadian Journal of Kidney Health and Disease. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Background: People with a recent history of homelessness are believed to be at high risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, when infected, complications of coronavirus disease 2019 (COVID-19). We describe and compare testing for SARS-CoV-2, test positivity and hospital admission, receipt of intensive care and mortality rates related to COVID-19 for people with a recent history of homelessness versus community-dwelling people as of July 31, 2020., Methods: We conducted a population-based retrospective cohort study in Ontario, Canada, between Jan. 23 and July 31, 2020, using linked health administrative data among people who either had a recent history of homelessness or were dwelling in the community. People were included if they were eligible for provincial health care coverage and not living in an institutionalized facility on Jan. 23, 2020. We examined testing for SARS-CoV-2, test positivity and complication outcomes of COVID-19 (hospital admission, admission to intensive care and death) within 21 days of a positive test result. Extended multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) in 3 time periods: preshutdown (Jan. 23-Mar. 13), peak (Mar. 14-June 16) and reopening (June 17-July 31)., Results: People with a recent history of homelessness ( n = 29 407) were more likely to be tested for SARS-CoV-2 in all 3 periods compared with community-dwelling people ( n = 14 494 301) (preshutdown adjusted HR 1.61, 95% confidence interval [CI] 1.22-2.11; peak adjusted HR 2.95, 95% CI 2.88-3.03; reopening adjusted HR 1.45, 95% CI 1.39-1.51). They were also more likely to have a positive test result (peak adjusted HR 3.66, 95% CI 3.22-4.16; reopening adjusted HR 1.76, 95% CI 1.15-2.71). In the peak period, people with a recent history of homelessness were over 20 times more likely to be admitted to hospital for COVID-19 (adjusted HR 20.35, 95% CI 16.23-25.53), over 10 times more likely to require intensive care for COVID-19 (adjusted HR 10.20, 95% CI 5.81-17.93) and over 5 times more likely to die within 21 days of their first positive test result (adjusted HR 5.73, 95% CI 3.01-10.91)., Interpretation: In Ontario, people with a recent history of homelessness were significantly more likely to be tested for SARS-CoV-2, to have a positive test result, to be admitted to hospital for COVID-19, to receive intensive care for COVID-19 and to die of COVID-19 compared with community-dwelling people. People with a recent history of homelessness should continue to be considered particularly vulnerable to SARS-CoV-2 infection and its complications., Competing Interests: Competing interests: Outside of the submitted work, Kristin Clemens has received a research award funded in part by AstraZeneca, she has attended Merck-sponsored conferences and she has received personal fees to deliver continuing medical education talks from Sutherland Global Services Canada ULC and the Canadian Medical and Surgical Knowledge Translation Research Group. No other competing interests were declared., (Copyright 2021, Joule Inc. or its licensors.)

Background and Objectives: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is commonly prescribed to patients with type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularly at higher doses. We compare the 1-year risk of death or hospitalization with congestive heart failure in patients with CKD newly prescribed sitagliptin at >50 versus ≤50 mg/d., Design, Setting, Participants, & Measurements: This population-based cohort study included older adults (>66 years) with type 2 diabetes and an eGFR<45 ml/min per 1.73 m 2 (but not receiving dialysis) who were newly prescribed sitagliptin between 2010 and 2017 in Ontario, Canada. We used inverse probability of treatment weighting on the basis of propensity scores to balance baseline characteristics. The primary composite outcome was death or hospitalization with congestive heart failure. Secondary outcomes included hospitalization with pancreatitis or hypoglycemia, all-cause hospitalization, and glycemic control. Weighted hazard ratios were obtained using Cox proportional hazards regression, and 95% confidence intervals were obtained using bootstrap variance estimators., Results: Of 9215 patients, 6518 started sitagliptin at >50 mg/d, and 2697 started sitagliptin at ≤50 mg/d. The 1-year risk of death or hospitalization with congestive heart failure did not differ significantly between groups (79 versus 126 events per 1000 person-years; weighted hazard ratio, 0.88; 95% confidence interval, 0.67 to 1.14); hospitalization with pancreatitis (weighted hazard ratio, 0.98; 95% confidence interval, 0.32 to 3.03) and hypoglycemia (weighted hazard ratio, 1.10; 95% confidence interval, 0.64 to 1.90) also did not differ significantly between groups. Patients starting sitagliptin at >50 mg/d had lower mean glycated hemoglobin concentrations (weighted between-group difference, -0.12%; 95% confidence interval, -0.19 to -0.06) and a lower risk of all-cause hospitalization (weighted hazard ratio, 0.81; 95% confidence interval, 0.66 to 0.98)., Conclusions: The risk of death or congestive heart failure was not higher in older adults with CKD starting sitagliptin at >50 versus ≤50 mg/d., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020&#95;11&#95;25&#95;CJN08310520&#95;final.mp3., (Copyright © 2020 by the American Society of Nephrology.)

Objective: The risk of adverse health events is expected to increase with hotter temperatures, particularly among the most vulnerable groups such as elderly persons and children. The objective of this study was to assess the association between extreme heat and daily emergency department visits among children (0 to 17 years) in Southwestern Ontario., Methods: We examined the average maximum temperature, relative humidity, and daily paediatric emergency department visits in June through August of 2002 to 2019. We reviewed emergency department visits from two academic hospitals. Daily meteorological data from the local weather station were obtained from Environment and Climate Change Canada., Results: Extreme heat, defined as the 99th percentile of the maximum temperature distribution, occurred at 33.1°C and was associated with an overall 22% increase in emergency department visits, compared to the reference temperature of 21°C. This association was mostly found between the second and fifth day after the exposure, suggesting a slightly delayed effect. The results of the sub-group analysis indicate that the risk of an emergency department visit due to infectious disease increases by 35% and the most pronounced association was noted in children aged 1 to 12 years., Conclusions: Extreme heat is associated with an increased incidence of emergency department visits in children. As temperatures continue to increase, strategies to mitigate heat-related health risks among children should be developed., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We provide an update on how commonly prescribed osteoporosis therapies are being initiated in older adults in Ontario. Patients newly prescribed denosumab are older, more often female, and have more comorbidities than those prescribed bisphosphonates. Their characteristics, monitoring, and persistence with prescribed therapy differ from clinical trial participants. Real-world studies on oral bisphosphonates and denosumab might be valuable., Purpose: To provide a contemporary view on oral bisphosphonate and denosumab prescribing to older adults in routine care., Methods: Using linked healthcare databases, we conducted a population-based cohort study of adults ≥ 66 years newly prescribed oral bisphosphonates or denosumab between February 2013 and March 2017 in Ontario, Canada. We captured their clinical characteristics, monitoring, and continuous use of prescribed therapies. We illustrate how "real-world" new users of bisphosphonates and denosumab differ from randomized controlled trial (RCT) participants., Results: There were 107,847 individuals newly prescribed oral bisphosphonates (n = 59,996) or denosumab (n = 47,851) over the study period. Compared with new users of oral bisphosphonates, denosumab users were older (mean age 79.1 vs. 75.7 years), more often female (97.2 vs. 71.8%), from non-rural areas (93.9 vs. 89.9%), and resided in long-term care (10.9 vs. 3.3%). They had more comorbidities including dementia, falls, and fractures. Following their new prescription, denosumab users had more frequent testing of serum calcium. Duration of continuous use of denosumab was longer than bisphosphonates, and more bisphosphonate users had evidence of treatment discontinuation (56.7 bisphosphonate vs. 33.8% denosumab users discontinued therapy at 365 days). Compared with RCT participants, a higher proportion of "real-world" bisphosphonate and denosumab users had comorbidities including advanced kidney disease., Conclusion: The clinical characteristics and monitoring of new users of bisphosphonates and denosumab generally align with practice guidelines, product monographs, and drug reimbursement criteria. Given differences between real-world users and RCT participants, there may be a role for safety and effectiveness studies of bisphosphonates and denosumab in routine care.

Background: Sex differences have been described in diabetes cardiovascular outcome trials (CVOTs)., Purpose: We systematically reviewed for baseline sex differences in cardiovascular (CV) risk factors and CV protection therapy in diabetes CVOTs., Data Sources: Randomized placebo-controlled trials examining the effect of diabetes medications on major adverse cardiovascular events in people ≥18 years of age with type 2 diabetes., Study Selection: Included trials reported baseline sex-specific CV risks and use of CV protection therapy., Data Extraction: Two reviewers independently abstracted study data., Data Synthesis: We included five CVOTs with 46,606 participants. We summarized sex-specific data using mean differences (MDs) and relative risks (RRs) and pooled estimates using random effects meta-analysis. There were fewer women than men in included trials (28.5-35.8% women). Women more often had stroke (RR 1.28; 95% CI 1.09, 1.50), heart failure (RR 1.30; 95% CI 1.21,1.40), and chronic kidney disease (RR 1.33; 95% CI 1.17; 1.51). They less often used statins (RR 0.90; 95% CI 0.86, 0.93), aspirin (RR 0.82; 95% CI 0.71, 0.95), and β-blockers (RR 0.93; 95% CI 0.88, 0.97) and had a higher systolic blood pressure (MD 1.66 mmHg; 95% CI 0.90, 2.41), LDL cholesterol (MD 0.34 mmol/L; 95% CI 0.29, 0.39), and hemoglobin A 1c (MD 0.11%; 95% CI 0.09, 0.14 [1.2 mmol/mol; 1.0, 1.5]) than men., Limitations: We could not carry out subgroup analyses due to the small number of studies. Our study is not generalizable to low CV risk groups nor to patients in routine care., Conclusions: There were baseline sex disparities in diabetes CVOTs. We suggest efforts to recruit women into trials and promote CV management across the sexes., (© 2020 by the American Diabetes Association.)

Background and Objectives: It is uncertain whether primary care physician continuity of care associates with a lower risk of death and hospitalization among patients transitioning to maintenance dialysis., Design, Setting, Participants, & Measurements: Using provincial-linked administrative databases in Ontario, Canada, we conducted a population-based study of incident patients who initiated maintenance dialysis between 2005 and 2014 and survived for at least 90 days. We defined high primary care physician continuity as both a high usual provider of care index (where >75% of primary care physician visits occurred with the same primary care physician) in the 2 years before dialysis (an established measure of primary care physician continuity) and at least one visit with the same primary care physician in the 90 days after dialysis initiation. We used propensity scores to match a group of patients with high and low continuity so that indicators of baseline health were similar. The primary outcome was all-cause mortality, and secondary outcomes included all-cause and disease-specific hospitalizations during the 2 years after maintenance dialysis initiation., Results: We identified 19,099 eligible patients. There were 6612 patients with high primary care physician continuity, of whom 6391 (97%) were matched to 6391 patients with low primary care physician continuity. High primary care physician continuity was not associated with a lower risk of mortality (14.5 deaths per 100 person-years versus 15.2 deaths per 100 person-years; hazard ratio, 0.96; 95% confidence interval, 0.89 to 1.02). There was no difference in the rate of all-cause hospitalizations (hazard ratio, 0.96; 95% confidence interval, 0.92 to 1.01), and high primary care physician continuity was not associated with a lower risk of any disease-specific hospitalization, except for those related to diabetes (hazard ratio, 0.88; 95% confidence interval, 0.80 to 0.97)., Conclusions: High primary care physician continuity before and during the transition to maintenance dialysis was not associated with a lower risk of mortality or all-cause hospitalization., (Copyright © 2020 by the American Society of Nephrology.)

Background: Regulatory agencies warn about the risk of acute kidney injury (AKI) after the initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors. Our objective was to quantify the 90-day risk of AKI in older adults after initiation of SGLT2 inhibitors in routine clinical practice., Methods: We conducted a population-based retrospective cohort study in Ontario, Canada, involving adults with diabetes who were aged 66 years or older and who were newly dispensed either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor in an outpatient setting between 2015 and 2017. We used inverse probability of treatment weighting based on a propensity score to balance the 2 groups on measured baseline characteristics. The primary outcome was 90-day risk of a hospital encounter (i.e., visit to the emergency department or admission to hospital) with AKI, which we defined by a 50% or greater increase in the concentration of serum creatinine from the baseline value or an absolute increase of at least 27 μmol/L after an SGLT2 or DDP4 inhibitor was dispensed. We obtained weighted risk ratios using modified Poisson regression and weighted risk differences using binomial regression., Results: We included 39 094 patients with a median age of 70 (interquartile range 68-74) years in the study. Relative to new use of a DPP4 inhibitor, initiation of a SGLT2 inhibitor was associated with a lower 90-day risk of a hospital encounter with AKI: 216 events in 19 611 patients (1.10%) versus 388 events in 19 483 patients (1.99%); weighted risk ratio 0.79 (95% confidence interval 0.64-0.98)., Interpretation: In routine care of older adults, new use of SGLT2 inhibitors compared with use of DPP4 inhibitors was associated with a lower risk of AKI. Together with previous evidence, our findings suggest that regulatory warnings about AKI risk with SGLT2 inhibitors are unwarranted., Competing Interests: Competing interests: David Cherney has received consulting fees or speaking honoraria or both from Bayer, Mitsubishi-Tanabe, Abbvie, BMS, Prometic, Novo-Nordisk, Janssen, Boehringer Ingelheim and Lilly, AstraZeneca, Merck and Sanofi, and has received operating funds from Sanofi, Novo-Nordisk, Janssen, Boehringer Ingelheim and Lilly, AstraZeneca and Merck Jacob Udell has received honoraria for advisory board participation from Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Merck, Novartis and Sanofi Pasteur, and grant support to his institutions from AstraZeneca. Kristin Clemens has received a Diabetes Canada Junior Investigator Award, sponsored by Astra Zeneca, and has also received speaker fees from Sutherland Global Services Canada ULC. She has attended conferences sponsored by Merck. Chirag Parikh has received consultant fees from Akebia Therapeutics and Genfit Biopharmaceutical, grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute, and other support from Renalytix AI. Navdeep Tangri has received personal fees from AstraZeneca, Otsuka, Janssen, and Boehringer Ingelheim and Lilly, and Tricida, grants from AstraZeneca and Tricida, and other support from Tricida. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Background: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization in young children in Canada, despite routine immunoprophylaxis in those with medical risk factors. We aimed to determine if cold temperatures are associated with RSV hospitalization., Methods: We conducted a population-based nested case-control study of children in Ontario, Canada, using health administrative data. We compared children hospitalized for RSV between September 1, 2011 and August 31, 2012 to age and sex matched controls. We used multivariable logistic regression to identify associations between minimum daily temperature and RSV hospitalizations with adjustment for sociodemographic and environmental factors., Results: We identified 1670 children with RSV hospitalizations during the study period and 6680 matched controls. Warmer temperatures (OR = 0.94, 95%CI: 0.93, 0.95) were associated with lower odds of RSV hospitalization. Southern ecozone (OR = 1.6, 95%CI: 1.2, 2.1), increased ozone concentration (OR = 1.03, 95%CI: 1.01, 1.06) and living in a lower income neighbourhood (OR = 1.3, 95%CI: 1.1, 1.5) significantly increased the odds of RSV hospitalization, as did living in a household with a larger number of siblings in a sub-cohort of children (OR = 1.34, 95%CI: 1.26, 1.41)., Conclusions: In Ontario, the likelihood of having an RSV hospitalization is associated with colder temperature exposures and socioeconomic factors.

Objective: To compare the safety of metformin vs sulfonylureas in patients with type 2 diabetes by chronic kidney disease (CKD) stage., Patients and Methods: This retrospective cohort study included adults in Manitoba, Canada, with type 2 diabetes, an incident monotherapy prescription for metformin or a sulfonylurea, and a serum creatinine measurement from April 1, 2006, to March 31, 2017. Patients were stratified by estimated glomerular filtration rate (eGFR) into the following groups: eGFR of 90 or greater, 60 to 89, 45 to 59, 30 to 44, or less than 30 mL/min/1.73 m 2 . Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. Baseline characteristics were used to calculate propensity scores and perform inverse probability of treatment weights analysis, and eGFR group was examined as an effect modifier for each outcome., Results: The cohort consisted of 21,996 individuals (19,990 metformin users and 2006 sulfonylurea users). Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.48; 95% CI, 0.40-0.58; P<.001), cardiovascular events (HR, 0.67; 95% CI, 0.52-0.86; P=.002), and major hypoglycemic episodes (HR, 0.14; 95% CI, 0.09-0.20; P<.001) when compared with sulfonylureas. CKD was a significant effect modifier for all-cause mortality (P=.002), but not for cardiovascular events or major hypoglycemic episodes., Conclusion: Sulfonylurea monotherapy is associated with higher risk for all-cause mortality, major hypoglycemic episodes, and cardiovascular events compared with metformin. Although the presence of CKD attenuated the mortality benefit, metformin may be a safer alternative to sulfonylureas in patients with CKD., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: To use the Canadian Network for Observational Drug Effect Studies (CNODES) to describe drug utilization of antidiabetic medications in four Canadian provinces., Methods: With the use of data from CNODES, we constructed cohorts of patients with type 2 diabetes in four Canadian provinces (Manitoba, Ontario, Quebec, and Saskatchewan) who received their first-ever prescription for a noninsulin antidiabetic medication during the study period, defined as the earliest date of data availability in each province (range: 1993-1998) to the latest date of the data extraction in each province (range: 2013-2014). Prescriptions rates were calculated for all prescriptions by class and described over time., Results: Across provinces, we identified 650 830 patients who initiated antidiabetic medications during the study period. In most provinces, the overall prescription rate of antidiabetic medications increased during the last two decades. Metformin particularly increased in popularity, surpassing sulfonylureas in all provinces as the most widely prescribed antidiabetic medication by the early 2000s. Thiazolidinediones grew in popularity from the onset of their availability until 2006 to 2007, at which point they rapidly declined. Dipeptidyl peptidase-4 inhibitors saw substantial growth in several provinces following their addition to provincial formularies in 2008 to 2012, while glucagon-like peptide-1 agonists experienced modest growth. Insulin prescription rates remained constant or steadily increased over the last two decades., Conclusions: CNODES can be used for cross-jurisdictional drug utilization studies. In Canada, trends in antidiabetic medication prescriptions followed changing guidelines reflecting up-to-date knowledge of drug effectiveness and safety., (© 2019 John Wiley & Sons, Ltd.)

Hemodialysis is a life-sustaining treatment for persons with kidney failure. However, those on hemodialysis still face a poor quality of life and a short life expectancy. High-quality research evidence from large randomized controlled trials is needed to identify interventions that improve the experiences, outcomes, and health care of persons receiving hemodialysis. With the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, the Innovative Clinical Trials in Hemodialysis Centers initiative brought together Canadian and international kidney researchers, patients, health care providers, and health administrators to participate in a workshop held in Toronto, Canada, on June 2 and 3, 2018. The workshop served to increase knowledge and awareness about the conduct of innovative, pragmatic, cluster-randomized registry trials embedded into routine hemodialysis care and provided an opportunity to discuss and build support for new trial ideas. The workshop content included structured presentations, facilitated group discussions, and expert panel feedback. Partnerships and promising trial ideas borne out of the workshop will continue to be developed to support the implementation of future large-scale trials., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Background: In older adults, hip fractures have been described to peak in cooler months. Seasonal differences in patient vulnerability to fracture and social/behavioural factors might contribute to these trends., Methods: Using linked health-care databases in Ontario Canada, we examined monthly variation in hip fracture hospitalizations in those > 65 years (2011-2015). We stratified results by age category (66-79, ≥80 years). We then examined for variation in the demographic and comorbidity profiles of patients across the months, and as an index of contributing social/behavioural factors, noted variation in health-care behaviours., Results: There were 47,971 and 52,088 hospitalizations for hip fracture in those 66-79, and ≥80 years, respectively. There was strong seasonality in fractures in both groups. Peaks occurred in October and December when patients appeared most vulnerable. Rates fell in the summer in those 66-79 years, and in the late winter in those ≥80 years (when health-care utilization also declined). A smaller peak in fractures occurred in May in both groups., Conclusions: Hip fractures peak in the autumn, early winter, and spring in Canada. A dip in fractures occurs in the late winter in the oldest old. Environmental factors might play a role, but seasonal vulnerability to fracture and winter isolation might also be influential., Competing Interests: Conflict of Interest Disclosures KC received a Diabetes Canada Junior Investigator Award sponsored by Astra Zeneca. She has also attended conferences sponsored by Merck. There are no other conflicts of interest to disclose and no endorsement by ICES, AMOSO, SSMD, LHRI or the MOHLTC is intended or should be inferred., (© 2019 Author(s). Published by the Canadian Geriatrics Society.)

Background: Patients with diabetes and advanced chronic kidney disease face a high health care burden. As part of a patient-oriented research initiative to identify ways to better support patients' diabetes care, we explored their health care experience and solutions for patient-centred diabetes care., Methods: We engaged 2 patients with advanced kidney disease and diabetes to join our multidisciplinary team as full research partners. They were involved in our design and conduct of the study, the analysis of the results and knowledge translation. We conducted qualitative interviews (1:1 semistructured interviews and focus groups) with patients with a history of both diabetes (type 1 or 2) and advanced kidney disease including those using dialysis. We identified overarching themes using individual and team analysis and conducted interviews until data saturation was reached., Results: Twelve participants were interviewed between October 2017 and February 2018. Six people were interviewed in 2 separate focus groups (consisting of 4 and 2 participants) and 6 participated in 1:1 interviews with our team. Participants described being burdened by medical appointments, strict conflicting diets, costly diabetes therapies and fragmented, siloed health care. They indicated that self-management support, education and coordinated diabetes care might better support their diabetes care., Interpretation: Patients with complex medical comorbidities face many challenges traversing a health care system organized around single diseases. Researchers and policy-makers should study and develop patient-centred diabetes care strategies to better support these high-risk patients., Competing Interests: Competing interests: Kristin Clemens received a Diabetes Canada Junior Investigator award in 2017, funded by AstraZeneca. She has attended conferences sponsored by Merck, unrelated to this work. Sonja Reichert has received fees for advisory board work from Sanofi, Novo Nordisk, AstraZeneca and Servier, unrelated to this work. She has received personal fees for presentations from Sanofi, Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Janssen, Eli Lilly, Merck and Abbott, unrelated to this work. Although no personal fees were obtained, she has acted as a subinvestigator on clinical trials for the following companies: Sanofi, Novo Nordisk, AstraZeneca, Boehringer Ingelheim, unrelated to this work. No other competing interests were declared., (Copyright 2019, Joule Inc. or its licensors.)