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Background Mental health problems, particularly anxiety and depression, are common in patients with chronic kidney disease (CKD) and negatively impact quality of life, treatment adherence and mortality. However, the degree to which mental health and addiction services are utilized by those with CKD is unknown. We examined the history of mental health and addiction service use of individuals across levels of kidney function. Methods We performed a population-based cross-sectional study using linked healthcare databases from Ontario, Canada from 2009 to 2017. We abstracted the prevalence of individuals with mental health and addiction service use within the previous 3 years across levels of kidney function [estimated glomerular filtration rate (eGFR) ≥60, 45 to <60, 30 to <45, 15 to <30, <15 ml/min/1.73 m2 and maintenance dialysis]. We calculated prevalence ratios (PRs) to compare prevalence across kidney function strata, while adjusting for age, sex, year of cohort entry, urban versus rural location, area-level marginalization and Charlson comorbidity index. Results Of 5 956 589 adults, 9% (n  = 534 605) had an eGFR <60 ml/min/1.73 m2 or were receiving maintenance dialysis. Fewer individuals with an eGFR <60 ml/min/1.73 m2 had a history of any mental health and addiction service utilization (crude prevalence range 28–31%) compared with individuals with an eGFR ≥60 ml/min/1.73 m2 (35%). Compared with an eGFR ≥60 ml/min/1.73 m2, the lowest prevalence of individuals with any mental health and addiction service utilization was among those with an eGFR of 15 to <30 ml/min/1.73 m2 {adjusted PR 0.86 [95% confidence interval (CI) 0.85 to 0.88]}, an eGFR <15 ml/min/1.73 m2 [adjusted PR 0.81 (95% CI 0.76–0.86)] and those receiving maintenance dialysis [adjusted PR 0.83 (95% CI 0.81–0.84)]. Less use of outpatient services accounted for differences in service utilization. Conclusions Mental health and addiction service utilization is common but less so in individuals with advanced CKD in Ontario, Canada. [ABSTRACT FROM AUTHOR]

For decades, researchers have used linkable administrative health data for evaluating the health care system, subject to local privacy legislation. In Ontario, Canada, the relevant privacy legislation permits some organizations (prescribed entities) to conduct this kind of research but is silent on their ability to identify and contact individuals in those datasets. Following consultation with the Office of the Information and Privacy Commissioner of Ontario, we developed a pilot study to identify and contact by mail a sample of people at high risk for kidney failure within the next 2 years, based on laboratory and administrative data from provincial datasets held by ICES, to ensure they receive needed kidney care. Before proceeding, we conducted six focus groups to understand the acceptability to the public and people living with chronic kidney disease of direct mail outreach to people at high risk of developing kidney failure. While virtually all participants indicated they would likely participate in the study, most felt strongly that the message should come directly from their primary care provider or whoever ordered the laboratory tests, rather than from an unknown organization. If this is not possible, they felt the health care provider should be made aware of the concern related to their kidney health. Most agreed that, if health authorities could identify people at high risk of a treatable life-threatening illness if caught early enough, there is a social responsibility to notify people. While privacy laws allow for free flow of health information among health care providers who provide direct clinical care, the proposed case-finding and outreach falls outside that model. Enabling this kind of information flow will require greater clarity in existing laws or revisions to these laws. This also requires adequate notification and culture change for health care providers and the public around information uses and flows. [ABSTRACT FROM AUTHOR]

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 m2). 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 m2. 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). [ABSTRACT FROM AUTHOR]

Introduction: The Alliance for Healthier Communities represents community‐governed healthcare organizations in Ontario, Canada including Community Health Centres, which provide primary care to more disadvantaged populations. Methods: In this experience report, we describe the Alliance's journey towards becoming a learning health system using examples for organizational culture, data and analytics, people and partnerships, client engagement, ethics and oversight, evaluation and dissemination, resources, identification and prioritization, and deliverables and impact. Results: Many of the foundational elements for a learning health system were already in place at the Alliance including an integrated and accessible data platform. Leadership championed and embraced the movement towards a learning health system, which led to restructuring of the organization. This included role changes for data support personnel, better communication, and dissemination plans, strategies to engage clinicians and other front‐line staff, restructuring of committees for more collaborative planning and prioritization of quality improvement and research initiatives, and the development of a new Practice‐Based Learning Network for more opportunities to use the data for research and evaluation. Conclusions: Next steps will focus on continued clinical engagement and partnerships as well as ongoing reflection on the transition and success of the learning health system work. [ABSTRACT FROM AUTHOR]

Background Chronic pain is common, and its management is complex in patients with chronic kidney disease (CKD), but limited data are available on opioid prescribing. We examined opioid prescribing for non-cancer and non-end-of-life care in patients with CKD. Methods This was a population-based retrospective cohort study using administrative databases in Ontario, Canada which included adults with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 from 1 November 2012 to 31 December 2018 and estimated the proportion of opioid prescriptions (type, duration, dose, potentially inappropriate prescribing, etc.) within 1 year of cohort entry. Prescriptions had to precede dialysis, kidney transplant or death. Results We included 680 445 adults with CKD, and 198 063 (29.1%) were prescribed opioids. Codeine (14.9%) and hydromorphone (7.2%) were the most common opioids. Among opioid users, 24.3% had repeated or long-term use, 26.1% were prescribed high doses and 56.8% were new users. Opioid users were more likely to be female, had cardiac disease or a mental health diagnosis, and had more healthcare visits. The proportions for potentially inappropriate prescribing indicators varied (e.g. 50.1% with eGFR <30 were prescribed codeine, and 20.6% of opioid users were concurrently prescribed benzodiazepines, while 7.2% with eGFR <30 mL/min/1.73 m2 were prescribed morphine, and 7.0% were received more than one opioid concurrently). Opioid prescriptions declined with time (2013 cohort: 31.1% versus 2018 cohort: 24.5%; p <0.0001), as did indicators of potentially inappropriate prescribing. Conclusions Opioid use was common in patients with CKD. While opioid prescriptions and potentially inappropriate prescribing have declined in recent years, interventions to improve pain management without the use of opioids and education on safer prescribing practices are needed. [ABSTRACT FROM AUTHOR]

Rationale, Aims and Objectives: A learning health system model can be used to efficiently evaluate and incorporate evidence‐based care into practice. However, there is a paucity of evidence describing key organizational attributes needed to ensure a successful learning health system within primary care. We interviewed stakeholders for a primary care learning health system in Ontario, Canada (the Alliance for Healthier Communities) to identify strengths and areas for improvement. Method: We conducted a qualitative descriptive study using individual semistructured interviews with Alliance stakeholders between December 2019 and March 2020. The Alliance delivers community‐governed primary healthcare through 109 organizations including Community Health Centres (CHCs). All CHC staff within the Alliance were invited to participate. Interviews were audio‐recorded and transcribed verbatim. We performed a thematic analysis using a team approach. Results: We interviewed 29 participants across six CHCs, including Executive Directors, managers, healthcare providers and data support staff. We observed three foundational elements necessary for a successful learning health system within primary care: shared organizational goals and culture, data quality and resources. Building on this foundation, people are needed to drive the learning health system, and this is conditional on their level of engagement. The main factors motivating staff member's engagement with the learning health system included their drive to help improve patient care, focusing on initiatives of personal interest and understanding the purpose of different initiatives. Areas for improvement were identified such as the ability to extract and use data to inform changes in real‐time, better engagement and protected time for providers to do improvement work, and more staff dedicated to data extraction and analysis. Conclusions: We identified key components needed to establish a learning health system in primary care. Similar primary care organizations in Canada and elsewhere can use these insights to guide their development as learning health systems. [ABSTRACT FROM AUTHOR]

Background: Printed educational materials (PEMs) have long been used to inform clinicians on evidence-based practices. However, the evidence for their effects on patient care and outcomes is unclear. In Ontario, despite widely available clinical practice guidelines recommending antihypertensives and cholesterol-lowering agents for patients with diabetes, prescriptions remain low. We aimed to determine whether PEMs can influence physicians to intensify prescribing of these medications. Methods: A pragmatic, 2 × 2 factorial, cluster randomized controlled trial was designed to ascertain the effect of two PEM formats on physician prescribing: a postcard-sized message ("outsert") or a longer narrative article ("insert"). Ontario family physician practices (clusters) were randomly allocated to receive the insert, outsert, both or neither. Physicians were eligible if they were in active practice and their patients were included if they were over 65 years with a diabetes diagnosis; both were unaware of the trial. Administrative databases at ICES (formerly the Institute for Clinical Evaluative Sciences) were used to link patients to their physician and to analyse prescribing patterns at baseline and 1 year following PEM mailout. The primary outcome was intensification defined as the addition of a new antihypertensive or cholesterol-lowering agent, or dose increase of a current drug, measured at the patient level. Analyses were by intention-to-treat and accounted for the clustering of patients to physicians. Results: We randomly assigned 4231 practices (39% of Ontario family physicians) with a total population of 185,526 patients (20% of patients with diabetes in Ontario primary care) to receive the insert, outsert, both, and neither; among these, 4118 practices were analysed (n = 1025, n = 1037, n = 1031, n = 1025, respectively). No significant treatment effect was found for the outsert (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.98 to 1.04) or the insert (OR 0.99, 95% CI 0.96 to 1.02). Percent of intensification in the four arms was similar (approximately 46%). Adjustment for physician characteristics (e.g., age, sex, practice location) had no impact on these findings. Conclusions: PEMs have no effect on physician's adherence to recommendations for the management of diabetes-related complications in Ontario. Further research should investigate the effect of other strategies to narrow this evidence-to-practice gap. Trial registration: ISRCTN72772651. Retrospectively registered 21 July 2005. [ABSTRACT FROM AUTHOR]

Background: Learning health systems have been gaining traction over the past decade. The purpose of this study was to understand the spread of learning health systems in primary care, including where they have been implemented, how they are operating, and potential challenges and solutions. Methods: We completed a scoping review by systematically searching OVID Medline®, Embase®, IEEE Xplore®, and reviewing specific journals from 2007 to 2020. We also completed a Google search to identify gray literature. Results: We reviewed 1924 articles through our database search and 51 articles from other sources, from which we identified 21 unique learning health systems based on 62 data sources. Only one of these learning health systems was implemented exclusively in a primary care setting, where all others were integrated health systems or networks that also included other care settings. Eighteen of the 21 were in the United States. Examples of how these learning health systems were being used included real-time clinical surveillance, quality improvement initiatives, pragmatic trials at the point of care, and decision support. Many challenges and potential solutions were identified regarding data, sustainability, promoting a learning culture, prioritization processes, involvement of community, and balancing quality improvement versus research. Conclusions: We identified 21 learning health systems, which all appear at an early stage of development, and only one was primary care only. We summarized and provided examples of integrated health systems and data networks that can be considered early models in the growing global movement to advance learning health systems in primary care. [ABSTRACT FROM AUTHOR]

Background The ability to identify patients with autosomal dominant polycystic kidney disease (ADPKD) and distinguish them from patients with similar conditions in healthcare administrative databases is uncertain. We aimed to measure the sensitivity and specificity of different ADPKD administrative coding algorithms in a clinic population with non-ADPKD and ADPKD kidney cystic disease. Methods We used a dataset of all patients who attended a hereditary kidney disease clinic in Toronto, Ontario, Canada between 1 January 2010 and 23 December 2014. This dataset included patients who met our reference standard definition of ADPKD or other cystic kidney disease. We linked this dataset to healthcare databases in Ontario. We developed eight algorithms to identify ADPKD using the International Classification of Diseases, 10th Revision (ICD-10) codes and provincial diagnostic billing codes. A patient was considered algorithm positive if any one of the codes in the algorithm appeared at least once between 1 April 2002 and 31 March 2015. Results The ICD-10 coding algorithm had a sensitivity of 33.7% [95% confidence interval (CI) 30.0–37.7] and a specificity of 86.2% (95% CI 75.7–92.5) for the identification of ADPKD. The provincial diagnostic billing code had a sensitivity of 91.1% (95% CI 88.5–93.1) and a specificity of 10.8% (95% CI 5.3–20.6). Conclusions ICD-10 coding may be useful to identify patients with a high chance of having ADPKD but fail to identify many patients with ADPKD. Provincial diagnosis billing codes identified most patients with ADPKD and also with other types of cystic kidney disease. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infection (IFI) in solid organ transplant (SOT) recipients is associated with significant morbidity and mortality. The long‐term probability of post‐transplant IFI is poorly understood. Methods: We conducted a population‐based cohort study using linked administrative healthcare databases from Ontario, Canada, to determine the incidence rate; 1‐, 5‐, and 10‐year cumulative probabilities of IFI; and post‐IFI all‐cause mortality in SOT recipients from 2002 to 2016. We also determined post‐IFI, death‐censored renal allograft failure. Results: We included 9326 SOT recipients (median follow‐up: 5.35 years). Overall, the incidence of IFI was 8.3 per 1000 person‐years. The 1‐year cumulative probability of IFI was 7.4% for lung, 5.4% for heart, 1.8% for liver, 1.2% for kidney‐pancreas, and 1.1% for kidney‐only allograft recipients. Lung transplant recipients had the highest incidence rate and 10‐year probability of IFI: 43.0 per 1000 person‐years and 26.4%, respectively. The 1‐year all‐cause mortality rate after IFI was 34.3%. IFI significantly increased the risk of mortality in SOT recipients over the entire follow‐up period (hazard ratio: 6.50, 95% CI: 5.69‐7.42). The 1‐year probability of death‐censored renal allograft failure after IFI was 9.8%. Conclusion: Long‐term cumulative probability of IFI varies widely among SOT recipients. Lung transplantation was associated with the highest incidence of IFI with considerable 1‐year all‐cause mortality. [ABSTRACT FROM AUTHOR]

Objectives Chronic kidney disease (CKD) is common; therefore, coordination of care between primary care and nephrology is important. Ontario Renal Network’s KidneyWise toolkit was developed to provide guidance on the detection and management of people with CKD in primary care ( www. kidneywise. ca). The aim of this study was to evaluate the impact of the April 2015 KidneyWise toolkit release on the characteristics of primary care referrals to nephrology. Design and setting The study was a prospective pre-post design conducted at two nephrology sites (community site: Trillium Health Partners in Mississauga, Ontario, Canada, and academic site: St Joseph’s Healthcare in Hamilton, Ontario, Canada). Referrals were compared during the 3-month time period immediately prior to, and during a 3-month period 1 year after, the toolkit release. Primary and secondary outcome measures The primary outcome was the change in proportion of referrals for CKD that met the KidneyWise criteria. Additional secondary referral and quality of care outcomes were also evaluated. Multivariable logistic regression was used to evaluate preselected variables for their independent association with referrals that met the KidneyWise criteria. Results The proportion of referrals for CKD among people who met the KidneyWise referral criteria did not significantly change from pre-KidneyWise to post-KidneyWise implementation (44.7% vs 45.8%, respectively, adjusted OR 1.16, 95% CI 0.85 to 1.59, p=0.36). The proportion of referrals for CKD that provided a urine albumin-creatinine ratio significantly increased post-KidneyWise (25.8% vs 43.8%, adjusted OR 1.45, 95% CI 1.06 to 1.97, p=0.02). The significant independent predictors of meeting the KidneyWise referral criteria were academic site, increased age and use of the KidneyWise referral form. Conclusions We did not observe any change in the proportion of appropriate referrals for CKD at two large nephrology centres 1 year after implementation of the KidneyWise toolkit. [ABSTRACT FROM AUTHOR]

Background: In 2007, an electronic repository called the Ontario Laboratories Information System (OLIS) was introduced to allow health care providers timely access to laboratory test results. Since not all laboratories began submitting their data to OLIS simultaneously, we sought to create a date-dependent table of geographic regions (forward sortation areas [FSAs]) from which people would likely present to a hospital linked to OLIS. Methods: In this descriptive study, we used administrative data to capture adults in Ontario who presented to the emergency department for any reason from 2007 to 2017. To assess changes over time, we classified all emergency department visits into fiscal quarters. The primary outcome measure was the proportion of people in a given FSA presenting to an emergency department at an OLIS-linked hospital (v. a hospital not linked to OLIS). To be included in the catchment area, at least 90% of all emergency department visits in a given quarter from a given FSA must have occurred at an OLIS-linked hospital. Results: By Dec. 31, 2017, 323 (61.4%) of 526 Ontario FSAs were in the catchment area (a population of about 8.5 million). There were no differences in selected demographic characteristics or comorbidities between people residing within the catchment area of OLIS-linked hospitals and those residing in the catchment area of unlinked hospitals on Dec. 31, 2017. We used the FSA information to construct a date-dependent table of geographic areas likely to have hospital laboratory data available in OLIS for future studies. Interpretation: We identified relevant Ontario geographic regions from which people would likely present to a hospital linked to OLIS. These geographic regions constitute a catchment area that may be used in future studies to capture adults who present to an OLIS-linked hospital with laboratory-defined conditions such as acute kidney injury, hyperkalemia and hyponatremia. [ABSTRACT FROM AUTHOR]

Background Clinical guidelines caution against nonsteroidal anti-inflammatory drug (NSAID) use in older adults. The study objective was to quantify the 30-day risk of acute kidney injury (AKI) and hyperkalemia in older adults after NSAID initiation and to develop a model to predict these outcomes. Methods We conducted a population-based retrospective cohort study in Ontario, Canada from 2007 to 2015 of patients ≥ 66 years. We matched 46 107 new NSAID users with 46 107 nonusers with similar baseline health. The primary outcome was 30-day risk of AKI and secondary outcomes were hyperkalemia and all-cause mortality. Results NSAID use versus nonuse was associated with a higher 30-day risk of AKI {380 [0.82%] versus 272 [0.59%]; odds ratio (OR) 1.41 [95% confidence interval (CI) 1.20–1.65]} and hyperkalemia [184 (0.40%) versus 123 (0.27%); OR 1.50 (95% CI 1.20–1.89); risk difference 0.23% (95% CI 0.13–0.34)]. There was no association between NSAID use and all-cause mortality. A prediction model incorporated six predictors of AKI or hyperkalemia: older age, male gender, lower baseline estimated glomerular filtration rate, higher baseline serum potassium, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use or diuretic use. This model had moderate discrimination [C-statistic 0.72 (95% CI 0.70–0.74)] and good calibration. Conclusions In older adults, new NSAID use compared with nonuse was associated with a higher 30-day risk of AKI and hyperkalemia but not all-cause mortality. Prescription NSAID use among many older adults may be safe, but providers should use caution and assess individual risk. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment.Methods: We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007-2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence.Results: We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014.Conclusion: Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population. [ABSTRACT FROM AUTHOR]

Background In primary care, patients with chronic kidney disease (CKD) are frequently prescribed excessive doses of antibiotics relative to their kidney function. We examined whether nephrology comanagement is associated with improved prescribing in primary care. Methods In a retrospective propensity score–matched cross-sectional study, we studied the appropriateness of antibiotic prescriptions by primary care physicians to Ontarians ≥66 years of age with CKD Stages 4 and 5 (estimated glomerular filtration rate <30 mL/min/1.73 m2 not receiving dialysis) from 1 April 2003 to 31 March 2014. Comanagement was defined as having at least one outpatient visit with a nephrologist within the year prior to antibiotic prescription date. We compared the rate of appropriately dosed antibiotics in primary care between 3937 patients who were comanaged by a nephrologist and 3937 patients who were not. Results Only 1184 (30%) of 3937 noncomanaged patients had appropriately dosed antibiotic prescriptions prescribed by a primary care physician. Nephrology comanagement was associated with an increased likelihood that an appropriately dosed prescription was prescribed by a primary care physician; however, the magnitude of the effect was modest [1342/3937 (34%); odds ratio 1.20 (95% confidence interval 1.09–1.32); P < 0.001]. Conclusion The majority of antibiotics prescribed by primary care physicians are inappropriately dosed in CKD patients, whether or not a nephrologist is comanaging the patient. Nephrologists have an opportunity to increase awareness of appropriate dosing of medications in primary care through the patients they comanage. [ABSTRACT FROM AUTHOR]

Background: The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. Methods: We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Results: Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Conclusion: Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia. [ABSTRACT FROM AUTHOR]

Background: Many respiratory tract infections are treated with macrolide antibiotics. Regulatory agencies warn that these antibiotics increase the risk of ventricular arrhythmia. We examined the 30-day risk of ventricular arrhythmia and all-cause mortality associated with macrolide antibiotics relative to nonmacrolide antibiotics.Methods: We conducted a population-based retrospective cohort study involving older adults (age > 65 yr) with a new prescription for an oral macrolide antibiotic (azithromycin, clarithromycin or erythromycin) in Ontario from 2002 to 2013. Our primary outcome was a hospital encounter with ventricular arrhythmia within 30 days after a new prescription. Our secondary outcome was 30-day all-cause mortality. We matched patients 1:1 using propensity scores to patients prescribed nonmacrolide antibiotics (amoxicillin, cefuroxime or levofloxacin). We used conditional logistic regression to measure the association between macrolide exposure and outcomes, and repeated the analysis in 4 subgroups defined by the presence or absence of chronic kidney disease, congestive heart failure, coronary artery disease and concurrent use of a drug known to prolong the QT interval.Results: Compared with nonmacrolide antibiotics, macrolide antibiotics were not associated with a higher risk of ventricular arrhythmia (0.03% v. 0.03%; relative risk [RR] 1.06, 95% confidence interval [CI] 0.83-1.36) and were associated with a lower risk of all-cause mortality (0.62% v. 0.76%; RR 0.82, 95% CI 0.78-0.86). These associations were similar in all subgroups.Interpretation: Among older adults, macrolide antibiotics were not associated with a higher 30-day risk of ventricular arrhythmia than nonmacrolide antibiotics. These findings suggest that current warnings from the US Food and Drug Administration may be overstated. [ABSTRACT FROM AUTHOR]

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Background: Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis.Objective: To investigate the risk for AKI and other adverse outcomes associated with use of atypical antipsychotic drugs versus nonuse.Design: Population-based cohort study.Setting: Ontario, Canada, from 2003 to 2012.Patients: Adults aged 65 years or older who received a new outpatient prescription for an oral atypical antipsychotic drug (n=97,777) matched 1:1 with those who did not receive such a prescription.Measurements: The primary outcome was hospitalization with AKI (assessed by using a hospital diagnosis code and, in a subpopulation, serum creatinine levels) within 90 days of prescription for atypical antipsychotic drugs.Results: Atypical antipsychotic drug use versus nonuse was associated with a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]). This association was consistent when AKI was assessed in a subpopulation for which information on serum creatinine levels was available (5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI, 0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all-cause mortality (RR, 2.39 [CI, 2.28 to 2.50]).Limitation: Only older adults were included in the study.Conclusion: Atypical antipsychotic drug use is associated with an increased risk for AKI and other adverse outcomes that may explain the observed association with AKI. The findings support current safety concerns about the use of these drugs in older adults.Primary Funding Source: Academic Medical Organization of Southwestern Ontario. [ABSTRACT FROM AUTHOR]

Background: Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis. Objective: To investigate the risk for AKI and other adverse outcomes associated with use of atypical antipsychotic drugs versus nonuse. Design: Population-based cohort study. Setting: Ontario, Canada, from 2003 to 2012. Patients: Adults aged 65 years or older who received a new outpatient prescription for an oral atypical antipsychotic drug (n = 97 777) matched 1:1 with those who did not receive such a prescription. Measurements: The primary outcome was hospitalization with AKI (assessed by using a hospital diagnosis code and, in a subpopulation, serum creatinine levels) within 90 days of prescription for atypical antipsychotic drugs. Results: Atypical antipsychotic drug use versus nonuse was associated with a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]). This association was consistent when AKI was assessed in a subpopulation for which information on serum creatinine levels was available (5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI, 0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all-cause mortality (RR, 2.39 [CI, 2.28 to 2.50]). Limitation: Only older adults were included in the study. Conclusion: Atypical antipsychotic drug use is associated with an increased risk for AKI and other adverse outcomes that may explain the observed association with AKI. The findings support current safety concerns about the use of these drugs in older adults. Primary Funding Source: Academic Medical Organization of Southwestern Ontario. [ABSTRACT FROM AUTHOR]

Individuals with moderate-to-severe reduced renal function have greater risk of gastrointestinal bleeding than those with normal renal function. We conducted a retrospective matched cohort study to assess whether living kidney donors share a similar risk. We reviewed pre-donation charts for living kidney donations from 1992 to 2009 in Ontario, Canada, and linked this information to healthcare databases. We selected healthy non-donors from the general population and matched ten non-donors to every donor. Of the 2009 donors and 20 090 matched non-donors, none had evidence of gastrointestinal bleeding prior to cohort entry. The cohort was followed for a median of 8.4 yr (maximum 19.7 yr; loss to follow-up <7%). There was no significant difference in the rate of hospitalization with gastrointestinal bleeding in donors compared to non-donors (18.5 vs. 14.9 events per 10 000 person-years; rate ratio 1.24; 95% confidence interval [CI] 0.85-1.81). Similar results were obtained when we assessed the time to first hospitalization with gastrointestinal bleeding (hazard ratio 1.25, 95% CI 0.87-1.79). In conclusion, we found living kidney donation was not associated with a higher risk of hospitalization with gastrointestinal bleeding. These results are reassuring for the safety of the practice. [ABSTRACT FROM AUTHOR]

IMPORTANCE The effect of surgeons' disrupted sleep on patient outcomes is not clearly defined. OBJECTIVE To assess if surgeons operating the night before have more complications of elective surgery performed the next day. DESIGN, SETTING, AND PARTICIPANTS Population-based, matched, retrospective cohort study using administrative health care databases in Ontario, Canada (2012 population, 13 505 900). Participants were 2078 patients who underwent elective laparoscopic cholecystectomies performed by surgeons who operated the night before, matched with 4 other elective laparoscopic cholecystectomy recipients (n = 8312). EXPOSURE In total, 94183 eligible elective laparoscopic cholecystectomies were performed between 2004 and 2011. Of these surgeries, there were 2078 procedures in which 331 different surgeons across 102 community hospitals had operated between midnight and 7 AM the night before. Each "at-risk" surgery was randomly matched with 4 other elective laparoscopic cholecystectomies (n = 8312) performed by the same surgeon, who had no evidence of having operated the night before. MAIN OUTCOMES AND MEASURES The primary outcome was conversion from a laparoscopic cholecystectomy to open cholecystectomy. Secondary outcomes included evidence of iatrogenic injuries or death. Risks were quantified using generalized estimating equations. RESULTS NO significant association was found in conversion rates to open operations between surgeons when they operated the night before compared with when they did not operate the previous night (46/2031 [2.2%] vs 157/8124 [1.9%]; adjusted odds ratio [OR], 1.18; 95% CI, 0.85-1.64). There was no association between operating the night before vs not operating the night before, and risk of iatrogenic injuries (14/2031 [0.7%] vs 72/8124 [0.9%]; adjusted OR, 0.77; 95% CI, 0.43-1.37) or death (<5/2031 [<0.2%] vs 7/8124 [0.1%]). CONCLUSIONS AND RELEVANCE No significant association was found between operating the night before and not operating the previous night for conversion to open cholecystectomy, risk of iatrogenic complications, or death for elective daytime cholecystectomy. These findings do not support safety concerns related to surgeons operating the night before performing elective surgery. [ABSTRACT FROM AUTHOR]

IMPORTANCE The effect of surgeons' disrupted sleep on patient outcomes is not clearly defined. OBJECTIVE To assess if surgeons operating the night before have more complications of elective surgery performed the next day. DESIGN, SETTING, AND PARTICIPANTS Population-based, matched, retrospective cohort study using administrative health care databases in Ontario, Canada (2012 population, 13 505 900). Participants were 2078 patients who underwent elective laparoscopic cholecystectomies performed by surgeons who operated the night before, matched with 4 other elective laparoscopic cholecystectomy recipients (n = 8312). EXPOSURE In total, 94 183 eligible elective laparoscopic cholecystectomies were performed between 2004 and 2011. Of these surgeries, there were 2078 procedures in which 331 different surgeons across 102 community hospitals had operated between midnight and 7 AM the night before. Each "at-risk" surgery was randomly matched with 4 other elective laparoscopic cholecystectomies (n = 8312) performed by the same surgeon, who had no evidence of having operated the night before. MAIN OUTCOMES AND MEASURES The primary outcome was conversion from a laparoscopic cholecystectomy to open cholecystectomy. Secondary outcomes included evidence of iatrogenic injuries or death. Risks were quantified using generalized estimating equations. RESULTS No significant association was found in conversion rates to open operations between surgeons when they operated the night before compared with when they did not operate the previous night (46/2031 [2.2%] vs 157/8124 [1.9%]; adjusted odds ratio [OR], 1.18; 95%CI, 0.85-1.64). There was no association between operating the night before vs not operating the night before, and risk of iatrogenic injuries (14/2031 [0.7%] vs 72/8124 [0.9%]; adjusted OR, 0.77; 95%CI, 0.43-1.37) or death (5/2031 [0.2%] vs 7/8124 [0.1%]). CONCLUSIONS AND RELEVANCE No significant association was found between operating the night before and not operating the previous night for conversion to open cholecystectomy, risk of iatrogenic complications, or death for elective daytime cholecystectomy. These findings do not support safety concerns related to surgeons operating the night before performing elective surgery. [ABSTRACT FROM AUTHOR]

Objective: Clarithromycin strongly inhibits enzyme cytochrome P450 3A4, preventing the metabolism of some other drugs, while azithromycin is a weak inhibitor. Accordingly, blood concentrations of other drugs increase with clarithromycin coprescription leading to adverse events. These macrolide antibiotics also differ on other properties that may impact outcomes. In this study, we compared outcomes in two groups of macrolide antibiotic users in the absence of potentially interacting drugs. Design: Population-based retrospective cohort study. Setting: Ontario, Canada, from 2003 to 2010. Patients: Patients (mean 74 years) prescribed clarithromycin (n=52 251) or azithromycin (referent group, n=46 618). Main outcomes: The primary outcomes were hospital admission within 30 days of a new antibiotic prescription with any of the 12 conditions examined separately (acute kidney injury, acute myocardial infarction, neuroimaging (proxy for delirium), hypotension, syncope, hyperkalaemia, hyponatraemia, hyperglycaemia, arrhythmia, ischaemic stroke, gastrointestinal bleeding and sepsis). The secondary outcome was mortality. Results: The baseline characteristics of the two groups, including patient demographics, comorbid conditions, infection type and prescribing physician specialty, were nearly identical. The median daily dose was 1000 mg for clarithromycin and 300 mg for azithromycin and the median duration of dispensing antibiotics was 10 and 5 days, respectively. There was no difference between the groups in the risk of hospitalisation for any condition studied (relative risk ranged from 0.67 to 1.23). Compared with azithromycin, clarithromycin was associated with a slightly higher risk of all-cause mortality (0.46% vs 0.37%, relative risk 1.25, 95% CI 1.03 to 1.52). Conclusions: Clarithromycin can be used to assess drug interactions in population-based studies with azithromycin serving as a control group. However, any differences in mortality observed between the two antibiotic groups in the setting of other drug use may be partially attributable to factors beyond the inhibition of drug metabolising enzymes and transporters, as the difference for this outcome was significant. [ABSTRACT FROM AUTHOR]

Background: Large, population-based administrative healthcare databases can be used to identify patients with chronic kidney disease (CKD) when serum creatinine laboratory results are unavailable. We examined the validity of algorithms that used combined hospital encounter and physician claims database codes for the detection of CKD in Ontario, Canada. Methods: We accrued 123,499 patients over the age of 65 from 2007 to 2010. All patients had a baseline serum creatinine value to estimate glomerular filtration rate (eGFR). We developed an algorithm of physician claims and hospital encounter codes to search administrative databases for the presence of CKD. We determined the sensitivity, specificity, positive and negative predictive values of this algorithm to detect our primary threshold of CKD, an eGFR <45 mL/min per 1.73 m2 (15.4% of patients). We also assessed serum creatinine and eGFR values in patients with and without CKD codes (algorithm positive and negative, respectively). Results: Our algorithm required evidence of at least one of eleven CKD codes and 7.7% of patients were algorithm positive. The sensitivity was 32.7% [95% confidence interval: (95% CI): 32.0 to 33.3%]. Sensitivity was lower in women compared to men (25.7 vs. 43.7%; p <0.001) and in the oldest age category (over 80 vs. 66 to 80; 28.4 vs. 37.6 %; p < 0.001). All specificities were over 94%. The positive and negative predictive values were 65.4% (95% CI: 64.4 to 66.3%) and 88.8% (95% CI: 88.6 to 89.0%), respectively. In algorithm positive patients, the median [interquartile range (IQR)] baseline serum creatinine value was 135 μmol/L (106 to 179 μmol/L) compared to 82 μmol/L (69 to 98 μmol/L) for algorithm negative patients. Corresponding eGFR values were 38 mL/min per 1.73 m2 (26 to 51 mL/min per 1.73 m2) vs. 69 mL/min per 1.73 m2 (56 to 82 mL/min per 1.73 m2), respectively. Conclusions: Patients with CKD as identified by our database algorithm had distinctly higher baseline serum creatinine values and lower eGFR values than those without such codes. However, because of limited sensitivity, the prevalence of CKD was underestimated. [ABSTRACT FROM AUTHOR]

Background: Patients should receive follow-up serum creatinine tests after an initial abnormal result to diagnose chronic kidney disease. However, half of the time this fails to occur in primary care. We interviewed primary care providers to better understand their perceptions of enablers and barriers to following this guideline-recommended care. Methods: We performed a qualitative descriptive study guided by the Theoretical Domains Framework (TDF), a framework for behavioural change. We used purposeful sampling to recruit primary care providers (physicians and nurse practitioners) based on provider and practice characteristics (rural, solo versus team practice, etc.) from Ontario, Canada. We completed one-on-one interviews with providers using a semi-structured and open-ended interview guide based on the 14 TDF domains. We alternated between data collection and analysis, where we used directed content analysis to identify frequent, important, and conflicting enablers and barriers. Results: We completed 13 interviews with nine primary care physicians and four nurse practitioners. Nine themes related to the TDF emerged from the data: 1) environmental context and resources, 2) knowledge, 3) memory, attention, and decision processes, 4) beliefs about consequences, 5) goals, 6) social or professional role, 7) behavioural regulation, 8) skills, and 9) optimism. Within these themes, we identified 16 enablers and five barriers. Some enablers included, providers' knowledge on appropriate testing, their motivation to order these tests, and their use of tools and resources to help order follow-up serum creatinine tests. However, providers perceived some barriers including that ordering confirmatory laboratory tests for chronic kidney disease was not always a priority in regards to other care they wish to provide. Providers also noted that a perceived barrier is patients not going to the laboratory to complete the test. Conclusions: We identified novel enablers and barriers to primary care providers completing guideline recommended repeat testing for the diagnosis of chronic kidney disease. Similar research is needed to understand the views of patients. These research findings can be used to inform strategies to improve the quality of care. [ABSTRACT FROM AUTHOR]

Background: Large, population-based administrative healthcare databases can be used to identify patients with chronic kidney disease (CKD) when serum creatinine laboratory results are unavailable. We examined the validity of algorithms that used combined hospital encounter and physician claims database codes for the detection of CKD in Ontario, Canada.Methods: We accrued 123,499 patients over the age of 65 from 2007 to 2010. All patients had a baseline serum creatinine value to estimate glomerular filtration rate (eGFR). We developed an algorithm of physician claims and hospital encounter codes to search administrative databases for the presence of CKD. We determined the sensitivity, specificity, positive and negative predictive values of this algorithm to detect our primary threshold of CKD, an eGFR <45 mL/min per 1.73 m² (15.4% of patients). We also assessed serum creatinine and eGFR values in patients with and without CKD codes (algorithm positive and negative, respectively).Results: Our algorithm required evidence of at least one of eleven CKD codes and 7.7% of patients were algorithm positive. The sensitivity was 32.7% [95% confidence interval: (95% CI): 32.0 to 33.3%]. Sensitivity was lower in women compared to men (25.7 vs. 43.7%; p <0.001) and in the oldest age category (over 80 vs. 66 to 80; 28.4 vs. 37.6 %; p < 0.001). All specificities were over 94%. The positive and negative predictive values were 65.4% (95% CI: 64.4 to 66.3%) and 88.8% (95% CI: 88.6 to 89.0%), respectively. In algorithm positive patients, the median [interquartile range (IQR)] baseline serum creatinine value was 135 μmol/L (106 to 179 μmol/L) compared to 82 μmol/L (69 to 98 μmol/L) for algorithm negative patients. Corresponding eGFR values were 38 mL/min per 1.73 m² (26 to 51 mL/min per 1.73 m²) vs. 69 mL/min per 1.73 m² (56 to 82 mL/min per 1.73 m²), respectively.Conclusions: Patients with CKD as identified by our database algorithm had distinctly higher baseline serum creatinine values and lower eGFR values than those without such codes. However, because of limited sensitivity, the prevalence of CKD was underestimated. [ABSTRACT FROM AUTHOR]