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Plain English summary Person-centred care (PCC) is a model of care where patient needs and preferences are included in decisions about care and treatment. To improve PCC in primary care in Alberta, Canada, we plan to use person-centred quality indicators (PC-QIs). Using PC-QIs involves surveying patients about their care experiences and using this information to make improvements. For example, if 20% of patients do not feel they are getting enough information, the clinic may create a checklist for the providers so information is not missed. We engaged a panel of 11 people, including patients, family doctors, and staff who support quality improvement in clinics across the province to decide together which PC-QIs primary care clinics in Alberta should use. We also asked the panel to decide the most important strategies that would make using the PC-QIs more successful. The panel chose PC-QIs related to: patient and caregiver involvement in decisions about care and treatment, a trusting relationship with the healthcare provider, having health information technology to support PCC, partnering with communities in healthcare, and the patient’s overall experience. The most important strategies were: developing partnerships among people working in primary care in Alberta, discussing their needs and common efforts for improving PCC, engaging “champions,” and securing funding that would be needed. Finally, we asked the panelists to share their experiences with participating in this process. Panelists found the process useful and that their input was valued. Most panelists would also like to continue to work together to put the PC-QIs into practice.

Summary: Background: Hearing loss (HL) is a leading cause of disability worldwide, but its clinical consequences and population burden have been incompletely studied. Methods: We did a retrospective population-based cohort study of 4,724,646 adults residing in Alberta between April 1, 2004 and March 31, 2019, of whom 152,766 (3.2%) had HL identified using administrative health data. We used administrative data to identify comorbidity and clinical outcomes, including death, myocardial infarction, stroke/transient ischemic attack, depression, dementia, placement in long-term care (LTC), hospitalization, emergency visits, pressure ulcers, adverse drug events and falls. We used Weibull survival models (binary outcomes) and negative binomial models (rate outcomes) to compare the likelihood of outcomes in those with vs without HL. We calculated population-attributable fractions to estimate the number of binary outcomes associated with HL. Findings: The age-sex-standardized prevalence of all 31 comorbidities at baseline was higher among participants with HL than those without. Over median follow-up of 14.4 y and after adjustment for potential confounders at baseline, participants with HL had higher rates of days in hospital (rate ratio 1.65, 95% CI 1.39, 1.97), falls (RR 1.72, 95% CI 1.59, 1.86), adverse drug events (RR 1.40, 95% CI 1.35, 1.45), and emergency visits (RR 1.21, 95% CI 1.14, 1.28) compared to those without, and higher adjusted hazards of death, myocardial infarction, stroke/transient ischemic attack, depression, heart failure, dementia, pressure ulcers and LTC placement. The estimated number of people with HL who required new LTC placement annually in Canada was 15,631, of which 1023 were attributable to HL. Corresponding estimates for new dementia among people with HL were 14,959 and 4350, and for stroke/TIA the estimates were 11,582 and 2242. Interpretation: HL is common, is often accompanied by substantial comorbidity, and is associated with significant increases in risk for a broad range of adverse clinical outcomes, some of which are potentially preventable. This high population health burden suggests that increased and coordinated investment is needed to improve the care of people with HL. Funding: Canadian Institutes of Health Research; David Freeze chair in health services research.

Rationale & Objective: The benefit–risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and

Introduction: Cardiac rehabilitation (CR) is a proven therapy for reducing cardiovascular death and hospitalization. Whether CR participation is associated with improved outcomes in patients with chronic kidney disease (CKD) is unknown. Methods: We obtained data on all adult patients in Calgary, Alberta, Canada with angiographically proven coronary artery disease from 1996 to 2016 referred to CR from The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology Rehabilitation. An estimated glomerular filtration rate (eGFR)

Background: Data on dissemination strategies that generate awareness of clinical pathways for kidney care are limited. Objective: This study reports the application of Google Analytics to describe the reach and use of the Chronic Kidney Disease Pathway (CKD-P) using a multi-faceted dissemination strategy. Design: The design of this study is a retrospective descriptive study. Setting: This study was conducted in Alberta, Canada. Patients: Individuals who accessed the CKD-P Web site between November 5, 2014, and May 31, 2019. Measurements: Dissemination activities included print, electronic, in-person meetings, and a laboratory prompt. We used Google Analytics over a 5-year period to evaluate the following CKD-P Web site user metrics: number of sessions, pageviews, visit duration, user path, and bounce rate (when an individual visits a single page of the Web site and leaves the Web site without interacting with additional pages). Methods: We plotted dissemination activities alongside Web site metrics using control charts and described the data using means and percentages. We performed chi-square test for trends to evaluate year-over-year usage. Results: There were 83 294 users, 90 805 sessions, and 231 684 pageviews. The overall bounce rate was 45.7%. Each user had an average of 1.5 sessions and a session duration of 2 minutes and 8 seconds. There was a significant positive trend for total annual users ( P = .008), new users ( P = .009), number of sessions ( P = .006), and pageviews per day ( P = .016). Limitations: We were unable to confirm if users were primary care providers and if word-of-mouth dissemination among providers/researchers drove people to use the CKD-P. Conclusions: Google Analytics was a useful and accessible tool for evaluating CKD-P reach and use trends. It was challenging to identify how individual dissemination activities contributed to CKD-P reach; however, repeated dissemination appeared to play a role in increasing CKD-P use. Trial registration: Not applicable—observational study design.

IntroductionInformation on early, guideline discordant referrals in nephrology is limited. Our objective was to investigate trends in referral patterns to nephrology for patients with chronic kidney disease (CKD).MethodsRetrospective cohort study of adults with ≥1 visits to a nephrologist from primary care with ≥1 serum creatinine and/or urine protein measurement ResultsOf 69,372 patients with CKD, 28,518 (41%) were referred in a guideline concordant manner. The overall rate of first outpatient visits to nephrology increased from 2006 to 2019, although guideline discordant referrals showed a greater increase (trend 21.9 per million population/year, 95% confidence interval 4.3, 39.4) versus guideline concordant referrals (trend 12.4 per million population/year, 95% confidence interval 5.7, 19.0). The guideline concordant cohort were more likely to be on renin-angiotensin system blockers or beta blockers (hazard ratio 1.14, 95% confidence interval 1.12, 1.16), and had a higher risk of CKD progression (hazard ratio 1.09, 95% confidence interval 1.06, 1.13), kidney failure (hazard ratio 7.65, 95% confidence interval 6.83, 8.56), cardiovascular event (hazard ratio 1.40, 95% confidence interval 1.35,1.45) and mortality (hazard ratio 1.58, 95% confidence interval 1.52, 1.63).ConclusionsA significant proportion nephrology referrals from primary care were not consistent with current guideline-recommended criteria for referral. Further work is needed to identify quality improvement initiatives aimed at enhancing referral patterns of patients with CKD.

Background Gaps in identification, medical management and appropriate referral for patients with chronic kidney disease (CKD) are evident.Objective We designed and implemented an interactive educational intervention (accredited workshop) to improve primary care providers’ awareness of tools to support guideline-concordant CKD management.Design We used the Kern method to design the educational intervention and targeted the accredited workshops to primary care team members (physicians, nurses and allied health) in Alberta, Canada. We conducted anonymous pre-workshop and post-workshop surveys to identify practice-specific barriers to care, identify potential solutions, and evaluate provider confidence pre-intervention and post-intervention. We used non-parametric statistics to analyse Likert-type survey data and descriptive content analysis to categorise responses to open-ended survey questions.Results We delivered 12 workshops to 114 providers from September 2017 through March 2019. Significant improvements (p

Background: Prior studies report high hospitalization rates among patients with chronic kidney disease (CKD) and approximately 10% to 20.9% of hospitalizations are potentially preventable. Objective: To determine the rate, proportion, and cost of potentially preventable hospitalizations and whether this varied by CKD category. Design: Retrospective cohort study using population-based data. Setting: Alberta, Canada. Patients: All adults with an outpatient serum creatinine measurement between January 1 and December 31, 2017 in the Alberta Kidney Disease Network data repository. Measurements: CKD risk categories were based on measures of proteinuria (where available), eGFR, and use of dialysis. Patients were linked to administrative data to capture frequency and cost of hospital encounters and followed until death or end of study (December 31, 2018). The outcomes of interest were the rate and cost of potentially preventable hospitalizations, as identified using the Canadian Institute for Health Information (CIHI)-defined ambulatory care sensitive condition (ACSC) algorithm and a CKD-related ACSC algorithm. Methods: Unadjusted and adjusted rates per 1000-patient years, proportions, and cost attributable to preventable hospitalizations were identified for the cohort as a whole and for patients within each CKD risk category. Results: Of the 1,110,895 adults with eGFR and proteinuria measurements, 181,422 had CKD. During a median follow-up of 1 year, there were 62,023 hospitalizations among patients with CKD resulting in a total cost of $946 million CAD; 6907 (11.1%) of these hospitalizations were for CIHI-defined ACSCs while 4323 (7.0%) were for CKD-related ACSCs. Adjusted rates of hospitalization for ACSCs increased with CKD risk category and were highest among patients treated with dialysis. Among CKD patients, the total cost of potentially preventable hospitalizations was $79 million and $58 million CAD for CIHI-defined and CKD-related ACSCs (8.4% and 6.2% of total hospitalization cost, respectively). Limitations: Based on the ACSC construct, we were unable to determine if these hospitalizations were truly preventable. Conclusions: Potentially preventable hospitalizations have a substantial cost and burden on the health care system among people with CKD. Effective strategies that reduce preventable admissions among CKD patients may lead to significant cost savings. Trial registration: Not applicable—observational study design

Background: Fatigue is a pervasive symptom among patients with chronic kidney disease (CKD) that is associated with several adverse outcomes, but the incidence of hospitalization for fatigue is unknown. Objective: To explore the association between estimated glomerular filtration rate (eGFR) and incidence of hospitalization for fatigue. Design: Population-based retrospective cohort study using a provincial administrative dataset. Setting: Alberta, Canada. Patients: People above age 18 who had at least 1 outpatient serum creatinine measurement taken in Alberta between January 1, 2009, and December 31, 2016. Measurements: The first outpatient serum creatinine was used to estimate GFR. Hospitalization for fatigue was identified using International Classification of Diseases, Tenth Revision (ICD-10) code R53.x. Methods: Patients were stratified by CKD category based on their index eGFR. We used negative binomial regression to determine if there was an increased incidence of hospitalization for fatigue by declining kidney function (reference eGFR ≥ 60 mL/min/1.73m 2 ). Estimates were stratified by age, and adjusted for age, sex, socioeconomic status, and comorbidity. Results: The study cohort consisted of 2 823 270 adults, with a mean age of 46.1 years and median follow-up duration of 6.0 years; 5 422 hospitalizations for fatigue occurred over 14 703 914 person-years of follow-up. Adjusted rates of hospitalization for fatigue increased with decreasing kidney function, across all age strata. The highest rates were seen in adults on dialysis (adjusted incident rate ratios 24.47, 6.66, and 3.13 for those aged 18 to 64, 65 to 74, and 75+, respectively, compared with eGFR ≥ 60 mL/min/1.73m 2 ). Limitations: Fatigue hospitalization codes have not been validated; reference group limited to adults with at least 1 outpatient serum creatinine measurement; remaining potential for residual confounding. Conclusions: Declining kidney function was associated with increased incidence of hospitalization for fatigue. Further research into ways to address fatigue in the CKD population is warranted. Trial Registration: Not applicable (not a clinical trial).

Background: In people with severe chronic kidney disease (CKD), there is an inverse relationship between age and kidney failure. If this relationship is the same at any age (linear), one effect (hazard ratio) will be sufficient for accurate risk prediction; if it is nonlinear, the effect will vary with age. Objective: To investigate the relationship between age and kidney failure in adults with category G4 chronic kidney disease (G4 CKD). Methods: We performed a population-based study using linked administrative databases in Alberta, Canada, to study adults with G4 CKD (estimated glomerular filtration rate [eGFR] = 15-30 mL/min/1.73 m 2 ) and without previously documented eGFR

Abstract Background Systematic reviews are infrequently used by health care managers (HCMs) and policy-makers (PMs) in decision-making. HCMs and PMs co-developed and tested novel systematic review of effects formats to increase their use. Methods A three-phased approach was used to evaluate the determinants to uptake of systematic reviews of effects and the usability of an innovative and a traditional systematic review of effects format. In phase 1, survey and interviews were conducted with HCMs and PMs in four Canadian provinces to determine perceptions of a traditional systematic review format. In phase 2, systematic review format prototypes were created by HCMs and PMs via Conceptboard©. In phase 3, prototypes underwent usability testing by HCMs and PMs. Results Two hundred two participants (80 HCMs, 122 PMs) completed the phase 1 survey. Respondents reported that inadequate format (Mdn = 4; IQR = 4; range = 1–7) and content (Mdn = 4; IQR = 3; range = 1–7) influenced their use of systematic reviews. Most respondents (76%; n = 136/180) reported they would be more likely to use systematic reviews if the format was modified. Findings from 11 interviews (5 HCMs, 6 PMs) revealed that participants preferred systematic reviews of effects that were easy to access and read and provided more information on intervention effectiveness and less information on review methodology. The mean System Usability Scale (SUS) score was 55.7 (standard deviation [SD] 17.2) for the traditional format; a SUS score

Introduction: Patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR)

Abstract Background Patients with CKD are at increased risk of potentially preventable hospital acquired complications (HACs). Understanding the economic consequences of preventable HACs, may define the scope and investment of initiatives aimed at prevention. Methods Adult patients hospitalized from April, 2003 to March, 2008 in Alberta, Canada comprised the study cohort. Healthcare costs were determined and categorized into ‘index hospitalization’ including hospital cost and in-hospital physician claims, and ‘post discharge’ including ambulatory care cost, physician claims, and readmission costs from discharge to 90 days. Multivariable regression was used to estimate the incremental healthcare costs associated with potentially preventable HACs. Results In fully adjusted models, the median incremental index hospitalization cost was CAN-$6169 (95% CI; 6003–6336) in CKD patients with ≥1 potentially preventable HACs, compared with those without. Post-discharge incremental costs were 1471(95% CI; 844–2099) in those patients with CKD who developed potentially preventable HACs within 90 days after discharge compared with patients without potentially preventable HACs. Additionally, the incremental costs associated with ≥1 potentially preventable HACs within 90 days from admission in patients with CKD were $7522 (95% CI; 7219–7824). A graded relation of the incremental costs was noted with the increasing number of complications. In patients without CKD but with ≥1 preventable HACs incremental costs within 90 days from hospital admission was $6688 (95% CI: 6612–6723). Conclusions Potentially preventable HACs are associated with substantial increases in healthcare costs in people with CKD. Investment in implementing targeted strategies to reduce HACs may have a significant benefit for patient and health system outcomes.

Background: Residents of rural areas of Alberta face significant barriers regarding access to specialist care, resulting in delays in provision of optimal care. Electronic referral and consultation systems are promising tools for facilitating timely access to specialist care, especially for people living in rural locations. Objective: To report our initial experience with the launch of an electronic advice request system for ambulatory kidney care in Alberta, Canada. Methods: We analyzed electronic advice requests for nephrology services in Alberta after the system’s pilot launch, from October 2016 to December 2017. Data for province-wide advice request utility by primary care providers (PCPs) were extracted from Alberta Netcare for analysis. Results: The total number of electronic advice requests directed to nephrology was 118 (mean number of requests: 2 per week). Only 31 (26.3%) of the cases required a face-to-face clinic visit with a nephrologist. Most (87; 73.7%) cases were managed by PCPs with ongoing nephrologist support via the advice request tool. Typical nephrologist response time was 5.7 ± 0.6 (mean ± SEM) days. Conclusion: These preliminary data suggest that the electronic advice request program has potential to enhance timely access to specialist kidney care and minimize unnecessary nephrologist visits while reducing response time. Broad implementation of this system may have a substantial positive impact on health outcomes and improve cost-effectiveness for nephrology care in the long term, particularly in rural communities of Alberta.

IntroductionElectronic consultation (eConsult)—provider-to-provider electronic asynchronous exchanges of patient health information at a distance—is emerging as a potential tool to improve the interface between primary care providers and specialists. Despite growing evidence that eConsult has clinical benefits, it is not widely adopted. We investigated factors influencing the adoption and implementation of eConsult services.MethodsWe applied established methods to guide the review, and the recently published Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews to report our findings. We searched five electronic databases and the grey literature for relevant studies. Two reviewers independently screened titles and full texts to identify studies that reported barriers to and/or facilitators of eConsult (asynchronous (store-and-forward) use of telemedicine to exchange patient health information between two providers (primary and secondary) at a distance using secure infrastructure). We extracted data on study characteristics and key barriers and facilitators were analysed thematically and classified using the Quadruple Aim framework taxonomy. No date or language restrictions were applied.ResultsAmong the 2579 publications retrieved, 130 studies met eligibility for the review. We identified and summarised key barriers to and facilitators of eConsult adoption and implementation across four domains: provider, patient, healthcare system and cost. Key barriers were increased workload for providers, privacy concerns and insufficient reimbursement for providers. Main facilitators were remote residence location, timely responses from specialists, utilisation of referral coordinators, addressing medicolegal concerns and incentives for providers to use eConsult.ConclusionThere are multiple barriers to and facilitators of eConsult adoption across the domains of Quadruple Aim framework. Our findings will inform the development of practice tools to support the wider adoption and scalability of eConsult implementation.

Background: As the burden of chronic kidney disease (CKD) continues to increase, many geographically dispersed Canadians have limited access to specialist nephrology care, which tends to be centralized in major urban areas. As a result, many rural/remote-dwellers in Canada experience poor quality of care and related adverse outcomes. It is imperative to develop alternative care delivery mechanisms to ensure optimal health outcomes for all Canadians. Objective: To investigate the feasibility and effectiveness of electronic consultation (eConsult) as a new model for interactions between specialists and primary care providers (PCPs) to improve access to care for patients with CKD. Design: This is a sequential, mixed methods study that will be conducted in 3 phases. Setting: The study will be conducted across the entire province of Alberta, supported by Alberta Kidney Care (formerly, Northern and Southern Alberta Renal Programs [NARP/SARP]). Patients: Patients suffering from CKD will be included in the study. Measurements: We will assess the barriers and enablers of implementation and adoption of an e-consultation protocol to facilitate access to care for patients with CKD in Alberta with a focus on rural/remote-dwellers with CKD. We will also evaluate the impact of the eConsult system (eg, improved access to specialist care, reduction in care gaps), assess the feasibility of province-wide implementation, and compare eConsult with practice facilitation versus eConsult alone in terms of access to specialist care, quality of care, and related outcomes. Methods: The study will be conducted in 3 phases. In phase 1, we will assess the perceptions of stakeholders (ie, PCPs, nephrologists, patients, policymakers, and other care providers) to improve CKD care delivery, quality, and outcomes in Alberta with focus groups and semistructured interviews. Phase 2 will engage specific family physicians for their input on key factors and logistical issues affecting the feasibility of implementing eConsult for the care of patients with CKD. Phase 3 will provide academic detailing including practice facilitation to clinics in Alberta to assess how eConsult with practice facilitation compares with eConsult alone in terms of access to specialist care, quality of care, and related outcomes. Results: We will assess stakeholder perceptions about potential barriers to and enablers of a new eConsult and decision support system strategy, focusing on elements that are most important for the design of a feasible and implementable intervention. We will develop, pilot test, and assess the impact of the eConsult model in improving access to specialist nephrology care and the feasibility of province-wide implementation. The final phase of the project will address key challenges for optimal care for patients with CKD living in rural, remote, and underserved areas of Alberta, particularly timely referral and disease management as well as the cost-effective benefits of eConsult. Limitations: Lack of high-speed Internet in many rural and remote areas of Alberta may lead to more time spent in completing the eConsult request online versus faxing a referral the traditional way. Allied health care staff (referral coordinators, administrative staff) require training to the eConsult system, and physicians at many remote sites do not have adequate staff to handle eConsult as an added task. Conclusions: Implementation of eConsult can favorably influence referral patterns, access to care, care quality, patient outcomes, and health care costs for people with CKD. Results of this study will inform the optimization of care for rural/remote-dwellers with CKD and will facilitate future partnerships with policymakers and provincial renal programs in Alberta to ensure optimal kidney health for all residents. Trial registration: Not required.

This data incorporates 2016 testing volumes ordered by family physicians and performed at Calgary Laboratory Services (CLS), the sole supplier of clinical laboratory services for the catchment area of the City of Calgary, Alberta, Canada. For each test, the mean number of tests ordered per patient was calculated over ordering Calgary physicians, along with arithmetic coefficients of variation (CV's). The latter parameter is reflective of variance in ordering practice among family physicians practicing in Calgary and is proposed as a benchmark measure for laboratory utilization in our accompanying research article [1]. The data table encompasses 358 tests ordered by at least 3 family physicians at a minimum total frequency of 100 within the 2016 study period and is presented in ascending order of rank in CV. Keywords: Clinical laboratory tests, Utilization, Variance, Laboratory medicine, Family medicine

Background: Self-management support interventions are widely accepted in chronic kidney disease (CKD) care; however, interventions rarely consider individual behaviors by incorporating a behavioral theoretical framework. The Theoretical Domains Framework (TDF) can be used to facilitate an understanding of patients and their caregivers’ behaviors to successfully self-manage CKD. Objectives: (1) To understand behaviors of patients with CKD and their caregivers and identify potential intervention approaches to support CKD self-management and (2) to explore relationships between the 14 TDF domains and CKD self-management. Design: Qualitative descriptive study using both content and thematic analysis Setting: Purposive criterion was used to recruit participants from across Canada. Patients: Canadian patients with CKD and their caregivers. Measurements: Focus groups and telephone interviews using a semistructured interview guide. Methods: We conducted a secondary analysis of qualitative data collected from focus groups and telephone interviews from July 2017 to January 2018. Two research team members coded the transcribed data to the 14 TDF domains using a modified approach of the Framework Method. We linked the common TDF domains to relevant intervention functions from the Behaviour Change Wheel (BCW) to identify potential intervention approaches. We also identified and mapped relationships between the relevant TDF domains to report emerging themes. Results: Six focus groups (37 participants) and 11 telephone interview transcripts were analyzed. Five TDF domains that influenced CKD self-management behavior were identified: environmental context and resources, knowledge, beliefs about capabilities, beliefs about consequences, and social influences. Four BCW intervention functions were identified: education, modeling, persuasion, and environmental restructuring. Four emergent themes, shaped by the populated 14 TDF domains, were identified: What does this mean for me? Help me help myself, How does this make me feel? and Who am I? Limitations: The TDF was not used to design the interview guide; therefore, there may be underrepresentation of some TDF domains relevant for self-management. Conclusion: Our findings highlight 5 TDF domains that can influence CKD self-management behavior and 4 possible intervention approaches to influence behavior change in patients with CKD and their caregivers. Emergent themes highlight participants’ interpretation of being diagnosed with CKD, their motivations, feelings, values, and altered identity. This work will inform the codesign of a behavior change intervention to enhance patient self-management of CKD.

Background: As the adverse clinical outcomes common in patients with chronic kidney disease (CKD) can be prevented or delayed, information on the cost of care across the spectrum of CKD can inform investments in CKD care. Objectives: To determine the cost of caring for patients with CKD who are not on dialysis or transplant at baseline. Design: Population-based cohort study using administrative health data. Setting: Alberta, Canada. Patients: Cohort of 219 641 adults with CKD categorized by estimated glomerular filtration rate (eGFR) between April 1, 2012, and March 31, 2014, into Kidney Disease: Improving Global Outcomes (KDIGO) CKD categories, excluding patients on dialysis or transplant at baseline. Measurements: The primary outcome was 1-year cumulative unadjusted health care costs, including the cost of drugs, physician visits, emergency department visits, outpatient procedures (including dialysis and other day medicine and surgery procedures), and hospitalizations for the year following each patient’s index date. Methods: Mean 1-year direct medical costs were estimated for the cohort as a whole and for patients in the different KDIGO CKD categories as defined at baseline. Costs were further categorized according to baseline demographic and clinical characteristics, and by type of care (ie, kidney care and cardiovascular care). Results: In 219 641 adults with CKD, the mean unadjusted cumulative 1-year cost of care was Can$14 634 per patient (median = Can$3672; Q1 = Can$1496, Q3 = Can$10 221). Costs were higher for those with more comorbidity, those with lower eGFR, and those with more severe albuminuria. The cost of kidney and cardiovascular care was Can$230 (1.6% of total costs) and Can$720 (4.9% of total costs), respectively, for the cohort overall. These costs increased substantially for patients with lower eGFR, averaging Can$14 169 (32.3% of total costs) and Can$2395 (5.5% of total costs) for kidney and cardiovascular care, respectively, for people with eGFR

Background: Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. Objective: To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. Design: Retrospective cohort study. Setting: We used linked health care databases in Alberta, Canada. Patients: We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. Measurements: The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. Methods: We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). Results: Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (−5.4 vs −1.9 mL/min/1.73 m 2 , P < .05). Limitations: We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. Conclusion: Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted.

The incidence of acute kidney injury (AKI) in hospitalized patients is rising, and survivors are at high risk for cardiovascular events and mortality. Effective strategies that improve long-term outcomes of AKI are unknown. Methods: A retrospective cohort study was performed between 2008 and 2011. All subjects were followed until 31 March 2013, with a minimum follow-up of 2 years. Participants were adults 18 years of age or older, who developed AKI during a hospitalization and had chronic kidney disease (CKD) following discharge (n = 19,707 mean age 69.9 years, mean postdischarge estimated glomerular filtration rate (eGFR) 43.0 ml/min/1.73 m2). Exposure to statins was examined prior to the index hospitalization as well as within 2 years following hospital discharge. The primary outcome was mortality; secondary outcomes included all-cause re-hospitalization and cardiovascular events. Results: Within 2 years of discharge, only 38.3% of the participants were prescribed a statin. After adjustment for comorbidities, statin use prior to admission, demographics, baseline kidney function, and a number of other factors, statin use was associated with lower mortality (hazard ratio, 0.74; 95% confidence interval, 0.69, 0.79) in AKI survivors with CKD. Patients who received a statin also had a lower risk of all cause rehospitalization (adjusted hazarad ratio, 0.90; 95% confidence interval, 0.85, 0.94). Statin use was not associated with a reduction in cardiovascular events. Discussion: Among AKI survivors with CKD, statin use was associated with a lower risk of mortality and rehospitalization rates. This finding suggests that there is an opportunity to improve postdischarge care in AKI survivors.

Background. The risk of mortality and graft loss is higher in kidney transplant recipients with reduced estimated glomerular filtration rate (eGFR) and albuminuria. It is unclear whether these markers are also associated with cardiovascular events. Methods. We examined linked healthcare databases in Alberta, Canada to identify kidney transplant recipients between 2002 and 2013 who had at least 1 outpatient serum creatinine and albuminuria measurement at 1-year posttransplant. We determined the relationship between categories of eGFR and albuminuria and the risk of subsequent cardiovascular events. Results. Among 1069 eligible kidney transplant recipients, the median age was 52 years, 37% were female, and 52% had eGFR ≥60 mL/min per 1.73 m2. Over a median follow-up of 6 years, the adjusted rate of all-cause mortality and cardiovascular events was 2.7-fold higher for recipients with eGFR 15-29 mL/min per 1.73 m2 and heavy albuminuria compared to recipients with eGFR ≥60 mL/min per 1.73 m2 and normal albuminuria (rate ratio, 2.7; 95% confidence interval, 1.3-5.7). Similarly, recipients with heavy albuminuria had a threefold increased risk of all-cause mortality and heart failure compared with recipients with eGFR ≥60 mL/min per 1.73 m2 and normal albuminuria. Conclusions. These findings suggest that eGFR and albuminuria should be used together to determine the risk of cardiovascular outcomes in transplant recipients.

Background: Previous guidelines recommend that living kidney donors receive lifelong annual follow-up care to assess renal health. Objective: To determine whether these best practice recommendations are currently being followed. Design: Retrospective cohort study using linked health care databases. Setting: Alberta, Canada (2002-2014). Patients: Living kidney donors. Measurements: We determined the proportion of donors who had annual outpatient physician visits and laboratory measurements for serum creatinine and albuminuria. Results: There were 534 living kidney donors with a median follow-up of 7 years (maximum 13 years). The median age at the time of donation was 41 years and 62% were women. Overall, 25% of donors had all 3 markers of care (physician visit, serum creatinine, albuminuria measurement) in each year of follow-up. Adherence to physician visits was higher than serum creatinine or albuminuria measurements (67% vs 31% vs 28% of donors, respectively). Donors with guideline-concordant care were more likely to be older, reside closer to the transplant center, and receive their nephrectomy in more recent years. Limitations: Our results may not be generalizable to other countries that do not have a similar universal health care system. Conclusions: These findings suggest significant evidence-practice gaps, in that the majority of donors saw a physician, but the minority had measurements of kidney function or albuminuria. Future interventions should target improving follow-up care for all donors.

Purpose of review This article serves to describe the Can-SOLVE CKD network, a program of research projects and infrastructure that has excited patients and given them hope that we can truly transform the care they receive. Issue Chronic kidney disease (CKD) is a complex disorder that affects more than 4 million Canadians and costs the Canadian health care system more than $40 billion per year. The evidence base for guiding care in CKD is small, and even in areas where evidence exists, uptake of evidence into clinical practice has been slow. Compounding these complexities are the variations in outcomes for patients with CKD and difficulties predicting who is most likely to develop complications over time. Clearly these gaps in our knowledge and understanding of CKD need to be filled, but the current state of CKD research is not where it needs to be. A culture of clinical trials and inquiry into the disease is lacking, and much of the existing evidence base addresses the concerns of the researchers but not necessarily those of the patients. Program overview The Canadian Institutes of Health Research (CIHR) has launched the national Strategy for Patient-Oriented Research (SPOR), a coalition of federal, provincial, and territorial partners dedicated to integrating research into care. Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) is one of five pan-Canadian chronic kidney disease networks supported through the SPOR. The vision of Can-SOLVE CKD is that by 2020 every Canadian with or at high risk for CKD will receive the best recommended care, experience optimal outcomes, and have the opportunity to participate in studies with novel therapies, regardless of age, sex, gender, location, or ethnicity. Program objective The overarching objective of Can-SOLVE CKD is to accelerate the translation of knowledge about CKD into clinical research and practice. By focusing on the patient’s voice and implementing relevant findings in real time, Can-SOLVE CKD will transform the care that CKD patients receive, and will improve kidney health for future generations.

People with chronic diseases experience barriers to managing their diseases and accessing available health services. Patient navigator programs are increasingly being used to help people with chronic diseases navigate and access health services.The objective of this review was to summarize the evidence for patient navigator programs in people with a broad range of chronic diseases, compared to usual care.We searched MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO, and Social Work Abstracts from inception to August 23, 2017. We also searched the reference lists of included articles. We included original reports of randomized controlled trials of patient navigator programs compared to usual care for adult and pediatric patients with any one of a defined set of chronic diseases.From a total of 14,672 abstracts, 67 unique studies fit our inclusion criteria. Of these, 44 were in cancer, 8 in diabetes, 7 in HIV/AIDS, 4 in cardiovascular disease, 2 in chronic kidney disease, 1 in dementia and 1 in patients with more than one condition. Program characteristics varied considerably. Primary outcomes were most commonly process measures, and 45 of 67 studies reported a statistically significant improvement in the primary outcome.Our findings indicate that patient navigator programs improve processes of care, although few studies assessed patient experience, clinical outcomes or costs. The inability to definitively outline successful components remains a key uncertainty in the use of patient navigator programs across chronic diseases. Given the increasing popularity of patient navigators, future studies should use a consistent definition for patient navigation and determine which elements of this intervention are most likely to lead to improved outcomes.PROSPERO #CRD42013005857.

Purpose of review: The purpose of this review is to contribute to the Choosing Wisely Canada campaign and develop a list of 5 items for nephrology health care professionals and patients to re-evaluate based on evidence that they are overused or misused. Sources of information: A working group was formed from the Canadian Society of Nephrology (CSN) Clinical Practice Guidelines Committee. This working group sequentially used a multistage Delphi method, a survey of CSN members, a modified Delphi process, and a comprehensive literature review to determine 10 candidate items representing potentially ineffective care in nephrology. An in-person vote by CSN members at their Annual General Meeting was used to rank each item based on their relevance to and potential impact on patients with kidney disease to derive the final 5 items on the list. Key messages: One hundred thirty-four of 609 (22%) CSN members responded to the survey, from which the CSN working group identified 10 candidate-misused items. Sixty-five CSN members voted on the ranking of these items. The top 5 recommendations selected for the final list were (1) do not initiate erythropoiesis-stimulating agents in patients with chronic kidney disease (CKD) with hemoglobin levels greater than or equal to 100 g/L without symptoms of anemia; (2) do not prescribe nonsteroidal anti-inflammatory drugs for individuals with hypertension or heart failure or CKD of all causes, including diabetes; (3) do not prescribe angiotensin-converting-enzyme inhibitors in combination with angiotensin II receptor blockers for the treatment of hypertension, diabetic nephropathy or heart failure; (4) do not initiate chronic dialysis without ensuring a shared decision-making process between patients, their families, and their nephrology health care team; and (5) do not initiate dialysis in outpatients with CKD category G5-ND in the absence of clinical indications. Limitations: A low survey response rate of both community and academic nephrologists could contribute to sampling bias. However, the purpose of this report is to generate discussion, rather than study practice variation. Implications: These 5 evidence-based recommendations aim to improve outcomes and individualize care for patients with kidney disease, while reducing inefficiencies and preventing harm.

Background: Health behaviour change is an important component of management for patients with chronic kidney disease (CKD); however, the optimal method to promote health behaviour change for self-management of CKD is unknown. The See Kidney Disease (SeeKD) targeted screening programme screened Canadians at risk for CKD and promoted health behaviour change through individual counselling and goal setting. Objectives: The objectives of this study are to determine the effectiveness of individual counselling sessions for eliciting behaviour change and to describe participant characteristics associated with behaviour change. Design: This is a cross-sectional, descriptive study. Setting: The study setting is the National SeeKD targeted screening programme. Patients: The participants are all ‘at risk’ patients who were screened for CKD and returned a follow-up health behaviour survey ( n = 1129). Measurements: Health behaviour change was defined as a self-reported change in lifestyle, including dietary changes or medication adherence. Methods: An individual counselling session was provided to participants by allied healthcare professionals to promote health behaviour change. A survey was mailed to all participants at risk of CKD within 2-4 weeks following the screening event to determine if behaviour changes had been initiated. Descriptive statistics were used to describe respondent characteristics and self-reported behaviour change following screening events. Results were stratified by estimated glomerular filtration rate (eGFR) (< 60 and >60 mL/min/1.73 m 2 ). Log binomial regression analysis was used to determine the predictors of behaviour change. Results: Of the 1129 respondents, the majority (89.8 %) reported making a health behaviour change after the screening event. Respondents who were overweight (body mass index [BMI] 25-29.9 kg/m 2 ) or obese (BMi ≥ 30.0 kg/m 2 ) were more likely to report a behaviour change (prevalence rate ratio (PRR) 0.66, 95 % confidence interval (CI) 0.44-0.99 and PRR 0.49, 95 % CI 0.30-0.80, respectively). Further, participants with a prior intent to change their behaviour were more likely to make a behaviour change (PRR 0.58, 95 % CI 0.35-0.96). Results did not vary by eGFR category. Limitations: We are unable to determine the effectiveness of the behaviour change intervention given the lack of a control group. Potential response bias and social desirability bias must also be considered when interpreting the study findings. Conclusions: Individual counselling and goal setting provided at screening events may stimulate behaviour change amongst individuals at risk for CKD. However, further research is required to determine if this behaviour change is sustained and the impact on CKD progression and outcomes.

Background: Guideline committees have identified the need for research to inform the provision of conservative care for older adults with stage 5 chronic kidney disease (CKD) who have a high burden of comorbidity or functional impairment. We will use both qualitative and quantitative methodologies to provide a comprehensive understanding of barriers and facilitators to care for these patients in primary care. Objectives: Our objectives are to (1) interview primary care physicians to determine their perspectives of conservative care for older adults with stage 5 CKD and (2) survey primary care physicians to determine the prevalence of key barriers and facilitators to provision of conservative care for older adults with stage 5 CKD. Design: A sequential exploratory mixed methods design was adopted for this study. The first phase of the study will involve fundamental qualitative description and the second phase will be a cross-sectional population-based survey. Setting: The research is conducted in Alberta, Canada. Participants: The participants are primary care physicians with experience in providing care for older adults with stage 5 CKD not planning on initiating dialysis. Methods: The first objective will be achieved by undertaking interviews with primary care physicians from southern Alberta. Participants will be selected purposively to include physicians with a range of characteristics (e.g., age, gender, and location of clinical practice). Interviews will be recorded, transcribed verbatim, and analyzed using conventional content analysis to generate themes. The second objective will be achieved by undertaking a population-based survey of primary care physicians in Alberta. The questionnaire will be developed based on the findings from the qualitative interviews and pilot tested for face and content validity. Physicians will be provided multiple options to complete the questionnaire including mail, fax, and online methods. Descriptive statistics and associations between demographic factors and barriers and facilitators to care will be analyzed using regression models. Limitations: A potential limitation of this mixed methods study is its cross-sectional nature. Conclusions: This work will inform development of clinical resources and tools for care of older adults with stage 5 CKD, to address barriers and enable facilitators to community-based conservative care.

Background: Many arteriovenous fistula (AVF) fail prior to use due to lack of maturation or thrombosis. Determining vascular function prior to surgery may be helpful to predict subsequent AVF success. This is a feasibility study to describe the vascular function in a cohort of chronic kidney disease (CKD) patients who are awaiting AVF creation. Methods: A prospective cohort of 28 CKD patients expected to progress to HD underwent arterial stiffness (pulse wave velocity, PWV) and endothelial function testing (flow mediated dilation FMD, and peripheral arterial tonometry, PAT) one week prior to AVF creation. AVF success was defined as maintaining patency and achieving maturation. Post operative fistula assessment at 8 weeks evaluated maturation (clinical assessment of adequate fistula flowand ultrasound diameter ≥ 0.5 cm). Results: The median age 72 years (62 – 78), 75% males, eGFR 15 ml/min/1.73 m 2 (12 – 18). 20 (71%) patients had successful AVF surgery with a mature AVF at 8 weeks. Patients with AVF success had higher mean PAT values 1.87 ± 0.52 than those with failed AVF 1.41 ± 0.24 p = 0.03. Conclusions: Microvascular endothelial function as measured using PAT may be useful as a predictor of AVF maturation and function. This simple non invasive marker of vascular function may be a useful tool to predict AVF outcomes.

Background: Lower estimated glomerular filtration rate is associated with reduced life expectancy. Whether this association is modified by the presence or absence of albuminuria, another cardinal finding of chronic kidney disease, is unknown. Objective: Our objective was to estimate the life expectancy of middle-aged men and women with varying levels of eGFR and concomitant albuminuria. Design: A retrospective cohort study. Setting: A large population-based cohort identified from the provincial laboratory registry in Alberta, Canada. Participants: Adults aged ≥30 years who had outpatient measures of serum creatinine and albuminuria between May 1, 2002 and March 31, 2008. Measurements: Predictor : Baseline levels of kidney function identified from serum creatinine and albuminuria measurements. Outcomes : all cause mortality during the follow-up. Methods: Patients were categorized based on their estimated glomerular filtration rate (eGFR) (≥60, 45–59, 30–44, and 15–29 mL/min/1 · 73 m 2 ) as well as albuminuria (normal, mild, and heavy) measured by albumin-to-creatinine ratio or urine dipstick. The abridged life table method was applied to calculate the life expectancies of men and women from age 40 to 80 years across combined eGFR and albuminuria categories. We also categorized participants by severity of kidney disease (low risk, moderately increased risk. high risk, and very high risk) using the combination of eGFR and albuminuria levels. Results: Among men aged 50 years and with eGFR ≥60 mL/min/1.73 m 2 , estimated life expectancy was 24.8 (95% CI: 24.6–25.0), 17.5 (95% CI: 17.1–17.9), and 13.5 (95% CI: 12.6–14.3) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for men with mild and heavy albuminuria was 7.3 (95% CI: 6.9–7.8) and 11.3 (95% CI: 10.5–12.2) years shorter than men with normal proteinuria, respectively. A reduction in life expectancy was associated with an increasing severity of kidney disease; 24.8 years for low risk (95% CI: 24.6–25.0), 19.1 years for moderately increased risk (95% CI: 18.7–19.5), 14.2 years for high risk (95% CI: 13.5–15.0), and 9.6 years for very high risk (95% CI: 8.4–10.8). Among women of similar age and kidney function, estimated life expectancy was 28.9 (95% CI: 28.7–29.1), 19.8 (95% CI: 19.2–20.3), and 14.8 (95% CI: 13.5–16.0) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for women with mild and heavy albuminuria was 9.1 (95% CI: 8.5–9.7) and 14.2 (95% CI: 12.9–15.4) years shorter than the women with normal proteinuria, respectively. For women also a graded reduction in life expectancy was observed across the increasing severity of kidney disease; 28.9 years for low risk (95% CI: 28.7–29.1), 22.5 years for moderately increased risk (95% CI: 22.0–22.9), 16.5 years for high risk (95% CI: 15.4–17.5), and 9.2 years for very high risk (95% CI: 7.8–10.7). Limitations: Possible misclassification of long-term kidney function categories cannot be eliminated. Possibility of confounding due to concomitant comorbidities cannot be ruled out. Conclusion: The presence and degree of albuminuria was associated with lower estimated life expectancy for both gender and was especially notable in those with eGFR ≥30 mL/min/1.73 m 2 . Life expectancy associated with a given level of eGFR differs substantially based on the presence and severity of albuminuria.

Background: Patients with proliferative lupus nephritis are at risk of frequent relapses. Whether low- dose prednisone prevents relapses is uncertain. Objectives: We undertook a pilot RCT to determine the feasibility of a larger trial. Design: Pilot randomized controlled trial. Setting: Single center Canadian outpatient nephrology clinic. Patients: Participants with systemic lupus erythematosus (SLE) and a history of class III or IV lupus nephritis that achieved at least partial remission and remained on prednisone were eligible. Measurements: Feasibility: proportion of eligible patients randomized and adherence to tapering regimen. Clinical: occurrence of renal or major non-renal flare of SLE. Methods: We conducted a blinded, two-parallel-group randomized controlled trial of prednisone 7.5 mg/day (continuation) compared to a matching placebo (withdrawal). Results: Of nineteen eligible patients screened, 15 (79%) were recruited and randomized; 8 to prednisone continuation and seven to withdrawal. All participants adhered to the tapering protocol to their assigned withdrawal or low-dose maintenance target. Over 36 months, the primary outcome occurred in four (50%) patients in the continuation group (three renal and one major non-renal flare), compared with one patient (14%) in the withdrawal group (one renal flare). Three participants (38%) in the continuation group had minor flares, while no patients in the withdrawal group did. Limitations: This pilot RCT was small and not designed to assess the efficacy or safety of maintenance with low-dose prednisone. Conclusions: The high proportion of eligible patients recruited, and success of protocol adherence suggest a large trial of prednisone maintenance therapy compared to withdrawal is feasible. Trial registration: Current Controlled Trials ISRCTN31327267.

Patients with chronic kidney disease (CKD) do not always receive care consistent with guidelines, in part due to complexities in CKD management, lack of randomized trial data to inform care, and a failure to disseminate best practice. At a 2007 conference of key Canadian stakeholders in kidney disease, attendees noted that the impact of Canadian Society of Nephrology (CSN) guidelines was attenuated given limited formal linkages between the CSN Clinical Practice Guidelines Group, kidney researchers, decision makers and knowledge users, and that further knowledge was required to guide care in patients with kidney disease. The idea for the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) developed from this meeting. CANN-NET is a pan-Canadian network established in partnership with CSN, the Kidney Foundation of Canada and other professional societies to improve the care and outcomes of patients with and at risk for kidney disease. The initial priority areas for knowledge translation include improving optimal timing of dialysis initiation, and increasing the appropriate use of home dialysis. Given the urgent need for new knowledge, CANN-NET has also brought together a national group of experienced Canadian researchers to address knowledge gaps by encouraging and supporting multicentre randomized trials in priority areas, including management of cardiovascular disease in patients with kidney failure.

Background: Quality of life of patients receiving dialysis has been rated as poor. Objective: To synthesize the views of Canadian patients on or nearing dialysis, and those who care for them. Design: Secondary analysis of a survey, distributed through dialysis centres, social media and the Kidney Foundation of Canada. Setting: Pan-Canadian convenience sample. Participants: Patients, their caregivers and health-care providers. Measurements: Text responses to open-ended questions on topics relevant to end-stage renal disease. Methods: Statements related to needs, beliefs or feelings were identified, and were analysed by thematic content analysis. Results: A total of 544 relevant statements from 189 respondents were included for the thematic content analysis. Four descriptive themes were identified through the content analysis: gaining knowledge, maintaining quality of life, sustaining psychosocial wellbeing and ensuring appropriate care. Respondents primarily identified a need for more information, better communication, increased psychosocial and financial support for patients and their families and a strong desire to maintain their previous lifestyle. Limitations: Convenience sample; questions were originally asked with a different intent (to identify patient-important research issues). Conclusions: Patients on or nearing dialysis and their caregivers identified four major themes, gaining knowledge, maintaining quality of life, sustaining psychosocial wellbeing and ensuring appropriate care, several of which could be addressed by the health care system without requiring significant resources. These include the development of patient materials and resources, or sharing of existing resources across Canadian renal programs, along with adopting better communication strategies. Other concerns, such as the need for increased psychosocial and financial support, require consideration by health care funders.

BackgroundPrescription drugs are used in people with hypertension, diabetes, and cardiovascular disease to manage their illness. Patient cost sharing strategies such as copayments and deductibles are often employed to lower expenditures for prescription drug insurance plans, but the impact on health outcomes in these patients is unclear.ObjectiveTo determine the association between drug insurance and patient cost sharing strategies on medication adherence, clinical and economic outcomes in those with chronic diseases (defined herein as diabetes, hypertension, hypercholesterolemia, coronary artery disease, and cerebrovascular disease).MethodsStudies were included if they examined various cost sharing strategies including copayments, coinsurance, fixed copayments, deductibles and maximum out-of-pocket expenditures. Value-based insurance design and reference based pricing studies were excluded. Two reviewers independently identified original intervention studies (randomized controlled trials, interrupted time series, and controlled before-after designs). MEDLINE, EMBASE, Cochrane Library, CINAHL, and relevant reference lists were searched until March 2013. Two reviewers independently assessed studies for inclusion, quality, and extracted data. Eleven studies, assessing the impact of seven policy changes, were included: 2 separate reports of one randomized controlled trial, 4 interrupted time series, and 5 controlled before-after studies.FindingsOutcomes included medication adherence, clinical events (myocardial infarction, stroke, death), quality of life, healthcare utilization, or cost. The heterogeneity among the studies precluded meta-analysis. Few studies reported the impact of cost sharing strategies on mortality, clinical and economic outcomes. The association between patient copayments and medication adherence varied across studies, ranging from no difference to significantly lower adherence, depending on the amount of the copayment.ConclusionLowering cost sharing in patients with chronic diseases may improve adherence, but the impact on clinical and economic outcomes is uncertain.

BACKGROUND: Anti-angiogenic therapy targeted at vascular endothelial growth factor (VEGF) is now used to treat several types of cancer. We did a systematic review of randomized controlled trials (RCTs) to summarize the adverse effects of vascular endothelial growth factor inhibitors (VEGFi), focusing on those with vascular pathogenesis. METHODS AND FINDINGS: We searched MEDLINE, EMBASE and Cochrane Library until April 19, 2012 to identify parallel RCTs comparing a VEGFi with a control among adults with any cancer. We pooled the risk of mortality, vascular events (myocardial infarction, stroke, heart failure, and thromboembolism), hypertension and new proteinuria using random-effects models and calculated unadjusted relative risk (RR). We also did meta-regression and assessed publication bias. We retrieved 83 comparisons from 72 studies (n = 38,078) on 11 different VEGFi from 7901 identified citations. The risk of mortality was significantly lower among VEGFi recipients than controls (pooled RR 0.96, 95% confidence interval [CI] 0.94 to 0.98, I2 = 0%, tau2 = 0; risk difference 2%). Compared to controls, VEGFi recipients had significantly higher risk of myocardial infarction (MI) (RR 3.54, 95% CI 1.61 to 7.80, I2 = 0%, tau2 = 0), arterial thrombotic events (RR 1.80, 95% CI 1.24 to 2.59, I2 = 0%, tau2 = 0); hypertension (RR 3.46, 95% CI 2.89 to 4.15, I2 = 58%, tau2 = 0.16), and new proteinuria (RR 2.51, 95% CI 1.60 to 3.94, I2 = 87%, tau2 = 0.65). The absolute risk difference was 0.8% for MI, 1% for arterial thrombotic events, 15% for hypertension and 12% for new proteinuria. Meta-regression did not suggest any statistically significant modifiers of the association between VEGFi treatment and any of the vascular events. Limitations include heterogeneity across the trials. CONCLUSIONS: VEGFi increases the risk of MI, hypertension, arterial thromboembolism and proteinuria. The absolute magnitude of the excess risk appears clinically relevant, as the number needed to harm ranges from 7 to 125. These adverse events must be weighed against the lower mortality associated with VEGFi treatment.

OBJECTIVE: To assess the potential impact on the risk of life-threatening asthma of current recommendations in pharmacotherapy, which emphasize the early use of steroids and the avoidance of beta-agonist overuse.

OBJECTIVE: To compare the prevalence ol exercise induced bronchial hyperresponsiveness in Inuit children with that or children in Montreal, and to identify possible genetic and environmental determinants of the differences observed.