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Competing Interests: Intérêts concurrents: Guylène Thériault a reçu des honoraires pour des présentations dans le cadre des campagnes Choisir avec soin et Pour une pratique éclairée sur des thématiques liées aux recommandations du Groupe d’étude canadien sur les soins de santé préventifs (Groupe d’étude) et sur le surdiagnostic ou la surutilisation des ressources. La Dre Thériault déclare également avoir reçu un soutien du Groupe d’étude pour assister à un congrès sur la prévention du surdiagnostic et d’autres réunions, et de la part de la campagne Choisir avec soin pour assister à sa conférence annuelle. La Dre Thériault fait partie du conseil d’administration de Choisir avec soin Québec. Laure Tessier et Heather Limburg signalent être à l’emploi à temps complet de l’Agence de la santé publique du Canada, qui finance le Groupe d’étude (le financement ne dépend aucunement du contenu de la logne directrice et le Groupe d’étude ne tient pas compte de la position de l’organisme subventionnaire pour formuler ses recommandations). Aucun autre membre du groupe de travail ou du Groupe d’étude n’a déclaré d’intérêts concurrents pertinents.

Background: Fragility fractures are a major health concern for older adults and can result in disability, admission to hospital and long-term care, and reduced quality of life. This Canadian Task Force on Preventive Health Care (task force) guideline provides evidence-based recommendations on screening to prevent fragility fractures in community-dwelling individuals aged 40 years and older who are not currently on preventive pharmacotherapy., Methods: We commissioned systematic reviews on benefits and harms of screening, predictive accuracy of risk assessment tools, patient acceptability and benefits of treatment. We analyzed treatment harms via a rapid overview of reviews. We further examined patient values and preferences via focus groups and engaged stakeholders at key points throughout the project. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence for each outcome and strength of recommendations, and adhered to Appraisal of Guidelines for Research and Evaluation (AGREE), Guidelines International Network and Guidance for Reporting Involvement of Patients and the Public (GRIPP-2) reporting guidance., Recommendations: We recommend "risk assessment-first" screening for prevention of fragility fractures in females aged 65 years and older, with initial application of the Canadian clinical Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD). The FRAX result should be used to facilitate shared decision-making about the possible benefits and harms of preventive pharmacotherapy. After this discussion, if preventive pharmacotherapy is being considered, clinicians should request BMD measurement using dual-energy x-ray absorptiometry (DXA) of the femoral neck, and re-estimate fracture risk by adding the BMD T-score into FRAX (conditional recommendation, low-certainty evidence). We recommend against screening females aged 40-64 years and males aged 40 years and older (strong recommendation, very low-certainty evidence). These recommendations apply to community-dwelling individuals who are not currently on pharmacotherapy to prevent fragility fractures., Interpretation: Risk assessment-first screening for females aged 65 years and older facilitates shared decision-making and allows patients to consider preventive pharmacotherapy within their individual risk context (before BMD). Recommendations against screening males and younger females emphasize the importance of good clinical practice, where clinicians are alert to changes in health that may indicate the patient has experienced or is at higher risk of fragility fracture., Competing Interests: Competing interests: Guylène Thériault reports receiving honoraria from presentations for Choosing Wisely and Practicing Wisely and on themes related to Canadian Task Force on Preventive Health Care (task force) recommendations and overdiagnosis or overuse. Dr. Thériault also reports receiving support from the task force for attending Preventing Overdiagnosis Conference and other meetings, and from Choosing Wisely for attending its annual conference. Dr. Thériault is on the board of Choosing Wisely Quebec. Laure Tessier and Heather Limburg report that they are employed full time by the Public Health Agency of Canada, which funds the task force (compensation does not depend on the content of the manuscript, and the task force does not consider the funding body’s views in developing recommendations). No other working group or task force member declared any relevant interests., (© 2023 CMA Impact Inc. or its licensors.)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have important kidney and cardiovascular benefits in adults with chronic kidney disease. Among adults with diabetes, we characterized the prevalence of chronic kidney disease eligible for SGLT2 inhibitor treatment, based on definitions of eligibility from trials and diabetes guidelines, and assessed the predictors of SGLT2 inhibitor use., Methods: We conducted a cross-sectional study using linked administrative data from Alberta Health in adults with diabetes (2002-2019). Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m 2 with severe or greater proteinuria (trial-based definition); or eGFR less than 60 mL/min/1.73 m 2 or moderate or greater proteinuria regardless of eGFR (diabetes guideline-based definition). Predictors (sociodemographic characteristics, comorbidities and health care utilization) of SGLT2 inhibitor use were identified using logistic regression., Results: Of 446 315 adults with diabetes, 76 630 (17.2%, guideline-based definition; 12 867 [2.9%], trial-based definition) had chronic kidney disease eligible for SGLT2 inhibitor treatment. A total of 7.1% used SGLT2 inhibitors. Older age, lower hemoglobin A 1c (HbA 1c ) levels, female sex, lower neighbourhood income, rural residence and hospital admission were among variables associated with nonuse of SGLT2 inhibitors (adjusted odds ratios [ORs] from 0.13 [age ≥ 85 yr] to 0.92 [rural residence], p < 0.05). Family physician visits were associated with higher SGLT2 inhibitor use (adjusted OR 4.01, p < 0.001 for > 4 visits/yr). Considering all adults, both with and without diabetes, 162 012 individuals with chronic kidney disease (5% of all Alberta adults) may benefit from treatment with SGLT2 inhibitors., Interpretation: Many adults with chronic kidney disease would derive heart and kidney benefits from treatment with SGLT2 inhibitors but had low SGLT2 inhibitor use as of 2019. Efforts will be needed to address lower use of SGLT2 inhibitors among female, older and lower-income adults, and to enhance primary care and promote awareness of the benefits of SGLT2 inhibitors independent of glycemic control., Competing Interests: Competing interests: Roseanne Yeung has previously received funding from the Novo Nordisk Alberta Diabetes Fund, a research grant administered by the University Hospital Foundation and Alberta Economic Development and Trade. Nairne Scott-Douglas has previously received research funding from Amgen and Bristol Myers Squibb. He has also received speaking honoraria and consulting fees from Amgen, Alexion, AstraZeneca, Janssen Pharmaceuticals, Novartis and Otsuka Pharmaceutical. Scott Klarenbach is co–scientific director of the Kidney Health Section of the Medicine Strategic Clinical Network, Alberta Health Services. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Data on the outcomes of noninfluenza respiratory virus (NIRV) infections among hospitalized adults are lacking. We aimed to study the burden, severity and outcomes of NIRV infections in this population., Methods: We analyzed pooled patient data from 2 hospital-based respiratory virus surveillance cohorts in 2 regions of Canada during 3 consecutive seasons (2015/16, 2016/17, 2017/18; n = 2119). We included patients aged ≥ 18 years who developed influenza-like illness or pneumonia and were hospitalized for management. We included patients confirmed positive for ≥ 1 virus by multiplex polymerase chain reaction assays (respiratory syncytial virus [RSV], human rhinovirus/enterovirus (hRV), human coronavirus (hCoV), metapneumovirus, parainfluenza virus, adenovirus, influenza viruses). We compared patient characteristics, clinical severity conventional outcomes (e.g., hospital length-of stay, 30-day mortality) and ordinal outcomes (5 levels: discharged, receiving convalescent care, acute ward or intensive care unit [ICU] care and death) for patients with NIRV infections and those with influenza., Results: Among 2119 adults who were admitted to hospital, 1156 patients (54.6%) had NIRV infections (hRV 14.9%, RSV 12.9%, hCoV 8.2%) and 963 patients (45.4%) had influenza ( n = 963). Patients with NIRVs were younger (mean 66.4 [standard deviation 20.4] yr), and more commonly had immunocompromising conditions (30.3%) and delay in diagnosis (median 4.0 [interquartile range (IQR) 2.0-7.0] days). Overall, 14.6% (12.4%-19.5%) of NIRV infections were acquired in hospital. Admission to ICU (18.2%, median 6.0 [IQR 3.0-13.0] d), hospital length-of-stay (median 5.0 [IQR 2.0-10.0] d) and 30-day mortality (8.4%; RSV 9.5%, hRV 6.6%, hCoV 9.2%) and the ordinal outcomes were similar for patients with NIRV infection and those with influenza. Age > 60 years, immunocompromised state and hospital-acquired viral infection were associated with worse outcomes. The estimated median cost per acute care admission was $6000 (IQR $2000-$16 000)., Interpretation: The burden of NIRV infection is substantial in adults admitted to hospital and associated outcomes may be as severe as for influenza, suggesting a need to prioritize therapeutics and vaccines for at-risk people., Competing Interests: Competing interests: Nelson Lee declares honoraria for consultancy work, speaking in educational programs or travel support from Shionogi, Gilead Sciences Canada, Janssen Pharmaceuticals, Sanofi-Pasteur, F. Hoffmann-La Roche, Genentech, CIDARA Therapeutics, outside the submitted work. Scott Klarenbach is supported by the Kidney Health Research Chair, and the Division of Nephrology at the University of Alberta, outside the submitted work., (© 2021 Joule Inc. or its licensors.)

Competing Interests: Intérêts concurrents: Harminder Singh a déclaré être gastroentérologue et effectuer des endoscopies dans le cadre de sa pratique clinique. Le Dr Singh signale aussi avoir reçu des honoraires personnels de Takeda Canada, Pendopharm et Amgen, à l’extérieur des travaux soumis. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Competing interests: Harminder Singh declared that he is a gastroenterologist and performs endoscopy as part of his clinical practice. Dr. Singh also reports receiving personal fees from Takeda Canada, Pendopharm and Amgen, outside the submitted work. No other competing interests were declared.

Background: Health care payers are interested in policy-level interventions to increase peritoneal dialysis use in end-stage renal disease. We examined whether increases in physician remuneration for peritoneal dialysis were associated with greater peritoneal dialysis use., Methods: We studied a cohort of patients in Alberta who started long-term dialysis with at least 90 days of preceding nephrologist care between Jan. 1, 2001, and Dec. 31, 2014. We compared peritoneal dialysis use 90 days after dialysis initiation in patients cared for by fee-for-service nephrologists and those cared for by salaried nephrologists before and after weekly peritoneal dialysis remuneration increased from $0 to $32 (fee change 1, Apr. 1, 2002), $49 to $71 (fee change 2, Apr. 1, 2007), and $71 to $135 (fee change 3, Apr. 1, 2009). Remuneration for peritoneal dialysis remained less than hemodialysis until fee change 3. We performed a patient-level differences-in-differences logistic regression, adjusted for demographic characteristics and comorbidities, as well as an unadjusted interrupted time-series analysis of monthly outcome data., Results: Our cohort included 4262 patients. There was no statistical evidence of a difference in the adjusted differences-indifferences estimator following fee change 1 (0.89, 95% confidence interval [CI] 0.44-1.81), 2 (1.15, 95% CI 0.73-1.83), or 3 (1.52, 95% CI 0.96-2.40). There was no significant difference in the immediate change or the trend over time in peritoneal dialysis use between fee-for-service and salaried groups following any of the fee changes in the interrupted time-series analysis., Interpretation: We identified no statistical evidence of an increase in peritoneal dialysis use following increased fee-for-service remuneration for peritoneal dialysis. It remains unclear what role, if any, physician payment plays in selection of dialysis modality., Competing Interests: Competing interests: Braden Manns held an unrestricted grant from Baxter from 2014 to 2017, outside the submitted work. No other competing interests were declared., (Copyright 2020, Joule Inc. or its licensors.)

Competing Interests: Competing interests: Loreen Gilmour is an employee of Alberta Health Services (AHS). Neesh Pannu and Scott Klarenback are remunerated through a contract with AHS. No other competing interests were declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy., Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer-Lemeshow goodness-of-fit test and Net Reclassification Improvement index., Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00-4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15-2.40), diabetes mellitus (1.61, 1.12-2.31), baseline estimated glomerular filtration rate (0.96, 0.95-0.97), increasing hemoglobin concentration (0.85, 0.77-0.93), proteinuria (1.65, 1.07-2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64-2.43), other cardiac procedure (v. CABG only, 3.11, 2.12-4.58) and emergent status for surgery booking (4.63, 2.61-8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79-0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score)., Interpretation: We have developed and validated a practical and accurate risk prediction model for acute kidney injury requiring renal replacement therapy after cardiac surgery based on routinely available preoperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk., (© 2016 Canadian Medical Association or its licensors.)

Background: Bariatric surgery in Canada is primarily delivered within publicly funded specialty clinics. Previous studies have demonstrated that bariatric surgery is superior to intensive medical management for reduction of weight and obesity-related comorbidities. Our objective was to compare the effectiveness and safety of laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (LSG) and adjustable gastric banding (LAGB) in a publicly funded, population-based bariatric treatment program., Methods: We followed consecutive bariatric surgery patients for 2 years. The primary outcome was weight change (in kilograms). Between-group changes were analyzed using multivariable regression. Last-observation-carried-forward imputation was used for missing data., Results: We included 150 consecutive patients (51 RYGB; 51 LSG; 48 LAGB) in our study. At baseline, mean age was 43.5 ± 9.5 years, 87.3% of patients were women, and preoperative body mass index (BMI) was 46.2 ± 7.4. Absolute and relative (% of baseline) weight loss at 2 years were 36.6 ± 19.5 kg (26.1 ± 12.2%) for RYGB, 21.4 ± 16.0 kg (16.4 ± 11.6%) for LSG and 7.0 ± 9.7 kg (5.8 ± 7.9%) for LAGB (p < 0.001). Change in BMI was greater for the RYGB (-13.0 ± 6.6) than both the LSG (-7.6 ± 5.7) and the LAGB (-2.6 ± 3.5) groups (p < 0.001). The reduction in diabetes, hypertension and dyslipidemia was greater after RYGB than after LAGB (all p < 0.05). There were no deaths. The anastomotic and staple leakage rate was 1.3%., Conclusion: In a publicly funded, population-based bariatric surgery program, RYGB and LSG demonstrated greater weight loss than the LAGB procedure. Bypass resulted in the greatest reduction in obesity-related comorbidities. All procedures were safe.

Background: Although statins have been shown to reduce the risk of cardiovascular events in patients at low cardiovascular risk, their absolute benefit is small in the short term, which may adversely affect cost-effectiveness. We sought to determine the long-term cost-effectiveness (beyond the duration of clinical trials) of low- and high-potency statins in patients at low cardiovascular risk and to estimate the impact on Canada's publicly funded health care system., Methods: Using Markov modelling, we performed a cost-utility analysis in which we compared low-potency statins (fluvastatin, lovastatin, pravastatin and simvastatin) and high-potency statins (atorvastatin and rosuvastatin) with no statins in a simulated cohort of low-risk patients over a lifetime horizon. Model outcomes included costs (in 2010 Canadian dollars), quality-adjusted life-years (QALYs) gained and the cost per QALY gained., Results: Over a lifetime horizon, the cost of managing a patient at low cardiovascular risk was estimated to be about $10,100 without statins, $15,200 with low-potency statins and $16,400 with high-potency statins. The cost per QALY gained with high-potency statins (v. no statins) was $21 300; the use of low-potency statins was not considered economically attractive. These results were robust to sensitivity analyses, although their use became economically unattractive when the duration of benefit from statin use was assumed to be less than 10 years., Interpretation: Use of high-potency statins in patients at low cardiovascular risk was associated with a cost per QALY gained that was economically attractive by current standards, assuming that the benefit from statin use would continue for at least 10 years. However, the overall expenditure on statins would be substantial, and the ramifications of this practice should be carefully considered by policy-makers.

Background: Statins were initially used to improve cardiovascular outcomes in people with established coronary artery disease, but recently their use has become more common in people at low cardiovascular risk. We did a systematic review of randomized trials to assess the efficacy and harms of statins in these individuals., Methods: We searched MEDLINE and EMBASE (to Jan. 28, 2011), registries of health technology assessments and clinical trials, and reference lists of relevant reviews. We included trials that randomly assigned participants at low cardiovascular risk to receive a statin versus a placebo or no statin. We defined low risk as an observed 10-year risk of less than 20% for cardiovascular-related death or nonfatal myocardial infarction, but we explored other definitions in sensitivity analyses., Results: We identified 29 eligible trials involving a total of 80,711 participants. All-cause mortality was significantly lower among patients receiving a statin than among controls (relative risk [RR] 0.90, 95% confidence interval [CI] 0.84-0.97) for trials with a 10-year risk of cardiovascular disease < 20% [primary analysis] and 0.83, 95% CI 0.73-0.94, for trials with 10-year risk < 10% [sensitivity analysis]). Patients in the statin group were also significantly less likely than controls to have nonfatal myocardial infarction (RR 0.64, 95% CI 0.49-0.84) and nonfatal stroke (RR 0.81, 95% CI 0.68-0.96). Neither metaregression nor stratified analyses suggested statistically significant differences in efficacy between high-and low-potency statins, or larger reductions in cholesterol., Interpretation: Statins were found to be efficacious in preventing death and cardiovascular morbidity in people at low cardiovascular risk. Reductions in relative risk were similar to those seen in patients with a history of coronary artery disease.

Background: Metformin is widely accepted as first-line pharmacotherapy for patients with type 2 diabetes mellitus when glycemic control cannot be achieved by lifestyle interventions alone. However, uncertainty exists regarding the optimal second-line therapy for patients whose diabetes is inadequately controlled by metformin monotherapy. Increased use of newer, more costly agents, along with the rising incidence of type 2 diabetes, carries significant budgetary implications for health care systems. We conducted this analysis to determine the relative costs, benefits and cost-effectiveness of options for second-line treatment of type 2 diabetes., Methods: We used the United Kingdom Prospective Diabetes Study Outcomes Model to forecast diabetes-related complications, quality-adjusted life-years and costs of alternative second-line therapies available in Canada for adults with type 2 diabetes inadequately controlled by metformin. We obtained clinical data from a systematic review and mixed treatment comparison meta-analysis, and we obtained information on costs and utilities from published sources. We performed extensive sensitivity analyses to test the robustness of results to variation in inputs and assumptions., Results: Sulphonylureas, when added to metformin, were associated with the most favourable cost-effectiveness estimate, with an incremental cost of $12 757 per quality-adjusted life-year gained, relative to continued metformin monotherapy. Treatment with other agents, including thiazolidinediones and dipeptidyl peptidase-4 inhibitors, had unfavourable cost-effectiveness estimates compared with sulphonylureas. These results were robust to extensive sensitivity analyses., Interpretation: For most patients with type 2 diabetes that is inadequately controlled with metformin monotherapy, the addition of a sulphonylurea represents the most cost-effective second-line therapy.

Background: The risks associated with using an angiotensin-converting-enzyme (ACE) inhibitor and an angiotensin-receptor blocker together are unclear. This study was designed to determine the safety of combination therapy with these two drugs in clinical practice., Methods: We conducted a population-based longitudinal analysis using linked administrative and laboratory data for elderly patients who were new users of an ACE inhibitor, an angiotensin-receptor blocker or a combination of both medications between May 1, 2002, and Dec. 31, 2006. We compared outcomes in patients given combination therapy versus patients given monotherapy using Cox proportional hazards analyses with adjustment for baseline characteristics., Results: Of the 32,312 new users of either medication (mean age 76.1 years, median creatinine level 92 μmol/L), 1750 (5.4%) received combination therapy. However, 1512 (86.4%) of the patients who were given combination therapy did not have trial-established indications such as heart failure or proteinuria. Renal dysfunction was more common among patients given combination therapy (5.2 [95% confidence interval (CI) 3.4 to 7.9] events per 1000 patients per month) than among patients given monotherapy (2.4 [95% CI 2.2 to 2.7] events per 1000 patients per month) (adjusted hazard ratio [HR] 2.36, 95% CI 1.51 to 3.71). Hyperkalemia was also more common among patients given combination therapy (2.5 [95% CI 1.4 to 4.3] events per 1000 patients per month) than among patients given monotherapy (0.9 [95% CI 0.8 to 1.0] events per 1000 patients per month) (adjusted HR 2.42, 95% CI 1.36 to 4.32). Most patients took combination therapy for only a short time (median three months before at least one agent was stopped)., Interpretation: Combination therapy was frequently prescribed for patients without established indications and was associated with an increased risk of adverse renal outcomes when compared with monotherapy. These results mirrored data from randomized controlled trials.

Background: The benefits of self-monitoring blood glucose levels are unclear in patients with type 2 diabetes mellitus who do not use insulin, but there are considerable costs. We sought to determine the cost effectiveness of self-monitoring for patients with type 2 diabetes not using insulin., Methods: We performed an incremental cost-effectiveness analysis of the self-monitoring of blood glucose in adults with type 2 diabetes not taking insulin. We used the United Kingdom Prospective Diabetes Study (UKPDS) model to forecast diabetes-related complications, corresponding quality-adjusted life years and costs. Clinical data were obtained from a systematic review comparing self-monitoring with no self-monitoring. Costs and utility decrements were derived from published sources. We performed sensitivity analyses to examine the robustness of the results., Results: Based on a clinically modest reduction in hemoglobin A(1C) of 0.25% (95% confidence interval 0.15-0.36) estimated from the systematic review, the UKPDS model predicted that self-monitoring performed 7 or more times per week reduced the lifetime incidence of diabetes-related complications compared with no self-monitoring, albeit at a higher cost (incremental cost per quality-adjusted life year $113,643). The results were largely unchanged in the sensitivity analysis, although the incremental cost per quality-adjusted life year fell within widely cited cost-effectiveness thresholds when testing frequency or the price per test strip was substantially reduced from the current levels., Interpretation: For most patients with type 2 diabetes not using insulin, use of blood glucose test strips for frequent self-monitoring (>or= 7 times per week) is unlikely to represent efficient use of finite health care resources, although periodic testing (e.g., 1 or 2 times per week) may be cost-effective. Reduced test strip price would likely also improve cost-effectiveness.

Background: Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy., Methods: We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment. We included RCTs involving anemic adults with cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and assessed clinical outcomes (all-cause mortality, cardiovascular events and hypertension, health-related quality of life, blood transfusions and tumour response) and harms (serious adverse events) between groups., Results: We identified 52 trials (n = 12 006) that met our selection criteria. The pooled all-cause mortality during treatment was significantly higher in the group receiving erythropoiesis-stimulating therapy than in the control group (relative risk [RR] 1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use of erythropoiesis-stimulating agents led to clinically detectable improvements in disease-specific measures of quality of life. It also reduced the use of blood transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events (RR 1.16, 95% CI 1.08 to 1.25)., Interpretation: Use of erythropoiesis-stimulating agents in patients with cancer-related anemia improved some disease-specific measures of quality of life and decreased the use of blood transfusions. However, it increased the risk of death and serious adverse events. Our findings suggest that such therapy not be used routinely as an alternative to blood transfusion in patients with anemia related to cancer.

Background: Many Canadian patients who receive hemodialysis live far from their attending nephrologist, which may affect clinical outcomes. We investigated whether patients receiving hemodialysis who live farther from their attending nephrologist are more likely to die than those who live closer., Methods: We studied a random sample of 18,722 patients who began hemodialysis between 1990 and 2000 in Canada. We calculated the distance between each patient's residence location at the start of dialysis and the practice location of their attending nephrologist. We used Cox proportional hazards models to examine the adjusted relation between distance and clinical outcomes (death from all causes, infectious causes and cardiovascular causes) over a follow-up period of up to 14 years., Results: During the follow-up period (median 2.5 yr, interquartile range 1.0-4.7 yr), 11,582 (62%) patients died. Compared with patients who lived within 50 km of their nephrologist, the adjusted hazard ratio of death among those who lived 50.1-150 km away was 1.06 (95% confidence interval [CI] 1.01-1.12), 1.13 (95% CI 1.04-1.22) for those who lived 150.1-300 km away and 1.13 (95% CI 1.03-1.24) for those who lived more than 300 km from their nephrologist (p for trend < 0.001). The risk of death from infectious causes increased with greater distance from the attending nephrologist (p for trend < 0.001). The risk of death from cardiovascular causes did not increase with distance from the attending nephrologist (p for trend = 0.21). Compared with patients who lived within 50 km of their nephrologist, the adjusted hazard ratio of death among those who lived more than 300 km away was 1.75 (95% CI 1.32-2.32) for infectious causes and 0.93 (95% CI 0.79-1.09) for cardiovascular causes., Conclusions: Mortality associated with hemodialysis was greater among patients who lived farther from their attending nephrologist, as compared with those who lived closer. This was especially evident for death from infectious causes.

Background: In a universal, public health care system, access to kidney transplantation should not be influenced by residence location. We determined the likelihood of kidney transplantation from deceased donors among Canadian dialysis patients living in 7 geographic regions. Within each region we also determined whether distance from the closest transplant centre was associated with the likelihood of transplantation., Methods: A random sample of 7034 subjects initiating dialysis in Canada between 1996 and 2000 was studied. We used Cox proportional hazards models to examine the relation between residence location and the likelihood of kidney transplantation from deceased donors over a median period of 2.4 years., Results: There were significant differences in the likelihood of kidney transplantation from deceased donors and predicted waiting times between the different geographic regions. For example, the adjusted relative likelihood of transplantation in Alberta was 3.74 (95% confidence interval [CI] 2.95-4.76) compared with the likelihood in Ontario (p < 0.001). These differences persisted after further adjustment for differences in the rate of deceased organ donation. Within regions, patients who resided 50.1-150 km, 150.1-300 km and more than 300 km from the closest transplant centre had a similar adjusted likelihood of receiving a kidney transplant as those who lived less than 50 km away., Interpretation: The adjusted likelihood of undergoing a kidney transplant from a deceased donor varied substantially between geographic regions in Canada. In contrast, the likelihood of transplantation within regions was not affected by distance from the closest transplant centre.