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1.  Comparison of Concurrent Complications of CKD by 2 Risk Categorization Systems 
Background
Using both estimated glomerular filtration rate (eGFR) and proteinuria to classify the severity of chronic kidney disease (CKD) has been proposed. The utility of a staging system incorporating both eGFR and proteinuria for guiding evaluation of concurrent CKD complications is not known.
Study design
Cross-sectional analysis
Setting & participants
30,528 participants in the US National Health and Nutrition Examination Survey conducted in 1988–1994 and 1999–2006 (n=8,242 for hyperparathyroidism).
Predictors
Classification system that uses both eGFR and proteinuria (alternative) and a system that primarily uses eGFR (NKF-KDOQI; the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative)
Outcomes
Prevalence of anemia, acidosis, hyperphosphatemia, hypoalbuminemia, hyperparathyroidism and hypertension
Measurements
GFR estimated from the CKD-Epidemiology Collaboration (CKD-EPI) equation and proteinuria assessed using urine albumin-creatinine ratio (ACR)
Results
The prevalence of hypoalbuminemia, hypertension and hyperparathyroidism increased with more severe CKD using the NKF-KDOQI system. For example, the prevalence of hyperparathyroidism was 9.1%, 11.1%, 28.2% and 72.5% for Stages 1, 2, 3 and 4, respectively. Similarly the prevalence of anemia, acidosis and hyperphosphatemia increased progressively from Stage 2 through 4. With the alternative system, the prevalence of anemia, hyperphosphatemia, hypertension and hyperparathyroidism was lower in Stage 3 compared to Stage 2. For example, the prevalence of hyperparathyroidism was 13.5%, 40.3%, 22.2%, and 63.4% for stages 1, 2, 3 and 4, respectively. Applying the alternative system, participants without each complication were more likely to be appropriately reclassified to lower stages (for example, overall net reclassification index of −6.5% for hyperparathyroidism). However, participants with complications (except for hypoalbuminemia) were more likely to be inappropriately reclassified to lower stages.
Limitations
Use of single creatinine to estimate GFR and single measure to assess ACR. Small number of participants with CKD Stage 4.
Conclusions
The NKF-KDOQI system may better identify patients with certain concurrent CKD complications compared to systems using eGFR and proteinuria.
doi:10.1053/j.ajkd.2011.09.021
PMCID: PMC3288542  PMID: 22113126
3.  Incidence and causes of end-stage renal disease among Aboriginal children and young adults 
Background:
Although Aboriginal adults have a higher risk of end-stage renal disease than non-Aboriginal adults, the incidence and causes of end-stage renal disease among Aboriginal children and young adults are not well described.
Methods:
We calculated age- and sex-specific incidences of end-stage renal disease among Aboriginal people less than 22 years of age using data from a national organ failure registry. Incidence rate ratios were used to compare rates between Aboriginal and white Canadians. To contrast causes of end-stage renal disease by ethnicity and age, we calculated the odds of congenital diseases, glomerulonephritis and diabetes for Aboriginal people and compared them with those for white people in the following age strata: 0 to less than 22 years, 22 to less than 40 years, 40 to less than 60 years and older than 60 years.
Results:
Incidence rate ratios of end-stage renal disease for Aboriginal children and young adults (age < 22 yr, v. white people) were 1.82 (95% confidence interval [CI] 1.40–2.38) for boys and 3.24 (95% CI 2.60–4.05) for girls. Compared with white people, congenital diseases were less common among Aboriginal people aged less than 22 years (odds ratio [OR] 0.56, 95% CI 0.36–0.86), and glomerulonephritis was more common (OR 2.18, 95% CI 1.55–3.07). An excess of glomerulonephritis, but not diabetes, was seen among Aboriginal people aged 22 to less than 40 years. The converse was true (higher risk of diabetes, lower risk of glomerulonephritis) among Aboriginal people aged 40 years and older.
Interpretation:
The incidence of end-stage renal disease is higher among Aboriginal children and young adults than among white children and young adults. This higher incidence may be driven by an increased risk of glomerulonephritis in this population.
doi:10.1503/cmaj.120427
PMCID: PMC3470642  PMID: 22927509
4.  Bariatric Surgery: A Systematic Review of the Clinical and Economic Evidence 
Journal of General Internal Medicine  2011;26(10):1183-1194.
CONTEXT
Use of bariatric surgery for severe obesity has increased dramatically.
OBJECTIVE
To systematically review 1. the clinical efficacy and safety, 2. cost-effectiveness of bariatric surgery, and 3. the association between number of surgeries performed (surgical volume) and outcomes.
DATA SOURCES
MEDLINE (from 1950), EMBASE (from 1980), CENTRAL, EconLit, EURON EED, Harvard Center for Risk Analysis, trial registries and HTA websites were searched to January 2011.
STUDY SELECTION
1. Randomized controlled trials (RCTs) and 2. cost-utility and cost-minimisation studies comparing a contemporary bariatric surgery (i.e., adjustable gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy) to another contemporary surgical comparator or a non-surgical treatment or 3. Any study reporting the association between surgical volume and outcome.
DATA EXTRACTION
Outcomes included changes in weight and obesity-related comorbidity, quality of life and mortality, surgical complications, resource utilization, and incremental cost-utility.
RESULTS
RCT data evaluating mortality and obesity-related comorbidity endpoints were lacking. A small RCT of 16 patients reported that adjustable gastric banding reduced weight by 27% (p < 0.01) compared to diet-treated controls over 40 weeks. Six small RCTs reported comparisons of commonly used, contemporary procedures. Gastric banding reduced weight to a lower extent than gastric bypass and sleeve gastrectomy and resulted in shorter operating times, fewer serious complications, lower weight loss efficacy, and more frequent reoperations compared to gastric bypass. Sleeve gastrectomy and gastric bypass reduced weight to a similar extent. A 2-year RCT in 50 adolescents reported that gastric banding substantially reduced weight compared to lifestyle modification (35 kg vs. 3 kg; p <0.001). Based on findings of 14 observational studies, higher volume centers and surgeons had lower mortality and complication rates. Surgery resulted in long-term incremental cost–utility ratios of $ <1.000–$40,000 (2009 USD) per quality-adjusted-life-year compared with non-surgical treatment.
CONCLUSIONS
Contemporary bariatric surgery appears to result in sustained weight reduction with acceptable costs but rigorous, longer-term (≥5 year) data are needed and a paucity of RCT data on mortality and obesity related comorbidity is evident. Procedure-specific variations in efficacy and risks exist and require further study to clarify the specific indications for and advantages of different procedures.
doi:10.1007/s11606-011-1721-x
PMCID: PMC3181300  PMID: 21538168
randomized controlled trials; clincical evidence; economic evidence; systematic review
5.  Evaluating the impact of a novel restricted reimbursement policy for quinolone antibiotics: A time series analysis 
Background
Publicly-funded drug plans often use prior authorization policies to limit drug prescribing. To guide physician prescribing of a class of antibiotics with broad antimicrobial activity (quinolone antibiotics) in accordance with new prescribing guidelines, Alberta’s provincial health ministry implemented a new mechanism for formulary restriction entitled the optional special authorization (OSA) program. We conducted an observational study to determine the impact of this new formulary restriction policy on antimicrobial prescription rates as well as any clinical consequences.
Methods
Quinolone antibiotic use, and adherence with quinolone prescribing guidelines, was assessed before and after implementation of the OSA program in patients with common outpatient infections using an administrative data cohort and a chart review cohort, respectively. At the same time this policy was implemented to limit quinolone prescribing, two new quinolone antibiotics were added to the formulary. Using administrative data, we analysed a total of 397,534 unique index visits with regard to overall antibiotic utilization, and through chart review, we analysed 1681 charts of patients with infections of interest to determine the indications for quinolone usage.
Results
Using segmented regression models adjusting for age, sex and physician enrollment in the OSA program, there was no statistically significant change in the monthly rate of all quinolone use (−3.5 (95% CI −5.5, 1.4) prescriptions per 1000 index visits) following implementation of the OSA program (p = 0.74). There was a significant level change in the rate of quinolone antibiotic use for urinary tract infection (−33.6 (95% CI: -23.8, -43.4) prescriptions and upper respiratory tract infection (−16.1 (95%CI: -11.6, -20.6) prescriptions per 1000 index visits. Among quinolone prescriptions identified on chart review, 42.5% and 58.5% were consistent with formulary guidelines before and after the implementation of the OSA program, respectively (p = 0.002). There was no change in hospitalization, mortality or use of physician services after implementation of the OSA program.
Conclusions
Despite the addition of two new quinolone antibiotics to the formulary, we found that there was no change in the use of quinolones after implementation of a new formulary restriction policy for outpatients with common outpatient infections.
doi:10.1186/1472-6963-12-290
PMCID: PMC3470979  PMID: 22935100
Formulary restriction; Antibiotic; Prior authorization; Prescription drugs
7.  Enrolment in primary care networks: impact on outcomes and processes of care for patients with diabetes 
Background:
Primary care networks are a newer model of primary care that focuses on improved access to care and the use of multidisciplinary teams for patients with chronic disease. We sought to determine the association between enrolment in primary care networks and the care and outcomes of patients with diabetes.
Methods:
We used administrative health care data to study the care and outcomes of patients with incident and prevalent diabetes separately. For patients with prevalent diabetes, we compared those whose care was managed by physicians who were or were not in a primary care network using propensity score matching. For patients with incident diabetes, we studied a cohort before and after primary care networks were established. Each cohort was further divided based on whether or not patients were cared for by physicians enrolled in a network. Our primary outcome was admissions to hospital or visits to emergency departments for ambulatory care sensitive conditions specific to diabetes.
Results:
Compared with patients whose prevalent diabetes is managed outside of primary care networks, patients in primary care networks had a lower rate of diabetes-specific ambulatory care sensitive conditions (adjusted incidence rate ratio 0.81, 95% confidence interval [CI] 0.75 to 0.87), were more likely to see an ophthalmologist or optometrist (risk ratio 1.19, 95% CI 1.17 to 1.21) and had better glycemic control (adjusted mean difference −0.067, 95% CI −0.081 to −0.052).
Interpretation:
Patients whose diabetes was managed in primary care networks received better care and had better clinical outcomes than patients whose condition was not managed in a network, although the differences were very small.
doi:10.1503/cmaj.110755
PMCID: PMC3273535  PMID: 22143232
10.  A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes 
BMC Medicine  2011;9:123.
Background
The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective.
Methods
We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed.
Results
Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34) compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806). One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively). No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners.
Conclusions
Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are needed to determine the role of hypocaloric sweeteners in a wider population health strategy to prevent, reduce and manage obesity and its consequences.
doi:10.1186/1741-7015-9-123
PMCID: PMC3286380  PMID: 22093544
11.  Cost-effectiveness of the use of low- and high-potency statins in people at low cardiovascular risk 
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.
doi:10.1503/cmaj.101281
PMCID: PMC3216439  PMID: 21989469
12.  Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis 
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.
doi:10.1503/cmaj.101280
PMCID: PMC3216447  PMID: 21989464
13.  Dialysis and transplantation among Aboriginal children with kidney failure 
Background:
Relatively little is known about the management and outcomes of Aboriginal children with renal failure in Canada. We evaluated differences in dialysis modality, time spent on dialysis, rates of kidney transplantation, and patient and allograft survival between Aboriginal children and non-Aboriginal children.
Methods:
For this population-based cohort study, we used data from a national pediatric end-stage renal disease database. Patients less than 18 years old who started renal replacement treatment (dialysis or kidney transplantation) in nine Canadian provinces (Quebec data were not available) and all three territories between 1992 and 2007 were followed until death, loss to follow-up or end of the study period. We compared initial modality of dialysis and time to first kidney transplant between Aboriginal children, white children and children of other ethnicity. We examined the association between ethnicity and likelihood of kidney transplantation using adjusted Cox proportional hazard models for Aboriginal and white children (data for the children of other ethnicity did not meet the assumptions of proportional hazards).
Results:
Among 843 pediatric patients included in the study, 104 (12.3%) were Aboriginal, 521 (61.8%) were white, and 218 (25.9%) were from other ethnic minorities. Hemodialysis was the initial modality of dialysis for 48.0% of the Aboriginal patients, 42.7% of the white patients and 62.6% of those of other ethnicity (p < 0.001). The time from start of dialysis to first kidney transplant was longer among the Aboriginal children (median 1.75 years, interquartile range 0.69–2.81) than among the children in the other two groups (p < 0.001). After adjustment for confounders, Aboriginal children were less likely than white children to receive a transplant from a living donor (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21–0.61) or a transplant from any donor (HR 0.54, 95% CI 0.40–0.74) during the study period.
Interpretation:
The time from start of dialysis to first kidney transplant was longer among Aboriginal children than among white children. Further evaluation is needed to determine barriers to transplantation among Aboriginal children.
doi:10.1503/cmaj.101840
PMCID: PMC3134757  PMID: 21609989
14.  Nocturnal Hypoxia and Loss of Kidney Function 
PLoS ONE  2011;6(4):e19029.
Background
Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown.
Methods
We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year.
Results
858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67).
Conclusion
Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function.
doi:10.1371/journal.pone.0019029
PMCID: PMC3084745  PMID: 21559506
15.  The safety of combining angiotensin-converting-enzyme inhibitors with angiotensin-receptor blockers in elderly patients: a population-based longitudinal analysis 
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.
doi:10.1503/cmaj.101333
PMCID: PMC3071385  PMID: 21422125
16.  Validation of a case definition to define chronic dialysis using outpatient administrative data 
Background
Administrative health care databases offer an efficient and accessible, though as-yet unvalidated, approach to studying outcomes of patients with chronic kidney disease and end-stage renal disease (ESRD). The objective of this study is to determine the validity of outpatient physician billing derived algorithms for defining chronic dialysis compared to a reference standard ESRD registry.
Methods
A cohort of incident dialysis patients (Jan. 1 - Dec. 31, 2008) and prevalent chronic dialysis patients (Jan 1, 2008) was selected from a geographically inclusive ESRD registry and administrative database. Four administrative data definitions were considered: at least 1 outpatient claim, at least 2 outpatient claims, at least 2 outpatient claims at least 90 days apart, and continuous outpatient claims at least 90 days apart with no gap in claims greater than 21 days. Measures of agreement of the four administrative data definitions were compared to a reference standard (ESRD registry). Basic patient characteristics are compared between all 5 patient groups.
Results
1,118,097 individuals formed the overall population and 2,227 chronic dialysis patients were included in the ESRD registry. The three definitions requiring at least 2 outpatient claims resulted in kappa statistics between 0.60-0.80 indicating "substantial" agreement. "At least 1 outpatient claim" resulted in "excellent" agreement with a kappa statistic of 0.81.
Conclusions
Of the four definitions, the simplest (at least 1 outpatient claim) performed comparatively to other definitions. The limitations of this work are the billing codes used are developed in Canada, however, other countries use similar billing practices and thus the codes could easily be mapped to other systems. Our reference standard ESRD registry may not capture all dialysis patients resulting in some misclassification. The registry is linked to on-going care so this is likely to be minimal. The definition utilized will vary with the research objective.
doi:10.1186/1471-2288-11-25
PMCID: PMC3055853  PMID: 21362182
17.  Design and implementation of the canadian kidney disease cohort study (CKDCS): A prospective observational study of incident hemodialysis patients 
BMC Nephrology  2011;12:10.
Background
Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD).
Methods/Design
The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions.
Preliminary Results
Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice.
Discussion
The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future.
doi:10.1186/1471-2369-12-10
PMCID: PMC3050805  PMID: 21324196
18.  Population based screening for chronic kidney disease: cost effectiveness study 
Objective To determine the cost effectiveness of one-off population based screening for chronic kidney disease based on estimated glomerular filtration rate.
Design Cost utility analysis of screening with estimated glomerular filtration rate alone compared with no screening (with allowance for incidental finding of cases of chronic kidney disease). Analyses were stratified by age, diabetes, and the presence or absence of proteinuria. Scenario and sensitivity analyses, including probabilistic sensitivity analysis, were performed. Costs were estimated in all adults and in subgroups defined by age, diabetes, and hypertension.
Setting Publicly funded Canadian healthcare system.
Participants Large population based laboratory cohort used to estimate mortality rates and incidence of end stage renal disease for patients with chronic kidney disease over a five year follow-up period. Patients had not previously undergone assessment of glomerular filtration rate.
Main outcome measures Lifetime costs, end stage renal disease, quality adjusted life years (QALYs) gained, and incremental cost per QALY gained.
Results Compared with no screening, population based screening for chronic kidney disease was associated with an incremental cost of $C463 (Canadian dollars in 2009; equivalent to about £275, €308, US $382) and a gain of 0.0044 QALYs per patient overall, representing a cost per QALY gained of $C104 900. In a cohort of 100 000 people, screening for chronic kidney disease would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 675 to 657. In subgroups of people with and without diabetes, the cost per QALY gained was $C22 600 and $C572 000, respectively. In a cohort of 100 000 people with diabetes, screening would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 1796 to 1741. In people without diabetes with and without hypertension, the cost per QALY gained was $C334 000 and $C1 411 100, respectively.
Conclusions Population based screening for chronic kidney disease with assessment of estimated glomerular filtration rate is not cost effective overall or in subgroups of people with hypertension or older people. Targeted screening of people with diabetes is associated with a cost per QALY that is similar to that accepted in other interventions funded by public healthcare systems.
doi:10.1136/bmj.c5869
PMCID: PMC2975430  PMID: 21059726
19.  Overview of the Canadian pediatric end-stage renal disease database 
BMC Nephrology  2010;11:21.
Background
Performing clinical research among pediatric end-stage renal disease patients is challenging. Barriers to successful initiation and completion of clinical research projects include small sample sizes and resultant limited statistical power and lack of longitudinal follow-up for hard clinical end-points in most single center studies.
Description
Existing longitudinal organ failure disease registry and administrative health datasets available within a universal access health care system can be used to study outcomes of end-stage renal disease among pediatric patients in Canada. To construct the Canadian Pediatric End-Stage Renal Disease database, registry data were linked to administrative health data through deterministic linkage techniques creating a research database which consists of socio-demographic variables, clinical variables, all-cause hospitalizations, and relevant outcomes (death and renal allograft loss) for this patient population. The research database also allows study of major cardiovascular events using previously validated administrative data definitions.
Conclusion
Organ failure registry linked to health administrative data can be a powerful tool to perform longitudinal studies in pediatric end-stage renal disease patients. The rich clinical and demographic information found in this database will facilitate study of important medical and non-medical risk factors for death, graft loss and cardiovascular disease among pediatric end-stage renal disease patients.
doi:10.1186/1471-2369-11-21
PMCID: PMC2940877  PMID: 20796306
20.  Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis 
BMC Nephrology  2010;11:13.
Background
Left ventricular (LV) hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP) and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis.
Methods
This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month). Agreement was assessed using Lin's concordance correlation coefficient (CCC) and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC).
Results
Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80) predictive power for LV hypertrophy.
Conclusions
A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.
doi:10.1186/1471-2369-11-13
PMCID: PMC2901323  PMID: 20576127
21.  Overview of the Alberta Kidney Disease Network 
BMC Nephrology  2009;10:30.
Background
The Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta.
Description
The laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality.
Conclusion
The unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions.
doi:10.1186/1471-2369-10-30
PMCID: PMC2770500  PMID: 19840369
22.  Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis 
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.
doi:10.1503/cmaj.090470
PMCID: PMC2683210  PMID: 19407261
23.  Trace elements in hemodialysis patients: a systematic review and meta-analysis 
BMC Medicine  2009;7:25.
Background
Hemodialysis patients are at risk for deficiency of essential trace elements and excess of toxic trace elements, both of which can affect health. We conducted a systematic review to summarize existing literature on trace element status in hemodialysis patients.
Methods
All studies which reported relevant data for chronic hemodialysis patients and a healthy control population were eligible, regardless of language or publication status. We included studies which measured at least one of the following elements in whole blood, serum, or plasma: antimony, arsenic, boron, cadmium, chromium, cobalt, copper, fluorine, iodine, lead, manganese, mercury, molybdenum, nickel, selenium, tellurium, thallium, vanadium, and zinc. We calculated differences between hemodialysis patients and controls using the differences in mean trace element level, divided by the pooled standard deviation.
Results
We identified 128 eligible studies. Available data suggested that levels of cadmium, chromium, copper, lead, and vanadium were higher and that levels of selenium, zinc and manganese were lower in hemodialysis patients, compared with controls. Pooled standard mean differences exceeded 0.8 standard deviation units (a large difference) higher than controls for cadmium, chromium, vanadium, and lower than controls for selenium, zinc, and manganese. No studies reported data on antimony, iodine, tellurium, and thallium concentrations.
Conclusion
Average blood levels of biologically important trace elements were substantially different in hemodialysis patients, compared with healthy controls. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation.
doi:10.1186/1741-7015-7-25
PMCID: PMC2698829  PMID: 19454005
25.  Access to health care among status Aboriginal people with chronic kidney disease 
Background
Ethnic disparities in access to health care and health outcomes are well documented. It is unclear whether similar differences exist between Aboriginal and non-Aboriginal people with chronic kidney disease in Canada. We determined whether access to care differed between status Aboriginal people (Aboriginal people registered under the federal Indian Act) and non-Aboriginal people with chronic kidney disease.
Methods
We identified 106 511 non-Aboriginal and 1182 Aboriginal patients with chronic kidney disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m2). We compared outcomes, including hospital admissions, that may have been preventable with appropriate outpatient care (ambulatory-care–sensitive conditions) as well as use of specialist services, including visits to nephrologists and general internists.
Results
Aboriginal people were almost twice as likely as non-Aboriginal people to be admitted to hospital for an ambulatory-care–sensitive condition (rate ratio 1.77, 95% confidence interval [CI] 1.46–2.13). Aboriginal people with severe chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m2) were 43% less likely than non-Aboriginal people with severe chronic kidney disease to visit a nephrologist (hazard ratio 0.57, 95% CI 0.39–0.83). There was no difference in the likelihood of visiting a general internist (hazard ratio 1.00, 95% CI 0.83–1.21).
Interpretation
Increased rates of hospital admissions for ambulatory-care–sensitive conditions and a reduced likelihood of nephrology visits suggest potential inequities in care among status Aboriginal people with chronic kidney disease. The extent to which this may contribute to the higher rate of kidney failure in this population requires further exploration.
doi:10.1503/cmaj.080063
PMCID: PMC2572655  PMID: 18981441

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