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1.  Chronic kidney disease in homeless persons in Mexico 
Kidney International Supplements  2013;3(2):250-253.
Little is known about the prevalence of chronic kidney disease (CKD) among the homeless in Mexico. The role of substance abuse, alcoholism, and homelessness in CKD has not been properly evaluated. We screened 260 homeless individuals in the state of Jalisco, Mexico, for the presence of CKD and its risk factors, and compared their characteristics with those from a separate cohort of poor Jalisco residents and with a survey of the general Mexican population. CKD was more prevalent among the homeless than among the poor Jalisco population (22% vs. 15.8%, P=0.0001); 16.5% had stage 3, 4.3% stage 4, and 1.2% stage 5. All were unaware of having CKD. Only 5.8% knew they had diabetes, but 19% had fasting blood sugar >126 mg/dl; 3.5% knew they were hypertensive but 31% had systolic blood pressure ⩾140 mm Hg or diastolic blood pressure ⩾90 mm Hg. Alcoholism was less common than in the poor Jalisco population (23.5% vs. 32.3%, P=0.002), but tobacco smoking (34.6% vs. 21.5%, P=0.0001) and substance abuse (18% vs. 1.1%, P=0.0001) were more prevalent among the homeless. Likewise, chronic viral infections such as HIV (4.5% vs. 0.3%, P=0.0001) and HCV (7.7% vs. 1.4%, P=0.0001) were also significantly higher among the homeless than in the general population. In conclusion, CKD and its risk factors are highly prevalent among the homeless individuals in Jalisco, Mexico. Lack of awareness of having diabetes and hypertension is highly common, as is substance abuse. Programs aiming to prevent CKD and its risk factors in Mexico should specifically target this high-risk population.
PMCID: PMC4089649  PMID: 25018992
chronic kidney disease; diabetes; homeless; hypertension
2.  A population-based study on care and clinical outcomes in remote dwellers with heavy proteinuria 
Kidney International Supplements  2013;3(2):254-258.
Patients with proteinuria are at high risk of cardiovascular and renal complications. Since this risk can be reduced by appropriate interventions, we hypothesized that remote dwellers, who are known to have lower access to health care, might have a higher risk of complications. Using a database of all adults with at least one measure of urine protein between May 2002 and March 2009, we examined the frequency of heavy proteinuria, quality of care delivery, and rates of adverse clinical outcomes across travel distance categories to the nearest nephrologist. Heavy proteinuria was defined by an albumin:creatinine ratio ⩾60 mg/mmol, protein:creatinine ratio ⩾100 mg/mmol, or protein ⩾2+ on dipstick urinalysis. Of 1,359,330 subjects in the study, 262,209 were remote dwellers. The overall prevalence of proteinuria was 2.3%, 2.9%, and 2.5% in those who live >200, 100.1–200, and 50.1–100 km, respectively, as compared to 1.5% in those who live within 50 km of the nearest nephrologist (P<0.001). Similarly, the prevalence of heavy proteinuria was increased among remote dwellers compared to urban dwellers (P=0.001 for trend). There were no differences in markers of good-quality care or the rate of adverse outcomes (all-cause mortality, heart failure, and renal outcomes) across distance categories. However, the rates of hospitalizations and stroke were significantly higher with increased distance from the nearest nephrologist (P<0.001and 0.02, respectively). In conclusion, heavy proteinuria was common in Alberta residents, especially in remote dwellers. Care seemed similar across distance categories of travel, but with higher risk of hospitalizations and stroke among remote dwellers. Further work is needed to understand the basis for the increased risk of hospitalizations and stroke.
PMCID: PMC4089650  PMID: 25018993
adverse clinical outcomes; population; proteinuria; quality of care; remote dwellers
3.  Multidisciplinary care for poor patients with chronic kidney disease in Mexico 
Kidney International Supplements  2013;3(2):178-183.
Coordinated multidisciplinary care (MDC) could improve management and outcomes of patients with chronic kidney disease (CKD). We opened a nurse-led, MDC CKD clinic in Guadalajara, Mexico. We report the clinic's results between March 2008 and July 2011. The records of 353 patients with CKD stage 3 and 4 were reviewed. Data were collected prospectively. Mean age was 59.1±15.5 years; 54.4% were female and 63.7% were diabetic. We observed significant changes in the quality of care between baseline and follow-up. Compliance with practice guidelines for angiotensin II receptor blockers (ARB) and beta blockers increased from 30.6% to 46.6%, and from 11% to 19%, respectively; for statins from 41.4% to 80.3% for erythropoietin and calcium binders from 10.5% to 23.4%, and from 41.9 to 82.6%, respectively. At last visit, 90% of patients were on ACE inhibitors/ARB. Blood pressure <130/80 mm Hg increased from 23% to 38%. Serum glucose ⩽130 mg/dl increased from 54.4% to 67.7%. Serum cholesterol >160 mg/dl decreased from 64.8% to 60.3%. At last visit, 70% of the patients had a serum Hgb ⩾11.0 g/dl, and 80.1% and 65.1% had a normal serum calcium and serum phosphate, respectively. In conclusion, we observed a trend in the improvement of quality of care of CKD patients similar to those reported by other MDC programs in the developed world. Our study demonstrated that a nurse-led MDC program could be successfully implemented in developing countries.
PMCID: PMC4089727  PMID: 25018984
chronic kidney disease; prevention; outcomes
4.  Likelihood of coronary angiography among First Nations patients with acute myocardial infarction 
Morbidity due to cardiovascular disease is high among First Nations people. The extent to which this may be related to the likelihood of coronary angiography is unclear. We examined the likelihood of coronary angiography after acute myocardial infarction (MI) among First Nations and non–First Nations patients.
Our study included adults with incident acute MI between 1997 and 2008 in Alberta. We determined the likelihood of angiography among First Nations and non–First Nations patients, adjusted for important confounders, using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database.
Of the 46 764 people with acute MI, 1043 (2.2%) were First Nations. First Nations patients were less likely to receive angiography within 1 day after acute MI (adjusted odds ratio [OR] 0.73, 95% confidence interval [CI] 0.62–0.87). Among First Nations and non–First Nations patients who underwent angiography (64.9%), there was no difference in the likelihood of percutaneous coronary intervention (PCI) (adjusted hazard ratio [HR] 0.92, 95% CI 0.83–1.02) or coronary artery bypass grafting (CABG) (adjusted HR 1.03, 95% CI 0.85–1.25). First Nations people had worse survival if they received medical management alone (adjusted HR 1.38, 95% CI 1.07–1.77) or if they underwent PCI (adjusted HR 1.38, 95% CI 1.06–1.80), whereas survival was similar among First Nations and non–First Nations patients who received CABG.
First Nations people were less likely to undergo angiography after acute MI and experienced worse long-term survival compared with non–First Nations people. Efforts to improve access to angiography for First Nations people may improve outcomes.
PMCID: PMC4081235  PMID: 24847149
5.  Systematic Review of the Risk of Adverse Outcomes Associated with Vascular Endothelial Growth Factor Inhibitors for the Treatment of Cancer 
PLoS ONE  2014;9(7):e101145.
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.
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.
PMCID: PMC4079504  PMID: 24988441
7.  Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: A randomized trial 
Arteriovenous grafts, an important option for hemodialysis vascular access, are prone to recurrent stenosis and thrombosis.
To determine the effect of fish oil on arteriovenous graft patency and cardiovascular events.
Design, Setting and Patients
Randomized, double-blind, controlled clinical trial (FISH Study) conducted at 15 North American dialysis centres from November 2003-December 2010 enrolled 201 participants with stage 5 chronic kidney disease (50% female, 63% Caucasian, 53% diabetic) and followed them for 12 months after graft creation
Random allocation to daily fish oil capsules (4×1 gram) or matching placebo on day 7 after graft creation.
Main Outcome Measure
The proportion of participants experiencing a graft thrombosis or radiological or surgical intervention during 12 months follow-up.
The risk of the primary outcome did not differ between fish oil and placebo recipients (48/99 [48%] versus 60/97 [62%]; relative risk 0.78 [95% CI, 0.60–1.03; P = 0.064]). However, the rate of graft failure was lower in the fish oil group (3.43 versus 5.95 per 1,000 access days; incidence rate ratio (IRR) 0.58 [95% CI, 0.44–0.75; P < 0.001). In the fish oil group, there were half as many thrombosis events (1.71 versus 3.41 per 1,000 access days; IRR 0.50 [95% CI, 0.35–0.72; P < 0.001); fewer corrective interventions (2.89 versus 4.92 per 1,000 access days; IRR 0.59 [95% CI, 0.44–0.78; P < 0.001), improved cardiovascular event-free survival; hazard ratio 0.43 [95% CI, 0.19–0.96; P=0.035) and lower systolic blood pressure by 12 months (average −3.61 versus + 4.49 mmHg [95% CI −15.4–−0.85]; P=0.014).
Conclusions: D
aily fish oil ingestion did not reduce the proportion of patients with loss of native patency within 12 months of graft creation; however, it did reduce the rate and time to thrombosis, the need for corrective interventions to maintain patency, and was associated with improved cardiovascular outcomes.
Trial registration Identifier: ISRCTN 15838383
PMCID: PMC4046844  PMID: 22550196
8.  Patient satisfaction with in-centre haemodialysis care: an international survey 
BMJ Open  2014;4(5):e005020.
To evaluate patient experiences of specific aspects of haemodialysis care across several countries.
Cross-sectional survey using the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) questionnaire.
Haemodialysis clinics within a single provider in Europe and South America.
2748 adults treated in haemodialysis.
Primary and secondary outcomes
The primary outcome was patient satisfaction with overall care. Secondary outcomes included patient experiences of individual aspects of dialysis care.
2145 (78.1%) adults responded to the questionnaire. Fewer than half (46.5% (95% CI 44.5% to 48.6%)) rated their overall care as excellent. Global perceptions of care were uninfluenced by most respondent characteristics except age and depressive symptoms; older respondents were less critical of their care (adjusted OR for excellent rating 1.44 (1.01 to 2.04)) and those with depressive symptoms were less satisfied (0.56 (0.44 to 0.71)). Aspects of care that respondents most frequently ranked as excellent were staff attention to dialysis vascular access (54% (52% to 56%)); caring of nurses (53% (51% to 55%)); staff responsiveness to pain or discomfort (51% (49% to 53%)); caring, helpfulness and sensitivity of dialysis staff (50% (48% to 52%)); and ease of reaching dialysis staff by telephone (48% (46% to 50%)). The aspects of care least frequently ranked as excellent were information provided when choosing a dialysis modality (23% (21% to 25%)), ease of seeing a social worker (28% (24% to 32%)), information provided about dialysis (34% (32% to 36%)), accuracy of information from nephrologist (eg, about prognosis or likelihood of a kidney transplant; 37% (35% to 39%)) and accuracy of nephrologists’ instructions (39% (36% to 41%)).
Haemodialysis patients are least satisfied with the complex aspects of care. Patients’ expectations for accurate information, prognosis, the likelihood of kidney transplantation and their options when choosing dialysis treatment need to be considered when planning healthcare research and practices.
PMCID: PMC4039823  PMID: 24840250
9.  The Association of Income with Health Behavior Change and Disease Monitoring among Patients with Chronic Disease 
PLoS ONE  2014;9(4):e94007.
Management of chronic diseases requires patients to adhere to recommended health behavior change and complete tests for monitoring. While studies have shown an association between low income and lack of adherence, the reasons why people with low income may be less likely to adhere are unclear. We sought to determine the association between household income and receipt of health behavior change advice, adherence to advice, receipt of recommended monitoring tests, and self-reported reasons for non-adherence/non-receipt.
We conducted a population-weighted survey, with 1849 respondents with cardiovascular-related chronic diseases (heart disease, hypertension, diabetes, stroke) from Western Canada (n = 1849). We used log-binomial regression to examine the association between household income and the outcome variables of interest: receipt of advice for and adherence to health behavior change (sodium reduction, dietary improvement, increased physical activity, smoking cessation, weight loss), reasons for non-adherence, receipt of recommended monitoring tests (cholesterol, blood glucose, blood pressure), and reasons for non-receipt of tests.
Behavior change advice was received equally by both low and high income respondents. Low income respondents were more likely than those with high income to not adhere to recommendations regarding smoking cessation (adjusted prevalence rate ratio (PRR): 1.55, 95%CI: 1.09–2.20), and more likely to not receive measurements of blood cholesterol (PRR: 1.72, 95%CI 1.24–2.40) or glucose (PRR: 1.80, 95%CI: 1.26–2.58). Those with low income were less likely to state that non-adherence/non-receipt was due to personal choice, and more likely to state that it was due to an extrinsic factor, such as cost or lack of accessibility.
There are important income-related differences in the patterns of health behavior change and disease monitoring, as well as reasons for non-adherence or non-receipt. Among those with low income, adherence to health behavior change and monitoring may be improved by addressing modifiable barriers such as cost and access.
PMCID: PMC3983092  PMID: 24722618
10.  Association between Drug Insurance Cost Sharing Strategies and Outcomes in Patients with Chronic Diseases: A Systematic Review 
PLoS ONE  2014;9(3):e89168.
Prescription 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.
To 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).
Studies 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.
Outcomes 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.
Lowering cost sharing in patients with chronic diseases may improve adherence, but the impact on clinical and economic outcomes is uncertain.
PMCID: PMC3965394  PMID: 24667163
11.  Benefits and harms of statin therapy for persons with chronic kidney disease: A systematic review and meta-analysis 
Annals of internal medicine  2012;157(4):263-275.
Statins have uncertain benefits in chronic kidney disease (CKD) as individual trials may have insufficient power to determine whether treatment effects differ with severity of CKD.
To summarize the benefits and harms of statin therapy for adults with CKD and examine whether effects of statins vary by kidney disease stage.
Data Sources
Cochrane and EMBASE databases (inception to February 2012).
Study Selection
Randomized trials comparing effects of statins with placebo, no treatment or another statin on mortality and cardiovascular outcomes.
Data Extraction
Two independent reviewers extracted data and assessed risk of bias.
Data Synthesis
Eighty trials (n=51,099) compared statin with placebo or no treatment. Treatment effects varied with stage of CKD. In persons not on dialysis, statins reduced all-cause (relative risk, 0·81, 95% confidence interval, 0·74-0·88) and cardiovascular (0·78, 0·68-0·89) mortality and cardiovascular events (0·76, 0·73-0·80) in moderate-high quality evidence. For persons on dialysis, statins had little or no effect on all-cause (0·96, 0·88-1·04) or cardiovascular (0.94, 0.82-1.07) mortality or cardiovascular events (0·95, 0·87-1·03) in moderate-high quality evidence. Effects of statins in kidney transplant recipients were uncertain. Statins had little or no effect on cancer, myalgia, liver function, or withdrawal from treatment, although adverse events were evaluated systematically in fewer than half of trials.
Reliance on post hoc subgroup data for earlier stages of CKD and lack of data for primary and secondary prevention.
Statins lower mortality and cardiovascular events in persons with early stages of CKD, have little or no effect in persons on dialysis, and have uncertain effects in kidney transplant recipients.
PMCID: PMC3955032  PMID: 22910937
12.  Age and the Association of Kidney Measures with Mortality and End-Stage Renal Disease 
Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial.
To evaluate possible effect modification (interaction) of age on the association of estimated GFR and albuminuria with clinical risk examining both relative and absolute risk.
Design, Setting, Participants
We investigated 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australesia, Europe, and North/South America conducted during 1972–2011 with mean follow-up time of 5.8 years (range 0–31 years).
Main Outcome Measures
Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholestserol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates.
Mortality (112,325 deaths) and ESRD (8,411 events) risk were higher at lower eGFR and higher albuminuria in every age category. In general/high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age: e.g., adjusted HRs (95% CI) at eGFR 45 vs. 80 ml/min/1.73m2 were 3.50 (2.55–4.81), 2.21 (2.02–2.41), 1.59 (1.42–1.77), and 1.35 (1.23–1.48) in age categories 18–54, 55–64, 65–74 and 75+ years, respectively (P-values for age interaction <0.05). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0–12.8], 12.2 [10.3–14.3], 13.3 [9.0–18.6], and 27.2 [13.5–45.5] excess deaths per 1,000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age were less evident, while differences in absolute risk were higher in the older age categories (7.5 [95% CI, 4.3–11.9], 12.2 [7.9–17.6], 22.7 [15.3–31.6], and 34.3 [19.5–52.4] excess deaths per 1,000 person-years, respectively by age category, at ACR 300 mg/g compared to 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories.
Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risks differences at older age.
PMCID: PMC3936348  PMID: 23111824
13.  Diabetes Guidelines 
PMCID: PMC3576447  PMID: 23423276
14.  Association between First Nations ethnicity and progression to kidney failure by presence and severity of albuminuria 
Despite a low prevalence of chronic kidney disease (estimated glomerular filtration rate [GFR] < 60 mL/min per 1.73 m2), First Nations people have high rates of kidney failure requiring chronic dialysis or kidney transplantation. We sought to examine whether the presence and severity of albuminuria contributes to the progression of chronic kidney disease to kidney failure among First Nations people.
We identified all adult residents of Alberta (age ≥ 18 yr) for whom an outpatient serum creatinine measurement was available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using urine dipsticks and categorized results as normal (i.e., no albuminuria), mild, heavy or unmeasured. Our primary outcome was progression to kidney failure (defined as the need for chronic dialysis or kidney transplantation, or a sustained doubling of serum creatinine levels). We calculated rates of progression to kidney failure by First Nations status, by estimated GFR and by albuminuria category. We determined the relative hazard of progression to kidney failure for First Nations compared with non–First Nations participants by level of albuminuria and estimated GFR.
Of the 1 816 824 participants we identified, 48 669 (2.7%) were First Nations. First Nations people were less likely to have normal albuminuria compared with non–First Nations people (38.7% v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold higher among First Nations people than among non–First Nations people, across all levels of albuminuria and estimated GFRs. Compared with non–First Nations people, First Nations people with an estimated GFR of 15.0–29.9 mL/min per 1.73 m2 had the highest risk of progression to kidney failure, with similar hazard ratios for those with normal and heavy albuminuria.
Albuminuria confers a similar risk of progression to kidney failure for First Nations and non–First Nations people.
PMCID: PMC3903763  PMID: 24295865
16.  Comparison of risk prediction using the CKD-EPI equation and the MDRD Study equation for estimated glomerular filtration rate 
JAMA : the journal of the American Medical Association  2012;307(18):10.1001/jama.2012.3954.
The CKD-EPI equation more accurately estimates glomerular filtration rate (eGFR) than the MDRD Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking.
To evaluate risk implications of eGFRCKD-EPI compared to eGFRMDRD in populations with a broad range of demographic and clinical characteristics.
Design, Setting, and Participants
Meta-analyses based on data from 1,130,472 adults (aged 18 years or older) from 25 general population, 7 high-risk (of vascular disease), and 13 chronic kidney disease (CKD) cohorts. Data transfer and analyses were conducted between March 2011 and March 2012.
Main Outcome Measures
All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7,644 events from 21 cohorts) during 9.4 million person-years of follow-up (median of mean follow-up time across cohorts was 7.4 years).
eGFR was classified into six categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 ml/min/1.73m2) by both equations. Compared to eGFRMDRD, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower eGFR category by the CKD-EPI equation, respectively, and the prevalence of CKD stage 3-5 (eGFR <60 ml/min/1.73m2) was reduced from 8.7% to 6.3%. 34.7% of participants with eGFRMDRD 45-59 were reclassified to eGFRCKD-EPI 60-89 and had lower incidence rates (per 1,000 person-years) of outcomes compared to those not reclassified (9.9 vs. 34.5 for all-cause mortality, 2.7 vs. 13.0 for cardiovascular mortality, and 0.5 vs. 0.8 for ESRD). The corresponding adjusted hazard ratios were 0.80 (95% confidence interval, 0.74 to 0.86) for all-cause mortality, 0.73 (0.65 to 0.82) for cardiovascular mortality, and 0.49 (0.27 to 0.88) for ESRD. Similar findings were observed in other eGFRMDRD categories. Net reclassification improvement (NRI) based on eGFR categories was significantly positive for all outcomes (range from 0.06 to 0.13, all P<0.001). NRI was similarly positive in most subgroups defined by age (< and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in high-risk and CKD cohorts were largely consistent with the general population cohorts.
The CKD-EPI equation classified fewer individuals as CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.
PMCID: PMC3837430  PMID: 22570462
17.  Patterns of engagement with the health care system and risk of subsequent hospitalization amongst patients with diabetes 
Re-hospitalization is common among patients with diabetes, and may be related to aspects of health care use. We sought to determine the association between patterns of health care engagement and risk of subsequent hospitalization within one year of discharge for patients with diabetes.
We identified adults with incident diabetes in Alberta, Canada, who had at least one hospitalization following their diabetes diagnosis between January 1, 2004 and March 31, 2011. We used Cox regression to estimate the association between factors related to health care engagement (prior emergency department use, primary care visits, and discharge disposition (i.e. whether the patient left against medical advice)) and the risk of subsequent all-cause hospitalization within one year.
Of the 33811 adults with diabetes and at least one hospitalization, 11095 (32.8%) experienced a subsequent all-cause hospitalization within a mean (standard deviation) follow-up time of 0.68 (0.3) years. Compared to patients with no emergency department visits, there was a 4 percent increased risk of a subsequent hospitalization for every emergency department visit occurring prior to the index hospitalization (adjusted Hazard Ratio [HR]: 1.04; 95% CI: 1.03–1.05). Limited and increased use of primary care was also associated with increased risk of a subsequent hospitalization. Compared to patients with 1–4 visits, patients with no visits to a primary care physician (adjusted HR: 1.11; 95% CI: 0.99–1.25) and those with 5–9 visits (adjusted HR: 1.06; 95% CI: 1.00–1.12) were more likely to experience a subsequent hospitalization. Finally, compared to patients discharged home, those leaving against medical advice were more likely to have a subsequent hospitalization (adjusted HR: 1.74; 95% CI: 1.50–2.02) and almost 3 times more likely to have a diabetes-specific subsequent event (adjusted HR: 2.86; 95% CI: 1.82–4.49).
Patterns of health care use and the circumstances surrounding hospital discharge are associated with an increased risk of subsequent hospitalization among patients with diabetes. Whether these patterns are related to the health care systems ability to manage complex patients within a primary care setting, or to access to primary care services, remains to be determined.
PMCID: PMC3851786  PMID: 24103159
Diabetes; Administrative data; Hospitalization
18.  Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis 
Lancet  2012;380(9854):1662-1673.
Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown.
We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes.
We analysed data for 1 024 977 participants (128 505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75 306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21 237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2–1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m2 [νs 95 mL/min per 1·73 m2], HR 1·35; 95% CI 1·18–1·55; νs 1·33; 1·19–1·48 and at ACR 30 mg/g [νs 5 mg/g], 1·50; 1·35–1·65 νs 1·52; 1·38–1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts.
Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes.
PMCID: PMC3771350  PMID: 23013602
19.  Comparison of Concurrent Complications of CKD by 2 Risk Categorization Systems 
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).
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)
Prevalence of anemia, acidosis, hyperphosphatemia, hypoalbuminemia, hyperparathyroidism and hypertension
GFR estimated from the CKD-Epidemiology Collaboration (CKD-EPI) equation and proteinuria assessed using urine albumin-creatinine ratio (ACR)
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.
Use of single creatinine to estimate GFR and single measure to assess ACR. Small number of participants with CKD Stage 4.
The NKF-KDOQI system may better identify patients with certain concurrent CKD complications compared to systems using eGFR and proteinuria.
PMCID: PMC3288542  PMID: 22113126
20.  Association between perceived unmet health care needs and risk of adverse health outcomes among patients with chronic medical conditions 
Open Medicine  2013;7(1):e21-e30.
Adults with chronic medical conditions are more likely to report unmet health care needs. Whether unmet health care needs are associated with an increased risk of adverse health outcomes is unclear.
Adults with at least one self-reported chronic condition (arthritis, chronic obstructive pulmonary disease, diabetes mellitus, heart disease, hypertension, mood disorder, stroke) from the 2001 and 2003 cycles of the Canadian Community Health Survey were linked to national hospitalization data. Participants were followed from the date of their survey until March 31, 2005, for the primary outcomes of all-cause and cause-specific admission to hospital. Secondary outcomes included length of stay, 30-day and 1-year all-cause readmission to hospital, and in-hospital death. Negative binomial regression models were used to estimate the association between unmet health care needs, admission to hospital, and length of stay, with adjustment for socio-demographic variables, health behaviours, and health status. Logistic regression was used to estimate the association between unmet needs, readmission, and in-hospital death. Further analyses were conducted by type of unmet need.
Of the 51 932 adults with self-reported chronic disease, 15.5% reported an unmet health care need. Participants with unmet health care needs had a risk of all-cause admission to hospital similar to that of patients with no unmet needs (adjusted rate ratio [RR] 1.04, 95% confidence interval [CI] 0.94–1.15). When stratified by type of need, participants who reported issues of limited resource availability had a slightly higher risk of hospital admission (RR 1.18, 95% CI 1.09–1.28). There was no association between unmet needs and length of stay, readmission, or in-hospital death.
Overall, unmet health care needs were not associated with an increased risk of admission to hospital among those with chronic conditions. However, certain types of unmet needs may be associated with higher or lower risk. Whether unmet needs are associated with other measures of resource use remains to be determined.
PMCID: PMC3654502  PMID: 23687534
21.  Association of enrolment in primary care networks with diabetes care and outcomes among First Nations and low-income Albertans 
Open Medicine  2012;6(4):e155-e165.
The prevalence of diabetes mellitus and its complications is higher among First Nations people and people with low socio-economic status (SES). Previous studies in Alberta have shown that provision of care through Primary Care Networks (PCNs) is associated with better quality of care and better outcomes for people with diabetes, possibly because of greater utilization of chronic disease management programs. However, it is unknown whether First Nations individuals and those in lower SES groups experience these benefits.
We used administrative and laboratory data for a population-based cohort analysis of Alberta residents under 65 years of age with diabetes. The primary outcome, assessed over a 1-year period, was admission to hospital or emergency department visit for a diabetes-specific ambulatory care sensitive condition (ACSC). Secondary outcomes were 2 quality-of-care indicators (likelihood of measurement of glycated hemoglobin [HbA1c] and or retinal screening) and 2 measures of health care utilization (visits to specialist and primary care physicians). We used negative binomial regression to determine the association between care within a PCN and hospital admission or emergency department visit for diabetes-specific ACSCs. We also assessed outcomes in 3 populations of interest (individuals receiving a health care subsidy [household income less than $39 250 and not eligible for Income Support], those receiving Income Support, and First Nations individuals) relative to the remainder of the population, controlling for whether care was provided in a PCN and adjusting for several baseline characteristics.
We identified a total of 106 653 patients with diabetes eligible for our study, of whom 43 327 (41%) received care in a PCN. Receiving care through a PCN was associated with lower rates of ACSC-related hospital admission or emergency department visits for all groups of interest, which suggests that PCNs had similar effects across each group. However, regardless of where care was provided, First Nations and low-SES patients had more than twice the adjusted rates of hospital admission or emergency department visits for diabetes-specific ACSCs than the general population and were less likely to receive guideline-recommended care, including measurement of HbA1c and retinal screening.
Care in a PCN was associated with lower risks of hospital admission or emergency department visits for diabetes-specific ACSCs, even within vulnerable groups such as First Nations people and those of low SES. However, differences in outcomes and quality-of-care indicators persisted for First Nations individuals and those of low SES, relative to the general population, irrespective of where care was provided.
PMCID: PMC3654512  PMID: 23687531
23.  Incidence and causes of end-stage renal disease among Aboriginal children and young adults 
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.
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.
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.
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.
PMCID: PMC3470642  PMID: 22927509
24.  Bariatric Surgery: A Systematic Review of the Clinical and Economic Evidence 
Journal of General Internal Medicine  2011;26(10):1183-1194.
Use of bariatric surgery for severe obesity has increased dramatically.
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.
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.
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.
Outcomes included changes in weight and obesity-related comorbidity, quality of life and mortality, surgical complications, resource utilization, and incremental cost-utility.
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.
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.
PMCID: PMC3181300  PMID: 21538168
randomized controlled trials; clincical evidence; economic evidence; systematic review
25.  Evaluating the impact of a novel restricted reimbursement policy for quinolone antibiotics: A time series analysis 
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.
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.
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.
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.
PMCID: PMC3470979  PMID: 22935100
Formulary restriction; Antibiotic; Prior authorization; Prescription drugs

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