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1.  Hypoglycemia Associated With Hospitalization and Adverse Events in Older People 
Diabetes Care  2013;36(11):3585-3590.
Little is known about the prognostic impact of hypoglycemia associated with hospitalization. We hypothesized that hospitalized hypoglycemia would be associated with increased long-term morbidity and mortality, irrespective of diabetes status.
We undertook a cohort study using linked administrative health care and laboratory databases in Alberta, Canada. From 1 January 2004 to 31 March 2009, we included all outpatients 66 years of age and older who had at least one serum creatinine and one A1C measured. To examine the independent association between hospitalized hypoglycemia and all-cause mortality, we used time-varying Cox proportional hazards (adjusted hazard ratio [aHR]), and for all-cause hospitalizations, we used Poisson regression (adjusted incidence rate ratio [aIRR]).
The cohort included 85,810 patients: mean age 75 years, 51% female, and 50% had diabetes defined by administrative data. Overall, 440 patients (0.5%) had severe hypoglycemia associated with hospitalization and most (93%) had diabetes. During 4 years of follow-up, 16,320 (19%) patients died. Hospitalized hypoglycemia was independently associated with increased mortality (60 vs. 19% mortality for no hypoglycemia; aHR 2.55 [95% CI 2.25–2.88]), and this increased in a dose-dependent manner (aHR no hypoglycemia = 1.0 vs. one episode = 2.49 vs. one or more = 3.78, P trend <0.001). Hospitalized hypoglycemia was also independently associated with subsequent hospitalizations (aIRR no hypoglycemia = 1.0 vs. one episode = 1.90 vs. one or more = 2.61, P trend <0.001) and recurrent hypoglycemia (aHR no hypoglycemia = 1.0 vs. one episode = 2.45 vs. one or more = 9.66, P trend <0.001).
Older people who have an episode of hospitalized hypoglycemia are easily identified and at substantially increased risk of morbidity and mortality.
PMCID: PMC3816904  PMID: 24089536
2.  Remembering the forgotten non-communicable diseases 
BMC Medicine  2014;12(1):200.
The forthcoming post-Millennium Development Goals era will bring about new challenges in global health. Low- and middle-income countries will have to contend with a dual burden of infectious and non-communicable diseases (NCDs). Some of these NCDs, such as neoplasms, COPD, cardiovascular diseases and diabetes, cause much health loss worldwide and are already widely recognised as doing so. However, 55% of the global NCD burden arises from other NCDs, which tend to be ignored in terms of premature mortality and quality of life reduction. Here, experts in some of these ‘forgotten NCDs’ review the clinical impact of these diseases along with the consequences of their ignoring their medical importance, and discuss ways in which they can be given higher global health priority in order to decrease the growing burden of disease and disability.
PMCID: PMC4207624  PMID: 25604462
Global health; Non-communicable diseases; Sickle cell disease; Chronic kidney disease; Asthma; Dementia; Gout; Substance abuse; Alcohol; Liver cirrhosis
3.  Age modification of diabetes-related hospitalization among First Nations adults in Alberta, Canada 
We sought to determine the modifying effects of age and multimorbidity on the association between First Nations status and hospitalizations for diabetes-specific ambulatory care sensitive conditions (ACSC).
We identified 183,654 adults with diabetes from Alberta Canada, and followed them for one year for the outcome of hospitalization or emergency department (ED) visit for a diabetes-specific ACSC. We used logistic regression to determine the association between First Nations status and the outcome, assessing for effect modification by age and multimorbidity with interaction terms. In a model adjusting for age, age2, baseline A1c, duration of diabetes, and multimorbidity, First Nations people were at greater risk than non-First Nations to experience a diabetes-specific hospitalization or ED visit (unadjusted odds ratio [OR] 3.74; 95% confidence interval [CI]: 3.45-4.07). After adjustment for relevant covariates, this association varied by age (interaction: p = 0.018): adjusted OR 3.94 (95% CI: 3.11-4.99) and 5.74 (95% CI: 3.36-9.80) for First Nations compared to non-First Nations at ages 30 and 80 years, respectively.
Compared with non-First Nations, older First Nations patients with diabetes are at greater risk for diabetes-specific hospitalizations. Older First Nations patients with diabetes should be given priority access to primary care services as they are at greatest risk for requiring hospitalization for stabilization of their condition.
PMCID: PMC4192759  PMID: 25309626
American indian; First Nations; Hospitalization; Diabetes mellitus; Risk adjustment
5.  Risk for recurrent coronary heart disease and all-cause mortality among individuals with chronic kidney disease compared with diabetes mellitus, metabolic syndrome, and cigarette smokers 
American heart journal  2013;166(2):373-380.e2.
Lipid-lowering guidelines endorse a low-density lipoprotein cholesterol goal of <100 mg/dL for people with coronary heart disease (CHD). A more stringent threshold of <70 mg/dL is recommended for those with CHD and “very high-risk” conditions such as diabetes mellitus, metabolic syndrome, or cigarette smoking. Whether chronic kidney disease (CKD) confers a similar risk for recurrent CHD events is unknown.
Methods and Results
We evaluated the risk for recurrent CHD events and all-cause mortality among 3,938 participants ≥45 years with CHD in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Chronic kidney disease was defined by estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urinary albumin to creatinine ratio ≥30 mg/g. Participants were categorized by the presence or absence of CKD and any very high-risk condition. Over a median of 4.1 years, the crude incidence (95% CI) of recurrent CHD events were 12.1 (9.0–15.2), 18.9 (15.5–22.3), 35.0 (25.4–44.6), and 34.2 (28.2–40.3) among those without CKD or high-risk conditions; very high-risk conditions alone; and CKD alone and both CKD and very high-risk conditions. After multivariable adjustment, compared with those without CKD or very high-risk conditions, the hazard ratio (95% CI) for recurrent CHD events was 1.45 (1.02–2.05), 2.24 (1.50–3.34), and 2.10 (1.47–2.98) among those with very high-risk conditions alone, CKD alone, and both CKD and very high-risk conditions, respectively. Results were consistent for all-cause mortality.
Chronic kidney disease is associated with risk for recurrent CHD events that approximates or is larger than other established very high-risk conditions.
PMCID: PMC4139360  PMID: 23895822
6.  Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol 
Systematic Reviews  2014;3:88.
To improve quality of care and patient outcomes, health system decision-makers need to identify and implement effective interventions. An increasing number of systematic reviews document the effects of quality improvement programs to assist decision-makers in developing new initiatives. However, limitations in the reporting of primary studies and current meta-analysis methods (including approaches for exploring heterogeneity) reduce the utility of existing syntheses for health system decision-makers. This study will explore the role of innovative meta-analysis approaches and the added value of enriched and updated data for increasing the utility of systematic reviews of complex interventions.
We will use the dataset from our recent systematic review of 142 randomized trials of diabetes quality improvement programs to evaluate novel approaches for exploring heterogeneity. These will include exploratory methods, such as multivariate meta-regression analyses and all-subsets combinatorial meta-analysis. We will then update our systematic review to include new trials and enrich the dataset by surveying authors of all included trials. In doing so, we will explore the impact of variables not, reported in previous publications, such as details of study context, on the effectiveness of the intervention. We will use innovative analytical methods on the enriched and updated dataset to identify key success factors in the implementation of quality improvement interventions for diabetes. Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results.
This study will inform future systematic reviews of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta-analysis. It will also result in an updated comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes.
Systematic review registration
PROSPERO registration no. CRD42013005165
PMCID: PMC4174390  PMID: 25115289
Diabetes care; Knowledge translation; Quality improvement interventions; Complex Interventions; Health system decision-makers; Systematic review; Meta-analysis; Implementation science; Heterogeneity; Hierarchical modeling
7.  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
8.  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
9.  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
10.  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
11.  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
13.  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
14.  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
15.  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
16.  Capacity and willingness of patients with chronic noncommunicable diseases to use information technology to help manage their condition: a cross-sectional study 
CMAJ Open  2014;2(2):E51-E59.
Health care providers have shown considerable interest in using information technologies such as email, text messages and video conferencing to facilitate the management of chronic noncommunicable diseases such as hypertension, diabetes mellitus and vascular disease. We sought to determine whether these technologies are available and appealing to the target population.
We analyzed cross-sectional data from a computer-assisted telephone survey, conducted by Statistics Canada in February and March 2012, of western Canadian adults with at least 1 chronic condition. Survey respondents were asked about their capacity (e.g., “Do you own a mobile phone?”) and willingness to use each of 3 information technologies (email, text messages and video conferencing) to interact with health care providers. For all analyses, Statistics Canada’s calibrated design weights and bootstrap weights were used to obtain population-level point estimates for proportions and odds ratios.
In total, 1849 (79.8%) of 2316 eligible people participated. Of the 1849 participants, 81.9% had hypertension, 26.2% had diabetes, 21.4% had heart disease, and 7.9% had stroke; 32.2% had more than 1 of the 4 chronic conditions of interest. High proportions of respondents owned a computer with Internet access (76.4%, 95% confidence interval [CI] 73.3%–79.3%) or a mobile phone (73.9%, 95% CI 70.7%–76.8%). About two-thirds of respondents were interested in using email to interact with a specialist (66.3%, 95% CI 63.0%–69.5%); respondents were less enthusiastic about using text messages (44.9%, 95% CI 41.2%–48.7%). Enthusiasm for video conferencing was more pronounced among those residing further from medical specialists than among those living closer. Among respondents who were potentially interested in video conferencing, almost 50% of remote dwellers would use this technology if it saved more than 60 minutes of travel time.
Many people were interested in using electronic technologies, especially video conferencing and email-based methods, to help manage their chronic condition. The effectiveness and cost implications of using email and video conferencing in the management of chronic disease deserve further consideration.
PMCID: PMC4084741  PMID: 25077130
17.  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
18.  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
19.  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
20.  Diabetes Guidelines 
PMCID: PMC3576447  PMID: 23423276
21.  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
22.  Access to primary care and other health care use among western Canadians with chronic conditions: a population-based survey 
CMAJ Open  2014;2(1):E27-E34.
For adults with chronic conditions, access to primary care, including multidisciplinary care, is associated with better outcomes. Few studies have assessed barriers to such care. We sought to describe barriers to primary care, including care from allied health professionals, for adults with chronic conditions.
We surveyed western Canadians aged 40 years or older who had hypertension, diabetes, heart disease or stroke about access to primary care and other use of health care. Using log binomial regression, we determined the association between sociodemographic variables and several indicators of access to primary care and care from allied health professionals.
Of the 2316 people who were approached, 1849 (79.8%) completed the survey. Most of the respondents (95.1%) had a regular medical doctor, but two-thirds (68.1%) did not have after-hours access. Only 6.1% indicated that allied health professionals were involved in their care, although most respondents (87.3%) indicated they would be willing to see a nurse practitioner if their primary care physician was not available. Respondents who were obese or less than 65 years of age were less likely to have a regular medical doctor. Individuals who had diabetes, lived in a rural area, were residents of Alberta or had poorer health were more likely to have allied health professionals involved in their care.
The survey results identified barriers to accessing primary care for people with chronic conditions. Opportunities for improving access to primary care may include greater involvement by allied health professionals, such as nurse practitioners.
PMCID: PMC3985957  PMID: 25077122
24.  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
25.  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

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