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1.  Comparative safety of anti-epileptic drugs among infants and children exposed in utero or during breastfeeding: protocol for a systematic review and network meta-analysis 
Systematic Reviews  2014;3:68.
Epilepsy affects about 1% of the general population. Anti-epileptic drugs (AEDs) prevent or terminate seizures in individuals with epilepsy. Pregnant women with epilepsy may continue taking AEDs. Many of these agents cross the placenta and increase the risk of major congenital malformations, early cognitive and developmental delays, and infant mortality. We aim to evaluate the comparative safety of AEDs approved for chronic use in Canada when administered to pregnant and breastfeeding women and the effects on their infants and children through a systematic review and network meta-analysis.
Studies examining the effects of AEDs administered to pregnant and breastfeeding women regardless of indication (e.g., epilepsy, migraine, pain, psychiatric disorders) on their infants and children will be included. We will include randomized clinical trials (RCTs), quasi-RCTs, non-RCTs, controlled before-after, interrupted time series, cohort, registry, and case-control studies. The main literature search will be executed in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We will seek unpublished literature through searches of trial protocol registries and conference abstracts. The literature search results screening, data abstraction, and risk of bias appraisal will be performed by two individuals, independently. Conflicts will be resolved through discussion. The risk of bias of experimental and quasi-experimental studies will be appraised using the Cochrane Effective Practice and Organization of Care Risk-of-Bias tool, methodological quality of observational studies will be appraised using the Newcastle-Ottawa Scale, and quality of reporting of safety outcomes will be conducted using the McMaster Quality Assessment Scale of Harms (McHarm) tool. If feasible and appropriate, we will conduct random effects meta-analysis. Network meta-analysis will be considered for outcomes that fulfill network meta-analysis assumptions.
The primary outcome is major congenital malformations (overall and by specific types), while secondary outcomes include fetal loss/miscarriage, minor congenital malformations (overall and by specific types), cognitive development, psychomotor development, small for gestational age, preterm delivery, and neonatal seizures.
Our systematic review will address safety concerns regarding the use of AEDs during pregnancy and breastfeeding. Our results will be useful to healthcare providers, policy-makers, and women of childbearing age who are taking anti-epileptic medications.
Systematic review registration
PROSPERO CRD42014008925.
PMCID: PMC4086277  PMID: 24964932
Anti-epileptic drug; Breastfeeding; Comparative safety; Congenital malformation; Epilepsy; Fetus; Infant; Network meta-analysis; Pregnancy; Systematic review
2.  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
3.  Safety and effectiveness of antiretroviral therapies for HIV-infected women and their infants and children: protocol for a systematic review and network meta-analysis 
Systematic Reviews  2014;3:51.
Antiretroviral therapy reduces mother-to-child transmission of human immunodeficiency virus (HIV) during pregnancy, delivery, and breastfeeding. However, these agents have been associated with preterm birth, anemia and low birth weight. We aim to evaluate the comparative safety and effectiveness of the use of antiretroviral drugs among HIV-infected women and the effects on their infants and children through a systematic review and network meta-analysis.
Studies examining the effects of six antiretroviral drug classes (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, co-receptor inhibitors) administered to HIV-infected pregnant women will be included. We will include randomized clinical trials (RCTs), quasi-RCTs, non-RCTs, controlled before-after, interrupted time series, cohort, registry, and case–control studies. No limitations will be imposed on publication status (that is, unpublished studies are eligible for inclusion), duration of follow-up, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in major electronic databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Gray literature will be identified through searching dissertation databases, trial protocol registries, and conference abstracts.
Two team members will independently screen all citations, full-text articles, and abstract data; conflicts will be resolved through discussion. The risk of bias and methodological quality will be appraised using appropriate tools (for example, Cochrane Collaboration’s tool for assessing risk of bias, Newcastle-Ottawa Scale, and McMaster Quality Assessment Scale of Harms). If feasible and appropriate, we will conduct random effects meta-analysis. Network meta-analysis will be considered for outcomes with the greatest number of treatment comparisons available that fulfill network meta-analysis assumptions (for example, consistency of evidence between direct and indirect data, and low statistical heterogeneity between included studies).
The primary effectiveness outcome is mother-to-child transmission of HIV, and the primary safety outcome is major congenital malformation (overall and specific types) among newborns of HIV-infected women. Secondary safety outcomes include stillbirths, infant/child death, preterm delivery, overall and specific minor congenital malformations, and small for gestational age infants.
Our systematic review will be of utility to healthcare providers, policy-makers, and HIV-positive women regarding the use of antiretroviral drugs.
Trial registration
PROSPERO registry number: CRD42014009071.
PMCID: PMC4039063  PMID: 24887455
antiretroviral therapy; breastfeeding; congenital malformation; human immunodeficiency virus; fetus; mother-to-child-transmission; pregnancy
5.  Regional variations in not treating diagnosed hypertension in Canada 
Improvements in the diagnosis and treatment of hypertension have been documented in Canada following implementation of a national program to improve hypertension management.
To determine whether there are regional variations in not treating diagnosed hypertension with drugs in Canada.
Using data from the Canadian Community Health Survey (CCHS) cycle 3.1 (2005), regional variation in drug treatment of diagnosed hypertension was examined. Also, national drug data from the Intercontinental Medical Statistics CompuScript database were analyzed to determine regional trends in total antihypertensive prescriptions in the period before and following the CCHS cycle 3.1.
The overall rate of untreated hypertension among those diagnosed with hypertension in Canada was 12.7%. The highest untreated rate among those diagnosed with hypertension was in the Northern region (29.2%) and the lowest was in the Atlantic region (8.8%). Alberta (16.5%) and British Columbia (BC) (15.4%) also had higher untreated rates, while Ontario (13.2%) was similar to Canada overall. Younger age, single/never married status, larger household size, lack of access to a family physician and daily smoking were all associated with a higher likelihood of not receiving antihypertensive treatment. Adjusting for demographic characteristics, diagnosed hypertensive patients in Alberta (adjusted OR 1.35 [95% CI 1.14 to 1.61]) and BC (adjusted OR 1.64 [95% CI 1.40 to 1.91]) were more likely to be untreated than those in Ontario. The largest overall percentage increase in total antihypertensive prescriptions following the CCHS (ie, 2006) occurred in BC and Ontario. In Alberta, it remained almost unchanged and declined in Manitoba.
Among adult Canadians diagnosed with hypertension, there were regional variations in the likelihood of not receiving antihypertensive therapy. Further research is required to understand the reasons for these variations to regionally target interventions and improve hypertension management in Canada.
PMCID: PMC2954533  PMID: 20931092
Canada; Hypertension; Regional variation; Treatment
6.  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
7.  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
Hypertension  2011;57(5):891-897.
We designed this study to explore to what extent the excess risk of cardiovascular events in diabetic individuals is attributable to hypertension. We retrospectively analyzed prospectively collected data from the Framingham Original and Offspring cohorts. Of the 1145 Framingham subjects newly diagnosed with diabetes who did not have a prior history of cardiovascular events, 663 (58%) had hypertension at the time diabetes was diagnosed. During 4154 person-years of follow-up, 125 died and 204 suffered a cardiovascular event. Framingham participants with hypertension at the time of diabetes diagnosis exhibited higher rates of all cause mortality (32 versus 20 per 1000 person years, p<0.001) and cardiovascular events (52 versus 31 per 1000 person years, p<0.001) compared with normotensive subjects with diabetes. After adjustment for demographic and clinical covariates, hypertension was associated with a 72% increase in the risk of all cause death and a 57% increase in the risk of any cardiovascular event in individuals with diabetes. The population attributable risk from hypertension in individuals with diabetes was 30% for all-cause death and 25% for any cardiovascular event (increasing to 44% and 41% respectively if the 110 normotensive subjects who developed hypertension during follow-up were excluded from the analysis). In comparison, after adjustment for concurrent hypertension, the population attributable risk from diabetes in Framingham subjects was 7% for all cause mortality and 9% for any CVD event. While diabetes is associated with increased risks of death and cardiovascular events in Framingham subjects, much of this excess risk is attributable to coexistent hypertension.
PMCID: PMC3785072  PMID: 21403089
diabetes; hypertension; Framingham; population attributable risk
9.  Vitamin D Levels Are Associated with Cardiac Autonomic Activity in Healthy Humans 
Nutrients  2013;5(6):2114-2127.
Vitamin D deficiency (≤50nmol/L 25-hydroxy vitamin D) is a cardiovascular (CV) risk factor that affects approximately one billion people worldwide, particularly those affected by chronic kidney disease (CKD). Individuals with CKD demonstrate abnormal cardiac autonomic nervous system activity, which has been linked to the significant rates of CV-related mortality in this population. Whether vitamin D deficiency has a direct association with regulation of cardiac autonomic activity has never been explored in humans. Methods: Thirty-four (34) healthy, normotensive subjects were studied and categorized based on 25-hydroxy vitamin D deficiency (deficient vs. non-deficient, n = 7 vs. 27), as well as 1,25-dihydroxy vitamin D levels (above vs. below 25th percentile, n = 8 vs. 26). Power spectral analysis of electrocardiogram recordings provided measures of cardiac autonomic activity across low frequency (LF) and high frequency (HF, representative of vagal contribution) bands, representative of the sympathetic and vagal limbs of the autonomic nervous system when transformed to normalized units (nu), respectively, as well as overall cardiosympathovagal balance (LF:HF) during graded angiotensin II (AngII) challenge (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min). Results: At baseline, significant suppression of sympathovagal balance was observed in the 25-hydroxy vitamin D-deficient participants (LF:HF, p = 0.02 vs. non-deficient), although no other differences were observed throughout AngII challenge. Participants in the lowest 1,25-dihydroxy VD quartile experienced significant withdrawal of inhibitory vagal control, as well as altered overall sympathovagal balance throughout AngII challenge (HF, mean difference = −6.98 ± 3 nu, p = 0.05; LF:HF, mean difference = 0.34 ± 0.1, p = 0.043 vs. above 25th percentile). Conclusions: Vitamin D deficiency is associated with suppression of resting cardiac autonomic activity, while low 1,25-dihydroxy vitamin D levels are associated with unfavourable cardiac autonomic activity during an acute AngII stressor, offering a potential pathophysiological mechanism that may be acting to elevate CV risk in in populations with low vitamin D status.
PMCID: PMC3725496  PMID: 23752493
vitamin D and cardiovascular disease; vitamin D deficiency; cholecalciferol; cardiac autonomic nervous system; heart rate variability; angiotensin II
11.  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
12.  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
13.  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
14.  Language barriers 
Canadian Family Physician  2012;58(12):e709-e716.
To assess use of regular medical doctors (RMDs), as well as awareness and use of telephone health lines or telehealth services, by official language minorities (OLMs) in Canada.
Analysis of data from the 2006 postcensal survey on the vitality of OLMs.
In total, 7691 English speakers in Quebec and 12 376 French speakers outside Quebec, grouped into those who experienced language barriers and those with no language barriers.
Main outcome measures
Health services utilization (HSU) by the presence of language barriers; HSU measures included having an RMD, use of an RMD’s services, and awareness of and use of telephone health lines or telehealth services. Multivariable models examined the associations between HSU and language barriers.
After adjusting for age and sex, English speakers residing in Quebec with limited proficiency in French were less likely to have RMDs (adjusted odds ratio [AOR] 0.66, 95% CI 0.50 to 0.87) and to use the services of their RMDs (AOR 0.65, 95% CI 0.50 to 0.86), but were more likely to be aware of the existence of (AOR 1.50, 95% CI 1.16 to 1.93) and to use (AOR 1.43, 95% CI 0.97 to 2.11) telephone health lines or telehealth services. This pattern of having and using RMDs and telehealth services was not observed for French speakers residing outside of Quebec.
Overall we found variation in HSU among the language barrier populations, with lower use observed in Quebec. Age older than 45 years, male sex, being married or in common-law relationships, and higher income were associated with having RMDs for OLMs.
PMCID: PMC3520678  PMID: 23242902
15.  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
16.  Experiences of French Speaking Immigrants and Non-immigrants Accessing Health Care Services in a Large Canadian City 
French speakers residing in predominantly English-speaking communities have been linked to difficulties accessing health care. This study examined health care access experiences of immigrants and non-immigrants who self-identify as Francophone or French speakers in a mainly English speaking province of Canada. We used semi-structured interviews to gather opinions of recent users of physician and hospital services (N = 26). Language barriers and difficulties finding family doctors were experienced by both French speaking immigrants and non-immigrants alike. This was exacerbated by a general preference for health services in French and less interest in using language interpreters during a medical consultation. Some participants experienced emotional distress, were discontent with care received, often delayed seeking care due to language barriers. Recent immigrants identified lack of insurance coverage for drugs, transportation difficulties and limited knowledge of the healthcare system as major detractors to achieving health. This study provided the groundwork for future research on health issues of official language minorities in Canada.
PMCID: PMC3509478  PMID: 23202772
immigrants; French language; health care access; family doctor; qualitative descriptive; official language minorities
17.  The impact of nocturnal hemodialysis on sexual function 
BMC Nephrology  2012;13:67.
Sexual dysfunction is common in patients with end stage renal disease (ESRD) and treatment options are limited. Observational studies suggest that nocturnal hemodialysis may improve sexual function. We compared sexual activity and responses to sexual related questions in the Kidney Disease Quality of Life Short Form questionnaire among patients randomized to frequent nocturnal or thrice weekly conventional hemodialysis.
We performed a secondary analysis of data from an RCT which enrolled 51 patients comparing frequent nocturnal and conventional thrice weekly hemodialysis. Sexual activity and responses to sexual related questions were assessed at baseline and six months using relevant questions from the Kidney Disease Quality of Life Short Form questionnaire.
Overall, there was no difference in sexual activity, or the extent to which people were bothered by the impact of kidney disease on their sex life between the two groups between randomization and 6 months. However, women and patients age < 60 who were randomized to frequent nocturnal hemodialysis were less bothered by the impact of kidney disease on their sex life at 6 months, compared with patients allocated to conventional hemodialysis (p = 0.005 and p = 0.024 respectively).
Our results suggest that frequent nocturnal hemodialysis is not associated with an improvement in sexual activity in all patients but might have an effect on the burden of kidney disease on sex life in women and patients less than 60 years of age. The validity of these subgroup findings require confirmation in future RCTs.
PMCID: PMC3457870  PMID: 22834992
Nocturnal hemodialysis; Sex; Sexual function; Frequent hemodialysis
18.  Association between chronic conditions and perceived unmet health care needs 
Open Medicine  2012;6(2):e48-e58.
Although effective treatments exist, many Canadians with chronic medical conditions do not receive the full care they require, possibly as a consequence of limited accessibility or availability. A commonly used indicator of inadequate access to or availability of care is the perception of unmet health care needs. The objective of this study was therefore to determine the association between chronic conditions and perceived unmet health care needs.
We extracted data for adult respondents from the combined 2001, 2003 and 2005 cross-sectional cycles of the Canadian Community Health Survey. Multivariate logistic regression was used to estimate the association between 7 high-prevalence and high-impact chronic conditions (arthritis, chronic obstructive pulmonary disease/emphysema, diabetes, heart disease, hypertension, mood disorder and stroke) and perceived unmet health care needs in the prior 12 months, adjusting for sociodemographic variables, health behaviours, health status and survey cycle.
Of the 360 105 adult respondents, 12.2% reported an unmet health care need. Compared with those without chronic conditions, respondents with at least one condition were more likely to report an unmet need (adjusted odds ratio [OR] 1.51, 95% confidence interval [CI] 1.45–1.59). Those with mood disorders were almost twice as likely to report an unmet need (OR 1.94, 95% CI 1.78–2.12), while those with diabetes or hypertension were less likely to report an unmet need (diabetes OR 0.85, 95% CI 0.76–0.94; hypertension OR 0.96, 95% CI 0.89–1.04). Furthermore, the likelihood of an unmet need increased with the number of chronic conditions (OR 1.71, 95% CI 1.56–1.88 for 3 or more conditions). Respondents with chronic conditions were more likely than those without to report an unmet need related to resource availability (OR 1.14, 95% CI 1.06–1.22).
Adults with chronic medical conditions are more likely to report an unmet health care need, and the likelihood increases with an increasing number of conditions. Whether these unmet needs are associated with worse outcomes, and whether interventions targeted to address these needs may improve outcomes for Canadians with chronic disease, remain to be determined.
PMCID: PMC3659214  PMID: 23696769
19.  Enrolment in primary care networks: impact on outcomes and processes of care for patients with diabetes 
Primary care networks are a newer model of primary care that focuses on improved access to care and the use of multidisciplinary teams for patients with chronic disease. We sought to determine the association between enrolment in primary care networks and the care and outcomes of patients with diabetes.
We used administrative health care data to study the care and outcomes of patients with incident and prevalent diabetes separately. For patients with prevalent diabetes, we compared those whose care was managed by physicians who were or were not in a primary care network using propensity score matching. For patients with incident diabetes, we studied a cohort before and after primary care networks were established. Each cohort was further divided based on whether or not patients were cared for by physicians enrolled in a network. Our primary outcome was admissions to hospital or visits to emergency departments for ambulatory care sensitive conditions specific to diabetes.
Compared with patients whose prevalent diabetes is managed outside of primary care networks, patients in primary care networks had a lower rate of diabetes-specific ambulatory care sensitive conditions (adjusted incidence rate ratio 0.81, 95% confidence interval [CI] 0.75 to 0.87), were more likely to see an ophthalmologist or optometrist (risk ratio 1.19, 95% CI 1.17 to 1.21) and had better glycemic control (adjusted mean difference −0.067, 95% CI −0.081 to −0.052).
Patients whose diabetes was managed in primary care networks received better care and had better clinical outcomes than patients whose condition was not managed in a network, although the differences were very small.
PMCID: PMC3273535  PMID: 22143232
20.  Evaluation of an electronic warfarin nomogram for anticoagulation of hemodialysis patients 
BMC Nephrology  2011;12:46.
Warfarin nomograms to guide dosing have been shown to improve control of the international normalized ratio (INR) in the general outpatient setting. However, the effectiveness of these nomograms in hemodialysis patients is unknown. We evaluated the effectiveness of anticoagulation using an electronic warfarin nomogram administered by nurses in outpatient hemodialysis patients, compared to physician directed therapy.
Hemodialysis patients at any of the six outpatient clinics in Calgary, Alberta, treated with warfarin anticoagulation were included. Two five-month time periods were compared: prior to and post implementation of the nomogram. The primary endpoint was adequacy of anticoagulation (proportion of INR measurements within range ± 0.5 units).
Overall, 67 patients were included in the pre- and 55 in the post-period (with 40 patients in both periods). Using generalized linear mixed models, the adequacy of INR control was similar in both periods for all range INR levels: in detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%); post 95.6% (95% CI: 89.4% - 98.3%); p = 0.95); INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%); post 77.4% (95% CI: 72.0% - 82.0%); p = 0.20); and, INR 2.5 to 3.5 (pre 84.3% (95% CI: 59.4% - 95.1%); post 66.8% (95% CI: 39.9% - 86.0%); p = 0.29). The mean number of INR measurements per patient decreased significantly between the pre- (30.5, 95% CI: 27.0 - 34.0) and post- (22.3, 95% CI: 18.4 - 26.1) (p = 0.003) period. There were 3 bleeding events in each of the periods.
An electronic warfarin anticoagulation nomogram administered by nurses achieved INR control similar to that of physician directed therapy among hemodialysis patients in an outpatient setting, with a significant reduction in frequency of testing. Future controlled trials are required to confirm the efficacy of this nomogram.
PMCID: PMC3189863  PMID: 21943221
Anticoagulation; Hemodialysis; Warfarin nomogram
21.  Recent epidemiologic trends of diabetes mellitus among status Aboriginal adults 
Little is known about longitudinal trends in diabetes mellitus among Aboriginal people in Canada. We compared the incidence and prevalence of diabetes, and its impact on mortality, among status Aboriginal adults and adults in the general population between 1995 and 2007.
We examined de-identified data from Alberta Health and Wellness administrative databases for status Aboriginal people (First Nations and Inuit people with treaty status) and members of the general public aged 20 years and older who received a diagnosis of diabetes mellitus from Apr. 1, 1995, to Mar. 31, 2007. We calculated the incidence and prevalence of diabetes and mortality rate ratios by sex and ethnicity in 2007. We examined the average relative changes per year for longitudinal trends.
The average relative change per year in the prevalence of diabetes showed a smaller increase over time in the Aboriginal population than in the general population (2.39 v. 4.09, p < 0.001). A similar finding was observed for the incidence of diabetes. In the Aboriginal population, we found that the increase in the average relative change per year was greater among men than among women (3.13 v. 1.88 for prevalence, p < 0.001; 2.60 v. 0.02 for incidence, p = 0.001). Mortality among people with diabetes decreased over time to a similar extent in both populations. Among people without diabetes, mortality decreased in the general population but was unchanged in the Aboriginal population (−1.92 v. 0.11, p = 0.04). Overall, mortality was higher in the Aboriginal population than in the general population regardless of diabetes status.
The increases in the incidence and prevalence of diabetes over the study period appeared to be slower in the status Aboriginal population than in the general population in Alberta, although the overall rates were higher in the Aboriginal population. Mortality decreased among people with diabetes in both populations but was higher overall in the Aboriginal population regardless of diabetes status.
PMCID: PMC3168663  PMID: 21788417
22.  Dialysis and transplantation among Aboriginal children with kidney failure 
Relatively little is known about the management and outcomes of Aboriginal children with renal failure in Canada. We evaluated differences in dialysis modality, time spent on dialysis, rates of kidney transplantation, and patient and allograft survival between Aboriginal children and non-Aboriginal children.
For this population-based cohort study, we used data from a national pediatric end-stage renal disease database. Patients less than 18 years old who started renal replacement treatment (dialysis or kidney transplantation) in nine Canadian provinces (Quebec data were not available) and all three territories between 1992 and 2007 were followed until death, loss to follow-up or end of the study period. We compared initial modality of dialysis and time to first kidney transplant between Aboriginal children, white children and children of other ethnicity. We examined the association between ethnicity and likelihood of kidney transplantation using adjusted Cox proportional hazard models for Aboriginal and white children (data for the children of other ethnicity did not meet the assumptions of proportional hazards).
Among 843 pediatric patients included in the study, 104 (12.3%) were Aboriginal, 521 (61.8%) were white, and 218 (25.9%) were from other ethnic minorities. Hemodialysis was the initial modality of dialysis for 48.0% of the Aboriginal patients, 42.7% of the white patients and 62.6% of those of other ethnicity (p < 0.001). The time from start of dialysis to first kidney transplant was longer among the Aboriginal children (median 1.75 years, interquartile range 0.69–2.81) than among the children in the other two groups (p < 0.001). After adjustment for confounders, Aboriginal children were less likely than white children to receive a transplant from a living donor (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21–0.61) or a transplant from any donor (HR 0.54, 95% CI 0.40–0.74) during the study period.
The time from start of dialysis to first kidney transplant was longer among Aboriginal children than among white children. Further evaluation is needed to determine barriers to transplantation among Aboriginal children.
PMCID: PMC3134757  PMID: 21609989
23.  The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: Part I – blood pressure measurement, diagnosis and assessment of risk 
To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension.
MEDLINE searches were conducted from November 2008 to October 2009 with the aid of a medical librarian. Reference lists were scanned, experts were contacted, and the personal files of authors and subgroup members were used to identify additional studies. Content and methodological experts assessed studies using prespecified, standardized evidence-based algorithms. Recommendations were based on evidence from peer-reviewed full-text articles only.
Recommendations for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals are outlined. Changes to the recommendations for 2010 relate to automated office blood pressure measurements. Automated office blood pressure measurements can be used in the assessment of office blood pressure. When used under proper conditions, an automated office systolic blood pressure of 135 mmHg or higher or diastolic blood pressure of 85 mmHg or higher should be considered analogous to a mean awake ambulatory systolic blood pressure of 135 mmHg or higher and diastolic blood pressure of 85 mmHg or higher, respectively.
All recommendations were graded according to strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. To be approved, all recommendations were required to be supported by at least 70% of task force members. These guidelines will continue to be updated annually.
PMCID: PMC2886554  PMID: 20485688
Blood pressure; Diagnosis; Guidelines; High blood pressure; Hypertension; Risk factors
24.  The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy 
To update the evidence-based recommendations for the prevention and treatment of hypertension in adults for 2010.
For lifestyle and pharmacological interventions, randomized trials and systematic reviews of trials were preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the general lack of long-term morbidity and mortality data in this field. Progressive renal impairment was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease.
A Cochrane Collaboration librarian conducted an independent MEDLINE search from 2008 to August 2009 to update the 2009 recommendations. To identify additional studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence.
For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to 1500 mg (65 mmol) per day in adults 50 years of age or younger, to 1300 mg (57 mmol) per day in adults 51 to 70 years of age, and to 1200 mg (52 mmol) per day in adults older than 70 years of age; perform 30 min to 60 min of moderate aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (less than 102 cm for men and less than 88 cm for women); limit alcohol consumption to no more than 14 standard drinks per week for men or nine standard drinks per week for women; follow a diet that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources, and that is low in saturated fat and cholesterol; and consider stress management in selected individuals with hypertension.
For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on the patient’s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in patients with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, considerations for initial therapy should include thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. The combination of ACE inhibitors and ARBs should not be used, unless compelling indications are present to suggest consideration of dual therapy.
Agents appropriate for first-line therapy for isolated systolic hypertension include thiazide diuretics, long-acting dihydropyridine CCBs or ARBs. In patients with coronary artery disease, ACE inhibitors, ARBs or beta-blockers are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. In selected high-risk patients in whom combination therapy is being considered, an ACE inhibitor plus a long-acting dihydropyridine CCB is preferable to an ACE inhibitor plus a thiazide diuretic. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian lipid treatment guidelines. Selected patients with hypertension who do not achieve thresholds for statin therapy, but who are otherwise at high risk for cardiovascular events, should nonetheless receive statin therapy. Once blood pressure is controlled, low-dose acetylsalicylic acid therapy should be considered.
All recommendations were graded according to the strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 80% consensus. These guidelines will continue to be updated annually.
The Canadian Hypertension Education Program process is sponsored by the Canadian Hypertension Society, Blood Pressure Canada, the Public Health Agency of Canada, the College of Family Physicians of Canada, the Canadian Pharmacists Association, the Canadian Council of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.
PMCID: PMC2886555  PMID: 20485689
Antihypertensive drugs; Blood pressure; Guidelines; High blood pressure; Hypertension; Lifestyle interventions
25.  Nocturnal Hypoxia and Loss of Kidney Function 
PLoS ONE  2011;6(4):e19029.
Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown.
We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year.
858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67).
Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function.
PMCID: PMC3084745  PMID: 21559506

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