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OBJECTIVES: To investigate if an association exists between being born large for gestational age (LGA) and verbal ability or externalizing behaviour problems at ages 4-5 years. METHOD: A secondary analysis was conducted using the National Longitudinal Survey of Children and Youth, including singleton births in 2004-2005 followed till 4-5 years (n = 1685). LGA was defined as a birth weight > 90th percentile. Outcomes included poor verbal ability (scoring < 15th percentile on the Revised Peabody Picture Vocabulary Test) and externalizing behaviour problems (scoring > 90th percentile on externalizing behaviour scales). Multivariable logistic regression with longitudinal standardized funnel weights and bootstrapping estimation were used. RESULTS: Infants born LGA were not found to be at increased risk for poor verbal ability (aOR: 1.16 [0.49,2.72] and aOR: 0.83 [0.37,1.87] for girls and boys, resp.) or externalizing behaviour problems (aOR: 1.24 [0.52,2.93] and aOR: 1.24 [0.66,2.36] for girls and boys, resp.). Social factors were found to impact developmental attainment. Maternal smoking led to an increased risk for externalizing behaviour problems (aOR: 3.33 [1.60,6.94] and aOR: 2.12 [1.09,4.13] for girls and boys, resp.). CONCLUSION: There is no evidence to suggest that infants born LGA are at increased risk for poor verbal ability or externalizing behaviour problems.

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BACKGROUND: Escherichia coli O157:H7 is a common cause of bacterial gastroenteritis and may increase the risk of hypertension. We studied the risk of hypertension in pregnancy following a large E. coli O157:H7 outbreak that occurred in Walkerton, Canada, in the year 2000. METHODS: We linked data collected from Walkerton residents to provincial healthcare databases. We studied the pregnancies of three groups of women: two groups from Walkerton (those with and without acute gastroenteritis during outbreak) and a third group from neighboring rural communities unaffected by the outbreak. The primary outcome was a composite of gestational hypertension or preeclampsia. Secondary outcomes were gestational hypertension and preeclampsia examined separately. RESULTS: The median time to pregnancy after cohort entry was five years. The composite outcome was not significantly higher among women with gastroenteritis during the outbreak compared with residents of neighboring communities (8 of 117 (6.8%) versus 96 of 2166 (4.4%) pregnancies, respectively; adjusted relative risk 1.5 (95% confidence interval (CI) 0.8 to 3.2)). When examined separately the risk of preeclampsia was significantly higher among women with gastroenteritis (4 of 117 (3.4%) versus 17 of 2166 (0.8%) pregnancies; adjusted relative risk 3.8 (95% CI 1.3 to 11.6)). However, the risk of preeclampsia was lower than expected in the referent group and overall there were a small number of events in all the groups. CONCLUSION: There was no significant association between E. coli O157:H7 gastroenteritis and our primary assessment of hypertension in pregnancy.

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BACKGROUND AND OBJECTIVES: The effect of increased fluid intake on kidney function is unclear. This study evaluates the relationship between urine volume and renal decline over 6 years in a large community-based cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective cohort study was undertaken in Canada from 2002 to 2008. We obtained 24-hour urine samples from adult participants with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) at study entry. Percentage annual change in eGFR from baseline was categorized as average decline <1% per year, between 1% and 4.9% (mild-to-moderate decline) or ≥5% (rapid decline). RESULTS: 2148 participants provided valid 24-hour urine samples, grouped as <1 L/d (14.5%); 1 to 1.9 L/d (51.5%); 2 to 2.9 L/d (26.3%); and ≥3 L/d (7.7%). Baseline eGFR for each category of urine volume was 90, 88, 84, and 87 ml/min per 1.73 m(2), respectively. Overall, eGFR declined by 1% per year, with 10% demonstrating rapid decline and 40% demonstrating mild-to-moderate decline. An inverse, graded relationship was evident between urine volume and eGFR decline: For each increasing category of 24-hour urine volume, percentage annual eGFR decline was progressively slower, from 1.3%, 1.0%, 0.8%, to 0.5%, respectively; P = 0.02. Compared with those with urine volume 1 to 1.9 L/d, those with urine volume ≥3 L/d were significantly less likely to demonstrate mild-to-moderate decline (adjusted odds ratio 0.66; 95% confidence interval 0.46 to 0.94) or rapid decline (adjusted odds ratio 0.46; 95% confidence interval 0.23 to 0.92); adjusted for age, gender, baseline eGFR, medication use for hypertension (including diuretics), proteinuria, diabetes, and cardiovascular disease. CONCLUSIONS: In this community-based cohort, decline in kidney function was significantly slower in those with higher versus lower urine volume.

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Rapid kidney function decline (RKFD) predicts cardiovascular morbidity and mortality, but serial assessment of estimated GFR (eGFR) is not cost-effective for the general population. Here, we evaluated the predictive value of albuminuria and three thresholds of dipstick proteinuria to identify RKFD in 2,574 participants in a community-based prospective cohort study with a median of 7 years follow-up. Median change in eGFR was -0.78 ml/min per 1.73 m(2) per year; with 8.5% experiencing RKFD, defined as a >5% annual eGFR decline from baseline. Of those with RKFD, 65% advanced to a new CKD stage compared with 19% of those without RKFD. Dipstick protein ≥ 1 g/L was a stronger predictor of RKFD than albuminuria. Overall, 2.5% screened positive for dipstick protein ≥ 1 g/L at baseline; one of every 2.6 patients would have RKFD if all were followed with serial eGFR measurement. Overall, the screening strategy correctly identified progression status for 90.8% of patients, mislabeled 1.5% as RKFD, and missed 7.7% with eventual RKFD. Among those with risk factors (cardiovascular disease, age >60, diabetes, or hypertension), the probability of identifying RKFD from serial eGFR measurements increased from 13 to 44% after incorporating dipstick protein (≥ 1 g/L threshold). In summary, inexpensive screening with urine dipstick should allow primary care physicians to follow fewer patients with serial eGFR assessment but still identify those with rapid decline of kidney function.

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Cystatin C may be a more accurate marker of the glomerular filtration rate (GFR) than creatinine. We evaluated the performance of the creatinine-based abbreviated modification of diet in renal disease (MDRD), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and 6 cystatin C-based equations in estimating GFR (eGFR) in a heterogeneous sample of patients. Measured GFR (mGFR) was obtained from the plasma clearance of 99mtechnetium Diethylenetriaminepentaacetic acid in 42 adult patients referred for nuclear GFR testing (January to March 2008). We evaluated the bias, precision, and accuracy of the abbreviated MDRD, CKD-EPI, Filler, Grubb, Hoek, Larsson, Le Bricon, and Rule eGFR equations. Participants had a mean mGFR of 70.9 mL/min/1.73 m2 (range: 22-125 mL/min/1.73 m2), a median age of 57 years (interquartile range: 45, 66), were 62% male, and were 38% liver transplant recipients. Correlation coefficients between eGFRs and mGFR ranged from 0.65 to 0.87 (each P<0.001). The cystatin C-based Hoek equation had the best overall performance with a low bias (-1.4 mL/min/1.73 m2), good precision (13.3 mL/min/1.73 m2), and greatest accuracy, with 93% of values within 30% of mGFR. Although the CKD-EPI equation had the lowest bias (-0.6 mL/min/1.73 m2), it had poor precision (20.7 mL/min/1.73 m2) and low accuracy, with only 69% of values within 30% of mGFR. The Hoek equation remained accurate and had the least bias when patients were grouped according to the history of liver transplantation and the mGFR above or below 60 mL/min/1.73 m2. In this heterogeneous sample, the cystatin C-based Hoek equation performed the best overall, regardless of mGFR level or history of liver transplantation.

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BACKGROUND: The use of arteriovenous fistulas (AVFs) among hemodialysis (HD) patients has been consistently associated with lower rates of morbidity and mortality; however, up to 30% of eligible patients refuse the creation or cannulation of an AVF. We aimed to understand the attitudes, beliefs, preferences and values of patients who refused creation or use of an AVF. METHODS: With qualitative methodology, we conducted semi-structured interviews with 13 HD patients (Canada, 2009), who previously refused creation or use of an AVF. Three independent analysts reviewed interview transcripts. RESULTS: We discovered three main themes that impacted the decision to refuse a fistula: (i) poor previous personal or vicarious experiences with the fistula, including cannulation, bleeding, time commitment and appearance; (ii) knowledge transfer and informed decision making. Patients identified information from other patients to be as important as information from health care workers, that information on vascular access (VA) was presented but not understood and that timing of information was crucial with information overload at the start of dialysis and (iii) maintenance of status quo and outlook on life. Some patients stated they live day-to-day without being influenced by the mortality risks with a catheter. CONCLUSIONS: AVF refusal is multifactorial and depends on individual patients. Although nephrologists consider the fistula to be the optimal VA, patients do not think in the same terms of reducing infection rates but focus on the practical day-to-day use of their VA and its influence on their quality of life and future outlook.

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BACKGROUND: Recent studies have reported a trend toward earlier initiation of dialysis (i.e., at higher levels of glomerular filtration rate) and an association between early initiation and increased risk of death. We examined trends in initiation of hemodialysis within Canada and compared the risk of death between patients with early and late initiation of dialysis. METHODS: The analytic cohort consisted of 25 910 patients at least 18 years of age who initiated hemodialysis, as identified from the Canadian Organ Replacement Register (2001-2007). We defined the initiation of dialysis as early if the estimated glomerular filtration rate was greater than 10.5 mL/min per 1.73 m². We fitted time-dependent proportional-hazards Cox models to compare the risk of death between patients with early and late initiation of dialysis. RESULTS: Between 2001 and 2007, mean estimated glomerular filtration rate at initiation of dialysis increased from 9.3 (standard deviation [SD] 5.2) to 10.2 (SD 7.1) (p < 0.001), and the proportion of early starts rose from 28% (95% confidence interval [CI] 27%-30%) to 36% (95% CI 34%-37%). Mean glomerular filtration rate was 15.5 (SD 7.7) mL/min per 1.73 m² among those with early initiation and 7.1 (SD 2.0) mL/min per 1.73 m² among those with late initiation. The unadjusted hazard ratio (HR) for mortality with early relative to late initiation was 1.48 (95% CI 1.43-1.54). The HR decreased to 1.18 (95% CI 1.13-1.23) after adjustment for demographic characteristics, serum albumin, primary cause of end-stage renal disease, vascular access type, comorbidities, late referral and transplant status. The mortality differential between early and late initiation per 1000 patient-years narrowed after one year of follow-up, but never crossed and began widening again after 24 months of follow-up. The differences were significant at 6, 12, 30 and 36 months. INTERPRETATION: In Canada, dialysis is being initiated at increasingly higher levels of glomerular filtration rate. A higher glomerular filtration rate at initiation of dialysis is associated with an increased risk of death that is not fully explained by differences in baseline characteristics.

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OBJECTIVES: To evaluate the risk for hypertension, renal impairment, and cardiovascular disease within eight years of gastroenteritis from drinking water contaminated with Escherichia coli O157:H7 and Campylobacter. DESIGN: A prospective cohort study. Setting Walkerton, Ontario, Canada. PARTICIPANTS: 1977 adult participants in the Walkerton Health Study recruited between 2002 and 2005 after an outbreak of gastroenteritis in May 2000, when a municipal water system was contaminated, with no pre-outbreak history of outcome measures. OUTCOME MEASURES: Information was collected annually via survey, physical examination, and laboratory assessment. Primary measures were acute gastroenteritis (diarrhoeal illness lasting >3 days, bloody diarrhoea, or >3 loose stools/day), hypertension (blood pressure ≥140/90 mm Hg), and renal impairment (microalbuminuria or estimated glomerular filtration rate <60 ml/min/1.73 m(2)). Self reported physician diagnosis of cardiovascular disease (myocardial infarction, stroke, or congestive heart failure) was a secondary outcome. RESULTS: Acute gastroenteritis at the time of the outbreak was reported by 1067 (54%) of participants. Incident hypertension was detected in 697 (35%) (294 (32%) of group not exposed to acute gastroenteritis v 403 (38%) of exposed group). While 572 (29%) had at least one indicator of renal impairment (266 (29%) of unexposed v 306 (29%) of exposed), only 30 (1.5%) had both (8 (0.9%) of unexposed v 22 (2.1%) of exposed). Cardiovascular disease was reported by 33/1749 (1.9%). The adjusted hazard ratios for hypertension and cardiovascular disease after acute gastroenteritis were 1.33 (95% confidence interval 1.14 to 1.54) and 2.13 (1.03 to 4.43) respectively. The adjusted hazard ratio for the presence of either indicator of renal impairment was 1.15 (0.97 to 1.35) and was 3.41 (1.51 to 7.71) for the presence of both. CONCLUSION: Gastroenteritis from drinking water contaminated with E coli O157:H7 and Campylobacter was associated with an increased risk for hypertension, renal impairment, and self reported cardiovascular disease. Annual monitoring of blood pressure and periodic monitoring of renal function may be warranted for individuals who experience E coli O157:H7 gastroenteritis.

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The authors evaluated the risk for pregnancy-related hypertension among previously healthy women who conceived within 5 years of exposure to drinking water contaminated with Escherichia coli O157.H7 in Walkerton, Canada (2000). Chronic hypertension was defined as systolic/diastolic blood pressure >/=140/90 mm Hg before 20 weeks gestation; gestational hypertension was defined as new onset systolic/diastolic blood pressure >/=140/90 mm Hg >/=20 weeks gestation. The incidence of hypertension was compared between women who were asymptomatic during the outbreak to those who experienced acute gastroenteritis. Blood pressure data were available for 135 of 148 eligible pregnancies. The adjusted relative risks for chronic and gestational hypertension were 1.5 (95% confidence interval [CI]: 0.3-7.7) and 1.0 (95% CI: 0.4-2.5), respectively. Mean arterial pressure before 20 weeks gestation was 2.7 mm Hg higher in women who had acute gastroenteritis (95% CI: 0.05-5.4). A trend toward higher chronic hypertension and mean arterial pressure in early pregnancy was observed among women who experienced gastroenteritis after exposure to bacterially-contaminated drinking water.

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OBJECTIVE: Childhood overweight and obesity may result in premature onset of cardiovascular risk factors such as hypertension. Rural populations in North America may be at increased risk for overweight. We evaluated whether overweight and obesity were associated with prehypertension and hypertension in a well-characterized population of children in rural Canada. METHODS: The study population for this cross-sectional study was composed of children (aged 4-17 years) who were participants of the Walkerton Health Study (Canada) in 2004. Prehypertension and hypertension were defined on the basis of percentiles from the average of 3 blood pressure measures taken on a single occasion. Percentiles for BMI and blood pressure were calculated by using the 2000 Centers for Disease Control and Prevention growth charts. Multinomial logistic regression was used to evaluate the odds for prehypertension and hypertension resulting from overweight and obesity. RESULTS: Of 675 children (98.7% white), 122 (18.1%) were overweight and 77 (11.4%) were obese. Prehypertension and hypertension were detected in 51 (7.6%) and 50 (7.4%), respectively. After adjustment for family history of hypertension and kidney disease, obesity was associated with both prehypertension and hypertension. Overweight was associated with hypertension but not prehypertension. These associations were observed across the genders and children aged <13 and >or=13 years, except that overweight was not associated with hypertension among girls. CONCLUSIONS: In this population of children who lived in a rural community in Canada, overweight and obesity were strongly associated with elevated blood pressure. Whether blood pressure normalizes with improvements in diet, physical activity, and environment is an area for additional study.

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Thrombotic thrombocytopenic purpura/Haemolytic uremic syndrome (TTP/HUS) is a thrombotic microangiopathy with a 6-month mortality rate of 16-29%. The present study described the clinical features, treatment regime and 6-month all-cause mortality rate of TTP/HUS patients at the London Health Sciences Centre (LHSC), Canada. Data for this retrospective cohort study were obtained from inpatient and outpatient records for all patients referred for plasma exchange therapy at LHSC, Canada between 1981 and 2006. Patients (n = 110) were categorized as: idiopathic primary (38%) or relapsed (16%), and secondary responsive (30%) or non-responsive (16%). Mortality data were available for all but three patients. The all-cause 6-month mortality rate was 19% overall and was 12% and 26% among idiopathic and secondary TTP/HUS patients, respectively. No mortality events occurred among the 17 idiopathic patients who relapsed. Relapsed patients had the least severe presenting characteristics, the fastest response time, and experienced significant improvement in the severity of clinical features between the first and final presentation. These findings suggest an excellent outcome for relapsed TTP/HUS patients. Patient education, surveillance, and aggressive plasma exchange therapy are hypothesized to improve the likelihood of survival: these hypotheses should be tested in a randomized controlled trial.

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The Kidney Disease Outcomes Quality Initiative has recommended the use of GFR estimating equations to detect silent chronic kidney disease (CKD) in the community. The benefit of general reporting of CKD must be balanced with the harm of mislabeling people who do not have CKD. The popular Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) GFR estimating equations were compared with the recently devised Rule equation in a representative community population sample (2166) divided into subsamples with (385) and without (1781) previous renal impairment. The prevalence of CKD was CG > MDRD >> Rule estimates. The magnitude of difference in prevalence of CKD as detected by the MDRD and CG versus the Rule equation increases markedly when the subsamples with (30.8 and 29.7 versus 17.5%) and without (12 and 11.3 versus 3.0%) previous kidney impairment are compared. General demographic and potential or known risk factors were used in a logistic regression model to assess the association with CKD. The MDRD estimates note female gender (odds ratio 2.19; 95% confidence interval 1.63 to 2.95) and both MDRD and the Rule equations identify hypertension and diabetes as significant CKD risk factors. All estimating equations identify age to be associated with CKD. The annualized serial decline in GFR was CG > MDRD > Rule estimates. Only the Rule GFR estimates detected a greater decline in renal impaired versus unimpaired populations. The calibrated Rule equation seems to perform better than CG and MDRD (CKD 3 versus 11.3 to 12%) but lacks validation against gold standards for community-based screening.

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This paper highlights the impact of survey weights on model fit in multiple linear regression with specific reference to the National Longitudinal Survey of Children and Youth (NLSCY) and provides recommendations for the treatment of influential observations. Multiple linear regression was used to estimate the association between child and family factors in the preschool years and vocabulary development at school age. Analyses were performed with and without survey weights. The model fit was assessed by examining the distribution of the studentized residuals and the change in the regression coefficients that would occur if an observation were removed. Two summary measures of influence, Dffits and Cook's D are reported. The models were refit excluding influential observations. Weighting of the linear model resulted in previously non-influential observations having an undue influence on the estimation of the regression parameters in the weighted model. The influential observations were driven primarily by the size of the survey weight as opposed to unusual values of x and y. Researchers working with large national health surveys such as the NLSCY and the National Population Health Survey (NPHS) are advised to include a detailed influence analysis before any final conclusions are made.

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