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Biomedical subjects

Bruce Culleton

Publications and source records attributed to Bruce Culleton.

13 recordsLinked to original sources
PubMed2006

Residence location and likelihood of kidney transplantation.

BACKGROUND: In a universal, public health care system, access to kidney transplantation should not be influenced by residence location. We determined the likelihood of kidney transplantation from deceased donors among Canadian dialysis patients living in 7 geographic regions. Within each region we also determined whether distance from the closest transplant centre was associated with the likelihood of transplantation. METHODS: A random sample of 7034 subjects initiating dialysis in Canada between 1996 and 2000 was studied. We used Cox proportional hazards models to examine the relation between residence location and the likelihood of kidney transplantation from deceased donors over a median period of 2.4 years. RESULTS: There were significant differences in the likelihood of kidney transplantation from deceased donors and predicted waiting times between the different geographic regions. For example, the adjusted relative likelihood of transplantation in Alberta was 3.74 (95% confidence interval [CI] 2.95-4.76) compared with the likelihood in Ontario (p < 0.001). These differences persisted after further adjustment for differences in the rate of deceased organ donation. Within regions, patients who resided 50.1-150 km, 150.1-300 km and more than 300 km from the closest transplant centre had a similar adjusted likelihood of receiving a kidney transplant as those who lived less than 50 km away. INTERPRETATION: The adjusted likelihood of undergoing a kidney transplant from a deceased donor varied substantially between geographic regions in Canada. In contrast, the likelihood of transplantation within regions was not affected by distance from the closest transplant centre.

Aged↗
PubMed2006

Chronic kidney disease and mortality risk: a systematic review.

Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.

Cardiovascular Diseases↗
PubMed2006

The 2006 Canadian Hypertension Education Program recommendations for the management of hypertension: Part II - Therapy.

OBJECTIVE: To provide updated, evidence-based recommendations for the management of hypertension in adults. OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, evidence from randomized, controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. For lifestyle interventions, blood pressure (BP) lowering was accepted as a primary outcome given the lack of long-term morbidity/mortality data in this field. For treatment of patients with kidney disease, the development of proteinuria or worsening of kidney function was also accepted as a clinically relevant primary outcome. EVIDENCE: MEDLINE searches were conducted from November 2004 to October 2005 to update the 2005 recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS: Lifestyle modifications to prevent and/or treat hypertension include the following: perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index of 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 in men or nine standard drinks per week in women; follow a diet that is reduced in saturated fat and cholesterol and that emphasizes fruits, vegetables and low-fat dairy products; restrict salt intake; and consider stress management in selected individuals. Treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and comorbid conditions. BP should be lowered to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease (regardless of the degree of proteinuria). Most adults with hypertension require more than one agent to achieve these target BPs. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), angiotensin-converting enzyme (ACE) inhibitors (in nonblack patients), long-acting calcium channel blockers or angiotensin receptor antagonists. Other agents for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine calcium channel blockers or angiotensin receptor antagonists. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or in patients without albuminuria, thiazides or dihydropyridine calcium channel blockers) are appropriate first-line therapies; and in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended. All hypertensive patients should have their fasting lipids screened, and those with dyslipidemia should be treated using the thresholds, targets and agents recommended by the Canadian Hypertension Education Program Working Group on the management of dyslipidemia and the prevention of cardiovascular disease. Selected patients with hypertension, but without dyslipidemia, should also receive statin therapy and/or acetylsalicylic acid therapy. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the 45 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

Advisory Committees↗
PubMed2005

Acute hepatic failure and multi-system organ failure secondary to replacement of the liver with metastatic melanoma.

BACKGROUND: Metastatic malignant melanoma to the liver resulting in fulminant hepatic failure is a rare occurrence. CASE PRESENTATION: A 46 year old man presented to hospital with massive hepatomegaly, elevated liver enzymes and increased lactate three weeks following resection of a malignant melanoma from his shoulder (Clark level 5). Initially stable, he decompensated 24 to 48 hours subsequent to presentation with respiratory failure requiring mechanical ventilation, distributive shock requiring high dose vasopressor infusion, coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and severe metabolic abnormalities including hyperkalemia, acidosis, hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive physiologic support he received palliation. Autopsy revealed >80% liver infiltration by metastatic malignant melanoma. CONCLUSION: We report a case of fulminant hepatic failure secondary to metastatic malignant melanoma infiltration of the liver.

Autopsy↗
PubMed2005

Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study.

Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. This phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis (HD) and peritoneal dialysis (PD) patients with PTH > or =300 pg/ml despite traditional therapy. A total of 395 patients received once-daily oral cinacalcet (260 HD, 34 PD) or placebo (89 HD, 12 PD) titrated from 30 to 180 mg to achieve a target intact PTH (iPTH) level of < or =250 pg/ml. During a 10-wk efficacy assessment phase, cinacalcet was more effective than control for PTH reduction outcomes, including proportion of patients with mean iPTH levels < or =300 pg/ml (46 versus 9%), proportion of patients with > or =30% reduction in iPTH from baseline (65 versus 13%), and proportion of patients with > or =20, > or =40, or > or =50% reduction from baseline. Cinacalcet had comparable efficacy in HD and PD patients; 50% of PD patients achieved a mean iPTH < or =300 pg/ml. Cinacalcet also significantly reduced serum calcium, phosphorus, and Ca x P levels compared with control treatment. The most common side effects, nausea and vomiting, were usually mild to moderate in severity and transient. Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH, Ca x P, calcium, and phosphorus levels in patients who received HD or PD. Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.

Administration, Oral↗
PubMed2005

A systematic review of the effect of nocturnal hemodialysis on blood pressure, left ventricular hypertrophy, anemia, mineral metabolism, and health-related quality of life.

BACKGROUND: Nocturnal hemodialysis is a novel form of dialysis where patients perform dialysis 6 nights per week while they sleep. Multiple publications report significant improvements in selected clinical outcomes, although the strength of these results is limited by shortcomings in study design. A systematic review of the current available literature was undertaken to examine the effect of nocturnal hemodialysis on key health outcomes. METHODS: An inclusive search of medical databases was undertaken to identify all nocturnal hemodialysis studies. These results were manually reviewed for relevance to nocturnal hemodialysis and its impact on the following predefined health outcomes: blood pressure control, left ventricular hypertrophy, anemia, mineral metabolism, and health related quality of life. Case reports, short-term studies (<4 weeks), studies without comparator groups, and studies not reporting data in a quantitative fashion were excluded. The results of the remaining studies were reported in tabular format. RESULTS: Of the initial 270 studies identified, only 14 met inclusion/exclusion criteria. No studies examining the impact of nocturnal hemodialysis on mortality were identified. All studies reported improved blood pressure control after conversion to nocturnal hemodialysis. Data regarding the other health outcomes of interest revealed mixed results. CONCLUSION: Nocturnal hemodialysis is a potential alternative to conventional intermittent hemodialysis. Before significant resources are invested in initiating nocturnal hemodialysis programs, further data on mortality and cardiovascular morbidity, preferably from randomized clinical trials, are required.

Anemia↗
PubMed2005

The 2005 Canadian Hypertension Education Program recommendations for the management of hypertension: part II - therapy.

OBJECTIVE: To provide updated, evidence-based recommendations for the management of hypertension in adults. OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was preferentially reviewed. While changes in cardiovascular morbidity and mortality were the primary outcomes of interest, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity/mortality data in this field, and for certain comorbid conditions, other relevant outcomes, such as development of proteinuria or worsening of kidney function, were considered. EVIDENCE: MEDLINE searches were conducted from November 2003 to October 2004 to update the 2004 recommendations. Reference lists were scanned, experts were contacted, and the personal files of the subgroup members and authors were used to identify additional published studies. All relevant articles were reviewed and appraised independently, using prespecified levels of evidence, by content and methodology experts. As per previous years, only studies that had been published in the peer-reviewed literature were included; evidence from abstracts, conference presentations and unpublished personal communications was not included. RECOMMENDATIONS: Lifestyle modifications to prevent and/or treat hypertension include the following: perform 30 min to 60 min of aerobic exercise on four to seven days of the week; maintain a healthy body weight (body mass index of 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 units per week in men or nine units per week in women; follow a reduced fat, low cholesterol diet with an adequate intake of potassium, magnesium and calcium; restrict salt intake; and consider stress management (in selected individuals). Treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and any comorbid conditions. Blood pressure should be lowered to 140/90 mmHg or less in all patients, and to 130/80 mmHg or less in those with diabetes mellitus or chronic kidney disease. Most adults with hypertension require more than one agent to achieve target blood pressures. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers and angiotensin receptor antagonists. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine calcium channel blockers and angiotensin receptor antagonists. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or thiazides in patients with diabetes mellitus without albuminuria) are appropriate first-line therapies; and in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended. All hypertensive patients should have their fasting lipids screened, and those with dyslipidemia should be treated using the thresholds, targets and agents recommended by the Canadian Hypertension Education Program Working Group on the management of dyslipidemia and the prevention of cardiovascular disease. Selected patients with hypertension, but without dyslipidemia, should also receive statin therapy and/or acetylsalicylic acid therapy. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the 43 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

Antihypertensive Agents↗
PubMed2004

Predictors of new-onset kidney disease in a community-based population.

CONTEXT: Kidney disease is associated with an increased risk for the development of cardiovascular disease and end-stage renal disease; however, risk factors for kidney disease have not been well studied. OBJECTIVE: To identify predictors of the development of new-onset kidney disease. DESIGN, SETTING, AND PARTICIPANTS: A community-based, longitudinal cohort study of 2585 participants who attended both a baseline examination in 1978-1982 and a follow-up examination in 1998-2001, and who were free of kidney disease at baseline. MAIN OUTCOME MEASURES: Kidney disease was assessed by the Modification of Diet in Renal Disease Study equation and defined by a glomerular filtration rate (GFR) in the fifth or lower percentile (< or =59.25 mL/min per 1.73 m2 in women, < or =64.25 mL/min per 1.73 m2 in men). Stepwise logistic regression was used to determine the impact of risk factors on the occurrence of new-onset kidney disease. Baseline and long-term, 12-year, averaged risk factor models were explored. RESULTS: At baseline, there were 1223 men and 1362 women, with a mean age of 43 years, who were free of preexisting kidney disease. After a mean follow-up of 18.5 years, 244 participants (9.4%) had developed kidney disease. In multivariable models, baseline age (odds ratio [OR], 2.36 per 10-year increment; 95% confidence interval [CI], 2.00-2.78), GFR (<90 mL/min per 1.73 m2: OR, 3.01; 95% CI, 1.98-4.58; 90-119 mL/min per 1.73 m2: OR, 1.84; 95% CI, 1.16-2.93), body mass index (OR, 1.23 per 1 SD; 95% CI, 1.08-1.41), diabetes (OR, 2.60; 95% CI, 1.44-4.70), and smoking (OR, 1.42; 95% CI, 1.06-1.91) were related to the development of kidney disease. In addition to baseline age and GFR, the long-term, averaged risk factors that were predictive of kidney disease included hypertension (OR, 1.57; 95% CI, 1.17-2.12), high-density lipoprotein cholesterol level (OR, 0.80 per 1 SD; 95% CI, 0.69-0.92), and diabetes (OR, 2.38; 95% CI, 1.45-3.92). Compared with a normal GFR (> or =120 mL/min per 1.73 m2), a mildly reduced GFR (<90 mL/min per 1.73 m2) predicted a 3-fold odds of progression to kidney disease (OR, 2.95; 95% CI, 1.94-4.49). CONCLUSIONS: Established cardiovascular disease risk factors are associated with the development of new-onset kidney disease. Patients with a mildly reduced GFR should be monitored for progression to kidney disease.

Adult↗
PubMed2004

Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: the Framingham Heart Study.

BACKGROUND: Among patients with end-stage renal disease (ESRD), the risk of cardiovascular disease is 10 to 20 times higher than the general population. Adults with ESRD have increased coronary-artery calcification (CAC) detected by electron-beam computed tomography (EBCT). Because the risk of coronary heart disease is increased even at moderate declines in kidney function, we sought to test whether high CAC scores are seen among those with mild reductions in kidney function. METHODS: Men and women free of symptomatic cardiovascular disease underwent EBCT. Coronary calcium was quantified using the method described by Agatston. Renal function was estimated by glomerular filtration rate (GFR). Spearman correlation coefficients were used to test the association between GFR and CAC. RESULTS: Three hundred nineteen subjects (162 men/157 women), mean age 60, were included. Mean GFR was 86 +/- 23 mL/min/1.73 m2 (range 31-169; 10% with GFR <60 mL/min/1.73 m2). The median CAC scores by quartile of GFR were 85.9, 48.1, 7.9, and 2.7. Overall, the unadjusted correlation of GFR and CAC was -0.28 (P < 0.0001). This remained significant after adjustment for age and sex (-0.11, P < 0.05), and additionally after adjustment for body mass index (-0.11, P < 0.05), hypertension (-0.11, P < 0.05), or total cholesterol (-0.12, P= 0.04). A similar correlation was noted after multivariable adjustment (-0.10, P < 0.08). CONCLUSION: Mild declines in kidney function are associated with subclinical coronary artery calcification in a sample of subjects free of clinically apparent cardiovascular disease. This might help explain the increased risk of cardiovascular disease among individuals with renal dysfunction. Larger ongoing studies are needed to better quantify this finding.

Adult↗
PubMed2002

Systematic error in the determination of nocturnal blood pressure dipping status by ambulatory blood pressure monitoring.

BACKGROUND: Vertical displacement of the arm relative to the heart causes inverse changes in blood pressure of approximately 0.8 mmHg for every centimetre change in arm position. Therefore a potential confounding issue in assessing diurnal variation in blood pressure during ambulatory blood pressure monitoring (ABPM) is arm position during sleep. An increase in the number of patients with 'excessive' nocturnal dipping (> 20% decrease in night/day blood pressure) was observed following the creation of an instructional videotape in which patients were advised to muffle the noise of the monitor with a pillow at night. This raised the possibility that patients were placing their arm on top of the pillow reducing nocturnal blood pressure readings. DESIGN: Ambulatory blood pressure monitoring data from 184 patients prior to and from 193 patients following specific instructions not to put their arm on top of the pillow was examined. RESULTS: Following the instructions, the percentage of patients with 'excessive' nocturnal dipping in blood pressure decreased (excessive systolic dipping 17.4 versus 8.8%, P = 0.014; excessive diastolic dipping 37 versus 24.4%, P = 0.01). Consistent with an increase in the ratio of nocturnal/day pressures, there was an increase in the percentage of patients with inadequate nocturnal dipping (< 10% decrease in night/day blood pressure; systolic dipping 33.7 versus 45.6%, P = 0.02; diastolic dipping 13.0 versus 31.6%, P < 0.001) CONCLUSION: Instructing patients to avoid resting their arm on a pillow at night has a substantial effect on the classification of nocturnal dipping status. Patients need clear instructions not to place their arm on a pillow at night during blood pressure monitoring.

Arm↗
PubMed2002

The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy.

OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually.

Antihypertensive Agents↗