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Biomedical subjects

R N Foley

Publications and source records attributed to R N Foley.

At least 19 recordsLinked to original sources

Comparative mortality of hemodialysis and peritoneal dialysis in Canada.

BACKGROUND: Comparisons of mortality rates in patients on hemodialysis versus those on peritoneal dialysis have been inconsistent. We hypothesized that comorbidity has an important effect on differential survival in these two groups of patients. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness collected prospectively, immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994; vital status was ascertained as of January 1, 1998. RESULTS: The mean follow-up was 24 months. Thirty-four percent of patients at baseline, 50% at three months, and 51% at six months used peritoneal dialysis. Values for a previously validated comorbidity score were higher for patients on hemodialysis at baseline (4.0 vs. 3.1, P < 0.001), three months (3.7 vs. 3.2, P = 0.001), and six months (3.6 vs. 3.2, P = 0.005). The overall mortality was 41%. The unadjusted peritoneal dialysis/hemodialysis mortality hazard ratios were 0.65 (95% CI, 0. 51 to 0.83, P = 0.0005), 0.84 (95% CI, 0.66 to 1.06, P = NS), and 0. 83 (95% CI, 0.64 to 1.08, P = NS) based on the modality of dialysis in use at baseline, three months, and six months, respectively. When adjusted for age, sex, diabetes, cardiac failure, myocardial infarction, peripheral vascular disease, malignancy, and acuity of renal failure, the corresponding hazard ratios were 0.79 (95% CI, 0. 62 to 1.01, P = NS), 1.00 (95% CI, 0.78 to 1.28, P = NS), and 0.95 (95% CI, 0.73 to 1.24, P = NS). Adjustment for a previously validated comorbidity score resulted in hazard ratios of 0.74 (95% CI, 0.58 to 0.94, P = 0.01), 0.94 (95% CI, 0.74 to 1.19, P = NS), and 0.88 (95% CI, 0.68 to 1.13, P = NS) at baseline, three months, and six months. There was no survival advantage for either modality in any of the major subgroups defined by age, sex, or diabetic status. CONCLUSIONS: The apparent survival advantage of peritoneal dialysis in Canada is due to lower comorbidity and a lower burden of acute onset end-stage renal disease at the inception of dialysis therapy. Hemodialysis and peritoneal dialysis, as practiced in Canada in the 1990s, are associated with similar overall survival rates.

Canada

Method of physician remuneration and rates of antibiotic prescription.

BACKGROUND: Rates of antibiotic prescription in Canada far exceed generally accepted rates of bacterial infection, which led the authors to postulate that rates of antibiotic prescription depend to some extent on factors unrelated to medical indication. The associations between antibiotic prescription rates and physician characteristics, in particular, method of remuneration and patient volume, were explored. METHODS: The authors evaluated all 153,047 antibiotic prescriptions generated by 476 Newfoundland general practitioners and paid for by the Newfoundland Drug Plan over the 1-year period ending Aug. 31 1996, and calculated rates of antibiotic prescription. Linear and logistic regression models controlling for several physician characteristics, specifically age, place of education (Canada or elsewhere), location of practice (urban or rural) and proportion of elderly patients seen, were used to analyse rates of antibiotic prescription. RESULTS: Fee-for-service payment (rather than salary) and greater volume of patients were strongly associated with higher antibiotic prescription rates. Fee-for-service physicians were much more likely than their salaried counterparts to prescribe at rates above the median value of 1.51 antibiotic prescriptions per unique patient per year. The association between rate of antibiotic prescription and patient volume (as measured by number of unique patients prescribed to) was evident for all physicians. However, the association was much stronger for fee-for-service physicians. Physicians with higher patient volumes prescribed antibiotics at higher rates. INTERPRETATION: In this study factors other than medical indication, in particular method of physician remuneration and patient volume, played a major role in determining antibiotic prescribing practices.

Adult

Long-term evolution of cardiomyopathy in dialysis patients.

BACKGROUND: Left ventricular enlargement is very common at the inception of dialysis therapy, and highly predictive of future cardiac morbidity and mortality. It is not known whether cardiac size increases further while on dialysis therapy and whether potentially reversible risk factors for later progression can be identified. METHODS; Baseline and yearly echocardiograms were performed in a prospective inception cohort of 433 dialysis patients. The mean patient follow-up was 41 months; 29 patients had four consecutive echocardiograms at yearly intervals. RESULTS: The patient subset with four echocardiograms was older (58 vs. 51 years, P = 0.02) and had a lower mass ventricular mass index (128 vs. 149 g/m2, P = 0.02) than the parent group. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive increases over time in posterior wall thickness (P = 0.015), left ventricular end-diastolic diameter, left ventricular mass index (P = 0.001), and cavity volume index (P = 0. 001). Mass-to-volume ratios did not change. The biggest changes in mass (18 g/m2 - 14%)and volume index (13 ml/m2 - 18%) occurred between baseline and year 1, although increases in both were seen after year 1. Hemodialysis versus peritoneal dialysis (41 g/m2, P = 0.008) and anemia (10 g/m2 per 1 g/dl drop in hemoglobin, P = 0.02) were associated with progressive left ventricular enlargement, but only within the first year of dialysis therapy. The left ventricular enlargement seen after year 1 was independent of anemia, blood pressure, serum albumin and mode of dialysis. CONCLUSIONS: Progressive cardiac enlargement, particularly left ventricular dilation with compensatory hypertrophy, continues after starting dialysis therapy. Most of the additional cardiac enlargement seems to occur in the first year of dialysis therapy, suggesting that intervention beyond one year may be relatively ineffective.

Blood Pressure

Mode of dialysis therapy and mortality in end-stage renal disease.

Despite considerable differences in technique and blood purification characteristics, hemodialysis and peritoneal dialysis have been thought to have similar patient outcomes. An inception cohort of 433 end-stage renal disease patients was followed prospectively for a mean of 41 mo. The outcomes of hemodialysis (HD) and peritoneal dialysis (PD) patients were compared using intention to treat analysis based on the mode of therapy at 3 mo. After adjustment for PD patients less likely to have chronic hypertension and more likely to have diabetes, ischemic heart disease, and cardiac failure at baseline (P < 0.05), a biphasic mortality pattern was observed. For the first 2 yr, there was no statistically significant difference in mortality. After 2 yr, mortality was greater among PD patients with an adjusted PD/HD hazard ratio of 1.57 (95% confidence interval [CI], 0.97 to 2.53). Both the occurrence (adjusted hazards ratio 6.87 [95% CI, 2.01 to 23.5]) and the direction (toward PD, adjusted hazards ratio 6.25 [95% CI, 1.54 to 25]) of a therapy switch were subsequently associated with mortality after 2 yr. Progressive clinical and echocardiographic cardiac disease were not responsible for this late mortality. Lower mean serum albumin levels in PD patients in the first 2 yr of therapy (3.5 +/- 0.5 versus 3.9 +/- 0.5 g/dl, P < 0.0001) accounted for a large proportion of the increase in subsequent mortality. Hemodialysis has a late survival advantage over peritoneal dialysis; antecedent hypoalbuminemia is a major marker of the increased late mortality in PD patients.

Adult

Cardiac disease in diabetic end-stage renal disease.

Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly. At baseline, diabetic patients (n = 116) had more echocardiographic concentric left ventricular hypertrophy (50 vs 38%, p = 0.04), clinically diagnosed ischaemic heart disease (32 vs 18%, p = 0.003) and cardiac failure (48 vs 24%, p < 0.00001) than non-diabetic patients (n = 317). After adjusting for age and sex, diabetic patients had similar rates of progression of echocardiographic disorders, and de novo cardiac failure, but higher rates of de novo clinically diagnosed ischaemic heart disease (RR 3.2, p = 0.0002), overall mortality (RR 2.3, p < 0.0001) and cardiovascular mortality (RR 2.6, p < 0.0001) than non-diabetic patients. Mortality was higher in diabetic patients following admission for clinically diagnosed ischaemic heart disease (RR 1.7, p = 0.05) and cardiac failure (RR 2.2, p = 0.0003). Among diabetic patients older age, left ventricular hypertrophy, smoking, clinically diagnosed ischaemic heart disease, cardiac failure and hypoalbuminaemia were independently associated with mortality. The excessive cardiac morbidity and mortality of diabetic patients seem to be mediated via ischaemic disease, rather than progression of cardiomyopathy while on dialysis therapy. Potentially remediable risk factors include smoking, left ventricular hypertrophy, and hypoalbuminaemia.

Adult

Cardiac disease in chronic uremia: clinical outcome and risk factors.

Cardiac disease is common and is the major killer in end-stage renal disease (ESRD). Cardiac failure is a highly malignant condition in ESRD patients. Cardiac failure mediates most of the adverse prognostic impact of ischemic heart disease. Left ventricular (LV) abnormalities are already present at initiation of dialysis therapy in approximately 80% of patients. These abnormalities (ie, systolic dysfunction in approximately 15%, LV dilatation with preserved systolic function in 30%, concentric LV hypertrophy [LVH] in 40%) independently predict ischemic heart disease and cardiac failure, and are the largest baseline predictor of mortality after 2 years on dialysis therapy. The associations between classical risk factors (eg, hyperlipidemia, smoking, hypertension) and cardiac outcomes in ESRD are inconsistent. "Uremic" risk factors represent a nascent, but potentially important field. In our prospective 10-year study of 433 patients starting renal replacement therapy, we identified the following as major independent risk factors for cardiac disease: (1) hypertension (concentric LVH, LV dilatation, ischemic heart disease, cardiac failure, inverse relationship with mortality); (2) anemia (LV dilatation, cardiac failure, death); and (3) hypoalbuminemia (ischemic heart disease, cardiac failure, death). Transplantation dramatically improved LV abnormalities, suggesting that a uremic environment is cardiotoxic. Multiple risk factors act in concert to produce cardiac disease in ESRD; many of these are avoidable, suggesting that the enormous burden of disease can be reduced considerably.

Chronic Disease

The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease.

To determine the possible association between anemia and clinical and echocardiographic cardiac disease, a cohort of 432 end-stage renal disease patients (261 on hemodialysis and 171 on peritoneal dialysis) who started dialysis therapy between 1982 and 1991 were followed prospectively for an average of 41 months. Baseline demographic, clinical, and echocardiographic assessments were performed, as well as monthly serial clinical and laboratory tests while the patients were on dialysis therapy. The mean (+/-SD) hemoglobin level during dialysis therapy was 8.8 +/- 1.5 g/dL. After adjusting for age, diabetes, and ischemic heart disease, as well as for blood pressure and serum albumin levels measured serially, each 1 g/dL decrease in mean hemoglobin was independently associated with the presence of left ventricular dilatation on repeat echocardiogram (odds ratio, 1.46; P = 0.018) and the development of de novo (relative risk [RR] = 1.28; P = 0.018) and recurrent (RR = 1.20; P = 0.046) cardiac failure. In addition, each 1 g/dL decrease in the mean hemoglobin level was independently associated with mortality while the patients were on dialysis therapy (RR = 1.14; P = 0.024). Anemia had no independent association with the development of ischemic heart disease while the patients were on dialysis therapy. Anemia, an easily reversible feature of end-stage renal disease, is an independent risk factor for clinical and echocardiographic cardiac disease, as well as mortality in end-stage renal disease patients.

Anemia

Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed prospectively for an average of 41 months. Baseline and annual demographic, clinical and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while on dialysis therapy. The average mean arterial blood pressure level during dialysis therapy was 101 +/- 11 mm Hg. After adjusting for age, diabetes and ischemic heart disease, as well as hemoglobin and serum albumin levels measured serially, each 10 mm Hg rise in mean arterial blood pressure was independently associated with: the presence of concentric LV hypertrophy (OR 1.48, P = 0.02), the change in LV mass index (beta = 5.4 g/m2, P = 0.027) and cavity volume (beta = 4.3 ml/m2, P = 0.048) on follow-up echocardiography, the development of de novo cardiac failure (RR 1.44, P = 0.007), and the development of de novo ischemic heart disease (RR 1.39, P = 0.05). The association with LV dilation was of borderline statistical significance (OR 1.48, P = 0.06). Mean arterial blood pressures greater than 106 mm Hg were associated with both echocardiographic and clinical endpoints. Paradoxically, low mean arterial blood pressure (RR 1.36 per 10 mm Hg fall, P = 0.009) was independently associated with mortality. The association of low blood pressure with mortality was a marker for having had cardiac failure prior to death. We conclude that even moderate hypertension worsens the echocardiographic and clinical outcome in ESRD patients, especially in those without previous clinical cardiac disease.

Adult

Outcome and risk factors of ischemic heart disease in chronic uremia.

To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of dialysis laboratory data were collected at monthly intervals, and clinical and echocardiographic data at yearly intervals. Twenty-two percent of patients (N = 95) had either a history of angina pectoris or myocardial infarction on starting dialysis therapy. Median time to onset of heart failure was 24 months in those with ischemic heart disease on initiation of dialysis, compared to 55 months in those without (P < 0.0001). This effect was independent of age, diabetes and underlying cardiomyopathy. Median survival was 44 months in those with ischemic disease compared to 56 months in those without (P = 0.0001). This adverse impact was independent of age and diabetes mellitus but, when cardiac failure was added to the Cox's model, ischemic heart disease was no longer an independent predictor of survival. De novo ischemic heart disease, not evident on starting dialysis therapy, occurred in 41 (9%) patients. When compared to patients who never developed ischemic disease (N = 296; 69%), significant and independent predictors of de novo disease were older age (P = 0.0007), diabetes mellitus (P = 0.0001), high blood pressure during follow up on dialysis (P = 0.02) and hypoalbuminemia (P = 0.03), whereas anemia was not an independent predictor. LV mass index was 174 +/- 7 g/m2 in those who developed de novo ischemic disease compared to 155 +/- 3 g/m2 (P < 0.001) in those who did not. Concentric LV hypertrophy, LV dilation and systolic dysfunction were independent risk factors for de novo ischemic heart disease. We conclude that ischemic heart disease occurs frequently in dialysis patients, that its adverse impact is mediated through the development of heart failure, and that the most important, potentially reversible risk factors are hypertension, hypoalbuminemia, and underlying cardiomyopathy.

Adult

Hypocalcemia, morbidity, and mortality in end-stage renal disease.

BACKGROUND: Hypocalcemia and hyperphosphatemia with secondary hyper-parathyroidism are characteristic of end-stage renal disease (ESRD). Although calcium levels critically affect almost all cellular processes, the impact of chronic hypocalcemia and other abnormalities of calcium-phosphate homeostasis on the prognosis of ESRD patients is unknown. METHODS: An inception cohort of 433 patients starting ESRD therapy was followed prospectively for an average of 41 months. Serum calcium and other parameters were measured monthly. The mean calcium levels were 9.4 +/- 0.7 mg/dl. 23% of the patients had mean calcium levels < 8.8 mg/dl. After adjusting for baseline age, diabetes mellitus, ischemic heart disease, smoking and cholesterol levels, as well as serial albumin, hemoglobin, mean arterial blood pressure, phosphate and alkaline phosphatase levels, chronic hypocalcemia was strongly associated with mortality (RR 2.10, p = 0.006 for a mean calcium level < 8.8 mg/dl). The association with mortality was similar in hemodialysis (RR 2.10, p = 0.006) and peritoneal dialysis patients (2.67, p = 0.034). Using similar covariate adjustment, chronic hypocalcemia was associated with de novo ischemic heart disease (RR 5.23, p < 0.001), recurrent ischemic heart disease (RR 2.46, p = 0.006), de novo cardiac failure (RR 2.64, p < 0.001), and recurrent cardiac failure (RR 3.30, p < 0.001). Hypocalcemia retained its independent impact on morbidity and mortality when analyzed as a time-dependent covariate. CONCLUSIONS: Chronic hypocalcemia, a very common, reversible feature of chronic uremia, is independently associated with morbidity and mortality in ESRD patients.

Alkaline Phosphatase

Ischemic heart disease in chronic uremia.

The burden of ischemic heart disease is high in dialysis patients. Ischemia may result from atherosclerotic and nonatherosclerotic disease and may cause myocardial infarction and angina. The impact of diminished perfusion is intricately associated with the underlying cardiomyopathy, both of which predispose to heart failure. The etiology of ischemia is complex and associated with the underlying cardiomyopathy, whether it be concentric left ventricular hypertrophy, left ventricular dilatation, or systolic dysfunction. Hypertension, diabetes, dyslipidemia, abnormalities of divalent ion metabolism, hypoalbuminemia, and left ventricular hypertrophy are probably adverse risk factors for ischemia, but the relative importance of each is unknown.

Arteriosclerosis

Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed up prospectively for an average of 41 months. Baseline and annual demographic, clinical, and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while patients were on dialysis therapy. Among hemodialysis patients, after adjustment was made for age, diabetes, and ischemic heart disease, as well as hemoglobin and blood pressure levels measured serially, a 10-g/L fall in mean serum albumin level was independently associated with the the development of de novo (relative risk [RR], 2.22; P = 0.001) and recurrent cardiac failure (RR, 3.84; P = 0.003), de novo (RR, 5.29; P = 0.001) and recurrent ischemic heart disease (RR, 4.24; P = 0.005), cardiac mortality (RR, 5.60; P = 0.001), and overall mortality (RR, 4.33; P < 0.001). Among peritoneal dialysis patients, a 10-g/L fall in mean serum albumin level was independently associated with the progression of left ventricular dilation as seen on follow-up echocardiography (beta, 13.4 mL/m2; P = 0.014), the development of de novo cardiac failure (RR, 4.16; P = 0.003), and overall mortality (RR, 2.06; P < 0.001). Hypoalbuminemia, a major adverse prognostic factor in dialysis patients, is strongly associated with cardiac disease.

Adult

Outcome and risk factors for left ventricular disorders in chronic uraemia.

BACKGROUND: Left ventricular disease occurs frequently in dialysis patients. It may be manifest as concentric LV hypertrophy, LV dilatation with or without LV hypertrophy, or systolic dysfunction. Little is known concerning the clinical outcome and risk factors for these disorders. METHODS: A cohort of 432 end-stage renal disease patients who survived at least 6 months had an echocardiogram on initiation of dialysis therapy. Clinical, laboratory and echocardiographic data was obtained annually during follow-up. RESULTS: On initiation of ESRD therapy 16% of patients had systolic dysfunction, 41% concentric LV hypertrophy, 28% LV dilatation, and only 16% had normal echocardiograms. Median time to development of heart failure was 19 months in patients with systolic dysfunction, 38 months in concentric LV hypertrophy and 38 months in LV dilatation. The relative risks of heart failure in the three groups were significantly worse than in the normal group, after adjusting for age, diabetes and ischaemic heart disease. Median survival was 38 months in systolic dysfunction, 48 months in concentric hypertrophy, 56 months in LV dilatation, and >66 months in the normal group. Two hundred and seventy-five patients had a follow-up echocardiogram 17 months after starting dialysis therapy together with serial measurement of potential risk factors prior to the echocardiogram. On follow-up echocardiogram the degree of concentric LV hypertrophy was independently related to hypertension while on dialysis, older age, and anaemia while on dialysis; the degree of LV dilatation was related to ischaemic heart disease, anaemia, hypertension and hypoalbuminemia while on dialysis; the degree of systolic dysfunction was associated with ischaemic heart disease and anaemia during follow-up. CONCLUSIONS: Manifestations of left ventricular disease are frequent and persistent in chronic uraemia, and are associated with high risks of heart failure and death. Potentially reversible risk factors include anaemia, hypertension, hypoalbuminaemia and ischaemic heart disease.

Adult