Preferences of Canadian patients and physicians for adjuvant treatments for melanoma.

Background: Past research suggests that patients with early- and late-stage melanoma will endure adverse events and inconvenient treatment regimens for improved survival. Evidence about the preferences of Canadian patients and physicians for novel adjuvant treatments for melanoma is unavailable. Methods: Patient and physician preferences for adjuvant treatments for melanoma were assessed in an online discrete choice experiment (dce). Treatment alternatives were characterized by 8 attributes with respect to dosing regimen, efficacy, and toxicities, with levels corresponding to those for dabrafenib-trametinib, nivolumab, pembrolizumab, and interferon. For patients, the effects of melanoma on quality of life and ability to work and perform activities of daily living were also assessed. Patients were recruited by Canadian melanoma patient advocacy groups through e-mail and social media. Physicians were recruited by e-mail. Results: Of 94 patients who started the survey, 51 completed 1 or more dce questions. Of 166 physicians sent the e-mail invitation, 18 completed 1 or more dce questions. For patients, an increased probability of remaining cancer-free over 21 months was the most important attribute. For physicians, an increased chance of the patient's remaining alive over 36 months was the most important attribute. Patients and physicians chose active treatment over no treatment 85% and 86% of the time respectively and a treatment with attributes consistent with dabrafenib-trametinib 71% and 67% of the time respectively. A substantial proportion of patients reported worrying about future diagnostic tests and their cancer coming back. Conclusions: Canadian patients and physicians are generally concordant in their preferences for adjuvant melanoma treatments, preferring active treatment to no treatment and dabrafenib-trametinib to other options.

Prevalence and correlates of anemia and uncontrolled anemia in chronic hemodialysis patients--the Campania Dialysis Registry.

BACKGROUND: This study investigated prevalence and correlates of anemia and uncontrolled anemia in chronic hemodialysis patients. METHODS: A cross-sectional analysis was performed on registry data for 2,746 chronic (>6 months) hemodialysis patients aged 25-84. Data collection included years of dialysis, hours of dialysis/wk, disease causing hemodialysis, body mass index (BMI), erythropoietin (EPO) treatment, hemoglobin, markers of viral hepatitis, serum albumin, calcium, and phosphorus. RESULTS: Prevalence was 88.7% for anemia (hemoglobin <11 g/100 mL and EPO treatment at any Hb level), 39.4% for uncontrolled anemia (hemoglobin<11 g/100 mL). Gender, years of dialysis, hereditary cystic kidney disease (HCKD), and low BMI (<24 kg/m2) were independent correlates of anemia (P<0.001). Gender, HCKD, low BMI, serum albumin and calcium were independent correlates of uncontrolled anemia (P<0.05). An interaction was found between age (not correlated with anemia and uncontrolled anemia) and the association of gender with uncontrolled anemia (P<0.05). EPO doses were higher in patients with high prevalence of uncontrolled anemia than in patients with low prevalence (i.e., women vs men, other diseases vs HCKD, low vs not-low BMI, P<0.01). Gender, years of dialysis, HCKD, BMI, serum albumin, and calcium were independent correlates of the hemoglobin/EPO dose ratio in patients on EPO treatment (P<0.05). CONCLUSION: Anemia and uncontrolled anemia are more frequent in hemodialysis patients with shortterm dialysis, diseases other than HCKD, low BMI, and female gender. Gender effect was lower in elderly patients. Uncontrolled anemia was also associated with low serum albumin and calcium, suggesting that these parameters are indices of EPO resistance.

Sevelamer worsens metabolic acidosis in hemodialysis patients.

BACKGROUND: Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate. METHODS: Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated. RESULTS: Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1 mEq/L, whereas it averaged 21.1 +/- 0.7 mEq/L in patients on calcium carbonate (p<0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p<0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.

[Urinary albumin excretion and coronary artery disease]. / Albumina urinaria e malattia coronarica nella popolazione di età 45-64 anni.

The moderate elevation in urinary albumin excretion defined as microalbuminuria is common in the population and associated with cardiovascular (CV) risk factors. Microalbuminuria prevalence is low in the absence of CV risk factors and progressively increases with the number of the individual's CV risk factors. The main correlate of microalbuminuria is blood pressure (BP). The relationship between BP and microalbuminuria is continuous and graded since the prevalence of microalbuminuria increases with the severity of hypertension. Among hypertensives receiving treatment, BP control is associated with a low prevalence of microalbuminuria. Therefore, BP appears as a determinant of microalbuminuria rather than a mere correlate. For hypercholesterolemia, smoking and diabetes, the data are less strong, but point to an independent positive association with microalbuminuria. Altogether, data indicate that microalbuminuria in the population reflects the presence of CV risk factors. Data concerning microalbuminuria and coronary heart disease (CHD) support this idea. There is a continuous and graded relationship between urinary albumin excretion and CHD prevalence. High urinary albumin excretion is a likely sign of vascular damage existing both at renal and cardiac levels and induced by one or more uncontrolled CV risk factors.

Nephrotic edema.

This article starts with a concise synopsis of the history of edema. The role of underfilling, overflow, antidiuretic hormone, and acquaporins is subsequently discussed. Emphasis is given to the use of diuretics in edematous patients. The role and risks of albumin infusion are illustrated. The new hypothesis of pulse reverse osmosis is discussed. The final section deals with the measurement of colloid osmotic pressure in the clinical setting.

Bioelectrical impedance analysis in heart transplantation: early and late changes.

The objectives of this study were to perform bioelectrical impedance analysis before and after heart transplantation with comparison to healthy subjects. Eight patients (7 men, 1 woman) before (day 0) and after transplantation (day 3, 7, 12, 15, and 180) and 24 healthy controls, matched for sex, age, and body mass were studied. Data collection included bioelectrical impedance analysis (resistance, reactance, and estimates of body water), clinical, and laboratory measurements. Compared with controls, patients had at baseline significantly higher reactance, not significantly different resistance, body weight, total body water, and intra- to extracellular water ratio. After surgery, for reactance, there was an acute decrease followed by a slow, progressive increase up to normal level by day 15. Resistance and body weight did not significantly change; the intra- to extracellular water ratio significantly decreased with stable total body water. Changes in reactance are the main effects induced on bioelectrical impedance by heart transplantation. Acutely, there is a large decrease which likely reflects changes both in water distribution and in cell membrane function. The late changes more likely reflect the shift of body water from the extra- to the intracellular space with stable total body water.

Pulse pressure and isolated systolic hypertension: association with microalbuminuria. The GUBBIO Study Collaborative Research Group.

BACKGROUND: The long-term risk of end-stage renal disease is high in persons with isolated systolic hypertension, that is, those with an elevation of pulse pressure and not of diastolic pressure. Other data suggest that pulse pressure is a predictor of the hypertension-induced organ damage. Microalbuminuria is considered an early sign of glomerular damage caused by hypertension. The study shows the relationship of pulse pressure and isolated systolic hypertension to microalbuminuria in nondiabetic subjects. METHODS: This is a cross sectional analysis for a population sample of 677 men and 890 women, aged 45 to 64 years, who were without diabetes mellitus and macroalbuminuria. Data collection included: overnight urinary albumin and creatinine excretion; fasting plasma glucose, cholesterol, and creatinine; creatinine clearance; and blood pressure, weight, height, medical history, and smoking habit. Pulse pressure was calculated as systolic minus diastolic pressure. Isolated systolic hypertension was defined as systolic pressure > or =140 mm Hg in persons not on antihypertensive drugs and with diastolic pressure <90 mm Hg. Microalbuminuria was defined as urinary albumin excretion > or =20 microg/min. RESULTS: Pulse pressure and isolated systolic hypertension were significantly related to urinary albumin excretion and the prevalence of microalbuminuria in univariate and multivariate analyses. Controlling for gender and other variables, the risk of microalbuminuria was 1.71 with a 15 mm Hg higher pulse pressure (95% CI, 1.31 to 2.22) and 4.95 in the presence of isolated systolic hypertension (95% CI, 3.15 to 7.76). CONCLUSIONS: In nondiabetic, middle-aged adults, pulse pressure and isolated systolic hypertension are directly related to microalbuminuria, independent of diastolic pressure and other correlates.

Glomerular filtration rate in severely overweight normotensive humans.

The study examined whether indexing glomerular filtration rate (GFR) for body surface area is appropriate for people who are severely overweight. Twenty normotensive adult men who were severely overweight but without microalbuminuria were enrolled into this study. The control group consisted of 20 healthy subjects matched for age, sex, and height. GFR was determined by measuring insulin with the continuous-infusion method. The clearance of endogenous creatinine was also measured after two daily urine collections. Renal plasma flow (RPF) was measured by p-aminohippurate clearance using the continuous-infusion method. Lean body weight was measured by impedentiometry. Adjusting for body surface area (in 1.73 m(2)) caused a significant reduction in GFR (P < 0.0001) in overweight humans (84.1 +/- 2.32 versus 109.6 +/- 3.07 mL/min/1.73 m(2)). The difference disappeared when GFR/height criteria were adopted. No difference between obese and healthy controls occurred after adjusting for lean body weight. Data for creatinine clearance paralleled those with insulin clearance; a significant reduction (P < 0.001) occurred after indexing for basal surface area, which disappeared after correction for height, as well as for lean body weight.

Bioelectrical impedance analysis before and after Novacor implantation.

In this study Bioelectrical Impedance Analysis was performed in 5 patients with end stage heart failure in whom a left ventricular assist device (Novacor) was successfully implanted. Whole body measurements of bioelectrical indices resistance and reactance were taken before surgery and 3, 7, 12, and 15 days after it. After surgery there was a significant decrease in reactance, indicating a shift of body fluids from intra- to extra-cellular space.

Body impedance studies in end-stage heart failure.

This study adds another category of patients to those amenable to body impedance analysis (BIA). BIA measurements were obtained for the first time in 23 male patients with end-stage heart failure who were waiting for heart transplantation, and the data were compared with those obtained in 69 healthy controls matched for age, sex, height and weight. The data indicate that in end-stage heart failure there is an increased reactance (p<0.01) and an altered intracellular water/extracellular water ratio (p<0.03) due to the increased intracellular water (p<0.01) and decreased extracellular water (p<0.01).

Systolic hypertension: the nephrologist's point of view.

The elevation of systolic blood pressure associated with aging has been considered for years a physiologic phenomenon. This idea was based on the repeated observation that, also after middle age, a large majority of individuals in industrialized countries experience a continuous and progressive increase over time in systolic blood pressure, not in diastolic blood pressure. However, some individuals in industrialized countries and most individuals in nonindustrialized countries do not acquire an increased systolic blood pressure over time proving that the age-associated rise in systolic blood pressure is not an inevitable phenomenon. The change in systolic blood pressure over time strongly reflects lifestyles. Diet-dependent factors such as body weight, alcohol intake, and balance between dietary salt and potassium, are important in favoring the age-associated increase in systolic blood pressure, independently of several confounders. Epidemiologic studies suggest that elevation of systolic blood pressure is a risk factor for cardiovascular diseases: it relates to high incidence of lethal and nonlethal cardiovascular events also in the presence of diastolic blood pressure in the nonhypertensive range. Controlled clinical trials show that the treatment of isolated systolic hypertension reduces the number of cardiovascular events. In addition to cardiovascular disease, systolic blood pressure relates also to microalbuminuria, an index of early glomerular damage, to long-term incidence of end-stage renal disease, and, in hemodialyzed patients, to premature death. Thus, high systolic blood pressure appears an unhealthy condition also for patients with or at risk for kidney diseases.

Headache and cardiovascular risk factors: positive association with hypertension.

The study analyzes the prevalence of cardiovascular risk factors in 1343 patients with severe headache (399 men and 944 women), aged 15 to 64 years; analyses were controlled for sex, age, and type and frequency of headache. Prevalence of various forms of headache was different between men and women. Age and days per year with headache were significantly different among various forms of headache. For men and women with headache, age directly related to prevalence of hypertension, hypercholesterolemia, and obesity. Due to low prevalence, analyses by age were not done for diabetes mellitus. For cigarette smoking, prevalence was not related to age in men, but was inversely related to age in women. With control for age, prevalence of cardiovascular risk factors was not significantly different among patients with different forms of headache, except for cluster headache. Among men with cluster headache, prevalence was high for cigarette smoking, but low for hypercholesterolemia. With control for age, days per year with headache did not relate to prevalence of cardiovascular risk factors except for cigarette smoking in men. Compared to data for a population sample used as control, patients with headache had higher prevalence of hypertension in both sexes, independent of age (odds ratio 1.51, 95% confidence interval 1.28 to 1.80); the difference between patients with headache and the control population was lower with increasing age. The high prevalence of hypertension among patients with headache was not due to overweight. The data indicate that headache is significantly associated with hypertension, but not with other cardiovascular risk factors.