The occurrence of increased intraperitoneal volume events in automated peritoneal dialysis in the US: role of programming, patient/user actions and ultrafiltration.

UNLABELLED: BACKGROUND, OBJECTIVES AND METHODS: Increased intraperitoneal volume (IIPV) can occur during automated peritoneal dialysis (APD). The contribution of factors such as cycler programming and patient/user actions to IIPV has not been previously explored. The relationship between IIPV and cycler programming, patient/user actions, and ultrafiltration over a two-year period was investigated using US data from Baxter cyclers. Drain/fill volume ratios of > 1.6 to ≤ 2.0 and > 2.0 were defined as Level I and Level II IIPV events, respectively. RESULTS: Level I IIPV events occurred in 2.39% of standard and 4.73% of small fill volume therapies, while Level II IIPV events occurred in 0.26% and 1.33% of therapies, respectively. IIPV events occurred significantly more often in association with tidal peritoneal dialysis (PD) compared to non-tidal PD therapies. In tidal therapies, IIPV events were primarily related to suboptimal programming of total ultrafiltration volume. Factors that increased the odds of IIPV events during standard therapies included programming the initial drain volume target to < 70% of the last fill, and setting minimum drain volumes to < 85% of the fill volume. Bypass of initial drain by patients/users was also associated with a significant increase in the odds of IIPV events in non-tidal, but not tidal PD. An increase in the odds for IIPV was also seen for standard therapies within the highest (> 1,245 mL) versus the lowest (< 427 mL) quartile of ultrafiltration. Similar trends were seen in small fill volume therapies. Clinical presentations associated with IIPV events were not assessed. CONCLUSIONS: IIPV events are more frequent in tidal and small fill volume therapies. The greatest potential for IIPV occurred when the total ultrafiltration was set too low for the patient's UF requirements during tidal therapy. Patient/user bypass of drains without reaching the target drain volume contributes significantly to IIPV events in non-tidal PD therapies. Poorly functioning PD catheters may be central to the cycler programming and patient/user actions that lead to IIPV.

Probability-based compatibility curves for calcium and phosphates in parenteral nutrition formulations.

BACKGROUND: The information content of the calcium phosphate compatibility curves for adult parenteral nutrition (PN) solutions may benefit from a more sophisticated statistical treatment. Binary logistic regression analyses were evaluated as part of an alternate method for generating formulation compatibility curves. MATERIALS AND METHODS: A commercial PN solution was challenged with a systematic array of calcium and phosphate concentrations. These formulations were then characterized for particulates by visual inspection, light obscuration, and filtration followed by optical microscopy. Logistic regression analyses of the data were compared with traditional treatments for generating compatibility curves. RESULTS: Assay-dependent differences were observed in the compatibility curves and associated probability contours; the microscopic method of precipitate detection generated the most robust results. Calcium and phosphate compatibility data generated from small-volume glass containers reasonably predicted the observed compatibility of clinically relevant flexible containers. CONCLUSIONS: The published methods for creating calcium and phosphate compatibility curves via connecting the highest passing or lowest failing calcium concentrations should be augmented or replaced by probability contours of the entire experimental design to determine zones of formulation incompatibilities. We recommend researchers evaluate their data with logistic regression analysis to help build a more comprehensive probabilistic database of compatibility information.

Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women.

Insulin resistance, obesity, and a sex hormone alteration have each been suggested as the underlying link for the constellation of risk factors for myocardial infarction (MI) commonly referred to as the metabolic syndrome or the insulin resistance syndrome. In an attempt to identify in women which of these variables is the most likely link, insulin, adiposity variables, sex hormones, and risk factors for MI were measured and their relationships analyzed statistically in 58 premenopausal and 20 postmenopausal healthy women. On controlling for age, visceral adipose tissue (VAT) correlated more strongly with risk factors for MI, insulin, and free testosterone (FT) than did total adipose tissue or subcutaneous adipose tissue. VAT, therefore, was used as the adiposity variable for further data analysis. Waist circumference was a better surrogate of VAT than was waist-hip ratio, which was a poor surrogate of VAT. VAT correlated positively with insulin, FT, triglyceride, and glucose, and negatively with high-density lipoprotein and sex hormone-binding globulin. On controlling for age, FT and insulin correlated with risk factors for MI and with each other, but on controlling for age and VAT, all of their correlations lost statistical significance except for FT-triglyceride and FT-insulin in the postmenopausal women. In conclusion, VAT accumulation in women, independently of other measures of adiposity, may largely explain the correlations of insulin, obesity, and sex hormones with risk factors for MI and may be the immediate underlying factor that links risk factors for MI to form the metabolic syndrome. Insulin resistance, which has been generally accepted to be the underlying factor, may be a component of the syndrome rather than its underlying link. We hypothesize that in women FT may effect preferential VAT accumulation and induce insulin resistance directly, as well as via VAT accumulation, so that a sex hormone alteration may underlie VAT accumulation and thus ultimately underlie the metabolic syndrome (with insulin resistance as a component).

Is atherosclerotic cardiovascular disease an endocrinological disorder? The estrogen-androgen paradox.

The strikingly lower incidence of myocardial infarction (MI) in premenopausal women than in men of the same age suggests an important role for sex hormones in the etiology of MI. Supporting such a role are studies, carried out mostly in men, that report abnormalities of sex hormone levels in patients with MI, correlations of sex hormone levels with degree of atherosclerosis and with levels of risk factors for MI, and changes in the levels of risk factors with administration of sex hormones. Studies have also reported a prospective relationship in men of testosterone level with progression of atherosclerosis, accumulation of visceral adipose tissue, and other risk factors for MI. Puzzling, however, is that neither the level of testosterone nor of estrogen was found to be predictive of coronary events in any of the eight prospective studies that have been carried out. Also puzzling is that whereas the gender difference in incidence of MI would suggest that testosterone promotes and/or estrogen prevents MI, the cross- sectional, hormone administration, and prospective studies have suggested that in men testosterone may prevent and estrogen promote MI. These studies have thus revealed an estrogen-androgen paradox: that endogenous sex hormones may relate both to atherosclerotic cardiovascular disease and its risk factors oppositely in women and men. Recently recognized experiments of nature and their knockout mouse models may present another manifestation of this estrogen-androgen paradox and could help resolve these apparent contradictions.

Are major risk factors for myocardial infarction the major predictors of degree of coronary artery disease in men?

Although numerous cross-sectional studies have reported associations of hypertension, hypercholesterolemia, diabetes, smoking, and/or obesity with the presence of coronary artery disease (CAD), correlations of these risk factors for myocardial infarction (MI) with the degree or progression of CAD have been less consistent. Nevertheless, these risk factors are generally assumed to be major determinants not only of MI, but of the degree of CAD as well. The present study is an attempt to evaluate the relationship of major risk factors for MI to degree of CAD. From 182 men who underwent diagnostic coronary arteriography, the 154 with CAD were selected for study. These 154 patients were divided into 2 groups, those with hypertension, hypercholesterolemia, diabetes, smoking, and/or obesity (n = 121) and those with none of these risk factors (n = 33). The mean degree of CAD in the group with risk factors for MI (44.4%) and in the group without (50.6%) was not significantly different (P =.15); nor was the increase in CAD with age augmented by the presence of these risk factors. On multiple regression analysis, none of these risk factors was associated with degree of CAD. Three other variables that were considered in this study, age, high-density lipoprotein-cholesterol (HDL-C), and free testosterone (FT), did show an independent association with degree of CAD. These findings, together with the findings of previous studies from other laboratories, raise the possibility that in men selected for coronary arteriography, age, HDL-C, and FT may be stronger predictors of degree of CAD than are blood pressure, cholesterol, diabetes, smoking, and body mass index (BMI).

Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction.

That sex hormones, insulin, and obesity all correlate with the constellation of risk factors for myocardial infarction (MI) that has come to be known as "syndrome X," the "insulin-resistance syndrome," or the "metabolic syndrome" suggests that any one or more of them could underlie and link the risk factors to form the constellation. That sex hormones, insulin, and obesity also correlate with each other complicates their identification as an underlying link. To compare the likelihood of each being a link, we measured and determined the interrelationships of sex hormones, insulin, adiposity variables, and risk factors for MI in 80 apparently healthy men. Of the adiposity variables, visceral adipose tissue (VAT) correlated more strongly with the risk factors for MI than did body mass index (BMI), total adipose tissue (TAT), subcutaneous adipose tissue (SCAT), waist-to-hip ratio (WHR), and waist circumference (W). Controlling for VAT eliminated all of the other adiposity correlations that had been significant. VAT, therefore, was used as the measure of adiposity for further data analysis. VAT correlated more strongly with risk factors for MI than did sex hormones and insulin, and most of the correlations of sex hormones and insulin with risk factors for MI lost statistical significance after controlling for VAT. Testosterone and the ratio of estradiol-to-testosterone (E/T) correlated with insulin; on controlling for VAT, only the E/T-insulin correlation remained significant (r =.38, P <.001) and on multiple linear regression analysis, insulin was associated with estradiol (P =.01) and testosterone (P =.04) independently of VAT and age. In conclusion, (1) VAT in men may largely explain the correlations of sex hormones, insulin, and obesity with the risk factors for MI measured, (2) VAT may be the principal factor in men, independently of other measures of adiposity, that links risk factors for MI to form the constellation, and (3) estradiol may play a more important role in the sex hormone-insulin relationship in men than has generally been considered.