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Biomedical subjects

Dominik E Uehlinger

Publications and source records attributed to Dominik E Uehlinger.

7 recordsLinked to original sources
PubMed2004

The willingness of patients to accept an additional mortality risk in order to improve renal graft survival.

BACKGROUND: This study was performed to assess renal transplant patient preferences with respect to the acceptance of an additional mortality risk induced by immunosuppressive therapy in order to prevent graft loss in case of acute rejection. METHODS: The two decision analysis tools standard gamble and time trade-off were used to interview 155 patients with a functioning renal graft, and 11 on dialysis awaiting transplantation. RESULTS: Defining the best possible outcome as being alive with a functioning graft (utility value = 1), and the worst outcome as dying (utility value = 0), median utility values of 0.68 (0.59 +/- 0.32, mean +/- SD) with standard gamble and of 0.65 (0.57 +/- 0.32) with time trade-off were obtained for the intermediate outcome (i.e., staying alive but returning to dialysis). Thirteen percent of the patients attributed a utility value of 0 to this intermediate outcome (i.e., they would rather die than return to dialysis), and 8% a utility value of 1 (i.e., they would take absolutely no risk from additional antirejection therapy). Individual utility values for returning to dialysis correlated with time on dialysis before transplantation (R= 0.76, P < 0.005), but no relationship was found between utility values and age, sex, religion, previous methods of dialysis, time with a functioning graft, number of transplantations, or time on the transplantation waiting list. CONCLUSION: The large interindividual variability of utility values precludes a prediction about the acceptance of a new therapeutic regimen by an individual patient. The assessment of the utility enables, however, a more objective judgment of the general acceptance of any possible risk/benefit ratio induced by a new immunosuppressive regimen in our patient population.

Adult↗
PubMed2003

Medical futility: predicting outcome of intensive care unit patients by nurses and doctors--a prospective comparative study.

OBJECTIVE: First, to assess the pattern of the prediction of intensive care unit patients' outcome with regard to survival and quality of life by nurses and doctors and, second, to compare these predictions with the quality of life reported by the surviving patients. DESIGN: Prospective opinion survey of critical care providers; comparison with follow-up for survival, functional status, and quality of life. SETTING: Six-bed medical intensive care unit subunit of a 1,000-bed tertiary care, university hospital. PATIENTS: All patients older than 18 yrs, admitted to the medical intensive care unit for >24 hrs over a 1-yr period (December 1997 to November 1998). INTERVENTIONS: Daily judgment of eventual futility of medical interventions by nurses and doctors with respect to survival and future quality of life. Telephone interviews with discharged patients for quality of life and functional status 6 months after intensive care unit admission. MEASUREMENTS AND MAIN RESULTS: Data regarding 521 patients including 1,932 daily judgments by nurses and doctors were analyzed. Disagreement on at least one of the daily judgments by nurses and doctors was found in 21% of all patients and in 63% of the dying patients. The disagreements more frequently concerned quality of life than survival. The higher the Simplified Acute Physiology Score and the longer the intensive care unit stay, the more divergent judgments were observed (p <.001). In surviving and dying patients, nurses gave more pessimistic judgment and considered withdrawal more often than did doctors (p <.001). Patients only rarely indicated bad quality of life (6%) and severe physical disability (2%) 6 months after intensive care unit admission. Compared with patients' own assessment, neither nurses nor doctors correctly predicted quality of life; false pessimistic and false optimistic appreciation was given. CONCLUSIONS: Disagreement between nurses and doctors was frequent with respect to their judgment of futility of medical interventions. Disagreements most often concerned the most severely ill patients. Nurses, being more pessimistic in general, were more often correct than doctors in the judgment of dying patients but proposed treatment withdrawal in some very sick patients who survived. Future quality of life cannot reliably be predicted either by doctors or by nurses.

Adolescent↗
PubMed2002

Assessment of former ICU patients' quality of life: comparison of different quality-of-life measures.

OBJECTIVE: To compare three different measures to assess quality of life (QOL) after an Intensive Care Unit (ICU) stay: a standardized telephone interview, a satisfaction scale, and the Sickness Impact Profile (SIP). DESIGN: Prospective study, evaluating QOL 6 months after ICU discharge. SETTING: Medical ICU of a Swiss tertiary-care university hospital. PATIENTS AND METHODS: Patients admitted to the ICU between July and November 1998 for more than 24 h were included. Six months after ICU discharge overall QOL and health-related QOL were evaluated. Of the 118 patients approached, 85 returned valid questionnaires. RESULTS: The majority of patients indicated good QOL 6 months after ICU stay on each measure. A correlation for both overall and health-related QOL was found between the SIP and the satisfaction scales, between SIP and the telephone interviews, between the telephone interviews and satisfaction scales. The correlation between rating by scale or telephone interview and SIP in patients with cardiovascular disease differed from patients with other diagnoses. CONCLUSIONS: For the global assessment of overall or health-related QOL after ICU stay, long questionnaires such as SIP may be replaced by a short, structured telephone interview or, better, by a satisfaction scale. Quantitative measures such as SIP may be needed for comparison of therapeutic interventions or specific functional or psychosocial aspects.

Activities of Daily Living↗
PubMed2002

Allometric scaling and maximum efficiency in physiological eigen time.

General optimization results from physics indicate that maximum efficiency of a process, in the sense of minimum overall entropy production, is achieved when the rate of entropy production is constant over time, however not in ordinary clock time but on an, in general varying, "eigen time" scale, intrinsic to the system. We identify the eigen time of a biological system with "physiological time," which generally scales with the 1/4 power of body mass, M(1/4), over a vast range of species. Since it is equally well established that metabolic rate scales as M(3/4), it follows that organisms produce entropy at the same intrinsic rate, fulfilling a necessary condition for maximum efficiency, and are all, furthermore, equally efficient on the physiological eigen time scale.

Animals↗
PubMed2002

Glycyrrhetinic acid decreases plasma potassium concentrations in patients with anuria.

ABSTRACT. Licorice-associated hypertension is thought to be due to increased renal sodium retention. The active compound of licorice, glycyrrhetinic acid (GA), inhibits renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) and by that mechanism increases access of cortisol to the mineralocorticoid receptor that causes renal sodium retention and potassium loss. In addition, a direct vascular effect of 11beta-HSD activity has recently been incriminated to promote hypertension, a contention based on in vitro observations. This investigation was designed to establish whether this extrarenal effect of 11beta-HSD is relevant for BP regulation and potassium concentrations in plasma. In a prospective, double-blind, cross-over study, seven patients with anuria on chronic hemodialysis were randomly assigned after a baseline period of 2 wk to placebo or GA (1 g/d) for 2 wk, separated by a washout phase of 3 wk. The ratio of plasma cortisol/cortisone, determined by gas chromatography-mass spectrometry, increased in all patients after GA intake (F = 9.705; P < 0.004), which indicates inhibition of 11beta-HSD. Twenty-four-hour BP values did not change throughout the study. The increase of the plasma cortisol/cortisone ratio was paralleled by a decline in the plasma potassium concentration in every patient. The mean +/- SD plasma potassium concentration decreased from 5.5 +/- 0.6 mM/L at baseline to 4.9 +/- 0.7 and 4.5 +/- 0.8 mM/L after 1 and 2 wk on GA, respectively (F = 9.934, P < 0.003). Extrarenal 11beta-HSD activity influences serum potassium concentrations but does not regulate BP independently of renal sodium retention.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2002

Population pharmacokinetic model to predict steady-state exposure to once-daily cyclosporin microemulsion in renal transplant recipients.

BACKGROUND: The microemulsion formulation of cyclosporin (CsA-ME) has a less variable absorption profile than the standard formulation (CsA-S), but only limited information is available about once-daily administration of CsA-ME. OBJECTIVE: To develop a population pharmacokinetic model for once-daily CsA-ME that enables the prediction of individual steady-state area under the concentration-time curve (AUC) on the basis of blood concentration measurements and patient covariates. PATIENTS AND METHODS: The steady-state pharmacokinetics of once-daily cyclosporin were studied in 60 stable renal transplant recipients before and after conversion from CsA-S to CsA-ME. For each formulation, 7 blood samples were collected from 50 patients (group A) at sparse timepoints over 2 weeks, and 10 blood samples were collected from 10 patients (group B) at fixed timepoints over 24 hours. A 2-compartment population model assuming time-lagged first-order oral absorption was fitted to the data from group A, using nonlinear mixed effects modelling (NONMEM). The data from group B were used to evaluate the predictive performance of the model. RESULTS: Mean [+/- SD; coefficient of variation (%CV)] CsA-S doses of 245mg (+/- 92) resulted in cyclosporin blood concentrations of 214 microg/L (+/- 70) after 12 hours and 108 microg/L (+/- 23) after 24 hours; the mean estimated AUC to 24 hours was 7658 microg x h/L (30%). With mean CsA-ME doses of 206mg (+/- 59), cyclosporin blood concentrations were 212 microg/L (+/- 33) and 132 microg/L (25%) after 12 and 24 hours, respectively, and the mean estimated AUC(24) was 9357 microg x h/L (23%). A strong correlation between 12-hour concentrations and AUC(24) was observed for CsA-ME (r = 0.95, p < 0.001), but not for CsA-S (r = 0.59, nonsignificant); the correlation between 24-hour trough concentrations and AUC(24) was weaker for both formulations (r = 0.64, p < 0.05 and r = 0.37, nonsignificant, respectively). On the basis of the population model derived from group A, the single best timepoint to predict AUC(24) from blood cyclosporin concentration was at 8 hours [AUC(24) (microg x h/L) = 19.6 x cyclosporin concentration at 8 hours (microg/L) + 3035], resulting in a prediction error of 8.3 +/- 6.6% when applied to the measured AUC(24) of group B. Adverse events were observed after conversion in 18 patients; these events generally resolved spontaneously or after dosage reduction, but twice-daily administration was required in some patients. CONCLUSIONS: Switching from once-daily CsA-S to CsA-ME results in more consistent and predictable cyclosporin pharmacokinetics. Adjustment of dosage or regimen may be required in some patients.

Adult↗