A pilot study assessing the influences of charge data and group process on diagnostic test ordering by residents.

PURPOSE: Providing charge data to resident physicians has been shown to reduce the amounts spent on diagnostic testing. This pilot study sought to determine the influences of charge data and group decision making on diagnostic test ordering by internal medicine residents. METHOD: In an interactive workshop, 23 internal medicine residents received a hypothetical case. They completed an 18-item questionnaire estimating charges for diagnostic tests and then "ordered" tests. The residents were then randomly divided into groups that either received charge data, received charge data after ordering tests, or received no charge data. The groups ordered tests by consensus. Tests were weighted for appropriateness (+1 to +6) and inappropriateness (-1 to -6). Analyses compared individual and group decisions and effect of availability of charge data. RESULTS: Residents with access to charge data spent less on tests, but also had lower appropriateness scores. The appropriateness of the diagnostic workup was better by groups than by individuals, but cost more. CONCLUSION: Cost-containment interventions targeted towards doctors in training need to address the effect on quality of care and the influence of the group process in clinical decision making. Group diagnostic decisions may be more costly, but more appropriate.

Self- and peer assessment in a first-year communication and interviewing course.

Peer and self-evaluation are crucial in the professional development of physicians. However, these skills must be learned, and there are barriers to their acceptance and successful utilization. To overcome these obstacles, it has been suggested that these concepts should be addressed longitudinally throughout medical education. Therefore, first-year medical students were introduced to peer and self-assessment as part of a videotape review during an interviewing course by having students complete written peer and self-assessments of the interviews. Students' self-assessments were compared with the assessments of peers and faculty. Written evaluations showed peers were more lenient than faculty and students were most critical of their own performances. Students could provide balanced assessments of their peers but were predominately negative regarding their own performances. It appears first-year students are capable of evaluating their peers but have difficulty accurately assessing their own performance. Further interventions are needed to foster self-assessment skills in first-year students.

Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial.

BACKGROUND: Most nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 (COX-1), whose inhibition is associated with gastrointestinal ulceration, and COX-2, whose inhibition is associated with therapeutic benefits. Although agents that do not produce COX-1 activity may have fewer adverse effects, targeted disruption of the COX-2 allele in mice has resulted in severe renal problems, suggesting that COX-2 inhibition may also produce adverse effects. OBJECTIVE: To determine the effect of rofecoxib, a member of the coxib class of drugs and a specific inhibitor of the COX-2 enzyme, on renal function in elderly patients. DESIGN: A randomized, three-period, single-dose crossover study and a randomized, parallel-group, multiple-dose study. SETTING: Clinical research units. PATIENTS: 75 patients 60 to 80 years of age. INTERVENTION: In the first study, single doses of rofecoxib, 250 mg (about 5-fold to 20-fold the recommended dose); indomethacin, 75 mg; and placebo were administered to 15 patients. In the second study, multiple doses of rofecoxib, 12.5 or 25 mg/d; indomethacin, 50 mg three times daily; or placebo were administered to 60 patients. Patients in both studies received a low-sodium diet MEASUREMENTS: Glomerular filtration rate, creatinine clearance, and urinary and serum sodium and potassium values. RESULTS: Compared with placebo, single doses of rofecoxib and indomethacin decreased the glomerular filtration rate by 0.23 m/s (P < 0.001) and 0.18 mL/s (P = 0.003), respectively. In contrast, respective decreases of 0.14, 0.13, and 0.10 mL/s were observed after multiple doses of rofecoxib, 12.5 mg/d (P = 0.019); rofecoxib, 25 mg (P = 0.029), and indomethacin (P = 0.086) were administered. Changes in creatinine clearance and serum and urinary sodium and potassium were less pronounced. CONCLUSIONS: The effects of COX-2 inhibition on renal function are similar to those observed with nonselective NSAIDs. Thus, COX-2 seems to play an important role in human renal function.

Stereoselective pharmacokinetics of ketoprofen and ketoprofen glucuronide in end-stage renal disease: evidence for a 'futile cycle' of elimination.

AIMS: To assess if futile cycling of ketoprofen occurs in patients with decreased renal function. METHODS: Ketoprofen was administered to six haemodialysis-dependent patients with end-stage renal disease as single (50 mg) or multiple doses (50 mg three times daily, for 7 days). Plasma and dialysate concentrations of the unconjugated and glucuronidated R- and S-enantiomers of ketoprofen were determined using h.p.l.c. following the single and multiple dosing. RESULTS: The oral clearance was decreased and terminal elimination half-lives of R- and S-ketoprofen and the corresponding acyl glucuronides were increased in functionally anephric patients compared with healthy subjects. In contrast with the R-isomers, S-ketoprofen and S-ketoprofen glucuronide exhibited an unexpected accumulation (2.7-3. 8 fold) after repeated dosing achieving S:R ratios of 3.3+/-1.7 and 11.2+/-5.3, respectively. The plasma dialysis clearances for R- and S-ketoprofen glucuronides were 49.4+/-19.8 and 39.0+/-15.9 ml min-1, respectively, and 10.8+/-17.6 and 13.3+/-23.5 ml min-1 for unconjugated R- and S-ketoprofen. CONCLUSIONS: The selective accumulation of S-ketoprofen and its acyl glucuronide are consistent with amplification of chiral inversion subsequent to futile cycling between R-ketoprofen and R-ketoprofen glucuronide. Severe renal insufficiency, and possibly more modest decrements, results in a disproportionate increase in systemic exposure to the S-enantiomer which inhibits both pathologic and homeostatic prostaglandin synthesis.

Effects of multidisciplinary case management in patients with chronic renal insufficiency.

PURPOSE: Though case management has been recommended to improve the outcomes of patients with costly or morbid conditions, it has seldom been studied in controlled trials. We performed a randomized, controlled clinical trial of an intensive, multidisciplinary case management program for patients with chronic renal insufficiency and followed patients for 5 years. PATIENTS AND METHODS: We enrolled 437 primary-care patients (73% of those eligible) with chronic renal insufficiency (estimated creatinine clearance consistently < 50 mL/min with the last serum creatinine level > 1.4 mg/dL) who were attending an urban academic general internal medicine practice. The intensive case management, administered during the first 2 years after enrollment, consisted of mandatory repeated consultations in a nephrology case management clinic staffed by two nephrologists, a renal nurse, a renal dietitian, and a social worker. Control patients received usual care. Primary outcome measurements included serum creatinine level, estimated creatinine clearance, health services use, and mortality in the 5 years after enrollment. Secondary measures included use of renal sparing and potentially nephrotoxic drugs. RESULTS: There were no differences in renal function, health services use, or mortality in the first, second, or third through fifth years after enrollment. There were significantly more outpatient visits among intervention patients, mainly because of the added visits to the nephrology case management clinic. There were also no significant differences in the use of renal sparing or selected potentially nephrotoxic drugs. The annual direct costs of the intervention were $89,355 ($484 per intervention patient). CONCLUSION: This intensive, multidisciplinary case-management intervention had no effect on the outcomes of care among primary-care patients with established chronic renal insufficiency. Such expensive and intrusive interventions, despite representing state-of-the-art care, should be tested prospectively before being widely introduced into practice.

Role of duration of diuretic effect in preventing sodium retention.

OBJECTIVE: To determine whether the duration of diuretic effect at the active nephron site enhances ability to excrete an exogenous salt load. METHODS: We conducted a study that involved eight patients with New York Heart Association class II to III congestive heart failure. In a randomized, crossover manner, each patient received 3.25 mg intravenous bumetanide at 0 hours and again at 6 hours or a loading dose of 0.5 mg bumetanide at 0 hours followed by a continuous infusion of 0.5 mg/hr for 6 hours. Response was followed for 12 hours; a total of 6.5 mg of bumetanide was administered in each arm of the study. Eight hours after dosing began, we administered approximately 80 mEq sodium intravenously and examined its excretion over 4 hours. RESULTS: The percentage of the load excreted was 86% +/- 15% versus 29% +/- 30% for the infusion and bolus regimens, respectively (p = 0.0005). More bumetanide was excreted during the infusion (667 +/- 133 micrograms versus 240 +/- 121 micrograms; p = 0.0002). During the infusion, however, more sodium was excreted relative to amounts of bumetanide, indicating that the efficiency of response was greater during the infusion, 0.10 +/- 0.02 mEq sodium per microgram bumetanide versus 0.07 +/- 0.05 mEq for the bolus (p = 0.0145). CONCLUSIONS: These data support the notions that a long-acting loop diuretic maintains its efficacy and that a longer duration of action facilitates excretion of a sodium load, such as that which might occur during dietary indiscretion.

Dopamine does not enhance furosemide-induced natriuresis in patients with congestive heart failure.

The objective of this study was to determine whether the addition of low-dose (renal-dose) dopamine to furosemide therapy enhances natriuresis in patients with compensated congestive heart failure, New York Heart Association Class II or III. We performed a randomized, controlled, open-label, crossover study wherein urinary sodium, creatinine, and furosemide excretion rates and GFR determined by inulin clearance rates were measured during each of three treatment interventions: furosemide infusion alone, dopamine infusion alone, and furosemide and dopamine infusions administered concurrently. Six of eight recruited subjects (4 male, 2 female) were able to complete the study. The baseline sodium excretion rate after equilibration on a metabolic diet was 6.7 +/- 0.7 mEq (mean +/- SE) over 3 h. Infusion of dopamine alone caused a slight nonsignificant increase in natriuresis to 36.7 +/- 8.5 mEq/3 h. Furosemide alone markedly increased sodium excretion to 276.6 +/- 47.2 mEq/3 h. No significant additional increment in natriuresis occurred when dopamine and furosemide were administered concurrently (253.8 +/- 73.6 mEq/3 h). Neither dopamine, furosemide, or their coadministration affected GFR. In conclusion, infusion of low-dose dopamine does not enhance furosemide-induced urinary sodium excretion rates in patients with compensated congestive heart failure, New York Heart Association Class II or III.

Stereoselective high-performance liquid chromatographic analysis of ketoprofen and its acyl glucuronides in chronic renal insufficiency.

A rapid, sensitive method was developed for the quantification of the R- and S-enantiomers of ketoprofen and their acyl glucuronide conjugates in the plasma and dialysate of hemodialysis-dependent anephric patients. Unconjugated R- and S-ketoprofen plasma concentrations were determined directly by liquid chromatography using a S,S-Whelk-O1 chiral stationary phase. R- and S-Ketoprofen glucuronide for use as standard were resolved using a C18 reversed-phase HPLC column with a mobile phase containing the ion-pair reagent tetrabutylammonium hydrogen sulfate. Plasma glucuronides, however, could not be directly quantified due to matrix interference. Therefore, the glucuronides were isolated using reversed-phase HPLC and quantified after alkaline hydrolysis using the S,S-Whelk-O1 chiral stationary phase column.

Correlates of health care satisfaction in inner-city patients with hypertension and chronic renal insufficiency.

Barriers to effective health care are potential contributors to the increased prevalence of hypertension and hypertension-related renal disease observed in black patients. We have enrolled 333 primarily elderly (mean age 69 years) black (87%) patients with hypertension and chronic renal insufficiency into a prospective randomized trial testing the effect of intense multidisciplinary management on progression of chronic renal insufficiency. These patients have an average 6 years of education and $400-$800 monthly household income: 57% have diabetes. Our baseline data include the Patient Satisfaction Questionnaire administered by home interviewers who also recorded sociodemographic data, medications and questionnaires regarding medication compliance and symptoms related to anti-hypertensive drugs. Inpatient and outpatient vital signs, test results and diagnoses came from patients' computerized medical records. We used multiple linear regression to identify correlates of overall satisfaction. We also analyzed three subscales: access to care, financial aspects and interpersonal manner of physicians. We included only variables with univariate correlations (P < 0.05) in the models. Decreased overall satisfaction correlated with more symptoms related to anti-hypertensive drugs (P < 0.001), lower medication compliance (P = 0.01), and higher diastolic blood pressure (P = 0.08). Decreased satisfaction with access to care correlated with more symptoms related to anti-hypertensive drugs (P < 0.001) and decreased medication compliance (P = 0.08). Decreased satisfaction with financial aspects of care correlated with more symptoms related to anti-hypertensive drugs (P < 0.001), lower medication compliance (P = 0.01) and more proteinuria (P = 0.02). Finally, decreased satisfaction with interpersonal manner of physicians correlated with lower medication compliance (P < 0.001), lower albumin (P = 0.01) and sodium (P = 0.04), and higher diastolic blood pressure (P = 0.04). These cross-sectional baseline data describe a group of mostly black inner-city patients with hypertension and chronic renal insufficiency in whom decreased satisfaction with care correlates with decreased medication compliance, increased symptoms related to anti-hypertensive drug therapy, higher diastolic blood pressure and more proteinuria. Our prospective study may help determine whether improving satisfaction improves compliance and blood pressure control, and forestalls complications in this high-risk population.

The Influence of Misoprostol on the Adverse Renal Effects and Stereospecific Pharmacokinetics of Ibuprofen in Chronic Renal Insufficiency.

The use of nonsteroidal anti-inflammatory drugs in patients with chronic renal insufficiency (CRI) may be complicated by renal functional abnormalities due to the inhibition of renal prostaglandins. We tested the hypothesis that administration of the oral PGE1 analog, misoprostol, could attenuate the adverse renal effects of ibuprofen in patients with CRI. Because the metabolism of misoprostol and the stereoinversion of R- to S-ibuprofen involve the same metabolic pathway, the stereospecific pharmacokinetics of ibuprofen were also evaluated. In a randomized, crossover trial of six stable CRI patients (Clcr 25--67 ml min(minus sign1)), in sodium balance on a 150 mEq Na(+) per day metabolic diet, we compared the effects of ibuprofen 600 mg qid with and without misoprostol 200 &mgr;g qid upon Clcr, Clinulin, Clpah, Na(+), and K(+) excretion during 4-h clearance studies. We also assessed stereospecific ibuprofen kinetics following single dose (acute) and after 7 days on drug(s) (chronic). Daily weights, supine blood pressures, electrolytes, osmolality, BUN, creatinine and 24-h urine collections for Clcr and Na(+) and K(+) excretions were obtained during chronic dosing. Supine and upright plasma renin activities were obtained prior to dosing and during chronic dosing for both treatment limbs. Ibuprofen alone resulted in an approximately 20% transient reduction in GFR, occurring 2--2.5 h following dosing in both the acute and chronic clearance studies. This was not affected by misoprostol. There was a greater degree of stimulation of PRA with the upright posture with misoprostol plus ibuprofen than with ibuprofen alone. There was a significant weight gain in both study limbs, but no effect of misoprostol (1.2 plus minus 0.2 kg ibuprofen alone and 1.0 plus minus 0.2 kg ibuprofen plus misoprostol, p = 0.13). Otherwise no clinically significant alteration in renal function occurred in either treatment limb. The presence of misoprostol did not alter the stereospecific pharmacokinetics of ibuprofen. We conclude that misoprostol does not significantly alter the renal effects of ibuprofen in patients with mild to moderate CRI.

The pharmacokinetics of intravenous and oral torsemide in patients with chronic renal insufficiency.

Torsemide is a diuretic that acts in the thick ascending limb of the loop of Henle. Unlike furosemide, it undergoes substantial hepatic elimination and should not accumulate in patients with renal insufficiency. Therefore the pharmacokinetics of intravenous and oral torsemide and its metabolites were investigated in patients with chronic renal insufficiency. Two groups of 24 patients stratified by creatinine clearance (30 to 60 ml/min and < 30 ml/min) were studied in two separate randomized dose escalating crossover studies, one using intravenous torsemide and the other using oral torsemide. The pharmacokinetics of both intravenous and oral torsemide were linear over the dosage range studied. Absolute bioavailability was essentially 100%. Renal clearance was greatly diminished and correlated with renal function. Total plasma clearance and half-life were not related to renal function and were found to be similar to those of healthy subjects. The substantial nonrenal clearance of torsemide prevents accumulation in patients with chronic renal insufficiency.

The pharmacodynamics of intravenous and oral torsemide in patients with chronic renal insufficiency.

The pharmacodynamics of intravenous and oral torsemide were determined in two randomized cross-over clinical trials in patients with chronic renal insufficiency. There was no significant difference in the rate or magnitude of the diuretic response between oral and intravenous administration. As has been shown with other loop diuretics, patients with chronic renal insufficiency have a reduced diuretic response compared with healthy subjects. This diuretic resistance is primarily related to a diminished delivery of drug to the urinary site of action. The response of torsemide at the tubular level is not different from that seen in subjects with normal renal function. Metabolites of torsemide do not appear to contribute to the diuretic response. A dose of 50 to 100 mg dependent on renal function is required to obtain a maximal response. A ceiling dose of approximately 100 mg in patients with chronic renal insufficiency is therefore recommended.

Clinical correlates of functional status in patients with chronic renal insufficiency.

Patients with end-stage renal disease (ESRD) are known to have significantly reduced functional abilities, as measured by the Sickness Impact Profile (SIP). We investigated the clinical correlates with SIP scores in a cohort of patients with lesser degrees of renal dysfunction recruited from an academic general medicine practice (mean calculated creatinine clearance, 25 mL/min). Of 603 eligible patients with chronic renal insufficiency (CRI) defined as a serum creatinine greater than 1.5 mg/dL and a calculated creatinine clearance less than 50 mL/min on two occasions more than 6 months apart, 360 (60%) agreed to participate. These patients were primarily elderly (mean age, 69 years) black (83%), women (69.2%), with an average of 6 years of education and a household income of $400 to $800 per month; 92% had hypertension and 57% had diabetes. The SIP was administered in-home by trained interviewers. Independent variables included demographic data, education, income, and medications (via interviewers), vital signs taken by a renal nurse, and diagnostic test results and diagnoses from patient's computerized records. The total SIP score was the dependent variable, and its physical and psychosocial subscales were also investigated. Variables with univariate correlations with total SIP (P < 0.05) were included in a multiple regression analysis. All variables with a multivariable P value less than 0.10 were included in the final model. The mean SIP score was 24.5 +/- 15.6, higher than that found in patients on dialysis. Significant (P < 0.05) independent correlates with higher SIP scores (greater disability) were lower educational level and income, prior diagnoses of coronary artery disease and stroke, and lower serum albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Case report: acyclovir neurotoxicity and nephrotoxicity--the role for hemodialysis.

Severe neurotoxicity and acute renal failure developed in a patient with newly diagnosed AIDS while receiving high-dosage intravenous acyclovir for disseminated herpes zoster. Hemodialysis resulted in a rapid resolution of neurologic symptoms and was associated with a reduction in plasma acyclovir concentration. Acute hemodialysis therapy should be considered in cases of serious neurotoxicity secondary to acyclovir, especially when accompanied by renal failure.

Continuous venovenous hemofiltration: an alternative to continuous arteriovenous hemofiltration and hemodiafiltration in acute renal failure.

Continuous venovenous hemofiltration (CVVH) has been used as an alternative to continuous arteriovenous hemofiltration (CAVH) and hemodiafiltration (CAVHD) in the management of critically ill patients with acute renal failure. This report describes our experience with the first 25 patients treated with CVVH at our institution. Vascular access was obtained through a single dual-lumen venous catheter. A blood pump was used to provide ultrafiltration pressure. An ultrafiltrate pump was incorporated to ensure predictable ultrafiltrate production rates. Safety features in the extracorporeal circuit included a venous drip chamber with bubble detector and an in-line pressure monitor. CVVH was initiated by a nephrologist and dialysis nurse and was maintained by the intensive care unit (ICU) nursing staff. Fifteen females and 10 males received CVVH therapy for a total of 193.5 days (average, 7.7 +/- 10.3 days; range, 0.5 to 48 days). Four of the 25 patients (16%) survived and were discharged from the hospital. Four additional patients (16%) survived the acute phase of their illness, but died from complications of their primary disease before discharge from the hospital. The mean weight change during CVVH was -7.9 +/- 7.0 kg (range, -26.5 to +2.9 kg). Metabolic waste products and electrolytes were adequately controlled by CVVH in all but one hypercatabolic patient. The mean heparin dose required was 6.5 +/- 4.2 U/kg/h and was adjusted to prevent filter clotting rather than to achieve a predetermined activated partial thromboplastin time (PTT). The median PTT was 35.8 seconds (range, 22.0 to 100; control, 19.5 to 29.5 seconds). Four episodes of volume-responsive hypotension occurred during the 193.5 treatment days. Only one patient experienced a hemorrhagic complication during CVVH. No patient experienced a complication related to vascular access. Twelve of 111 total hemofilters were changed because of clot formation. CVVH was well tolerated by patients and managed efficiently by the ICU nursing staff.(ABSTRACT TRUNCATED AT 250 WORDS)

Loop diuretics for chronic renal insufficiency: a continuous infusion is more efficacious than bolus therapy.

OBJECTIVE: To test the hypothesis that a continuous, low-dose infusion of a loop diuretic is more efficacious and better tolerated than conventional intermittent bolus therapy in patients with severe chronic renal insufficiency (CRI). DESIGN: Randomized, crossover clinical trial with subjects serving as their own controls. SETTING: The General Clinical Research Center of Indiana University Hospital, Indianapolis, Indiana. PATIENTS: Eight adult volunteers with severe stable CRI (mean creatinine clearance, 0.28 mL/s; range, 0.15 to 0.47 mL/s) were recruited from the outpatient nephrology clinics of Indiana University Medical Center. INTERVENTIONS: On admission, diuretic drugs were withdrawn and patients were equilibrated on an 80 mmol/d sodium, 60 mmol/d potassium metabolic diet. Patients were randomized to receive a 12-mg intravenous dose of bumetanide given either as two 6-mg bolus doses separated by 6 hours or as the same total dose administered as a 12-hour continuous infusion. When sodium balance was re-established, each patient was crossed over to the alternative study limb. All patients completed both phases of the study. MEASUREMENTS AND RESULTS: Comparable amounts of bumetanide appeared in the urine during the study period (infusion, 912 +/- 428 micrograms; bolus, 944 +/- 421 micrograms; difference, 32 micrograms; 95% CI, -16 micrograms to 80 micrograms, P = 0.16). The continuous infusion resulted in significantly greater net sodium excretion (infusion, 236 +/- 77 mmol; bolus, 188 +/- 50 mmol; difference, 48 mmol; CI, 16 mmol to 80 mmol, P = 0.01). No patient had episodes of drug-induced myalgias during the continuous infusion compared with 3 of 8 patients with bolus therapy. CONCLUSIONS: In patients with severe CRI, a continuous intravenous infusion of bumetanide is more effective and less toxic than conventional intermittent bolus therapy. Continuous administration will probably be useful in patients with severe CRI who have not achieved an adequate natriuresis or who show evidence of drug toxicity with standard diuretic dosing regimens. A similar benefit may occur in selected diuretic-resistant patients with cardiac or hepatic disease, and studies in these patients seem warranted.