Joseph M. Messana

Cyclosporine for plaque-type psoriasis: Results of a multidose, double-blind trial

BACKGROUND Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and side effects. METHODS In a 16-week, double-blind trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while maintaining blinding. RESULTS The psoriasis improved in a dose-dependent fashion. After eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients receiving 3, 5, and 7.5 mg of cyclosporine per kilogram per day, respectively, were rated as being clear or almost clear of psoriasis; each group had significant improvement (P less than 0.0001) as compared with the group receiving vehicle, in which none of the patients were rated as clear or almost clear. The patients who received 5 mg per kilogram were the least likely to require dosage adjustments because of side effects or a lack of efficacy. The glomerular filtration rate, measured in a subgroup of 34 patients receiving cyclosporine, decreased by a median of 16 percent. Higher doses of cyclosporine had greater adverse effects on systolic blood pressure, glomerular filtration rate, and serum levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type hypersensitivity reactions to skin-test antigens were reduced by cyclosporine administration. Cyclosporine appears to become concentrated in skin. CONCLUSIONS Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined.

Comparing continuous hemofiltration with hemodialysis in patients with severe acute renal failure.

Continuous venovenous hemofiltration (CVVH) or CVVH with additional diffusive dialysis (CVVH-D) has theoretical advantages in treating severe acute renal failure (ARF), but no prospective clinical trials or restrospective comparison studies have clearly shown its superiority over intermittent hemodialysis (HD). To evaluate this question, all 349 adult patients with ARF receiving renal replacement therapy (RRT) at our medical center during 1995 and 1996 were analyzed using multivariate Cox proportional hazards methods. Initial univariate analysis showed the odds of death when receiving initial CVVH to be more than twice those when receiving initial HD (risk for death, 2.03; P < 0.01). Progressive exclusion of patients in whom the RRT modality might not be open to choice and the risk for death was very high (systolic blood pressure < 90 mm Hg; total bilirubin level > 15 mg/dL; or total RRT < 48 hours) for total RRT left 227 patients in whom the risk for death was 1.09 (95% confidence interval [CI], 0.67 to 1.80; P = 0.72) for initial CVVH, virtually equivalent to the risk for initial HD. Comorbid indicators significantly associated with death or failure to recover renal function included: older age; medical rather than surgical diagnosis; preexisting infection or trauma and liver disease as primary diagnoses; and abnormal bilirubin level or vital signs at initiation of RRT. These results show that the high crude mortality rate of patients undergoing CVVH was related to severity of illness and not the treatment choice itself. With the addition of more inclusive comorbidity data and a broader spectrum of interim outcomes, this type of analysis is a practical alternative to what would almost assuredly be a cumbersome and costly prospective, controlled trial comparing traditional HD with CVVH.

System and method for determining blood flow rate in a vessel

A system and method are provided for determining the performance of a vessel, such as a hemodialysis access, which communicates blood between two locations of a patient. A conduit, such as an external dialysis circuit or an intravascular catheter, is provided in fluid communication with the vessel, and has a diversion point for diverting blood from the vessel into the conduit. The system further includes means for determining a flow rate of the diverted blood through the conduit. A first sensor in communication with the vessel generates at least one signal that is a function of a blood flow rate in the vessel downstream from the diversion point, wherein the downstream flow rate depends on the determined conduit flow rate and the performance of the vessel can be determined based on the signal. In addition, a processor can be provided in communication with the first sensor for determining a flow rate in the vessel upstream from the diversion point from the signal and the conduit flow rate. In a preferred embodiment, the first sensor is an ultrasonic sensor, and the at least one signal represents a time-averaged mean Doppler velocity of blood flow. Still further, additional sensors may be employed to provide a measure of the upstream flow rate as well as the conduit flow rate.

Dialysis Dose Scaled to Body Surface Area and Size-Adjusted, Sex-Specific Patient Mortality

BACKGROUND AND OBJECTIVES When hemodialysis dose is scaled to body water (V), women typically receive a greater dose than men, but their survival is not better given a similar dose. This study sought to determine whether rescaling dose to body surface area (SA) might reveal different associations among dose, sex, and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Single-pool Kt/V (spKt/V), equilibrated Kt/V, and standard Kt/V (stdKt/V) were computed using urea kinetic modeling on a prevalent cohort of 7229 patients undergoing thrice-weekly hemodialysis. Data were obtained from the Centers for Medicare & Medicaid Services 2008 ESRD Clinical Performance Measures Project. SA-normalized stdKt/V (SAN-stdKt/V) was calculated as stdKt/V × ratio of anthropometric volume to SA/17.5. Patients were grouped into sex-specific dose quintiles (reference: quintile 1 for men). Adjusted hazard ratios (HRs) for 1-year mortality were calculated using Cox regression. RESULTS spKt/V was higher in women (1.7 ± 0.3) than in men (1.5 ± 0.2; P<0.001), but SAN-stdKt/V was lower (women: 2.3 ± 0.2; men: 2.5 ± 0.3; P<0.001). For both sexes, mortality decreased as spKt/V increased, until spKt/V was 1.6-1.7 (quintile 4 for men: HR, 0.62; quintile 3 for women: HR, 0.64); no benefit was observed with higher spKt/V. HR for mortality decreased further at higher SAN-stdKt/V in both sexes (quintile 5 for men: HR, 0.69; quintile 5 for women: HR, 0.60). CONCLUSIONS SA-based dialysis dose results in dose-mortality relationships substantially different from those with volume-based dosing. SAN-stdKt/V analyses suggest women may be relatively underdosed when treated by V-based dosing. SAN-stdKt/V as a measure for dialysis dose may warrant further study.

Peritoneal dialysis in end-stage renal disease patients with preexisting chronic liver disease and ascites

PURPOSE Hemodialysis in patients with chronic liver disease and ascites may be complicated by intradialytic hypotension, limiting the amount of ultrafiltration and resulting in massive ascites. Successful maintenance peritoneal dialysis (PD) has not been previously reported as an alternative to hemodialysis in this population. PATIENTS AND METHODS Nine patients with chronic renal failure, chronic liver disease, and tense ascites prior to beginning PD are described. All chronic PD catheters were placed percutaneously by the nephrology staff. Seven patients were maintained primarily on continuous ambulatory peritoneal dialysis, whereas two were on intermittent peritoneal dialysis. RESULTS PD catheters were placed without serious hemorrhage or bowel injury. PD provided adequate clearance and volume maintenance for each patient. Fifteen episodes of peritonitis occurred in 18 patient-years of PD. All episodes of peritonitis were successfully treated with intraperitoneal antibiotics without catheter removal. Only one patient had a decline in the serum albumin level of 0.5 g/dL or more during the course of chronic PD. Three of the nine patients are still alive and on PD for durations of 18 to 24 months. One patient insidiously developed sclerosing peritonitis after 8 years on PD and is now on hemodialysis, and another patient switched to hemodialysis because she was no longer able to care for herself or to manage her PD. Four patients died while maintained on PD; three deaths were due to complications of liver failure within the first 4 months of PD and the fourth was due to empyema after 4 years of PD. CONCLUSION PD can be used successfully to treat chronic renal failure in patients with chronic liver disease and ascites when the liver disease itself is not rapidly fatal. PD may be better tolerated than hemodialysis and perhaps should be the renal replacement treatment of choice in these patients.

Dialysis staff influence patients in formulating their advance directives

Patients on chronic dialysis were surveyed to determine the degree to which completion of advance directives (ADs) was influenced by personal factors that patients bring to their dialysis situation (eg, demographic characteristics or personal preferences) and by environmental factors that are not under their control (eg, interaction with dialysis staff or hospital system). Of the 113 questionnaires distributed to the population of 40 hemodialysis and 73 peritoneal dialysis patients, 90 (80%) were completed. Although only 17% of the respondents had actually completed written ADs previously, respondents seemed to have a good general understanding of ADs, as evidenced by the 80% overall accuracy on a 19-question portion of the survey that tested knowledge regarding ADs. While a few personal factors, such as gender, dialysis, modality, perceived quality of life, and attitude toward death, were associated with completion of ADs, most other demographic variables, including age, marital status, religion, work status, number of years of education, disability status, locus of control, renal diagnosis, and number of years on dialysis, were not correlated. More prominently correlated with completion of ADs were environmental factors, such as having dialysis staff discuss ADs with patients, patients being asked to complete ADs at the time of hospitalization, and perception of staff as being comfortable discussing ADs with patients. The overall results of the survey suggest that discussing ADs as an ongoing activity may have been positively influenced by the Federal Patient Self-Determination Act of 1991.(ABSTRACT TRUNCATED AT 250 WORDS)

Variable flow Doppler for hemodialysis access evaluation : Theory and clinical feasibility

Access thrombosis remains an enormous problem for patients on hemodialysis. Current evidence suggests that decreasing access blood flow rate is an important predictor of future access thrombosis and failure. This article describes a method for determining access volume flow and detecting access pathology. The Doppler ultrasound signal downstream from the arterial needle as a function of the variable hemodialysis blood pump flow rate, is used to determine access blood flow. By using this variable flow (VF) Doppler technique compared with duplex volume flow estimates measured in 18 accesses (16 patients with 12 polytetrafluorethylene [PTFE] grafts and 6 autogenous fistulas), the results showed a correlation of 0.83 (p < 0.0001) between these methods. In grafts with lower blood flow rates, aberrant flow patterns were observed, including stagnant or reversed flow during diastole while forward flow was maintained during systole. When reversed diastolic flow was severe, it was accompanied by access recirculation. In conclusion, we report the theory and clinical feasibility of determining access blood flow by using a VF Doppler technique. Measurements are made without the need to determine the access cross sectional area required for duplex volume flow calculations and without the need to reverse the lines required for various indicator dilution techniques. Important information is also obtained about aberrant flow patterns in patients at risk of access failure.

Renal Replacement Therapy in the Elderly: Medical, Ethical, and Psychosocial Considerations

As patients over the age of 65 become the fastest growing segment of our treated end-stage renal disease (ESRD) population, nephrologists and allied healthcare workers who care for these patients must become well versed in the many issues specific to this group. Elderly patients contribute the greatest fraction to the incidence and prevalence of the United States ESRD population. Their life expectancy is greatly reduced compared with age-matched counterparts from the general population. Cardiac disease is the leading cause of death. Although renal transplantation remains the most successful form of renal replacement therapy, only a small fraction of elderly ESRD patients are transplanted. The renal research community has made great strides in improving patient outcomes on dialysis over the last decade in many areas; however, little attention has been focused on the elderly ESRD patient. The substantial mortality and comorbidity experienced by this population makes their management an ongoing challenge. Many unresolved issues remain for elderly ESRD patients in the timing of dialysis initiation, choice of dialytic therapy, use of renal transplantation, and management of cardiovascular disease. It is anticipated that future research in these areas will identify optimal treatment strategies for elderly ESRD patients starting on dialysis and improve patient outcomes.

Comparison of toxicity of radiocontrast agents to renal tubule cells in vitro.

We have previously reported that radiocontrast agents induce direct renal tubule cell toxicity in vitro. The observed toxic effects were markedly potentiated by concomitant hypoxia. In addition, we have reported that the ionic radiocontrast agent diatrizoic acid is more toxic than the nonionic radiocontrast agent iopamidol in this system. Using suspensions enriched in rabbit renal proximal tubule segments, we compared the direct toxicities of the ionic dimeric ioxaglic acid to the nonionic monomeric compound iopamidol. Toxicity was assessed by comparing tubule potassium and calcium content, ATP levels, and respiratory rates after exposure to clinically achievable concentrations of radiocontrast agents. Ioxaglate (25 mM) produced significant declines in tubule cation content and respiratory rate with 30 min of hypoxia followed by 60 min of reoxygenation compared to molar-equivalent concentrations of iopamidol under similar conditions. Meglumine, a cationic compound frequently present in ionic contrast agent solutions, and ioxaglate tubule toxicity was additive. Iopamidol and ioxaglate exhibited similar tubule cell toxicity when comparison was based on iodine content. These experimental results suggest that the intrinsic nephrotoxic potential of ioxaglic acid is greater than that of iopamidol on a molar basis, but that the nephrotoxic potential of the two radiocontrast agents is similar when comparison is based upon iodine content.

Using Knowledge of Multiple Levels of Variation in Care to Target Performance Incentives to Providers

Background:In developing “pay-for-performance” and capitation systems that provide incentives for improving the quality and efficiency of care, policymakers need to determine which healthcare providers to evaluate and reward. Objectives:This study demonstrates methods for determining and understanding the relative contributions of facilities and physicians to the quality and cost of care. Specifically, this study distinguishes levels of variation in resource utilization (RU), based on research to support the development of an expanded Medicare dialysis prospective payment system. Research Design:Mixed models were used to estimate the variation in RU across institutional providers, physicians, patients, and months (within patients), after adjusting for case-mix. Subjects:The study includes 10,367 Medicare hemodialysis patients treated in a 4.2% stratified random sample of dialysis facilities in 2003. Measures:Monthly RU was measured by the average Medicare allowable charge per dialysis session for separately billable dialysis-related services (mainly injectable medications and laboratory tests) from Medicare claims. Results:There was financially significant variation in RU across institutional providers and to a lesser degree across physicians, after adjusting for differences in case-mix. The remaining variation in RU reflects unexplained differences across patients that persist over time and transitory fluctuations for individual patients. Conclusions:The greater variation in RU occurring across dialysis facilities than across physicians is consistent with targeting payments to facilities, but alignment of incentives between facilities and physicians remains an important goal. Similar analytic methods may be useful in designing payment policies that reward providers for improving the quality of care.