A randomized, prospective, pharmacoeconomic trial of tacrolimus versus cyclosporine in combination with thymoglobulin in renal transplant recipients.

Background: To date, the clinical trials of tacrolimus (TAC) versus cyclosporine modified (CsA), have not defined which agent is more cost-effective for immunosuppression in renal transplant recipients especially in a quadruple immunosuppressive regimen.

Methods: The objective of this randomized, prospective study was to compare the clinical and economic outcomes of TAC versus CsA, in a regimen that consisted of Thymoglobulin induction, an antimetabolite, and prednisone. Between December 2000 and October 2002, 200 patients were enrolled and randomized in a 2:1 fashion (TAC n=134, CsA n=66).

Liver transplantation for hepatocellular carcinoma: expanding special priority to include stage III disease.

Hypothesis: After liver transplantation, patients with stage III hepatocellular carcinoma (HCC) experience survivals similar to those of patients with less advanced disease and of matched control subjects.

Design: Retrospective review of prospectively collected database.

Setting: University hospital.

Guidelines for the treatment and management of new-onset diabetes after transplantation.

Although graft and patient survival after solid organ transplantation have improved markedly in recent years, transplant recipients continue to experience an increased prevalence of cardiovascular disease (CVD) compared with the general population. A number of factors are known to impact on the increased risk of CVD in this population, including hypertension, dyslipidemia and diabetes mellitus. Of these factors, new-onset diabetes after transplantation has been identified as one of the most important, being associated with reduced graft function and patient survival, and increased risk of graft loss.

Consequences of eliminating HLA-B in deceased donor kidney allocation to increase minority transplantation.

HLA matching contributes to the disparity in Caucasian compared to minority kidney transplantation. HLA-B locus matching was eliminated from kidney allocation to shift a projected 166 organs from Caucasians to minorities annually. This study estimated the economic and quality-of-life impact of this policy.

Effective strategy to guide pathology test ordering in surgical patients.

Background: Ordering of pathology testing by junior medical staff is often a haphazard process with little regard to the appropriateness of test ordering. The aim of the present study was to reduce ordering of inappropriate pathology tests in surgical patients attending the pre-admission clinic (PAC) through the introduction of a protocol-based test ordering system and to create an environment where such improvement can be sustained.

Methods: This is a prospective study with a retrospective control group.

Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction.

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR).

Maintenance immunosuppression use and the associated risk of avascular necrosis after kidney transplantation in the United States.

Background: Avascular necrosis (AVN) after renal transplantation has been largely attributed to the use of corticosteroids. However, other risk factors such as microvascular thrombosis and hyperlipidemia have been well described and may be of increased importance in the era of early steroid cessation and avoidance. We hypothesized that maintenance immunosuppressive medications known to be associated with these risk factors for AVN would also be associated with a higher risk of AVN.

Incidence and predictors of myocardial infarction after kidney transplantation.

The risk and predictors of post-kidney transplantation myocardial infarction (PTMI) are not well described. Registry data collected by the United States Renal Data System were used to investigate retrospectively PTMI among adult first renal allograft recipients who received a transplant in 1995 to 2000 and had Medicare as the primary payer. PTMI events were ascertained from billing and death records, and participants were followed for up to 3 yr after transplant or until the end of observation (December 31, 2000).

Impact of diabetes and hepatitis after kidney transplantation on patients who are affected by hepatitis C virus.

Complications associated with use of donor hepatitis C-positive kidneys (DHCV+) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000.

The impact of transplantation with deceased donor hepatitis c-positive kidneys on survival in wait-listed long-term dialysis patients.

Whether transplantation of deceased donor kidney allografts from donors with antibodies against hepatitis C virus (HCV) confers a survival advantage compared with remaining on the kidney transplant waiting list is not yet known. We studied 38,270 USRDS Medicare beneficiaries awaiting kidney transplantation who presented with end-stage renal disease from April 1, 1995 to July 31, 2000. Cox regression was used to compare the adjusted hazard ratios for death among recipients of kidneys from deceased donors, and donors with antibodies against hepatitis C (DHCV+), controlling for demographics and comorbidities.

Long-term outcome of gastrointestinal complications in renal transplant patients treated with mycophenolate mofetil.

This study examined consequences of gastrointestinal (GI) complications and mycophenolate mofetil (MMF) discontinuation on long-term outcomes in patients who received MMF at transplantation and had graft function 12 months post-transplantation. Data were obtained from the United States Renal Data System for cadaveric renal transplant recipients between 1995 and 1998. GI complications or MMF discontinuation occurred in 27.

Cyclosporine minimization and cost reduction in renal transplant recipients receiving a C2-monitored, cyclosporine-based quadruple immunosuppressive regimen.

Background: Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700 mg/dL during the first 6 months after renal transplantation is recommended for triple immunosuppressive regimens. This trial determines whether lower C2 levels could be targeted safely in de novo kidney transplant recipients under a quadruple regimen compared with a similar cohort monitored with trough (C0) levels.

Methods: This single-center, sequential, cohort-designed trial included patients who received Thymoglobulin, corticosteroids, an antimetabolite, and cyclosporine monitored by C2 (n=50) or C0 (n=50).

Potential living kidney donors' health education use and comfort with donation.

Context: Much living kidney donation research focuses on actual donors rather than all donors who are evaluated by the transplant center.

Objective: To determine (1) what concerns and benefits potential donors saw possible from donation, (2) how they educated themselves before contacting the transplant center, and (3) who were the most comfortable donors.

Design: A telephone survey of 91 potential donors before transplant evaluation.

Cost-effectiveness of extending Medicare coverage of immunosuppressive medications to the life of a kidney transplant.

Unless they maintain Medicare status through disability or age, kidney transplant recipients lose their Medicare coverage of immunosuppression 3 years after transplantation. A significant transplant survival advantage has previously been demonstrated by the extension of Medicare immunosuppressive medication coverage from 1 year to 3 years, which occurred between 1993 and 1995. The United States Renal Data System (USRDS) was analyzed for recipients of kidney transplants from 1995 to 1999.

Five-year follow up of thymoglobulin versus ATGAM induction in adult renal transplantation.

Background: One-year results of a randomized, double-blinded trial of Thymoglobulin versus Atgam for induction therapy in renal transplantation revealed that Thymoglobulin was associated with higher event-free survival (94% vs. 63%), less acute rejection (4% vs. 25%), and better graft survival.

Comparison of comorbidity indices for patients with head and neck cancer.

Background: Comorbidity is an important prognostic factor for elderly patients with head and neck cancer. Investigators are faced with the dilemma of selecting the appropriate comorbidity instrument for outcomes research in cancer. The goal of this study was to compare 2 general comorbidity indices with 2 disease-specific indices.

Pharmacokinetics of tacrolimus in kidney transplant recipients: twice daily versus once daily dosing.

Tacrolimus a macrolide immunosuppressant that is routinely given in two equally divided doses every 12 h. However, the time-dependent pharmacokinetics of tacrolimus suggest that once daily morning administration of tacrolimus may produce appropriate drug exposure. The purpose of this pilot study was to compare the pharmacokinetics and safety of twice vs.

Payment for living donor (vendor) kidneys: a cost-effectiveness analysis.

The supply of kidneys does not meet the demand. As a consequence, the waiting time for a cadaver kidney continues to lengthen, and there is renewed debate about payment for living donors. To facilitate this debate, we studied what amount of payment would be cost-effective for society, i.

Three-year posttransplant graft survival in renal-transplant patients with graft function at 6 months receiving tacrolimus or cyclosporine microemulsion within a triple-drug regimen.

Background: Registry data can provide valuable information about possible treatment effects; however, pretreatment differences in patient characteristics may influence treatment assignment. Careful analysis must therefore be undertaken when evaluating treatment differences in the context of nonrandomized studies so that the impact of treatment selection bias is minimized.

Methods: A multivariable risk factor analysis of adult patients registered in the US Renal Data System who received a primary renal allograft during 1995 to 1998 was undertaken to compare 3-year graft survival using tacrolimus or Neoral with mycophenolate mofetil (MMF) and steroids.

Costs and consequences of cytomegalovirus disease.

The impact of prophylactic oral ganciclovir therapy on the incidence of cytomegalovirus (CMV) disease, patient and graft survival, and costs in patients receiving kidney and liver transplants is described. CMV disease is a common cause of morbidity and mortality in solid organ transplant recipients unless prophylactic drug therapy is used. Prophylactic oral ganciclovir therapy reduces the incidence of CMV disease in kidney and liver transplant recipients.

Nomogram for predicting the likelihood of delayed graft function in adult cadaveric renal transplant recipients.

Delayed graft function (DGF) is the need for dialysis in the first week after transplantation. Studied were risk factors for DGF in adult (age >/=16 yr) cadaveric renal transplant recipients by means of a multivariable modeling procedure. Only donor and recipient factors known before transplantation were chosen so that the probabilities of DGF could be calculated before transplantation and appropriate preventative measures taken.

The relative contributions of carboxylesterase and beta-glucuronidase in the formation of SN-38 in human colorectal tumours.

Irinotecan (CPT-11) is a prodrug that is used to treat metastatic colorectal cancer. It is activated to the topoisomerase poison SN-38 by carboxylesterases. SN-38 is subsequently metabolised to its inactive glucuronide, SN-38G, which can however be reactivated to SN-38 by beta-glucuronidase.

Early mobilization of patients hospitalized with community-acquired pneumonia.

Study Objective: To determine if early mobilization (EM) of hospitalized adults with community-acquired pneumonia (CAP) reduces hospital length of stay.

Design: Group randomized trial.

Setting: Three Midwestern hospitals.