Search PubMed⌕ Search

Biomedical subjects

J A Lowell

Publications and source records attributed to J A Lowell.

At least 19 recordsLinked to original sources

Effect of extended coverage of immunosuppressive medications by medicare on the survival of cadaveric renal transplants.

Between 1993 and 1995, Medicare extended its coverage of maintenance immunosuppression medications following renal transplantation from 1 to 3 years. We hypothesized that Medicare's extension of immunosuppressive coverage would improve graft survival among low-income transplant recipients. We merged patient-level clinical data from the USRDS-distributed UNOS registry of kidney transplants throughout the USA with median family income for each patient's ZIP code from the 1990 Census. We were able to merge median incomes to 10,837 first cadaveric renal transplants performed in 1992-93 and 16,732 performed in 1995-97. Each of these chronological cohorts was divided into two groups, those with family incomes above (high-income group) and those below (low-income group) $36,033. There were no differences in graft survival at 1 year based on income in either chronological era. However, when Medicare covered immunosuppression medications for just 1 year, the low-income group of 1-year graft survivors had a 4.5% lower graft survival at the end of 3 years post-transplant (p < 0.001). During the 1995-97 period, during which Medicare provided 3 years' immunosuppression coverage, the low-income and high-income groups had equivalent graft survival at 3 years post-transplant.

Cadaver↗

The economic impact of preservation time in cadaveric liver transplantation.

There has been considerable recent debate concerning the reconfiguration of the cadaveric liver allocation system with the intent to allocate livers to more severely ill patients over greater distances. We sought to assess the economic implications of longer preservation times in cadaveric liver transplantation that may be seen in a restructured allocation system. A total of 683 patients with nonfulminant liver disease, aged 16 years or older, receiving a cadaveric donor liver as their only transplant, were drawn from a prospective cohort of patients who received transplants between January 1991 and July 1994 at the University of California, San Francisco, the Mayo Clinic, Rochester, Minnesota, or the University of Nebraska, Omaha. The primary outcome measure was standardized hospitalization resource utilization from the day of transplantation through discharge. Secondary outcome measures included 2-year patient survival, and 2-year retransplantation rates. Results indicated that each 1-h increase in preservation time was associated with a 1.4% increase in standardized hospital resource utilization (p = 0.014). The effects on 2-year patient survival and retransplantation rates were not measurably affected by an increase in preservation time. We conclude that policies that increase preservation time may be expected to increase the cost of liver transplantation.

Body Constitution↗

Renal transplantation following previous heart, liver, and lung transplantation: an 8-year single-center experience.

BACKGROUND: Long-term follow-up of heart, liver, and lung transplantation has led to an increased recognition of secondary end-stage renal failure (ESRF) in transplant recipients. This study examines our center's experience with renal transplantation following previous solid organ transplantation. METHODS: From January 1, 1992, to September 30, 1999, our center performed 18 renal transplants in previous solid organ recipients. During the same period, 815 total renal transplants were performed. One- and 3-year graft and patient survival, recipient demographics, donor type, and reason for transplantation were compared between these groups. RESULTS: Of the 18 recipients, 7 had prior heart transplants, 4 had prior liver transplants, and 7 had prior lung transplants. Cyclosporine toxicity contributed to renal failure in 17 (94.4%) of the patients-either as a sole factor (11 patients) or in combination with hypertension, renal artery stenosis, or tacrolimus toxicity (6 patients). Kaplan-Meier 1- and 3-year patient survival was 82.9% and 73.7%, compared with 95.5% and 90.7% in all renal transplant recipients. No surviving patient has suffered renal allograft loss. Mean current creatinine level is 1.4 mg/dL. CONCLUSIONS: Renal transplantation is an excellent therapy for ESRF following prior solid organ transplantation. One and 3-year patient and graft survival demonstrate the utility of renal transplantation in this patient population.

Follow-Up Studies↗

Posttransplant lymphoproliferative disease in children: correlation of histology to clinical behavior.

PURPOSE: To determine whether the morphologic features of posttransplant lymphoproliferative disease (PTLD) correlated to a response to therapy. PATIENTS AND METHODS: We reviewed our experience with PTLD in the pediatric population. We identified 32 patients with a total of 36 episodes of PTLD. The diagnosis was confirmed by tissue examination and classified according to the degree of monomorphic features of the lesion. Thirty-four of 36 episodes were managed with immunosuppression reduction, and the patients were assessed for their response to this strategy. Chemotherapy was used to treat 10 of 15 patients who had progressive disease, and their subsequent course was also analyzed. RESULTS: Sixteen of 17 (94%) patients with polymorphic morphology responded to immunosuppression reduction compared with only 5 of 17 (29%) patients with monomorphic features (P < 0.001). All of the patients with progressive disease who did not receive additional therapy died. Standard chemotherapy regimens for lymphoma were administered to 10 patients with progressive disease, with a high response rate (90%), durable remissions, and acceptable toxicity. CONCLUSIONS: We conclude that the morphologic characteristics of PTLD provide information to potentially help guide treatment strategies in the management of this disease. Standard chemotherapy regimens for malignant lymphoma appear to be a viable treatment option for patients with progressive disease, although further investigation is needed.

Adolescent↗

The Barnes-Jewish Hospital/Washington University Renal Transplant Program: comparison of two eras 1991-1994 and 1995-2000.

The first cadaveric transplant at Barnes-Jewish Hospital/Washington University was performed in 1963, the first living related transplant in 1965, and the first living unrelated transplant in 1983. Changes in the renal transplant program initiated in 1993 and 1994 resulted in many improvements over the past decade. Our comparison of 2 modern eras of transplant, 1991-1994 and 1995-2000, showed the following: 1. No significant differences in patient and donor characteristics. 2. Trends toward greater use of living donors (p = 0.07), older cadaveric donors (p = 0.084) and particularly cadaveric donors > 55 years of age (p = 0.09). 3. Decreasing mean CIT: 19.2 hours vs. 14.2 hours (p < 0.001). 4. Decreasing use of donors with CIT > 24 hours: 22% to 3%, (p < 0.001). 5. Decreased rate of DGF: 13% vs. 8% (p = 0.044). 6. Decreased rate of symptomatic CMV: 35% vs. 14% (p < 0.001). 7. Decreased rate of PTLD: 3.5% vs. 0.5% (p = 0.004). 8. Decreased one-year rate of acute rejection: 41% vs. 15% (p < 0.001). 9. Current one-year rate of acute rejection < 8%. 10. Decreased length of initial hospital stay: 12.7 days to 8.0 days (p < 0.001). 11. Decreased length of hospital in the first year after transplant: 10.6 days vs. 6.4 days (p < 0.001). 12. There were no improvements in patient and graft survival at one and 3 years. a. one-year patient survival rates: 95% vs. 96%. b. 3-year patient survival rates: 90% vs. 90%. c. one-year death-censored graft survival rates: 91% vs. 94%. d. 3-year death-censored graft survival rates: 87% vs. 88%.

Academic Medical Centers↗

Economic cost of expanded criteria donors in cadaveric renal transplantation: analysis of Medicare payments.

BACKGROUND: The use of expanded criteria donors (ECDs) in cadaveric renal transplantation is increasing in the US. We assess the economic impact of the use of ECDs to the Medicare end stage renal disease program. METHODS: The United Nations for Organ Sharing renal transplant registry was merged to Medicare claims data for 42,868 cadaveric renal transplants performed between 1991-1996 using USRDS identifiers. Only recipients for whom Medicare was the primary payer were considered, leaving 34,534 transplants. An ECD was defined as (1) age < or =5 or > or =55 years, (2) nonheart-beating donors, donor history of (3) hypertension or (4) diabetes. High-risk recipients (HRR) were age >60 years, or a retransplant. Medicare payments from the pretransplant dialysis period were projected forward to provide a financial "breakeven point" with transplantation. RESULTS: There were 25,600 non-HRR transplants, with 5,718 (22%) using ECDs, and 8,934 HRR transplants, of which 2,200 (25%) used ECDs. The 5-year present value of payments for non-ECD/non-HRR donor/recipient pairings was $121,698 vs. $143,329 for ECD/non-HRR pairings (P<0.0001) and, similarly was $134,185 for non-ECD/HRR pairings vs. $165,716 for ECD/HRR pairings (P<0.0001). The break even point with hemodialysis ranged from 4.4 years for non-ECD/ non-HRR pairings to 13 years for the ECD/HRR combinations but was sensitive to small changes in graft survival. Transplantation was always less expensive than hemodialysis in the long run. CONCLUSIONS: The impact of ECDs on Medicare payments is most pronounced in high-risk recipients. Cadaveric renal transplantation is a cost-saving treatment strategy for the Medicare ESRD program regardless of recipient risk status or the use of ECDs.

Aged↗

The economic benefit of allocation of kidneys based on cross-reactive group matching.

BACKGROUND: Recently the United Network for Organ Sharing (UNOS) began a pilot study to evaluate prospectively the merits of an allocation of cadaveric kidneys based on broader classes of HLA antigens, called cross-reactive groups (CREG). The objectives of the pilot study consider patient outcomes, but not the potential economic impact of a CREG-based allocation. This study predicts the impact of a CREG-based local allocation of cadaveric kidneys on 3-year Medicare payments and graft survival. METHODS: The UNOS renal transplant registry was merged to Medicare claims data for 1991-1997 by the United States Renal Data System. Average accumulated Medicare payments and graft survival up to 3 years posttransplant for first cadaveric renal transplant recipients were stratified by cross-reactive group mismatch categories. The economic impact was defined as the difference in average 3-year costs per transplant between the current and proposed allocation algorithms. Average 3-year costs were computed as a weighted average of costs, where the weights were the actual and predicted distributions of transplants across cross-reactive group categories. RESULTS: Results suggest that an organ allocation based on cross-reactive group matching criteria would result in a 3-year cost savings of $1,231 (2%) per transplant, and an average 3-year graft survival improvement of 0.6%. CONCLUSIONS: Cost savings and graft survival improvements can be expected if CREG criteria were to replace current criteria in the current allocation policy for cadaveric kidneys, although the savings appear to be smaller than may be achievable through expanded HLA matching.

Algorithms↗

Cadaveric versus living donor kidney transplantation: a Medicare payment analysis.

BACKGROUND: We found previously that the clinical advantages of living donor (LD) renal transplantation lead to financial cost savings compared to either cadaveric donation (CAD) or dialysis. Here, we analyze the sources of the cost savings of LD versus CAD kidney transplantation. METHODS: We used United States Renal Data System data to merge United Network for Organ Sharing registry information with Medicare claims data for 1991-1996. Information was available for 42,868 CAD and 13,754 LD transplants. More than 5 million Medicare payment records were analyzed. We calculated the difference in average payments made by Medicare for CAD and LD for services provided during the first posttransplant year. RESULTS: Average total payments were $39,534 and $24,652 for CAD and LD, respectively (P<0.0001) during the first posttransplant year. The largest source of the difference in payments was in inpatient hospitals, representing $10,653.67 (P<0.0001). For patients who had Medicare as the primary payer, average transplant charges were significantly higher for CAD donation ($79,730 vs. $69,547, P<0.0001); average transplant payments demonstrated no statistical differences ($28,483 vs. $28,447, P = 0.858). Therefore, inferred profitability was significantly higher for LD. CONCLUSIONS: Medicare payments are remarkably lower for LD compared to CAD in every category. The single largest cost saving comes from inpatient hospital services. A portion of the savings from LD could be invested in programs to expand living kidney donation.

Cadaver↗

Economics of the antithymocyte globulins Thymoglobulin and Atgam in the treatment of acute renal transplant rejection.

OBJECTIVE: To evaluate the economic implications for transplant centres, Medicare and society of treatment of corticosteroid-resistant Banff Grades I, II and III acute kidney transplant rejection with the antithymocyte globulins Thymoglobulin or Atgam. DESIGN AND SETTING: This was a cost analysis of a randomised double-blind multicentre clinical trial comparing the safety and efficacy of Thymoglobulin and Atgam that was performed at 25 centres in the US in 1994 to 1996. PATIENTS AND PARTICIPANTS: The study enrolled 163 patients, 82 in the Thymoglobulin arm and 81 in the Atgam arm. METHODS: Estimates of the cost of care from the initiation of rejection therapy to 90 days post-therapy were derived from various publicly available sources and applied to patient-specific clinical events documented in the clinical trial. Patients received either intravenous Thymoglobulin (1.5 mg/kg/day) for an average of 10 days or intravenous Atgam (15 mg/kg/day) for an average of 9.7 days. RESULTS: On average, Thymoglobulin provided significant cost savings compared with Atgam from the perspective of society [$US5977 (1996 values); 95% confidence interval (CI) $US3719 to $US8254], Medicare ($US4967; 95% CI $US3256 to $US6678) and the transplant centre ($US3087; 95% CI $US1512 to $US4667). The overall advantage attributable to Thymoglobulin was primarily due to savings from fewer recurrent rejection treatments and less frequent return to dialysis. CONCLUSIONS: Treatment of acute renal transplant rejection with Thymoglobulin is a cost saving strategy when compared with treatment with Atgam.

Acute Disease↗

The economic implications of HLA matching in cadaveric renal transplantation.

BACKGROUND: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria is controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. METHODS: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. RESULTS: Average Medicare payments for renal transplant recipients in the three years after transplantation increased from 60,436 dollars per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to 80,807 dollars for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P<0.001). By three years after transplantation, the average Medicare payments were 64,119 dollars for transplantations of kidneys with less than 12 hours of cold ischemia time and 74,997 dollars for those with more than 36 hours (P<0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings (4,290 dollars per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold ischemia time were considered. CONCLUSIONS: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold ischemia time were greater than the advantages of optimizing HLA matching.

Cadaver↗

A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients.

BACKGROUND: The aim of this study was to compare the efficacy and safety of Thymoglobulin (a rabbit-derived polyclonal antibody) to Atgam (a horse-derived polyclonal antibody) for induction in adult renal transplant recipients. METHODS: Transplant recipients (n=72) were randomized 2:1 in a double-blinded fashion to receive Thymoglobulin (n=48) at 1.5 mg/kg intravenously or Atgam (n=24) at 15 mg/kg intravenously, intraoperatively, then daily for at least 6 days. Recipients were observed for at least 1 year of follow-up. RESULTS: By 1 year after transplantation, 4% of Thymoglobulin-treated patients experienced acute rejection compared with 25% of Atgam-treated patients (P=0.014). The rate of acute rejection was lower with Thymoglobulin than Atgam (relative risk=0.09; P=0.009). Rejection was less severe with Thymoglobulin than Atgam (P=0.02). No recurrent rejection occurred with Thymoglobulin compared with 33% with Atgam (P=NS). Patient survival was not different, but the composite end point of freedom from death, graft loss, or rejection, the "event-free survival," was superior with Thymoglobulin (94%) compared with Atgam (63%; P=0.0005). Fewer adverse events occurred with Thymoglobulin (P=0.013). Leukopenia was more common with Thymoglobulin than Atgam (56% vs. 4%; P<0.0001) during induction. The mean absolute lymphocyte count remained below baseline with Thymoglobulin throughout the study (P<0.007), but with Atgam, significant lymphocyte reductions occurred only at day 7. The incidence of cytomegalovirus disease was less with Thymoglobulin than Atgam at 6 months (10% vs. 33%; P=0.025). CONCLUSIONS: Brief (7-day) induction with Thymoglobulin resulted in less frequent and less severe rejection, a better event-free survival, less cytomegalovirus disease, fewer serious adverse events, but more frequent early leukopenia than induction with Atgam. These results may in fact be explained by a more profound and durable beneficial lymphopenia.

Adolescent↗

Unusual presentations of nonmycotic hepatic artery pseudoaneurysms after liver transplantation.

The clinical presentation and causes of hepatic artery pseudoaneurysm vary widely in the postoperative liver transplant recipient, although infection is the most common cause. Although uncommon, hepatic artery complications continue to be an important source of morbidity in liver transplant recipients. Thrombosis, stenosis, and pseudoaneurysm formation are the most common posttransplantation arterial complications. Pseudoaneurysms are most commonly mycotic in origin. Prompt recognition of hepatic artery pseudoaneurysms with aggressive intervention (both surgical and angiographic) may decrease the morbidity associated with this rare clinical entity. The records of 263 consecutive patients who underwent orthotopic liver transplantation between 1991 and 1996 were reviewed retrospectively and assessed for hepatic artery complications. Two patients (0.7%) developed hepatic artery pseudoaneurysm, neither associated with infection. Both patients required operative repair and are doing well without vascular complications at a mean follow-up of 22.5 months. The clinical presentation and causes of hepatic artery pseudoaneurysm vary widely in the postoperative liver transplant recipient. Prompt recognition of hepatic artery pseudoaneurysms with aggressive intervention (both surgical and angiographic) may decrease the morbidity associated with this rare clinical entity.

Adult↗

Reducing the shortage of donor livers: what would It take to reliably split livers for transplantation into two adult recipients?

This article examines the scientific, technical, and administrative barriers to splitting donor livers for use in two adults. The main scientific barrier is that cadaveric donor livers at their current level of postoperative function are not sufficiently large to support life in two adult recipients. However, glycogenation of livers from young donors may be a method to overcome this problem in the short term. The three technical obstacles to splitting the liver in the midplane are anatomic anomalies that complicate or prevent splitting, the means to detect these anomalies, and the surgical methods to accomplish the split. Anatomic anomalies affecting the biliary drainage and arterial supply of the liver are the most important limiting technical factors. Administrative accommodations in the current methods of organ allocation will be needed if split-liver transplantation in adults is to succeed. A nationwide view of organ allocation requires that the total number of lives saved by the procedure be the priority outcome nationally. If liver transplantation is viewed from this perspective, split-liver transplantation for adults would be a high priority, and incentives should be set to encourage it.

Adult↗