A consolidated biovigilance system for blood, tissue and organs: one size does not fit all.

Biovigilance systems to assess and analyze risks for disease transmission through the transfer of organs, tissue, cells and blood between people is part of administrative oversight and has impact upon clinical practice and policy. In 2009, a formal recommendation by the Public Health Service requested that Health and Human Services fund and support efforts to consolidate national biovigilance efforts. There are differences in the biovigilance issues involved in organ and tissue donation/transplantation. If disease avoidance is made the dominant principle guiding organ donor testing, an unintended consequence may be an increase in deaths on the waiting list. We propose that overall benefit for the organ transplant recipient, tempered by patient informed awareness of limited organ availability and assessment processes, should be the guiding principle of such a system.

Waiting list removal rates among patients with chronic and malignant liver diseases.

Equitable liver allocation should ensure that nonelective removal rates are fairly distributed among waiting candidates. We compared removal rates for adults entered with nonmalignant (NM) (N = 9379) and hepatocellular cancer (HCC) (N = 2052) diagnoses on the Organ Procurement and Transplantation Network (OPTN) list between April 30, 2003, and December 31, 2004. Unadjusted removal rates for NM vs. HCC diagnoses were 9.4% vs. 8.7%, 13.5% vs. 16.9% and 19.1% vs. 31.8% at 90, 180 and 365 days, respectively after listing. For NM candidates, model for end-stage liver disease (MELD) score (RR = 1.16), age (RR = 1.03) and metabolic disease diagnoses (RR = 1.66) had higher risks of removal; and PSC (RR = 0.62) and alcoholic cirrhosis (RR = 0.82) had lower risks of removal. For HCC candidates, MELD score at listing (RR = 1.09), AFP (RR = 1.02), maximum tumor size (RR = 1.16) and age at listing (RR = 1.02) had increased risks of removal. The equation 1 - 0.920 exp[0.09369 (MELD at listing - 12.48) + 0.00193 (AFP - 97.4) + 0.1505 (maximum tumor size - 2.59) defined the probability of dropout for HCC candidates within 90 days of listing. We conclude that factors associated with the risk of removal for HCC are different from NM candidates, although MELD score at listing remains the most predictive for both groups. Liver transplant candidates with HCC may be prioritized using a risk score analogous to the MELD score.

Excellent liver transplant survival rates under the MELD/PELD system.

The MELD/PELD (M/P) system for liver allocation was implemented on February 27, 2002, in the United States. Since then sufficient time has elapsed to allow for assessment of posttransplant survival rates under this system. We analyzed 4163 deceased donor liver transplants performed between February 27, 2002, and December 31, 2003, for whom follow-up reporting was 95% and 67% complete at 6 and 12 months, respectively. Kaplan-Meier survival analysis revealed 1-year patient and graft survival rates for status 1 of 76.9% and 70.4%, respectively, and 87.3% and 82.9% for patients prioritized by M/P (P < .0001 for status 1 vs M/P). When adult candidates were stratified by MELD score quartile at transplant, 1-year survival rates were 89.5%, 88.3%, 86.6%, and 78.1% for lowest to highest quartile (P = .0002) and graft survival rates were similarly distributed (85.0%, 84.5%, 82.7%, 73.0%, P < .0001). Candidates with hepatocellular cancer (89.6%) and other MELD score exceptions (88.8%) had slightly higher 1-year survival rates compared with standard MELD recipients (86.0%), which did not reach statistical significance (P = .089). Pediatric recipients had slightly better patient (88.7%) and graft (86.5%) survival rates at 1 year than adults but there were no significant differences among the PELD strata due to small numbers of patients in each PELD quartile. We conclude that patient and graft survival have remained excellent since implementation of the MELD/PELD system. Although recipients with MELD scores in the highest quartile have reduced survival compared with other quartiles, their 1-year survival rate is acceptable when their extreme risk of dying without a transplant is taken into consideration.

MELD/PELD: one year later.

The liver allocation policy in the United States was changed on February 27, 2002, to a continuous scale with almost no weight given to time waiting on the list. This was based on the dissatisfaction with the old categorical system and an understanding that waiting time as not a good discriminator of medical urgency. To assess the effects of this change, liver allocation results for the first 6 months of this new system (February 27, 2002, to August 30, 2002, era 2) with the corresponding 6 month period 1 year earlier (February 27, 2001, to August 30, 2001, era 1) were compared. Fewer registrations on the waiting list, fewer removals from the waiting list because of death or "too sick," and an increase in the number of cadaveric transplants under the new system were observed. Patients with hepatocellular cancer received additional priority with the new policy and there was a significant increase in the number of candidates transplanted with this diagnosis in era 2. Early posttransplant patient survival has not changed under the new system. Although there are many areas for improvement, which will be addressed in future refinements, the new US liver allocation plan has provided a more objective, patient-specific system to better rank waiting liver transplant candidates.

Living-donor versus cadaveric liver transplantation for non-resectable small hepatocellular carcinoma and compensated cirrhosis: a decision analysis.

BACKGROUND: Cadaveric liver transplantation is effective for nonresectable early hepatocellular carcinoma. However, the scarcity of cadaveric organs has prompted some centers to use living donors, which guarantees transplantation, but entails a risk to the donor. In the absence of controlled trials, decision analysis can be used to help explicate the tradeoffs involved when considering living donor versus cadaveric liver transplantation for nonresectable early hepatocellular carcinoma. METHODS: Using a Markov model, a hypothetical cohort of patients with Child's A cirrhosis and a single 3.5-cm tumor received one of three strategies: 1) no transplant; 2) intent to perform cadaveric liver transplantation; or 3) living donor liver transplantation. Data were obtained from natural history and retrospective studies. All probabilities in the model were varied simultaneously using a Monte Carlo simulation. RESULTS: Living-donor liver transplantation was the best strategy, improving life expectancy by 4.5 years compared with cadaveric liver transplantation. This strategy remained dominant even when varying severity of cirrhosis, age, tumor doubling time, tumor growth pattern, blood type, regional transplant volume, initial tumor size, and rate of progression of cirrhosis. CONCLUSIONS: Living-donor liver transplantation should confer a substantial survival advantage for patients with compensated cirrhosis and non-resectable early stage hepatocellular carcinoma.

Preliminary results of a liver allocation plan using a continuous medical severity score that de-emphasizes waiting time.

Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P =.002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P =.10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 (P =.005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P =.04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2. Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy.

Liver transplant waiting time does not correlate with waiting list mortality: implications for liver allocation policy.

Factors associated with the risk for mortality once placed on the liver transplant waiting list and how this risk relates to center-specific waiting time and transplant activity have not been adequately evaluated. We performed this study to determine the association between center-specific waiting time and waiting list mortality among liver transplant candidates stratified by medical urgency at the time of registration. A Cox proportional hazards model was used to calculate 2-year mortality risk for a cohort of 16, 414 registrants added to the United Network for Organ Sharing liver transplant waiting list between January 1, 1997, and December 31, 1997. After controlling for confounding variables, we calculated the mortality risk for centers, organ procurement organizations (OPOs), and states. The relation between center-specific waiting list mortality risk and median waiting time or transplant activity was determined by linear regression. In multivariate analyses, higher initial medical urgency status (relative risk [RR] = 12.8; P <.001), increasing age (P <.001), black ethnicity (RR = 1.29; P <.001), history of previous transplant (RR = 1.2; P =.009), certain liver diagnoses, and smaller center size (RR = 1.39; P =.008) were associated with significantly increased waiting list mortality. Candidates with blood type A (RR = 0.87; P <.001) and those with cholestatic cirrhosis as the primary diagnosis (RR = 0.73; P < 0. 001) had a reduced risk for dying. There were significant variations in 2-year waiting list mortality risk among centers, OPOs, and states. However, when stratified by medical urgency status at waiting list entry, center-specific waiting time and transplantation rates accounted for almost none of the center-specific waiting list mortality. Although there are variations in waiting list mortality risk among centers, OPOs, and states, there is very little relation between center-specific waiting list mortality and center-specific median waiting time or center-specific transplantation rates when stratified by medical urgency. Waiting time and center transplant rates should not influence liver allocation policy.

How much do immigration and trade affect labor market outcomes?

"This paper provides new estimates of the impact of immigration and trade on the U.S. labor market.... We examine the relation between economic outcomes for native workers and immigrant flows to regional labor markets.... We...use the factor proportions approach to examine the contributions of immigration and trade to recent changes in U.S. educational wage differentials and attempt to provide a broader assessment of the impact of immigration on the incomes of U.S. natives." Comments and discussion by John DiNardo, John M. Abowd, and others are included (pp. 68-85).

Multiple organ failure after liver transplantation.

OBJECTIVE: To examine the effect of multiple organ failure after liver transplantation on mortality and resource utilization. DESIGN: Retrospective cohort study. SETTING: Surgical intensive care unit in a tertiary care university hospital. PATIENTS: Consecutive series of 113 adults undergoing liver transplantation between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or had incomplete records (n = 7). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We prospectively developed definitions for organ failure, and quantitated the frequency and related outcomes for mortality and resource utilization. Multiple organ failure was defined as the presence of two or more organ failures. Patients were grouped according to the presence (n = 31) or absence (n = 65) of multiple organ failure. Preoperative severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE II) and United Network for Organ Sharing (UNOS) scoring systems. Postoperative outcome data, including hospital survival rate, hospital length of stay, and charges were recorded. The frequency of multiple organ failure after liver transplantation was 32%. The mortality rate in the patients who developed multiple organ failure was 42% vs. only 2% in those patients without multiple organ failure (p < .0001). Patients with four or more organ failures had a 100% mortality rate. Postoperative multiple organ failure was associated with increased hospital length of stay (46 +/- 7 days vs. 29 +/- 2 days; p = .026) and increased hospital charges ($271,497 +/- 29,994 vs. $136,372 +/- 8,310; p < .0001). Higher preoperative APACHE II and UNOS scores predicted postoperative multiple organ failure, but were less accurate tools for predicting risk of death. CONCLUSIONS: Multiple organ failure is associated with death and increased resource utilization in liver transplantation. Pretransplantation severity of illness, as measured by APACHE II and UNOS scoring systems, is an important determinant of postoperative multiple organ failure and outcome.

Immigration from poor to wealthy countries: experience of the United States.

PIP: The U.S. experience with immigration from poor countries is examined using the results of two projects carried out by the National Bureau of Economic Research. Questions considered include what determines the supply of immigrants, how such immigrants fare in the U.S. job market, and how this immigration affects the prospects of native-born workers.^ieng

The labour-market consequences of generational crowding.

PIP: This paper attempts to distinguish between two alternative views of the labour-market problems faced by young workers in a number of industrialized countries in the 1970s and early 1980s. The first view is that the low relative earnings and high unemployment rates experienced by these cohorts were largely age-related; the second is that they are a consequence of large cohort size. A multi-country empirical analysis indicates that large cohort size tends to have a negative effect on the expected earnings...of a cohort there is, moreover, a marked tradeoff between the relative-earnings effect and the relative-employment effect, with large cohort sizes reducing relative earnings in some countries and relative employment in others. More detailed data for the U.S.A. show that the relatively low wages and high unemployment of the 'unlucky' cohorts have tended to converge to the patterns that would have resulted had the cohorts been more 'normal' in size, but that their lifetime income has been permanently reduced. Finally, baby-boom cohorts in several countries are shown to have been absorbed in a wide range of industries rather than through expansion of the traditionally youth-intensive industries. (author's modified)^ieng

Case-mix and treatment in end-stage renal disease: hemodialysis v peritoneal dialysis.

The University of Southern California School of Medicine conducted a nationwide survey of 336 nephrologists to obtain demographic and clinical data on 6,411 patients with end-stage renal disease (ESRD). Patient demographic data, along with ESRD etiology and comorbid conditions noted by the physician, were compared across various modalities of dialysis. Characteristics of the treatment provided were differentiated by the mode of dialysis and the location of the patient encounter. Results of the analysis show that patients on peritoneal dialysis are more likely to be female and have higher rates of diabetes compared with hemodialysis (HD) patients. Statistically, patients on intermittent peritoneal dialysis are older, more likely to be black, and have a higher incidence of cardiovascular conditions. Continuous ambulatory peritoneal dialysis patients have greatest problem severity and require more physician time and more complex services, whereas home HD patients require the greatest number of diagnostic tests and therapeutic procedures. Hospital inpatient care shows greater case-mix severity and more intensive treatment, but this does not differ by the mode of dialysis. Finally, patients of freestanding dialysis facilities are more likely to have hypertensive renal disease, whereas patients at hospital-based facilities are older, more likely to be seen in the hospital, have more urgent and severe problems during dialysis rounds, and require more physician time, more complex services, and more diagnostic tests and therapeutic procedures.