Evaluation of research products released during a national project funded by the Italian Ministry of Health.

Evaluation of research products released during activities that have received public funds should be a mandatory practice. In this study, we evaluated the research products released during the research program "Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation" (SITF Project), funded by the Italian Ministry of Health. The SITF Project prefigured the participation of Italian transplantation centers with more advanced experience in the field of liver transplantation. The research products released during the SITF Project were evaluated according to Guidelines for Research Evaluation of the Committee for Evaluation of Research (CIVR) from the Italian Ministry of Education, University and Research. Thus, we considered as the research products released during the SITF Project the number of articles published in English language in peer-reviewed scientific journals by each operative unit (OU), as returned by PubMed. The articles were included on the basis of relationship with the research lines of the SITF Project and availability of the impact factor (IF) calculated by Thomson Scientific for each journal. Following these criteria, 62 research products were released during the executive phase of the SITF Project (January 1, 2004-December 31, 2005). All research products were original articles, with no reviews or letters. The articles were published in 10 different scientific journals (mean IF, 2.64+/-1.74). Spearman's rank test found a weak negative correlation between journal IF and number of published articles (r= -.2919; P= .413). Although the OU involved in the coordination of the SITF Project released a relatively high number of articles (n=8; IF, 0.923+/-0.352), several other OUs obtained better results for number of articles (9-11) and/or IF (3.071+/-2.248 or 2.959+/-1.779). In projects that benefit from public funds, the potential negative impact of coordination activities to scientific production should be adequately considered.

Evaluation of an information system for kidney transplantation in adult and pediatric recipients using the RAND/UCLA Appropriateness Method.

In the mid-1980s, RAND Corporation and University of California Los Angeles (UCLA) developed the RAND/UCLA Appropriateness Method (RAM) to evaluate the correctness of medical and surgical procedures. In this study, the RAND/UCLA Appropriateness Method was used to evaluate the appropriateness of a dataset concerning kidney transplantation in adult and pediatric recipients for an information system funded by the Italian Ministry of Health. The original dataset was obtained using an interdisciplinary pool of regional experts (n=60). This dataset held 514 items about kidney transplantation in adult (n=268) and pediatric (n=246) recipients. The items were stratified as 3 main groups: pretransplantation items (adult, n=141; pediatric, n=122), transplantation items (adult, n=49; pediatric, n=45), and early posttransplantation and follow-up items (adult, n=78; pediatric, n=79). In the second round, the dataset was subjected to an extraregional panel of independent experts (n=9) to assess each item using a score ranging from 1 to 9 based on increasing appropriateness. The expert-opinion process returned for adult and pediatric kidney recipient items whole mean scores of 8.52+/-0.32 and 8.65+/-0.32, respectively. Overall agreement, uncertainty, and disagreement between experts about item appropriateness concerning adult kidney recipients were 94.6%, 5.4%, and 0%, respectively. For pediatric kidney recipients, overall agreement, uncertainty, and disagreement between experts about item appropriateness were 96.9%, 2.35%, and 0.07%, respectively. This study supported the use of a structured expert-opinion process as an effective strategy to evaluate the appropriateness of large datasets for kidney transplantation in both adult and pediatric recipients.

Model for End-Stage Liver Disease (MELD) score and organ allocation from cadaveric donors for 198 liver transplantation procedures performed in a single center.

Since February 2002, the United Network for Organ Sharing (UNOS) proposed to adopt a modified version of the Model for End-Stage Liver Disease (MELD) to assign priority on the waiting list for orthotopic liver transplantation (OLT). In this study, we evaluated the impact of MELD score on liver allocation in a single center series of 198 liver recipients (mean age of patients, 52.21+/-8.92 years), considering the relationship between clinical urgency derived from MELD score (overall MELD, 18.7+/-6.83; MELD <15 in 69 patients, MELD >or=15 in 129 patients) and geographical distribution of cadaveric donors (inside/outside Liguria Region, 125/73). The waiting time for OLT was 230+/-248 days, whereas the 3-month and 1-year patient survivals were 87.37% and 79.79%, respectively. No difference was observed for MELD score retrospectively calculated for patients who underwent OLT before February 2002 (n=71) compared with MELD score calculated for patients who received a liver thereafter (18.26+/-6.68 vs 18.94+/-6.92; P= .504). No significant difference was found in waiting time before and after adoption of MELD score (213+/-183 vs 238+/-278 days; P= .500), or by stratifying patients for MELD <15/>or=15 (225+/-234 vs 232+/-256 days; P= .851). Using the geographical distribution of donors as a grouping variable (outside vs inside Liguria Region), no significance occurred for MELD score (19.68+/-7.42 vs 18.17+/-6.42; P= .135) or waiting time (211+/-226 vs 242+/-261 days; P= .394). In our series, more OLTs were performed among sicker patients and no differences were found in the management of livers procured from cadaveric donors outside or inside Liguria Region. However, further efforts are needed to reduce the waiting time among patients with higher MELD scores.

Sirolimus therapy in liver transplant patients: an initial experience at a single center.

Sirolimus (SRL) is an mTOR inhibitor that has been shown, in contrast to calcineurin inhibitors (CNI), to inhibit cancers in experimental models. Since February 2005, we introduced SRL in liver transplant patients in group a, in whom the primary disease was hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic or autoimmune liver cirrhosis, and group b, HCC-negative patients who developed posttransplantation cancers de novo. Of 18 patients in group a, 11 received SRL ab initio (subgroup a1), starting for 10 patients at 66.1+/-29.2 days after surgical healing and after 10 days in 1 case; the remaining 7 patients (subgroup a2) received SRL at 31.2+/-24.2 months. Three patients in group b, included 1 with Kaposi's sarcoma, 1 with bladder cancer, and 1 with thyroid cancer. In this group, SRL was introduced at 80.8+/-40.4 months. In all patients but one, who received a single 5 mg loading dose, SRL was started at 2 mg/d and adjusted to 6 to 8 ng/mL blood levels. CNI drugs, present as primary therapy, were gradually tapered to low levels and eventually stopped. The following observations were drawn from this initial experience: (1) 4/21 (19.0%) patients had to discontinue SRL because of early and late side effects: thrombocytopenia (n=2) and headache with leukopenia and leg edema associated with knee joint arthralgia (n=2); (2) 14 patients (11 in group a and 3 in group b) are still on SRL monotherapy; (3) 1 HCC recurrence and 1 de novo pancreatic adenocarcinoma were observed at 14 and 16 months, respectively (at the time of transplantation, both patients were beyond the MIlan HCC criteria), and (4) 1 patient, from subgroup a1, died after 99 days due to pneumonitis and possible relation to SRL lung toxicity. In conclusion, SRL appeared to be an effective immunosuppressant that could be used as monotherapy in liver transplant patients. Any conclusion on SRL anticancer effects can only come from randomized large studies after long follow-up.

Application of the RAND/UCLA Appropriateness Method to evaluate an information system for kidney/pancreas transplantation in adult recipients.

With the aim to evaluate the correctness of medical and surgical procedures, RAND Corporation and University of California Los Angeles (UCLA) developed the RAND/UCLA Appropriateness Method (RAM). In this study, the RAM was applied to evaluate the appropriateness of a dataset concerning kidney/pancreas transplantation in adult recipients for an information system funded by the Italian Ministry of Health. The original dataset was obtained using an interdisciplinary pool of experts (n=60) involved in kidney/pancreas transplantation activity in the Liguria Region. This dataset held 291 items, stratified as pretransplantation items (n=158), transplantation items (n=49), and early posttransplantation and follow-up items (n=84). In the second round, the dataset was subjected to an extraregional panel of independent experts (n=9) to assess each item using a score ranging from 1 to 9 based on increasing appropriateness. The expert-opinion process returned a whole mean score of 8.47+/-0.43 (95% confidence interval [CI] 8.30-8.63). Overall agreement, uncertainty, and disagreement between experts about item appropriateness were 98.5%, 1.49%, and 0%, respectively. Agreement/uncertainty for pretransplantation, transplantation, and posttransplantation items were 99.87%/0.12%, 100%/0%, and 96.37%/3.62%, respectively. This study supported the utility of a structured expert-opinion process as an effective strategy to evaluate the appropriateness of large datasets for kidney/pancreas transplantation in adult recipients.

Application of a Bayesian simulation model to a database for split liver transplantation on two adult recipients in the environment of WinBUGS (Bayesian Inference Using Gibbs Sampling).

A Bayesian simulation model has been applied to a database developed for split liver transplantation on two adult recipients (SLT A/A) in the context of a macroregional project funded by the Italian Ministry of Health. The model was entered within Bayesian inference Using Gibbs Sampling (WinBUGS), a free software for Bayesian analysis of complex statistical models using Markov chain Monte Carlo techniques developed by the MRC Biostatistics Unit Cambridge jointly with the Imperial College School of Medicine at St Mary's, London. The model was built by using data entry performed from January 1, 2005 to August 5, 2005. In that period, 20 potential donors suitable for the SLT A/A procedure were entered into the database. We only selected the continuous and dichotomous donor-related variables (DRV, n = 62) for which almost one data entry procedure. The model assumed that a database user learned during data entry procedures for each donor, and that the probability of a successful input may depend on the number of previous errors and corrections. After binary transformation of the DRV (value 0 for each input record, value 1 for each no input record), we calculated an overall value of 0.28 +/- 0.27 (median: 0.3; 95% confidence interval: from 0.18 to 0.629). The transformed DRV were entered within the WinBUGS environment after model specification, assuming as success (y = 1) each procedure of input record, and as failure (y = 0) each procedure of no input record. A unequivocal convergence was obtained after 10,000 iterations, and a simulation run was launched for a further 10,000 updates. We obtained a negligible Monte Carlo error and a fine profile in the kernel density plot. This study supported the application of simulation models to databases concerning liver transplantation as a useful strategy to identify a critical state in the data entry process.

A preliminary data entry analysis on a multicentric informative system for split liver transplantation in two adult recipients.

In the context of the national research program "Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation" (SITF project), funded by the Italian Ministry of Health, an experimental and multicentric Web-based information system was developed to automate theoretical matching between a potential donor and two adult recipients for in situ split liver transplantation (SLT A/A). Data entry in the SITF database was performed in addition to activities formally required for patient and donor management by national legislation and guidelines. Data entry carried out within the SITF database from January 1, 2005 to August 8, 2005 was processed by stratifying original variables as donor- and patient-related. Only records required for donor-recipients matching had a mandatory data entry. The donor subset showed data entry procedures in 62 variables for 20 potential donors, whereas in the patient subset, we found 28 variables for 100 potential liver recipients. In the donor subset, 1004 records were filled, for a raw completeness of 77.08%. After adjustment for appropriateness, there were 935 remaining records with an adjusted completeness of 76.64% (P = .823). In the patient subset, 2653 records were filled, for a raw completeness of 98.69%. No difference in patient subset records was found after rechecking for appropriateness. A significant difference occurred for adjusted completeness between the donor versus the patient subsets (P < .0001). The results of this study suggested that only the presence of mandatory donor records may produce a consistent database suitable for SLT A/A.

Split liver network: a collaborative internet-based scenario to expand the organ pool.

BACKGROUND: Split liver transplantation (SLT) has become a crucial option to maximize the liver pool, while organ procurement organizations (OPOs) usually allocate whole livers to single centers. In 2003, Italian Ministry of Health funded the Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation project with the goal to establish sharing criteria for SLT for two adults (SLT A/A), involving Italian transplantation centers, the North Italy Transplant OPO, and the Italian National Transplant Center. METHODS: SITF group defined donor/recipient inclusion criteria, setting minimum graft/recipient weight ratio (GRWR) at 1.2%. Donors and recipients on waiting list were shared on an Internet secured Web-based application (Split Liver Network [SLN]). SLN performs real-time matches between the registered donor and all patients on the bases of GRWR, displaying a size-based list of matched donor/patients, figuring hemiliver allocation once the whole organ is referred to a specific center. RESULTS: In the 2005 period, 47 donors and 124 patients were entered by nine centers, and six hemiliver allocations for three SLT A/A procedures were performed. By retrospective simulation of 32 donors and 613 recipients in the Nord Italia Transplant area, matchable recipients were available for all donors, while blood group frequency seemed a determining factor, more than donor body weight. COMMENTS: SLN hemiliver allocation might increase matching possibilities, offering a timely transplant for recipients of rare group, small-size, or in need of short wait. Our experience suggests that such an environment may be helpful to share a macroregional pool of liver recipients and to optimize SLT.

Application of the RAND/UCLA appropriateness method to evaluate an informative system for liver transplantation in adult and pediatric recipients.

The Delphi Method (DM) is the most frequently used technique to acquire structured expert-opinion elicitation (EOE). It has been increasingly applied to construct guidelines in medicine and to evaluate the appropriateness of clinical procedures. In this study, the RAND/UCLA appropriateness method was used as a structured EOE process to evaluate the appropriateness of a dataset concerning liver transplantation in adult and pediatric recipients for an information system funded by the Italian Ministry of Health. The original dataset was obtained using an interdisciplinary pool of regional experts (n = 60). This dataset held 280 items stratified into three groups: I. pretransplant items (n = 123); II. transplant items (n = 65); III. early posttransplant and follow-up items (n = 92). In the second DM round, the dataset was subjected to an extraregional panel of independent experts (n = 9) to assess a score ranging from 1 to 9 on each item based on increasing appropriateness, according to the RAND/UCLA Appropriateness Method. Overall agreement, uncertainty, and disagreement between experts was 95.89%, 3.12%, and 0.99%, respectively. For each group, agreement-uncertainty-disagreement were 99.35%/0.65%/0% (group I), 91.53%/5.30%/3.17% (group II), and 96.87%/3.13%/0% (group III), respectively. This study supported the use of a structured EOE process to evaluate the appropriateness of a large dataset for liver transplantation activity.

Medical report type in liver transplantation as a quality system document: new prospects for computerization.

The usage of a computerized system to organize data and ease the activity procedures of liver transplantation is useful in clinical transplantation. Preliminary cognitive research on systems of clinical transplantation database concerning medical reports was performed to verify their development level. The survey highlighted that, so far, there has been no experimentation that can be applied to a medical report type devoted to liver transplantation. Regulations in force substantially point out that the medical report ought to contain all items that have to be taken into account in handling the patient from pretransplantation to follow-up. The Department of Transplantation of Genoa chose its medical report model for liver transplantation. The medical report model included the following items: personal data; case history; diagnosis; initial examination for prelisting; fitness for transplantation; assistance context; clinical data including subjective, objective, and instrumental parameters; pharmacological therapies; informed consent, evaluation of fitness; nursing data; counseling and clinical evaluations according to protocols and guidelines of the national transplantation centers. If the computing is well trained, it is supposed to help maintain a whole data view provided it is supplied information in an adequate way. Immediate clinical procedural advantages and useful scientific observations may be obtained from a high-quality database. In fact, all functions have to be applied to specific clinical, administrative needs to be remotely shared and conveniently integrated with each other to make the liver transplantation medical report an easy and handy instrument for inputting and handling data. It must be a precise, complete instrument that may be accessible in real time from any site connected with the intranet network, be unchangeable, and be protected to ensure certification and forensic medicine value.

Innovative strategies to expand cadaveric donor pool for liver transplantation (SITF project): a network between Italian transplantation centers supported by the Ministry of Health.

In 2002, the Italian Ministry of Health (IMH) launched a formal call for health research programs within the Research and Development (R&D) Policy. In this context, the research program "Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation" (SITF Project) has been proposed. The SITF Project has been formally approved by IMH as a 2-year research program included in the R&D Policy. The main goals of the SITF Project are to improve matching criteria for split liver transplantation (SLT) in both pediatric and adult recipients, to promote an increase of the SLT/full- size liver transplantation ratio at the national level, and, especially, to establish shared criteria for SLT in 2 adult recipients. The original executive plan of the SITF Project prefigured the participation of both the Italian transplantation centers with more advanced experience in the field of SLT, and institutional partnership, such as Nord Italia Transplant (NITp) and Italian National Transplant Center. A first Web public area concerning the SITF Project has been activated, as well as a reserved Web area with the aim to share cadaveric donors and patients in the waiting lists between Operative Units involved in the research program. For this objective, the first version Oracle-based database able to perform an automatic matching between a single cadaveric donor and 2 potential adult recipients has been released at the beginning of 2005. The SITF Project represents a new approach in the management of SLT for 2 adult recipients in Italy and a model for a functional network between Italian transplantation centers.

Preliminary results of an expert-opinion elicitation process to prioritize an informative system funded by Italian Ministry of Health for cadaveric donor management, organ allocation, and transplantation activity.

Expert-opinion elicitation (EOE) is a heuristic process for gathering evidence and data or answering questions on issues/problems of concern. The Delphi method (DM) is the most frequent technique used to obtain structured elicitation of expert opinions. It has been increasingly applied in medicine to produce guidelines and to evaluate the appropriateness of diagnostic procedures. In this study, a DM has been used as structured EOE process to assess the appropriateness and clinical priority of a data set-based informative system in the context of the Liguria-Trento Transplant Network (LTTN) Project, funded by Italian Ministry of Health. The original data set was obtained by using an interdisciplinary pool of regional experts (n = 60). This data set held 1506 items stratified in 21 categories at various surgical phases (preoperative, intraoperative, and postoperative) and transplantation types (liver, kidney, and kidney/pancreas) in adult and pediatric recipients. Some categories included cadaveric donor management, organ allocation, and acute liver failure. In the second DM round, the data set was subjected to a panel of extraregional, independent experts (n = 9) to assess scores ranging from 1 to 9 on each item, based on increasing appropriateness/priority, according to RAND/UCLA Appropriateness Method. The overall agreement between experts was 95.88%, whereas disagreement and uncertainty were 0.13% and 3.98%, respectively. A major uncertainty occurred for the data set concerning the multiorgan cadaveric donor, for liver transplantation, and for kidney transplantation in adult recipients. The use of a structured EOE process may represent an effective strategy to define the appropriateness and prioritization criteria of a large data set in the field of solid organ transplantation.

First results of Liguria-Trento transplant network project: a model for a macroregional network and real-time registry in Italy.

In Italy, health-care telematic is funded and supported at the level of national government or regional institutions. In 1999, the Italian Ministry of Health started to fund the Liguria-Trento Transplant Network (LTTN) project, a health research project with the aim to build an informative system for donor management and transplantation activity in a macroregional area. At the time of LTTN project proposal, no published Transplant Network Informative System fulfilled Italian rules on telematic management of electronic documentation concerning transplantation activity. Partnership of LTTN project were two Regional Transplant Coordinating Centres, Nord Italia Transplant Interregional Coordinating Centre and the Italian Institute of Health/National Transplant Coordinating Centre. Project Total Quality Management methods were adopted. Technological and case analysis followed ANSI-HL7, CEN-TC251, and Object-Oriented Software Engineering standards. A low-tech prototype powered by a web access relational database is running on a transplant network including web-based clients located in 17 intensive care units, in Nord Italia Transplant Interregional Coordinating Centre, and at the Italian Institute of Health/National Transplant Coordinating Centre. LTTN registry includes pretransplant, surgical, and posttransplant phases regarding liver, kidney, pancreas, and kidney-pancreas transplantation in adult and pediatric recipients. Clinical specifications were prioritized in agreement with the RAND/UCLA appropriateness method. Further implementation will include formal rules for data access and output release, fault tolerance, and a continuous registry evolution plan.