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Biomedical subjects

G Barosi

Publications and source records attributed to G Barosi.

At least 19 recordsLinked to original sources

Strategies for dissemination and implementation of guidelines.

Interventions designed to effectively implement and disseminate clinical practice guidelines (CPG) fall into different categories. A systematic review of the effectiveness and costs of different guideline development, dissemination and implementation strategies was recently undertaken by the Health Technology Assessment (HTA) Programme in UK. Overall, the majority of comparisons reporting dichotomous process data observed improvement in care. However, there was considerable variation in the observed effects both within and across interventions. Evaluation studies provided evidence that adherence of physicians to CPG is a strong predictor of the stroke outcome. Cochrane Collaboration performed a systematic review including studies published up to 2004 that compared integrated clinical pathways (ICP) for stroke care with standard medical care. They found no significant difference between ICP and control groups in terms of death or discharge destination. Patients managed with a care pathway were more dependent at discharge, less likely to suffer a urinary tract infection, less likely to be readmitted and more likely to have neuroimaging. A positive effect was reported from a validation study of a multifaceted strategy for stroke care ICP implementation in Italy.

Health Plan Implementation↗

Diagnostic and clinical relevance of the number of circulating CD34(+) cells in myelofibrosis with myeloid metaplasia.

The absolute content of CD34(+) cells in the peripheral blood of 84 patients with myelofibrosis with myeloid metaplasia (MMM) and 23 patients with other Philadelphia-negative (Ph(-)) chronic myeloproliferative disorders (CMDs) was investigated. In MMM, the median absolute number of circulating CD34(+) cells was consistently high (91.6 x 10(6)/L; range, 0-2460 x 10(6)/L). Receiver operating characteristic curve analysis showed that 15 x 10(6)/L as a decision criterion for CD34(+) cells produced an almost complete discrimination between MMM patients out of therapy and other Ph(-) CMDs (positive predictive value, 98.4%; negative predictive value, 85.0%). MMM patients with higher numbers of CD34(+) cells had a significantly longer disease duration (P =.019) and higher spleen volume index (P =.014), liver volume (P =.000), percentage of circulating immature myeloid cells (P =.020), and percentage of myeloid blasts (P =.000). When CD34(+) cells were correlated with the use of Dupriez risk stratification, CD34(+) cells increased significantly from low-risk (median, 68.1 x 10(6)/L) to intermediate-risk (median, 112.8 x 10(6)/L) and high-risk patients (median 666.1 x 10(6)/L) (F = 4.95; P =.009). When CD34(+) cells were correlated with a severity score on the basis of both myeloproliferative and myelodepletive characteristics of the disease, only the myeloproliferation index was significantly associated with CD34(+) cell level (F = 5.7; P =.000). Overall survival and interval to blast transformation from the time of CD34(+) cell analysis were significantly shorter in patients with more than 300 x 10(6)/L CD34(+) cells (P =.005 and.0005, respectively). In conclusion, the absolute number of CD34(+) circulating cells allows MMM to be distinguished from other Ph(-) CMDs; it is strongly associated with the extent of myeloproliferation and predicts evolution toward blast transformation.

Adult↗

Low-molecular-weight heparin versus warfarin for secondary prophylaxis of venous thromboembolism: a cost-effectiveness analysis.

PURPOSE: To compare the cost effectiveness of low-molecular-weight heparin with that of oral anticoagulants in preventing recurrences after an episode of venous thromboembolism. METHODS: A decision tree was used to assess the cost and the expected quality-adjusted years of life (QALY) after treatment with either low-molecular-weight heparin or warfarin, based on pooled data from six published trials. Preferences were elicited with a modified time trade-off method in a sample of patients attending an anticoagulation clinic. RESULTS: Compared with warfarin, low-molecular-weight heparin significantly decreased the rate of minor bleeding (odds ratio [OR] = 0.24; 95% confidence interval [CI]: 0.14 to 0.43) but not recurrent deep vein thromboses (OR = 0.77; 95% CI: 0.43 to 1.35). Patients' preference for warfarin (0.988, on a 0 to 1 scale) was lower than that for low-molecular-weight heparin (0.992), but the difference was not statistically significant. A Monte Carlo analysis estimated that low-molecular-weight heparin saved an average of 13 quality-adjusted days compared with warfarin, at a cost of $6,583 per QALY (95% CI: $5,525 to $7,625) based on costs in Italy and $28,231 per QALY (95% CI: $20,872 to $36,773) based on costs in the United States. When we included rebound recurrences after interruption of therapy, which were more common with low-molecular-weight heparin, treatment with low-molecular-weight heparin cost $53,166 per QALY in Italy and $177,166 per QALY in the United States. CONCLUSIONS: Low-molecular-weight heparin might be a cost-effective drug for secondary prophylaxis of venous thromboembolism, especially in patients at high risk of recurrence and where the drug's cost is lower. The apparent increase in recurrence after interruption of therapy needs to be investigated more thoroughly before low-molecular-weight heparin can be recommended routinely.

Administration, Oral↗

Myelofibrosis with myeloid metaplasia in adult individuals 30 years old or younger: presenting features, evolution and survival.

Myelofibrosis with myeloid metaplasia (MMM) usually affects older people and is associated with a median survival of 3.5-5 yr. Survival of MMM patients 55 yr old or younger is longer, but there is no information on the youngest subset. The presenting features, evolution and survival were analyzed in 9 patients with MMM aged 30 yr or less, representing 2.8% of two series including 323 cases. Age ranged from 17 to 30 yr; 3 patients were males and 6 females. Five patients were asymptomatic and none had constitutional symptoms. Anemia was observed in 4 patients, being severe in only one. The WBC count was normal in 7 patients and 2 had mild leukocytosis; moderate thrombocytosis was observed in 7 patients. No patient showed blood blast cells or bone marrow cytogenetic abnormalities. With a median follow-up of 6.8 (range 0.8-28) yr, 2 patients died 10.7 and 9.9 yr from diagnosis, one from complications of bone marrow transplantation performed after progression of the disease and the other from gastrointestinal bleeding secondary to portal hypertension. Among remaining patients, one developed Budd-Chiari syndrome, another was lost to follow-up at 3 yr, and 5 remain asymptomatic and currently without treatment (one had been splenectomized at diagnosis). These results indicate that in most young adults with MMM the disease presents without adverse prognostic factors and may remain stable for years, which may be of interest when considering the treatment of such patients.

Adolescent↗

Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia.

We administered the anti-angiogenic drug thalidomide to 21 patients (12 men) with myelofibrosis with myeloid metaplasia (MMM), who were not responsive to standard treatment. Patients received thalidomide at an escalating dose from 100 to 400 mg/d. Administration of the drug was discontinued before the planned 6 months of treatment in 19 patients (90.5%), mainly because of somnolence and/or fatigue, neurological symptoms or neutropenia. Of the 13 evaluable patients (who received more than 30 d of therapy), anaemia improved in three out of seven (43%) who were treated because of anaemia; thrombocytopenia improved in two out of three (66.6%) who were treated because of thrombocytopenia; splenomegaly was reduced in four (30.8%). Undesired increases in white blood cell and platelet counts were observed in three (23.1%) and five (38.5%) patients respectively. A severity score, indexed on haematological and clinical parameters, improved in two patients (15.4%), but worsened in five (38.5%). In conclusion, standard-dose thalidomide in MMM patients is burdened with a high rate of side-effects, which prevent prolonged treatment. Because the drug is effective in improving anaemia and thrombocytopenia and in reducing splenomegaly, low-dose therapy warrants evaluation. The unexpected observation of leucocytosis and thrombocytosis suggests biological studies and better criteria for selection of patients for treatment.

Adult↗

Cost-effectiveness of screening and extended anticoagulation for carriers of both factor V Leiden and prothrombin G20210A.

Carriers of a double thrombophilic mutation (factor V Leiden and prothrombin G20210A) are at high risk of a recurrent venous thromboembolism (VTE), and may benefit from a longer course of secondary prophylaxis. We examined the costs and health benefits of screening for both the mutations, provided that double heterozygotes undergo 2 years of anticoagulation as compared to the standard 6 months. We thus pooled the available evidence and calculated that the OR for recurrence in double heterozygotes was 5.9 (95% CI 2.65-13.20). A Markov model tracked patients' health lifelong, and calculated that prolonged prophylaxis saved 26 quality-adjusted days of life and $410 per double heterozygote treated. Screening all the patients with venous thromboembolism thus provided one additional day of life at the cost of 13624 $/QALY (95% CI 12 965-22 889). Screening was not cost-effective in those cohorts with a low prevalence of the mutations, a high bleeding risk or in those where prophylaxis prevented <65% of recurrences. Screening for factor V Leiden and prothrombin G20210A, with prolonged prophylaxis of double carriers, is cost-effective in most patients with VTE.

Aged↗

Deciding when to intervene: a Markov decision process approach.

The aim of this paper is to point out the difference between static and dynamic approaches to choosing the optimal time for intervention. The paper demonstrates that classical approaches, such as decision trees and influence diagrams, hardly cope with dynamic problems: they cannot simulate all the real-world strategies and consequently can only calculate suboptimal solutions. A dynamic formalism based on Markov decision processes (MPPs) is then proposed and applied to a medical problem: the prophylactic surgery in mild hereditary spherocytosis. The paper compares the proposed approach with a static approach on the same medical problem. The policy provided by the dynamic approach achieved significant gain over the static policy by delaying the intervention time in some categories of patients. The calculations are carried out with DT-Planner, a graphical decision aid specifically built for dealing with dynamic decision processes.

Cholecystectomy↗

Cost-effectiveness of epoetin and autologous blood donationin reducing allogeneic blood transfusions incoronary artery bypass graft surgery.

BACKGROUND: Coronary artery bypass graft (CABG) surgery accounts for a substantial portion of all allogeneic units of blood transfused. Drugs and autologous blood donation (ABD) are alternative or adjunctive methods for reducing complications and costs induced by allogeneic blood transfusions. Recombinant human erythropoietin (epoetin) has the potential to decrease perioperative need for allogeneic blood during CABG, but its high cost calls for a careful economic evaluation before it can be recommended for widespread use. STUDY DESIGN AND METHODS: A decision tree was used to compare a hypothetical strategy of no epoetin with one in which epoetin was utilized to control blood transfusion needs in CABG; each strategy was tested with and without ABD. The impact of these strategies on both the quality-adjusted life years (QALYs) and costs ($US) was calculated. RESULTS: Using epoetin alone and with ABD, respectively, avoided the transfusion of 0.61 and 1.35 units of allogeneic blood per patient and saved 0.000086 and 0.000146 QALYs per patient. This made cost-effectiveness (CE) higher than $7 million and $5 million for each QALY saved, respectively. ABD alone cost more than $1 million per QALY saved. If the risk of bacterial infections following allogeneic transfusions was included in the model, epoetin alone cost $6288 per QALY saved, while ABD, both alone and with epoetin, saved money. CONCLUSION: On the basis of the existing evidence, neither of the blood-saving strategies modeled was a cost-effective means of avoiding the deleterious health effects of perioperative blood transfusions in CABG. However, if allogeneic blood-related infections were to be considered, both ABD and epoetin would be acceptable interventions.

Aged↗

Preoperative predictors of the need for allogeneic blood transfusion in lung cancer surgery.

BACKGROUND: The use of blood-saving techniques in elective surgery can produce a favorable cost-benefit ratio only when there is a reasonable likelihood that transfusion will be required. To apply a targeted blood-sparing technique in lung cancer surgery, the patient's preoperative characteristics that predict the use of allogeneic blood transfusion (ABT) in this practice were investigated. STUDY DESIGN AND METHODS: One hundred seventy-three consecutive patients who underwent primary lung cancer surgery were included in this retrospective study. Clinical and epidemiologic variables, lung tumor extension (TNM staging), and surgery type were analyzed by logistic regression to discover the preoperative predictors of ABT. RESULTS: Thirty patients, 17.3 percent of all who underwent surgery and 19.9 percent of those who underwent resolvent surgery, received ABT. Excluding a patient who needed 18 units of RBCs, the number of ABT units required by transfused patients was 1. 93 +/- 0.88 (mean +/- SD). Extensive surgery, patient's age (< or =64 years), and elevated erythrocyte sedimentation rate (>45 mm/hour) were the preoperative variables that influenced the need for ABT. The definitive predictive model was able to recognize 82.3 percent of patients who received ABT and 95.6 percent of those who did not. CONCLUSION: A predictive model can preoperatively identify patients at risk for needing ABT in lung cancer surgery. The model could be utilized to tailor blood-sparing intervention programs.

Adult↗

Extended anticoagulation for prevention of recurrent venous thromboembolism in carriers of factor V Leiden--cost-effectiveness analysis.

There is much debate over the appropriateness of prescribing prolonged anticoagulation to heterozygous carriers of factor V Leiden suffering a first episode of deep vein thrombosis (DVT). We, thus used meta-analysis to estimate from six eligible studies the summary odds-ratio of recurrent DVT in carriers of factor V Leiden versus non-carriers: 1.36 (CI, 1.05-1.78). After that, we used a decision model to compare lifelong costs and benefits of 6 months standard anticoagulation with those of screening for carriers of factor V Leiden and extending for 2 years their anticoagulation. Screening was a cost-effective strategy, since it provided 2 additional quality-adjusted days of life per patient at the cost of $12,833 per quality-adjusted year of life saved, as compared to standard management. However, screening was not cost-effective in patients who were predicted to incur fatal bleeding at a rate higher than 0.34% per year or recurrent DVT at a rate lower than 9% in the first 2 years. The screening policy was cost-saving if restricted to patients with idiopathic DVT and compliant to warfarin therapy.

Anticoagulants↗

A model for analysing the cost of autologous peripheral blood progenitor cell (PBPC) transplantation.

Data from autologous peripheral blood progenitor cell (PBPC) transplant recipients were used for cost analysis and modelling so as to link the main intervention procedures and clinical events to resource use and costs. This cohort consisted of 64 patients from 4 to 62 years old at transplantation (mean, 36.9 years) who underwent a first transplant between August 1994 and May 1997. The main indications for transplantation were non-Hodgkin's lymphomas (47%), multiple myeloma (30%) and Hodgkin's lymphomas (15%). The course of a patient during the whole transplant procedure was modelled using a Markov chain of six states of health: (1) mobilisation and recovery of PBPC; (2) post-mobilisation phase; (3) conditioning and transplant; (4) critical haematological reconstitution; (5) non-critical haematological reconstitution; (6) death. The probability of transition between the different health states, together with the estimated costs, were the input for the Markov model. The model also managed transition probabilities depending both on the current health state and on various demographic, clinical and procedure-related covariates unique to the patient. The expected time spent in each clinical state and the expected total cost were, therefore, estimated. This analysis gave an actual total cost per transplanted patient of $26,600 (95% range: $24,700 to $43,500) while mean duration was 197 days. The expenses for in-hospital stay accounted for 80% of the costs. Both the probability of staying in the different states, and the consequent cost were dependent on the number of CD34-positive cells collected, the phase and the type of the disease, the subset of patients (either children or adults), and the post-transplant G-CSF prophylaxis. The sensitivity of the estimates to alternative assumptions was studied, and the method of comparing alternative future scenarios by the model was explored.

Adolescent↗

The Italian Consensus Conference on Diagnostic Criteria for Myelofibrosis with Myeloid Metaplasia.

The purpose of this work was to develop a definition of myelofibrosis with myeloid metaplasia (MMM) using diagnostic criteria that would remain valid within the set of patients with chronic myeloproliferative disorders or myelodysplastic syndromes. A list of 12 names for the disease and 37 diagnostic criteria were proposed to a Consensus Panel of 12 Italian experts who ranked them in order so as to identify a core set of criteria. The Panel was then asked to score the diagnosis of 46 patient profiles as appropriate or not appropriate for MMM. Using the experts' consensus as the gold standard, the performance of 90 possible definitions of the disease obtained through the core set was evaluated. 'Myelofibrosis with myeloid metaplasia' ranked as the preferred name of the disease. Necessary criteria consisted of 'diffuse bone marrow fibrosis' and 'absence of Philadelphia chromosome or BCR-ABL rearrangement in peripheral blood cells'. The six optional criteria in the core set consisted of: splenomegaly of any grade; anisopoikilocytosis with tear-drop erythrocytes; the presence of circulating immature myeloid cells; the presence of circulating erythroblasts: the presence of clusters of megakaryoblasts and anomalous megakaryocytes in bone marrow sections; myeloid metaplasia. The definition of the disease with the highest final score was as follows: necessary criteria plus any other two criteria when splenomegaly is present or any four when splenomegaly is absent. The use of this definition will help to standardize the conduct and reporting of clinical studies and should help practitioners in clinical practice.

Humans↗

Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines.

PURPOSE: Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder characterized by bone marrow fibrosis and extramedullary hematopoiesis. Recent studies provide definite diagnostic criteria and prognostic classifications of the disease, and allogeneic stem-cell transplantation (SCT) now offers a chance of curing the disease. In order to put diagnostic criteria and prognostic classifications of the disease into the perspective of developing guidelines for treatment strategies, all studies published in the English literature over the last 30 years were reviewed. MATERIALS AND METHODS: Studies were identified through a MEDLINE search (1966 to present) and from the bibliographies of relevant articles. RESULTS: The Italian Consensus Conference on diagnostic criteria is a structured enterprise aimed at formulating a definition of MMM that will be used for enrolling patients onto clinical studies. It relies on the obligatory presence of myelofibrosis and on the exclusion of the BCR-ABL rearrangement or Philadelphia chromosome, in association with combinations of traditional features. Prognostic scores allow us to identify classes of patients on the basis of hemoglobin, age, WBC count, and chromosomal abnormalities. Several nonrandomized studies have indicated that allogeneic SCT for patients under the age of 55 is effective in prolonging survival in more than 50% of cases and in possibly curing the disease. Patients with the most severe prognosis are candidates. CONCLUSION: "Consensus" methodology offers a definition of MMM useful for conducting and reporting clinical studies. A detailed knowledge of prognostic factors can help to delineate guidelines for addressing patients with allogeneic SCT.

Age Factors↗