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Introduction: The supplementation of alanyl-glutamine dipeptide in critically ill patients necessitating total parenteral nutrition (TPN) improves clinical outcomes, reducing mortality, infection rate, and shortening intensive care unit (ICU) hospital lengths of stay (LOSs), as compared to standard TPN regimens.Methods: A Discrete Event Simulation model that incorporates outcomes rates from 200 Italian ICUs for over 60,000 patients, alanyl-glutamine dipeptide efficacy data synthesized by means of a Bayesian random effects meta-analysis, and national cost data has been developed to evaluate the alternatives from the cost perspective of the hospital. Simulated clinical outcomes are death and infection rates in ICU, death rate in general ward, and hospital LOSs. Sensitivity analyses are performed by varying all uncertain parameter values in a plausible range.Results: The internal validation process confirmed the accuracy of the model in replicating observed clinical data. Alanyl-glutamine dipeptide on average results more effective and less costly than standard TPN: reduced mortality rate (24.6% ± 1.6% vs. 34.5% ± 2.1%), infection rate (13.8% ± 2.9% vs. 18.8% ± 3.9%), and hospital LOS (24.9 ± 0.3 vs. 26.0 ± 0.3 days) come at a lower total cost per patient (23,409 ± 3,345 vs. 24,161 ± 3,523 Euro).Treatment cost is completely offset by savings on ICU and antibiotic costs. Sensitivity analyses confirmed the robustness of these results.Conclusions: Alanyl-glutamine dipeptide is expected to improve clinical outcomes and to do so with a concurrent saving for the Italian hospital.

Background: Chronic Obstructive Pulmonary Disease (COPD) affects about 4.5% of the Italian population, representing one of most burdensome public health problems. Literature data report an annual health care expenditure ranging between € 1,300 and € 4,500 per patient, of which drug costs are a limited share. In 1998 the WHO started GOLD program in order to ameliorate COPD patient management. As a part of his program, periodically updated guidelines are produced with the aim of defining an efficient diagnostic-therapeutic pathway managed by a multidisciplinary team and based on the optimization of the use of drugs and diagnostic tests and the reduction of exposure to risk factors.Objective: to estimate the economic consequences of GOLD guidelines adoption in the Italian clinical practice.Methods: a decision analytic model capable of calculating the impact on the National Health Service budget of an ameliorated adherence to GOLD guidelines (GOLD GL strategy), basing on the needed variations in health care strategies on a defined patient cohort treated with the current approach (CURRENT strategy). The simulation runs on a cohort representing Italian COPD patients over 45 years who transit through 5 Markov health states (4 GOLD stages and death), according to patient characteristics (age, gender, FEV1), with a time horizon of 3 years. Stage-specific drug consumption of the CURRENT strategy is based on data of 3,113 patients collected by three Health Local Units involved in a larger clinical audit project. The consumption of other health resources, i.e. medical visits and inpatient care, is estimated based on a multicentre observational Italian study. The GOLD GL strategy includes spirometry-based staging on the totality of the simulated patients, the development of a therapeutic strategy including the redefinition of pharmacological therapy based on guideline recommendations and experts opinion, and variation of other health resources consumption based on observational data. Costs of health care resources are calculated based on published micro-costing analysis and current prices and tariffs.Results: the model estimates an adjunctive cost of about 19 million of Euros with the GOLD GL strategy, just for the the spirometry-based restaging of about 40% of the over 1 million and 250 thousand prevalent Italian COPD patients. Furthermore, in the first year of the analysis, the redefinition of the best clinical management strategy for all patients would cost about 100 million Euros, which are to be added to the more than 320 million Euros associated with adaptation of the GOLD stage specific pharmacological therapy, consisting mainly in a higher usage of long-acting beta agonist/corticosteroid combinations, only partially offset by the lower prescription of corticosteroid alone. Based on Italian observational data, the consumption of other health care resources with the GOLD GL strategy is reduced by about 44%, reflected in an estimated cost saving of more than 850 millions of Euros. For the first analysis year, the net cost saving associated with full GOLD guideline adoption is estimated equal to 410 millions of Euros; this value decreases by 11% and 21% respectively in the second and third years.Conclusion: our model estimates that the adoption of GOLD guidelines in the Italian clinical practice is associated to an average cost saving of about 300 Euros per patient/year.

The XENDOS study showed that behavioural and pharmacological therapy can decrease the risk of metabolic disorders in obese patients.A probabilistic Bayesian Markov model simulating the outcomes of orlistat treatment on the obese Italian population has been developed with the WinBUGS software. The model integrates an algorithm to estimate cardiovascular risk based on Framingham Heart Study equations. Analyses adopted the societal cost perspective, including direct medical costs borne by both the National Health Service and the patient, since orlistat is not included in the Italian reimbursement list.The simulation on the Italian obese population estimated an average increase in quality-adjusted life expectancy, a reduction of cardiovascular events and new diabetes cases. The average incremental cost-utility ratio is euro75.3 (7.6-180.6) x 1000/QALY. The subgroup analysis showed that the benefits are relatively greater in older patients and in patients with impaired glucose tolerance (IGT). Two hypotheses have been explored to estimate the impact of a potential reimbursement decision by the Italian NHS: (1) orlistat is given to every obese patient; (2) orlistat is given only to obese IGT patients with a previous glucose tolerance general screening program to assess their eligibility. The cost utility of the strategies are euro42.3 (-22.16-108.7) and euro10.16 (-60.4-38.76) x 1000/QALY, respectively.Orlistat shows a good pharmacoeconomic profile and, in particular, the strategy of a screening programme to identify and treat the IGT subgroup has a cost-utility value of about euro10000/QALY. This value is lower than that of several therapeutic strategies commonly accepted and reimbursed in developed countries.

Roberto W Dal Negro,1,2 Luca Bonadiman,1 Paola Turco,2 Silvia Tognella,3 Sergio Iannazzo41National Center for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy; 2Research and Clinical Governance, Verona, Italy; 3General Hospital, ULSS 22 Regione Veneto, Bussolengo, Italy; 4SIHS Health Economics Consulting, Torino, ItalyBackground: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide, and its epidemiological, clinical, and socioeconomic impact is progressively increasing. A first estimate of the economic burden of COPD in Italy was conducted in 2008 (the SIRIO [Social Impact of Respiratory Integrated Outcomes] study). The aim of the present study is to provide an updated picture of the COPD economic burden in Italy.Methods: Sequential patients presenting at the specialist center for the first time during the period 2008–2012 and with record file complete (demographic, clinical, lung function, and therapeutic data; health care resources consumed in the 12 months before the enrollment and for the 3 subsequent years) were selected from the institutional database.Results: Two hundred and seventy-five COPD patients fitting the inclusion criteria were selected (226 males; mean age: 70.9 years [standard deviation: ±8.4 years]; 45.8% were from the north, 25.1% from central Italy, and 29.1% from south Italy). COPD-related average costs per patient in the 12 months before enrollment were as follows: hospitalization: €1,970; outpatient care: €463; pharmaceutical: €499; and indirect costs: €358. Average direct costs and total societal costs were €2,932 and €3,291, respectively. Direct cost was €2,461 (hospitalization: €1,570; outpatient: €344; and pharmaceutical: €547) in the first year of follow-up, while total societal cost was €2,707. No significant difference was reported in any cost category between sexes.Conclusion: The therapeutic approach followed in a specialist center, based on the application of clinical guidelines, has been shown to be a highly effective investment for the long-term management of COPD. A small increase of pharmaceutical costs per year allowed a substantial saving in terms of hospitalizations, costs related to outpatient services, and indirect costs.Keywords: COPD, health costs, pharmacoeconomic, sex dependency

Cardiovascular disease (CVD) remains one of the leading causes of mortality and morbidity worldwide. Since several pharmacological approaches are available for the reduction of incidence and severity of cardiovascular events and health resources in modern managed care systems are limited, the evaluation of the clinical and economical consequences of any treatment is very valuable for decison-makers and physicians. In this article we present a flexible pharmacoeconomic model that permits the calculation of the marginal costeffectiveness of cardiovascular prevention with ramipril, a drug of the class of ACE-inhibitors. The clinical data used for the modelization are derived from the HOPE (Heart Outcomes Prevention Evaluation) study, a landmark cardiovascular prevention study that showed how the benefits of ACE-inhibition with ramipril go beyond the effects on blood pressure, while Italian epidemiological, demographic and economical data make the results appliable to the Italian population. The model, structured as a decision tree comparing the alternatives “to treat” or “not to treat” with Markow chains at the terminal nodes, calculates the marginal cost-effectiveness of the preventive treatment in terms of cost/year of live saved. The model is characterized by high flexibility, as it allows health decision-makers to set epidemiological and economical data in order to reflect the local population at high risk for developing cardiovascular diseas. The model was tested on a high risk population, formed by all acute myocardial infarction survivors in Italy, and indicated that life-long treatment of this patients would yield significant clinical benefits, with a cost/ effectiveness of 3,932 euro/year of life saved. This value is well below the standards that are considered acceptable, and offsprings from the partial offset of pharmaceutical costs caused by the reduction in the expenses for diagnosis and treatment of the cardiovascular events avoided with the preventive therapy.

An area-under-the-curve Markov model was designed to evaluate the cost-effectiveness of ponatinib as a third line treatment of Chronic Myeloid Leukemia-Chronic Phase (CML-CP) with reference to Italy. As for current guidelines, comparators were dasatinib, nilotinib, bosutinib, allogeneic stem cell transplantation (SCT), hydroxyurea. The economic perspective was the Italian National Health Service's (NHS), where costs for treatment drugs, monitoring and follow-up, adverse events, SCT procedure were considered on a lifetime span. Costs (mainly based on current tariffs in Italy) and benefits (QALYs) were discounted at a 3.5% annual rate. Ponatinib resulted dominant versus SCT. The lowest ICER was €13,090 (ponatinib vs hydroxyurea); the highest was €22,529 (ponatinib vs dasatinib). Sensitivity analysis – both deterministic (one way) and probabilistic – was focused on the comparison between ponatinib and dasatinib. The deterministic analysis showed that the most critical parameter in the model was ponatinib pri...

The affiliation listed for author Sergio Iannazzo for the article “Economic Evaluation of Intravenous Iodinated Contrast Media in Italy” was incorrect. The study and writeup were completed while Sergio Iannazzo was an IMS Health employee, and the author's correct affiliation for this paper is “IMS Health Italy.” The publisher regrets the error.

• Conclusions To assess the economic and clinical impact of the use of peginterferon α-2a (40KD) versus LAM for the treatment of HBeAg-negative CHB and versus IFN for the treatment of HBeAg-positive CHB disease in Italy. • Objective Chronic Hepatitis B (CHB) is caused by chronic infection with Hepatitis B Virus (HBV) and represents a major global health problem. Traditional CHB treatments are lamivudine (LAM) and interferon α-2a (IFN). Peginterferon α-2a (PEG) has been recently approved for the treatment of CHB disease.

s / Digestive and Liver Disease 45 (2013) e367–e371 e369 accumulation was evaluated by AdipoRed assay, apoptosis by the Caspase-3 activity and annexin V/FITC-PI assays. Reactive oxygen species (ROS) was measured using Dihydrorhodamine123. mRNA and protein expression of p53 and lipid metabolism-related genes were evaluated by qRT-PCR and Western blotting, respectively. Transfection of the wt-p53 in Huh7.5.1 was done using Lipofectamine 2000. Results: FFAs treatment was not cytotoxic and enhanced intracellular lipid content, with a statistically significant difference between HepG2 and Huh7.5.1. FFAs overload induced a similar down-regulation of the de novo lipid synthesis genes in both cell lines. Conversely, FFAs modulated the fatty acid b-oxidation pathway (FAO) in an opposite way between HepG2 and Huh7.5.1. Following the FFAs treatment, p53 and its active forms were up-regulated in HepG2 and down-regulated in Huh7.5.1 cells. Transfection of wt-p53 in Huh7.5.1 cells reverts the different lipid metabolism behavior observed in these cells. Apoptosis and ROS were higher in HepG2 respect to Huh7.5.1 cells. Conclusions: We highlight the important role of the p53domain containing residue 220 in regulating FAO pathway. These results prompt us to consider the Y220C mutation paradoxically protective against steatosis and maybe against its progression. These findings may in part explain the occurrence of neoplastic nodules in steatotic patients who never develop cirrhosis, suggesting theopportunity of sequencingp53 topredict liver transformation in the presence of hepatic steatosis. http://dx.doi.org/10.1016/j.dld.2013.09.010 BUDGET IMPACT ANALYSIS OF A PERSONALIZED HBEAG NEGATIVE CHB ANTIVIRAL THERAPY MODEL S. Iannazzo1,∗, M. De Francesco1, B. Coco2, M.R. Brunetto2, R. Tomic3, D. Paolini3, G. Palmieri3, F. Bonino4 1 IMS RWE Solutions and HEOR, Milan, Italy 2 Hepatology-Unit, University Hospital (AOUP), Pisa, Italy 3 Roche S.p.A. Monza, Italy 4 General Medicine II Digestive and Liver Disease Unit, University Hospital (AOUP), Pisa, Italy Introduction: A finite 48-weeks course of peg-interferon (PEG) can induce off-therapy immune control of chronic hepatitis B (CHB) leading to HBsAg clearance/anti-HBs seroconversion. The alternative option is direct inhibition of viral replication by continuous administration of nucleosides analogues (NUCs) which generally yields higher success rates, but at the price of a life-long treatment. Exploiting the early identification of PEG-non-responders by combined HBV-DNA and HBsAg quantification at week-12 (stopping-rule), a new sequential therapeutic strategy may benefit both patients and payers. Aim: Pharmacoeconomic analysis may help assessing the economic impact of therapeutic alternatives through the development of simulation models. We evaluated the impact of the adoption of PEG-week-12-stopping-rule in the treatment of HBeAg-negative CHB in Italy with this pharmacoeconomic technique. Methods and results: A Markov model was developed over a 5 year horizon to simulate the course of CHB through virologic response, relapse, HBsAg clearance, compensated and decompensated cirrhosis, hepatocarcinoma, liver transplant, post-liver transplant and death. Transition probabilities between states were derived from the literature. The current mix of treatment with NUCs (entecavir, tenofovir, adefovir, lamivudine and telbivudine) and PEG (with no stopping rule) was compared with a mix based on a hypothetical uptake of PEG (with the stopping rule). The percentage of uptake from NUCs started at 25%, increasing over time. The estimated budget impact resulted in a saving of approximately D 74 million, 95% of which accounted for drug cost. The beneficial impact of the stopping-rule became clear from the second year, when a break-even point was reached. Conclusion: The estimated savings in drug costs following the uptake of PEG+ stopping-rule in the treatment of CHB HBeAg negative patients demonstrate a potentially advantageous profile of such a strategy that could allow for more efficient use of health care resources. http://dx.doi.org/10.1016/j.dld.2013.09.011 IDENTIFICATION AND CONSUMPTION OF HEPATOPATHIC PATIENTS IN TUSCANY REGION: LIMITS AND OPPORTUNITIES OF ADMINISTRATIVE DATA M. Vainieri1,∗, B. Bini1, B. Coco2, F. Oliveri2, M.R. Brunetto2, F. Bonino3, S. Nuti1 1 Institute of Management – Laboratorio Management e Sanita, Scuola Superiore Sant’Anna of Pisa, Pisa, Italy 2 Hepatology Unit, University Hospital of Pisa, Pisa, Italy 3 General Medicine Unit 2, Department of Internal Medicine, University Hospital of Pisa, Pisa, Italy Introduction: Most studies concerning prevalence or cost effectiveness are based on the enrolment of patients or people throughout health centers and clinical data. However local, regional and central government have access to a wide number of information using administrative data. What are the limits and opportunities of administrative data? Aim: The objectives of the study were to identify hepatopatic patient and its consumption using administrative data. Methods: This study identified and analysed the hepatopathic patient consumptions throughout the linkage of hospitalization, exemption, outpatient and pharmaceutical records of the Tuscany Region in 2010. The analysis can be divided into two steps: 1. The selection criteria to identify hepatopatic patients throughout hospitalization, outpatient, pharmaceutical and exemption administrative datasets (identification of the key tracing information from each dataset). 2. The analysis of consumption in terms of tariffs was carried out for the four groups: asymptomatic hepatopathy; symptomatic cirrhosis; hepatocellular carcinoma; transplant. Results: With the above selection criteria we identified around 1.37% of the Tuscan population over 14 years old who executed at least one tracing exam or treatment or got the exemption for hepatopatic diseases. The 85% of epatopatic identified belongs to the first group, asymptomatic hepatopathy, which includes viral and non viral ephatitis and colangio hepatopathy. The analysis of the overall healthcare expenditure for the hepatopathy patients, including also expenses for illness not directly connected with hepatopathy, highlighted that the median healthcare expenditure for the four groups is the following: D 1888 for asymptomatic hepatopathy; D 6591 for symptomatic cirrhosis; D 8221 hepatocellular carcinoma; and D 9812 for transplant. Conclusions: There are a number of limits in the usage of the administrative data, however local and regional managersmay use e370 Abstracts / Digestive and Liver Disease 45 (2013) e367–e371 administrative data to activate learning processes that can help a better planning of resources and evaluation purposes based on benchmarking. Indeed administrative data allow to monitor and compare performance across providers over timewith small effort. http://dx.doi.org/10.1016/j.dld.2013.09.012 IDENTIFICATION OF RESPONDERS TO SORAFENIB IN HEPATOCELLULAR CARCINOMA: IS TUMOUR VOLUME MEASUREMENT THE WAY FORWARD? R. Sacco1,∗, I. Bargellini2, A. Scionti2, V. Mismas1, G. Masi3, C. Vivaldi3, C. Caparello3, R. Fiorile1, F. Letterio1, G. Bresci1, C. Bartolozzi1 1 Department of Gastroenterology, Pisa University Hospital, Pisa, Italy 2 Department of Radiology, Pisa University Hospital, Pisa, Italy 3 Department of Oncology, Pisa University Hospital

Objectives Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs. Methods A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists. Results Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin ). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained. Conclusions Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

**Background:** Patients developing acute kidney injury (AKI) during critical illness or major surgery are at risk for renal sequelae such as costly and invasive acute renal replacement therapy (RRT) and chronic dialysis (CD). Rates of renal injury may be reduced with use of chloride-restrictive intravenous (IV) resuscitation fluids instead of chloride-liberal fluids. **Objectives:** To compare the cost-effectiveness of chloride-restrictive versus chloride-liberal crystalloid fluids used during fluid resuscitation or for the maintenance of hydration among patients hospitalized in the US for critical illnesses or major surgery. **Methods:** Clinical outcomes and costs for a simulated patient cohort (starting age 60 years) receiving either chloride-restrictive or chloride-liberal crystalloids were estimated using a decision tree for the first 90-day period after IV fluid initiation followed by a Markov model over the remainder of the cohort lifespan. Outcomes modeled in the decision tree were AKI development, recovery from AKI, progression to acute RRT, progression to CD, and death. Health states included in the Markov model were dialysis free without prior AKI, dialysis-free following AKI, CD, and death. Estimates of clinical parameters were taken from a recent meta-analysis, other published studies, and the US Renal Data System. Direct healthcare costs (in 2015 USD) were included for IV fluids, RRT, and CD. US-normalized health-state utilities were used to calculate quality-adjusted life years (QALYs). **Results:** In the cohort of 100 patients, AKI was predicted to develop in the first 90 days in 36 patients receiving chloride-liberal crystalloids versus 22 receiving chloride-restrictive crystalloids. Higher costs of chloride-restrictive crystalloids were offset by savings from avoided renal adverse events. Chloride-liberal crystalloids were dominant over chloride-restrictive crystalloids, gaining 93.5 life-years and 81.4 QALYs while saving $298 576 over the cohort lifespan. One-way sensitivity analyses indicated results were most sensitive to the relative risk for AKI development and relatively insensitive to fluid cost. In probabilistic sensitivity analyses with 1000 iterations, chloride-restrictive crystalloids were dominant in 94.7% of iterations, with incremental cost-effectiveness ratios below $50 000/QALY in 99.6%. **Conclusions:** This analysis predicts improved patient survival and fewer renal complications with chloriderestrictive IV fluids, yielding net savings versus chloride-liberal fluids. Results require confirmation in adequately powered head-to-head randomized trials.