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Andrea Spini,1 Luca L’Abbate,2 Ylenia Ingrasciotta,1 Giorgia Pellegrini,1 Massimo Carollo,1 Valentina Ientile,2 Olivia Leoni,3 Martina Zanforlini,4 Domenica Ancona,5 Paolo Stella,5 Anna Cavazzana,6 Angela Scapin,6 Sara Lopes,7 Valeria Belleudi,7 Gianluca Trifirò1 1Department of Diagnostics and Public Health, University of Verona, Verona, Italy; 2Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy; 3Lombardy Regional Centre of Pharmacovigilance and Regional Epidemiologic Observatory, Milan, Italy; 4Azienda Regionale per l’Innovazione e gli Acquisti, S.p.A, Milan, Italy; 5Apulian Regional Health Department, Bari, Italy; 6Azienda Zero, Regione Veneto, Italy; 7Department of Epidemiology, Lazio Regional Health Service, Rome, ItalyCorrespondence: Gianluca Trifirò, Department of Diagnostics and Public Health, University of Verona, P. le L.A. Scuro 10, Verona, 37134, Italy, Tel +39 045 802 7679, Email gianluca.trifiro@univr.itPurpose: This research aimed to develop and validate a META-algorithm combining individual immune-mediated inflammatory disease (IMID)-specific algorithms to identify the exact IMID indications for incident biological drug users from claims data within the context of the Italian VALORE project.Methods and Patients: All subjects with at least one dispensing of TNF-alpha inhibitors, anti-interleukin agents, and selective immunosuppressants approved for IMIDs were identified from claims databases of Latium region in Italy (observation period: 2010– 2020). Validated coding algorithms for identifying individual IMIDs from claims databases were found from published literature and combined into a META-algorithm. Positive predictive value (PPV), sensitivity (Se), negative predictive value (NPV), specificity (Sp), and accuracy (Acc) were estimated for each indication against the electronic therapeutic plans (ETPs) of the Latium region as the reference standard. Lastly, the frequency of the indication of use across individual biologic drugs was compared with that reported in three other Italian regions (Lombardy, Apulia, and the Veneto region).Results: In total, 9755 incident biological drug users with a single IMID indication were identified. Using the newly developed META-algorithm, an indication of use was detected in 95% (n=9255) of the total cohort. The estimated Acc, Se, Sp, PPV, and NPV, against the reference standard were as follows: 0.96, 0.86, 0.97, 0.82, and 0.98 for Crohn’s disease, 0.96, 0.80, 0.98, 0.85, and 0.97 for ulcerative colitis, 0.93, 0.76, 0.99, 0.95, and 0.92 for rheumatoid arthritis, 0.97, 0.75, 0.99, 0.85, and 0.98 for spondylarthritis, and 0.91, 0.92, 0.91, 0.88, and 0.94 for psoriatic arthritis/psoriasis, respectively. Additionally, no substantial difference was observed in the frequency of indication of use by active ingredient among Latium and the other three Italian regions included in the study.Conclusion: The newly developed META-algorithm demonstrated high validity estimates in the Italian claims data and was capable of discriminating with good performance among the most frequent IMID indications.Plain Language Summary: In the claims database, the lack of information on the indication of use represents a well-known limitation for the conduct of observational studies. This study was conducted to develop and validate a META-algorithm that accurately identifies the exact indication for the use of biological drugs in treating various immune-mediated inflammatory diseases. Using claims databases from the Latium region, we developed and validated a META-algorithm. The META-algorithm combines disease-specific algorithms for different immune-mediated inflammatory diseases (ie, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, spondyloarthritis, psoriasis, and psoriatic arthritis) and was tested against a reference standard (electronic therapeutic plans of the Lazio region). The META-algorithm reported high validity estimates and was able to distinguish with a good performance among the most frequent IMIDs as indications for use. Applying this META-algorithm may facilitate post-marketing surveillance of biological drugs such as TNF-alpha inhibitors, anti-interleukin, and selective immunosuppressants in specific therapeutic areas in an Italian setting.Keywords: immune-mediated inflammatory diseases, biological drugs, validation, claims data, META-algorithm, indication for use

Marco Finocchietti,1,* Maria Lucia Marino,1,* Alessandro C Rosa,1 Arianna Bellini,1 Lucia Masiero,2 Massimo Cardillo,2 Marco Massari,3 Stefania Spila Alegiani,3 Silvia Pierobon,4 Eliana Ferroni,4 Martina Zanforlini,5 Olivia Leoni,6 Stefano Ledda,7 Donatella Garau,7 Marina Davoli,1 Antonio Addis,1 Valeria Belleudi1 On behalf of CESIT Study Group1Department of Epidemiology, Lazio Regional Health Service-ASL Roma 1, Rome, Italy; 2Italian National Transplant Center, Istituto Superiore di Sanità, Rome, Italy; 3National Center for Drug Research and Evaluation, Istituto Superiore Di Sanità, Rome, Italy; 4Azienda Zero, Veneto Region, Padua, Italy; 5The innovation and procurement regional company, A.R.I.A. S.p.A.-Lombardy Region, Milan, Italy; 6Regional Epidemiological Observatory, Lombardy Region, Milan, Italy; 7General Directorate for Health, Sardinia Region, Cagliari, Italy*These authors contributed equally to this workCorrespondence: Valeria Belleudi, Department of Epidemiology, ASL Roma 1, Lazio Region, Via Cristoforo Colombo, 112, Roma, 00147, Italy, Tel +39.06.99722133, Fax +39.06.99722111, Email v.belleudi@deplazio.itPurpose: This study evaluates the use, benefit-risk profile, and economic impact of generic immunosuppressants (tacrolimus-TAC, cyclosporine-CsA, and mycophenolate-MYC) in kidney and liver transplant recipients compared to brand-name drugs.Patients and Methods: A retrospective multicentre observational study, involving four Italian regions, was conducted based on the national transplant Information system and regional healthcare claims data. The analysis focused on incident patients who received kidney and liver transplants between 2013 and 2019 and evaluated the use of generic of CsA, TAC, and MYC during the 30-day period following discharge. For each type of transplant and immunosuppressive agent, the benefit-risk profile of generic vs branded drugs in a two-year window was estimated by multivariate Cox models (HR; 95% CI). Furthermore, the potential cost savings per person associated with one year of treatment using generics were calculated.Results: The utilization of generic drugs showed a significant increase; over the study years, the proportion of users among kidney recipients ranged from 14.2% to 40.5% for TAC, from 36.9% to 56.7% for MYC, and from 18.2% to 94.7% for CsA. A great variability in generic uptake for region was found. A comparable risk-benefit profile between generic and branded formulations was shown for all immunosuppressors considered. Choosing generic immunosuppressants during maintenance could result in yearly savings of around 2000 euros per person for each therapy ingredient.Conclusion: The study shows an increasing proportion of patients using generic immunosuppressive drugs over time suggesting a growing acceptance of generics within the transplant community and reveals comparable risk-benefit profiles between the generic and branded formulations of TAC, CsA, and MYC. A significant variability in the use of generics immunosuppressive agents was found both at the regional level and among transplant centers and future research should delve into regional prescribing variations.Keywords: transplant, maintenance therapy, tacrolimus, cyclosporine, mycophenolate, uptake generics, risk-benefit profile, sustainability

Andrea Spini,1 Luca L’Abbate,2 Ylenia Ingrasciotta,1 Giorgia Pellegrini,1 Massimo Carollo,1 Valentina Ientile,2 Olivia Leoni,3 Martina Zanforlini,4 Domenica Ancona,5 Paolo Stella,5 Anna Cavazzana,6 Angela Scapin,6 Sara Lopes,7 Valeria Belleudi,7 Gianluca Trifirò1 1Department of Diagnostics and Public Health, University of Verona, Verona, Italy; 2Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy; 3Lombardy Regional Centre of Pharmacovigilance and Regional Epidemiologic Observatory, Milan, Italy; 4Azienda Regionale per l’Innovazione e gli Acquisti, S.p.A, Milan, Italy; 5Apulian Regional Health Department, Bari, Italy; 6Azienda Zero, Regione Veneto, Italy; 7Department of Epidemiology, Lazio Regional Health Service, Rome, ItalyCorrespondence: Gianluca Trifirò, Department of Diagnostics and Public Health, University of Verona, P. le L.A. Scuro 10, Verona, 37134, Italy, Tel +39 045 802 7679, Email gianluca.trifiro@univr.it

Abstract Background The inverse association between socioeconomic position (SEP) and health has been extensively explored in Italy; however few studies have been carried out on the relationship between income inequalities and health status or health services utilisation, particularly at a local level. The objective of this study is to test the association between the demand for hospital care and a small area indicator based on income in four Italian cities, over a four-year period (1997-2000), in the adult population. Methods Census Block (median 260 residents) Median per capita Income (CBMI) was computed through record linkage between 1998 national tax and local population registries in the cities of Rome, Turin, Milan and Bologna (total population approximately 5.5 million). CBMI was linked to acute hospital discharges among residents, based on patient's residence. Age-standardized gender-specific hospitalisation rates were computed by CBMI quintiles (first quintile indicating lowest income), overall, and by city and year. Heterogeneity of the association between income level and hospitalisation was analysed through a Poisson model. Results We found an inverse association between small area income level and hospitalisation rates, which decreased continuously from 153 per 1000 inhabitants in the first quintile to 107 per 1000 inhabitants in the fifth quintile. Income differences in hospitalisation were confirmed in each city and year. However, the magnitude of the association and the absolute level of hospitalisation rates were quite different in each city and tended to slightly decrease over time in all cities considered, except Bologna. Conclusion Our study confirms an inverse association between income level and the use of hospitalization in four Italian cities, using a small area economic indicator, based on population tax data. Further analysis of the association between income and cause-specific hospitalization rates will allow to better understand the capability of the Italian National Health System to compel with socio-economic inequalities in health needs. Furthermore the SEP indicator we propose can represent a contribution to the improvement of tools for monitoring inequalities in health and in health services utilization.

Abstract Background Data from scientific literature show that about 63% of abstracts presented at biomedical conferences will be published in full. Some studies have indicated that full publication is associated with the direction of results (publication bias). No study has looked into the occurrence of publication bias in the field of addiction. Objectives To investigate whether the significance or direction of results of abstracts presented at the major international scientific conference on addiction is associated with full publication Methods The conference proceedings of the US Annual Meeting of the College on Problems of Drug Dependence (CPDD), were handsearched for abstracts of randomized controlled trials and controlled clinical trials that evaluated interventions for prevention, rehabilitation and treatment of drug addiction in humans (years searched 1993–2002). Data regarding the study designs and outcomes reported were extracted. Subsequent publication in peer reviewed journals was searched in MEDLINE and EMBASE databases, as of March 2006. Results Out of 5919 abstracts presented, 581 met the inclusion criteria; 359 (62%) conference abstracts had been published in a broad variety of peer reviewed journals (average time of publication 2.6 years, SD +/- 1.78). The proportion of published studies was almost the same for randomized controlled trials (62.4%) and controlled clinical trials (59.5%) while studies that reported positive results were significantly more likely to be published (74.5%) than those that did not report statistical results (60.9%.), negative or null results (47.1%) and no results (38.6%), Abstracts reporting positive results had a significantly higher probability of being published in full, while abstracts reporting null or negative results were half as likely to be published compared with positive ones (HR = 0.48; 95%CI 0.30–0.74) Conclusion Clinical trials were the minority of abstracts presented at the CPDD; we found evidence of possible publication bias in the field of addiction, with negative or null results having half the likelihood of being published than positive ones.

Abstract Background Socioeconomic status could affect the demand for hospital care. The aim of the present study was to assess the role of age, socioeconomic status and comorbidity on acute hospital admissions among elderly. Methods We retrospectively examined the discharge abstracts data of acute care hospital admissions of residents in Rome aged 75 or more years in the period 1997–2000. We used the Hospital Information System of Rome, the Tax Register, and the Population Register of Rome for socio-economic data. The rate of hospitalization, modified Charlson's index of comorbidity, and level of income in the census tract of residence were obtained. Rate ratios and 95% confidence limits were computed to assess the relationship between income deciles and rate of hospitalization. Cross-tabulation was used to explore the distribution of the index of comorbidity by deciles of income. Analyses were repeated for patients grouped according to selected diseases. Results Age was associated with a marginal increase in the rate of hospitalization. However, the hospitalization rate was inversely related to income in both sexes. Higher income was associated with lower comorbidity. The same associations were observed in patients admitted with a principal diagnosis of chronic condition (diabetes mellitus, heart failure, chron obstructive pulmonary disease) or stroke, but not hip fracture. Conclusion Lower social status and associated comorbidity, more than age per se, are associated with a higher rate of hospitalization in very old patients.

Objectives: To investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk-benefit profiles in clinical practice., Design: Retrospective multicentrer cohort study., Setting: Four Italian regions (Lombardy, Veneto, Lazio, Sardinia)., Methods: Data were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI)., Main Outcome Measures: Mortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use., Results: The study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk-benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65)., Conclusions: The study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)