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Umberto Restelli,1,2 Davide Croce,1,2 Valeria Pacelli,1 Fabio Ciceri,3,4 Corrado Girmenia51Center for Health Economics, Social and Health Care Management, LIUC - Università Cattaneo, Castellanza, VA, Italy; 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3Hematology and BMT Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; 4University Vita-Salute San Raffaele, Milan, Italy; 5Department of Haematology, Oncology and Dermatology, Azienda Policlinico Umberto I, Sapienza University, Rome, ItalyBackground: The aim of the analysis is to assess the efficiency of the allocation of economic resources related to the use of letermovir cytomegalovirus (CMV) prophylaxis in adult seropositive recipients (R+) patients receiving an allogenic hematopoietic stem cell transplantation (HSCT), compared with a no-prophylaxis strategy, assuming preemptive antiviral administration in both groups from the perspective of the Italian National Health Service (NHS), through a cost-effectiveness analysis.Methods: The model used is based on a decision tree which simulates on a lifetime horizon the progression of CMV infection, considering two alternatives: the use of letermovir CMV prophylaxis, followed by preemptive therapy in case of clinically significant CMV infection, or the avoided use of letermovir CMV prophylaxis, considering direct medical costs (referred to 2018) and quality-adjusted life years (QALYs), both discounted considering a 3% annual rate. Two scenarios were considered, representing the differences related to regional contexts and clinical practice of different typologies of hospitals (public or private accredited with Regional Health Services).Results: The use of letermovir prophylaxis compared with no prophylaxis strategy would lead to an increase of QALYs and direct medical costs in the two scenarios considered, with a mean increase of 0.45 QALYs, and an increase of direct medical costs of 10,222.4 € and of 10,809.9 € in the two scenarios. The incremental cost-effectiveness ratios are equal to 22,564 €/QALY and 23,861 €/QALY. The probabilistic sensitivity analysis conducted showed a percentage of results below the threshold of 40,000 €/QALY of 67.4% and 71.3%; and below a threshold of 25,000 €/QALY equal to 50.4% and to 53.0%.Conclusions: The use of letermovir CMV prophylaxis in adult R+ patients receiving allogenic HSCT, compared with a no-prophylaxis strategy, would be cost-effective for the Italian NHS considering the incremental cost-effectiveness thresholds of 40,000 €/QALY and of 25,000 €/QALY.Keywords: cytomegalovirus, letermovir, allogenic hematopoietic stem cell transplantation, cost-effectiveness analysis

Introduction: The use of oral tenofovir/emtricitabine (FTC/TDF) for pre-exposure prophylaxis (PrEP) among high-risk people without Human Immunodeficiency Virus (HIV), is emerging as an innovative strategy to decrease HIV epidemic. The study aims at evaluating the implications related to PrEP introduction, from a multidimensional point of view, as required by Health Technology Assessment (HTA) approach, with a particular attention on sustainability and social factors, influencing PrEP implementation., Methods: An analysis was conducted involving 35 Italian Infectious Disease Departments. The introduction of PrEP (applied both as "add-on" and "substitute" prevention strategy) into the clinical practice was compared with a baseline scenario, consisting of condoms among men who have sex with men, and serodiscordant couples, and the use of Needle Syringe Programme among injection drugs users The above scenarios were analysed by means of a Health Technology Assessment (HTA) approach. The 9 EUnetHTA Core Model domains were assessed through comparative information, retrieved from literature evidence, and collection of qualitative and quantitative information, derived from real-world evidence, in particular from 35 Infectious Disease Departments and potential PrEP' users involved. A final multi-criteria decision analysis approach (MCDA) was implemented to simulate the appraisal phase and providing evidence-based information with regard to the preferable technology., Results: Despite the improvement in patients' quality of life, PrEP would generate the development of other sexually transmitted and blood-borne diseases, with a consequent decrease of patients' safety in case of PrEP applied as a "substitute" prevention strategy. In addition, PrEP would generate an increase in staff workflow, with investment in medical supplies and training courses. PrEP would lead to significant economic investments both for the NHS (+40%), and for citizens (+2,377%) if used as an add-on strategy, assuming FTC/TDF patent cost. With the off-patent drug, the NHS would benefit from an advantage (37%), and a shrink of the patients' expenditure emerged (+682%). More economic resources are required if PrEP is applied as a substitute strategy, considering both the patent (NHS: 212%; citizens: 3,423%) and the off-patent drug (NHS: 73%; citizens: 1,077%). Conclusions. The most cost-containing strategy would be the use of PrEP, as an add-on strategy, with a consequent improvement in patients' safety, even if drug-related adverse events would be considered. The implementation of the off-patent drug would decrease the economic burden of the innovative prevention strategy. Hence, the organizational aspects related to its adoption would be deeply investigated, with the potential opportunity to create specific ambulatories devoted to PrEP users' especially for medium and big size hospitals., (©2020 Pacini Editore SRL, Pisa, Italy.)

Objective: The aim of the analysis is to assess the organisational and economic consequences of adopting an early discharge strategy for the treatment of acute bacterial skin and skin structure infection (ABSSSI) and osteomyelitis within infectious disease departments., Setting: Infectious disease departments in Greece, Italy and Spain., Participants: No patients were involved in the analysis performed., Interventions: An analytic framework was developed to consider two alternative scenarios: standard hospitalisation care or an early discharge strategy for patients hospitalised due to ABSSSI and osteomyelitis, from the perspective of the National Health Services of Greece, Italy and Spain. The variables considered were: the number of annual hospitalisations eligible for early discharge, the antibiotic treatments considered (ie, oral antibiotics and intravenous long-acting antibiotics), diagnosis-related group (DRG) reimbursements, number of days of hospitalisation, incidence and costs of hospital-acquired infections, additional follow-up visits and intravenous administrations. Data were based on published literature and expert opinions., Primary and Secondary Outcome Measures: Number of days of hospitalisation avoided and direct medical costs avoided., Results: The total number of days of hospitalisation avoided on a yearly basis would be between 2216 and 5595 in Greece (-8/-21 hospital beds), between 15 848 and 38 444 in Italy (-57/-135 hospital beds) and between 7529 and 23 520 in Spain (-27/-85 hospital beds). From an economic perspective, the impact of the early discharge scenario is a reduction between €45 036 and €149 552 in Greece, a reduction between €182 132 and €437 990 in Italy and a reduction between €292 284 and €884 035 in Spain., Conclusions: The early discharge strategy presented would have a positive organisational impact on National Health Services, leading to potential savings in beds, and to a reduction of hospital-acquired infections and costs., Competing Interests: Competing interests: UR, MB, DC, VP and AV declares grants from Angelini during the conduct of the study; SG declares personal fees from Angelini during the conduct of the study, and grants form Astellas Pharma and Pfizer. SM and SMG declare personal fees from Angelini during the conduct of the study. GR declares personal fees from Angelini during the conduct of the study, and personal fees from Gilead, MSD and ViiV. MS is employed by Angelini. AG declares grants from Angelini and is partly supported by the NIHR Biomedical Research Centre, Oxford., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of this study was to compare the cytotoxic effects of the fluoroquinolone ofloxacin with that of the aminoglycoside netilmicin. Human corneal epithelial cells (HCE-T) and human conjunctival epithelial cells (Wong-Kilbourne derivative of Chang conjunctiva) were exposed to antibiotics (0.08-5.0 mg/mL) for 4 or 24 hours. Cell proliferation and viability were assessed with the MTT assay, neutral red uptake, and bromo deoxy uridine incorporation. In both cell lines, ofloxacin inhibited cell proliferation and viability. These effects were time and dose dependent. Concentrations of ofloxacin ranging from 0.4 to 2.4 mg/mL (0.04% to 0.24%) produced a 50% inhibition of proliferation and viability. In contrast, netilmicin induced no toxic effect. The differences between ofloxacin and netilmicin were highly statistically significant (p < 0.001). This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is compromised.

Objectives: In the present work, a method to induce experimental allergic encephalomyelitis (EAE) in female SJL/J mice was developed and validated in our laboratory. Although the latter is a popular animal model to mimic human multiple sclerosis, it remains to be clarified if: (1) the measurement of circulating antibodies against myelin antigens can be used as an index to predict the development of clinical EAE, as well as the severity of disease, and (2) the genetic susceptibility of this strain is associated with altered hypothalamo-pituitary-adrenal (HPA) function., Methods and Results: We observed that SJL/J mice display a strong humoral response to immunization with myelin basic protein (MBP), as assessed by the titration of circulating anti-MBP antibodies. However, there was no apparent correlation between the presence and amount of circulating antibodies and the occurrence or severity of disease. Concerning the responsiveness of the HPA axis, we observed that circulating corticosterone levels are not modified at all during the induction of EAE, whereas an increase is observed at a later stage of the disease., Conclusions: The above profile is strongly reminiscent of the HPA axis response to the induction of EAE in Lewis rats, suggesting that the susceptibility of SJL/J mice to EAE may similarly be caused, at least in part, by blunted HPA reactivity to immune challenges., (Copyright 2002 S. Karger AG, Basel)