Search

Elisa Giacomini, Valentina Perrone, Davide Alessandrini, Daniela Paoli, Carmela Nappi, Luca Degli Esposti CliCon S.r.l. Health, Economics & Outcomes Research, Ravenna, ItalyCorrespondence: Valentina PerroneClicon S.r.l, Health, Economics and Outcomes Research, Via Salara, 36, Ravenna, 48100, ItalyTel +39 544 38393Fax +39 544 212699Email valentina.perrone@clicon.itAbstract: The 20th century witnessed the dawn of the antibiotic revolution and is now facing the rising phenomenon of antibiotic resistance. In this narrative review, we aim to describe antibiotic resistance in clinical practice settings through population-based studies from different countries reporting the role of misuse of antibiotics in the development of resistance and the clinical and economic burden associated. The misuse of antibiotics was documented in the wide population as well as in hospitals and care facilities. It was mainly reported as over-use and inappropriate prescribing. Improper dosage regimens and longer treatment duration were regarded as pivotal factors related to antibiotic resistance; the emerging strategy of “antibiotic-de-escalation” could be the key to overcome these issues. The investigation of the self-medication attitude revealed widespread antibiotic use without following medical instructions or medical consultation. Moreover, several studies established the association of antibiotic resistance with increased risk of longer hospitalizations and mortality, highlighting the heavy clinical and economic burden of this phenomenon. In this narrative review, the widespread inappropriate use of antibiotics emerged as one of the main causes of antibiotic resistance, which negative outcomes call for the development of antibiotic stewardship programs and global surveillance networks.Keywords: antibiotic utilization, antimicrobial resistance, real-world

Luca Degli Esposti,1 Stefano Buda,1 Carmela Nappi,1 Daniela Paoli,2 Valentina Perrone1 On behalf of Network Health-DB1CliCon S.r.l. – Health, Economics & Outcome Research, Ravenna, Italy; 2Health-DB, Ravenna, ItalyCorrespondence: Luca Degli EspostiCliCon S.r.l., Health, Economics & Outcomes Research, Via Salara, 36, Ravenna 48100, ItalyTel +39 (0)544 38393Fax +39 (0)544 212699Email luca.degliesposti@clicon.itAbstract: Poor medication adherence leads to worsening of clinical outcomes and increases healthcare costs, especially in the context of chronic conditions. The effects of new COVID-19 infection and the measures taken in response to the outbreak are further increasing the concerns about medication adherence. Patients with chronic diseases, many of whom are older adults, have been strongly recommended to stay at home and avoid social contacts even with family members, who often provide support for regular use of therapies. Moreover, the mobilization of health personnel to the frontline of the COVID-19 infection could limit access to healthcare services. Within the Health-DB project, the Fail-To-Refill monitoring system was designed to evaluate the lack of adherence to chronic therapies in Italian clinical practice settings. Considering the date and dose coverage of last prescription, all patients due to refill this prescription for a chronic therapy in the last month were identified, and it was verified if they had the refill. The proposed future analysis, based on the data linkage between the current administrative flows of the Italian Local Health Units involved, will be carried out on a monthly basis from the beginning of the infection, and the “post-Covid-19” results will be compared with “pre-COVID-19” results, calculated for the last three years for patients with chronic therapies. Preliminary data herein presented showed a trend of increased failed refill during the months of lockdown for lipid-lowering and biologic therapies. The pre-COVID-19 trend compared to that of post-COVID-19 in the next months will be useful to estimate the percentage of failure to refill truly related to COVID-19 and on the measures adopted. The identification of patients that do not refill their prescriptions allows healthcare professionals to put in place actions aimed to promptly correct the lack of adherence, thus reducing the associated negative outcomes.Keywords: chronic disease, real-world data, SARS-CoV-2, treatment adherence

Diego Sangiorgi,1 Valentina Perrone,1 Stefano Buda,1 Lucio Boglione,2 Giuseppe Cariti,2 Cinira Lefevre,3 Carmela Nappi,4 Luca Degli Esposti1 1Health, Economics and Outcomes Research, CliCon Srl, Ravenna, Italy; 2Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy; 3Center of Observational Research and Data Sciences, Bristol-Myers Squibb, Rueil-Malmaison, France; 4Health Economics, Bristol-Myers Squibb S.r.l., Rome, Italy Objective: The objectives of this study were to estimate the prevalence of Hepatitis C among six Italian Local Health Units (LHUs), to describe patient and antiviral drug characteristics, and to estimate the health care consumption rates and related costs for the management of patients affected by hepatitis C virus (HCV) infection by using data from routine clinical practice.Methods: We conducted a retrospective study using administrative databases of six Italian LHUs. All patients who had a record related to HCV during the enrollment period (July 1, 2009, to December 31, 2014) and who had at least 6 months of data available prior to the first HCV record were included. The date of the first record related to HCV during the enrollment period was considered as a proxy of diagnosis and used as the index date. Patients were followed from the index date up to 1 year, death, or exiting the database. Using the overall cohort of HCV adult patients as the numerator, we estimated the prevalence of HCV among six LHUs. The denominators were obtained from the National Institute of Statistics (N=1,665,682). We also evaluated descriptive patient’s characteristics and treatment patterns, and estimated health care consumption rates and related costs for the management of the HCV patients. Results: A total of 7,550 patients were analyzed, of whom 57% were male with a mean age of 57.6±16.4 years. The prevalence of HCV was estimated to be 0.45% (95% confidence interval 0.44–0.46). During the follow-up period, 78.6% of HCV patients had received no antiviral treatment. The annual health care cost associated with HCV infection was €6,022.7 (±7,922.6) while the cost specific to HCV care was €3,154.6 (±4,972.0)Conclusion: Our findings showed that, in the Italian real-world setting, only a small proportion of HCV-infected patients received an antiviral treatment. Despite the current low prevalence of HCV, the economic impact of such disease remains high. Keywords: hepatitis C virus infection, prevalence, antiviral drug, health care resources use, real-world data

Umberto Restelli,1,2 Massimiliano Fabbiani,3 Simona Di Giambenedetto,3 Carmela Nappi,4 Davide Croce,1,2 1Centre for Research on Health Economics, Social and Health Care Management (CREMS), LIUC – Università Cattaneo, Castellanza, Italy; 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, 4Health Economics, Bristol-Myers Squibb S.r.l., Rome, Italy Background: This analysis aimed at evaluating the impact of a therapeutic strategy of treatment simplification of atazanavir (ATV)+ ritonavir (r) + lamivudine (3TC) in virologically suppressed patients receiving ATV+r+2 nucleoside reverse transcriptase inhibitors (NRTIs) on the budget of the Italian National Health Service (NHS).Methods: A budget impact model with a 5-year time horizon was developed based on the clinical data of Atlas-M trial at 48 weeks (in terms of percentage of patients experiencing virologic failure and adverse events), from the Italian NHS perspective. A scenario in which the simplification strategy was not considered was compared with three scenarios in which, among a target population of 1,892 patients, different simplification strategies were taken into consideration in terms of percentage of patients simplified on a yearly basis among those eligible for simplification. The costs considered were direct medical costs related to antiretroviral drugs, adverse events management, and monitoring activities.Results: The percentage of patients of the target population receiving ATV+r+3TC varies among the scenarios and is between 18.7% and 46.9% in year 1, increasing up to 56.3% and 84.4% in year 5. The antiretroviral treatment simplification strategy considered would lead to lower costs for the Italian NHS in a 5-year time horizon between –28.7 million € and –16.0 million €, with a reduction of costs between –22.1% (–3.6 million €) and –8.8% (–1.4 million €) in year 1 and up to –39.9% (–6.9 million €) and –26.6% (–4.6 million €) in year 5.Conclusion: The therapy simplification for patients receiving ATV+r+2 NRTIs to ATV+r+3TC at a national level would lead to a reduction of direct medical costs over a 5-year period for the Italian NHS. Keywords: protease inhibitor, economic evaluation, cost, de-intensification, antiretroviral therapy, Italian National Health Service

Umberto Restelli,1,2 Massimiliano Fabbiani,3 Simona Di Giambenedetto,3 Carmela Nappi,4 Davide Croce,1,21Center for Health Economics, Social and Health Care Management, LIUC – Università Cattaneo, Castellanza, Italy; 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, 4Health Economics, Bristol Myers Squibb S.r.l., Rome, ItalyIn 2017, the authors published an article to assess the financial consequences for the Italian National Health Service, over a 5-year period, of the adoption of a simplification strategy to atazanavir (ATV) + ritonavir (r) + lamivudine (3TC) dual therapy of HIVpositive patients receiving ATV plus two nucleoside reverse transcriptase inhibitors (NRTIs) starting from data of the Atlas-M trial at 48 weeks.1Consequently to the publication of the clinical results of the Atlas-M trial at 96 weeks, we updated the model implemented for the analysis, considering the most recent evidence.2The model was adapted considering the transitions among antiretroviral therapies (ARTs) observed in the trial, as reported in Figure 1, for years 1 and 2, and maintaining for years 3, 4, and 5 the same differential effectiveness (percentage of patients without virologic failure) observed between 48 and 96 weeks. In detail, the percentage of virologic failures considered in year 1 were 4.51% for ATV+r+2 NRTI and 0.76% for ATV+r+3TC; and in each following year were 8.66% for ATV+r+2 NRTI and 3.05% for ATV+r+3TC.

Diego Sangiorgi,1 Maurizio Benucci,2 Carmela Nappi,3 Valentina Perrone,1 Stefano Buda,1 Luca Degli Esposti11CliCon S.r.l., Health, Economics and Outcomes Research, Ravenna, 2Unit of Rheumatology, S. Giovanni di Dio Hospital, Florence, 3Bristol Myers Squibb S.r.l., Rome, ItalyObjectives: The use of biologic agents has revolutionized the management of rheumatoid arthritis (RA) in the past 2 decades. These biologic agents directly target molecules and cells involved in the pathogenesis of RA. The purpose of this study was to assess the usage of biologic agents in terms of persistence to treatment, dose escalation, and consumption of health care resources (hospitalizations, drugs, and outpatients service) in the real clinical practice in naïve patients with RA.Methods: We conducted a real-world, retrospective, observational cohort study based on data obtained from administrative databases of three Local Health Units in Italy. The population included adults diagnosed with RA who had at least one prescription between January 1, 2009 and December 31, 2011, for a biologic that was approved for treatment of RA. The patients were followed for 12 months after enrollment. The clinical characteristics of the patients enrolled in this study were also investigated in the 1-year period before the index date. The main and secondary endpoints were evaluated only in biologic-naïve patients without switches. The overall health care costs for patients were evaluated.Results: A total of 594 patients met the study criteria (mean age 53.5±13.5, female:male ratio =3:1). Thirty-nine percent received etanercept, 25% adalimumab, 14% infliximab, 10% abatacept, 9% tocilizumab, and 3% golimumab. After 1 year of observation, patients showed similar use of other RA-related medication. For the naïve patients without switches, the persistence levels were: 78% for etanercept, 72% for tocilizumab, 71% for adalimumab, 69% for infliximab, and 64% for abatacept. For all agents, dose escalation was 21.4% for infliximab, 11.5% for adalimumab, 5.6% for abatacept, 4% for tocilizumab, and 3.8% for etanercept. The annual costs per treated patients were €12,803 for adalimumab, €11,924 for etanercept, €11,830 for tocilizumab, €11,201 for infliximab, and €10,943 for abatacept.Conclusion: The role of biologic therapies in the treatment of RA continues to evolve; our study reflects real-world drug utilization data in adult patients with RA. These observations could be used by decision makers to support formulary decisions, although further research is needed using a larger sample to validate these results.Keywords: rheumatoid arthritis, biologic agents, real-world data

The article studies the effects of dispersion and frequency on the dielectric constant of the Y[Ba.sub.2][Cu.sub.3][O.sub.7] Josephson junctions that are fabricated on substrates with different angles tilted around the axis.

A prototype detector for X-rays with imaging capability entirely based on aluminum both for the absorber and lateral superconducting tunnel junctions is presented.