The Early Access and the Potential Cost Savings by the Compassionate Use of Onco-haematological Drugs: Results from the Italian Study Compass-O.

BACKGROUND: Compassionate drug use (CDU) provides early access to not yet authorised medicines and is funded by pharmaceutical companies. The observational retrospective study Compass-O monitored the CDU of onco-haematological drugs, managed by seven Italian units for cytotoxic drug preparations (Unità Farmaci Antiblastici [UFA]), between 1 January, 2016 and 31 December, 2021. OBJECTIVE: We aimed to evaluate the CDU of onco-haematological drugs managed by seven Italian UFA, between 2016 and 2021. METHODS: The seven UFA provided anonymised data concerning CDU approved in the study period. The early access and potential cost savings for the National Health System (Servizio Sanitario Nazionale [SSN]) were analysed for CDU concerning drug-therapeutic indication combinations with complete data and reimbursed by SSN up to December 2023 (date of study execution), according to the executive decision of the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]). Both analyses distinguished solid/liquid tumours and categorised the combinations as innovative (fully/conditionally) or non-innovative based on AIFA assessments. RESULTS: Compass-O collected 783 CDU authorisations, with 572 (73.1%) analysable in terms of early access and cost savings. On average, early access amounted to 514 days and the total cost savings was €376,115,801. Compassionate drug use approvals involved mainly solid tumours (93.7% vs 6.3% for liquid tumours), and the combination of trastuzumab emtansine-breast cancer was the most dispensed (n = 73; early access = 426 days; potential cost savings: €610,388). Out of 572 CDU approvals, 200 (35%) were innovative drug-therapeutic indication combinations, with 598 days of early access and a total potential saving of €113,124,069. CONCLUSIONS: The study Compass-O showed a significant economic burden of CDU and a relevant need for early access, particularly for innovative drugs. However, there is currently no structured monitoring of CDU in Italy, suggesting the need for a national observatory, of which Compass-O can be the pilot phase.

Primary Sjögren's syndrome in Italy: Real-world evidence of a rare disease through administrative healthcare data.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with significant impact on morbidity, mortality, and quality of life. This study aimed to evaluate epidemiology, healthcare needs and related costs of pSS patients from the Italian National Health Service perspective. METHODS: From the Fondazione Ricerca e Salute's database (∼5 million inhabitants/year), pSS prevalence in 2018 was calculated. Demographics, mean healthcare consumptions and direct costs at one year following index date (first in-hospital diagnosis/disease waiver claim) were analysed through an individual direct matched pair case-control analysis (age, sex, residency). RESULTS: In Italy, 3.8/10,000 inhabitants were identified as affected by pSS (1,746 case: 1,746 controls) in 2018. In the year following index date, 53.7% of cases and 42.7% of controls received ≥1 drug (p<0.001); mean per capita cost was €501 and €161, respectively (p<0.01). At least one hospitalization occurred to 7.8% of cases and 3.9% of controls (p<0.001) with mean per capita costs of €416 and €129, respectively (p = 0.46). At least one outpatient specialist service was performed in 49.8% of cases and 30.6% of controls (p<0.001); mean per capita costs were €200 and €75, respectively (p<0.01). Overall, mean annual costs were €1,171 per case and €372 per control (p < 0.01). CONCLUSION: According to results of this population-based study, the prevalence of pSS in Italy appears to be consistent with the definition of rare disease. Patients with pSS have higher pharmacological, in-hospital and outpatient specialist care needs, leading to three-times higher overall cost for the INHS, compared to the general population.

Italian healthcare resource consumption for patients on hemodialysis treated for chronic kidney disease-associated pruritus (CKD-aP).

Background: Chronic kidney disease-associated pruritus (CKD-aP) affects patients on hemodialysis. This study identified hemodialysis patients presumably affected or not affected by CKD-aP and integrated healthcare costs, from the perspective of the Italian administrative healthcare data. Methods: Through cross-linkage of Italian administrative healthcare data collected between 2015 and 2017 (accrual period) in the database of Fondazione ReS (Ricerca e Salute), patients undergoing in-hospital/outpatient hemodialysis were selected. Cohorts with and without CKD-aP were created based on the presence/absence of CKD-aP-related treatment (according to common clinical practice and guidelines) supplies and assessed in terms of CKD-aP-related treatments and mean healthcare costs per capita paid by the Italian National Health Service (INHS). Results: Of 1,239 people on hemodialysis for ≥2 years, CKD-aP affected 218 patients. Patients with CKD-aP were older and with more comorbidities. During the follow-up year, on average, the INHS spent €37,065 per case, €31,286 per control and € 35,988 per non-CKD-aP subject. High-efficiency dialytic therapies performed to people on hemodialysis with CKD-aP largely weighed on the overall mean annual cost. Conclusions: This real-world study identified patients on chronic hemodialysis potentially treated for CKD-aP. Interestingly, high-efficiency dialysis seems the most frequent and expensive choice for the treatment of CKD-aP. The discovery of appropriate and effective treatments for this condition might offer cost offsets.

Novel potassium binders to optimize RAASi therapy in heart failure: A systematic review and meta-analysis.

AIMS: Hyperkalemia often occurs among heart failure (HF) patients, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest potassium levels variations raise the risk of mortality and prompt patients to discontinue disease-modifying treatment, as RAASi. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are effective in reducing potassium levels and are approved for the treatment of hyperkalemia in HF, but whether their use results in a real optimization of HF treatment remains to be seen. The aim of the present meta-analysis was to assess the efficacy of NPB on the optimization of RAASi therapy in HF patients. METHODS AND RESULTS: PubMed, Web of Science and Clinicaltrial.gov were searched without restrictions from inception to 06 August 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified primary outcome was the optimization of RAASi therapy in HF patients, defined as the proportion of patients on RAASi at the end of follow-up. Secondary outcomes were hyperkalemia events, reduction in potassium levels, and adverse drugs reactions. Six studies with a total of 1390 patients were included. NPB improved RAASi therapy optimization in HF by 14% (95% CI: 4-26%), decreased hyperkalemia events by 29% (95% CI: 55-92%), and reduced potassium levels by 0.31 mEq/L (95% CI: 0.18-0.44) compared to placebo, maintaining a good safety profile. CONCLUSION: NPB are effective in allowing RAASi therapy optimization in patients affected by HF, in reducing hyperkalemia events and potassium levels. SYSTEMATIC REVIEW REGISTRATION: CRD42022351811 URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351811.

[The population affected by neovascular age-related macular degeneration and treated with anti-Vegf through Italian administrative healthcare data.] / La popolazione con degenerazione maculare neovascolare correlata all'età trattata con anti-Vegf attraverso i dati amministrativi sanitari.

INTRODUCTION: The neo-vascular age-related macular degeneration (nAmd) is a frequent cause of vision loss, although the intravitreal (Ivt) injections of anti-Vegf (vascular endothelial growth factor) have improved functional outcomes. This study has assessed the healthcare and economic burden on the Italian national health service (Inhs) for patients with nAmd and new users of anti-Vegf. METHODS: From the database of Fondazione Ricerca e Salute (ReS), people aged ≥55 and with an in-hospital diagnosis of nAmd and/or an injection of anti-Vegf (aflibercept, ranibizumab, pegaptanib; index date) in 2018 are selected. Those with other conditions treated with anti-Vegf and with an Ivt injection before 2018 are excluded. New users of anti-Vegf are analyzed by sex, age, comorbidities, Ivt administrations, switch of anti-Vegf, local outpatient specialist services (with some focuses) and direct healthcare costs charged to the Inhs Results. In 2018, of 8125 inhabitants aged ≥55 with nAmd (4.6x1000 inhab.; mean age 76±9; F: 50%), 1513 (19%) are new users of Ivt anti-Vegf (mean age 74±9), whose incidence (0.9x1000) increased with age until 84 years old. A proportion of 60.7% had ≥2 comorbidities (mainly hypertension, dyslipidemia and diabetes). Within the 2nd follow-up year, only 598 patients are still treated (60% were lost). On average, 4.8 Ivt injections in the first and 3.1 in the second year are registered. On average, the total cost charged to the Inhs per new user of anti-Vegf was € 6726 (Ivt anti-Vegf accounted for the 76%) and € 3282 (hospitalizations for causes different from nAmd accounted for the 47%), during the first and the second year, respectively. CONCLUSIONS: This analysis suggests that in Italy people with nAmd and new users of anti-Vegf are elderly, affected by many comorbidities, treated with Ivt anti-VEGF less than what is required and authorized to achieve a benefit, undergo very few follow-up outpatient specialist visits and tests and, within the 2nd year, their hospitalizations for causes different from nAmd mainly weighs on the total expenditure charged to the Inhs.

Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration.

PURPOSE: Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses. METHODS: We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose. RESULTS: Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610-2757] to 780 [372-1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42-7.71] to 2.35% [1.24-4.96], p = 0.003. CONCLUSIONS: A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.

Left atrium decompression devices across the spectrum of ejection fraction in heart failure: an updated systematic review and meta-regression analysis.

BACKGROUND: In patients affected by heart failure (HF) with reduced ejection fraction (HFrEF), pharmacological treatments have been proven to alleviate symptoms and improve prognosis, while no treatment other than sodium-glucose co-transporter-2 inhibitors have demonstrated significant effects in HF with preserved ejection fraction (HFpEF). Left atrium decompression devices (LADd) have been recently investigated as a new interventional approach in patients with HFpEF. OBJECTIVES: To assess the efficacy of LADd on soft endpoints in HF patients across the spectrum of ejection fraction. METHODS: PubMed and Web of Science were searched without restrictions from inception to 28 May 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified main outcomes were the change from baseline in 6-min walking distance (6MWD), NYHA class and health-related quality of life (HRQoL). Secondary outcomes were reduction in HF hospitalizations, echocardiographic, and hemodynamic parameters. RESULTS: Eleven studies, with a total of 547 patients, were included. LADd significantly improved 6MWD by 43.95 m (95% CI 29.64-58.26 m), decreased NYHA class by 0.93 (95% CI 1.20-0.67), and improved HRQoL questionnaire by 20.45 points (95% CI 13.77-27.14) with better results for all outcomes in patients with lower EFs. CONCLUSION: The present meta-analysis suggests that LADd are favorable in improving 6MWD, NYHA class, and HRQoL in HF across a wide spectrum of ejection fraction, with better outcomes in patients with lower EFs. TRIAL REGISTRATION: CRD42022336077, URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336077 .

Acute myeloid leukemia: Incidence, transplantation and survival through Italian administrative healthcare data.

OBJECTIVE: To identify newly diagnosed patients with acute myeloid leukemia in 2017 treated with intensive chemotherapy or unfit for intensive chemotherapy, and to assess their probability of receiving allogeneic stem cell transplantation and survival, from the Italian National Health Service perspective. PATIENTS AND METHODS: From the Ricerca e Salute database, adults with an in-hospital diagnosis of acute myeloid leukemia (International Classification of Disease-9th version-Clinical Modification code 205.0x) in 2017 (index date), without any identifying acute myeloid leukemia criteria within the preceding year, were selected. Among them, subjects treated with intensive chemotherapy (chemotherapy during an overnight hospitalization) within one year after index date were identified. The remaining were considered unfit for intensive chemotherapy. Gender, age and comorbidities were described. Within the follow-up period, probabilities of in-hospital allogeneic stem cell transplantation and overall survival were assessed through Kaplan Meier analyses. RESULTS: From 4,840,063 beneficiaries of the Italian National Health Service, 368 newly acute myeloid leukemia diagnosed adults (9.0 *100,000) were selected. Males comprised 57%. Mean age was 68±15. There were 197 patients treated with intensive chemotherapy. The remaining 171 unfit for intensive chemotherapy were older (72±14) and with more comorbidities (e.g. hypertension, chronic lung diseases and chronic kidney disease). Only patients treated with intensive chemotherapy underwent an allogeneic stem cell transplantation (41; 33%) during the one year after the index date. Within the first and second follow-up year, respectively: 41.1% and 26.9% of subjects treated with intensive chemotherapy (144) survived (median survival time: 7.8 months); 25.7% and 18.7% of those unfit for intensive chemotherapy (139) survived (1.2 months). Difference was significant (p<0.0001). Within one and two years after transplantation (41 patients), 73.5% and 67.3% of subjects survived, respectively. CONCLUSION: This study, by showing the incidence of acute myeloid leukemia in Italy in 2017, the proportion of patients treated with intensive chemotherapy from the new diagnosis, the use of allogeneic stem cell transplantation and two-year survival, integrated evidence on large and unselected populations and may help to improve treatment strategies of older acute myeloid leukemia patients.

[Community acquired pneumoniae and chronic obstructive pulmonary disease: the RWE analysis of events that required hospitalizations, and healthcare integrated costs.] / Polmonite acquisita in comunità e broncopneumopatia cronica-ostruttiva: analisi RWE degli eventi che hanno richiesto il ricovero ospedaliero e dei costi assistenziali associati.

INTRODUCTION: The community-acquired pneumonia (Cap) and the acute exacerbation of chronic obstructive pulmonary disease (Aecopd) frequently receive wrong therapies, leading to the increase of healthcare consumption resources, direct and indirect costs, and antimicrobial resistance. This study identified Cap and Aecopd hospitalized events, and analyzed them in terms of comorbidities, antibiotic use, re-hospitalizations, diagnostics and costs, from the perspective of the Italian national health service (Inhs). METHODS: From the database of Fondazione Ricerca e Salute (ReS), hospitalizations for Cap and Aecopd from 2016 to 2019. Demographics, comorbidities and mean in-hospital stay at the baseline, antibiotics reimbursed by the Inhs within 15 days before and after the index event, outpatient diagnostics performed before the event and in-hospital diagnostics, and direct costs charged to the Inhs, are assessed. RESULTS: From 2016 to 2019 (~5 million inhabitants/year), 31,355 events of Cap (1.7x1000/year) and 42,489 events of Aecopd (4.3x1000 inhabitants aged ≥45/year) were identified, of which 32% and 26.5%, respectively, were treated with antibiotics before the hospitalization. The highest frequency of hospitalizations and comorbidities, and the longest mean in-hospital stays are found among elderly. Events not treated before and after the hospitalization showed the longest in-hospital stay. More than 12 Ddd (defined daily dose) are dispensed after the discharge. Local outpatient diagnostics are performed before the admission to <1% of the events; in-hospital diagnostics are registered in 5.6% and 1.2% of Cap and Aecopd, respectively, discharge forms. About 8% and 24% of Cap and Aecopd, respectively, are re-hospitalized during one subsequent year, mainly within one month. The mean expenditures per event of Cap and Aecopd were € 3646 and € 4424, respectively: hospitalizations, antibiotics and diagnostics accounted for the 99%, 1% and <0.1% of the total expense, respectively. CONCLUSIONS: This study provided a very high dispensation of antibiotics after the hospitalization for Cap and Aecopd, while a very low use of differential diagnostics available within the observed periods, to the detriment of the enforcement actions proposed at institutional levels.

[Occurrence of cardiovascular events within a large population of patients affected by rheumatoid arthritis with or without diabetes.] / Sviluppo di eventi cardiovascolari in un'ampia popolazione di pazienti affetti da artrite reumatoide con o senza diabete.

INTRODUCTION: Rheumatoid arthritis (Ra) and diabetes are often associated with chronic multimorbidity and share the high risk of development of major cardiovascular events (Mace). This study aimed to identify and analyse patients with only Ra, Ra + diabetes, and only diabetes, in terms of comorbidities and new occurrence of Cv events, from the perspective of the Italian national health service (Inhs). METHODS: Starting from the Fondazione ricerca e salute (ReS)'s database, through the record linkage of administrative healthcare data, cohorts with only Ra, Ra + diabetes and only diabetes have been selected, characterized (age and sex), and analysed by comorbidity (depression, dyslipidemia, hypertension, hemorrhagic stroke and ischemic stroke/transient ischemic attack - Tia, coronary artery disease - Cad, heart failure - Hf, chronic liver disease, periphery artery disease - Pad, chronic kidney disease, asthma/chronic obstructive pulmonary disease - Copd, neoplasia) and by new Cv events (Hf, Cad and ischemic stroke/Tia) within two follow-up years (Kaplan-Meier curves). A logistic regression model defined contribution and type of association of some variables on new Cv events. RESULTS: In 2018, from 5.375.531 Inhs beneficiaries in the ReS database, 13.698 (0.25%) were affected by only Ra, 1728 (0.03%) by Ra + diabetes, 347,659 (6.8%) by only diabetes. The only Ra cohort was composed by more females, younger and with less comorbidities patients. Proportions of 79.3%, 70.8% and 38.5% of patients with Ra + diabetes, only diabetes and only Ra were affected by 2 to ≥4 comorbidities: among patients with Ra + diabetes, comorbidities showed the highest frequencies, mainly hypertension, dyslipidemia and asthma/Copd. Within two follow-up years, about 8% of patients with diabetes with/without Ra developed a new Cv event (vs 3% with only Ra). The presence of Ra/diabetes or Ra + diabetes, male sex, older age and comorbidities of interest resulted significantly (p<0.01) associated with a higher Cv risk. CONCLUSIONS: Comorbidities and the co-presence of diabetes in patients with Ra determine a complicated framework with high risk of Cv events. It is worthy include more complex patients in clinical trials, in order to generate evidence useful for even more multidisciplinary medical teams.

[A view of care pathways approved by Italian Regions, to face the challenge of the community-based healthcare: a quali-quantitative analysis of the Pdta Net database.] / Conoscere i percorsi diagnostico-terapeutici assistenziali (Pdta) regionali approvati in Italia per affrontare il cambiamento della assistenza di prossimità: analisi quali-quantitativa del database Pdta Net.

INTRODUCTION: The adoption of a Care Pathway (CP) allows the healthcare management of patients suffering from high-epidemiological impact chronic diseases. The continuity of care of these patients is one of the main purposes of the community-based healthcare reform, foreseen in the 6th Mission of the National recovery and resilience plan. Fondazio-ne Ricerca e Salute (ReS) collects and analyses regional CPs approved in Italy, through the Pdta Net database. METHODS: Fondazione ReS has retrieved all the CPs approved by Italian Regions and Autonomous provinces until 12/31/2021 within institutional websites, through specific keywords. The quali- and quantitative analysis of CPs was based on the approving Region, the publication year, the disease (distinguishing between high-epidemiological impact chronic diseases and rare conditions) and clinical area. Following the 5-year experience gained by Fondazione ReS in terms of CPs' aims and organization for the full realization of an evidence-based healthcare of chronic patients, all data collected until 12/31/2021 underwent an in-depth double-blinded quality control. This control was aimed to make the Pdta Net database as representative as possible of the existing documents closest to a real CP. RESULTS: From 2005 to 2021, 729 regional CPs have been approved: 404 on high-impact chronic diseases and 220 on rare conditions. The CPs of chronic diseases, mostly edited by Piemonte (45 CPs), Campania (34) and Toscana (33) Regions, mainly concern on diabetes (19), chronic obstructive pulmonary disease (15), heart failure (13), stroke, multiple sclerosis and colorectal neoplasms (12 each one), breast cancer (11), dementia and chronic kidney disease (10 each one). Most of the CPs on rare diseases have been edited by Regions with an established Rare Disease Network, i.e., Lombardia (125 CPs), Lazio (74) and Toscana (40): neurology (61) and oncology (52) were the most represented clinical areas. CONCLUSIONS: The high number of CPs approved in Italy confirms an increasing interest of the healthcare institutions. The collected CPs show an extreme variety of titles, text structures and disease choices. Given the absence of an institutional observatory and of devotees of shared and harmonized CPs, annually Pdta Net makes available an updated and complete overview of these governance tools, which are essential for the upcoming changes of the Italian national health service.

Antiplatelet Therapy during the First Year after Acute Coronary Syndrome in a Contemporary Italian Community of over 5 Million Subjects.

Background: Patterns of real-world antiplatelet therapy (APT) are reported to differ from guideline recommendations. This study describes patterns of APT during the year following a hospital diagnosis of acute coronary syndrome (ACS) and possible implications in terms of revascularization rates, rehospitalizations, and costs for the Italian National Health Service. Methods: From >5 million people, patients discharged (=index date) with primary/secondary ACS diagnosis in 2017 were identified by cross-linkage of administrative health data collected by the Ricerca e Salute (ReS) Foundation. Patients were characterized by revascularization rates at index date, APT at one month and one year (with appropriate coverage defined as ≥80% of defined daily doses), and rehospitalizations and healthcare costs during follow-up. Results: From the 2017 ReS database, 7966 (1.46 × 1000 inhabitants) were discharged alive with an ACS diagnosis. Most were >69 years and male. Of these, 83% (6640/7966) received ≥1 recommended antiplatelet agent within one month (treated group): 23% (1870/7966) as single and 60% (4770/7966) as dual APT. Among the 53% undergoing revascularization, 81% received dual APT at one month. Of the 78% with the same APT at one year, 66% showed appropriate coverage. For subjects treated and untreated with APT at one month, one-year rehospitalization rates were 54% and 66%, respectively, and mean per capita costs were EUR 14,316 and EUR 16,552, respectively (hospitalization driving >80% of costs). Conclusions: Among survivors of a hospitalized ACS diagnosis, this analysis shows relatively high APT under-treatment at one month and one year, associated with fewer index revascularization rates, more rehospitalizations, and greater costs. Further initiatives to understand undertreatment and poor adherence should lead to improved health management and savings.

Prescription Pattern of Monoamine Oxidase B Inhibitors Combined with Levodopa: A Retrospective Observational Analysis of Italian Healthcare Administrative Databases.

BACKGROUND: Parkinson's disease is still incurable, and several factors are considered when defining pharmacological therapy. OBJECTIVE: The aim of this study was to describe the prescription pattern of monoamine oxidase B inhibitors (MAO-BIs) marketed in Italy (selegiline, rasagiline, safinamide) as an add-on to levodopa among new users of MAO-BIs, from the perspective of the Italian National Health Service. PATIENTS AND METHODS: Through cross-linkage of administrative healthcare data in the Ricerca e Salute (ReS) database, adults with a supply of one or more MAO-BIs in 2017, and with no other MAO-BI use since 2013, were selected. Levodopa had to be supplied within 30 days before/after the MAO-BI. The incidence, use, sex, age, comorbidities, 2-year prescription patterns (i.e., switches, proportion of treated patients per semester/year, mean daily milligrams/monthly tablets supplied, discontinuation, change to other anti-Parkinson drug) of patients taking MAO-BIs were provided. RESULTS: In 2017, 1059 new users received an MAO-BI (incidence 22.6 × 100,000 adults) combined with levodopa: 502 subjects (10.7 × 100,000) were treated with selegiline, 161 (3.4 × 100,000) were treated with rasagiline, and 396 (8.4 × 100,000) were treated with safinamide. The cohorts mainly consisted of males with a median age of ≥ 74 years. Treatment incidences increased with age. Switches occurred in 18.0%, 11.0%, and 4.3% of the selegiline, rasagiline, and safinamide cohorts, respectively. Most of the patients switching from selegiline/safinamide changed to rasagiline, while most of the patients switching from rasagiline changed to safinamide. From the first to second years, patient numbers reduced by ≤ 50%, and the daily milligrams/monthly tablets slightly increased. Six-month discontinuation occurred in > 50% of all cohorts, and ≥ 65% of discontinuing patients changed to another anti-Parkinson drug. CONCLUSIONS: This analysis described the heterogeneous use of MAO-BIs as an add-on to levodopa in Italy. Further clinical trials and real-world studies are encouraged to update the few existing guidelines and to align clinical practice strategies.

[Uremic pruritus through healthcare administrative data].

Background: This retrospective observational study aimed at describing patients on hemodialysis with/without uremic pruritus (UP), their healthcare resource consumption and costs from the perspective of the Italian National Health Service (INHS). Methods: Through the cross-linkage of the healthcare administrative data collected in the ReS (Ricerca e Salute) database from 2015 to 2017, patients undergoing in-hospital/outpatient hemodialysis (index date) for ≥2 years were selected. After the exclusion of subjects with other causes of pruritus, UP/non-UP cohorts were created based on the presence/absence of UP-related treatment supplies and characterized. Treatments, hospitalizations and costs were analyzed. Results: Of 1239 patients on hemodialysis for ≥2 years (20.2% of all hemodialysis subjects), 218 (17.6%) were affected by UP. Both cohorts were mostly males and elderly. One year before and after the index date, 58.1% and 65.1% of UP patients received UP-related treatments, of which >50% were treated with antihistamines (mostly cetirizine), 10% gabapentin and 1.4% ultraviolet light therapy. The mean annual overall cost per patient with/without UP was €37,065/€35,988. Outpatient specialist services accounted for 80% (>77% hemodialysis), hospitalizations for 10% (>60% hemodialysis). Conclusions: Though the prevalence of UP and related healthcare costs charged to the INHS were underestimated, the burden of UP was not negligible. High-efficiency dialytic therapies performed 3 to UP patients seemed to largely weigh on the overall mean annual cost. The availability of specific and effective treatments for UP might offer cost and healthcare offsets.

Acute lower respiratory infections: real-world evidence of antibiotic prescription pattern and costs from a large administrative Italian database.

OBJECTIVE: This observational retrospective analysis aimed to describe antibiotic prescription pattern in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and community-acquired pneumonia (CAP) and their costs, from the Italian National Health Service perspective. METHODS: From the ReS database, a cross-linkage of Italian healthcare administrative databases through a unique anonymous code allowed to select subjects aged ≥12 years, supplied with at least an antibacterial for systemic use (ATC code: J01) from 01/01/2017 to 12/31/2017 and evaluable until the end of 2018. Prescriptions of different antibiotics on the same date were excluded. The prescription pattern was assessed for patients with an AECOPD (aged ≥50) or a CAP event (aged ≥12) in 2017. A 30-day cost analysis after the antibacterial supply and according to absence/presence (15 days before/after the supply) of AECOPD/CAP hospitalization was performed. RESULTS: In 2017, among patients aged ≥12 (~5 million), 1,845,268 were supplied with ≥1 antibacterial (37.2%). Antibacterial prescriptions potentially related to AECOPD were 39,940 and 4,059 to CAP: quinolones were the most prescribed (37.2% and 39.0%, respectively), followed by third-generation cephalosporins (25.5%; 27.5%), penicillins (15.4%; 14.9%), and macrolides (14.4%; 11.3%); the 30-day mean cost was €709 and €2,889. An association AECOPD/CAP-antibacterial supply costed more when the hospitalization occurred 15 days after the antibiotic supply (€5,006 and €4,966, respectively). CONCLUSIONS: Findings confirmed the very high use of antimicrobials in Italy and highlighted the urgent need of improving current prescribing practices and developing new molecules, to stop the incessant spread of antimicrobial resistance and related socioeconomic impacts.

Through this retrospective observational analysis of the Fondazione ReS (Ricerca e Salute) database, collecting Italian healthcare administrative data, antibacterial for systemic use supplied to subjects aged ≥12 years in 2017 were identified as potentially prescribed to treat an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (39,940; 91%) or an event of community-acquired pneumonia (CAP) (4,059; 9%). The most used antimicrobials were quinolones (37.2% and 39.0% of antibiotics related to AECOPD and CAP, respectively), third-generation cephalosporins (25.5%; 27.5%), penicillins (15.4%; 14.9%), and macrolides (14.4%; 11.3%). Costs of each patient supplied with the antibacterial to treat AECOPD/CAP were assessed within 30 days after the antibacterial supply. Overall, the integrated cost of the association AECOPD/CAP-antibacterial was higher if the patient was hospitalized due to AECOPD/CAP before the antibacterial supply (€5,006/€4,966, respectively). The integrated expenditure of a patient treated for AECOPD not requiring hospitalization was €647. Findings showed a substantial antimicrobial use in Italy for the 2 acute lower respiratory tract infections, highlightening the need of improving the current prescribing practice or developing new molecules. This study also provided healthcare integrated costs of these associations as a proxy of the complexity and frailty of patients experiencing an AECOPD/CAP event.

[Catheter ablation in hospitalized patients diagnosed with atrial fibrillation: real-world evidence from Italian health administrative databases.] / Ablazione transcatetere nei pazienti ricoverati con diagnosi di fibrillazione atriale: real-world evidence da database amministrativi sanitari italiani.

BACKGROUND: Catheter ablation (CA) is recommended for treating paroxysmal/persistent atrial fibrillation (AF) as an alternative to antiarrhythmic drugs after failure or intolerance, or as first-line in limited cases. This study has described patients affected by AF and treated or not with CA, from the perspective of the Italian National Healthcare System (INHS). METHODS: From the healthcare administrative data collected in the ReS (Ricerca e Salute) database, from 2016 to 2017, patients with main/secondary diagnosis of AF (index date) were split into two cohorts by presence/absence of CA procedure in the same hospital discharge form. The cohorts were characterized by gender, age, comorbidities. Consumptions (DDD) of antiarrhythmic, anticoagulant, antiplatelet and antihypertensive drugs, hospitalizations for AF, hemorrhagic stroke/intracranial hemorrhage, ischemic stroke/transient ischemic attack, extra cranial major bleeding and heart failure, outpatient specialist care and healthcare costs paid by the INHS were assessed. RESULTS: Out of >5 million inhabitants in 2016-2017, 33,940 patients were hospitalized with a diagnosis of AF, 990 (2.9%) were treated with CA in the same hospitalization (32,950 without CA). Patients with CA were mostly males (66.8%; 48.5% without CA). On average, they were aged (±SD) 65±12 (78±11 without CA) and affected by one comorbidity (≥3 in patients without CA). During the observational period, beta-blockers were the most prescribed to both cohorts, followed by antiarrhythmic drugs to patients with CA and by direct oral anticoagulants to those without. The 29.7% of subjects with CA were hospitalized due to relevant cardiovascular diagnoses during the previous year (7.4% without CA) and 93.4% in the first follow-up year (29.7% without CA). The 80-90% of cohorts resorted to the outpatient specialist care. Electrocardiograms and the cardiology visits were performed to the 62.5% and 31.1% of the cohort with CA (39.5% and 13% without CA) in the first follow-up year. On average, the INHS spent about € 4000 in the previous year and around € 10,000 in the first follow-up year per patient of both cohorts, while around € 3000 and € 4000 for a patient respectively with and without CA. At least half of the total costs were due to hospitalizations, followed by pharmaceuticals and outpatient specialist care. CONCLUSIONS: This study confirm a post-CA suboptimal monitoring.

[Chronic use of the unfixed combination of ACE-inhibitors and beta-blockers in Italy from 2013 to 2019 through the healthcare administrative data.] / Uso cronico dell'associazione estemporanea ACE-inibitori e beta-bloccanti in Italia dal 2013 al 2019 attraverso i dati amministrativi sanitari.

INTRODUCTION: The association between an ACE-inhibitor and a beta-blocker is recommended in case of complicated arterial hypertension and heart failure with reduced ejection fraction. This retrospective drug-utilization study has described its chronic use from the Italian National Healthcare Service perspective. METHODS: From the ReS (Ricerca e Salute) database, collecting Italian healthcare administrative data, patients receiving an ACE-inhibitor or a beta-blocker from 2013 to 2019 were selected. The prevalence of use (patients treated/1000 inhabitants) and of continuous treatment (patients treated for ≥80% period from the supply to the end of the same year - by means of dosage units - per 1000 inhabitants) of each single active substance were assessed. Among patients continuously treated, those supplied with an ACE-inhibitor and a beta-blocker (unfixed and fixed combinations) were analyzed in terms of prevalence of continuous treatment. Subjects treated with the unfixed combination ramipril-bisoprolol in 2019 were characterized by gender and age. RESULTS: The prevalence of ACE-inhibitors' use increased from 49.7/1000 inhab. in 2013 to 50.2 in 2019: ramipril was the most supplied each year (28.9 to 31.6/1000 inhab.). The prevalence of continuous treatment increased from 27.4 to 28.3/1000 inhab.: ramipril the most continuously dispensed (16 to 18/1000 inhab.). The prevalence of beta-blockers' use increased from 61.0 to 90.4/1000 inhab.: bisoprolol the most supplied and with the highest increase (27.1 to 52.2/1000 inhab.). The prevalence of continuous treatment increased from 33.1 to 55.8/1000 inhab.: bisoprolol the most continuously dispensed (18 to 37/1000 inhab.). Among patients with continuous supplies, from 49,843 a 51,496 were treated with associations between an ACE-inhibitor and a beta-blocker on an ongoing basis. Half of them were continuously treated with the unfixed combination ramipril-bisoprolol (4.3 to 4.8/1000 inhab.). In 2019, subjects with continuous supplies of ramipril-bisoprolol were mainly males (63.4%) and elderly (mean age 71±12), and the prevalence of use increased with age. CONCLUSIONS: These findings, together with recommendations from the main international guidelines encourage to make available also ramipril and bisoprolol as fixed dose combination, in order to simplify the therapy administration and improve the adherence, especially among elderly and patients with multimorbidity.

Coronary Artery Disease in Patients Older than 35 and Eligible for Cardiovascular Secondary Prevention: An Italian Retrospective Observational Analysis of Healthcare Administrative Databases.

BACKGROUND: This study describes patients with coronary artery disease (CAD) who are eligible for secondary prevention and assesses their healthcare consumption and costs from the perspective of the Italian National Health Service (INHS). METHODS: From the Fondazione Ricerca e Salute's database, which collects Italian healthcare administrative data, all patients aged ≥ 35, with ≥1 primary in-hospital CAD diagnosis and/or procedure on the coronary arteries, or with the specific disease exemption code, and who are suitable for long-term secondary prevention treatments, were identified in 2018 and analyzed. Demographics, comorbidities, one-year supplied drugs, hospitalizations, and costs were analyzed. RESULTS: From >3 million inhabitants aged ≥ 35, 46,063 (1.3%) were identified (72.1% males, mean age 70 ± 12; approximately 50% with ≥3 comorbidities). During a one-year follow-up, 96.4% were treated with ≥1 drug for secondary prevention (mainly antiplatelets and lipid lowering agents), 69.4% with ≥1 concomitant cardiovascular drug, and 95.8% with ≥1 concomitant non-cardiovascular therapy. Within one year, 30.6% of patients were hospitalized at least once, mostly due to non-cardiovascular events. Calculated by mean, the INHS paid EUR 6078 per patient. CONCLUSIONS: This analysis confirms the relevant burden of CAD for patients with many comorbidities and who are frequently hospitalized, and the burden on the INHS. A multidisciplinary healthcare approach is encouraged to improve patients' outcomes and reduce costs for the INHS.

[Second-generation antipsychotics and cardio-metabolic events: real-world analysis and healthcare costs]. / Antipsicotici di seconda generazione ed eventi cardio-metabolici: analisi real-world e costi assistenziali.

OBJECTIVE: This analysis has identified and characterized new users of second-generation antipsychotics (SGA) in Italy and has assessed the occurrence of cardio-metabolic (CM) events over 3 years after the SGA starting therapy and the annual healthcare costs, in the perspective of the Italian National Health System (INHS). METHODS: Starting from the Fondazione ReS (Ricerca e Salute)'s database, adults treated with SGA in 2015 (index supply) were selected. By analyzing 2 previous years, treatment incidence and presence/absence of CM diseases or predisposing conditions (PC) to these events were defined and 3 cohorts were identified: A) with CM or predisposing conditions, B) only with PC, C) without neither CM nor predisposing conditions. Cohorts B and C were paired with patients with the same clinical profiles but without any SGA supply. Into cohorts and related paired groups, CM diseases/predisposing conditions occurred (cases) during the 3-year follow-up after the index supply were searched. Cases were compared with related control groups in terms of probability of CM disease/predisposing conditions occurrence (survival analysis to the event - Kaplan-Meier curves). RESULTS: Among more than 4 million adults, 12,218 were incident to SGA (2.8 x1,000): 2,732 composed cohort A (22.5%) with median age 80 (69;87), 1,492 cohort B (12.3%) with median age 77 (63;85), 7,904 cohort C (65.2%) with median age 60 (37;84). They were mostly females. The treatment incidence increased with age. The probabilities of CM events were: 15.8% and 13.3% among cases and controls of cohort B, and 7.5% and 5.1% among cases and controls of cohort C. Probabilities of predisposing conditions occurrence were 10% and 7.0% among cases and controls of cohort C. All differences were significant (p<0.01). The mean integrated healthcare cost was similar between case and control. Hospitalizations accounted for the most expenditure. DISCUSSION AND CONCLUSION: CM events or predisposing conditions occurrence in the elderly is both a clinical and an economic issue for the INHS. The proper therapeutic choice and monitoring of patient treated with antipsychotics must be encouraged.