[The care pathway of patients with diffuse large B-cell lymphoma described through Italian administrative healthcare data.] / Il percorso di cura dei pazienti con linfoma diffuso a grandi cellule B descritto attraverso i dati amministrativi.

INTRODUCTION: The diffuse large B-cell lymphoma (Dlbcl) is the most common non-Hodgkin lymphoma and at highest incidence among the elderly. Despite the improved outcomes of patients treated with the first-line (1L) standard of care until the end of 2022, composed by rituximab and polychemotherapy (R-Chop), during the last 20 years, the rate of relapsed and refractory Dlbcl (rrDlbcl) remains elevated. This study has identified and analyzed patients newly diagnosed with Dlbcl and treated with 1L, from the perspective of the Italian National Health Service (Ssn). METHODS: From the administrative database of Fondazione Ricerca e Salute (ReS) including ~5.5 million inhabitants/year in Italy, adults with a new in-hospital Dlbcl diagnosis (index date) and treated with 1L in 2018, 2019, 2020 and 2021 were identified and characterized in terms of demographics and comorbidities during a period (from 4 to 8 years) preceding index date. From 1 to 4 years following index date (follow-up), overall survival (Kaplan-Meier curves), percentage distribution of patients by line of therapy including dispensation/administration of chemo-immunotherapy, hemopoietic stem cell transplantation (Hsct), and direct healthcare costs charge to the Ssn, were evaluated. RESULTS: Overall, from the ReS database, 206 patients newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 in Italy (incidence from 0.9 to 1.7 x100,000 adult inhabitants) were identified. They were mainly older (median age 68 [56; 75] years), males (56%) and affected by ≥2 comorbidities (52%), mostly cardiometabolic. During 4 years of follow-up, 56% of cases in 2018 survived. During the first follow-up year: 73%, 80%, 100% and 35% of cases in 2018, 2019, 2020 and 2021, respectively, received a 2L; 42% and 64% of cases in 2018 and 2020, respectively, received a 3L. At least one Hsct was found as a 2L among cases in 2018, 2020 and 2021. On average, each patient newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 caused a total expenditure directly charged to the Ssn ranging from € 20,000 to € 30,000 during the first follow-up year (chemo-immunotherapy accounted for 40-53%), which reduced with time in favor of other drugs and Hsct. CONCLUSIONS: This analysis confirms the high rate of rrDlbcl and the high economic impact charged to the SSN to support first the chemo-immunotherapy, then the chronic care and the absence of standardized further lines of therapy for patients with rrDlbcl.

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.

[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.

Do more targets allow more cancer treatments, or not?

The three current oncology models (histological, agnostic and mutational) mainly differ in clinical, technological and organisational aspects, leading to different regulatory procedures and implications in antineoplastic therapy access by patients. Within the histological and agnostic models, Regulatory Agencies authorise target therapies and define their price, reimbursement, prescription and access based on results from clinical trials including patients affected by the same tumour (histological) or subjects with specific genetic mutations regardless of the tumour site or the histology (agnostic). The mutational model has been developed to identify specific actionable molecular alterations found by next-generation sequencing test-based large platforms on solid and liquid biopsies. Nevertheless, due to the highly uncertain efficacy and possible toxicity of drugs tested within this model, regulatory procedures based on histological or agnostic oncology cannot be followed. Multidisciplinary skills are required (e.g. the molecular tumour board's (MTB) representatives) to identify the best association between the genomic profile and the drug planned to be used, but quality requirements, practices and procedures of these discussions still need to be standardised. Real-world evidence from clinical practice (i.e. genomic findings, clinical data and MTBs' choices) lacks, therefore, it is urgently needed as opposed to limited findings from clinical trials. A potential solution for an appropriate access to the therapy chosen by the mutational model can be the indication-value-based sub iudice procedure of authorisation. The access to therapies suggested by extensive molecular profiling could be easily implementable within the Italian national health system, thanks to the existing regulatory procedures, i.e. the managed-entry agreements and the antineoplastic drug monitoring registries, alongside those granted by conventional studies (phase I, II, III, IV) conducted according to the histological and agnostic models.

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.

[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.

How many and who are patients with heart failure eligible to SGLT2 inhibitors? Responses from the combination of administrative healthcare and primary care databases.

BACKGROUND: Recent successful findings (i.e. DAPA-HF trial) in patients with heart failure (HF) with/without diabetes treated with sodium-glucose co-transporter inhibitors (SGLT2-I) have fostered real-world data analyses. Fondazione Ricerca e Salute's (ReSD) administrative and Health Search's (HSD) primary healthcare databases were combined in the ReS-HS DB Consortium, to identify and characterize HF-patients eligible to SGLT2-I, and assess their costs charged to the Italian National Health Service (INHS). METHODS AND RESULTS: Eligibility to SGLT2-I was HF diagnosis, age ≥ 18 years, reduced (≤40%) ejection fraction (HFrEF) and glomerular filtration rate (GFR) ≥30 ml/min. The HSD, including 13,313 HF-patients (1.5% of the total HSD population) was used to develop and test the algorithms for imputing HFrEF and GFR ≥ 30 ml/min, based on a set of covariates, to the ReSD, including 67,369 (1.5% of the total ReSD population). Subjects eligible to SGLT2-I were 2187 in HSD (61.1% of HFrEF); after the imputation, 15,145 in ReSD (58.8% of HFrEF). Prevalence of eligibility to SGLT2-I was higher in males then in females and increased with age; diabetic patients were 44.3% and 33.4% of HSD and ReSD populations eligible to SGLT2-I, respectively. Estimated from ReSD, the mean annual cost charged to the INHS per patient with HF eligible to SGLT2-I was €7122 (68% due to hospitalizations). CONCLUSIONS: Approximately 20% of patients with HF was eligible to SGLT2-I. Real-world data can identify, quantify and characterize patients eligible to SGLT2-Is and assess related costs for the health care system, thus providing useful information to Regulatory Decision makers.

[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.

[The tools for the governance of mutational oncology and agnostic drugs: from place in therapy to place in pathway.] / Gli strumenti per la governance dell'oncologia mutazionale e dei farmaci agnostici: dal place in therapy al place in pathway.

In the oncology, the construction, implementation and evaluation of the care pathway must consider the integration of the "histological approach" with the "mutational" one, focused on the identification of specific molecular alterations to which the so-called "agnostic drugs" are targeted. To investigate this issue, a specific Working Group of the MaCroScopio Project (observatory on chronicity) was held in which the leading Italian experts in the oncology and regulatory field participated. From their articles, collected in this dossier, it clearly emerges the need of appropriate tools to manage the intrinsic complexity of the new mutational model and the challenges posed by agnostic drugs; among these Molecular Tumor Board, care pathway and Real-World Data. All this, to promote, for new oncological drugs, the transition from the classic study of the "place in therapy" to the "place in pathway", aimed to build the clinical, regulatory and institutional bases on which mutational oncology is based and make it a reality for all patients who need it.

[Mutational oncology of lung cancer: molecular markers, drugs, negotiation conditions and experiences in national reference centers.] / L'oncologia mutazionale del carcinoma polmonare: marcatori molecolari, farmaci, condizioni negoziali ed esperienze in centri di riferimento nazionale.

The gradual availability of genomic profiling tests and the "agnostic approvals" from FDA and EMA have opened the oncology mutational model phase, which complements and integrates the traditional hystological approach. The non-small-cell lung cancer (NSCLC) is characterized by many molecular alterations and represents the need of a change from the traditional diagnostic, therapeutic and organisational paradigms to the "mutational" ones. From the Italian National Healthcare System point of view, access and reimbursement of drugs based on the hystological model were managed thorugh the Italian Medicines Agency's (AIFA) monitoring registries and the managed entry agreements: risk-sharing, cost-sharing and payment by results. The Italian reference oncological centres, which contributed to this report with their experiences, have shown the heterogenous approach to the molecular diagnostics (included next generation system tests). Facing the high complexity of the mutational model, outcomes handling and genomic profiling tests access inevitably result different among centres. The activation of multidisciplinary groups for the government of clinical processes, appropriateness and economic sustainability are essential. The Molecular Tumor Board (MTB) allows the management of such complexity, the interpretation of genomic profiling outcomes and the choice of drugs that are alrealdy authorized by AIFA, off-label or still under investigation. Moreover, in order to guarantee the uniformity, the data traceability and the transparency of assessment reports, a network of MTB must be validated by AIFA through specific criteria. To date, the oncological centres presented by this report are undergoing the experimental phase of the national genomic operating system implementation and represent the starting point of the deep organisational changement to the mutational approach and of its real and appropriate integration into the daily clinical practice.

Real-world Prescription Pattern, Discontinuation and Costs of Ibrutinib-Naïve Patients with Chronic Lymphocytic Leukemia: An Italian Healthcare Administrative Database Analysis.

BACKGROUND AND OBJECTIVE: In order to integrate the existing and inconsistent information from clinical trials and real-world practice on chronic lymphocytic leukemia (CLL) treated with ibrutinib, this analysis aimed to describe the prescription pattern of new users of ibrutinib affected by CLL, focusing on discontinuation, severe adverse events (AEs) and change of treatment, and to assess the integrated healthcare expenditure from the Italian National Health System (INHS) perspective. METHODS: Starting from the ReS database, adults with at least a supply of ibrutinib (ATC code L01XE27) were selected from 01/01/2016 to 12/31/2017. Those without any ibrutinib supply in the year before the index prescription were considered new users. Out of them, only patients with at least a primary or secondary in-hospital diagnosis of CLL (ICD-9-CM code 204.1*) from 01/01/2013 to 12/31/2018 were further broken down according to the ibrutinib's line treatment (first line-FL; second or later line-SLL) and analysed. They were characterized by sex and age in the selection period. Mean annual consumption (defined daily doses [DDD]), treatment discontinuation, changes of therapy, interruptions and healthcare costs in charge of the INHS were assessed during two follow-up years. RESULTS: Out of more than 5 million inhabitants of the ReS database, 69 new ibrutinib users and diagnosed with CLL in 2016 (incidence: 1.6 × 100,000) and 41 in 2017 (incidence: 0.9 × 100,000) were selected. Of these, 21 (19.1%) were FL ibrutinib users and 89 (80.9%) were SLL ones, mostly males and with mean ages (±SD) of 65 ± 14 and 70 ± 10, respectively. The mean annual consumption among FL users decreased from 222.2 DDD per patient treated to 216.0 DDD, while increased among SLL patients from 238.6 DDD to 260.1 DDD, in the first and second follow-up year, respectively. The discontinuation rate was about 40% in the first year, similarly among FL and SLL users. SLL patients discontinued more frequently (52.8% vs 20.0%) in the second year. Very few AEs were recorded. The 62.5% of FL and 55.6% of SLL users discontinuing ibrutinib in 1-year follow-up, while one SLL patient (5.3%) in the second year changed therapy. The 20.0% and 15.9% of all new users in first and second year interrupted ibrutinib. The total integrated cost of FL patients was €55,732 reducing by about €15,000, while it was €58,716 for SLL ones decreasing by €6,000, respectively, in the first and in the second year. Pharmaceuticals were the key cost driver (ibrutinib accounted for more than 77%). CONCLUSIONS: This analysis on Italian administrative data provided results about prescription patterns of ibrutinib FL and SLL new users with CLL, focusing on discontinuation, treatment change and healthcare costs over 2-year follow-up, and contributed to improve the knowledge on this hard-to-treat disease.

[Real-world analysis of obstructive respiratory tract disorders: characterization, health care and costs.] / Analisi real-world dei disturbi ostruttivi delle vie respiratorie: caratterizzazione, assistenza sanitaria e costi.

INTRODUCTION: This analysis has described the burden of patients with asthma, chronic obstructive pulmonary disease (COPD), asthma/COPD mixed conditions or undefined obstructive diseases (UODs), from the Italian National Health System point of view. METHODS: In the accrual period (2015), starting from the ReS database, a record linkage among demographic, pharmaceuticals, hospitalizations and outpatient specialist services databases has identified patients affected by only asthma, only COPD, asthma/COPD and UODs. From the less recent date of identification, each patient was analyzed in one previous year and in two years of follow-up (at most up to 12/31/2017). In the accrual period, in the previous one and in 2-year follow-up sinus polyps was researched. One-year free filled respiratory (ATC code R03) and concomitant prescriptions, outpatient specialist services, hospitalizations were described. Two-year costs were assessed annually. RESULTS: In 2015, 110,453 subjects with asthma (16.6 x1000 ≥12 years old), 229,747 with COPD, 8828 with asthma/COPD (55.5 x1000 and 2.1 x1000 ≥40 years, respectively) and 75,072 with UODs (27.2 x1000 subjects aged 40 to 65) were selected. Sinus polyps was found in 753 patients with asthma, 181 with COPD and 122 with asthma/COPD. A very high use of inhaled corticosteroids - ICS (R03AB) as monotherapy and as fixed association ICS/LABA and of cardiovascular drugs was highlighted among patients with COPD and asthma/COPD. The spirometry test was used in 21.4% patients with asthma/COPD, in 9.2% with asthma, in 8.6% with COPD and in 5.8% with UODs. Subjects with COPD and asthma/COPD were the most frequently hospitalized, mainly due to respiratory and cardiovascular causes, and those with the longest in-hospital stay. On average, the mean overall one-year expenditure per COPD or asthma/COPD patient was three times higher than per asthma or UOD one (€3508/€3613 vs €942/€1394, respectively). CONCLUSIONS: Concomitant drugs and hospitalizations due to other causes than respiratory ones accounted for the highest expenses. In general, comorbidities and cardiopulmonary complications played a key role in obstructive airway disease managing and controlling, by determining unsustainable socio-economic impacts.

ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation: the (ORIGAMI) study.

AIMS: The ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation (ORIGAMI) study investigates the safety and efficacy of Edoxaban administered via PEG in patients with atrial fibrillation and a clinical indication for a long-term anticoagulation. DESIGN: In this prospective, single-centre observational study, 12 PEG-treated patients with indication to anticoagulation will receive edoxaban via PEG and will be followed up to 6 months. Plasma antifactor Xa activity and edoxaban concentrations will be assessed. Thromboembolic (ischaemic stroke, systemic embolism, venous thromboembolism) and bleeding events (Bleeding Academic Research Consortium and Thrombolysis in Myocardial Infarction) will be recorded at 1 and 6 months. PRELIMINARY RESULTS: A retrospective analysis of five atrial fibrillation cases undergoing PEG implantation at our Institution who received edoxaban via PEG showed plasma anti-FXa levels at a steady state of 146 ±â€Š15 ng/ml, without major adverse event at a mean follow-up of 6 months. CONCLUSION: ORIGAMI prospectively investigates PEG-administration of edoxaban in PEG-treated patients requiring long-term anticoagulation. Our preliminary retrospective data support this route of DOAC administration. CLINICALTRIALSGOV IDENTIFIER: NCT04271293.

HR+/HER2- Metastatic Breast Cancer: Epidemiology, Prescription Patterns, Healthcare Resource Utilisation and Costs from a Large Italian Real-World Database.

BACKGROUND AND OBJECTIVE: Breast cancer is the second leading cause of cancer death worldwide. The economic burden of breast cancer is crucial for the sustainability of healthcare systems. The objective of this study was to estimate the burden of HR+/HER2- metastatic breast cancer (MBC) in Italy, in terms of incidence, prescription patterns, healthcare resource utilisation and costs for the National Health System (NHS). METHODS: A cohort study based on healthcare administrative data (ReS database), covering > 10 million Italians, was performed. Incident cases of HR+/HER2- MBC were identified among adult women in 2013. The cohort was followed-up for 2 years to describe healthcare utilisation and integrated costs (pharmaceuticals, hospitalisations and outpatient services) for NHS. Prescription patterns were described as first-line choice and therapeutic changes. Specific therapeutic changes were used as proxies of disease progression. A survival analysis was performed to estimate the time from diagnosis to first disease progression. RESULTS: Of 5174,723 women, 355 cases of de novo HR+/HER2- MBC were selected (incidence: 6.9 per 100,000). During the 1st follow-up year, they generated an average cost of €7543, whereas €4834 in the 2nd year. The 85.9% received a monotherapy, while the 14.1% received a combination therapy. The most used monotherapy was nonsteroidal-aromatase-inhibitors (45.9%), while the most prescribed combination was tamoxifen + luteinizing hormone releasing hormone (LHRH) analogues (6.2%). Therapeutic changes occurred in 45.4% of patients, especially from chemotherapy to nonsteroidal-aromatase-inhibitors, after an average of 276.8 days from the first treatment. Disease progression was identified in 22.5% of patients occurring after a mean 13 ± 6 months from diagnosis. CONCLUSIONS: This detailed picture of HR+/HER2- MBC, based on real-world data, could be helpful in health technology assessment and expenditure forecasts of future therapeutic strategies for this condition in Italy.

[Facts and figures of clinical pathways in Italy: results from the PDTA Net project.] / I numeri dei percorsi diagnostico-terapeutici assistenziali (PDTA) in Italia: risultati dal progetto PDTA Net.

The approval of clinical pathways (CPWs) represents a key step to focus the care management on the patient. The PDTA Net project, by ReS Foundation and CINECA, aims to create a reference tool to study how the local organizational models influence healthcare and clinical outcomes. The article shows the analysis of all CPWs approved by Italian Regions and Autonomous Provinces until 31/12/2018. The search for documents was performed on the institutional websites through specific keywords. CPWs were filled into a database, according to the Region, publication year, disease of interest (distinguishing between chronic diseases with high epidemiological impact and rare diseases) and relevant clinical area. All documents were analyzed by geographical and temporal distribution, the latter also according to ministerial measures. From 2005 to 2018, 536 Regional CPWs were approved (316 for chronic diseases with a high epidemiological impact and 220 for rare diseases). The Regions with the highest number of CPWs of chronic diseases were Umbria (34 CPWs) and Piemonte (33). The most addressed clinical areas were: oncology (72), neurology (60), cardiology (34) and metabolic disorders (22). The most issued diseases were: diabetes (17), trauma/polytrauma (15), chronic obstructive pulmonary disease and multiple sclerosis (12 each), stroke (11), rheumatoid arthritis, breast cancer and colorectal neoplasms (10 each). The publication of the documents was affected by ministerial measures (Balduzzi Law, National Chronicity Plan, Diabetic Disease Plan and National Dementia Plan). The majority of CPWs on rare diseases was retrieved in Regions with activated Rare Disease Networks: Lombardia (110 CPWs), Lazio (64) and Toscana (17). This study showed that, to date, in Italy there are several CPWs published at Regional level, nevertheless their structure and application are heterogeneous and strongly influenced by the National Plans. All analyzed documents are available through the web platform of the project https://fondazioneres.it/pdta/. This project could be useful for health system stakeholders, in order to encourage the transition to new health governance and making CPWs effective governance tools.

The Burden of Chronic Heart Failure in Primary Care in Italy.

INTRODUCTION: Chronic heart failure (CHF) is a major public health concern. From a public health perspective, the epidemiology of CHF needs to be distinguished from that of its related acute form. Data stemming from primary care are crucial to better know and update the prevalence and incidence rates of CHF. AIM: To update the epidemiology of CHF in an Italian primary care setting and to describe socio-demographic, lifestyle, and clinical characteristics of these patients. METHODS: A population-based study was conducted among 800 Italian general practitioners collecting data in a dedicated database. Information was extracted from adult subjects with a diagnosis of CHF from 2002 to 2013, and the prevalence and incidence rate of CHF were calculated. The study population was described in terms of socio-demographic, lifestyle, and clinical characteristics. RESULTS: A total of 13,633 patients with CHF were identified. Overall, the prevalence of CHF was 1.25% (95% CI 1.23-1.27), and the incidence rate was 1.99 per 1000 person-years (95% CI 1.81-2.08). In this population, smoking, alcohol use, and obesity were present in 2.93, 0.45, and 10.80% of cases, respectively. Hypertension (58.40%), chronic kidney disease (51.36%), dyslipidaemia (44.62%), ischaemic heart disease (25.75%), and atrial fibrillation (25.32%) were the most represented comorbidities. CONCLUSION: This study provides an updated epidemiological scenario of CHF in a primary care setting in Italy. These data may be useful to weight the social and economic impact of CHF and to plan strategies for improving the clinical care of CHF in general practice.

Clinically important drug-drug interactions in poly-treated elderly outpatients: a campaign to improve appropriateness in general practice.

AIMS: The aim was to assess the impact of a campaign for general practitioners (GPs) to reduce clinically-important drug-drug interactions (DDIs) in poly-treated elderly patients. METHODS: We compiled a list of 53 DDIs and analyzed reimbursed prescriptions dispensed to poly-treated (≥four drugs) elderly (>65 years) patients in the Emilia Romagna region during January 2011-June 2011 (first pre-intervention period), January 2012-June 2012 (second pre-intervention period) and January 2013-June 2013 (post-intervention period). Educational initiatives to GPs were completed in July 2012-December 2012. Pre-test/post-test analysis (2013 vs. 2012) was performed, also using predicted 2013 data (P < 0.01 for statistical significance). RESULTS: Despite the slight increase in poly-therapy rate (16% in 2013, +1.5% from 2011), we found a stable or slightly declining number of potential DDIs for each elderly poly-treated patient (~1.5). In 2013, 11 DDIs exceeded 5% of prevalence rate: antidiabetics-ß-adrenoceptor blockers ranked first (20.3%), followed by ACE Inhibitors (ACEIs)/sartans-non steroidal anti-inflammatory drugs (NSAIDs) (16.4%), diuretics-NSAIDs (13.6%), selective serotonin re-uptake inhibitors (SSRIs)-NSAIDs/acetyl salicylic acid (ASA) (12.7%) and corticosteroids-NSAIDs/ASA (9.7%). A remarkable reduction emerged for NSAID-related DDIs (diuretics-NSAIDs peaked -14.5%; P < 0.01), whereas prevalence of antidiabetics-ß-adrenoceptor blockers increased (+7.9%; P < 0.01). When using predicted values, the statistical significance disappeared for antidiabetics-ß-adrenoceptor blockers (+1.3%; P = 0.04), whereas it persisted for almost all NSAIDs-related DDIs: ACEIs/sartans-NSAIDs (-3.0%), diuretics-NSAIDs (-6.0%), SSRIs-NSAIDs/ASA (-5.9%). CONCLUSIONS: This campaign contained the burden of DDIs in poly-treated elderly patients by 1) reducing most prevalent DDIs, especially NSAIDs-related DDIs and 2) balancing the observed rise in poly-therapy rate with stable rate in overall prescriptions of potentially interacting drugs per patient.

Social and clinical descriptors of antipsychotic prescription.

OBJECTIVE: To identify descriptors of Antipsychotic (AP) prescription, focusing on second generation antipsychotics (SGAs), polypharmacy, and long-acting injections (LAIs). METHODS: Outpatients of the Bologna-Community-Mental-Health-Centres with at least one AP prescription were selected. Patients' characteristics, service utilization, and AP prescriptions were collected from administrative databases. Prescriptions were grouped by class (SGA vs. First Generation Antipsychotics), drug combination (polypharmacy vs. monotherapy), and preparation (LAIs vs. regular administration). Multi-variate analyses were performed to identify prescription descriptors among socio-demographic and clinical variables. RESULTS: Among 6,074 patients and 41,121 AP prescriptions, SGAs were used in 70.7% of subjects, AP polypharmacy in 25.3%, and LAIs in 17.5%. SGAs were prescribed more often for young, Italian patients, with higher education, voluntary hospitalization, and high number of visits. Descriptors of AP polypharmacy were: high number of visits and hospitalization, length of treatment, non-urban residency, male gender, unemployment. Characteristics associated to LAI prescription were: long duration of treatment, high number of visits, compulsory admissions, non-Italian nationality, male gender, age > 34, low education, unmarried status. CONCLUSIONS: Besides illness severity, this study identified different socio-demographic descriptors of AP choices, raising concerns on the equity of treatments. Efforts should be directed to investigate appropriateness of AP treatments especially in social disadvantaged populations.