Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients.

Aim: We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. Methods and Results: We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Conclusions: Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks.

Changes in first-line injectable disease-modifying therapy for multiple sclerosis: predictors of non-adherence, switching, discontinuation, and interruption of drugs.

This study was aimed to describe changes of Disease-Modifying Treatments (DMT) in an Italian cohort of patients with multiple sclerosis (MS) and to identify predictors of therapeutic modifications. Patients with MS and treated with the first-line injectable DMT (interferons-IFNs or glatiramer) between 1/7/2009 and 31/10/2012 were selected from administrative databases of the MS Center of Cagliari (Sardinia, Italy). Socio-demographic, therapeutic, and clinical information was collected in the 6 months preceding the index date. All patients were followed for 36 months to evaluate therapeutic changes in terms of non-adherence, switch, temporary discontinuation, and permanent interruption. Predictors of changes were estimated by multivariable regression models. Data on 1698 patients were collected: glatiramer was prescribed in 27% of cases, IFNß-1b in 22%, IFNß-1a-im in 20%, IFNß-1a-sc-44mcg in 19%, and IFNß-1a-sc-22mcg in 12%. Non-adherence was observed in 25% of cases, therapeutic switch in 30%, discontinuation in 37%, and permanent interruption in 28%. The risk of non-adherence was higher for IFNß-1b, compared with IFNß-1a-im (adjOR = 1.73). Therapeutic switch occurred especially in patients recently diagnosed (each year from diagnosis causes a decrease of this risk adjHR = 0.97); the risk of discontinuation was higher with EDSS = 4-6 and 7-9 (adjHR = 1.52 and 4.42, respectively). The risk of permanent interruption increased with the augmentation of disability (adjHR = 1.67 and 5.43 for EDSS 4-6 and 7-9). This study mirrored a detailed framework of DMT prescription and identified factors related to changes in the MS therapy. These findings could support healthcare providers in the evaluation and maximization of benefits associated with a long-term DMT.

Prescribing pattern and resource utilization of monoamine oxidase-B inhibitors in Parkinson treatment: comparison between rasagiline and selegiline.

Difference between selegiline and rasagiline for effectiveness in Parkinson's disease (PD) is uncertain, nevertheless their costs highly differ: rasagiline is more expensive than selegiline. This study was aimed to compare prescribing pattern and resource utilization in PD patients treated with rasagiline or selegiline. Historic cohort study, based on databases of three Italian Local Health Authorities was performed. Patients with PD and receiving rasagiline or selegiline between 01-07-2009 and 31-12-2011 were selected and followed-up for 12 months. As outcomes, and relevant costs, were evaluated: (a) anti-parkinson prescriptions; (b) hospitalization for PD and for fracture; (c) antiinflammatory and antirheumatic prescriptions; (d) antipsychotic prescriptions; (e) hospitalization for cardiovascular diseases; (f) cardiovascular prescriptions; (g) ambulatory visits or diagnostic tests. Average annual cost per patient was considered for both PD-related expenditure (a + b + c) and overall cost (a + b + c + d + e + f + g). Differences between rasagiline and selegiline were analysed by generalized linear model. Overall 1607 patients were selected: 63.7 % under selegiline and 36.2 % under rasagiline. Hospitalizations for PD occurred more in rasagiline group than in selegiline one (13.6 vs. 8.0 %, p < 0.001), whereas hospitalizations for fractures less in rasagiline group than in selegiline one (1.4 vs. 3.8 %, p = 0.005). Dopamine agonists (66.0 vs. 31.0 %, p < 0.001) and levodopa (73.9 vs. 49.0 %, p < 0.001) were prescribed more frequently in rasagiline group than in selegiline one. The choice to prescribe rasagiline produced a statistically significant increase in both overall cost (+2404 €, p < 0.001) and PD-related cost (+2363 €, p < 0.001). In conclusion, prescribing patterns and health resource utilization highly differ between rasagiline and selegiline. There is no homogeneous prescription behaviour among clinicians in preferring one or the other MOAB-I, on the basis of demographic, clinical and therapeutic characteristics of patients with PD.

Pharmaco-utilisation and related costs of drugs used to treat schizophrenia and bipolar disorder in Italy: the IBIS study.

BACKGROUND: Schizophrenia and bipolar disorder (BD) are psychiatric diseases that are commonly managed with antipsychotics. Treatment pathways are highly variable and no universal treatment guidelines are available. The primary objective of the Italian Burden of Illness in Schizophrenia and BD (IBIS) study was to describe pharmaco-utilisation of antipsychotic treatments and characteristics of patients affected by schizophrenia or BD. A secondary objective was to describe costs of illness for patients with schizophrenia or BD. METHODS: IBIS was a multicentre, real-world, retrospective, observational cohort study based on data obtained from administrative databases of 16 Local Health Units in Italy (~7.5 million individuals). Patients with schizophrenia or BD ≥18 years of age treated with antipsychotics between 1 January 2008 and 31 December 2009 were included in the primary analysis. Pharmaco-utilisation data were gathered over a follow-up period of 12 months. RESULTS: Patients with schizophrenia and BD received a wide variety of antipsychotic medications. The proportion of patients on antipsychotic monotherapy was 68% in patients with schizophrenia and 70% in patients with BD. In patients with schizophrenia, ~1/3 of patients receiving antipsychotic monotherapy also received mood stabilisers and/or antidepressants (34.7%) compared with over half of those on antipsychotic polytherapy (52.2%). In patients with BD, use of mood stabilisers and/or antidepressants was even higher; 76.9% of patients receiving antipsychotic monotherapy also received mood stabilisers and/or antidepressants compared with 85.5% of patients on antipsychotic polytherapy. Switch therapy was more frequent in patients with BD than in patients with schizophrenia, whereas add-on therapy was more frequent in patients with schizophrenia than in patients with BD. The mean total disease-related cost per patient per annum was higher in patients with schizophrenia (€4,157) than in patients with BD (€3,301). The number and cost of hospitalisations was higher in patients with BD, whereas the number and cost of nursing home stays was higher in patients with schizophrenia. CONCLUSION: Use of administrative databases has permitted retrieval of comprehensive information about therapeutic pathways, diagnostic history and costs in patients affected by schizophrenia or BD. A need for personalised treatment pathways has been described. TRIAL REGISTRATION: clinicaltrials.gov: NCT01392482 ; first received June 29, 2011.

Estimation of patients affected by inflammatory bowel disease potentially eligible for biological treatment in a real-world setting.

BACKGROUND/AIMS: This analysis estimated the number of inflammatory bowel disease (IBD) patients presenting criteria of eligibility for biological therapies in an Italian real-world setting. METHODS: An observational analysis was performed on administrative databases of a sample of Local Health Units, covering 11.3% of the national population. Adult IBD patients (CD or UC) from 2010 to the end of data availability were included. Eligibility criteria for biologics were the following: Criterion A, steroid-refractory active disease; Criterion B, steroid-dependent patients; Criterion C, intolerance or contraindication to conventional therapies; Criterion D, severe relapsing disease; Criterion E (CD only), highly active CD disease and poor prognosis. RESULTS: Of 26,781 IBD patient identified, 18,264 (68.2%) were treated: 3,125 (11.7%) with biologics and 15,139 (56.5%) non-biotreated. Among non-biotreated, 7,651 (28.6%) met at least one eligibility criterion for biologics, with criterion B (steroid-dependence) and criterion D (relapse) as the most represented (58-27% and 56-76%, respectively). Data reportioned to the Italian population estimated 67,635 patients as potentially eligible for biologics. CONCLUSIONS: This real-world analysis showed a trend towards undertreatment with biologics in IBD patients with 28.6% being potentially eligible, suggesting that an unmet medical need still exists among the Italian general clinical practice for IBD management.

Surgical Treatment of Active Endocarditis Pre- and Post-COVID-19 Pandemic Onset.

BACKGROUND: Despite advanced diagnosis and treatment, infective endocarditis (IE) is a potentially life-threatening condition. The impact of COVID-19 on the diagnosis and outcome of the surgical treatment of IE is uncertain. The aim of this study was to analyze the incidence, characteristics, and outcomes of surgically treated IE before and after the COVID-19 pandemic. METHODS: This study retrospectively analyzed the data of 535 patients who underwent valve surgical procedures for IE between January 2010 and December 2022 in a single cardiac surgery center. Patients were divided into two groups depending on the date of their operation: before (n = 393) and after (n = 142) COVID-19 onset. In order to balance the groups, inverse probability of treatment weighting (IPTW) calculated from the propensity score (PS) was applied. Weighted univariate logistic regressions were reported for outcomes; weights were derived from IPTW. Interrupted time series analysis (ITSA) according to Linden's method was used to evaluate the changes in the manifestation of IE after 11 March 2020. RESULTS: Patients from the post-COVID-19 cohort (after 11 March 2020) had a greater number of comorbidities such as diabetes (29.6% vs. 16.3% p = 0.001), hypertension (71.1% vs. 59.5% p = 0.015), and preoperative kidney injury requiring dialysis (9.2% vs. 2.5% p = 0.002), but the median additive and logistic EuroSCORE were not statistically different. In the post-COVID-19 group, we observed a greater prevalence of Staphylococcus aureus-related endocarditis (24.5% vs. 15.4% p = 0.026), a consequent reduction in Staphylococcus non aureus-related endocarditis (12.2% vs. 20.1% p = 0.048), and a decrease in aortic valve replacements (43.0% vs. 53.9%), while the number of mitral valve replacements and repair was greater (21.1% vs. 15.0% and 6.3% vs. 4.3%, respectively). No differences were found in the two groups concerning early death, death, or relapse at 1 year after surgery. Data obtained by multivariable analysis identified preoperative renal dysfunction requiring dialysis as the only common risk factor for early mortality via stratifying by time periods in analysis. CONCLUSIONS: The incidence of surgically treated IE significantly increases after the COVID-19 pandemic with a higher incidence of mitral valve involvement with respect to the aortic valve. Although a delay in surgical timing occurred during the COVID-19 pandemic, data in terms of mortality and outcomes were largely unaffected.

Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis.

BACKGROUND: The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. METHODS: For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. FINDINGS: 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. INTERPRETATION: In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. FUNDING: The Cardiovascular Research Foundation.

How many hypertensive patients can be controlled in "real life": an improvement strategy in primary care.

BACKGROUND: It is well known that hypertension control is non-satisfactory, but it is not clear how many hypertensive patients can be controlled in real life. We addressed this question implementing a simple, multifaceted improvement strategy in family practice. METHODS: Eighteen General Practitioner (GPs) agreed upon a simple improvement strategy including: 1) the use of occasional direct/indirect contacts (prescription refilling) to decrease missing blood pressure (BP) recording, and to increase therapeutic adherence, 2) the use of home BP measurements in non-controlled patients, 3) the addition of a new drug in non-controlled, but adequately adherent patients. Results were assessed after one year by automatic data extraction from the clinical records of all hypertensive subjects. RESULTS: The patients with a diagnosis of hypertension increased from 6.309 (age 58.5 +/- 12.4; M 45.5%) to 6.717 (age 58.6 +/- 12.9; M 45.7%): prevalence 25.3% to 27.0%. The BP recording increased: 4,305 patients (68.2%) vs 4,948 patients (78.4%) (+ 10.2%, ci 9.4%-10.9%; p < 0.001), as well as the BP control: 3,203 (50.8% of all the diagnosed hypertensive patients and 74.4% of the subjects with recorded BP value) vs 4,043 (64.1% of all the diagnosed hypertensive patients and 81.7% of the subjects with recorded BP value) (+ 13.3%, ci 12.5%-14.2%; p < 0.001 and + 7.3%, ci 6.7%-8.0%; p < 0.001). CONCLUSIONS: Almost 82% of hypertensive subjects who contact their doctors can be easily controlled. Most non-controlled patients simply don't see their GPs; in almost all the remaining non-controlled patients GPs fail to increase drug therapy. A further improvement is therefore possible.

[The therapeutic management and economic burden of patients with chronic kidney disease non-dialysis-dependent with anemia and ESA treated: findings from a real-world study in Italy].

Background. This real-world study aimed to provide insights on the characteristics, drug utilization, and economic burden of chronic kidney disease non-dialysis-dependent (NDD-CKD) patients with anemia prescribed Erythropoiesis Stimulating Agents (ESA) in Italian clinical practice settings. Methods. A retrospective analysis was performed based on administrative and laboratory databases covering around 1.5 million subjects across Italy. Adult patients with a record for NDD-CKD stage 3a-5 and anemia during 2014-2016 were identified. Eligibility to ESA was defined as the presence of ≥ 2 records of Hb < 11 g/dL over 6 months, and patients eligible and currently treated with ESA were included. Results. Overall, 101,143 NDD-CKD patients were screened for inclusion, of which 40,020 were anemic. A total of 25,360 anemic patients were eligible to ESA treatment and 3,238 (12.8%) were prescribed ESA and included. The mean age was 76.9 years and 51.1% was male. More frequently observed comorbidities were hypertension (over 90% in each stage), followed by diabetes (37.8-43.2%) and cardiovascular condition (20.5-28.9%). Adherence to ESA was observed in 47.9% of patients, with a downward trend while progressing across stages (from 65.8% stage 3a to 35% stage 5). A consistent proportion of patients did not have nephrology visits during the 2 years of follow-up. Costs were mainly due to all drugs (€4,391) followed by all-cause hospitalization (€3,591) and laboratory tests (€1,460). Conclusions. Findings from the study highlight an under-use of ESA in the management of anemia in NDD-CKD as well as a sub-optimal adherence to ESA and showed a great economic burden for anemic NDD-CKD patients.

Incidence and Predictors of Switching and Dose Change of Direct Oral Anticoagulants among Elderly Patients with Nonvalvular Atrial Fibrillation: A 5-Year Analysis of a Large Administrative Database.

In the last decade, novel oral anticoagulants (NOACs) have emerged as prominent therapeutic options in non-valvular atrial fibrillation (NVAF). We analysed the clinical burden and the switching rate between all available NOACs, and their dosage change over a period of 5 years in a representative population of patients with NVAF aged between 70 and 75 years. Methods and Results: This is a retrospective observational study on administrative databases, covering approximately 6.2 million health-assisted individuals by the Italian National Health System (around 11% of the entire Italian residents). Out of 4640 NVAF patients treated with NOACs and aged 70-75 years in 2017, 3772 (81.3%) patients were still in treatment with NOAC up to 2021 and among them, 3389 (73.0%) patients remained in treatment with the same NOAC during 2017-2021. In fact, 10.2% of patients switched NOAC type and 10.3% changed the dose of the same NOAC. Overall, after switching, the dabigatran and rivaroxaban groups lost, respectively, 13.5% and 2.8% of patients, while apixaban and edoxaban resulted in a relative percentage increase of 6.8% and 44.6% of patients, respectively. By a logistic regression analysis, the treatment with rivaroxaban, apixaban, and edoxaban (respect to dabigatran) was associated with a significant risk reduction of switch of 57%, 68%, and 44%, respectively. On the other hand, several features of high risk were associated with dose reduction. Conclusions. In our 5-year analysis of a large administrative database, a switching among NOACs or a change in NOAC dosages occurred in around 20% of elderly patients with NVAF. The type of NOAC was associated with a high switching rate, while several characteristics of high risk resulted as predictors of dose reduction of NOACs. Moreover, a worsening trend of clinical conditions occurred in patients maintaining the same NOAC treatment across 2017-2021.

Description of characteristics, management of care and healthcare direct costs of patients with HR+/HER2- early breast cancer in Italy: a real-world study involving administrative and pathological anatomy databases.

BACKGROUND: Healthcare administrative and pathological anatomy data were used to identify Italian patients with early breast cancer (EBC) with HR+/HER2- status at high risk of recurrence, evaluating drug utilization and other healthcare resource use in clinical practice. METHODS: This retrospective analysis, based on 9.4 million of Italian National Health Service beneficiaries, included adult patients with hospitalization discharge diagnosis for EBC in 01/2015-12/2020. Those with HR+/HER2- status were selected; among them, patients that underwent removal of lymph nodes (LN) were analyzed. RESULTS: Of 24,137 patients with EBC and HR+/HER2- status, 3619 patients (15%) had documented LN removal. Overall, 4.7% of HR+/HER2- patients and 9.9% of patients with LN removal experienced distant relapse over a median follow-up of 33.2 months (Q1-Q3: 17.0-50.6). Local relapse occurred in approximately 9.1-9.3% of patients in each group. Among the 1,175 patients with LN removal that had available pathological anatomy data, 399 (34.0%) had pathological high-risk characteristics and 13.3% experienced distant relapse. CONCLUSIONS: One in ten patients with EBC who underwent LN removal experienced a relapse, highlighting the strong need to prevent early recurrence.

Analysis of Drug Utilization in Patients with Psoriasis: A Real-World Retrospective Study Among the Italian Population.

Purpose: An Italian real-world retrospective study was conducted in patients with psoriasis (PSO) to evaluate their characteristics, treatment patterns, and biological/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) drug utilization. Patients and Methods: The retrospective analysis was carried out on real-world data collected from administrative databases of selected Italian health-departments; the dataset covered approximately 22% of the Italian population. PSO patients (identified by PSO hospitalization, and/or active exemption code and/or a topical anti-psoriatic medication prescription) were included. In prevalent patients identified during 2017-2018-2019-2020, baseline characteristics and treatment patterns were investigated. Moreover, b/tsDMARD drug utilization (focusing on persistence, monthly dosage, and mean duration between prescriptions) was evaluated in bionaïve patients included during 2015 and 2018. Results: PSO was diagnosed in 241,552 (in 2017), 269,856 (in 2018), 293,905 (in 2019) and 301,639 (in 2020) patients. At the index date, almost 50% of patients had not received systemic medications, and 2% had received biological treatment. Among the b/tsDMARD-treated patients, a decrease in the use of tumour necrosis factor (TNF) inhibitors (60.0-36.4%, from 2017 to 2020) and an increase in the use of interleukin (IL) inhibitors (36.3-50.6%, from 2017 to 2020) were observed. In 2018, the persistence rates of TNF inhibitors and IL inhibitors in bionaïve patients ranged from 60.8-79.7% and 83.3-87.9%, respectively. Conclusion: This real-world study of PSO drug utilization in Italy showed that a significant number of patients were not treated with systemic medications and only 2% of patients were treated with biologics. An increase in the use of IL inhibitors and a decrease in the prescription of TNF inhibitors over years were found. Patients treated with biologics were highly persistent with treatment. These data provide insight into routine clinical practice for PSO patients in Italy, suggesting that the optimization of treatment for PSO still represents an unmet medical need.

Real-world analysis of the economic and therapeutic burden in advanced breast cancer patients in Italy.

BACKGROUND: This real-world analysis evaluated drug utilization focusing on wastage and healthcare costs for treatment of patients with advanced breast cancer (aBC) hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) in Italy. METHODS: A retrospective analysis was conducted on administrative data covering about 13.3 million health-assisted individuals. Across January/2017-June/2021, all patients with HR+/HER2-aBC were identified by ≥ 1 prescription for cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). Cost analysis was performed and updated referring to the prices of November 2021. RESULTS: Overall, 3,647 HR+/HER2-aBC patients were included (2,627 palbociclib treated, 729 ribociclib treated, and 291 abemaciclib treated). After 12 months of follow-up, 35% of palbociclib patients had a dose reduction (on average 8.9 wasted pills/patient), 44.7% of abemaciclib patients had a dose reduction (on average 6.7 wasted pills/patient), 22.1% of ribociclib patients had a dose reduction (no wasted pills). Therapy wastage added up to 528,716€ for palbociclib-treated patients (524€/patient) and 5,738€ in abemaciclib-treated patients (151€/patient). No wastage was attributed to ribociclib. CONCLUSIONS: Dose reduction was associated with drug wastage in palbociclib and abemaciclib-treated patients, but not in ribociclib-treated ones. These findings might be helpful to policy decision-makers who, for healthcare strategies implementation, among several variables should consider the possible restraining of drug wastage.

Real-World Evaluation of the Management, Treatment Pathways and Outcome of Melanoma Patients with Target Therapies in Italy.

INTRODUCTION: In recent years, an increasing trend in the incidence of melanoma has been observed in Europe. Although early diagnosis and prompt intervention with local resection often results in positive outcomes, conversely, metastatic disease is still clinically challenging with a poor prognosis and a 5-year survival of around 30%. The growing awareness of melanoma biology and of antitumor immune responses has allowed the development of novel therapies targeted at specific molecular alterations occurring at advanced stages. This real-world analysis examined patients with melanoma in Italy, focusing on treatment patterns, outcome, time to discontinuation (TTD), and resource consumption. METHODS: Two retrospective observational analyses were conducted for BRAF+ patients with metastatic melanoma and those with a positive sentinel lymph node biopsy in an adjuvant setting, retrieving data from the administrative databases covering 13.3 million residents. The cohort melanoma BRAF+ in metastatic setting comprised 729 patients with targeted therapy (TT) (n = 671 with TT as first line and 79 as second line). RESULTS: Median TTD was 10.6 months in first line and 8.1 months in second line. Median overall survival from the start of first TT line was 27 months and was 11.8 months for patients with brain metastasis. In the dabrafenib plus trametinib patients, main healthcare resource consumption tended to increase in the presence of brain metastasis. The cohort with a positive sentinel lymph node biopsy under adjuvant therapy (n = 289) included 8% patients treated with dabrafenib plus trametinib or tested BRAF+, 5% BRAF wild-type, and 10% under immunotherapy. CONCLUSION: Our findings provided an overview on TT utilization on metastatic melanoma patients in real clinical practice and highlighted an increased burden in brain metastatic patients.

Epidemiology, Patients' Journey and Healthcare Costs in Early-Stage Non-Small-Cell Lung Carcinoma: A Real-World Evidence Analysis in Italy.

This real-world analysis aims to estimate the epidemiology and economic burden related to early-stage non-small-cell lung carcinoma (eNSCLC) in the clinical practice Italian setting. An observational analysis was performed using administrative databases linked to pathological anatomy data, covering around 2.5 mln health-assisted individuals. From 2015 to mid-2021, eNSCLC patients staged II-IIIA treated with chemotherapy after surgery were included. Patients were stratified into those presenting loco-regional or metastatic recurrence during follow-up and annualized healthcare direct costs covered by the Italian National Health System (INHS) were estimated. In 2019-2020, the prevalence of eNSCLC was 104.3-117.1/million health-assisted subjects, and the annual incidence was 38.6-30.3/million. Data projected to the Italian population estimated 6206 (2019) and 6967 (2020) prevalent and 2297 (2019) and 1803 (2020) incident cases. Overall, 458 eNSCLC patients were included. Of them, 52.4% of patients had a recurrence (5% loco-regional-recurrence, 47.4% metastatic-recurrence). Healthcare total direct costs/patient averaged EUR 23,607, in particular, in the first year after recurrence, costs averaged EUR 22,493 and EUR 29,337 in loco-regional and metastatic-recurrence patients, respectively. This analysis showed that about one-half of eNSCLC patients stage II-IIIA experience a recurrence, and in recurrence patients, total direct costs were almost two-fold those of no-recurrence patients. These data highlighted an unmet clinical need, as the therapeutic optimization of patients at early stages.

A retrospective analysis of treatment patterns, drug discontinuation and healthcare costs in Crohn's disease patients treated with biologics.

BACKGROUND/AIMS: This real-world analysis evaluated the persistence and direct healthcare costs of Crohn's Disease (CD) patients treated with biologics in Italy. METHODS: A retrospective analysis on administrative databases of Italian healthcare entities, covering 10.4 million residents, was performed. Adult CD patients under biologics between 2015 and 2020 were included and attributed to first/second treatment line based on absence/presence of biologic prescriptions 5-years before index-date (first biologic prescription). RESULTS: Of 16,374 CD patients identified, 1,398 (8.5%) were biologic-treated: 1,256 (89.8%) in first line and 135 (9.7%) in second line. Kaplan-Meier curves estimated a higher persistence for ustekinumab-treated patients followed by vedolizumab, infliximab and adalimumab, in both lines. Considering baseline variables and adalimumab as reference, infliximab in first line (HR: 0.537) and ustekinumab in first (HR: 0.057) and second line (HR: 0.213) were associated with significantly reduced risk of drug-discontinuation. First line total/average healthcare direct-costs were €13,637, €11,201, €17,104 and €18,340 in patients persistent on adalimumab, infliximab, ustekinumab and vedolizumab, respectively. CONCLUSIONS: This real-world analysis showed differences in persistence over 12-months between biologic treatments, being higher in ustekinumab-treated group, followed by vedolizumab, infliximab and adalimumab. Patients' management was associated with comparable direct healthcare costs among treatment lines, mainly driven by drug-related expenses.

Less Is More? Combined Approaches to Improve Mortality and Morbidity after Aortic Valve Replacement.

BACKGROUND: Nowadays, one of the main goals of aortic valve surgery is to reduce the biological impact, mortality, and complications. It is well-known that long operative times in terms of the extracorporeal circulation, but above all, of the aortic cross-clamp time (ACC), represent a risk factor for mortality in patients undergoing cardiac surgery. In order to shorten the aortic cross-clamp time, many technological improvements, such as sutureless prostheses, have been introduced, but their actual effectiveness has not been proven yet. The aim of this study was to assess the 30-day outcomes of patients undergoing aortic valve replacement surgery, focusing on the ACC length. METHODS: All 3139 patients undergoing aortic valve replacement between January 2013 and July 2022 at our institution were enrolled. The data were retrospectively collected and the baseline characteristics and intraoperative variables were recorded. In order to adjust the results according to the differences in the baseline characteristics, propensity score matching was performed and four groups of 351 patients were obtained based on the first, second, third, and fourth quartile of the ACC time. RESULTS: The patient population included 132 redo surgeries (9.4%) and 61 cases of active endocarditis (4.3%), with an overall median EuroSCORE II of 1.8 (IQR 1.2-3.1). An increase across the groups was observed in terms of the acute kidney failure (p < 0.001) incidence, the number of blood transfusions (p = 0.022), prolonged hospital stays (p < 0.001), the and respiratory failure (p < 0.001) incidence. A p of < 0.1 was found for the 30-day mortality (p = 0.079). The predictors of an early 30-day mortality were standard full sternotomy (OR 2.48, 95% CI 1.14-5.40, p = 0.022), EuroSCORE II (OR 1.10, 95% CI 1.05-1.16, p < 0.001), and a trend for a longer ACC time (Q4 vs. Q1: OR 2.62, 95% CI 0.89-7.68, p = 0.080). CONCLUSIONS: Shortening the operative times resulted in marked improvements of the patients' outcomes. The combined use of minimally invasive approaches and sutureless aortic valve prostheses allows for a lower 30-day events rate. New technologies should be assessed to obtain the best results with the least risk.

Estimation of patients with psoriasis potentially eligible and currently untreated with biological drugs in Italy.

BACKGROUND: Psoriasis (PSO) patients can benefit from the growing availability of novel biological agents, that are often underused or discontinued. This real-world analysis estimated PSO patients potentially eligible and currently untreated with biologics in Italy. METHODS: An observational analysis was performed on administrative databases of a pool of healthcare entities, covering 11.3% of Italian population. During the inclusion period (2010- 2020), patients were identified by: 1) at least one prescription of topical drugs for PSO; or 2) active exemption for PSO; or 3) at least one PSO hospital discharge diagnosis. The index-date was the first PSO identification across inclusion period. Eligibility for biologics was evaluated prior to index-date (characterization period) through two not-mutually exclusive criteria: Criterion A, failure of at least one systemic treatment, and/or Criterion B, onset of psoriatic arthritis (PsA). Data were re-proportioned to the Italian population. RESULTS: The study sample showed a PSO prevalence of 2%. Projection to 2020 national population (N=59,236.213) estimated 1.43 million Italian patients affected by PSO: 95% treated with conventional therapies, 4% with biologics, and 1% untreated. Among those non-treated with biologics, 3.8% of overall PSO patients met one or both eligibility criteria for biologics, specifically 25% met criterion A (failure to conventional treatments), 68% criterion B (PsA co-diagnosis), and 7% met both. About half of them had 1 or 2 comorbidities and 30% above 3. CONCLUSIONS: These findings from real clinical practice estimated about 4% PSO patients potentially eligible for biologics, but still untreated, with nearly one-third exhibiting a complex comorbidity profile.

Post-Operative Delirium and Cognitive Dysfunction in Aged Patients Undergoing Cardiac Surgery: A Randomized Comparison between Two Blood Oxygenators.

In elderly patients undergoing cardiac surgery, extracorporeal circulation affects the incidence of post-operative delirium and cognitive impairment with an impact on quality of life and mortality. In this study, a new oxygenator system (RemoweLL 2) was tested against a conventional system to assess its efficacy in reducing the onset of postoperative delirium and cognitive dysfunction and the levels of serum inflammatory markers. A total of 154 patients (>65 y.o.) undergoing cardiopulmonary bypass (CPB) were enrolled and randomly assigned to oxygenator RemoweLL 2 (n = 81) or to gold standard device Inspire (n = 73) between September 2019 and March 2022. The aims of the study were to assess the incidence of delirium and the cognitive decline by neuropsychiatric tests and the MoCa test intra-hospital and at 6 months after CPB. Inflammation biomarkers in both groups were also evaluated. Before the CPB, the experimental groups were comparable for all variables. After CPB, the incidence of severe post-operative delirium showed a better trend (p = 0.093) in patients assigned to RemoweLL 2 (16.0%) versus Inspire (26.0%). Differences in enolase levels (p = 0.049), white blood cells (p = 0.006), and neutrophils (p = 0.003) in favor of RemoweLL 2 were also found. The use of novel and better construction technologies in CPB oxygenator devices results in measurable better neurocognitive and neurological outcomes in the elderly population undergoing CPB.

The Economic Burden of Chronic Myeloid Leukemia in Patients with Later Lines: Findings from a Real-World Analysis in Italy.

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematopoietic myeloproliferative disorder that accounts for 20% of all leukemias of adults. The introduction of tyrosine kinase inhibitors (TKIs) (imatinib, bosutinib, dasatinib, nilotinib, ponatinib) has yielded significant benefits for patients with CML in terms of survival and quality of life. This real-world analysis evaluated the economic burden for managing patients with CML in 2nd or ≥ 3rd TKI lines in Italian settings of clinical practice. METHODS: A retrospective observational analysis was performed exploiting the administrative databases of a sample of entities covering around 15 million inhabitants. From 2015 to 2018, the study included adult patients with at least one prescription for TKIs, (and for some TKI with at least one hospitalization discharge diagnosis for CML, or at least one prescription for BCR-ABL examination). The index date was the first TKI prescription. Healthcare resource consumption and costs for patients with CML in 2nd and ≥ 3rd line treatment with TKIs were analyzed for drug prescriptions, hospitalizations, specialist visits, and diagnostic services. RESULTS: In total 635 patients were included, 491 in 2nd line and 144 in 3rd line with TKIs. Dasatinib was the most frequently prescribed drug in 2nd line (28.9%) and imatinib in later lines (26.4%). With progressing lines of treatment, healthcare consumption showed a trend towards increased non-TKI prescriptions per patient (8 for 2nd line and 9.7 for ≥ 3rd line). The management of patients with CML in later lines resulted in increased overall healthcare burden, with hospitalizations accounting for about half of total expenditure, whatever the treatment line and type of TKI. CONCLUSIONS: This analysis in Italian real-life clinical practice reported economic expenditure for patients with CML in 2nd or ≥ 3rd lines with TKIs, mostly burdened by hospitalizations. Such clinical complexity suggests that further efforts are needed to improve the therapeutic management of later lines of CML.