A retrospective Italian analysis on the characteristics of invasive fungal infections in the intensive care unit setting: CHARTER-IFI study.

BACKGROUND: Invasive fungal infections (IFI), prevalent in critically ill ICU patients, have gained attention due to post-COVID-19 epidemiological shifts. Notably, COVID-19-associated aspergillosis and candidiasis pose significant risks. WHO recognises key fungal pathogens, emphasising the need for enhanced research and interventions. METHODS: The CHARTER-IFI study retrospectively examines 186,310 individuals admitted to ICUs in Italy from 01/01/2012-01/09/2023, utilising administrative databases covering around 10 million inhabitants. Adult patients were included having at least one ICU discharge diagnosis of IFI at their first IFI-related hospitalisation and having at least 12 months of available data prior to this hospitalisation. RESULTS: A total of 746 IFI patients discharged from ICU (incidence of 4.0 per 1000 ICU-hospitalised patients), were included. Median age was 68 years, 63% were males, and the overall Charlson Comorbidity Index was 2.2. The top three diagnoses were candidiasis (N = 501, 2.7/1000 ICU-hospitalised patients), aspergillosis (N = 71, 0.4/1000), and pneumocystosis (N = 55, 0.3/1000). The evaluation of the comorbidity profile in IFI patients revealed the presence of hypertension (60.5%), use of systemic GC/antibacterials (45.3% during 12 months before and 18.6% during 3 months before hospital admission), cancer (23.1%), diabetes (24.3%) and cardiovascular diseases (23.9%). The mean (±SD) length of hospitalisation in ICU was 19.9 ± 24.1 days (median 11 days), and deaths occurred in 36.1% of IFI patients (within 30 days from discharge). CONCLUSIONS: This retrospective analysis among ICU-hospitalised patients described the burden of IFI in ICU, and its understanding could be crucial to strengthen surveillance, investments in research, and public health interventions as required by WHO.

Improving statin treatment strategies to reduce LDL-cholesterol: factors associated with targets' attainment in subjects with and without type 2 diabetes.

BACKGROUND: This cross-sectional study aimed to identify actionable factors to improve LDL-cholesterol target achievement and overcome underuse of lipid-lowering treatments in high- or very-high-cardiovascular risk patients. METHODS: We evaluated healthcare records of 934,332 subjects from North-Italy, including subjects with available lipid profile and being on statin treatments up to December 2018. A 6-month-period defined adherence with proportion-of-days-covered ≥ 80%. Treatment was classified as high-intensity-statin (HIS) + ezetimibe, HIS-alone, non-HIS (NHIS) + ezetimibe or NHIS alone. RESULTS: We included 27,374 subjects without and 10,459 with diabetes. Among these, 30% and 36% were on secondary prevention, respectively. Adherence was high (78-100%) and increased with treatment intensity and in secondary prevention. Treatment intensity increased in secondary prevention, but only 42% were on HIS. 2019-guidelines LDL-cholesterol targets were achieved in few patients and more often among those with diabetes (7.4% vs. 10.7%, p < 0.001). Patients in secondary prevention had mean LDL-cholesterol levels aligned slightly above 70 mg/dl (range between 68 and 73 mg/dl and between 73 and 85 mg/dl in patients with and without diabetes, respectively). Moreover, the differences in mean LDL-cholesterol levels observed across patients using treatments with well-stablished different LDL-lowering effect were null or much smaller than expected (HIS vs. NHIS from - 3 to - 11%, p < 0.001, HIS + ezetimibe vs. HIS-from - 4 to + 5% n.s.). These findings, given the observational design of the study, might suggest that a "treat to absolute LDL-cholesterol levels" approach (e.g., targeting LDLc of 70 mg/dl) was mainly used by physicians rather than an approach to also achieve the recommended 50% reduction in LDL-cholesterol levels. Our analyses suggested that female sex, younger age, higher HDL-c, and elevated triglycerides are those factors delaying prescription of statin treatments, both in patients with and without diabetes and in those on secondary prevention. CONCLUSIONS: Among patients on statin treatment and high adherence, only a small proportion of patients achieved LDL-cholesterol targets. Late initiation of high-intensity treatments, particularly among those with misperceived low-risk (e.g., female subjects or those with high HDL-cholesterol), appears as pivotal factors needing to be modified to improve CVD prevention.

A Retrospective Observational Real-Word Analysis of the Adherence, Healthcare Resource Consumption and Costs in Patients Treated with Bisoprolol/Perindopril as Single-Pill or Free Combination.

INTRODUCTION: The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or free-equivalent combination (FEC) of perindopril and bisoprolol (PER/BIS) in a large Italian population. METHODS: This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or FEC between January 2017-June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as FEC (± 1 month) or SPC. Before comparing the SPC and FEC cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Drug utilization was investigated as adherence (defined by the proportion of days covered, PDC) and persistence (evaluated by Kaplan-Meier curves). Hospitalizations and mean annual direct healthcare costs (due to drug prescriptions, hospitalizations and use of outpatient services) were analyzed during follow-up. RESULTS: The original cohort included 11,440 and 6521 patients taking the SPC and FEC PER/BIS combination, respectively. After PSM, two balanced SPC and FEC cohorts of 4688 patients were obtained (mean age 70 years, approximately 50% male, 24% in secondary prevention). The proportion of adherent patients (PDC ≥ 80%) was higher for those on SPC (45.5%) than those on FEC (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% of patients in the SPC cohort and 41.7% in the FEC cohort (p < 0.001). The SPC cohort had fewer cardiovascular (CV) hospitalizations (5.3%) than the free-combination cohort (7.4%), p < 0.001. Mean annual total healthcare costs were lower in the SPC (1999€) than in the FEC (2359€) cohort (p < 0.001). CONCLUSION: In a real-world setting, patients treated with PER/BIS SPC showed higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on FEC of the same drugs.

Patients with cardiovascular conditions often need to take many pills. This may result in patients not taking their pills as prescribed (i.e., low adherence) and compromise the potential benefits derived from prescription of cardiovascular protective drugs. Simplifying treatment by combining drugs into a single pill can improve adherence and, consequently, patient outcomes. In this analysis using data from real clinical practice, we explored whether using a single pill of perindopril and bisoprolol is associated with higher levels of adherence, lower proportion of patients with hospitalizations and lower economic costs than using the same drugs prescribed as free-equivalent combination in a large sample of the Italian population of approximately 7 million people. We identified two groups of patients taking single pill or free-equivalent combination of perindopril and bisoprolol (4688 patients in each cohort). Over 1-year follow-up, patients taking single pill were more likely to be adherent and were less likely to stop taking their treatment. They also had fewer cardiovascular hospitalizations with shorter hospital admission and had lower healthcare direct costs. In conclusion, simplifying treatment by combining perindopril and bisoprolol in a single pill instead of two may have a positive effect on adherence, outcomes and healthcare costs already after 1 year.

Differential Adherence to Free and Single-Pill Combination of Rosuvastatin/Ezetimibe: Findings from a Real-World Analysis in Italy.

INTRODUCTION: Adherence to cardiovascular drug treatment can significantly benefit from a reduced pill burden, but data on this matter derived from real-life settings are currently scanty. This analysis assessed the possible changes in adherence in patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free multi-pill combination who switched to ROS/EZE as single-pill combination in the setting of real clinical practice in Italy. METHODS: A retrospective analysis was conducted on the administrative databases for a catchment area of about seven million health-assisted residents. Adults receiving ROS/EZE as a single-pill combination from January 2010 to June 2020 (followed up to 2021) were identified. The date of the first prescription of single-pill combination of ROS/EZE was considered as the index date. The analysis included the users of ROS/EZE as a free combination during the year before the index date. Baseline demographic and clinical characteristics were collected during the period of data availability prior to the index date. Adherence to therapy was evaluated as proportion of days covered (PDC), namely the percentage of days during which a patient had access to medication, in the 12-month interval preceding or following the index date (PDC < 25% non-adherence; PDC = 25-75% partial adherence; PDC > 75% adherence). RESULTS: A total of 1219 patients (61.1% male, aged 66.2 ± 10.4 years) were included. Cardiovascular comorbidities were found in 83.3% of them, diabetes in 26.4%, and a combination of both in 16.2%. Single-pill combination of ROS/EZE was associated with a higher proportion of adherent patients compared to free-pill combination (75.2% vs 51.8%, p < 0.001). CONCLUSIONS: This real-world analysis suggested that switching from a regimen based on separate pills to one based on a single-pill combination resulted in improved adherence to ROS/EZE therapy.

Lipid-lowering therapy to control low-density lipoprotein (LDL) cholesterol levels is essential for cardiovascular risk prevention. Successful therapy depends on the type of lipid-lowering therapy, i.e., low or high statin intensity and combination of statins with ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and adherence to therapy, i.e., whether the patient actually takes their pills as prescribed. If there are fewer pills to be taken, this can help patients to follow their treatment. Single-pill combinations of two drugs could facilitate adherence and thus the chances of reaching the recommended lipid targets. Here, we analyzed a sample of Italian patients with dyslipidemia to examine whether the switch from a free combination of two separate pills of rosuvastatin and ezetimibe to a single-pill combination of the same drugs could improve adherence to therapy. We found that the proportion of adherent patients increased from about just over half (51.8%) to about three-fourths (75.1%) when switching from two-pill to single-pill combination of rosuvastatin and ezetimibe. These findings suggest that simplifying therapy can help improve patient adherence, which is essential for reaching lipid targets and ultimately for alleviating atherosclerotic cardiovascular disease.

Real-World Treatment Patterns and Healthcare Resource Use for Ulcerative Colitis and Crohn's Disease in Italy.

INTRODUCTION: Real-world data are used to inform decision-makers and optimise therapeutic management for patients with ulcerative colitis (UC) and Crohn's disease (CD). We analysed data on the epidemiology (by using proxies of prevalence and incidence), patient characteristics, treatment patterns and associated healthcare direct costs for the management of patients with UC and patients with CD in Italy. METHODS: This retrospective observational study used administrative databases from eight Local Health Units geographically distributed across Italy. Adult patients with a hospitalisation and/or an exemption for UC or CD were included. Study outcomes were summarised descriptively, and limited statistical tests were performed. RESULTS: At baseline, 9255 adults with UC and 4747 adults with CD were included. Mean (standard deviation) age at inclusion was 54.0 (18.4)/48.6 (18.1) years, for UC/CD. The estimated average incidence of UC and CD for the period 2013-2020 was 36.5 and 18.7 per 100,000, respectively. The most frequently prescribed drug category for patients with UC/CD was conventional treatment [mesalazine and topical corticosteroids (67.4%/61.1%), immunomodulators and systemic corticosteroids (43.2%/47.7%)], followed by biologic treatments (2.1%/5.1%). The mean annual total direct cost per patient was 7678 euro (€), for UC and €6925 for CD. CONCLUSION: This analysis, carried-out in an Italian clinical setting, may help to optimise therapy for patients with UC and CD and provide relevant clinical practice data to inform decision-makers.

Data from clinical practice can be used to guide healthcare decisions and optimise treatment for patients with ulcerative colitis and Crohn's disease. This study used anonymised patient information from almost four million individuals across Italy to describe the epidemiology, patient characteristics, treatment patterns and healthcare costs of patients with ulcerative colitis and Crohn's disease. Adults with an Italian National Health System code in their records associated with the diagnosis of ulcerative colitis or Crohn's disease were included. Baseline characteristics were balanced between groups and rates of perceived incidence were numerically similar to the results reported in similar Italian studies. This study found that patients with ulcerative colitis and Crohn's disease were most often prescribed conventional treatments, and biological treatments were least-commonly prescribed. More than half of patients with ulcerative colitis and nearly half of those with Crohn's disease were persistent with first (index) treatment of mesalazine and topical corticosteroids and with biologic index treatment during the follow-up period. Switch occurred in up to approximately a quarter of patients with ulcerative colitis and Crohn's disease. The main factors that predicted switch were index biologic for ulcerative colitis and baseline comorbidities for Crohn's disease. The average direct cost per patient in 1 year was 7678 euro (€) for ulcerative colitis and €6925 for Crohn's disease. The results of this analysis may help to optimise therapy for patients with ulcerative colitis and Crohn's disease, and to inform decision-makers in healthcare systems on which treatment options provide value for money and benefit patients.

Clinical and economic burden of respiratory syncytial virus in children aged 0-5 years in Italy.

BACKGROUND: Respiratory syncytial virus (RSV) is among the leading causes of hospitalization due to lower respiratory tract infections (LRTIs) in children younger than 5 years worldwide and the second cause of infant death after malaria. RSV infection occurs in almost all the infants before the second year of life with variable clinical severity, often requiring medical assistance. This analysis investigated patients aged 0-5 years with RSV infection focusing on epidemiology, clinical features, and economic burden of RSV-associated hospitalizations in a setting of Italian real clinical practice. METHODS: An observational retrospective analysis was conducted on administrative databases of healthcare entities covering around 2.6 million residents of whom 120,000 health-assisted infants aged < 5 years. From 2010 to 2018, pediatric patients were included in the presence of hospitalization discharge diagnosis for RSV infections, and RSV-related acute bronchiolitis or pneumonia. Epidemiology, demographics, clinical picture and costs were evaluated in RSV-infected patients, overall and stratified by age ranges (0-1, 1-2, 2-5 years) and compared with an age-matched general population. RESULTS: Overall 1378 RSV-infected children aged 0-5 years were included. Among them, the annual incidence rate of RSV-related hospitalizations was 175-195/100,000 people, with a peak in neonates aged < 1 year (689-806/100,000). While nearly 85% of infected infants were healthy, the remaining 15% presented previous hospitalization for known RSV risk factors, like preterm birth, or congenital heart, lung, and immune diseases. The economic analysis revealed that direct healthcare costs per patient/year were markedly higher in RSV patients than in the general population (3605€ vs 344€). CONCLUSIONS: These findings derived from the real clinical practice in Italy confirmed that RSV has an important epidemiological, clinical, and economic burden among children aged 0-5 years. While the complex management of at-risk infants was confirmed, our data also highlighted the significant impact of RSV infection in infants born at term or otherwise healthy, demonstrating that all infants need protection against RSV disease, reducing then the risk of medium and long-term complications, such as wheezing and asthma.

Burden of Illness in Follicular Lymphoma with Multiple Lines of Treatment, Italian RWE Analysis.

This real-world analysis investigated patients with follicular lymphoma in Italy receiving three or more treatment lines (≥3L), focusing on therapeutic pathways with their rebounds on healthcare resource consumptions and costs. Data were retrieved from administrative databases from healthcare entities covering about 13.3 million residents. Adults diagnosed with follicular lymphoma were identified between January 2015 and June 2020, and among them 2434 patients with ≥3L of treatment during the data availability interval (January 2009 to June 2021) were included. Of them, 1318 were in 3L, 494 in 4L and 622 in ≥5L. A relevant proportion of patients (12-32%) switched to a later line within the same calendar year. At 3-year follow-up (median), 34% patients died. Total mean annual expenses were euro 14,508 in the year preceding inclusion and rose to euro 21,081 at 1-year follow-up (on average euro 22,230/patient/year for the whole follow-up), with hospitalization and drug expenses as weightiest cost items. In conclusion, the clinical and economic burden of follicular lymphoma increases along with later treatment lines. The high mortality rates indicate that further efforts are needed to optimize disease management.

Real world study on prevalence, treatment and economic burden of myasthenia gravis in Italy.

The purpose of this study was to investigate the epidemiology, management, and economic burden of myasthenia gravis in settings of real clinical practice. The analysis used administrative databases covering around 12 million subjects across Italy and included all adult patients with hospitalization discharge diagnosis or active exemption code for myasthenia gravis or with ≥1 pyridostigmine prescription from 2011 to 2018. The estimated prevalence of myasthenia gravis during 2018 was in the range 13.5-29.3/100,000 people (depending on the criteria applied), corresponding to 8190-17,728 alive patients, when reproportioning data to the entire Italian population. Overall 4397 patients with myasthenia gravis (mean age 61.7 years, 46.6% males) were included. A large pyridostigmine use was observed (84.0%-46.8% from 1st to 3rd year of follow-up), followed by corticosteroids (54.5%-44.6% from 1st to 3rd year of follow-up) and non-steroidal immunosuppressants (16% over follow-up). Total direct healthcare costs for myasthenia gravis were 4-times higher than those of the general population (€3771 and €869, respectively), and up to 9-fold increased when considering patients with exacerbation (€7827). These findings showed the epidemiologic burden of myasthenia gravis and the complexity of the therapeutic management for the affected patients, with large use of treatments and elevated healthcare expenditures.

Real-World Analysis of Outcomes and Economic Burden in Patients with Chronic Kidney Disease with and without Secondary Hyperparathyroidism among a Sample of the Italian Population.

This real-world analysis evaluated the clinical and economic burden of non-dialysis-dependent CKD patients with and without secondary hyperparathyroidism (sHPT) in Italy. An observational retrospective study was conducted using administrative databases containing a pool of healthcare entities covering 2.45 million health-assisted individuals. Adult patients with hospitalization discharge diagnoses for CKD stages 3, 4, and 5 were included from 1 January 2012 to 31 March 2015 and stratified using the presence/absence of sHPT. Of the 5710 patients, 3119 were CKD-only (62%) and 1915 were CKD + sHPT (38%). The groups were balanced using Propensity Score Matching (PSM). Kaplan-Meier curves revealed that progression to dialysis and cumulative mortality had a higher incidence in the CKD + sHPT versus CKD-only group in CKD stage 3 patients and the overall population. The total direct healthcare costs/patient at one-year follow-up were significantly higher in CKD + sHPT versus CKD-only patients (EUR 8593 vs. EUR 5671, p < 0.001), mostly burdened by expenses for drugs (EUR 2250 vs. EUR 1537, p < 0.001), hospitalizations (EUR 4628 vs. EUR 3479, p < 0.001), and outpatient services (EUR 1715 vs. EUR 654, p < 0.001). These findings suggest that sHPT, even at an early CKD stage, results in faster progression to dialysis, increased mortality, and higher healthcare expenditures, thus indicating that timely intervention can ameliorate the management of CKD patients affected by sHPT.

Profile, Healthcare Resource Consumption and Related Costs in ANCA-Associated Vasculitis Patients: A Real-World Analysis in Italy.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare autoimmune diseases triggering inflammation of small vessels. This real-world analysis was focused on the most common AAV forms, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), to describe patients' demographic and clinical characteristics, therapeutic management, disease progression, and the related economic burden. METHODS: A retrospective analysis was conducted on administrative databases of a representative sample of Italian healthcare entities, covering approximately 12 million residents. Between January 2010 and December 2020, adult GPA patients were identified by payment waiver code or hospitalization discharge diagnosis, and MPA patients by payment waiver code with or without hospitalization discharge diagnosis. Clinical outcomes were evaluated through AAV-related hospitalizations, renal failure onset, and mortality. Economic analysis included healthcare resource utilization deriving from drugs, hospitalizations, and outpatient specialist services. The related mean direct costs year/patient were also calculated in patients stratified by presence/absence of glucocorticoid therapy and type of inclusion criterion (hospitalization/payment waiver code). RESULTS: Overall, 859 AAV patients were divided into GPA (n = 713; 83%) and MPA (n = 146; 17%) cohorts. Outcome indicators highlighted a clinically worse phenotype associated with GPA compared to MPA. Cost analysis during follow-up showed tendentially increased expenditures in glucocorticoid-treated patients versus untreated (overall AAV: €8728 vs. €7911; GPA: €9292 vs. €9143; MPA: €5967 vs. €2390), mainly driven by drugs (AAV: €2404 vs. €874; GPA: €2510 vs. €878; MPA: €1881 vs. €854) and hospitalizations. CONCLUSION: Among AAV forms, GPA resulted in a worse clinical picture, higher mortality, and increased costs. This is the first real-world pharmaco-economic analysis on AAV patients stratified by glucocorticoid use on disease management expenditures. In both GPA and MPA patients, glucocorticoid treatment resulted in higher healthcare costs, mostly attributable to medications, and then hospitalizations, confirming the clinical complexity and economic burden for management of patients with autoimmune diseases under chronic immunosuppression.

The Influence of Iron-Deficiency Anaemia (IDA) Therapy on Clinical Outcomes and Healthcare Resource Consumptions in Chronic Kidney Disease Patients Affected by IDA: A Real-Word Evidence Study among the Italian Population.

Anaemia is a uraemia-related complication frequently found in non-dialysis-dependent chronic kidney disease (ND-CKD) patients, with iron-deficiency anaemia (IDA) as the main underlying mechanism. Given the suboptimal anaemia management in ND-CKD patients with a co-diagnosis of IDA, this study evaluated the role of IDA therapy on clinical outcomes and healthcare resource consumptions in an Italian clinical setting. A retrospective observational real-world analysis was performed on administrative databases of healthcare entities, covering around 6.9 million health-assisted individuals. From January 2010 to March 2019, ND-CKD patients were included and diagnosed with IDA in the presence of two low-haemoglobin (Hb) measurements. Patients were divided into IDA-treated and untreated, based on the prescription of iron [Anatomical-Therapeutic Chemical (ATC) code B03A] or anti-anaemia preparations (ATC code B03X), and evaluated during a 6-month follow-up from the index date [first low haemoglobin (Hb) detection]. IDA treatment resulted in significantly decreased incidence of all cause-related, cardiovascular-related, and IDA-related hospitalizations (treated vs. untreated: 44.5% vs. 81.8%, 12.3% vs. 25.3%, and 16.2% vs. 26.2%, respectively, p < 0.001). A healthcare direct cost estimation showed that overall mean expenditure per patient reduced by 47% with IDA treatment (5245€ vs. 9918€, p < 0.001), mainly attributable to hospitalizations (3767€ vs. 8486€, p < 0.001). This real-life analysis on Italian ND-CKD-IDA patients indicates that IDA therapy administration provides significant benefits in terms of patients' clinical outcomes and healthcare cost savings.

The Epidemiology, Treatment Patterns and Economic Burden of Different Phenotypes of Multiple Sclerosis in Italy: Relapsing-Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis.

Purpose: A retrospective analysis of real-world data was performed to assess the epidemiology and economic burden of multiple sclerosis (MS), relapsing-remitting MS (RRMS), and secondary-progressive MS (SPMS) in Italy. Patients and Methods: An observational study on administrative databases from a sample of Italian entities was carried-out. Between 01/2010-12/2017, patients with ≥1 MS diagnosis code (ICD-9-CM:340 and/or exemption code:046) and/or ≥1 disease-modifying therapies (DMTs) prescription, were included. Among MS-cohort, SPMS patients were identified by ≥2 hospitalizations or by ≥2 drug prescriptions related to MS progression. MS patients not fulfilling SPMS criteria were included as RRMS. Mean annual healthcare costs were reported during follow-up and stratified by DMT treatment/untreatment. Results: Overall, 9543 MS patients were included; 8397 with RRMS and 1146 with SPMS. Estimated prevalence of MS was 141.6/100,000 inhabitants (RRMS 124.4/100,000 and SPMS 17.2/100,000). Mean annual cost for untreated and treated patient was respectively: €3638 and €11796 (MS-cohort), €3183 and €11486 (RRMS-cohort), €6317 and €15511 (SPMS-cohort). The first-line DMT treatment duration averaged 27.4 ± 22.8 months; the mean cost was 19004€ for the whole period. The second-line DMT treatment lasted on average 31.1 ± 24.5 months; the mean cost was 47293€ for the whole period. Conclusion: This study provided insights into the MS epidemiology in Italy and its economic burden. Healthcare costs associated with MS management were mainly driven by DMTs expenditure. A trend of higher healthcare-resource consumption was observed among SPMS-cohort.

Direct Healthcare Costs by Level of Adherence of a Real-World Population of Statin Users in Italy.

Purpose: This real-world study investigates the direct healthcare costs from the perspective of the Italian Healthcare National Service of experienced statin users according to their level of adherence to therapy and to their cardiovascular (CV) profile in Italian settings of outpatients clinical practice. Patients and Methods: A retrospective observational analysis was performed based on administrative databases covering approximately 6 million health-assisted individuals. Adult patients with statins prescription between January 2014 and December 2016 were screened, and first prescription within this period was the index date. Follow-up lasted 1 year after index date. Only patients receiving statins prior index date (experienced statin users) were included and distributed in clusters based on their CV profile. Adherence was calculated during follow-up as proportion of days covered (PDC) and classified in low adherence (PDC<40%), partial adherence (PDC=40-79%) and adherence (PDC≥80%). Mean direct healthcare costs of drugs, hospitalizations, and outpatient services were evaluated during follow-up. Results: A total of 436,623 experienced statin users were included and distributed as follows: 5.5% in the previous CV events, 22.6% in diabetes, 55.7% in CV treatments and 16.2% in the no comorbidity cluster. Total mean annual cost/patient decreased from low adherent to adherent patients from €4826 to €3497 in previous CV events, from €2815 to €2360 in diabetes cluster, from €2077 to €1863 for patients with CV treatments. Same trend was reported for the cost item related to hospitalizations, which was the major determinant of the total costs. In previous CV event cluster, adherence was associated to a saving of €879 on total costs. Conclusion: The study highlighted a decrease in overall mean costs as adherence levels increase, particularly for patients with previous CV events, showing how improving adherence could be associated to cost savings and suggesting suited strategy based on CV profile should be undertaken for adherence optimization.

Real-World Evaluation of Calcimimetics for the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease, in an Italian Clinical Setting.

This Italian real-world data analysis evaluated the pharmaco-utilization of calcimimetics, cinacalcet or etelcalcetide, and the economic burden of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients. From 1 January 2010 to 30 June 2020, adult patients with: (i) ≥1 prescription of etelcalcetide or cinacalcet, (ii) ≥3 hemodialysis/week, and (iii) without parathyroidectomy, were included. Based on the drug firstly prescribed, patients were allocated into etelcalcetide- and cinacalcet-treated cohorts, and the propensity score matching (PSM) methodology was applied to abate potential cohorts' unbalances. Overall, 1752 cinacalcet- and 527 etelcalcetide-treated patients were enrolled. In cinacalcet- and etelcalcetide-treated patients, respectively, the most frequent comorbidities were hypertension (75.3% and 74.4%), diabetes mellitus (21.0% and 21.3%), and cardiovascular disease (18.1% and 13.3%, p < 0.01). In covariate-balanced cohorts, the treatment adherence and persistence rates were significantly higher in the etelcalcetide-treated (80.1% and 62.7%, respectively) vs. cinacalcet-treated cohort (62.3% and 54.7%, respectively). After PSM, the total costs for the management of cinacalcet- and etelcalcetide-treated patients, respectively, averaged EUR 23,480 and EUR 22,958, with the disease-specific drug costs (EUR 2629 vs. EUR 2355, p < 0.05) and disease-specific hospitalization costs (EUR 1241 vs. EUR 855) in cinacalcet- and etelcalcetide-treated patients. These results showed that, in etelcalcetide-treated patients, a higher treatment adherence and persistence was found, with disease-specific costs savings, especially those related to drugs and hospitalizations.

Retrospective Analysis of the Pharmaco-Utilization of VEGF Inhibitors and Health Care Costs among Patients with Wet Age-Related Macular Degeneration and Other Ocular Diseases in Italy.

This Italian retrospective study aimed to analyze the pharmaco-utilization of anti-VEGF drugs and health care costs among patients with wet age-related macular degeneration (wAMD) or other ocular diseases. A retrospective analysis was performed on administrative databases of Italian entities covering approximately six million individuals. Across January 2010-December 2017, patients aged ≥50 years with a prescription of intravitreal anti-VEGFs were included as "wAMD" patients [by wAMD hospitalization or intravitreal injections] or as "other ocular diseases" patients [by hospitalization for other ocular disorders or intravitreal injections, with concomitant diabetes diagnosis or dexamethasone treatment]. The date of first matching of inclusion criteria was index-date. wAMD-cohort. Overall, 3879 patients were included; at index-date, 82.2% were treated with Ranibizumab, 15.8% with Aflibercept, and 2% with Pegaptanib. During the follow-up, the mean/annual anti-VEGF prescription [3.6 (first-year)-0.8 (third-year)] and the total expenditure [5799.84 € (first-year)-3212.84 € (third-year)] decreased. Other ocular diseases-cohort. Overall, 2646 patients were enclosed; 85.9% were treated with Ranibizumab, 13.5% with Aflibercept, and 0.6% with Pegaptanib. During the follow-up, the mean/annual anti-VEGF prescription [3.3 (first-year)-0.5 (third-year)] and the total cost [7196.83 € (first-year)-5162.68 € (third-year)] decreased. This observational study highlighted a decline in anti-VEGF prescriptions over time in both cohorts, suggesting a trend of under-treatment that could worsen the patients' clinical outcomes and increase health care resource consumption.

Analysis of Patients with Focal Epilepsy and Drug-Resistant Epilepsy in Italy: Evaluation of Their Characteristics, Therapeutic Pathway and the Consumption of Healthcare Resources.

Purpose: A retrospective analysis was conducted to estimate the number of patients with focal epilepsy and drug-resistant epilepsy (DRE) and their characteristics, the therapeutic patterns, the consumption of health resources in a real-world Italian setting. Patients and Methods: A retrospective study was carried out on the administrative databases of a sample of Italian Health Departments, covering approximately 8.7 million health-assisted individuals. All adult patients with at least one hospitalization for focal epilepsy and an electroencephalogram (between 01/2010 and 12/2019), and at least one prescription of antiseizure medication (ASM) (between 01/2011 and 12/2018) were included in the study. Patients with at least two treatment failures and treated with a subsequent ASM were considered DRE. Results: Overall, 1897 patients with focal epilepsy (mean age 56 years, 47% male) were identified, of which 485 (25.6%) with DRE (mean age 53 years, 43% male). Among patients with focal epilepsy and DRE, respectively, 48% and 54% had essential hypertension, 23.4% and 26.6% had cardiovascular disease, and 46.3% and 62.1% had peptic ulcer/prescription of gastric secretion inhibitors. During follow-up, patients with focal epilepsy maintained first-line treatment for 53.9 months; among these, 52% passed to the second-line, and 485 (25.6% of the total) began third-line treatment. In patients with focal epilepsy, the mean cost was € 4448 (of which € 1410 were epilepsy-related), and in DRE patients total expenditures averages € 5825 (of which € 2165 were epilepsy-related). In both patients with focal epilepsy and DRE, hospitalizations represented the most impacting item of expenditure. Conclusion: The present analysis conducted in a setting of Italian clinical practice has shown that 25% of patients with focal epilepsy were resistant to antiepileptic treatments. Furthermore, these results showed that health-care costs for the management of epileptic patients were mainly accountable for the costs related to the disease-management and to hospitalizations.

Cardiovascular Risk Profile in Prostate Cancer Patients Treated with GnRH Agonists versus Antagonists: An Italian Real-World Analysis.

PURPOSE: To evaluate and compare the incidence of cardiovascular (CV) events in a large contemporary cohort of patients diagnosed with prostate cancer (PCa) and in treatment with GnRH agonists or GnRH antagonists. PATIENTS AND METHODS: An Italian observational retrospective cohort study based on administrative databases of three local health units and two Regions was performed. PCa patients treated with GnRH agonists or antagonist were included between January 01, 2013 and December 31, 2016. Index date (ID) was the date of first GnRH agonist/antagonist prescription during inclusion period. Follow-up was from ID to December 31, 2017. Patients were excluded if they were under abiraterone treatment or combination therapy with antiandrogens during follow-up. The incidence rate of CV events (acute myocardial infarction, ischemic heart diseases, cerebrovascular diseases, cardiac dysrhythmias, heart failure, atherosclerosis, aneurism, other CV-related conditions) was calculated among patients not switching to androgen deprivation therapy (ADT) in the overall cohort and in a sub-cohort of patients without previous CV events. RESULTS: In total, 9785 (mean age 76.8 ± 8.5) patients were included: 9158 (93.6%) were treated with a GnRH agonist and 627 (6.4%) with a GnRH antagonist. Of them, 9627 did not switch to ADT and were considered in the analyses. The incidence of CV events was significantly higher in patients treated with GnRH agonists rather than antagonists (8.8 vs 6.2, p=0.002). Mean time to CV event was beyond 1 year of treatment in both groups. In the multivariable regression analysis, the risk of experiencing CV events was significantly lower in patients treated with GnRH antagonist rather than those treated with GnRH agonists [HR (95% CI): 0.76 (0.60-0.95), p=0.018]. These findings were confirmed in the sub-cohort of patients without previous CV events. CONCLUSION: This Italian observational study shows that most patients received a GnRH agonist rather than a GnRH antagonist prescription. GnRH antagonist seems to have a better CV risk profile than GnRH agonist, both in patients with and without a history of CV events.

Treatment patterns, health resource consumption, and costs of patients with migraine in an Italian real-world setting.

OBJECTIVE: This study aimed to describe the demographic and clinical characteristics of migraineurs prescribed ≥1 migraine prophylactic therapy, and to analyze their therapeutic pathways, healthcare resource consumption, and related costs. METHODS: This retrospective analysis was based on administrative databases from two regions and three local health units in Italy. Adult patients with ≥1 discharge diagnosis for migraine or ≥1 prescription for migraine-specific drugs, or ≥1 emergency room visit for migraine from 1 January 2010 to 31 December 2016 were included if they had received ≥1 migraine prophylactic therapy between 1 January 2011 and 31 December 2015 (enrollment period). The first date of the last migraine prophylactic treatment was considered as the index date (ID). Patients were characterized 1-year prior ID and followed-up for 1 year afterwards. RESULTS: Of the 166,362 identified migraineurs, 32,794 (mean age: 45.9 ± 13.9 years, 19.2% male) who received migraine prophylaxis were included in the analysis. At ID, 31,629 patients had received 1 prophylactic treatment with antidepressants (51.2%), neuromodulators (28.1%), beta blockers (12.4%), other migraine preparations (7.8%), and botulinum toxin A (0.5%). Focusing on patients with one prophylactic treatment at ID, 85.4% did not have any previous therapeutic failures whereas 14.6% had ≥1 previous failure. During follow-up, 5% of patients made a therapeutic switch after a mean period of 103.4 ± 97.9 days. Total mean annual cost for patients receiving migraine prophylaxis was 1193.64€ during characterization and 1303.86€ during follow-up periods. CONCLUSION: This real-world study gave insights on the characterization of migraineurs and patterns of prophylaxis utilization in Italian clinical settings, showing an underuse of prophylactic agents.

Association of Hypertriglyceridemia with All-Cause Mortality and Atherosclerotic Cardiovascular Events in a Low-Risk Italian Population: The TG-REAL Retrospective Cohort Analysis.

Background Evidence regarding the relationships among high plasma triglycerides (TG), all-cause mortality, and atherosclerotic cardiovascular disease (ASCVD) events in low-to-moderate risk individuals is limited. The aim of this study was to determine whether the presence of high TG levels influences the risk of all-cause mortality and ASCVD events in a population cohort followed in the real-world clinical setting. Methods and Results A retrospective longitudinal cohort analysis using administrative databases of 3 Italian Local Health Units was performed. All individuals with at least one TG measurement between January 1, 2010 and December 31, 2015 were followed through December 2016. Outcome measures included incident ASCVD events and all-cause mortality. Individuals with normal TG levels (<150 mg/dL) were compared with those with high (150-500 mg/dL) and very high TG (>500 mg/dL). 158 042 individuals (142 289 with normal, 15 558 with high, and 195 with very high TG) were considered. In the whole cohort, the overall incidence rates of ASCVD and all-cause mortality were 7.2 and 17.1 per 1000 person-years, respectively. After multivariate adjustment for potential confounders, individuals with high and very high TG showed a significantly increased risk of all-cause mortality (hazard ratio [HR]=1.49 [95% confidence interval (CI) 1.36-1.63], P<0.001, and HR=3.08 [95% CI 1.46-6.50], P<0.01, respectively) and incident ASCVD events (HR=1.61 [95% CI 1.43-1.82], P<0.001, and HR=2.30 [95% CI 1.02-5.18], P<0.05, respectively) as compared to those with normal TG. Conclusions Moderate-to-severe elevation of TG is associated with a significantly increased risk of all-cause mortality and ASCVD events in a large cohort of low-to-moderate cardiovascular risk individuals in a real-world clinical setting.

Trends in Prescription and Determinants of Persistence to Antihypertensive Therapy : The PAPEETE Study.

OBJECTIVES: To assess trends in prescriptions, determinants and timing of treatment discontinuation and/or changes in antihypertensive drug therapy in a cohort of hypertensive patients living in Pavia, a city in the north of Italy. METHODS: The cohort included 61 493 patients aged ≥18 years who received their first antihypertensive drug prescription (monotherapy, fixed or extemporaneous combination) during the period 2003-6. Patients were classified as 'persistent' if 12 months after the beginning of treatment they were still taking a regular therapy (same drug = 'same therapy users', added one or more drugs = 'add-on therapy users', different drug = 'switchers'). Otherwise, they were classified as 'non-persistent' (stopping therapy after the first prescription = 'occasional users'; stopping treatment early = 'stoppers'; taking medicines in an erratic fashion = 'intermittent users'). RESULTS: ACE inhibitors were the most frequently prescribed drugs (22.8%), followed by ß-adrenoceptor antagonists (ß-blockers) [14.3%], diuretics (13.9%), Ca(2+) antagonists (11.4%) and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) [9.3%]. After 12 months, persistent patients were only 11.2% (same therapy users 6.7%, switchers 3.2%, add-on therapy users 1.3%). Non-persistent patients were 88.8% (35.3% occasional users, 20.6% stoppers, 32.8% intermittent users). Patient-related predictors of persistence were older age, male sex, concomitant treatment with antidiabetic and hypolipidaemic drugs and previous hospitalizations for cardiovascular events. Highest level of persistence was seen in patients starting with ARBs (18.8%), followed by ACE inhibitors (11.4%), ß-blockers (11.0%), Ca(2+) antagonists (10.8%) and diuretics (3.0%). Among ARBs, considering separately monotherapy and fixed-combination therapy, highest level of persistence was observed in patients starting with candesartan, irbesartan, valsartan and telmisartan given in monotherapy, and with valsartan and telmisartan given in fixed-dose combination. CONCLUSIONS: Persistence to antihypertensive treatment at 12 months is only 11.2%, being the lowest with diuretics (3.0%) and the highest with ARBs (18.8%).