Organization, Clinical and Management Indicators on the First Year of Activity of an Outpatient Clinic Dedicated to the Diagnosis and Treatment of Severe Asthma in Italy.

PURPOSE: A Regional Technical Commission was set in 2017 by Veneto region (Italy) to provide opinions and recommendations on drug prescriptions and to implement treatment-pathway guidelines for severe asthma. In this observational study, we describe the first structured, integrated, multidisciplinary, patient-centered outpatient clinic for the care of severe-asthma patients in Italy, and characterize patients referring to the center for specialist visits. PATIENTS AND METHODS: To characterize patients that accessed the outpatient clinic in 2018, data on demographic characteristics, treatments, severity of asthma, phenotypes, and relevant comorbidities by phenotype were collected. Use of biologic agents and indicators of the performance of the outpatient clinic were described. RESULTS: A structured multidisciplinary outpatient pathway for taking charge of patients and for administration and monitoring of biological agents was developed. A total of 146 patients accessed the outpatient clinic in 2018: 62.3% had uncontrolled asthma upon admission and 27.4% were already being treated with biologic agents. Among patients with uncontrolled asthma, 66% had severe uncontrolled asthma, 22% had moderate-severe uncontrolled asthma, and 12% had mild-moderate uncontrolled asthma. Main asthma phenotypes in uncontrolled-asthma patients were allergic (58% of patients), eosinophilic (22%), allergic plus eosinophilic (10%) and non-atopic asthma (10%). Among patients affected by severe asthma, 47% had allergic asthma, 28% had eosinophilic asthma, 13% had allergic plus eosinophilic asthma, and 12% had non-atopic asthma. Nasal polyps were more frequent in eosinophilic and allergic plus eosinophilic asthma, while gastro-esophageal reflux disease was more frequent in non-atopic asthma. CONCLUSION: This structure of an outpatient clinic for the treatment of severe asthma, with its dedicated pathway and multidisciplinary approach, may allow a stricter control of asthma and optimization of therapies, as well as minimization of drug misuse.

Cinacalcet adherence in dialysis patients with secondary hyperparathyroidism in Lombardy Region: clinical implications and costs.

BACKGROUND: Patients on dialysis often have secondary hyperparathyroidism (SHPT), a disorder associated with renal osteodystrophy, progressive vascular calcification, cardiovascular disease, and death. The objective of this retrospective observational study was to evaluate, in dialysis patients with SHPT, the impact of different levels of adherence to cinacalcet therapy on hospitalisations and direct healthcare costs charged to the Lombardy Regional Health Service (Italy). METHODS: Data recorded in the administrative databases on all citizens undergoing dialysis between 1 January 2011 and 31 December 2011 were selected. For the aim of this study, patients with SHPT already on dialysis in the first 6 months of 2009 who had been treated with cinacalcet for at least 365 days were selected and retrospectively analysed through to end of 2012. Healthcare resource utilisation, cinacalcet adherence, and costs for medication, hospitalisations, and diagnostic/therapeutic procedures were estimated. RESULTS: A total of 994 patients were identified (mean age 63.0 years, females 43.5%). The first patient tertile had an adherence to cinacalcet of <64.1%, whereas the third had an adherence of over 91.5%. Patients in the third adherence tertile experienced fewer all-causes hospitalisations than those in the first tertile (-19.2%; p=0.01423), fractures (-37.1%; p=0.59422), cardiovascular disease (-23.8%; p=0.04025), and sepsis (-32.3%; p=0.01386). The increase in costs for cinacalcet-adherent patients is almost completely offset by the reduction in costs for hospitalisations. CONCLUSIONS: The results of the analysis suggest that there may be some correlation between a high level of cinacalcet adherence and a decrease in hospitalisations.

Real-world data on healthcare resource consumption and costs before and after kidney transplantation.

End-stage renal disease (ESRD) is increasing worldwide as a consequence of population aging and increasing chronic illness. Treatment consists mostly of dialysis and kidney transplantation (KTx), and KTx offers advantages for life expectancy and long-term cost reductions compared with dialysis. This study uses the administrative database of the Lombardy Region to analyze the costs of a cohort of patients with ESRD receiving KTx, covering a time period of 24 months before transplant to 12 months after. During 2011, 276 patients underwent kidney transplantation (8.7% preemptive and 91.3% non-preemptive). In the period before transplantation, the main cost driver was dialysis (66.6% for the period from -24 to -12 months and 73.8% for the period from -12 to 0 months), while in the 12 months after KTx, the most relevant cost was surgery. The total cost -24 to -12 months pre-KTx was 35 049.2€; the cost -12 to 0 months was 36 745.9€; and the cost 12 months after KTx was 43 805.8€. Non-preemptive patients showed much higher costs both pre- and post-KTx than preemptive patients. This study highlights how KTx modifies the resource consumption and costs composition of patients with ESRD vs those undergoing dialysis treatment and how KTx may be economically beneficial, especially preemptive intervention.

Economic impact of the use of rifaximin 550 mg twice daily for the treatment of overt hepatic encephalopathy in Italy.

PURPOSE: Hepatic encephalopathy (HE) is associated with a reduced survival, an increased risk of hospitalization for recurrences, and a reduced health-related quality of life. The purpose of the present economic analysis was to evaluate the impact on the Italian National Health Service (INHS) expenditure of the treatment with rifaximin 550 mg twice daily (Tixteller®/Tixtar®) for the reduction of the recurrences of overt HE, with respect to the current treatment approach. PATIENTS AND METHODS: Costs associated with patients treated with rifaximin 550 mg twice daily were estimated considering the reduction in hospitalizations for HE recurrences revealed by registrative clinical trial (-50%) applied to the hospitalization rate (42.5%) emerging from an Italian observational real-world study; costs associated with patients not treated with rifaximin were estimated based on the hospitalization rate, resulting from the same Italian observational study. Sensitivity analyses considering possible different discount levels to INHS structures for rifaximin were performed. The INHS perspective for a period of 3 years was considered. RESULTS: The treatment with rifaximin 550 mg twice daily, although increasing drug costs, is associated with a reduction in hospitalizations for HE recurrences that leads to an overall reduction of total costs charged to INHS, which could be estimated, based on the forecasted uptake of the treatment, at about €130,000 in the first year, reaching ~€260,000 in the third year. Considering a possible discount for rifaximin 550 mg to INHS structure of 20%, the total saving at the third year accounts for ~€3,000,000. Moreover, a relevant reduction in the number of hospitalizations and bed days is associated with rifaximin treatment. CONCLUSION: The treatment with rifaximin 550 mg twice daily, even if associated with an increase in drug expenditure, results in a reduction in total health care costs charged to INHS due to a reduction in hospitalizations for HE recurrences.

Healthcare costs of the progression of chronic kidney disease and different dialysis techniques estimated through administrative database analysis.

BACKGROUND: Chronic kidney disease (CKD) progression is associated with significant comorbidities and costs. In Italy, limited evidence of healthcare resource consumption and costs is available. We therefore aimed to investigate the direct healthcare costs in charge to the Lombardy Regional Health Service (RHS) for the treatment of CKD patients in the first year after starting hemodialysis and in the 2 years prior to dialysis. METHODS: Citizens resident in the Lombardy Region (Italy) who initiated dialysis in the year 2011 (Jan 1 to Dec 31) were selected and data were extracted from Lombardy Regional databases on their direct healthcare costs in the first year after starting dialysis and in the 2 years prior to it was analyzed. Drugs, hospitalizations, diagnostic procedures and outpatient costs covered by RHS were estimated. Patients treated for acute kidney injury, or who died or stopped dialysis during the observational period were excluded. RESULTS: From the regional population (>9,700,000 inhabitants), 1067 patients (34.3 % females) initiating dialysis were identified, of whom 82 % underwent only hemodialysis (HD), 13 % only peritoneal dialysis (PD) and the remaining 5 % both treatments. Direct healthcare costs/patient were € 5239, € 12,303 and € 38,821 (€ 40,132 for HD vs. € 30,444 for PD patients) for the periods 24-12 months pre-dialysis, 12-0 months pre-dialysis, and in the first year of dialysis, respectively. CONCLUSIONS: This study highlights a significant economic burden related to CKD and an increase in direct healthcare costs associated with the start of dialysis, pointing to the importance of prevention programs and early diagnosis.

Impact of hospitalizations for bronchiolitis in preterm infants on long-term health care costs in Italy: a retrospective case-control study.

PURPOSE: Bronchiolitis is an acute inflammatory injury of the bronchioles, and is the most frequent cause of hospitalization for lower respiratory tract infections in preterm infants. This was a retrospective, observational, case-control study conducted in Italy, based on administrative database analysis. The aim of this study was to evaluate differences in health care costs of preterm infants with and without early hospitalization for bronchiolitis. PATIENTS AND METHODS: Preterm infants born in the period between January 1, 2009 and December 31, 2010 and hospitalized for bronchiolitis in the first year of life were selected from the ARNO Observatory database and observed for the first 4 years of life. These preterm infants were compared (paired 1-3) with preterm infants who were not hospitalized for bronchiolitis in the first year of life and with similar characteristics. Only direct health care costs reimbursed by the Italian National Health Service were considered for this study (drugs, hospitalizations, and diagnostic/therapeutic procedures). RESULTS: Of 40,823 newborns in the accrual period, 863 were preterm with no evidence of prophylaxis, and 22 preterm infants were hospitalized for bronchiolitis (cases) and paired with 62 controls. Overall, cases had 74% higher average cost per infant in the first 4 years of life than controls (18,624€ versus 10,189€, respectively). The major cost drivers were hospitalizations, accounting for >90% in both the populations. The increase in total yearly health care cost between cases and controls remained substantial even in the fourth year of life for all cost items. A relevant increase in hospitalizations and drug consumption linked to respiratory tract diseases was noted in infants hospitalized for bronchiolitis during the entire follow-up period. CONCLUSION: Preterm infants hospitalized for bronchiolitis in the first year of life were associated with increased resource consumption and costs throughout the entire period of observation; even in the fourth year, the difference versus paired controls was relevant.

Inhalation errors due to device switch in patients with chronic obstructive pulmonary disease and asthma: critical health and economic issues.

BACKGROUND: Different inhalation devices are characterized by different techniques of use. The untrained switching of device in chronic obstructive pulmonary disease (COPD) and asthma patients may be associated with inadequate inhalation technique and, consequently, could lead to a reduction in adherence to treatment and limit control of the disease. The aim of this analysis was to estimate the potential economic impact related to errors in inhalation in patients switching device without adequate training. METHODS: An Italian real-practice study conducted in patients affected by COPD and asthma has shown an increase in health care resource consumption associated with misuse of inhalers. Particularly, significantly higher rates of hospitalizations, emergency room visits (ER), and pharmacological treatments (steroids and antimicrobials) were observed. In this analysis, those differences in resource consumption were monetized considering the Italian National Health Service (INHS) perspective. RESULTS: Comparing a hypothetical cohort of 100 COPD patients with at least a critical error in inhalation vs 100 COPD patients without errors in inhalation, a yearly excess of 11.5 hospitalizations, 13 ER visits, 19.5 antimicrobial courses, and 47 corticosteroid courses for the first population were revealed. In the same way, considering 100 asthma patients with at least a critical error in inhalation vs 100 asthma patients without errors in inhalation, the first population is associated with a yearly excess of 19 hospitalizations, 26.5 ER visits, 4.5 antimicrobial courses, and 21.5 corticosteroid courses. These differences in resource consumption could be associated with an increase in health care expenditure for INHS, due to inhalation errors, of €23,444/yr in COPD and €44,104/yr in asthma for the considered cohorts of 100 patients. CONCLUSION: This evaluation highlights that misuse of inhaler devices, due to inadequate training or nonconsented switch of inhaled medications, is associated with a decrease in disease control and an increase in health care resource consumption and costs.

Overt hepatic encephalopathy in Italy: clinical outcomes and healthcare costs.

PURPOSE: Hepatic encephalopathy (HE) is a recurrent severe complication of progressive hepatic cirrhosis. The aim of this study is to evaluate the average annual direct healthcare costs for the treatment of patients with overt HE in Italy. PATIENTS AND METHODS: This retrospective, observational study analyzed information from the database of ARNO Observatory. Patients with at least one hospitalization due to overt HE in the period from January 1, 2011 to December 31, 2011, were selected and observed during the year following the hospitalization. Costs for drugs, diagnostic and therapeutic procedures, and hospitalizations were estimated from the Italian National Health Service perspective. RESULTS: Out of a population of 2,678,462 subjects, 381 patients were identified, of whom, 21.5% died during the first hospitalization and 5.8% during the follow-up; the survival rate was 72.7% at the end of the observation period. The direct healthcare costs per patient amounted to €13,393/year (15,295 USD) (88% for hospitalizations, 8% for drugs, and 4% for diagnostic procedures). During the follow-up, 42.5% of patients had at least one rehospitalization due to HE. Patients readmitted for HE had an average annual cost of €21,272 (24,293 USD), almost doubled if compared to patients without readmissions (€12,098 [13,816 USD]). CONCLUSION: This analysis showed that patients with HE had relevant direct healthcare costs, in which hospitalizations were the most important cost drivers.

Evaluating targets and costs of treatment for secondary hyperparathyroidism in incident dialysis patients: the FARO-2 study.

BACKGROUND: The aim of this analysis was to estimate biochemical parameters and the costs of treatment of secondary hyperparathyroidism (SHPT) in a subpopulation of the FARO-2 study. METHODS: The FARO-2 observational study aimed at evaluating the patterns of treatment for SHPT in naïve hemodialysis patients. Data related to pharmacological treatments and biochemical parameters (parathyroid hormone [PTH], calcium, phosphate) were recorded at entry to hemodialysis (baseline) and 6 months later (second survey). The analysis was performed from the Italian National Health Service perspective. RESULTS: Two prominent treatment groups were identified, ie, one on oral calcitriol (n=105) and the other on intravenous paricalcitol (n=33); the intravenous calcitriol and intravenous paricalcitol + cinacalcet combination groups were not analyzed due to low patient numbers. At baseline, serum PTH levels were significantly higher in the intravenous paricalcitol group (P<0.0001). At the second survey, the intravenous paricalcitol group showed a higher percentage of patients at target for PTH than in the oral calcitriol group without changing the percentage of patients at target for phosphate. Moreover, between baseline and the second survey, intravenous paricalcitol significantly increased both the percentage of patients at target for PTH (P=0.033) and the percentage of patients at target for the combined endpoint PTH, calcium, and phosphate (P=0.001). The per-patient weekly pharmaceutical costs related to SHPT treatment, erythropoietin-stimulating agents and phosphate binders accounted for 186.32€ and 219.94€ at baseline for oral calcitriol and intravenous paricalcitol, respectively, while after 6 months, the costs were 180.51€ and 198.79€, respectively. Either at the beginning of dialysis or 6 months later, the total cost of SHPT treatment was not significantly lower in the oral calcitriol group compared with the intravenous paricalcitol group, with a difference among groups that decreased by 46% between the two observations. The cost of erythropoietin stimulating agents at the second survey was lower (-22%) in the intravenous paricalcitol group than in the oral calcitriol group (132.13€ versus 168.36€, respectively). CONCLUSION: Intravenous paricalcitol significantly increased the percentage of patients at target for the combined endpoint of PTH, calcium, and phosphate (P=0.001). The total cost of treatment for the patients treated with intravenous paricalcitol 6 months after entry to dialysis was not significantly higher than the cost for patients treated with oral calcitriol.

Gender, socioeconomic position, revascularization procedures and mortality in patients presenting with STEMI and NSTEMI in the era of primary PCI. Differences or inequities?

BACKGROUND: Several studies have reported gender and socioeconomic differences in the use of revascularization procedures in patients with acute myocardial infarction. However, it is not clear whether these differences influence patients' survival. Moreover, most of the studies neither considered STEMI and NSTEMI separately, nor included primary PCI, which nowadays is the treatment of choice in case of AMI. In an unselected population of patients admitted to hospital with a first episode of STEMI and NSTEMI we examined gender and socioeconomic differences in the use of cardiac invasive procedures and in one-year mortality. METHODS: Subjects hospitalized with a first episode of STEMI (n=3506) or NSTEMI (n=2286) were selected from the Piedmont (Italy) hospital discharge database. We considered the percentage of patients undergoing PCI, primary PCI and CABG, and in-hospital mortality. Out of hospital mortality was calculated through record linkage with the regional register. The relation between outcomes and gender or educational level was investigated using appropriate multivariate regression models adjusting for available confounders. RESULTS: After adjustment for age, comorbidity and hospital characteristics, women and low educated patients had a lower probability of undergoing revascularization procedures. However, neither in-hospital, nor 30-day, nor 1-year mortality showed gender or social disparities. CONCLUSIONS: Despite gender and socioeconomic differences in the use of revascularization, no differences emerged in in-hospital and 1-year mortality. These findings could suggest that patients are differently, but equitably, treated; differences are more likely due to an inability to fully adjust for clinical conditions rather than to a selection process at admission.

Outcomes and costs of treating chronic obstructive pulmonary disease with inhaled fixed combinations: the Italian perspective of the PATHOS study.

PURPOSE: Fixed-dose combinations of inhaled corticosteroids and long-acting ß2-agonists have proven to prevent and reduce chronic obstructive pulmonary disease (COPD) exacerbations. The aim of this analysis was to explore the clinical consequences and direct health care costs of applying the findings of the PATHOS (An Investigation of the Past 10 Years Health Care for Primary Care Patients with Chronic Obstructive Pulmonary Disease) study to the Italian context. PATIENTS AND METHODS: Effectiveness data from the PATHOS study, a population-based, retrospective, observational registry study conducted in Sweden, in terms of reduction in COPD and pneumonia-related hospitalizations, were considered, in order to estimate the differences in resource consumption between patients treated with budesonide/formoterol and fluticasone/salmeterol. The base case considers the average dosages of the two drugs reported in the PATHOS study and the actual public price in charges to the Italian National Health Service, while the difference in hospitalization rates reported in the PATHOS study was costed based on Italian real-world data. RESULTS: The PATHOS study demonstrated a significant reduction in COPD hospitalizations and pneumonia-related hospitalizations in patients treated with budesonide/formoterol versus fluticasone/salmeterol (-29.1% and -42%, respectively). In the base case, the treatment of a patient for 1 year with budesonide/formoterol led to a saving of €499.90 (€195.10 for drugs, €193.10 for COPD hospitalizations, and €111.70 for pneumonia hospitalizations) corresponding to a -27.6% difference compared with fluticasone/salmeterol treatment. CONCLUSION: Treatment of COPD with budesonide/formoterol compared with fluticasone/salmeterol could lead to a reduction in direct health care costs, with relevant improvement in clinical outcomes.

Resource consumption and healthcare costs of acute coronary syndrome: a retrospective observational administrative database analysis.

The objective of this study was to estimate resource consumption and direct healthcare costs of patients with a first hospitalization for acute coronary syndrome (ACS) in 2008 in the Piedmont Region, Italy. Subjects hospitalized with a first episode of ACS in 2008 were selected from the regional hospital discharge database. All hospitalizations, drug prescriptions, and outpatient episodes of care in the 12 months following discharge were considered to estimate resource consumption and direct healthcare costs from the Piedmont Regional Health Service perspective. The analysis was carried out separately for ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA) populations. In the accrual period, 7765 subjects (1.75‰ of the total population) were hospitalized for ACS (64.2% men). The average age was 66.5 for men and 75.4 for women. The average in-hospital mortality was 6.5% (n = 508). The total ACS population was classified as: STEMI 45.2%, NSTEMI 29.4%, and UA 25.4%. The average yearly costs per patient alive at the end of follow-up (n = 6851) were 14,160.8&OV0556; (18,678.7 USD): 83.9% for inpatient admissions [11,881.2&OV0556; (15,671.8 USD)], 9.3% for drugs [1311.6&OV0556; (1730.1 USD)], 5.0% for diagnostic and therapeutic procedures and outpatient visits [708.2&OV0556; (934.1 USD)], and 1.8% for 1-day hospital stays [259.8&OV0556; (342.7 USD)]. The average yearly direct healthcare costs by ACS event were 14,984.5&OV0556; (19,765.2 USD) for STEMI, 14,554.1&OV0556; (19,197.4 USD) for NSTEMI, and 12,481.5&OV0556; (16,463.6 USD) for UA. In each subpopulation, costs were significantly higher for men than for women. ACS imposes a significant burden in terms of morbidity and mortality and generates major public health service costs.

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study.

BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study. MATERIALS AND METHODS: In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective. RESULTS: Four cohorts were identified: patients treated with oral (PO) calcitriol (n=182), intravenous (IV) calcitriol (n=34), IV paricalcitol (n=62), and IV paricalcitol+cinacalcet therapy (n=20); the cinacalcet monotherapy group was not analysed due to low number of patients (n=9). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300 pg/ml; p<0.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitol+cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort's PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (p=0.020, p=0.012, and p=0.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitol+cinacalcet cohort (p<0.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns. CONCLUSIONS: The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitol+calcimemtics (p<0.001), without a significant difference in terms of baseline severity and PTH control.