Assessment of patients affected by rheumatoid arthritis eligible for biotechnological agents and evaluation of their healthcare resource utilization and related costs.

OBJECTIVE: To provide estimates of patients with rheumatoid arthritis (RA) eligible for biotechnological therapy and to evaluate their healthcare costs. METHOD: An observational analysis was performed based on data-linkage between administrative databases of selected Italian Regional/Local healthcare departments. Data were then re-proportioned to the Italian population. Patients with RA diagnosis defined by discharge diagnosis and/or exemption code during 01/01/2013- 31/12/2017 were included. The criteria applied to evaluate the elegibility for biotechnological therapy were: 1) methotrexate (MTX)-treatment failure ≥6 months and start of a different conventional-synthetic diseasemodifying antirheumatic drugs (csDMARD); 2) corticosteroid ≥6 months with dosage ≥7.5 mg/die; 3) MTX-contraindication (therapy or hospitalization for renal damage/interstizial lung disease/hepatic failure). Mean annual costs per patient included drugs, hospitalizations, outpatient services. RESULTS: Data re-proportioned to the Italian population estimated 318,328 RA patients: 43,361 with, 274,967 without biotechnological agents. Among the latter, 26,487(9.6%) patients met ≥1 criteria applied for eligibility: 1,896 had MTX-treatment failure and started another csDMARD; 15,833 received corticosteroid ≥7.5 mg/die; 7,788 had MTX-contraindication. Regarding patients fulfilling two criteria, 107 had MTX-treatment failure followed by another csDMARDs and corticosteroid ≥7.5 mg/die, 53 were treated with another csDMARDs after MTX-treatment failure and also presented MTX-contraindication, 810 had corticosteroid ≥7.5 mg/die and MTX-contraindication. Mean total annual costs for patients estimated eligible for biotechnological therapy was € 3,132, of which € 177 related to drugs indicated for RA and € 2,955 related to other direct costs. CONCLUSIONS: According to our estimates, around 10% RA patients not currently treated with biotechnological agents are eligible for such therapies, highlighting a trend of under-use in clinical practice for RA management.

Multidisciplinary model for hospital-territory integrated management of patient with bone fragility: primary and secondary prevention of fractures according to severity and complexity.

The aim of this study was to promote the construction of a real network and a shared diagnostic and therapeutic management model between hospitals and out-of-hospital healthcare services to capture as many patients with bone fragility as possible. Starting from the analysis of the clinical competences present in the province of Pavia, the bone specialists (BSs) organized some educational events involving both general practitioners (GPs) and hospital specialists. The Fracture Liaison Service (FLS) model, the revision of Note 79, the national plan for chronicity and the health reform of the Lombardy Regional Authority supported the structure of our model, in which the roles of clinicians are well defined and based on the complexity and severity of patients. In our method the GP has a central role as clinical manager, facilitating patient management and communication between the specialists and the BS. In January 2019, the Therapeutic Care Diagnostic Path (PDTA) shared between 2 bone specialists (BSs), 9 GPs, as reference treaters, and a multidisciplinary group of 25 specialists of the Province of Pavia was defined. The strategic directions of the two largest public hospitals in Pavia have supported the PDTA, which was validated by the quality departments of the hospitals themselves. Finally, sixty GPs belonging to the network have joined the PDTA. This model is the first example of integrated management between hospitals and out-of-hospital healthcare services for the primary and secondary prevention of fragility fractures (FF), where the GPs play a pivotal role as managers and supervisors to ensure proper care to chronic patients according to their levels of severity.

Clinical Characteristics And Health Care Resources In Patients Treated With Oral Anticoagulants: Evidences From Italian Administrative Databases.

OBJECTIVES: 1) To evaluate anticoagulation treatment patterns and health care resource use in adult patients with a discharge diagnosis of non-valvular atrial fibrillation (NVAF) in an Italian real-world setting and 2) to describe the characteristics of NVAF patients in relation to treatment. DESIGN: A retrospective cohort study in a "real-world" setting. SETTING: Data were analysed by integrating administrative databases that included approximately 2,000,000 individuals assisted by the National Health System from two Italian Local Health Units. PARTICIPANTS: All adult patients with at least one hospital discharge or ≥2 outpatient visits with a diagnosis code for NVAF from 1/01/2011 to 31/12/2015 were included. MAIN OUTCOME MEASURES: Anticoagulation treatment patterns, health care resource use and major bleeding events that occurred during the follow-up period were evaluated. RESULTS: 32,863 NVAF patients were included, of whom 7,831 had at least one prescription of oral anticoagulants. Among them, 6,876 patients were vitamin K antagonists (VKA) users and 955 were non-vitamin K antagonist oral anticoagulant (NOAC) users at index date (ID). During the follow-up period, the use of antiplatelet drugs was higher among VKA-naïve users than the NOAC-naïve users. Among NOAC users, 76.1% showed an adherence level ≥80% during follow-up. The rate of bleeding events resulted higher for VKA patients compared to NOAC patients. The unadjusted incidence rate was 10.46 per 1000 person-year for VKA patients and 4.55 per 1,000 person-years for NOAC patients. The overall annual cost (in term of drugs, hospitalisations and outpatient specialist services) was € 5,156.13 for VKA and € 4,630.57 for NOAC. CONCLUSION: This unselected cohort study, on NVAF patients being prescribed oral anticoagulants, highlights that VKA was largely prescribed and the great majority of patients on NOACs were adherent to treatment. Most of the OAC patients still received antiplatelet agents in combination, and in NOAC patients, we registered a lower number of bleeding events compared with VKA.

Explorative analysis of gender-specific characteristics in patients with heart failure in an Italian hospital.

Sex-related differences have been shown to deeply affect health-related aspects of patients. However, the lack of gender-specific analysis makes it difficult to advance personalized medicine in terms of a gender-based approach. The aim of the present study was to describe gender-specific features of patients diagnosed with heart failure (HF), with a focus on the clinical presentation. Data were collected from a properly designed database and referred to an Italian hospital. Patients aged ≥18 years with a primary or secondary diagnosis of HF between 1 January 2012 and 31 December 2016 were included, and their demographic and clinical characteristics were analyzed according to gender. Of the 719 HF patients included, 317 (44.1%) were male and 402 (55.9%) were female. Women tended to be older compared to men (82.4±8.8 years and 77.1±10.6 years, respectively). As for clinical presentation, 62.1% of female and 38.3% of male patients had preserved ejection fraction, and 56.1% of men and 58.2% of women suffered from atrial fibrillation. The left atrium was partially compromised in 62.4% of male and 63% of female patients, while right atrium dysfunction tended to be more frequent in male patients compared to female patients (29.1% and 25.5%, respectively). In conclusion, gender-specific features of a cohort of HF patients from a clinical setting were accurately described.

Therapeutic strategies utilization and resource consumption in patients treated for psoriatic arthritis: findings from a real-world analysis in an Italian setting.

PURPOSE: The purpose of this study was to analyze the therapeutic strategies and estimate the health care resource consumption in patients with psoriatic arthritis (PsA). PATIENTS AND METHODS: An observational retrospective cohort analysis of administrative databases of six Italian Local Health Units was performed. Patients ≥18 years with a hospitalization discharge diagnosis of PsA (International Classification of Diseases, Ninth Revision code: 696.0) or exemption code (045.696.0) for PsA from January 1, 2010 to December 31, 2015 (inclusion period), with at least one prescription of any therapy used for PsA were included. The index date (ID) was the first date matching with at least one of the inclusion criteria during the inclusion period. All patients were followed up after the ID until the end of data availability. Baseline C-reactive protein (CRP) levels (±6 months in relation to the ID) were also analyzed. RESULTS: A total of 2,408 (prevalence 0.83 per 1,000) patients with PsA (male 52%; median age 54 years) were included in the study; patients were already treated for PsA in 42.4% of cases. At 1 year of follow-up, 73% of the patients received one systemic drug, while 22% of patients received two systemic drugs; in addition, our results show an increase in the number of add-on or switches in a longer follow-up period. The utilization of biologic agents was higher among patients with previous PsA treatment, showing a progression of the pathology. Overall, a medium/high level of CRP at baseline was observed among more than half of the overall sample, with slight changes across subgroups in analysis. The average health care costs were €1,966.4 and €13,914 per year for patients treated with conventional systemic therapy and biological agents, respectively. CONCLUSION: A better knowledge of prescription therapeutic scheme and economic burden of PsA could stimulate the rational development of health programs aimed at potentiating services for its management.

The cost of atrial fibrillation in Italy: a five-year analysis of healthcare expenditure in the general population. From the Italian Survey of Atrial Fibrillation Management (ISAF) study.

OBJECTIVE: Atrial fibrillation (AF) is a relevant item of expenditure for the National Healthcare systems. The aim of the study was to estimate the annual costs of AF in Italy. PATIENTS AND METHODS: The Italian Survey of Atrial Fibrillation Management Study enrolled 6.036 patients with AF among 295.906 subjects representative of the Italian population. Data were collected by 233 General Practitioners (GPs) distributed across Italy. Quantities of resources used during the 5 years preceding the ISAF screening were inferred from the survey data and multiplied by the current Italian unit costs of 2015 in order to estimate the mean per patient annual cumulative cost of AF. Patients were subdivided on the basis of the number of hospitalizations, invasive/non-invasive diagnostic tests and invasive therapeutic procedures in 3 different clinical subsets: "low cost", " medium cost" and "high cost clinical scenario". RESULTS: The estimated mean costs per patient per year were 613 €, 891 € and 1213 € for the "Low cost", "Medium cost" and "High Cost Clinical Scenario" respectively. Hospitalizations and inpatient interventional procedures accounted for more than 80% of the cumulative annual costs. The mean annual costs among patients pursuing "Rhythm control" strategy was 956 €. CONCLUSIONS: In Italy, the estimated costs of AF per patient per year are lower than those reported in other developed countries and vary widely related to the different characteristics of AF patients. Hospitalizations and interventional procedures are the main drivers of costs. The mean annual cost of AF is mainly influenced by the duration of the period of observation and the patients' characteristics. Measures to reduce hospitalizations are needed.

Hyperuricemia is associated with increased hospitalization risk and healthcare costs: Evidence from an administrative database in Italy.

BACKGROUND AND AIM: Chronic hyperuricemia is responsible for a relevant burden of articular diseases and cardio-nephrometabolic disorders. We evaluated the effect of high serum uric acid (SUA) levels on hospitalization risk and mortality and on healthcare costs in a real-life setting. METHODS AND RESULTS: We conducted a retrospective analysis using a large administrative database and a clinical registry among 112,170 subjects from three Italian local health units. Individuals were divided into four groups according to their SUA levels: <6 mg/dL (66.5%), >6 mg/dL and ≤7 mg/dL (19.3%), >7 mg/dL and ≤8 mg/dL (8.7%), and >8 mg/dL (5.5%). Compared to those with SUA level of <6 mg/dL, the risk of hospitalization related to gout and/or nephrolithiasis was higher in the three groups of patients with higher SUA levels (1.51, P = 0.100; 2.21, P = 0.005; and 1.17, P = 0.703, respectively). A similar trend was also observed for hospitalization due to chronic kidney disease (CKD) (1.31, P < 0.001; 1.40, P < 0.001; and 2.18, P < 0.001, respectively) and cardiovascular disease (CVD) (1.08, P < 0.001; 1.23, P < 0.001; and 1.67, P < 0.001, respectively) and for all-cause mortality (0.97, P = 0.309; 1.21, P < 0.001; and 2.15, P < 0.001). The mean annual healthcare costs were higher in patients with higher SUA level (€2752, €2957, €3386, and €4607, respectively) mainly because of a progressive increase in hospitalization costs per patient (from € 1515 for SUA <6 mg/dL to € 3096 for SUA >8 mg/dL). CONCLUSIONS: Increased SUA levels are associated with an increased risk of hospitalizations related to hyperuricemia, CKD, and CVDs and total mortality, and consequently with higher total healthcare costs and hospitalization costs per patient.

Costs associated with emergency care and hospitalization for severe hypoglycemia.

BACKGROUND AND AIMS: We aimed to determine the direct economic cost of the management of severe hypoglycemia among people with diabetes in Italy. METHODS AND RESULTS: Data of cases with an acceptance diagnosis of hypoglycemia between January 2011 and June 2012 were collected in 46 Emergency Departments (EDs). Emergency care costs were computed by estimating the average cost per ambulance service, ED visit and short-term (<24 h) observation period. Hospitalization expenditure was estimated using the average cost reimbursed by the Italian healthcare system for hospital admission per patient with diabetes in a specific hospital ward. We retrieved 3516 hypoglycemic episodes occurring in subjects with diabetes. Half the cases (51.8%) required referral to EDs by means of the emergency ambulance services. A total of 1751 cases (49.8%) received an ED visit followed by discharge; 604 cases (17.2%) received a short-term observation period; 1161 (33.1%) were hospitalized. Unit costs for emergency care management were estimated at €205 for an ambulance call, €23 for an ED visit, and €220 for a short-term observation. The mean hospitalization cost was estimated at €5317; the average cost per each severe hypoglycemic event totaled €1911. From a base case assumption, the total direct cost of severe hypoglycemia in patients with diabetes in Italy was estimated to be approximately €23 million per year. CONCLUSION: Severe hypoglycemia in patients with diabetes constitutes a remarkable economic burden for national healthcare systems. Measures for preventing hypoglycemia are mandatory in diabetes management programs considering the impact on patients and on health spending.

Adherence to therapeutic and diagnostic recommendations in patients with femur fracture and at risk of re-fracture or death: results of an analysis of administrative databases.

The aim of the present study was to evaluate the application into clinical practice of therapeutic and diagnostic recommendations for the prevention of bone re-fracture in postmenopausal women after an hospitalization for hip fracture in clinical practice and to assess the relationship between the application of diagnostic recommendations and re-fracture or death risk. A retrospective cohort analysis was conducted. All female patients, at least 65 years old, and with an hospitalization with main or secondary diagnosis of hip fracture during the period 1 January 2006 - 31 December 2008, were included. Besides demographic characteristics and comorbidities, drug treatment prescriptions related to bone fracture or supplementary with calcium or vitamin D and prescriptions of recommended laboratory and instrumental diagnostic tests (e.g. spine radiography), were analysed. A total of 5,636 patients were included in the study. The prescription of a drug treatment aimed to reduce the risk of re-fracture was found in 16.3% of patients, among them 76.3% (699 patients) used bisphosphonates only, 17.1% (157 patients) strontium ranelate only and 4.9% (45 patients) used more than one treatment during the observation period. Among the patients who did not receive drug treatment, 17.5% made use of only supplemental calcium and vitamin D. The remaining part of patients (69.1%) received no treatment. The prescription of at least one laboratory test of first and second level was performed, respectively, on 53.7% and 43.1% of included patients, whereas the prescription of at least one instrumental test of first and second level was performed, respectively, on 5.9% and 0.8%. Although it is established that the prescription of the recommended tests and appropriate drug treatment are significantly associated with reduced risk of re-fracture and death, today the application of these recommendations is reduced.

Use of antihypertensive and lipid-lowering drugs: the management of cardiovascular risk in clinical practice.

The objective of the study was to analyse the treatment of high blood pressure (BP) and hypercholesterolaemia, as well as the effect of individual or combined antihypertensive-hypocholesterolaemic therapy on BP control and on circulating cholesterol. A retrospective study was performed using clinical data recorded in the general practitioner's database. The sample included all patients, aged > or =18 years, with BP reading or low-density lipoprotein (LDL) cholesterol measurement recorded between January 2003 and December 2004. BP and LDL cholesterol targets were defined using cutoffs based on the guidelines of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7) and the National Cholesterol Education Program (NCEP/ATPIII). The study included 4764 patients (mean age 67.6+/-11.8 years, 43.5% males). Target BP was achieved in a higher number of patients under combined antihypertensive-hypocholesterolaemic therapy than in those treated only with antihypertensives: 57.0 vs 50.0% in patients with history of cardio/cerebrovascular (CV) hospitalization, 27.0 vs 16.9% in patients with diabetes or chronic renal insufficiency (CRI) and 59.7 vs 49.1% in patients with no CV hospitalization nor diabetes and nor CRI. The LDL cholesterol target was achieved in 61.3% of the subjects: it was independent on the therapy (individual or combined), but related to the degree of cardiovascular risk. Analysing the data contained in the general medicine database made it possible to evaluate the treatment of high BP and hypercholesterolaemia in relation to cardiovascular risk in clinical practice and to establish the need to pay greater attention to achieving the objective set by guidelines.

Pharmacoutilization and costs of osteoarthritis: changes induced by the introduction of a cyclooxygenase-2 inhibitor into clinical practice.

OBJECTIVE: To establish whether the introduction of a cyclooxygenase-2 inhibitor has led to changes in pharmacoutilization in the treatment of osteoarthritis (OA) in clinical practice. METHODS: Administrative and general practice databases were cross-linked to analyse the use of non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective agents (GPAs) before and after the introduction of rofecoxib. Costs of treatment and costs of hospitalization for gastrointestinal events were also considered. RESULTS: A total of 3090 patients were evaluated. A significant reduction in the use of GPAs in the rofecoxib group was observed, corresponding to reductions of 64 and 59.7% compared to NSAIDs among patients in incident and prevalent cases respectively. The weighted mean daily cost of therapy with rofecoxib in incident cases was 1.88 euro, 7.4% lower than that of NSAIDs (2.03), and in prevalent cases it was 1.87 euro, 28.1% higher than that of NSAIDs (1.46). Although the rate of hospitalization was similar, there was an additional daily cost per patient of 186.6 for patients being treated with NSAIDs and 21.6 euro for those being treated with rofecoxib. CONCLUSIONS: The cyclooxygenase-2 inhibitor rofecoxib determined substantial changes in the pharmacoutilization and costs of OA.

[Evaluation model of the effect of Rofecoxib on the co-prescription of gastroprotective agents observed during the treatment of osteoarthritis]. / Modello valutativo dell'effetto sulla co-prescrizione di gastroprotettori osservato durante il trattamento dell'artrosi con Rofecoxib.

OBJECTIVE: This study was conducted to define an evaluation model to estimate changes in the co-prescription of gastroprotective agents (GPAs) induced by rofecoxib in the treatment of osteoarthritis (OA). METHODS: On the basis of a cross-linking information, which were stored in different administrative and clinical databases, a multivariate regression analysis was used to develop the model. Data were collected by 30 general practitioners of the Local Health Unit of Ravenna (middle-north of Italy). RESULTS: The study population consisted of 2,944 patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) and 487 treated with rofecoxib. Patients treated with rofecoxib generally presented a higher number of gastrointestinal damage risk factors and also a lower level of GPAs co-prescription compared to those treated with NSAIDs. Including in the model variables such as type of anti-inflammatory treatment (NSAIDs or rofecoxib), gender, age by class, previous hospital admissions due to gastrointestinal complications, number of different NSAIDs used, and prescription of corticosteroids, the regression equation and its coefficients were identified. A non-linear relationship between the percentage of patients treated with rofecoxib and the relative reduction of GPAs co-prescription was found. It has been estimated the basis of the registered percentage of patients treated with rofecoxib (17,6%) adjusting for gastrointestinal damage risk factors, and on a 63% (CI95%: 55%-70%) relative reduction of GPA use with rofecoxib with respect to NSAIDs was estimated. CONCLUSIONS: Based on data collected in the clinical practice after the introduction of rofecoxib, a model evaluating the relationship between the frequency of its use in the OA population and the expected reduction of GPAs, has been developed.

Pharmacoutilization of antihypertensive drugs: a model of analysis.

OBJECTIVES: To identify clinical and economic indicators of pharmacoutilization of antihypertensive drugs. PATIENTS AND METHODS: 4614 subjects receiving a first prescription for amlodipine, atenolol, fosinopril, indapamide, or losartan were included in the study. All prescriptions filled during the study period from January 1, 1997 to December 31, 1998 were considered. A retrospective analysis was carried out on information recorded in the drug database. The percentage of patients continuing, discontinuing, and switching the initial treatment, duration of treatment, and doses used were calculated together with total costs. RESULTS: A large proportion of patients (65.1%) discontinued the treatment. From the analysis of the mean daily dose taken by patients who continued the treatment, it was found that many subjects took a drug dosage which was below the therapeutic dose range, whereas the administration of doses above the therapeutic range occurred only occasionally. Continuation of treatment accounted for 48.1% of total costs, switching accounted for 20.8%, and discontinuation represented 31.1% of total expenditures. CONCLUSIONS: With adequate markers, helpful data can be collected for monitoring the quality of antihypertensive drug prescriptions and the rational usage of resources in the general practice setting.

The PANDORA project: results of the cost of illness analysis.

AIMS: To evaluate the cost of illness from hypertension for the Italian National Health System (NHS). METHODS AND RESULTS: A prospective analysis was carried out on clinical and economic data recorded in the general practitioners' (GPs) database. Twenty-one GPs working in the Ravenna area in Italy took part in the project on a voluntary basis. The study included 1047 hypertensive patients enrolled between 1 June and 31 December 1997 and continued for 365 days from the date of enrolment. The following costs were calculated: antihypertensive drugs, laboratory tests and instrumental procedures, GP visits for blood pressure control, specialist visits, casualty visits, hospitalisation due to cardiovascular problems. In the whole sample, the most relevant cost is due to antihypertensive drugs (42.7%), followed by hospital admission (28.4%), GP visits (15.1%) and tests (10.6%). The total mean cost was significantly lower in incident (no previous treatment) than in prevalent patients (already treated) (457 512 vs 725 573 Italian Lira (ITL), P < 0.05) and in older rather than in younger patients (1171 410 vs 796 452 (ITL) P < 0.05). (In the text the equivalent is given in Euros, Pounds Sterling and US dollars). CONCLUSION: Our study should be considered as preliminary, nevertheless it could represent a step towards the evaluation of the true cost of hypertension.