Chronic treatment of COPD: state of the art and real-world analysis of healthcare costs based on medication adherence data.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD), represents a serious and growing health problem worldwide. Healthcare should be conceived and structured in a proactive logic mode predicting to promote prevention and supporting the patient in the path of care. This desirable approach could reduce the impact of chronicity on patient' quality of life and health care costs. In this context, the theme of therapeutic adherence represents one of the priorities on which to intervene. OBJECTIVE: To show a real life picture of the health expenditure and economics consequences due to non-adherent COPD therapy. MATERIALS AND METHODS: Patients with a COPD diagnosis were selected from the Regional Health Information System Edotto; consumption data was also obtained from the same patients and was based on data relating to prescriptions dispensed by affiliated pharmacies belonging to the Local Health Agency of the province of Barletta-Andria-Trani (LHA BT) in a time period including 2017 and 2018. The assisted patients not adhering to COPD treatment (medication possession ratio between 20% and 80%) in 2017 were included in the analysis. The system Edotto was used to verify how many of them had become adherent in 2018. For both groups of patients, the average cost per patient was assessed, both in terms of pharmaceutical expenditure and hospitalizations due to COPD. RESULTS: Of the 66 patients not adhering to the treatment in 2017, 66.67% (44 patients) became adherent to therapy and 33.33% (22 patients) remained non-adherent to treatment during 2018. The total cost (pharmaceutical expenditure ATC-R03 and the cost derived from hospitalizations due to COPD) for non-adherent patient during 2018 was 73% increase compared to the cost of the patient adhering to treatment (p=.000317), thus resulting a saving of € 992.56 per adherent patient. CONCLUSIONS: Adherence to COPD therapy can improve patient health and reduce healthcare costs.

Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project.

BACKGROUND: Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. OBJECTIVE: The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. METHODS: A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010-2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. RESULTS: From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015-2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. CONCLUSION: The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010-2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings.

Analysis of the Introduction in Clinical Practice of New Oral Anticoagulants in Local Health Agency BT: Translation of the Clinical Trial Data to a Local Health Care Area.

The commercial release of the New Oral Anticoagulants (NOACs) has been the most significant change in anticoagulant therapy in recent years. The work aimed to evaluate the economic and health impact for the Local Health Agency Barletta-Andria-Trani (BT). Through the Regional Information System data about naïve patients on NOAC treatment and patients on anti-vitamin-k (VKA), treatments were extrapolated. We assessed therapeutic continuity, pharmaceutical expenditure, hospitalizations, and deaths in 2017 and 2018. Therapeutic continuity was similar in the two groups. The number and the average cost of hospitalizations for a patient treated with VKAs were almost constant, while those of patients treated with NOACs decreased. The treatment of adult-aged naïve patients with NOACs, compared to VKAs therapy, involves an increase in expenditure of about 100€ for a patient, but the reduced hospitalizations could generate, in the long term, saving for the Health System. Clinical data, according to the Real-World Data, confirmed the safety and effectiveness of these drugs. However, attention to the special population is necessary to improve the safety and effectiveness of NOACs. Innovative formulations for pediatric patients are being developed. The challenge for Health Systems is the appropriate use of available resources through health interventions with transversal competences.

Post-marketing surveillance of adverse events following measles, mumps, rubella and varicella (MMRV) vaccine: retrospecive study in apulia region (ITALY), 2009-2017.

Since 2006, some Italian Regions introduced the active offer of measles, mumps, rubella, and varicella (MMRV) vaccine for all newborns during the second years of life. In 2011, Italian Drug Authority (AIFA) recommended the discontinuation of the MMRV use for an increased risk of febrile seizures following vaccination; furthermore, some Regions (such as Apulia, that introduced MMRV offer in 2009) chose to continue the use of MMRV and Ministry of Health recommended to guarantee supplemental monitoring of safety of the vaccine. In Italy, the surveillance of Adverse Events following immunization (AEFIs) is currently carried out by AIFA and Regional Health Authorities; this paper aims to summarize the results of MMRV-vaccine surveillance of AEFIs program carried out in Apulia. From the AIFA database, we selected MMRV AEFIs that occurred in Apulia (about 4,000,000 inhabitants) from 2009 to 2017. For serious AEFIs, we applied the WHO causality assessment algorithm, using for cases hospitalized information from individual medical records. In the 8 years of observation, 155 MMRV-AEFIs (reporting rate: 37.9×100,000 doses) occurred of which 26 were classified as serious (6.3×100,000 doses) and 22 led to hospitalization. Performing causality assessment, for 10 the classification was "consistent causal association to immunization" (reporting rate: 2.4×100000 doses), for 2 indeterminate, for 13 "inconsistent causal association to immunization" and for 1 not-classifiable. No case of febrile seizure resulted consistent to vaccination. All consistent serious AEFIs were completely resolved at subsequent follow-up.

Element shape design of 2-D CMUT arrays for reducing grating lobes.

Fully populated two-dimensional (2-D) arrays are needed to produce high quality ultrasonic volumetric images for real-time applications, but they present many challenges for their physical realization because of the large number of elements. In fact, lambda/2 and lambda minimum spacing between elements is required, respectively, for pyramidal and rectilinear scanning in order to avoid unwanted grating lobes (GLs). However, in past years, capacitive micromachined ultrasonic transducer (CMUT) technology has made possible the production of arrays with large flexibility in element shape and size. In this paper, this property is analyzed, and a new element shape, based on the concept of spatial interpenetration of adjacent elements, is proposed in order to design fully populated 2-D CMUT arrays with a low number of elements, whose beam characteristics are valid for volumetric imaging. Through the use of simulations, it is demonstrated that arrays with pitch larger than lambda (up to 3lambda) used for rectilinear scanning, have notably lower GLs than the equivalent standard arrays designed according to the classical squared element shape. As consequence, the proposed geometry has the advantage of reducing the number of elements (up to a factor of 9) and of enlarging the element size, implying an increase of the SNR relative to the single element. When beam steering is required, arrays can be designed with pitch equal to lambda, reducing the number of elements by a factor of 4 if the maximum steering angle is limited to +/-15 degrees .