A Novel Approach for Nanosponge: Wool Waste as a Building Block for the Synthesis of Keratin-Based Nanosponge and Perspective Application in Wastewater Treatment.

Wool waste is a huge environmental problem that needs to be addressed in order to avoid the continuous accumulation of biohazardous waste in landfills. In recent years, wool has proven to be an excellent source of keratin that can be used for various purposes. But never before has keratin from wool waste been used as a building block to synthesize a well-known class of biopolymers called nanosponges. Typically, nanosponges are produced by the reaction of cyclodextrins with an appropriate cross-linker to obtain an insoluble hyper-cross-linked polymer, which has applications in various fields. For this reason, a novel, affordable approach for the synthesis of a novel class of nanosponge using wool keratin as the building block has been presented. The keratin nanosponge was synthesized by reacting keratin with pyromellitic dianhydride as a cross-linking agent. The formation of a cross-linked polymer was successfully confirmed by CHNS-elemental analysis, TGA, DSC, FTIR-ATR, SEM, and water absorption capacity measurements. Surprisingly, the keratin-based nanosponge showed ∼50% uptake of heavy metals after only 24 h of contact time. The adsorption kinetics was also evaluated, indicating a pseudo-second-order model fit and the mechanism is predominantly the intraparticle diffusion process. The novel synthesized nanosponge proved to be a possible alternative for wastewater treatment.

Advanced Therapy Medicinal Products: Availability, Access and Expenditure in Italy.

BACKGROUND: Advanced therapy medicinal products (ATMPs) are an innovative output of biomedical research, characterized by a high level of uncertainty on long-term efficacy and safety, elevated price tags and often complex administration. All these elements compounded make their European authorization, national price negotiation for reimbursement and subsequent dispensation and administration to the patient less straightforward and often less successful than for less innovative drugs. To assess if these hurdles have affected patient access and how are ATMPs used in Italy, we have analysed availability, access and expenditure of ATMPs in the period spanning from 2016 to 2023. METHODS: We have analysed real world data on the duration of ATMP regulatory evaluations for authorisation and reimbursement, time to first patient access and expenditure for ATMPs through the Italian National Health System (INHS) expenditure data flow, as well as information on patient mobility and availability of health facilities specialized in administering ATMPs. FINDINGS: Of the 18 ATMPs currently authorized in Europe, 9 are reimbursed by the INHS, but only 6 were actually used, generating a cumulative expenditure of roughly 300 Mln€ from 2016 to 2023, largely owing to CAR-T therapies. Time to patient access reaches an average of 340.6 days from the day publication in the official Gazette of the reimbursement decision to first patient treatment in one of the 107 health facilities authorized for ATMP administration, after an even longer evaluation time by regulatory agencies. CONCLUSION: Since the first reimbursement decision for an ATMP in Italy, back in 2016, these innovative drugs became progressively more and more available, both in terms of numbers and in terms of coverage across the country. Almost all Italian regions have at least one centre for ATMP administration and has performed a treatment in 2023. Notwithstanding their high per-treatment prices, ATMPs currently have a rather contained expenditure, however it is bound to keep growing in the next few years.

Antihypertensive therapy during pregnancy: the prescription pattern in Italy.

Drug use during pregnancy should be evidence-based and favor the safest and most appropriate prescription. The Italian Medicines Agency (AIFA) coordinates a network focusing on monitoring medication use in pregnancy. Hypertensive disorders are common medical complication of pregnancy and antihypertensive therapy is prescribed to reduce the risk of adverse feto-maternal complications. The objective of this study is to highlight the prescription pattern of antihypertensive drugs before pregnancy, during pregnancy and in the postpartum period in Italy and to evaluate their use with a specific attention to the prescription pattern of drugs considered safe during pregnancy. A multi-database cross-sectional population study using a Common Data Model (CDM) was performed. We selected all women aged 15-49 years living in eight Italian regions who gave birth in hospital between 1 April 2016 and 31 March 2018. In a cohort of 449.012 women, corresponding to 59% of Italian deliveries occurred in the study period, the prevalence of prescription of antihypertensive drugs in the pre-conceptional period was 1.2%, in pregnancy 2.0% and in the postpartum period 2.9%. Beta-blockers were the most prescribed drugs before pregnancy (0.28%-0.30%). Calcium channel blockers were the most prescribed drugs during pregnancy, with a prevalence of 0.23%, 0.33%, 0.75% in each trimester. Alfa-2-adrenergic receptor agonists were the second most prescribed during pregnancy with a prevalence of 0.16%, 0.26% and 0.55% in each trimester. The prescription of drugs contraindicated during pregnancy was below 0.5%. Only a small percentage of women switched from a contraindicated drug to a drug compatible with pregnancy. The analysis showed little variability between the different Italian regions. In general, the prescription of antihypertensive drugs in the Italian Mom-Network is coherent with the drugs compatible with pregnancy.

[Haemophilia B therapy: impact of the reimbursability of a long-acting recombinant factor on pharmaceutical expenditure in Italy]. / Terapia dell'emofilia B: impatto dell'ammissione alla rimborsabilità di un fattore ricombinante long-acting sulla spesa farmaceutica in Italia.

OBJECTIVES: to assess the variability in expenditure compared to 2022 assuming different rates of shifting of therapy days from current active ingredients used for the treatment of haemophilia B to nonacog beta pegolDesign: descriptive cross-sectional study. SETTING AND PARTICIPANTS: consumption in the year 2022 (data source: Medicines Utilisation Monitoring Centre, Italian Medicines Agency) of all medicinal products available in Italy containing coagulation factor IX. MAIN OUTCOMES MEASURES: for each active ingredient, the total number of therapy days and the variability in expenditure compared to 2022 were estimated on the basis of a switch of therapy days, between 5% and 20%, to nonacog beta pegol. RESULTS: on the basis of considered scenarios, the analysis shows that the total annual expenditure for clotting factors used in the treatment of haemophilia B could remain at most unchanged or reduced. Particularly, the extent of the reduction in spending could vary from 0.11% to 2.26%. This trend would be in contrast to the stable increase seen in recent years, particularly in 2022. CONCLUSIONS: this predictive spending assessment may be useful in evaluating the economic impact from new treatment options, such as etranacogene dezaparvovec gene therapy already approved by the European Medicines Agency and the Food and Drug Administration, and to improve pharmaceutical governance.

Patterns of community antibiotic use with reference to the AWaRe classification of the World Health Organization.

Background: Monitoring consumption through quality indicators and providing feedback is an important activity within programmes for improving antibiotic prescription. This study aims to describe the use of antibiotics for systemic use in community setting in Italy and to compare prescription patterns among regions based on quality prescription indicators to identify any inter-regional variability. Methods: The 2021 consumption (calculated as DDDs per 1000 inhabitants per day) of antibiotics for systemic use (reimbursed or purchased privately) in community setting were considered. The WHO AWaRe system was used to classify antibiotics into Access, Watch and Reserve groups, using the 60% of prescribed antibiotics belonging to the Access group out of the total DDDs as AWaRe target. The correlation between regional consumption and percentages of DDDs in the Access group was assessed through linear regression. A further indicator 'ratio of broad to narrow-spectrum antibacterials' was also calculated to compare the spectrum of prescribed antibiotics. Findings: Overall community antibiotic consumption in Italy in 2021 was 15.6 DDDs per 1000 inhabitants per day, with an increasing trend from north (13.0 DDDs) to south (19.5 DDDs) and the percentages of non-reimbursed consumption decreasing from north (33.1%) to south (21.5%). Only three regions out of 21 reached the AWaRe target (regional range 47.4%-62.9%), with a negative correlation between regional consumption and percentages of antibiotics belonging to the Access group (correlation coefficient -0.8; R 2 = 0.64; P value < 0.001). The 'ratio of broad to narrow-spectrum antibacterials' was 8.5 at national level, with the highest value in the centre (11.0) compared to the south (9.1) and north (7.0). Conclusion: The percentage of consumption of Access group antibiotics correlates very well with regional consumption in Italy, indicating that regions with higher antibiotics consumption also have worse prescribing patterns with a greater impact on bacterial resistance. Additional data are needed to better describe prescription patterns from an antimicrobial stewardship perspective.

Evaluating the potential of ethyl cellulose/eudragit-based griseofulvin loaded nanosponge matrix for topical antifungal drug delivery in a sustained release pattern.

Fungal infections are very alarming nowadays and are common throughout the world. Severe fungal infections may lead to a significant risk of mortality and morbidity worldwide. Sustained delivery of antifungal agents is needed to mitigate this problem. In the current study, an attempt has been made to formulate griseofulvin-loaded nanosponges using the quasi-emulsion solvent diffusion technique. For characterization, griseofulvin loaded nanosponges were tested by different instrumental techniques such as optical microscopy, scanning electron microscopy (SEM), powder X-ray diffractometer (PXRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). The antifungal activity of the nanosponges was assessed against Candida albican strain using the agar well-diffusion method. Finally, the drug-loaded nanosponges' in vitro sustained release activity was evaluated. FTIR spectra showed no chemical interference between the drug and polymers. Some of the peaks of the drug are not visible in the FTIR spectrum, which suggests drug entrapment. PXRD data showed that the drug lost its high crystallinity when entrapped in the nanosponge matrix. From the morphological studies via SEM and TEM, a brief idea of the surface morphology of the nanosponges was obtained. The small pores throughout the structure proved its high porosity. The antifungal sensitivity assay was successful, and a zone of inhibition was observed in all the formulations. The in-vitro drug release study showed sustained behaviour. The sustaining effect was due to the polymer and cross-linker used, which gave rise to a porous scaffold matrix. From the results, it can be concluded that griseofulvin-loaded nanosponges can be used for antifungal drug delivery against various topical skin infections.

Enhancing Heart Transplantation: Utilizing Gas-Loaded Nanocarriers to Mitigate Cold/Hypoxia Stress.

Gas-loaded nanocarriers (G-LN) show promise in improving heart transplantation (HTx) outcomes. Given their success in reducing cell death during normothermic hypoxia/reoxygenation (H/R) in vitro, we tested their integration into cardioplegic solutions and static cold storage (SCS) during simulated HTx. Wistar rat hearts underwent four hours of SCS with four G-LN variants: O2- or N2-cyclic-nigerosyl-nigerose-nanomonomers (CNN), and O2- or N2-cyclic-nigerosyl-nigerose-nanosponges (CNN-NS). We monitored physiological-hemodynamic parameters and molecular markers during reperfusion to assess cell damage/protection. Hearts treated with nanomonomers (N2-CNN or O2-CNN) showed improvements in left ventricular developed pressure (LVDP) and a trend towards faster recovery of the rate pressure product (RPP) compared to controls. However, nanosponges (N2-CNN-NS or O2-CNN-NS) did not show similar improvements. None of the groups exhibited an increase in diastolic left ventricular pressure (contracture index) during reperfusion. Redox markers and apoptosis/autophagy pathways indicated an increase in Beclin 1 for O2-CNN and in p22phox for N2-CNN, suggesting alterations in autophagy and the redox environment during late reperfusion, which might explain the gradual decline in heart performance. The study highlights the potential of nanomonomers to improve early cardiac performance and mitigate cold/H/R-induced stunning in HTx. These early improvements suggest a promising avenue for increasing HTx success. Nevertheless, further research and optimization are needed before clinical application.

Impact of COVID-19 pandemic on prescription of psychotropic medications in the Italian paediatric population during 2020.

BACKGROUND: There is a global perception that psychotropic utilization in children and adolescents is increasing, especially with the onset of COVID-19 pandemic. Available literature data on paediatric psychotropic medication prescriptions in Italy are limited to one or few regions and not updated. The aim of this study was to provide updated data on psychotropic prescriptions referred to the whole Italian paediatric population, as overall and by subgroups of medications and to evaluate if the COVID-19 pandemic during 2020 had an impact on prescription rates. METHODS: A descriptive study on psychotropic drug utilization in children and adolescents (< 18 years) resident in all Italian regions during 2020 was performed. Patients registered in the Pharmaceutical Prescriptions database with at least one prescription/dispensing of a psychotropic medication (antipsychotics-N05A), (antidepressants-N06A) and (psychostimulants-N06BA) during the study period were considered. The indicators used were the prescription rate (number of prescriptions per 1000 children) and prevalence of use (proportion of the paediatric population with at least one prescription in the relevant year). RESULTS: During the 2020 the prevalence of psychotropic drug use in the paediatric population was 0.3%, increased of 7.8% if compared to 2019. The same trend was observed for the prescription rate, which recorded an average of 28.2 per 1000 children with an increase of 11.6% if compared to previous year, representing the 0.6% of the overall drug use in this age group. The data showed a growing trend prescription by age, reaching the peak in adolescents aged 12-17 years old, with a prescription rate of 65 per 1000 children and a prevalence of 0.71%. Considering the subgroups of psychotropic medications, the highest prevalence of use was found for antipsychotic drugs, received by the 0.19% of the paediatric population during 2020. CONCLUSIONS: Psychotropic drug utilization in children and adolescents has grown during 2020 in Italy and worldwide, raising alarms from health care clinicians and patient advocates about the increase of burden of mental diseases in paediatric population during the COVID-19 pandemic. A more systematic monitoring of the use of psychotropic medications should be implemented in all countries for collecting relevant information about children and adolescents taking psychotropic drugs, in order to address the present and the future of the mental health of the paediatric population.

Plant-derived bioactive compounds for the inhibition of biofilm formation: a comprehensive review.

Biofilm formation is a widespread phenomenon that impacts different fields, including the food industry, agriculture, health care and the environment. Accordingly, there is a serious need for new methods of managing the problem of biofilm formation. Natural products have historically been a rich source of varied compounds with a wide variety of biological functions, including antibiofilm agents. In this review, we critically highlight and discuss the recent progress in understanding the antibiofilm effects of several bioactive compounds isolated from different plants, and in elucidating the underlying mechanisms of action and the factors influencing their adhesion. The literature shows that bioactive compounds have promising antibiofilm potential against both Gram-negative and Gram-positive bacterial and fungal strains, via several mechanisms of action, such as suppressing the formation of the polymer matrix, limiting O2 consumption, inhibiting microbial DNA replication, decreasing hydrophobicity of cell surfaces and blocking the quorum sensing network. This antibiofilm activity is influenced by several environmental factors, such as nutritional cues, pH values, O2 availability and temperature. This review demonstrates that several bioactive compounds could mitigate the problem of biofilm production. However, toxicological assessment and pharmacokinetic investigations of these molecules are strongly required to validate their safety.

Evaluation of the Swelling Properties and Sorption Capacity of Maltodextrin-Based Cross-Linked Polymers.

The development of polymers obtained from renewable sources such as polysaccharides has gained scientific and industrial attention. Cross-linked bio-derived cationic polymers were synthesized via a sustainable approach exploiting a commercial maltodextrin product, namely, Glucidex 2®, as the building block, while diglycidyl ethers and triglycidyl ethers were used as the cross-linking agents. The polymer products were characterized via FTIR-ATR, TGA, DSC, XRD, SEM, elemental analysis, and zeta-potential measurements, to investigate their composition, structure, and properties. Polydispersed amorphous granules displaying thermal stabilities higher than 250 °C, nitrogen contents ranging from 0.8 wt % and 1.1 wt %, and zeta potential values between 10 mV and 15 mV were observed. Subsequently, water absorption capacity measurements ranging from 800% to 1500%, cross-linking density determination, and rheological evaluations demonstrated the promising gel-forming properties of the studied systems. Finally, nitrate, sulfate, and phosphate removal tests were performed to assess the possibility of employing the studied polymer products as suitable sorbents for water remediation. The results obtained from the ion chromatography technique showed high sorption rates, with 80% of nitrates, over 90% of sulfates, and total phosphates removal.

Blind Spots in Development of Nanomedicines.

The field of nanomedicine demonstrates immense advantages and noteworthy expansion compared to conventional drug delivery systems like tablet, capsules, etc. Despite the innumerable advantages, it holds certain shortcomings in the form of blind spots that need to be assessed before the successful clinical translation. This perspective highlights the foremost blind spots in nanomedicine and emphasizes the challenges faced before the entry into the market, including the need for provision of safety and efficacy data by the regulatory agencies like FDA. The significant revolution of nanomedicine in the human life, particularly in patient well-being, necessitates to identify the blind spots and overcome them for effective management and treatment of ailments.

Unveiling the synergy: a combined experimental and theoretical study of ß-cyclodextrin with melatonin.

Melatonin (MT) is a vital hormone controlling biorhythms, and optimizing its release in the human body is crucial. To address MT's unfavorable pharmacokinetics, we explored the inclusion complexes of MT with ß-cyclodextrin (ß-CD). Nano spray drying was applied to efficiently synthesize these complexes in three molar ratios (MT : ß-CD = 1 : 1, 2 : 1, and 1 : 2), reducing reagent use and expediting inclusion. The complex powders were characterized through thermal analyses (TGA and DSC), Fourier transform infrared spectroscopy (FTIR), and in vitro MT release measurements via high-performance liquid chromatography (HPLC). In parallel, computational studies were conducted, examining the stability of MT : ß-CD complexes by means of unbiased semi-empirical conformational searches refined by DFT, which produced a distribution of MT : ß-CD binding enthalpies. Computational findings highlighted that these complexes are stabilized by specific hydrogen bonds and non-specific dispersive forces, with stronger binding in the 1 : 1 complex, which was corroborated by in vitro release data. Furthermore, the alignment between simulated and experimental FTIR spectra demonstrated the quality of both the structural model and computational methodology, which was crucial to enhance our comprehension of optimizing MT's release for therapeutic applications.

Preliminary assessment of environmental safety (ecosafety) of dextrin-based nanosponges for environmental applications.

The ability to employ waste products, such as vegetable scraps, as raw materials for the synthesis of new promising adsorbing materials is at the base of the circular economy and end of waste concepts. Dextrin-based nanosponges (D_NS), both cyclodextrin (CD) and maltodextrin (MD), have shown remarkable adsorption abilities in the removal of toxic compounds from water and wastewater, thus representing a bio-based low-cost solution which is establishing itself in the market. Nevertheless, their environmental safety for either aquatic or terrestrial organisms has been overlooked, raising concern in terms of potential hazards to natural ecosystems. Here, the environmental safety (ecosafety) of six newly synthesized batches of D_NS was determined along with their full characterization by means of dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transformed infrared spectroscopy with attenuated total reflection (FTIR-ATR) and transmission electron microscopy (SEM). Ecotoxicity evaluation was performed using a battery of model organisms and ecotoxicity assays, such as the microalgae growth inhibition test using the freshwater Raphidocelis subcapitata and the marine diatom Dunaliella tertiolecta, regeneration assay using the freshwater cnidarian Hydra vulgaris and immobilization assay with the marine brine shrimp Artemia franciscana. Impact on seedling germination of a terrestrial plant of commercial interest, Cucurbita pepo was also investigated. Ecotoxicity data showed mild to low toxicity of the six batches, up to 1 mg/mL, in the following order: R. subcapitata > H. vulgaris > D. tertiolecta > A. franciscana > C. pepo. The only exception was represented by one batch (NS-Q+_BDE_(GLU2) which resulted highly toxic for both freshwater species, R. subcapitata and H. vulgaris. Those criticalities were solved with the synthesis of a fresh new batch and were hence attributed to the single synthesis and not to the specific D_NS formulation. No effect on germination of pumpkin but rather more a stimulative effect was observed. To our knowledge this is the first evaluation of the environmental safety of D_ NS. As such we emphasize that current formulations and exposure levels in the range of mg/mL do not harm aquatic and terrestrial species thus representing an ecosafe solution also for environmental applications.

Enhancing Vitamin D3 Efficacy: Insights from Complexation with Cyclodextrin Nanosponges and Its Impact on Gut-Brain Axes in Physiology and IBS Syndrome.

Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (ßNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut-brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut-brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%.

Effectiveness of different local actions to control vitamin D prescription in Italy.

INTRODUCTION: In the last decade, the significant expenditure and consumption increase of vitamin D in Italy led some regions to adopt strategies to improve prescribing appropriateness and contain expenditure. MATERIALS AND METHODS: Using the statistical analysis method of interrupted time series for consumption and expenditure of cholecalciferol, different types of interventions adopted in four Italian regions and their efficacy were evaluated. RESULTS: Molise achieved the best results by adopting a health professionals' education program in addition to a prescriber-sanction system. Emilia-Romagna also opted for a medical education strategy, but the results were less relevant due to the lack of penalties. Lazio obtained a slowdown in consumption growth by targeting on the utilization of lower-cost per defined daily dose (DDD) packs and adopting a therapeutic plan. Sardinia showed a decrease in expenditure by adopting a target threshold of lower-cost formulation. CONCLUSION: The reimbursement of the lowest-cost packs within the National Health Service (NHS) undoubtedly influences spending trend, but it does not solve prescriptive inappropriateness.

Antidiabetic Therapy during Pregnancy: The Prescription Pattern in Italy.

Pregestational and gestational diabetes mellitus are relevant complications of pregnancy, and antidiabetic drugs are prescribed to obtain glycemic control and improve perinatal outcomes. The objective of this study was to describe the prescription pattern of antidiabetics before, during and after pregnancy in Italy and to evaluate its concordance with the Italian guideline on treatment of diabetes mellitus. A multi-database cross-sectional population study using a Common Data Model was performed. In a cohort of about 450,000 women, the prescribing profile of antidiabetics seemed to be in line with the Italian guideline, which currently does not recommend the use of oral antidiabetics and non-insulin injection, even if practice is still heterogeneous (up to 3.8% in the third trimester used oral antidiabetics). A substantial variability in the prescription pattern was observed among the Italian regions considered: the highest increase was registered in Tuscany (4.2%) while the lowest was in Lombardy (1.5%). Women with multiple births had a higher proportion of antidiabetic prescriptions than women with singleton births both in the preconception period and during pregnancy (1.3% vs. 0.7%; 3.4% vs. 2.6%) and used metformin more frequently. The consumption of antidiabetics in foreign women was higher than Italians (second trimester: 1.8% vs. 0.9%, third trimester: 3.6% vs. 1.8%).

Financial Outcomes of Managed Entry Agreements for Pharmaceuticals in Italy.

Importance: Most countries in the Organisation for Economic Co-operation and Development apply managed entry agreements (MEAs), reimbursement arrangements between manufacturers and payers, to pharmaceuticals. Few data exist regarding their ability to lower expenditures. Objective: To analyze the financial outcomes of MEAs for pharmaceuticals from 2019 to 2021 in Italy. Design, Setting, and Participants: In this observational study of MEAs and pharmaceutical spending in Italy, medications that were monitored through individually collected data and generated paybacks from manufacturers during the 2019 to 2021 study period were included in the analysis. Payback data were collected through pharmaceutical spending monitoring activities conducted by the Agenzia Italiana del Farmaco (Italian Medicines Agency). Expenditure data were collected through the Italian Drug Traceability System. Products were categorized by type of MEA: financial-based, outcome-based, or mixed. Main Outcomes and Measures: The main outcome was median payback as a proportion of expenditure by category of MEA. Results were also provided by subtype: cost sharing or capping models for financial-based MEAs and risk-sharing or payment-by-result models for outcome-based MEAs. Mixed MEAs were considered when medications had multiple indications with different MEA types. Results: A total of 73 medications with MEAs generated a payback by manufacturers during the study period. Six were either not reimbursable or delivered within the Italian National Health Service, and 5 had incomplete data. Of the 62 medications analyzed, 24 (38.7%) had financial-based MEAs, 30 (48.4%) had outcome-based MEAs, and 8 (12.9%) had mixed MEAs. A total payback amount of €327.5 million was calculated during the 3 years, corresponding to 0.9% of the €41.1 billion of total expenditures for medications purchased by public health facilities in Italy. Financial-based MEAs returned the highest payback revenues, €158.1 million; the outcome-based MEAs and mixed MEAs generated smaller paybacks of €74.5 million and €94.9 million, respectively. Overall, the median proportion of payback to expenditure on the medications analyzed was 3.8%. For mixed MEAs, the payback-to-expenditure proportion was 6.7%; for outcome-based MEAs, 3.3%; and for financial-based MEAs, 3.7%. Conclusions and Relevance: This observational study found limited evidence that MEAs lower pharmaceutical expenditures. Determining criteria for prioritizing MEA use, identifying potential design changes, and improving implementation may be needed in the future.

[The organization of pharmaceutical care in the territory has no effect on patient compliance: the case of direct or account distribution of antidiabetics]. / L'organizzazione dell'assistenza farmaceutica sul territorio non ha effetto sulla compliance del paziente: il caso della distribuzione diretta o per conto degli antidiabetici.

OBJECTIVES: the objective of the study is to assess the effect of the delivery channel on adherence, persistence and potential wastage of new antidiabetic drugs. DESIGN: longitudinal descriptive observational study. New users were defined as subjects who received a first prescription of drugs belonging to the antidiabetic category in the period between 01.01.2021 and 31.03.2021 (index date) and who did not receive prescriptions for drugs belonging to the same category in the previous 6 months, as of 01.07.2020. Each subject was followed for a follow-up period of 9 months. SETTING AND PARTICIPANTS: the study examined adherence and persistence to treatment with antidiabetic drugs in Italy for patients aged>=45 years (information flow of pharmaceutical services performed in direct distribution and on behalf established by Ministerial Decree Health 31 July, 2007). MAIN OUTCOME MEASURES: adherence to treatment measured by the Medication Possession Rate (MPR) indicator, defined as the ratio of the number of days of therapy dispensed (calculated from DDDs) to the number of days covered by drug therapy; persistence to treatment defined as "time elapsed between the initiation and discontinuation of a prescribed drug therapy" estimated by as "time elapsed between the initiation and discontinuation of a drug therapy" estimated by Cox semi-parametric model; difference in terms of waste understood as the number of packs not fully used by non-persistent subjects. RESULTS: the analysis showed that there were no significant differences between the dispensing channels in adherence, persistence, and medication wastage (defined as the distribution of packages to non-persistent patients). Specifically, it turns out that the percentage of highly adherent subjects at 9 months is 62.2 for those on treatment in the direct distribution channel and 64.6 for those on treatment with account distribution; with regard to persistence at 9 months, however, a difference of less than one percentage point was observed between the two channels. Although this study focused on a specific therapeutic class, the results can be generalised to other high-prevalence chronic diseases. However, some limitations of the study were pointed out, such as the difficulty of replicating the results due to the variability of data depending on the drug category and the time period considered. CONCLUSIONS: the choice of distribution channel for antidiabetic drugs should not be based on adherence or persistence to treatment, but on other determinants such as cost of service and logistical complications.