Monitoring the community use of antibiotics in Italy within the National Action Plan on antimicrobial resistance.

BACKGROUND: In Italy both the consumption of antibiotics and the prevalence of bacterial resistance are higher than in other European countries. In 2017, the first National Action Plan on Antimicrobial Resistance (PNCAR) was adopted in Italy. In response to the PNCAR two national reports on antibiotic use in the human setting have been published. This article's aim is to describe the pattern of antibiotic consumption in the community setting in Italy from 2013 to 2018. METHODS: To analyse the consumption for reimbursed antibiotics dispensed by community pharmacies different data sources were used. Consumption was measured in terms of defined daily dose (DDD), prescriptions or prevalence of use. RESULTS: In 2018, the consumption of antibiotics in Italy amounted to 16.1 DDD per 1000 inhabitants per day. The rates of consumption by geographical area were: 12.7 DDD in the north, 16.9 in the centre and 20.4 in the south. The use was greater in the extreme age groups than in the population aged from 20 to 64 years. The consumption was higher in winter season, with high peaks in the incidence of flu syndromes. In the paediatric population, a utilization rate of 1010 prescriptions per 1000 children, with a prevalence of use of 40.8%, was found. CONCLUSION: The study provides useful information on the geographical variability of antibiotic use in Italy to guide decision makers in the introduction of tailored interventions, as suggested by PNCAR, aimed at promoting a more rational use of antibiotics for humans and reducing antimicrobial resistance.

Real world data to identify target population for new CAR-T therapies.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma often refractory to currently available treatments (immuno-chemotherapy/autologous-stem-cell-transplantation-ASCT). Recently, new cell therapies have been approved for patients failing two conventional treatments, CAR-T (Chimeric-Antigen-Receptor-T-cell), committing payers in planning and implementing their use. We aim to define, using Real World Data (RWD), a reproducible procedure that allows identification of CAR-T target population for DLBCL. METHODS: Through the linking of electronic healthcare datasets (EHD), we identified patients with non-Hodgkin's Lymphoma (NHL), resident in Lazio region (2010-2015), aged ≥20 years. DLBCL patients were followed using pathological anatomy (PA) reports, up to 3 years. To be defined as relapsed after two treatment lines, patients must have had new chemotherapy and/or NHL hospitalization after ASCT or at the end of the second chemotherapy. The incident rate of second relapse (R2-rate) was extended to the population without PA reports. RESULT: NHL incident patients were 7384, 68% presented a PA report and, 29% of these had DLBCL codes. Patients who relapsed after two treatment lines were 47 (39%) in the subgroup of patients who received ASCT and 138 (41%) in that with second chemotherapy treatment. Patients in the two subgroups were very different in terms of age and comorbidity. The annual incident number of DLBCL was estimated to be 329 which multiplied by R2-rate (13.7%) gives 45 patients per year eligible for CAR-T. DISCUSSION: This study shows how RWD allows the identification of a target population with new advanced therapies. This approach is rigorous, transparent and verifiable over time.

Using GRADE methodology to assess innovation of new medicinal products in Italy.

AIM: In April 2017 the Italian Medicine Agency (AIFA) developed new criteria to grant any new medicinal product with an innovative designation. The aim of this study is to describe this new model and how it works. METHODS: A retrospective descriptive analysis was performed on the results of the assessment process of innovativeness of new medicinal products (or therapeutic indications) based on the AIFA's new innovation criteria (therapeutic need, added therapeutic value and quality of clinical evidence through GRADE methodology) carried out between April 2017 and February 2019 and made publicly available on the AIFA website starting from January 2018. RESULTS: A total of 37 full reports (22 for oncological indications) explaining the rationale for the AIFA's decision is made publicly available on the agency's website. A total of 12 therapeutic indications (5 oncological) were evaluated as fully innovative, 13 indications (11 oncological) were evaluated as conditionally innovative, while 12 indications (6 oncological) as non-innovative. CONCLUSION: The new AIFA innovation criteria resulted in a much more flexible and transparent model to define and assess what constitutes a therapeutic innovation. In particular, the choice of AIFA to use the GRADE methodology to evaluate the quality of clinical evidence within a process of drug innovativeness assessment is essential for the early identification of the discrepancy between the need for patients of a rapid access to innovative therapies and the available clinical data needed to make decisions on drug innovativeness.

Postnatal depression screening in a paediatric primary care setting in Italy.

BACKGROUND: Postnatal depression is a non-psychotic depressive disorder that begins within 4 weeks of childbirth and occurs in 13% of mothers and 10% of fathers. A prospective study with the aim to evaluate the prevalence of postnatal depression by screening parents with the Edinburgh Postnatal Depression Scale (EPDS) in the Italian paediatric primary care setting was performed. METHODS: Mothers and fathers of infants born between 1 February and 31 July 2012, living in Italy's Milan-1 local health unit area, represented the target population of this pilot study. Parents attending well-child visits at any of the family paediatricians' offices between 60 to 90 days postpartum were asked to participate in the screening and to fill out the EPDS questionnaire. A cut-off score of 12 was used to identify parents with postnatal depression symptoms. Maternal and paternal socio-demographic variables and information concerning pregnancy and delivery were also collected. To investigate the association between screening positivity (dependent variable) and socio-demographic variables and factors related to pregnancy and delivery, a Pearson's χ2 test was used. Moreover, a stepwise multivariate logistic regression was carried out to evaluate the risk factors that most influence the probability of suffering from postnatal depression. RESULTS: In all, 126 out of 2706 (4.7%, 95% CI 3.9-5.5%) mothers and 24 out of 1420 (1.7%, 95% CI 1.0-2.4%) fathers were found to be positive for depressive symptoms. Women with mood disorders and anxiety during pregnancy were at increased risk of postpartum depression (OR 22.9, 95% CI 12.1-43.4). Only 11 mothers (8.7%) positive to EPDS screening attended a psychiatric service, and for 8 of them the diagnosis of postnatal depression was confirmed. CONCLUSIONS: The prevalence of postnatal depression was lower than previously reported. Routine screening resulted ineffective, since few mothers found positive for depression symptoms decided to attend psychiatric services.

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.

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.

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.

The use of medications approved for alcohol use disorders in Italy.

Background: Italy has the highest per capita alcohol consumption among European countries. Several pharmacological treatments for alcohol use disorders (AUDs) are currently available in Italy, but no consumption data are available. A first analysis of national drug consumption, comprising the whole Italian population over a long-term period covering the COVID-19 pandemic, was performed. Methods: To analyze the consumption of medications indicated for therapy of alcohol dependence, different national data sources were used. Consumption was measured as a defined daily dose (DDD) per 1,000,000 inhabitants per day. Results: In 2020, the total consumption of medicines used in the treatment of AUDs amounted to 310.3 DDD per 1 million inhabitants per day (0.018% of the overall drug consumption in Italy) with a decreasing gradient from the north (373.9 DDD) to the south (250.7 DDD). 53.2% of the overall doses were dispensed by public healthcare facilities and 23.5% by community pharmacies, while the remaining 23.3% were purchased privately. The temporal trend of consumption seemed to be stable across the last few years, although an impact of the COVID-19 pandemic was observed. Disulfiram was the most consumed medicine over years. Conclusion: All Italian regions offer pharmacological treatments to patients with AUDs, but differences in the number of dispensed doses suggest a different local organization of patient care, which can be partly explained by the different severity of the clinical condition of residing patients. Pharmacotherapy of alcoholism should be deeply investigated to describe the clinical characteristics of treated patients (i.e., comorbidities) and evaluate the appropriateness of prescribed medications.

Access and use of WHO essential medicines in Italy.

Background: Many countries use the WHO Essential Medicines List (EML) as a guide for health policy choices to promote the efficient use of healthcare resources or adopt the concept of essential medicines (EMs) to develop their own national list of essential medicines. The aim of this study is to analyse the availability and use of medicines included in the 22nd WHO EML in Italy. Methods: Using the ATC code (5th level), a comparison was made between the medicines included in the WHO EML and those retrieved from the Italian Medicines Agency (AIFA) database. The availability (regulatory and reimbursement status) of EMs, as well as the market share in expenditure (million euros) and consumption [measured in WHO-defined daily doses (DDDs)], compared to all reimbursed medicines in 2021, were analysed. Results: In 2021, approximately 85.2% (n = 414) of medicines included in the WHO EML were commonly marketed in Italy. Of these, 396 EMs were fully reimbursed by the Italian National Healthcare Service (INHS), corresponding to 81.5% (396/486) of the WHO EML, while the remaining 18.5% (90/486) were neither authorised (n = 72) nor reimbursed (n = 18). The study found a low coverage for anti-parasitic, insecticides, and repellent products (ATC P) in addition to medicines for the genitourinary system and sex hormones (ATC G). Even though medicines on the WHO EML, including therapeutic alternatives, accounted for ~48.5% of the expenditure for medicines reimbursed by INHS, the list covered 74% of all national drug consumed. Novel high-cost therapies indicated in high-prevalence diseases and rare conditions, mostly antineoplastic and immune-modulating agents (ATC L) not included in the WHO EML, were also guaranteed. Conclusions: In Italy, high coverage of EMs was found. It was largely reimbursed by the INHS, even when compared to other European countries. Essential medicines represented a high percentage of the overall expenditure and consumption in Italy. The WHO EML could be an important tool to guide the health policy choices of high-income countries, although a more frequent update and easier access to information on rejected medicines are needed.

Hospital Antibiotic Use during COVID-19 Pandemic in Italy.

Antimicrobial resistance (AMR) represents a major issue in healthcare being correlated to global inappropriate use of antibiotics. The aim of this study was to compare the data on hospital antibiotic consumption in 2020-2021 with those related to 2019 in order to evaluate the impact of the COVID-19 pandemic on antibiotic prescriptions and appropriate use at national level and in the different geographical areas. To estimate the consumption of antibiotics, two indicators were calculated: "number of DDD per 1000 inhabitants per day" and "number of DDD per 100 hospitalisation days". Consumption data on antibiotics dispensed in public health facilities were based on the Italian "traceability of medicines" information flow. Data on hospitalisation days were extracted from the Italian "hospital discharge form" flow. Pearson correlation analysis was performed between the number of patients hospitalised for COVID-19 and the consumption of antibiotics in public healthcare facilities. During 2020, about 1.7 DDD/1000 inhabitants per day (12.3% of the overall consumption of reimbursed antibiotics) were dispensed exclusively in Italian hospitals (+0.8% compared to 2019). Considering the number of DDD per 100 hospitalisation days, consumption increased by 19.3% in 2020 compared to 2019. Comparing the first semester of 2020 and 2019, a decrease of DDD/1000 inhabitants per day was observed (-1.6%) at national level, with opposite trends in the different geographical areas; an increase in the use of azithromycin and carbapenems was also observed, with a stable consumption of third-generation cephalosporins. The use of antibiotics in the second semester of 2020 compared to the same period of 2019 showed a clear reduction at national level (-8.5%), appreciable to a similar extent in all geographic areas. In the first semester of 2021 compared to the same period of 2020, there was a huge reduction (-31.4%) in consumption at national level. However, the variations were heterogeneous between different geographical areas. To our knowledge, this study represents the most comprehensive analysis performed on antibiotic consumption data in hospital settings in Italy during the COVID-19 pandemic to date. Despite international and national guideline recommendations, a substantial overall increase in antibiotic prescriptions was observed during the COVID-19 pandemic, with variability in terms of geographical distribution and prescription strategies. These findings may be related to the dichotomy between perceived and real significance of guidelines, expert panels, or consensus. Therefore, new approaches or strategies to antimicrobial stewardship should be proposed.

[Parole chiave. Appropriatezza prescrittiva, consumi farmaceutici, emofilia, fattori della coagulazione, malattia di von Willebrand, malattie emorragiche congenite.] / Strategie terapeutiche per il trattamento delle malattie emorragiche congenite.

Therapeutic strategies for the treatment of congenital bleeding disorders. Congenital hemorrhagic diseases (CHDs) are a group of rare disorders caused by quantitative or qualitative deficiency of one or more coagulation factors. Haemophilia A, Haemophilia B, and von Willebrand disease are the most common congenital bleeding disorders. Over the past decades, the evolution of CHDs treatments has resulted in an increase in the average life expectancy of patients and in an improvement in their quality of life; it has also enabled the prevention of bleeding complications much more effectively than in the past. This has been possible, especially for haemophilia, mainly because of earlier diagnosis, introduction of recombinant factors, especially long-acting factors, and availability of new non-substitutive therapies. In 2021, there was an increase in the overall expenditure and consumption of coagulation factors in Italy; the increase concerned especially the long-acting recombinant factors used in the treatment of Haemophilia A and B and the monoclonal antibody emicizumab. Waiting for innovative therapies that can enable individually tailored therapies, special attention must be paid to prescriptive appropriateness and to identify the best diagnostic and therapeutic care pathways for patients.

[Pharmacotherapy of Hemophilia A: expenditure and consumption for the year 2022 and future expenditure scenarios.] / Terapia dell'emofilia A: spesa e consumo per l'anno 2022 e scenari di spesa futura.

In 2021, the national expenditure for blood coagulation factors was 541.4 million, growing steadily over the past decade. Hemophilia A is the congenital hemorrhagic disease with the highest drug consumption and expenditure. It has also the highest annual increase. Data from the OsMed report showed an increased use of long-acting recombinant factors and a concomitant reduction in consumption of short-acting ones and also an increasing trend of emicizumab. Based on these findings, two possible expenditure scenarios were described: 1) assuming a 25% of reduction in consumption of short-acting recombinant factors with proportional redistribution to the consumption observed in 2022 for long-acting recombinant factors; 2) assuming that all new patients with a moderate and severe form of the disease will start prophylaxis with emicizumab and also calculating different switch percentages (20%, 30%, 50% or 70%). The first hypothesis showed a potential increase in expenditure of 3.3% (approximately 10 million euros) switching from short- to long-acting factors. In the second one, based on estimated number of patients with Hemophilia A on treatment, a total expenditure of about 457.6 million euros was estimated. Based on these findings, different expenditure outlooks were hypothesized and that there should be a switch from the recombinant factors to emicizumab. Specifically, an expenditure increase of 8% in the case of 20% switch and 28.1% in the case of 70% switch were estimated.

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%).

Monitoring medicine prescriptions before, during and after pregnancy in Italy.

BACKGROUND: The use of medications during pregnancy is a common event worldwide. Monitoring medicine prescriptions in clinical practice is a necessary step in assessing the impact of therapeutic choices in pregnant women as well as the adherence to clinical guidelines. The aim of this study was to provide prevalence data on medication use before, during and after pregnancy in the Italian population. METHODS: A retrospective prevalence study using administrative healthcare databases was conducted. A cohort of 449,012 pregnant women (15-49 years) residing in eight Italian regions (59% of national population), who delivered in 2016-2018, were enrolled. The prevalence of medication use was estimated as the proportion (%) of pregnant women with any prescription. RESULTS: About 73.1% of enrolled women received at least one drug prescription during pregnancy, 57.1% in pre-pregnancy and 59.3% in postpartum period. The prevalence of drug prescriptions increased with maternal age, especially during the 1st trimester of pregnancy. The most prescribed medicine was folic acid (34.6%), followed by progesterone (19%), both concentrated in 1st trimester of pregnancy (29.2% and 14.8%, respectively). Eight of the top 30 most prescribed medications were antibiotics, whose prevalence was higher during 2nd trimester of pregnancy in women ≥ 40 years (21.6%). An increase in prescriptions of anti-hypertensives, antidiabetics, thyroid hormone and heparin preparations was observed during pregnancy; on the contrary, a decrease was found for chronic therapies, such as anti-epileptics or lipid-modifying agents. CONCLUSIONS: This study represents the largest and most representative population-based study illustrating the medication prescription patterns before, during and after pregnancy in Italy. The observed prescriptive trends were comparable to those reported in other European countries. Given the limited information on medication use in Italian pregnant women, the performed analyses provide an updated overview of drug prescribing in this population, which can help to identify critical aspects in clinical practice and to improve the medical care of pregnant and childbearing women in Italy.

Ocular medicines in children: the regulatory situation related to clinical research.

BACKGROUND: Many ocular medications are prescribed for paediatric patients, but the evidence for their rational use is very scant. This study was planned to compare the availability and the licensing status of ocular medications marketed in Italy, the United Kingdom (UK), and the United States of America (USA) related to the amount of published and un-published RCTs testing these drugs in the paediatric population. METHODS: A quantitative analysis was performed to evaluate the number of ocular medications with a paediatric license in Italy, the UK, and the USA. A literature search was also performed in MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) on ophthalmic pharmacological therapy in children aged < 18 years, published up to December 2010. A search in the international clinical trial registries, the list of paediatric investigation plans (PIPs) approved by European Medicines Agency (EMA), and the table of medicines with new paediatric information approved by Food and Drug Administration (FDA) was also performed. RESULTS: In all, of 197 drugs identified, 68 (35%) single drugs are licensed for paediatric use at least in one considered country, while 23 (12%) were marketed in all three countries. More specifically, in Italy 43 single drugs (48% of those marketed) had a paediatric license, while 39 (64%) did in the UK and 22 (54%) did in the USA. Only 13 drugs were marketed with a paediatric license in all countries. The percentage of drugs licensed for paediatric use and for which at least one RCT had been performed ranged between 51% in Italy and 55% in the USA. No published RCTs were found for 11 (48%) drugs licensed for paediatric use in all three countries. In all, 74 (35%) of the retrieved RCTs involved mydriatic/cycloplegic medications.A total of 62 RCTs (56% completed) on 46 drugs were found in the international clinical trial registries. Cyclosporin and bevacizumab were being studied in many ongoing trials. Twenty-six drugs had new paediatric information approved by FDA based on new paediatric clinical trials, while only 4 PIPs were approved by EMA. CONCLUSIONS: There is a pressing need for further research and clinical development in the pediatric ophthalmic area, where effective up-to-date treatments, and additional research and education on use in children, remain priorities.

Drug Prescriptions in the Outpatient Management of COVID-19: Evidence-Based Recommendations Versus Real Practice.

Background: Evidence-based recommendations for outpatient management of COVID-19 were published by the Italian Medicines Agency (AIFA) to limit the use of off-label treatments. The aim of this study is to measure the use of outpatient drug treatments in a COVID-19-positive population, taking into account the Italian regulatory agency's advices. Methods: A descriptive observational study was conducted. All patients testing positive for COVID-19 residing in Lazio region, Italy, with diagnosis date between March 2020 and May 2021 were selected, and outpatient medicine prescription patterns were identified. Results: Independent of AIFA recommendations, the use of drug therapy in the management of outpatient COVID-19 cases was frequent (about one-third of the cases). The most used drug therapy was antibiotics, specifically azithromycin, despite the negative recommendation of AIFA, while the use of corticosteroids increased after the positive recommendation of regulatory agency for the use in subjects with severe COVID-19 disease. The use of hydroxychloroquine was limited to the early pandemic period where evidence on its potential benefit was controversial. Antithrombotics were widely used in outpatient settings, even if their use was recommended for hospitalized patients. Conclusion: In this study, we show a frequent use of drug therapy in the management of outpatient cases of COVID-19, mainly attributable to antibiotics use. Our research highlights the discrepancy between recommendations for care and clinical practice and the need for strategies to bridge gaps in evidence-informed decision-making.

Drug Prescriptions among Italian and Immigrant Pregnant Women Resident in Italy: A Cross-Sectional Population-Based Study.

Ensuring drug safety for pregnant women through prescription drug monitoring is essential. The aim of this study was to describe the prescription pattern of medicines among pregnant immigrant women from countries with high migratory pressure (HMPCs) compared to pregnant Italian women. The prevalence of drug prescriptions among the two study populations was analysed through record linkage procedures applied to the administrative databases of eight Italian regions, from 2016 to 2018. The overall prevalence of drug prescription was calculated considering all women who received at least one prescription during the study period. Immigrants had a lower prevalence of drug prescriptions before (51.0% vs. 58.6%) and after pregnancy (55.1% vs. 60. 3%). Conversely, during pregnancy, they obtained a slightly higher number of prescriptions (74.9% vs. 72.8%). The most prescribed class of drugs was the blood and haematopoietic organs category (category ATC B) (56.4% vs. 45.9%, immigrants compared to Italians), followed by antimicrobials (31.3% vs. 33.7%). Most prescriptions were appropriate, while folic acid administration 3 months before conception was low for both study groups (3.9% immigrants and 6.2% Italians). Progesterone seemingly was prescribed against early pregnancy loss, more frequently among Italians (16.5% vs. 8.1% immigrants). Few inappropriate medications were prescribed among antihypertensives, statins and anti-inflammatory drugs in both study groups.

[The use of antibiotics in Italy. The national OsMed report 2019.] / L'uso degli antibiotici in Italia. Il rapporto nazionale OsMed 2019.

The OsMed report "The use of antibiotics in Italy - 2019", produced by the Italian Medicines Agency, shows how the prescriptions of these drugs are still too high in our country, albeit with high variability between different regions. A significant degree of inappropriate use of antibiotics also emerges, especially in respiratory infections. In general, the results highlight the need to implement prevention and control actions in order to counter antibiotic resistance.

The Assessment of the Innovativeness of a New Medicine in Italy.

Objectives: Starting from April 2017, the Italian Medicine Agency (AIFA) has approved new criteria for defining any new medicinal product with an innovative indication. The purpose of the study is to analyze the activity of innovativeness evaluation according to the new approach, to estimate the weight of each criterion considered for innovativeness definition, and to evaluate how the new approach works in terms of consistency and reproducibility. Methods: A retrospective analysis was performed on the final reports evaluating the drug innovativeness assessment published on the AIFA's website between April 2017 and January 2021. Descriptive statistics, chi-square test, whether the conditions were respected, or Fisher's exact test was used to explore the association between characteristics of drugs and the innovativeness status and the association between the three criteria. Profiles of the decision process and their relationship with innovativeness response were described. In order to evaluate the weight of each criterion in predicting the innovativeness status, a Classification Tree (CT) algorithm was applied. Results: Overall, of the 109 published drugs reports, 37 (33.9%) were recognized as fully innovative, 29 (26.6%) were considered conditionally innovative, while for 43 (39.4%) reports innovativeness was not recognized. Considering the three criteria of the decision process, the added therapeutic value was the only criterion statistically associated with a drug's degree of innovation (p < 0.001). The therapeutic need and the quality of clinical evidence were statistically associated (p = 0.008) even if only a mild association was observed. The added therapeutic value was the most important variable in predicting the innovativeness status according to the classification tree (CT) model applied, achieving an accuracy of 89.4%. No difference was found between orphans and non-orphan drugs or oncological and non-oncological drugs. Discussion: The added therapeutic value is the most important criterion of the multidimensional approach for the innovativeness status definition of a new medical product. A mild association was found between the therapeutic need and the quality of evidence. Overall, similar decision profiles bring the same evaluation of innovativeness status, indicating a good consistency and reproducibility between decisions.

[Social inequalities in the use of medicines for the treatment of the major chronic diseases. Evidence from the AIFA Atlas.] / Disuguaglianze sociali nell'uso dei farmaci per la cura delle malattie croniche. Le principali evidenze dall'Atlante AIFA.

The Atlas of social inequalities in the use of medicines for the treatment of the major chronic diseases is the first national report published on social inequalities in the context of pharmaceutical care in Italy. The results highlighted how the socioeconomic position was strongly correlated with the use of medicines: for many therapeutic categories, the highest per capita consumption rates were recorded in the areas with a higher socioeconomic deprivation index. On the other hand, no correlations emerged between the level of deprivation and adherence and persistence to pharmacological treatment.