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.

[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.

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.

Anti-dementia drugs: a descriptive study of the prescription pattern in Italy.

INTRODUCTION: Acetylcholinesterase inhibitors (AChEIs) and memantine are currently the only anti-dementia drugs (ADDs) approved for treating Alzheimer's disease (AD) in Italy. This nationwide study aims to characterize dementia drug utilization in a population > 65 years, during 2018-2020. METHODS: Different administrative healthcare databases were queried to collect both aggregate and individual data. RESULTS: ADD consumption remained stable throughout the study period (~ 9 DDD/1000 inhabitants per day). AChEI consumption was over 5 DDD/1000 inhabitants per day. Memantine consumption was nearly 4 DDD/1000 inhabitants per day, representing 40% of ADD consumption. The prevalence of use of memantine represented nearly half of ADD consumption, substantially unchanged over the 3 years. Comparing the AD prevalence with the prevalence of ADDs use, the gap becomes wider as age increases. In 2019, the proportion of private purchases of ADDs was 38%, mostly represented by donepezil and rivastigmine. In 2020, memantine was the only ADD with an increase in consumption (Δ% 19-20, 1.3%). DISCUSSION: To our knowledge, this study represents the first attempt to investigate the ADD prescription pattern in Italy with a Public Health approach. In 2019, the proportion of ADD private purchases point out several issues concerning the reimbursability of ADDs. From a regulatory perspective, ADDs can be reimbursed by the National Health System only to patients diagnosed with AD; therefore, the off-label use of ADDs in patients with mild cognitive impairment may partially explain this phenomenon. The study extends knowledge on the use of ADDs, providing comparisons with studies from other countries that investigate the prescription pattern of ADDs.

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.

Impact of COVID-19 pandemic on medication use in the older Italian population.

OBJECTIVE: This study aims to analyse the impact of the pandemic on the amount of use and new medication dispensation for chronic diseases in the Italian population aged 65 years and older (almost 14 million inhabitants). METHODS: The "Pharmaceutical Prescriptions database", which gathers data on medications, reimbursed by the National Health Service and dispensed by community pharmacies, was employed. Data were analysed as amount of use (defined daily dose-DDD per 1000 inhabitants); variation in DDD between 2020 and 2019 was calculated for the 30 categories with major consumption in 2020. Trends in prevalence and incidence of dispensations between 2020 and 2019 were calculated for four categories: antidiabetics, antihypertensives, antidepressants and drugs for respiratory diseases. RESULTS: All medications showed a negative variation in DDD/1000 inhabitants between 2020 and 2019 except for anticoagulants (+ 5%). The percentage variation ranged from - 27.7% for antibiotics to - 6.4% for antipsychotics in 85 + year-old persons, but increased for most classes in the youngest (65-69 years). On the other hand, a decrease of the dispensation incidence of antidiabetics, antihypertensives, antidepressants and drugs for pulmonary disease was high, especially in the two extreme age groups, the youngest and the oldest one. CONCLUSIONS AND RELEVANCE: Great variation in medication use between 2020 and 2019 was observed probably reflecting the low rate of infectious diseases due to the widespread use of protective devices and self-isolation, reduced healthcare access because of the lockdowns and the fear of going to hospital, and the reduction of screening and diagnostics due to health-care system overload.

Medication Use and Costs Among Older Adults Aged 90 Years and Older in Italy.

Older adults are often affected by multiple chronic conditions and experience geriatric syndromes that may affect the risk/benefit profile of medications. Little is known about the use of such medications in the older population. This article describes medication use and costs in Italian adults aged ≥90 years. Data from the 2019 Pharmaceutical Prescriptions database, concerning data on medications reimbursed by the Italian National Health Service, were analyzed in terms of prevalence and amount of use expressed as defined daily dose/1,000 users (DDD/1,000 users/day), accounting for different age-groups and sex. All individuals aged ≥90 years used at least one medication, with a mean number of 3128 DDD/1,000 users/day corresponding to an annual cost of 683 euros per user. Both use and costs linearly decreased with increasing age, with men accounting for a higher amount of DDD/1,000 users and costs than women across all age-groups. Antihypertensives (1330 DDD/1,000 inhabitants), antiplatelet agents (337 DDD/1,000 inhabitants), medications for peptic ulcer and gastroesophageal reflux (328 DDD/1,000 inhabitants), and lipid-lowering agents (166 DDD/1,000 inhabitants) were the most frequently used medications. We observed a progressive decrease in the usage of the majority of medications with increasing age, with the exception of antibiotics and antipsychotics. Individuals aged ≥90 years used a lower DDD/1,000 users, with an associated decrease in annual costs. The persistent use of preventive medications highlights the potential lack of awareness regarding medication rationalization and guidance for optimizing prescriptions. Our findings highlight the need for further initiatives to improve medications' appropriateness in these older age-groups.

Orphan Drug Prices and Epidemiology of Rare Diseases: A Cross-Sectional Study in Italy in the Years 2014-2019.

INTRODUCTION: It is well acknowledged that the price of orphan drugs is normally higher than that resulting from the value-based pricing. A correlation between the cost of therapy for orphan drugs and the epidemiology (prevalence and incidence) of the related rare disease can be hypothesized. METHODS: This analysis includes all approved orphan drugs by European Medicines Agency whose reimbursement was granted for the first therapeutic indication in the years 2014-2019 in Italy. Regression and correlation analyses were performed to analyze the possible correlations between the logarithm of the annual therapy cost and the epidemiology of the rare diseases, between orphan drugs consumption and epidemiology of related rare disease and between therapy cost and the consumption. RESULTS: The regression analysis between the annual cost of therapy estimated on the published ex-factory price and the prevalence showed a slightly decreasing, not statistically significant, trend (coefficient: -0.10, p-value: 0.41). The results were similar when using the price resulting from the application of Managed Entry Agreements (coefficient: -0.11, p-value: 0.40). The regression analysis between sales volume and prevalence showed a positive slope without an acceptable level of significance (p-value: 0.04). The correlation analysis between the therapy cost and the sales volume highlighted again an absence of significant association, similarly if considering only ATC L orphan drugs, or the incidence. DISCUSSION: The definition of the price of an orphan drug seems not to depend on the rarity of the disease, and sales volumes do not correlate with the epidemiology of the rare disease and with the annual cost of therapy.

[Medicines use in older adults in Italy. The OsMed National Report 2019.] / Uso dei farmaci nella popolazione anziana in Italia. Il Rapporto Nazionale OsMed 2019.

The "National Report on Medicines use in older adults in Italy. Year 2019" provides a summary of data concerning the expenditure and consumption of medicines in individuals aged 65 or above in Italy. In addition to general characteristics and considerations, analyzes conducted on specific conditions, situations and settings are reported, such as the concomitant use in patients with chronic diseases, the use of medicines in hospitals and RSA and the impact of the covid-19 pandemic. Four local experiences related to deprescribing interventions are then reported, which highlight the feasibility and value of this approach.

[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.

[Medicines use in Italy. 2020 OsMed National Report.] / L'uso dei farmaci in Italia. Il Rapporto Nazionale OsMed 2020.

The 2020 National Report "Medicines use in Italy", produced by the National Observatory on the Use of Medicines (OsMed) of the Italian Medicines Agency (AIFA), describes the Italian pharmaceutical assistance through different available information flows that allow to recompose pharmaceutical territorial and hospital assistance, concerning both the national health service and private citizens. In the Report the results of numerous analyzes, both general and focused on specific therapeutic categories and classes, relating to pharmaceutical expenditure and consumption, are reported, but it is also present an in-depth analysis about monitoring registries and conditional reimbursement agreements, and a comparison between the most relevant Italian data and those of nine other European countries.

[Therapeutic drug plans: how many and which ones? Overview of a prescriptive and care appropriateness tool.] / Piani Terapeutici dei farmaci: quanti e quali? Fotografia di uno strumento di appropriatezza prescrittiva e assistenziale.

Therapeutic plans (TPs) were introduced in Italy in 2004 in order to ensure the continuity in the prescription of new drugs between specialist physicians and general practitioners (GPs). Over the years this prescription tool was updated several times: starting from a paper form without any template ("paper TP") to a template defined by AIFA to collect specific clinical information, up to a web-based form to collect all information into a database. Over time-critical issues concerning its usefulness have been raised, especially when AIFA established several extensions for TP validity to ensure the social distancing required by the covid-19 pandemic. Therefore, after several years from their establishment, pending adoption of necessary implementing of Ministerial Decree of 25th March 2020, a check of the actual impact of TPs is required, in order to plan their review. This study provide a detailed overview of all TPs active in Italy at the 11th May 2020. From Farmadati database, all drugs reimbursed by the National Health Service (class A drugs) and requiring TP were selected. The consumption of these drugs has been derived from OsMed Reports that make available data of medicines consumption and expenditure in the general population in Italy. The analysis showed that TP is required for the prescription of 935 medicinal products (9.6% of class-A drugs) and 147 different active substances (belonging to 34 different Therapeutic Groups and 66 subgroups). Out of these, 67 (46%) required a paper TP without any template, 72 (49%) a paper TP on AIFA template, and 8 (5%) a web-based TP. The Therapeutic Group with the largest number of active ingredients with TP were antidiabetics (19.7%), followed by immunomodulating and immunosuppressants (9.5%) and medications for asthma and COPD (6.8%). Consumption analysis of drugs with TP showed that this prescription tool covers 943,899,598 DDD per year, equal to 2,586,026 DDD/day. This means that TPs have a very high impact in terms of the prevalence of patients treated on the entire care process. Of all annual DDDs prescribed on TP, 46.8% concerned drugs with TP on template AIFA, 34.5% drugs with web-based TP, while the remaining 18.7% drugs with paper TP without a template. This analysis may provide the basis for an analytical case-by-case review of TP maintenance needs, trying to maximize the benefits of this tool and to reduce its possible adverse effects. This review could be helpful to ensure the appropriateness in the drug uses, to enhance the role of general medicine, and to simplify the pathways of millions of patients ensuring the continuity of their care.

[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.

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.

The Severity of Acute Illness and Functional Trajectories in Hospitalized Older Medical Patients.

BACKGROUND: Acute diseases and hospitalization are associated with functional deterioration in older persons. Although most of the functional decline occurs before hospitalization in response to the acute diseases, the role played by comorbidity in the functional trajectories around hospitalization is unclear. METHODS: Observational prospective study of 696 elderly individuals hospitalized in two Italian general medicine wards. Functional status of the elderly patients at 2 weeks before hospitalization (baseline), at hospital admission, and at discharge was measured by the Barthel Index. Comorbidity was measured at admission by the Geriatric Index of Comorbidity (GIC), a tool mostly based on illness severity. The association of GIC with changes in functional status before hospitalization (between baseline and admission), during hospitalization (between admission and discharge), and in the overall period between baseline and discharge was assessed by logistic regression analyses. Hospitalization-associated disability (HAD) was defined as a functional decline between baseline and discharge. RESULTS: Illness severity (GIC 3-4 vs 1-2: odds ratio [OR] 2.2, 95% CI [confidence interval] 1.5-3.3, p < .0001) and older age significantly predicted prehospital functional decline (between baseline and admission). Illness severity (OR 1.9, 95% CI 1.2-3, p = .004) and older age were also predictive of HAD, even after adjustment for each coded primary discharge diagnosis. After adjustment for the occurrence of prehospital functional decline, however, illness severity and older age were not predictive of HAD anymore. CONCLUSIONS: The severity of illnesses was strongly associated with adverse functional outcomes around hospitalization, but frailty, intended as functional vulnerability to the acute disease before hospitalization, was a stronger predictor of HAD than illness severity and age.

Hope in cancer patients: the relational domain as a crucial factor.

AIMS AND BACKGROUND: Hope is crucial for patients with cancer. We explored the determinants of hope in patients with cancer using a questionnaire administered over the course of 1 day to an unselected sample of patients at an Italian cancer center. METHODS: A team of oncologists, statisticians, and chaplains developed a questionnaire with medical, psychological, spiritual, and religious content. A cross-sectional study was conducted on 320 patients who answered the questionnaire. RESULTS: In the group of participants, 92.8% had a religious belief. Women, patients with limited formal education, and believers were more hopeful. Patients placed trust in God, their partners and children, scientific research, and doctors. On univariate and multivariate analysis, hope was found sensitive to patients' sharing their experiences with others (including family and friends), their positive perception of the people around them, and their relationship with doctors and nurses. CONCLUSIONS: If validated in further studies, these results support the notion that a patient with cancer's sense of hope is sensitive to the quality of relationships with caregivers. This may be important to health care organization and resource allocation.