From Prioritization to Universal Treatment: Successes and Challenges of Hepatitis C Virus Elimination in Italy.

Italy has had the highest prevalence of hepatitis C virus (HCV) infection and mortality from HCV-related liver cancer in Europe. Although direct-acting antivirals (DAA) were initially restricted to persons with advanced fibrosis, their use has since been extended to all infected individuals; more than 244 000 persons have been treated to date. HCV liver-related mortality is expected to decline by 75% by 2030, achieving the World Health Organization target for mortality. However, Italy risks failing to meet the overall goal of eliminating HCV infection by 2030. In this light, €71.5 million have been allocated for screening initially specific target populations (persons who inject drugs, prison inmates, and the 1969-1989 birth cohort). Herein, we outline the challenges and recommendations for how to move Italy toward HCV elimination, including expanding screening programs in other populations, increasing awareness through strategic communication, sustaining DAA access, and tailoring care models to meet the needs of key populations.

Optimizing diagnostic algorithms to advance Hepatitis C elimination in Italy: A cost effectiveness evaluation.

OBJECTIVES: Optimized diagnostic algorithms to detect active infections are crucial to achieving HCV elimination. We evaluated the cost effectiveness and sustainability of different algorithms for HCV active infection diagnosis, in a context of a high endemic country for HCV infection. METHODS: A Markov disease progression model, simulating six diagnostic algorithms in the birth cohort 1969-1989 over a 10-year horizon from a healthcare perspective was used. Conventionally diagnosis of active HCV infection is through detection of antibodies (HCV-Ab) detection followed by HCV-RNA or HCV core antigen (HCV-Ag) confirmatory testing either on a second sample or by same sample reflex testing. The undiagnosed and unconfirmed rates were evaluated by assays false negative estimates and each algorithm patients' drop-off. Age, liver disease stages distribution, liver disease stage costs, treatment effectiveness and costs were used to evaluate the quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratios (ICER). RESULTS: The reference option was Rapid HCV-Ab followed by second sample HCV-Ag testing which produced the lowest QALYs (866,835 QALYs). The highest gains in health (QALYs=974,458) was obtained by HCV-RNA reflex testing which produced a high cost-effective ICER (€891/QALY). Reflex testing (same sample-single visit) vs two patients' visits algorithms, yielded the highest QALYs and high cost-effective ICERs (€566 and €635/QALY for HCV-Ag and HCV-RNA, respectively), confirmed in 99.9% of the 5,000 probabilistic simulations. CONCLUSIONS: Our data confirm, by a cost effectiveness point of view, the EASL and WHO clinical practice guidelines recommending HCV reflex testing as most cost effective diagnostic option vs other diagnostic pathways.

Direct and indirect costs of cluster headache: a prospective analysis in a tertiary level headache centre.

BACKGROUND: Cluster headache (CH) is the most frequent trigemino-autonomic cephalgia. CH can manifest as episodic (ECH) or chronic cluster headache (CCH) causing significant burden of disease and requiring attack therapy and prophylactic treatment. The few data available on the economic burden of CH come from retrospective studies based on questionnaires, population surveys and medical insurance claims database. Although all these studies showed an important economic burden, they provided different estimates depending on variability of CH awareness and management, healthcare systems, available therapies and use of treatments according to different guidelines. METHODS: This prospective study aimed to quantify the total direct and indirect cost of ECH and CCH over a cluster period, both for the patient and for the National Health System (NHS), using data from subjects who consecutively attended an Italian tertiary headache centre between January 1, 2018 and December 31, 2018. RESULTS: A total 108 patients (89 ECH, 19 CCH) were included. Mean attack frequency was 2.3 ± 1.4 per day. Mean total cost of a CH bout was €4398 per patient and total cost of CCH was 5.4 times higher than ECH (€13,350 vs. €2487, p <  0.001). Direct costs represented the 72.1% of total cost and were covered for the 94.8% by the NHS. The costs for any item of expense were higher for CCH than for ECH (p <  0.001). Mean indirect costs for a CH bout were €1226 per patient and were higher for CCH compared to ECH (€3.538 vs. €732), but the difference was not significant. Days with reduced productive capacity impacted for the 64.6% of the total indirect costs. The analysis of the impact CH on work showed that 27%% of patients felt that CH had limited their career, 40% had changed their work pattern, 20% had changed their place of employment and 10% had lost a job due to the disease. CONCLUSION: Our results provide a valuable estimate of the direct and indirect costs of ECH and CCH in the specific setting of a tertiary headache centre and confirm the high economic impact of CH on both the NHS and patients.

Budget impact of bimonthly use of cetuximab in patients diagnosed with metastatic colorectal cancer.

Aim: Cetuximab is used for the treatment of RAS wild-type metastatic colorectal cancer patients. Standard administration schedule is once a week; however, the bioequivalence of an every-other-week (EOW) schedule was demonstrated. Methods: We compared a base case scenario of 100% weekly administration to an EOW at 50 or 100%. Medical examinations, patient management and loss of productivity were considered. Results: Base case was estimated at €100.6 million versus €92.8 million and €84.9 million of EOW 50 and 100%, which showed a cost reduction of 8 and 16%, respectively. Indirect costs accounted for 65% in both scenarios. Conclusion: The adoption of an EOW administration schedule of cetuximab reduced direct and indirect costs substantially.

Cost of chronic and episodic migraine patients in continuous treatment for two years in a tertiary level headache Centre.

BACKGROUND: Migraine is one of the most common neurological diseases and an estimated 1.04 billion people worldwide have been diagnosed with migraine. Available data suggest that migraine is world widely associated with a high economic burden, but there is great variability in estimated costs that depends on the geographical, methodological and temporal differences between the studies. The purpose of this study was to quantify the annual direct cost of episodic migraine (EM) and chronic migraine (CM), both for the patient and for the National Health System (NHS), using data from subjects who attended an Italian tertiary headache centre. Furthermore, we evaluated comparatively the impact of gender and age on the economic burden of migraine. METHODS: We conducted a retrospective and non-interventional observational analysis of the electronic medical records of subjects with EM and CM who consecutively attended the Regional Referral Headache Centre of Rome and undergoing continuous treatment in the 2 years prior to 31 January 2019. This approach was intended to prevent distorsions due to natural fluctuations in migraine status over time. The collected data included demographic characteristics, number of specialist visits, consumption of medications, diagnostic tests, accesses in the emergency department (ED) and days of hospitalization due to the pathology. RESULTS: Our sample consisted of 548 patients (85.4% women and 14.6% men): 65.5% had CM and 34.5% had EM. The average annual expenditure per patient was €1482. 82.8% of the total cost (€1227) was covered by the NHS. The main item of expenditure were medications that represented 86.8% (€1286), followed by specialist visits (10.2%), hospitalizations for (1.9%), diagnostic tests for (1%) and ED visits for (0.1%). Costs were significantly higher for women than men (€1517 vs. €1274, p = 0.013) and increased with age (p = 0.002). The annual direct cost of CM was 4.8-fold higher than that of EM (€2037 vs. €427, p = 0.001). CONCLUSION: Our results provide a valuable estimate of the annual direct cost of CM and EM patients in the specific setting of a tertiary headache centre and confirm the high economic impact of migraine on both the NHS and patients.

Impact of new DAA therapy on real clinical practice: a multicenter region-wide cohort study.

BACKGROUND: Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. METHODS: The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient's level and random slope at the level of the time; i.e. either before or after therapy. RESULTS: Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient's baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. CONCLUSION: Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

Cost-effectiveness analysis of the nine-valent HPV vaccine in Italy.

BACKGROUND: In Italy HPV vaccination with the quadrivalent vaccine (Gardasil®) is offered actively and free of charge to girls aged 12 since 2007. A nine-valent vaccine (Gardasil 9®) received the European market authorization in 2015 to protect, with only 2 doses, against around 90% of all HPV positive cancers, over 80% of high-grade precancerous lesions and 90% of genital warts caused by HPV types 6/11. METHODS: A dynamic transmission model simulating the natural history of HPV-infections was calibrated to the Italian setting and used to estimate costs and QALYs associated with vaccination strategies. The analyses compared two strategies with the nine-valent vaccine (cervical cancer screening and vaccination in girls only or vaccination in boys and girls) to four alternative strategies (cervical cancer screening and vaccination with quadrialent vaccine in girls only, in both boys and girls, with bivalent vaccine in girls and screening strategy only). The National Health Service perspective was considered. CONCLUSION: The switch to the nine-valent vaccine in Italy can further reduce the burden associated to cervical cancer and HPV-related diseases and is highly cost-effective. RESULTS: Compared to the current vaccination program with quadrivalent vaccine, the nine-valent vaccine in a programme including girls and boys shows further reductions of 17% in the incidence of cervical cancer, 35 and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new technology is associated with an ICER of 10,463€ per QALY gained in universal vaccination, decreasing to 4483€ when considering the vaccine switch for girls-only.

[The economic value of vaccinations: a systematic review of Italian economic evaluations and HTA reports]. / Le implicazioni economiche delle vaccinazioni: una revisione sistematica delle valutazioni economiche e di HTA condotte in Italia.

INTRODUCTION: Decision-making in healthcare should rely on evidence-based approaches able to make possible a transparent and robust assessment of all the aspects related to health technologies. One of the assessment elements is represented by the efficiency that is the specific objective of economic evaluations and also of Health Technology Assessment (HTA). The collection and synthesis of evidence is the first indispensable step in order to foster a proper convey of scientific knowledge to the decision-makers. This work, carried out within a broader project on the transfer of evidence from the scientific to the decision making world, is aimed to release an overview of economic evaluations and HTA on vaccines conducted in Italy. The project was carried out within the activities of the ISPOR Italy-Rome Chapter. METHODS: A systematic review of Italian economic evaluations and HTA performed on vaccines and published up to May 2015 was carried out. PubMed, Scopus and the NIHR HTA databases were queried and a hand-search was performed on key journals in the field (Global & Regional Health Technology Assessment; PharmacoEconomics Italian Research Articles; Giornale italiano di HTA; Politiche Sanitarie; HTA Focus - Pills of Clinical Governance; Pillole di Farmacoeconomia; Giornale Italiano di Farmacoeconomia e Farmacoutilizzazione; IJPH; Quaderni dell'IJPH). Studies were considered eligible if showing the results of a full economic evaluations and if performed in Italy. RESULTS: The literature search yielded 10 HTA reports and 33 economic evaluations. Among the latter, 20 (60,6%) were cost-effectiveness analyses. Ten studies (23,3%) assessed the vaccination against S. pneumoniae figuring out that it is cost-effectiveness and even costsaving in cases of newborns and subjects at risk. Nine studies (20,9%) addressed influenza vaccination and demonstrated its dominance on non-vaccination in the elderly. Eight studies (18,6%) evaluated the HPV vaccines concluding that they are cost-effective. Five studies (11,6%) devoted to anti-rotavirus vaccination showing its dominance on non-vaccination, in particular from the society perspective. Vaccination against pertussis, hepatitis B, chicken pox, measles, rubella, mumps were eventually shown cost-saving. The vaccine against Neisseria meningitidis was considered potentially cost-effective. CONCLUSION: The Italian scientific evidence on efficiency of vaccination is broad and allows concluding that vaccinations are value for money interventions.

Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study.

BACKGROUND: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE: The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS: We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS: In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS: Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.

Screening strategy to advance HCV elimination in Italy: a cost-consequence analysis.

BACKGROUND AND AIMS: Italy has the greatest burden of hepatitis C virus (HCV) infection in Western Europe. The screening strategy represents a crucial prevention tool to achieve HCV elimination in Italy. We evaluated the cost-consequences of different screening strategies for the diagnosis of HCV active infection in the birth cohort 1948-1968 to achieve the HCV elimination goal. METHODS: We designed a probabilistic model to estimate the clinical, and economic outcomes of different screening coverage uptakes, considering the direct costs of HCV management according to each liver fibrosis stage, in the Italian context. A decision probabilistic tree simulates 4 years of HCV testing of the 1948-1968 general population birth cohort, (15,485,565 individuals to be tested) considering different coverage rates. A No-screening scenario was compared with two alternative screening scenarios that represented different coverage rates each year: (1) Incremental approach (coverage rates equal to 5%, 10%, 30%, and 50% at years 1, 2, 3, and 4, respectively) and (2) Fast approach (50% coverage rate at years 1, 2, 3 and 4). Overall 106,200 cases were previously estimated to have an HCV active infection. A liver disease progression Markov model was considered for an additional 6 years (horizon-time 10 years). RESULTS: The highest increased number of deaths and clinical events are reported for the No-screening scenario (21,719 cumulative deaths at the end of ten years; 10,148 cases with HCC and/or 7618 cases with Decompensated Cirrhosis). Following the Fast-screening scenario, the reductions in clinical outcomes and deaths were higher compared with No-screening and Incremental-screening. At ten years time horizon, less than 5696 liver deaths (PSA CI95%: - 3873 to 7519), 3,549 HCC (PSA CI95%: - 2413 to 4684) and less than 3005 liver decompensations (PSA CI 95%: - 2104 to 3907) were estimated compared with the Incremental-scenario. The overall costs of the Fast-screening, including the costs of the DAA and liver disease management of the infected patients for 10 years, are estimated to be € 43,107,543 more than no-investment in screening and € 62,289,549 less compared with the overall costs estimated by the Incremental-scenario. CONCLUSION: It is necessary to guarantee dedicated funds and efficiency of the system for the cost-efficacious screening of the 1948-1968 birth cohort in Italy. A delay in HCV diagnosis and treatment in the general population, yet not addressed for the HCV free-of-charge screening, will have important clinical and economic consequences in Italy.

Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes.

INTRODUCTION: We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU). RESEARCH DESIGN AND METHODS: Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU. RESULTS: Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively. CONCLUSIONS: Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.

Projecting the economic burden of chronic kidney disease at the patient level (Inside CKD): a microsimulation modelling study.

Background: The growing burden of chronic kidney disease (CKD) places substantial financial pressures on patients, healthcare systems, and society. An understanding of the costs attributed to CKD and kidney replacement therapy (KRT) is essential for evidence-based policy making. Inside CKD maps and projects the economic burden of CKD across 31 countries/regions from 2022 to 2027. Methods: A microsimulation model was developed that generated virtual populations using national demographics, relevant literature, and renal registries for the 31 countries/regions included. Patient-level country/region-specific cost data were extracted via a pragmatic local literature review and under advisement from local experts. Direct cost projections were generated for diagnosed CKD (by age, stage 3a-5), KRT (by modality), cardiovascular complications (heart failure, myocardial infarction, stroke), and comorbidities (hypertension, type 2 diabetes). Findings: For the 31 countries/regions, Inside CKD projected that annual direct costs (US$) of diagnosed CKD and KRT would increase by 9.3% between 2022 and 2027, from $372.0 billion to $406.7 billion. Annual KRT-associated costs were projected to increase by 10.0% from $169.6 billion to $186.6 billion between 2022 and 2027. By 2027, patients receiving KRT are projected to constitute 5.3% of the diagnosed CKD population but contribute 45.9% of the total costs. Interpretation: The economic burden of CKD is projected to increase from 2022 to 2027. KRT contributes disproportionately to this burden. Earlier diagnosis and proactive management could slow disease progression, potentially alleviating the substantial costs associated with later CKD stages. Data presented here can be used to inform healthcare resource allocation and shape future policy. Funding: AstraZeneca.

An Analysis of the Distribution of Direct Cost of Diabetes Care in Selected Districts in Italy.

INTRODUCTION: This study aims to define the distribution of direct healthcare costs for people with diabetes treated in two healthcare regions in Italy, based on number of comorbidities and treatment regimen. METHODS: This was a retrospective analysis using data from two local health authority administrative databases (Campania and Umbria) in Italy for the years 2014-2018. Data on hospital care, pharmaceutical and specialist outpatient and laboratory assistance were collected. All people with diabetes in 2014-2018 were identified on the basis of at least one prescription of hypoglycemic drugs (ATC A10), hospitalization with primary or secondary diagnosis of diabetes mellitus (ICD9CM 250.xx) or diabetes exemption code (code 013). Subjects were stratified into three groups according to their pharmaceutical prescriptions during the year: Type 1/type 2 diabetes (T1D/T2D) treated with multiple daily injections with insulin (MDI), type 2 diabetes on basal insulin only (T2D-Basal) and type 2 diabetes not on insulin therapy (T2D-Oral). RESULTS: We identified 304,779 people with diabetes during the period for which data was obtained. Analysis was undertaken on 288,097 subjects treated with glucose-lowering drugs (13% T1D/T2D-MDI, 13% T2D-Basal, 74% T2D-Oral). Average annual cost per patient for the year 2018 across the total cohort was similar for people with T1D/T2D-MDI and people with T2D-Basal (respectively €2580 and €2254) and significantly lower for T2D-Oral (€1145). Cost of hospitalization was the main driver (47% for T1D/T2D-MDI, 45% for T2D-Basal, 45% for T2D-Oral) followed by drugs/devices (35%, 39%, 43%) and outpatient services (18%, 16%, 12%). Average costs increased considerably with increasing comorbidities: from €459 with diabetes only to €7464 for a patient with four comorbidities. Similar trends were found across all subgroups analysis. CONCLUSION: Annual cost of treatment for people with diabetes is similar for those treated with MDI or with basal insulin only, with hospitalization being the main cost driver. This indicates that both patient groups should benefit from having access to scanning continuous glucose monitoring (CGM) technology which is known to be associated with significantly reduced hospitalization for acute diabetes events, compared to self-monitored blood glucose (SMBG) testing.

Towards the eradication of HPV infection through universal specific vaccination.

BACKGROUND: The Human Papillomavirus (HPV) is generally recognized to be the direct cause of cervical cancer. The development of effective anti-HPV vaccines, included in the portfolio of recommended vaccinations for any given community, led to the consolidation in many countries of immunization programs to prevent HPV-related cervical cancers. In recent years, increasing evidence in epidemiology and molecular biology have supported the oncogenic role of HPV in the development of other neoplasm including condylomas and penile, anal, vulvar, vaginal, and oro-pharyngeal cancers. Men play a key role in the paradigm of HPV infection: both as patients and as part of the mechanisms of transmission. Data show they are affected almost as often as women. Moreover, no screening procedures for HPV-related disease prevention are applied in men, who fail to undergo routine medical testing by any medical specialist at all. They also do not benefit from government prevention strategies. DISCUSSION: A panel of experts convened to focus on scientific, medical, and economic studies, and on the achievements from health organizations' intervention programs on the matter. One of the goals was to discuss on the critical issues emerging from the ongoing global implementation of HPV vaccination. A second goal was to identify contributions which could overcome the barriers that impede or delay effective vaccination programs whose purpose is to eradicate the HPV infection both in women and men. SUMMARY: The reviewed studies on the natural history of HPV infection and related diseases in women and men, the increasing experience of HPV vaccination in women, the analysis of clinical effectiveness vs economic efficacy of HPV vaccination, are even more supportive of the economic sustainability of vaccination programs both in women and men. Those achievements address increasing and needed attention to the issue of social equity in healthcare for both genders.

COVID-19 Outbreak: A Call to Arms for the World Healthcare Systems.

Coronavirus Disease 2019 (COVID-19) outbreak has placed a strong pressure on worldwide healthcare systems over the last years, testing their capacity to withstand stress [...].

Understanding the potential of digital therapies in implementing the standard of care for depression in Europe.

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

Socio-economic impact of epilepsy in Italy.

The World Health Assembly recognizes the growing economic and societal burden of neurological disorders, a leading cause of disability and the second cause of mortality in the world. In this context we analysed the socio-economic impact of epilepsy in Italy with a specific focus on hospitalizations and costs related to disability pensions (DPs) and ordinary disability allowances. In the case of epilepsy, between 2009 and 2015 we observed an alarming increasing trend for DPs (+26%), indicating that substantial expenses must be supported throughout the patients' lifetimes by both the social security system and the National Health Service (NHS) on top of the impact on caregivers. We also analysed the hospital expenditure on epilepsy through the information available in the Hospital Discharge Cards between 2015 and 2018. Almost all admissions (76% ordinary hospitalizations, 24% day hospitals) were acute (95%), followed by rehabilitation (4%) and long-term care (1%). The cost of acute and ordinary hospitalizations was by far the highest in 2018, the last year of analysis. This large expense due to hospitalizations could be reduced through the implementation of different organizational and management approaches. Our recommendation is that the policy maker should consider the best approach to ensure an early diagnosis for patients and provide early access to drugs and/or surgery. Finally, the adoption of new innovative treatments should improve effectiveness and, at the same time, reduce the expense of the NHS, of the social system as a whole, with a tangible improvement in patients' quality of life.

The Impact of COVID-19 Vaccination on the Italian Healthcare System: A Scenario Analysis.

BACKGROUND AND OBJECTIVE: During 2020, the only instruments for fighting against the pandemic peaks were lockdowns, physical distancing, closure of schools and non-essential businesses, and travel restrictions. The new vaccination strategy adopted in Italy in 2021 represented a new perspective for policymakers. OBJECTIVE: The aim of this study was to estimate the effects of the national immunisation strategy for coronavirus disease 2019 (COVID-19) in Italy on the national healthcare system. METHODS: An epidemiological scenario analysis was developed in order to simulate the impact of the COVID-19 pandemic on the Italian national healthcare system in 2021. Hospitalisations, intensive care unit (ICU) admissions and death rates were modelled based on 2020 data. Costs were estimated using hospital admissions from the Policlinico of Tor Vergata Hospital in Rome. Two scenarios were tested, one with vaccination and the second without. RESULTS: The roll-out of vaccinations to protect against COVID-19 was estimated to prevent 52,115 deaths in 2021, 45.2% less than what was expected in the absence of immunisation. Based on the assumptions underlying the two epidemiological scenarios, our model predicted an overall reduction of 2.4 million hospital admissions and 259,000 ICU admissions (74.9% and 71.3% less, respectively, than the world without vaccinations between June and December 2021). Overall, in Italy, the model estimated over €3.0 billion costs of hospitalisations due to COVID-19 in 2020. In 2021, vaccines prevented around 36% of the overall costs. CONCLUSIONS: This is the first study highlighting the effect of vaccines on the Italian healthcare system in terms of avoided cases, hospitalisations and costs. Our results have the potential to inform policymakers and the general population on the benefits of vaccinations.

HPV Vaccination during the COVID-19 Pandemic in Italy: Opportunity Loss or Incremental Cost.

OBJECTIVES: Italy was the first European country to introduce universal vaccination of adolescents, for both males and females, against Human Papilloma Virus (HPV) starting in 2017 with the NIP 2017-2019's release. However, vaccine coverage rates (VCRs) among adolescents have shown a precarious take-off since the NIP's release, and this situation worsened due to the impact of the COVID-19 pandemic in 2020. The aim of this work is to estimate the epidemiological and economic impact of drops in VCRs due to the pandemic on those generations that missed the vaccination appointment and to discuss alternative scenarios in light of the national data. METHODS: Through an analysis of the official ministerial HPV vaccination reports, a model was developed to estimate the number of 12-year-old males and females who were not vaccinated against HPV during the period 2017-2021. Based on previously published models that estimate the incidence and the economic impact of HPV-related diseases in Italy, a new model was developed to estimate the impact of the aggregated HPV VCRs achieved in Italy between 2017 and 2021. RESULTS: Overall, in 2021, 723,375 girls and 1,011,906 boys born between 2005 and 2009 were not vaccinated against HPV in Italy (42% and 52% of these cohorts, respectively). As compared with the 95% target provided by the Italian NIP, between 505,000 and 634,000 girls will not be protected against a large number of HPV-related diseases. For boys, the number of the unvaccinated population compared to the applicable target is over 615,000 in the 'best case scenario' and over 749,000 in the 'worst case scenario'. Overall, between 1.1 and 1.3 million young adolescents born between 2005 and 2009 will not be protected against HPV-related diseases over their lifetime with expected lifetime costs of non-vaccination that will be over EUR 905 million. If the 95% optimal VCRs were achieved, the model estimates a cost reduction equal to EUR 529 million, the net of the costs incurred to implement the vaccination program. CONCLUSION: Suboptimal vaccination coverage represents a missed opportunity, not only because of the increased burden of HPV-related diseases, but also in terms of economic loss. Thus, reaching national HPV immunization goals is a public health priority.

Health and Economic Impact of Atrial Fibrillation of Workers in Italy: Social Security Benefits.

BACKGROUND: The aim of this research was to analyze trends in social security applications in Italy as a result of the onset of atrial fibrillation, analyzing data pertaining to the classification of professions and assessing the economic impact on the social security system. METHODS: We analyzed all applications for invalidity allowances and invalidity pensions throughout Italy over a 10-year period from 01.01.2009 to 31.12.2019, giving specific attention to all reports indicating atrial fibrillation as the principal diagnosis (Cod. ICD-9-CM 427.31). We then extracted the relative expenditure data for said benefits. The results of all analyses have been collated in tables. RESULTS: Over the period in question, a total of 3468 applications for assistance were filed throughout Italy indicating a diagnosis of atrial fibrillation, of which 58% were rejected, 41% qualified for an invalidity allowance, and only 1.1% qualified for a pension. On average, every year, 1100 workers received social security benefits as a result of a diagnosis of atrial fibrillation, which equates to an average annual expenditure of EUR 10 million. A comparison of the data from the first observation year (2009) with data from the last (2019) shows a rising trend in the number of beneficiaries and consequently in expenses. CONCLUSIONS: The social security assistance provided by the Italian government by means of the National Institute of Social Security is fundamental to social cohesion and to those who are either permanently disabled from working or those with a significantly diminished earning capacity. This assistance is associated with a significant financial cost, which requires careful monitoring.