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Objectives We conducted a cost–benefit analysis of the pediatric National Immunization Program (NIP) in Italy.Methods An economic model evaluated the benefit–cost ratio (BCR) of the Italian pediatric NIP, including 10 pathogens for mandatory vaccines and 4 pathogens for recommended vaccines for children aged 0–10 years from the healthcare-sector and societal perspectives. Separate decision trees were used to model each vaccine-preventable disease (VPD). The 2020 birth cohort (n = 420,084) was followed over their lifetime; the model projected and compared discounted disease cases, life-years, quality-adjusted life-years (QALYs), and costs (2021 euros) with and without immunization (based on current and pre – vaccine era disease incidence estimates, respectively).Results The pediatric NIP was estimated to prevent 1.8 million cases of VPDs and 3,330 deaths, resulting in 45,900 fewer life-years lost and 57,000 fewer QALYs lost. Vaccination costs of €285 million were offset by disease cost savings of €1.6 billion, resulting in a BCR of 5.6 from a societal perspective (BCR = 1.7 from a healthcare-sector perspective). When QALYs gained were valued, the BCR increased to 15.6.Conclusions The benefits of the Italian pediatric NIP, including averted disease-related morbidity, mortality, and associated costs, highlight the value of continued investment in pediatric immunization.

Background Protection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance.Research design and methods An umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women.Results The literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9).Conclusions Rather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.

ABSTRACTBackground The breadth of protection of National Immunisation Programmes (NIPs) across Europe varies, however, this has not been assessed within published literature. Therefore, a framework was developed to assess the comprehensiveness of pediatric NIPs in Europe. This study aimed to validate and further develop criteria used to cluster countries into three tiers.Research design and methods Independent Europe-based experts (n = 23) in the field of pediatric vaccination were invited to participate in a double-blinded modified Delphi panel, with two online survey rounds and a virtual consensus meeting. Consensus was defined as ≥ 80% of experts rating their agreement/disagreement on a 9-point Likert scale.Results The number of preventable diseases covered by an NIP, simplification of the vaccination calendar, strengthened protection by increasing serotype, degree of funding and epidemiological factors were considered key concepts for consideration of the comprehensiveness of pediatric NIPs in Europe. Experts highlighted that the framework should be extended to include adolescent vaccines and populations up to 18 years of age. Consensus regarding further amendments to the framework was also reached.Conclusions This Delphi panel validated a framework to assess the comprehensiveness of European NIPs. The framework can be used to facilitate discussions to help countries improve and expand the breadth of protection provided by their NIP.

Abstract Introduction Despite new anti-seizure medications (ASMs) being introduced into clinical practice, about one-third of people with epilepsy do not reach seizure control. Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. In randomized controlled trials, adjunctive cenobamate reduced the frequency of focal seizures in people with uncontrolled epilepsy. Studies performed in real-world settings are useful to complement this evidence and better characterize the drug profile. Methods The Italian BLESS (“Cenobamate in Adults With Focal-Onset Seizures”) study is an observational cohort study aimed to evaluate the effectiveness, tolerability, and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy in the context of real-world clinical practice. The study is ongoing and conducted at 50 centers in Italy. This first interim analysis includes participants enrolled until June 2023 and with 12-week outcome data available. Results Forty participants with a median age of 36.5 (interquartile range [IQR] 26.0–47.5) years were included. The median monthly seizure frequency at baseline was 6.0 (IQR 2.5–17.3) seizures and 31 (77.5%) participants had failed four or more ASMs before cenobamate. At 12 weeks from starting cenobamate, the median reduction in monthly seizure frequency was 52.8% (IQR 27.1–80.3%); 22 (55.0%) participants had a ≥ 50% reduction in baseline seizure frequency and six (15.0%) reached seizure freedom. The median number of concomitant ASMs decreased from 3 (IQR 2–3) at baseline to 2 (IQR 2–3) at 12 weeks and the proportion of patients treated with > 2 concomitant ASMs decreased from 52.5% to 40.0%. Seven (17.5%) patients reported a total of 12 adverse events, 11 of which were considered adverse drug reactions to cenobamate. Conclusion In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control and a reduction of the burden of concomitant ASMs. Trial Registration Number NCT05859854 (ClinicalTrials.gov Identifier).

Abstract The epilepsy diagnosis still represents a complex process, with misdiagnosis reaching 40%. We aimed at building an automatable workflow, helping the clinicians in the diagnosis of temporal lobe epilepsy (TLE). We hypothesized that neuronal avalanches (NA) represent a feature better encapsulating the rich brain dynamics compared to classically used functional connectivity measures (Imaginary Coherence; ImCoh). We analyzed large-scale activation bursts (NA) from source estimation of resting-state electroencephalography. Using a support vector machine, we reached a classification accuracy of TLE versus controls of 0.86 ± 0.08 (SD) and an area under the curve of 0.93 ± 0.07. The use of NA features increase by around 16% the accuracy of diagnosis prediction compared to ImCoh. Classification accuracy increased with larger signal duration, reaching a plateau at 5 min of recording. To summarize, NA represents an interpretable feature for an automated epilepsy identification, being related with intrinsic neuronal timescales of pathology-relevant regions.

Abstract Familial epilepsy with auditory features (FEAF), previously known as autosomal‐dominant lateral temporal lobe epilepsy (ADLTE) is a genetically heterogeneous syndrome, clinically characterized by focal seizures with prominent auditory symptoms. It is inherited with autosomal‐dominant pattern with reduced penetrance (about 70%). Sporadic epilepsy with auditory features cases are more frequent and clinically indistinguishable from familial cases. One causal gene, MICAL‐1, encodes MICAL‐1, an intracellular multi‐domain enzyme that is an important regulator of filamentous actin (F‐actin) structures. Pathogenic variants in MICAL‐1 account for approximately 7% of FEAF families. Here, we describe a de novo MICAL‐1 pathogenic variant, p.Arg915Cys, in a sporadic case, an affected 21‐year‐old Italian man with no family history of epilepsy. Genetic testing was performed in the patient and his parents, using a next‐generation sequencing panel. In cell‐based assay, this variant significantly increased MICAL‐1 oxidoreductase activity, which likely resulted in dysregulation of F‐actin organization. This finding provides further support for a gain‐of‐function effect underlying MICAL‐1‐mediated epilepsy pathogenesis, as previously seen with other pathogenic variants. Furthermore, the case study provides evidence that de novo MICAL‐1 pathogenic variants can occur in sporadic cases with epilepsy with auditory feature (EAF). Plain Language Summary In this study, we report a new MICAL‐1 pathogenic variant in a patient without family history for epilepsy, not inherited from his parents. MICAL‐1 is a protein with enzymatic activity that reorganizes the structure of the cell. We proved the pathological effect of this variant by testing its enzymatic activity and found an increase of this activity. This result suggests that non‐familial cases should be tested to find novel pathogenic variants in this gene.

BackgroundDespite strong evidence supporting COVID-19 vaccine efficacy and safety, a proportion of the population remains hesitant to receive immunization. Discrete choice experiments (DCEs) can help assess preferences and decision-making drivers. ObjectiveWe aim to (1) elicit preferences for COVID-19 vaccines in Canada, Germany, the United Kingdom, and the United States; (2) understand which vaccine attributes people there value; and (3) gain insight into the choices that different population subgroups make regarding COVID-19 vaccines. MethodsParticipants in the 2019nCoV-408 study were aged ≥18 years; self-reported antivaccinationists were excluded. A DCE with a series of 2 hypothetical vaccine options was embedded into a survey to determine participant treatment preferences (primary objective). Survey questions covered vaccine preference, previous COVID-19 experiences, and demographics, which were summarized using descriptive statistics to understand the study participants’ backgrounds. In the DCE, participants were provided choice pairs: 1 set with and 1 without an “opt-out” option. Each participant viewed 11 unique vaccine profiles. Vaccine attributes consisted of type (messenger RNA or protein), level of protection against any or severe COVID-19, risk of side effects (common and serious), and potential coadministration of COVID-19 and influenza vaccines. Attribute level selections were included for protection and safety (degree of effectiveness and side effect risk, respectively). Participants were stratified by vaccination status (unvaccinated, or partially or fully vaccinated) and disease risk group (high-risk or non–high-risk). A conditional logit model was used to analyze DCE data to estimate preferences of vaccine attributes, with the percentage relative importance calculated to allow for its ranking. Each model was run twice to account for sets with and without the opt-out options. ResultsThe mean age of participants (N=2000) was 48 (SD 18.8) years, and 51.25% (1025/2000) were male. The DCE revealed that the most important COVID-19 vaccine attributes were protection against severe COVID-19 or any severity of COVID-19 and common side effects. Protection against severe COVID-19 was the most important attribute for fully vaccinated participants, which significantly differed from the unvaccinated or partially vaccinated subgroup (relative importance 34.8% vs 30.6%; P=.049). Avoiding serious vaccine side effects was a significantly higher priority for the unvaccinated or partially versus fully vaccinated subgroup (relative importance 10.7% vs 8.2%; P=.044). Attributes with significant differences in the relative importance between the high-risk versus non–high-risk subgroups were protection against severe COVID-19 (38.2% vs 31.5%; P

The exchange of knowledge and best practices in adult immunization are essential to improve vaccination strategies across the European region. Italy has made groundbreaking progress in the field, being one of the first countries to propose a life-course vaccination schedule, broadening the traditional focus on childhood immunization to include adults. All vaccines included in Italy’s vaccination schedule are free of charge. Moreover, the country’s National Immunization Plan sets clear coverage targets, immunization priorities, and actions to reduce disparities. However, the fragmentation of its National Health System following the constitutional reform of 2001 has led to an increased complexity and regional inequalities regarding immunization. Other challenges the country faces include growing vaccine hesitancy, data gaps and underserved populations. This review describes Italy’s adult immunization system, from policy to implementation. The successes, challenges and lessons learned were shared during the first Adult Immunization Board country meeting in Italy, where local experts, healthcare providers, public health representatives, and policymakers engaged in collaborative discussions and shared insights through case studies and presentations (December 2023). These insights are reviewed and discussed in this manuscript.

ABSTRACTVaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023 included recommendations for co-administration of pediatric vaccines, including the four-component vaccine for meningococcus B (4CMenB), pneumococcal conjugate vaccine (PCV), hexavalent vaccines, and oral rotavirus vaccines. Safety is a major concern when considering vaccine co-administration; therefore, a literature review of the available evidence on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines was performed. Of 763 publications screened, two studies were reviewed that reported safety data on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines in infants aged 0–24 months. Overall, these studies supported that there were no significant safety signals when co-administering 4CMenB with PCV, hexavalent/pentavalent, and rotavirus vaccines, compared with individual vaccination. This review provides key insights for healthcare professionals on the tolerability of co-administering 4CMenB with routine vaccines.

Summary: Background: Variants in GABRB2, encoding the β2 subunit of the γ-aminobutyric acid type A (GABAA) receptor, can result in a diverse range of conditions, ranging from febrile seizures to severe developmental and epileptic encephalopathies. However, the mechanisms underlying the risk of developing milder vs more severe forms of disorder remain unclear. In this study, we conducted a comprehensive genotype–phenotype correlation analysis in a cohort of individuals with GABRB2 variants. Methods: Genetic and electroclinical data of 42 individuals harbouring 26 different GABRB2 variants were collected and accompanied by electrophysiological analysis of the effects of the variants on receptor function. Findings: Electrophysiological assessments of α1β2γ2 receptors revealed that 25/26 variants caused dysfunction to core receptor properties such as GABA sensitivity. Of these, 17 resulted in gain-of-function (GOF) while eight yielded loss-of-function traits (LOF). Genotype-phenotype correlation analysis revealed that individuals harbouring GOF variants suffered from severe developmental delay/intellectual disability (DD/ID, 74%), movement disorders such as dystonia or dyskinesia (59%), microcephaly (50%) and high risk of early mortality (26%). Conversely, LOF variants were associated with milder disease manifestations. Individuals with these variants typically exhibited fever-triggered seizures (92%), milder degrees of DD/ID (85%), and maintained ambulatory function (85%). Notably, severe movement disorders or microcephaly were not reported in individuals with loss-of-function variants. Interpretation: The data reveals that genetic variants in GABRB2 can lead to both gain and loss-of-function, and this divergence is correlated with distinct disease manifestations. Utilising this information, we constructed a diagnostic flowchart that aids in predicting the pathogenicity of recently identified variants by considering clinical phenotypes. Funding: This work was funded by the Australian National Health & Medical Research Council, the Novo Nordisk Foundation and The Lundbeck Foundation.

Introduction Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants’ genetic profiles.Methods and analysis EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms.Ethics and dissemination To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET_62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters).

Abstract Introduction The study aimed to evaluate the effectiveness and safety of brivaracetam (BRV) as conversion monotherapy in adults with focal epilepsy treated in the context of real-world clinical practice. Methods This was a retrospective, observational, non-interventional study in adults with focal epilepsy who converted to BRV monotherapy following the withdrawal of background antiseizure medications (ASMs). Primary effectiveness outcome was the retention rate of BRV as single ASM at 6 and 12 months. Secondary outcomes included the 6- and 12-month rates of seizure freedom. Safety and tolerability outcomes included the frequency and type of adverse events (AEs) and the occurrence of treatment discontinuation due to AEs. Results A total of 44 participants with a median age of 63.5 (interquartile range 44–73.5) years were included; 17 subjects were seizure free at baseline, and 9 of them switched from levetiracetam because of lack of tolerability. The retention rate of BRV monotherapy was 88.6% (39/44) at 6 months and 83.9% (26/31) at 12 months. The rates of seizure freedom were 72.7% (32/44) in subjects with 6-month follow-up and 58.1% (18/31) in subjects with 12-month follow-up. The median maintenance dosage of BRV monotherapy was 150 (100–200) mg/day at 6 months and 125 (100–200) mg/day in subjects with 12-month follow-up. Adverse events were recorded in 6/44 (13.6%) participants and led to BRV discontinuation in 2/44 (4.5%) cases. The reported AEs were somnolence (n = 3), fatigue (n = 2), and irritability (n = 1); no serious AEs were experienced. In 21/44 (47.7%) participants, BRV monotherapy resulted from the direct switch from levetiracetam. The rates of treatment retention and seizure freedom at 6 and 12 months were higher among people who switched from levetiracetam to BRV monotherapy. Conclusion Brivaracetam may be a valuable treatment of focal seizures in people who converted to monotherapy in a real-life setting.

Abstract The global invasive meningococcal disease (IMD) landscape changed considerably during the COVID-19 pandemic, as evidenced by decreased incidence rates due to COVID-19 mitigation measures, such as limited social contact, physical distancing, mask wearing, and hand washing. Vaccination rates were also lower during the pandemic relative to pre-pandemic levels. Although policymakers may have shifted their focus away from IMD vaccination programs to COVID-19 vaccination programs, strong arguments support implementation and prioritization of IMD vaccination programs; IMD cases have increased in some countries and IMD rates may even have exceeded pre-pandemic levels. Additional concerns include increased susceptibility due to vaccination coverage gaps, increased incidence of other respiratory pathogens, immunity debt from lockdown restrictions, and increased IMD epidemiologic variability. The full range of benefits of widely available and effective meningococcal vaccines needs to be considered, especially in health technology assessments, where the broad benefits of these vaccines are neither accurately quantified nor captured in implementation policy decisions. Importantly, implementation of meningococcal vaccination programs in the current IMD climate also appeals to broader healthcare principles, including preparedness rather than reactive approaches, generally accepted benefit–risk approaches to vaccination, historical precedent, and the World Health Organization's goal of defeating meningitis by 2030. Countries should therefore act swiftly to bolster existing meningococcal vaccination strategies to provide broad coverage across age groups and serogroups given the recent increases in IMD incidence.

ABSTRACTIntroduction Diabetic patients are at a higher risk of getting pneumococcal disease and are therefore recommended to get vaccinated. The aim of our systematic review is the retrieval and analysis of all available evidence on the effect of pneumococcal vaccination on the risk of hospitalization and death in adult patients with diabetes.Research design and methods MEDLINEand EMBASE were searched from inception until January 2023. We included all studies investigating whether pneumococcal vaccination reduces the risk of dying or being hospitalized in diabetic patients. The Newcastle-Ottawa scale was used to assess risk of bias. Results Only two studies, encompassing a total of 68,246 subjects, were considered eligible for inclusion and of high quality. In both studies polysaccharide pneumococcal vaccination was associated with a reduction of the risk of hospitalization or death in adult diabetic patients (aHR: 0.76 in one study, aOR: 0.97 in the other one). However, in neither of the two included studies the lower risk was statistically significant.Conclusions Further research is needed due to the potentially major clinical implications for diabetic patients. The results of this systematic review can serve as a foundation for future studies, indicating the importance of continuing research in this area to improve patient outcomes.

Introduction The introduction of effective human papillomavirus (HPV) vaccination, screening, and treatment programs has led the World Health Organization to call for the global elimination of cervical cancer. Assessing progress toward this goal is supported through monitoring vaccination coverage and its impact. Areas covered We performed a targeted review to assess the characteristics of HPV-related data systems from seven high-income countries (HICs) that represented varied approaches, including Australia, Canada, France, Italy, Scotland, Sweden, and the United States (US). Included data systems focused on preventive and early detection measures: HPV vaccination and cervical screening programs, as well as HPV-related disease outcomes. Differences were observed in approach to development of data systems, along with variation in geographical scope and methods of data collection. Expert opinion A challenge exists in how to best follow-up the ongoing global-scale elimination efforts in a comprehensive manner. These sources provide a wealth of information regarding the strengths and limitations of, and notable variation among, current data systems used in HICs. This review can inform improvements to existing prevention programs and the implementation of new programs in other countries, and thus support optimization of cervical cancer prevention policy.

Introduction Studies on quadrivalent measles, mumps, rubella, and varicella (MMRV) vaccines have indicated a twofold increased relative risk of febrile convulsion (FC) after the first dose compared to MMR and V administered at the same medical visit (MMR+V). Areas covered This narrative review contextualizes FC occurrence after the first MMRV vaccine dose from a clinical perspective and outlines approaches to attenuate FC occurrence post-vaccination. Expert opinion While the relative FC risk increases after the first dose of MMRV compared to MMR+V vaccine in measles-naïve infants, the attributable risk is low versus the overall FC risk in the pediatric population triggered by other causes, like natural exposure to pathogens or routine vaccination. No increased risk of FC has been reported after MMRV co-administration with other routine vaccines compared to MMRV alone. Based on our findings and considering the MMRV vaccination benefits (fewer injections, higher coverage, better vaccination compliance), the overall benefit-risk profile of MMRV vaccine is considered to remain positive. Potential occurrence of FC in predisposed children (e.g. with personal/family history of FC) may be attenuated if they receive MMR+V instead of MMRV as the first dose. It is also important to monitor vaccinees for fever during the first 2 weeks post-vaccination.

Background/Objectives. Many vaccines have been developed in recent decades, and many more will be available in the future. When new safe and effective vaccines are available, decision-makers must extensively assess them before including them in the national immunization plan and issuing recommendations. The Health Technology Assessment (HTA) could be an objective, transparent, and comprehensive approach to guiding the decision-making process for the use of vaccines. Objectives and Methods. The aim of this study was to review the indications for HTA use contained in Italian institutional documents on vaccination, namely the National Immunization Plans (NIPs) and available full Italian HTA reports on vaccines, assessing their availability at the time of national recommendations’ introductions. Results. HTA has been recognised as an eligible approach to deciding upon the introduction of vaccines through the NIPs of 2012–2014 and 2017–2019, and the last NIP, of 2023–2025, highlights the lack of funding dedicated to the production of independent HTA reports that can be used for issuing recommendations. In 2007–2023, twenty full HTA reports on vaccines were published in Italy: eight reports on influenza vaccines, five on Human Papilloma Virus (HPV), three each on meningococcal and pneumococcal vaccines, and one on rotavirus vaccine. HTA was applied with different purposes, namely the evaluation of new vaccines or their re-assessment, but it was not always timely with respect to both the marketing authorisation and the issuing of national recommendations for use. Conclusions. As HTA can be considered the best tool to disentangle the overall value of vaccines, it would be desirable for it to be used more and more to provide the evidence for efficient resource use. This calls for action to improve the transfer of HTA results to decision-makers, to try to fill the gap between research and decision and foster evidence-based recommendations.

Background: Varicella infections follow a benign course in around 90% of cases, with more severe forms occurring in adults. To identify potential pockets of susceptibility and to improve targeted immunization strategies, this study aims to critically assess immunological status by evaluating varicella seroprevalence among adults (18–99 years) in the province of Florence (Italy), nearly a decade after Tuscany introduced the vaccination program. Methods: A convenience sample of 430 subjects aged 18 to 94 years (mean age 51.8 ± 18.8 years), stratified by age and sex (53.7% of subjects were female; N = 231), was collected between 2018 and 2019. Sero-analytical analyses were conducted utilizing EUROIMMUN Anti-VZV ELISA (IgG) kits. Results: Most of them were of Italian nationality (87.4%; N = 376). Among the 430 tested samples, 385 (89.5%) were positive and 39 (9.1%) were negative. The remaining six sera (1.4%), confirmed as equivocal, were excluded from further analysis. No significant differences were found based on sex (p-value = 0.706) or nationality (p-value = 0.112). The application of trend tests (Mantel–Haenszel; Kendall Tau-b) showed a significant trend (p < 0.024 and p < 0.032, respectively), with an increasing probability of finding a positive anti-varicella serological status passing from a lower age group (84.2%) to a higher one (93.0%). By considering the female population aged 18–49 years, the seroprevalence of anti-varicella antibodies was found to be 88.4%, with a susceptibility of 11.6%, highlighting the risk of acquiring infection during pregnancy. Conclusions: The introduction of varicella vaccination has had a significant impact on public health in Tuscany and in Italy more generally. However, further efforts should be made to reduce the number of individuals still susceptible in adulthood, with particular attention given to women of childbearing age and the promotion of vaccination through mass and social media and institutional websites.

Abstract Background A comprehensive and agreed-upon definition of vaccine literacy (VL) could support the understanding of vaccination and help policy-makers and individuals make informed decisions about vaccines. Methods To shed some light on this debate and provide clarity, a scoping review was conducted to collect, summarize, and analyse available definitions of VL. Based on the findings of the scoping review, a new and comprehensive definition was proposed by a panel of experts. Results Fifty-three articles were included, and two of them appeared to be the milestones around which the other definitions were grouped. The new definition proposed by the panel of experts included not only the personal perspective, but also the community, population, and organizational perspectives. Moreover, due to the increasing complexity of the social context with respect to the ability to navigate, understand, and use information and services, the definition of organizational vaccine literacy and the attributes of a vaccine literate healthcare organization have been proposed. Conclusion The new definition can contribute to the overall paradigm of health literacy and its distinct component of vaccine literacy, possibly improving the implementation of public health strategies to allow vaccination to be understood as a social practice by the entire community. This study describes the conceptual foundations, the competencies, and the civic orientation to be considered when developing measurement tools devoted to assessing VL at the different levels and in different contexts.

Human Papilloma Virus (HPV) infection and HPV-related cancers can be prevented through vaccinations and mass cervical screening programmes. The Ministry of Health in Italy provides recommendations on primary and secondary prevention of HPV-related diseases, but the 19 Italian regions and 2 autonomous provinces have organisational and decision-making autonomy, with differences in the strategies for offering prevention. The aim of this study is to describe the HPV vaccination and cervical screening offered in all Italian regions. Regional official documents up until 31 December 2021 were first identified. Subsequently, primary and secondary prevention experts from each region were interviewed to validate the previously collected data. The National Immunisation Plan (NIP) 2017–2019 recommends HPV vaccination from the age of 11 for both sexes, with a coverage target of 95%. HPV vaccination is offered free of charge or co-payment. All regions have screening programmes for cervical cancer, using PAP or HPV-DNA tests every three to five years. All regions have an electronic registry for vaccination and screening status. All regions have developed awareness-raising campaigns. It is important to harmonise regional policies with the implementation of information systems integration. The collected data could enhance both regional and national public health initiatives, bolstering the resilience of vaccination programs.

The recent scientific literature abounds in proposals of seizure forecasting methods that exploit machine learning to automatically analyze electroencephalogram (EEG) signals. Deep learning algorithms seem to achieve a particularly remarkable performance, suggesting that the implementation of clinical devices for seizure prediction might be within reach. However, most of the research evaluated the robustness of automatic forecasting methods through randomized cross-validation techniques, while clinical applications require much more stringent validation based on patient-independent testing. In this study, we show that automatic seizure forecasting can be performed, to some extent, even on independent patients who have never been seen during the training phase, thanks to the implementation of a simple calibration pipeline that can fine-tune deep learning models, even on a single epileptic event recorded from a new patient. We evaluate our calibration procedure using two datasets containing EEG signals recorded from a large cohort of epileptic subjects, demonstrating that the forecast accuracy of deep learning methods can increase on average by more than 20%, and that performance improves systematically in all independent patients. We further show that our calibration procedure works best for deep learning models, but can also be successfully applied to machine learning algorithms based on engineered signal features. Although our method still requires at least one epileptic event per patient to calibrate the forecasting model, we conclude that focusing on realistic validation methods allows to more reliably compare different machine learning approaches for seizure prediction, enabling the implementation of robust and effective forecasting systems that can be used in daily healthcare practice.

Patients with cancer can be immunocompromised because of their disease and/or due to anticancer therapy. In this population, severe influenza virus infections are associated with an elevated risk of morbidity and mortality. Influenza vaccination is therefore highly recommended in cancer patients, including those receiving anticancer therapy. However, vaccination coverage remains far below the recommended target for vulnerable subjects. Six specialists in oncology, hematology, immunology, and public health/vaccinology convened with the objective of developing strategies, based on evidence and clinical experience, for improving influenza vaccination coverage in cancer patients. This viewpoint provides an overview of current influenza vaccination recommendations in cancer patients, discusses barriers to vaccination coverage, and presents strategies for overcoming said barriers. New immunization issues raised by the COVID-19 pandemic are also addressed. Future directions include improving public education on influenza vaccination, providing the media with accurate information, improving knowledge among healthcare professionals, improving access to vaccines for cancer patients, co-administration of the influenza and COVID-19 vaccines, increased collaboration between oncologists and other health professionals, increased accessibility of digital vaccination registries to specialists, shared information platforms, and promoting immunization campaigns by healthcare systems with the support of scientific societies.

Abstract Objective Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add‐on treatment. Methods We performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add‐on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency, and adverse events were recorded at 3, 6, and 12 months after PER introduction. Subanalyses by early or late use of PER and by concomitant ASM were also conducted. Results Five hundred and three patients were included (age 36.5 ± 19.9 years). Eighty‐one percent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the subanalyses, although patients who used PER as early add‐on, as compared with late add‐on, more often reached early seizure freedom at 3‐month follow‐up (66% vs 53%, P = .05). Treatment‐emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. Significance This study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real‐life conditions. We provide robust data about its effectiveness as only add‐on treatment even in patients with a long‐standing history of epilepsy and previously treated with many ASMs.

IntroductionDevelopment of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public–private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017–2018 to its final season in 2021–2022.MethodsIn 2021–2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis.ResultsIn 2021–2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%−93%) for any vaccine and 81% (22%−95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%−83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%−97%) for any vaccine in adults 18–64 years (TND hospital setting), and 38% (1%−62%) in children 6 months−6 years (population-based cohort, mixed setting).DiscussionOver five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.

IntroductionThe PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date.MethodsThis post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs.ResultsThe Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031).DiscussionThis study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.

Although relatively specific anatomo-electro-clinical features of temporal lobe epilepsy (TLE) with bilateral ictal involvement (bitemporal epilepsy—BTLE) have been described, differentiating between BTLE and unilateral TLE (UTLE) remains challenging. Surgery is often the treatment of choice for drug-resistant UTLE, whereas its use is more controversial in BTLE. It is currently unclear whether neuropsychological assessment can contribute to the differential diagnosis. We retrospectively reviewed the neuropsychological evaluation of 46 consecutive patients with refractory TLE. Eighteen patients were diagnosed with BTLE on the basis of ictal electro-clinical data, in particular a video EEG recording of at least one seizure simultaneously involving the two temporal lobes without the possibility of lateralizing its onset or at least two different seizures independently arising from the two temporal lobes. Twenty-eight patients were classified as UTLE. Presurgery evaluation data were used in this study. Compared with UTLE, BTLE was associated with a lower intelligence quotient (IQ) and more severe impairment in long-term memory, the latter remaining significant even after controlling for IQ. No significant differences were found between right and left UTLE. In conclusion, BTLE and UTLE are associated with relatively distinct neuropsychological profiles, further supporting their classification as different disorders within the TLE spectrum.

Background: Human respiratory syncytial virus (hRSV) is a key contributor to lower respiratory tract infections (LRTIs), affecting children aged 0–5 years and often leading to outpatient visits, emergency department utilization, and hospitalization. With the development of hRSV vaccines for mitigation, understanding the epidemiological impact of hRSV infections among 0–5-year-old pediatric outpatients in Italy is crucial. Methods: This systematic review conducted searches on PubMed, Embase, Scopus, and the International HTA Database, yielding 20,845 English and Italian records from January 2000 to July 2022. Results: Six eligible articles were identified following inclusion and exclusion criteria. These studies demonstrated hRSV-positivity proportions ranging from 18% to 41% in pediatric outpatients with respiratory infections. However, data comparability was hindered by diverse diagnostic approaches, data sources, sample populations, and study designs. Notably, hRSV-positivity showed temporal variability, rising from 23.8% (2001–2002) to 40.6% (2019–2020). This trend could stem from evolving epidemiological factors, heightened clinician awareness in hRSV diagnosis, or more sensitive molecular techniques. Conclusion: As the first review of its kind, this study underscores the need for more comprehensive data to inform effective preventive strategies against hRSV-related burdens in pediatric outpatients.

Abstract Background In the European Union it is mandatory to include paper package leaflets (PPL) with all medicines, including vaccines, to inform the recipient. However, it is difficult to meet the necessity for localized PPLs in each of the 24 official European languages. Replacing PPLs with electronic versions offers many advantages including redistribution across nations, reduced storage space, accessibility by the visually impaired, easily updated information or the addition of video content. We wanted to assess the attitudes of patients (vaccine recipients or their parents) to the potential of replacing PPL with electronic versions. Methods We surveyed vaccinees or their parents in four European countries—Belgium, Italy, Bulgaria and France—for their actual use of vaccine PPLs and their opinions about switching to an electronic package leaflet. Our survey was conducted online because of the COVID-19 pandemic and resulted in 2518 responses to a questionnaire targeted at three specific groups with particular information needs: parents of young children, pregnant women and the elderly (≥ 60 years). Results Our main findings are that currently vaccine PPLs are rarely used and frequently unavailable for the vaccinee. Across the four countries surveyed 55–82% of vaccinees would accept an electronic version, as did 64% when there was an option to request a printout of the leaflet. Conclusions We found that switching to electronic versions of vaccine PPLs is an acceptable alternative for the public, potentially increasing the quality and amount of information reaching vaccinees while eliminating some barriers to redistribution of vaccines between countries.

The ongoing COVID-19 pandemic highlights that complications and mortality associated with infectious diseases increase with age. Various vaccines are recommended for adults, but coverage rates remain suboptimal. Although co-administration would improve vaccine uptake and timely immunization, this is not routine practice in adults. We review key data on co-administration of vaccines in children and adults to reassure healthcare providers about its safety and advantages. In European countries and the United States, combined tetanus, diphtheria, and acellular pertussis boosters as well as meningococcal and human papillomavirus vaccines are recommended for healthy adolescents and adults of certain ages. Vaccination against influenza (annually), pneumococcal disease, and herpes zoster is recommended for older adults and specific risk groups. While co-administration is well established in children, it is less common in adults. Travelers can also receive multiple co-administered vaccines. Pediatric and travel vaccine co-administration has a well-established positive benefit-risk profile and is an efficient and cost-saving strategy to improve coverage. Healthcare providers could more often recommend and practice vaccine co-administration; this would not risk patient safety and health, would improve protection against vaccine-preventable diseases, and would help comply with national vaccination calendars. Recommending bodies may consider revising vaccination schedules to reduce the number of visits.

Rotavirus (RV) causes up to half of hospital and community acute gastroenteritis (AGE) cases in young children in Italy. Two RV vaccines, available since 2006, are human RV (HRV) and human bovine RV (HBRV). This report looks back at the implementation of RV vaccination with HRV in Italy, and at HRV current and future perspectives. Initial regional policies led to national implementation by 2018, after scientific societies’ disease awareness efforts. Following vaccination, RV hospitalizations declined significantly, and cost savings were observed. The two-dose HRV vaccine is easily administered during compulsory vaccine visits, helping increase coverage. Intussusception, a serious event in children

Abstract Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections in infants and the second most frequent cause of death during the first year of life. This highly contagious seasonal virus is responsible for approximately 3 million hospitalizations and 120,000 deaths annually among children under the age of 5 years. Bronchiolitis is the most common severe manifestation; however, RSV infections are associated with an increased long-term risk for recurring wheezing and the development of asthma. There is an unmet need for new agents and a universal strategy to prevent RSV infections starting at the time of birth. RSV is active between November and April in Italy, and prevention strategies must ensure that all neonates and infants under 1 year of age are protected during the endemic season, regardless of gestational age at birth and timing of birth relative to the epidemic season. Approaches under development include maternal vaccines to protect neonates during their first months, monoclonal antibodies to provide immediate protection lasting up to 5 months, and pediatric vaccines for longer-lasting protection. Meanwhile, improvements are needed in infection surveillance and reporting to improve case identification and better characterize seasonal trends in infections along the Italian peninsula. Rapid diagnostic tests and confirmatory laboratory testing should be used for the differential diagnosis of respiratory pathogens in children. Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations.

Abstract Background When use of a single antiseizure medication (ASM) fails to induce seizure remission, add-on therapy is justified. Perampanel (PER) is approved in Europe as adjunctive therapy for focal, focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures. Aim of the study was to establish whether PER is suitable for first add-on use. Methods A Delphi methodology was adopted to assess consensus on a list of 39 statements produced by an Expert Board of 5 epileptologists. Using an iterative process, statements were finalized by a Delphi Panel of 84 Italian pediatric and adult neurologists. Each statement was rated anonymously to determine level of agreement on a 9-point Likert scale. Consensus was established as agreement by at least 80% of the panelists. The relevance of each statement was also assessed on a 3-point scale. Results Consensus was achieved for 37 statements. Characteristics of PER considered to justify its use as first add-on include evidence of a positive impact on quality of life based on long term retention data, efficacy, tolerability, and ease of use; no worsening of cognitive functions and sleep quality; a low potential for drug interactions; a unique mechanism of action. Potential unfavorable factors are the need for a relatively slow dose titration; the potential occurrence of behavioral adverse effects; lack of information on safety when used in pregnancy; limited access to plasma PER levels. Conclusion Perampanel has many features which justify its use as a first add-on. Choice of an ASM as first add-on should be tailored to individual characteristics.

Vulvar and vaginal cancers are relatively rare cancers, but their incidence is increasing worldwide. Overall, 78% of vaginal cancers and 25% of vulvar cancers are associated with Human papillomavirus (HPV) infection. Immunization could be an option for the management of these cases. We researched and assessed the evidence on the efficacy of HPV vaccination administered to women previously treated with surgery, radiotherapy, or chemotherapy with respect to the recurrence of vulvovaginal disease. From 2006 to November 2022, only one study evaluated the efficacy of HPV vaccination with respect to preventing vulvovaginal recurrences in treated women and showed that a quadrivalent HPV vaccine administered after the surgical treatment of vulvar high-grade squamous intraepithelial lesion (HSIL) can reduce vulvar recurrence of the disease. Therefore, the efficacy of HPV vaccination with respect to vulvovaginal recurrence is still an unexplored field. Further studies are needed to produce stronger evidence in order to appropriately support interventions to protect women’s health.

There is an increasing interest in applying artificial intelligence techniques to forecast epileptic seizures. In particular, machine learning algorithms could extract nonlinear statistical regularities from electroencephalographic (EEG) time series that can anticipate abnormal brain activity. The recent literature reports promising results in seizure detection and prediction tasks using machine and deep learning methods. However, performance evaluation is often based on questionable randomized cross-validation schemes, which can introduce correlated signals (e.g., EEG data recorded from the same patient during nearby periods of the day) into the partitioning of training and test sets. The present study demonstrates that the use of more stringent evaluation strategies, such as those based on leave-one-patient-out partitioning, leads to a drop in accuracy from about 80% to 50% for a standard eXtreme Gradient Boosting (XGBoost) classifier on two different data sets. Our findings suggest that the definition of rigorous evaluation protocols is crucial to ensure the generalizability of predictive models before proceeding to clinical trials.

Simultaneous administration of different vaccines is a strategy to increase the possibility to receive vaccines at appropriate age, safely and effectively, reducing the number of sessions and allowing a more acceptable integration of new vaccines into National Immunization Programs (NIPs). Co-administration can be performed when there are specific indications in the Summary of Product Characteristics (SmPC) of the vaccines; but, in absence of these indications, the practice is possible if there are no specific contraindications nor scientific evidence to discourage simultaneous administration. The aim of this work is to review the safety and efficacy of co-administration of the tetravalent measles, mumps, rubella, and varicella (MMRV) and the meningococcal C (Men C) conjugate vaccines after 12 months of age. Several studies demonstrated that MMRV and Men C conjugate vaccines can be administered concomitantly without a negative impact on the safety and immunogenicity of either vaccines, inducing highly immunogenic responses.

Abstract The Human Papillomavirus (HPV) Prevention and Control Board is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV control programs. In response to drastic drop of vaccine coverage following the adverse event crisis in Carmen del Bolivar, Colombia, the HPV Prevention and Control Board in collaboration with the Colombian National Cancer Institute and Colombian League Against Cancer convened a meeting in Bogota, Columbia (November 2018). The goal of the meeting was to bring together national and international group of experts to report the disease burden, epidemiology and surveillance of HPV and HPV-related cancers, to discuss the successes and especially the challenges of HPV vaccination and screening in Colombia, as well as the lessons learnt from neighbouring countries. The meeting provided a platform to confer various stakeholder’s perspectives, including the role of the Colombian healthcare system and to catalyse various parts of the public health community in Colombia into effective action. The conclusion of the meeting included following suggestions to strengthen HPV prevention and control: 1) Re-introducing school-based vaccine programs, 2) Integrating primary and secondary prevention programs, 3) Developing an innovative crisis communication plan targeting healthcare workers, teachers and general population, 4) Building trust through efficient and timely communication, 5) Building strong relationship with media to ensure a stable vaccination campaign support, and 6) Promoting empathy among healthcare professionals towards patients to build trust and communicate effectively.

Healthcare workers (HCWs) are considered high-risk subjects for Hepatitis B Virus (HBV) infection due to occupational exposure to blood and body fluids. Vaccination represents the core strategy for HBV infection prevention. Following our previous publication on this topic, we aimed to assess the effectiveness of booster vaccine doses in eliciting the immunological response in seronegative (

Despite high rates of vaccination, pertussis resurgence has been reported worldwide in recent years, including in Italy, especially in older adults. Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with progressive inflammation of the respiratory tract. Regional population studies have shown the prevalence of COPD in Italy to be approximately 15% with an age-dependent increase in proportion of COPD cases. Emerging data shows that individuals with COPD are at high risk of contracting pertussis. Furthermore, those who develop pertussis could experience exacerbation of their pre-existent COPD and further susceptibility to other infections. Immunization programs in Italy currently recommend a decennial reduced-antigen-content diphtheria-tetanus-acellular pertussis booster vaccine dose for adults. Active measures to encourage booster vaccination, especially for high-risk adults such as those with COPD, could positively impact pertussis morbidity and the associated healthcare burden.

Both our research and that published by Sticchi et al. on immunological memory against hepatitis B virus (HBV) in health-care workers (HCWs) vaccinated as infants or adolescents confirm that in those testing negative after the primary course, one additional (fourth) booster dose is able to elicit an anti-HBs response in >85% subjects. The fifth and the sixth doses further contribute substantially to a high overall response rate. The rate of subjects showing an anamnestic response after the booster dose was almost six-fold higher in HCWs compared to chronic patients. Since universal vaccination in Italy resulted in a significant decrease in HBV infections, special attention and testing should be addressed to those affected by chronic diseases.

Routine childhood vaccinations are key for the protection of children from a variety of serious and potentially fatal diseases. Current pediatric vaccine schedules mainly cover active vaccines. Active vaccination in infants is a highly effective approach against several infectious diseases; however, thus far, for some important viral pathogens, including respiratory syncytial virus (RSV), vaccine development and license by healthcare authorities have not been accomplished. Nirsevimab is a human-derived, highly potent monoclonal antibody (mAb) with an extended half-life for RSV prophylaxis in all infants. In this manuscript, we consider the potential implications for the introduction of an anti-viral mAb, such as nirsevimab, into the routine pediatric vaccine schedule, as well as considerations for coadministration. Specifically, we present evidence on the general mechanism of action of anti-viral mAbs and experience with palivizumab, the only approved mAb for the prevention of RSV infection in preterm infants, infants with chronic lung disease of prematurity and certain infants with hemodynamically significant heart disease. Palivizumab has been used for over two decades in infants who also receive routine vaccinations without any alerts concerning the safety and efficacy of coadministration. Immunization guidelines (Advisory Committee on Immunization Practices, Joint Committee on Vaccination and Immunization, National Advisory Committee on Immunization, Centers for Disease Control and Prevention, American Academy of Pediatrics, The Association of the Scientific Medical Societies in Germany) support coadministration of palivizumab with routine pediatric vaccines, noting that immunobiologics, such as palivizumab, do not interfere with the immune response to licensed live or inactivated active vaccines. Based on the mechanism of action of the new generation of anti-viral mAbs, such as nirsevimab, which is highly specific targeting viral antigenic sites, it is unlikely that it could interfere with the immune response to other vaccines. Taken together, we anticipate that nirsevimab could be concomitantly administered to infants with routine pediatric vaccines during the same clinic visit.

COVID-19 represents a major public health issue in Italy; estimating the size of the outbreak could direct public health policies and inform us of the extent of the reorganization needed in the healthcare system, the efficacy of quarantine measures, and eventually on the achievement of herd immunity. To chart the real extent of COVID-19 infection in Italy official data need to be interpreted, considering various aspects such as the ''suspected-case'' definition that changed during recent months, the management of asymptomatic and untested symptomatic cases, the system for reporting deaths, and short-term fluctuations. All these aspects should be considered when reflecting on the meaning of the official COVID-19 figures in Italy. Regionalization of the healthcare system and fragmentation of data represent real challenges in the management of the COVID-19 outbreak in Italy. The authors’ opinion is that transparent and accurate reporting could guide policy-making and help reorganize health services.

Introduction: Influenza vaccination is recommended for caregivers of elderly people. In a study aimed at assessing the level of health literacy (HL) in a sample non-familial caregivers in the Florence Health District (Tuscany), data were collected regarding access and adherence to the flu vaccination campaigns. Methods: The sample consists of 47 non-familial paid caregivers. We collected information regarding socio-demographic characteristics, services provided and daily work time, whether or not influenza vaccination was administered for the 2016/2017 season and in the previous three years. The level of HL was assessed through the Newest Vital Sign. Results: 63.8% of non-familial caregivers have not joined the flu campaigns over the last four years, 14.9% have been vaccinated only sometimes (in some epidemic seasons), and 21.3% have received a flu shot in all the seasons investigated. Most of the non-familial caregivers who do not get vaccinated (27.7%) do not perceive that they are in direct contact with a person at-risk; those who get the vaccine regularly (12.8%) reported they want to protect the assisted person as motivation for vaccine uptake. Vaccination was not associated with HL. Conclusion: Adhesion to anti-flu vaccination campaigns for these homecare workers has been resulted rather poor. Coverage does not seem to be related with HL level. It seems appropriate to promote extensively flu vaccination among family carers by actively offering the vaccination in appropriate forms, places and times, to avoid serious consequences on elderly people with higher risk of comorbidity and frailty.

Introduction: Vaccination is a crucial tool for the primary prevention of infectious diseases. Thanks to widespread vaccination, in the last century smallpox has been eradicated, and the Americas and Europe have become polio-free. Areas covered: The aim of our study was to assess vaccination coverage in childhood up to booster preschool age in order to update the analysis on European trends of immunization coverage in the last nine years (2009–2017) and to assess the impact of different national policies on vaccine uptake. Expert opinion: Despite the good results, several EU countries are going through unprecedented outbreaks of vaccine-preventable diseases due to insufficient coverage. The increase of vaccine hesitancy has made it difficult to reach and maintain high rates of vaccination coverage. Enforcing mandatory vaccinations is one of the strategies adopted by some countries, like Italy and France, to increase coverage. However, each country should find the most suitable way to keep up with vaccination coverages according to own cultural and organizational background.

Abstract Background A controversy exists about the potential effect of childhood varicella vaccination on Herpes Zoster (HZ) incidence. Mathematical models projected temporary HZ incidence increase after vaccine introduction that was not confirmed by real-world evidence. These models assume that absence of contacts with infected children would prevent exogenous boosting of Varicella-Zoster-Virus (VZV) immunity and they do not include an endogenous VZV immunity-boosting mechanism following asymptomatic VZV reactivation. This study aims to explore the effect of various assumptions on exogenous and endogenous VZV immunity-boosting on HZ incidence in the general population after introduction of routine childhood varicella vaccination. Methods An age-structured dynamic transmission model was adapted and fitted to the seroprevalence of varicella in France in absence of vaccination using the empirical contact matrix. A two-dose childhood varicella vaccination schedule was introduced at 12 and 18 months. Vaccine efficacy was assumed at 65%/95% (dose 1/dose 2), and coverage at 90%/80% (dose 1/dose 2). Exogenous boosting intensity was based on assumptions regarding HZ-immunity duration, age-dependent boosting effect, and HZ reactivation rates fitted to observed HZ incidence. Endogenous boosting was the same as pre-vaccination exogenous boosting but constant over time, whilst exogenous boosting depended on the force of infection. Five scenarios were tested with different weightings of exogenous (Exo) - endogenous (Endo) boosting: 100%Exo–0%Endo, 75%Exo–25%Endo, 50%Exo–50%Endo, 25%Exo–75%Endo, 0%Exo–100%Endo. Results HZ incidence before varicella vaccination, all ages combined, was estimated at 3.96 per 1000 person-years; it decreased by 64% by year 80 post vaccine introduction, for all boosting assumptions. The 100%Exo-0%Endo boosting scenario, predicted an increase in HZ incidence for the first 21 years post vaccine introduction with a maximum increase of 3.7% (4.1/1000) at year 9. However, with 0%Exo-100%Endo boosting scenario an immediate HZ decline was projected. The maximum HZ incidence increases at 10, 3, and 2 years post vaccination were 1.8% (75%Exo-25%Endo), 0.8% (50%Exo-50%Endo) and 0.2% (25%Exo-75%Endo), respectively. Conclusions Assuming modest levels of endogenous boosting, the increase in HZ incidence following childhood varicella vaccination was smaller and lasted for a shorter period compared with 100%Exo-0%Endo boosting assumption. Endogenous boosting mechanism could partly explain the divergence between previous HZ-incidence projections and real-world evidence.

Background: Healthcare students that refuse to get vaccinated may expose themselves and their patients to several vaccine-preventable diseases, especially during outbreaks or at peak epidemic activity, becoming a threat to themselves and their patients. This study aimed to assess their attitudes towards and perception of vaccines and vaccination. Methods: An anonymous questionnaire was shared with medical students, pharmacy students and medical residents in Hygiene and Preventive Medicine at the University of Florence (Italy), in February 2021. The questionnaire contained 39 questions with open, multi-choice, yes–no, Likert scale answers. A Vaccine Hesitancy Index (VHI) was then calculated. A descriptive statistical analysis was performed. Results: A total of 473 students participated in this study. All students were in favour of vaccination (99.2%) but a relatively low number of participants judged their level of knowledge about vaccinations as “good” (21.8%) or “excellent” (0.6%). About half of students declared that they are not adequately trained during their academic courses. The VHI showed low levels of vaccine hesitancy (mean ± SD 0.38 ± 0.16); moreover, the students were willing to get vaccinated against SARS-CoV-2 when recommended (88.2%) and thought that these vaccines are generally safe. Few students considered the development of SARS-CoV-2 vaccines (13.1%) and the procedures for evaluating clinical trials for marketing authorisation of these vaccines (12.9%) too fast to guarantee their efficacy and safety. Conclusions: Since vaccination and vaccine hesitancy and acceptance topics are being paid increasing attention by the population, new strategies to increase future healthcare professionals’ willingness to promote vaccination and get vaccinated, as well as knowledge on vaccines and vaccination, will be of the utmost importance to fight vaccine preventable diseases.

In Italy, the paper package leaflet (PPL) is the official document that is approved by the Italian Medicines Agency (AIFA) for each medicine. PPLs of all medicines, including vaccines, are freely available online by accessing the AIFA website. To investigate people’s attitudes toward possible access to the PPLs of vaccines and the acceptability of switching to an electronic package leaflet (e-leaflet) in the future, we surveyed three target groups (pregnant women, young parents, and older people) in Italy, via an online survey. We collected 321 questionnaires from the cohorts, which comprised 104 pregnant women, 105 young parents, and 112 older people. The results indicate in all target groups that health care professionals (HCPs) do not usually offer the vaccine PPL during the vaccination session: only about 10.7% of respondents receive the PPL without asking for it, with pregnant women receiving it the most frequently. The acceptance rate for switching from a PPL to an e-leaflet is fairly high in all target groups (76.9% in pregnant women, 81.9% in young parents, and 66.1% in the elderly), especially if the option exists to request a paper print, to make sure that people with a low level of digital skills can access the PPL information as well. HCPs have an important role in ensuring access to the PPLs of vaccines. HCPs should be trained to inform their patients about the different options for accessing the PPLs (as well as online access) to increase their patients’ knowledge and satisfaction.

Background: Training future healthcare professionals on vaccination through specific courses is important to properly promote active immunization among the general population and to fight fake news and false beliefs on vaccinations. The aim of the study was to assess the impact of an elective course about vaccinations on the knowledge of medical students, pharmacy students, and medical resident in Hygiene and Preventive Medicine in Italy. Methods: The participants were asked to complete an anonymous questionnaire before and after an elective teaching activity (ETA) on vaccination. The two questionnaires contained the same 30 questions and focused on different aspects of vaccines and vaccination. The students who had attended the seminar were allowed to fulfil the post-lecture questionnaire. Both descriptive and inferential analysis were performed on the results; in particular, Student’s t-test for independent samples was used to compare the total score obtained before and after attending the ETA. Results: A total of 449 students participated in the ETA. Overall, the participation in the ETA allowed them to significantly improve their final score (+27.28%, p < 0.001). Good results were obtained even when comparing the three groups (medical students, pharmacy students and medical residents) separately. Females improved more than males, especially among pharmacy students. Discussion: The present study highlights the importance and the impact that extracurricular activities can have in improving knowledge about vaccinations. With vaccination and vaccine hesitancy and acceptance topics with increasing attention paid by the population, especially after the COVID-19 pandemic, it is fundamental to develop new strategies to increase future healthcare professionals’ knowledge about vaccinations.