The district operation centres in one of the largest local health authorities in Italy to manage COVID-19 surveillance and homecare: first implementation and results of a survey addressed to general practitioners.

BACKGROUND: COVID-19 pandemic represented a shock for healthcare systems. Italy was one of the first country to deal with a huge number of patients to be diagnosed, isolated, and treated with scarce evidence-based guidelines and resources. Several organizational and structural changes were needed to face the pandemic at local level. The article aims at studying the perceived impact of the newly implemented District Operation Centres (DOCs) of Local Health Authority (LHA) Roma 1 in managing active surveillance and home care of COVID-19 patients and their close contacts in cooperation with general practitioners (GPs). METHODS: A questionnaire, developed according to Delphi methodology, was validated by 7 experts and administered to a randomized sample of GPs and family paediatricians (FPs). All medical doctors selected received a phone interview between December 2020 and January 2021. The questionnaire investigated general characteristics of the sample, relations with DOC and its usefulness, and potential developments. A descriptive analysis was performed and inferential statistical tests were used to assess differences. RESULTS: In April 2020 the LHA Roma 1 implemented one DOCs in each local health district. 215 medical doctors were interviewed, reaching the sample target for health districts (80% CL and 10% MOE) and the whole LHA (90% CL and 5% MOE). Several aspects in the management of COVID-19 cases and close contacts of COVID-19 cases, and of the support of DOCs to GPs/FPs were investigated. More than 55% of the GPs and FPs interviewed found the DOCs useful and more than 78% would recommend a service DOC-like to other LHAs. The medical professionals interviewed would use DOCs in the future as support in treating vulnerable patients, utilizing digital health tools, enlisting specialist doctors, establishing networks, and facilitating professional counselling by nurses. CONCLUSIONS: This study is an attempt to evaluate an organizational change happened during COVID-19 pandemic. DOCs were created to support GPs and FPs as a link between primary healthcare and public health. Although several difficulties were disclosed, DOCs' experience can help to overcome the fragmentation of the systems and the duality between primary care and public health and make the system more resilient.

Evaluation of Immune Infiltrates in Ovarian Endometriosis and Endometriosis-Associated Ovarian Cancer: Relationship with Histological and Clinical Features.

BACKGROUND: the association between ovarian endometriosis (OE) and endometriosis-associated ovarian cancer (EAOC) is extensively documented, and misfunction of the immune system might be involved. The primary objective of this study was to identify and compare the spatial distribution of tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) in OE and EAOC. Secondary objectives included the analysis of the relationship between immunosuppressive populations and T-cell exhaustion markers in both groups. METHODS: TILs (CD3, CD4, and CD8) and macrophages (CD163) were assessed by immunochemistry. Exhaustion markers (PD-1, TIM3, CD39, and FOXP3) and their relationship with tumour-associated macrophages (CD163) were assessed by immunofluorescence on paraffin-embedded samples from n = 43 OE and n = 54 EAOC patients. RESULTS: we observed a predominantly intraepithelial CD3+ distribution in OE but both an intraepithelial and stromal pattern in EAOC (p < 0.001). TILs were more abundant in OE (p < 0.001), but higher TILs significantly correlated with a longer overall survival and disease-free survival in EAOC (p < 0.05). CD39 and FOXP3 significantly correlated with each other and CD163 (p < 0.05) at the epithelial level in moderate/intense CD4 EAOC, whereas in moderate/intense CD8+, PD-1+ and TIM3+ significantly correlated (p = 0.009). Finally, T-cell exhaustion markers FOXP3-CD39 were decreased and PD-1-TIM3 were significantly increased in EAOC (p < 0.05). CONCLUSIONS: the dysregulation of TILs, TAMs, and T-cell exhaustion might play a role in the malignization of OE to EAOC.

Demographic and epidemiological characteristics of Ukrainian refugees in an Italian Local Health Authority.

BACKGROUND: The Russian invasion of Ukraine caused millions of Ukrainian refugees to flee to other nations. To provide the most appropriate assistance, host nations necessitate up-to-date information regarding Ukrainian refugee's demographic and epidemiological conditions. We aim to investigate the demographic composition, the COVID-19 vaccinations performed, specialist care provided and the prevalence of non-communicable diseases (NCDs) in refugees assisted by an Italian Local Health Authority (LHA). METHODS: We conducted a retrospective cross-sectional analysis from March to June 2022, analyzing the demographic and epidemiological status of Ukrainians. Statistical analyses were carried out to assess possible associations between NCDs distribution, age and gender. RESULTS: LHA Roma 1 assisted 9349 Ukrainian refugees. Of these, 2784 (29.8%) were males and 6565 (70.2%) were females, with a median age of 25 years. Two thousand four hundred and eighty-five Ukrainian refugees were vaccinated against COVID-19. Among them, 401 (16.1%) had at least one NCD. The most frequent groups of diseases were related to the circulatory system (50.6%), the endocrine system (24.9%), and mental and behavioral disorders (6.5%). CONCLUSION: Refugees need healthcare services targeted mainly towards minors and females. It is essential to analyze and monitor the demographic and epidemiological conditions to provide evidence about patient management and the best care integrated into the health service of host countries.

Ukrainian refugee crisis management in the Local Health Authority Roma 1: the challenges of implementing public health policies and lessons learned.

BACKGROUND: The conflict between Russia and Ukraine has strained the health systems of countries that welcome war refugees on all levels, from national to local. Despite the Public Health guidelines regarding assistance being published on the topic, the scientific literature currently lacks evidence on the experience of applying theory in practice. This study aims to describe evidence-based practices that were implemented and to provide a detailed description of emerging problems and solutions pertaining Ukrainian refugee assistance in the context of one of the biggest Local Health Authorities in Italy (LHA Roma 1). METHODS: LHA Roma 1 developed a strategic plan based on local expertise, national and international guidelines to ensure infectious disease prevention and control, as well as continuity of care for non-communicable diseases and mental health. RESULTS: The insertion of Ukrainian refugees in the National Health System through an identification code assignment and other services such as COVID-19 swab and vaccination were provided either in one of the three major assistance hubs or in local district level ambulatories spread throughout the LHA. Many challenges were faced during the implementation phase of the outlined practice guidelines, which required sensible and timely solutions. These challenges include the necessity of rapid resource provision, overcoming linguistic and cultural barriers, guaranteeing a standard of care across multiple sites and coordination of interventions. Public Private Partnerships, the creation of a centralized multicultural and multidisciplinary team and the mutually beneficial collaboration with the local Ukrainian community were essential to guarantee the success of all operations. CONCLUSIONS: The experience of LHA Roma 1 helps shed light on the importance of leadership in emergency settings and how a dynamic relationship between policy and practice would allow each intervention to be modulated according to the local environment, to better realize the potential of local realities to provide appropriate health interventions to all those in need.

The "Lazio ADVICE" telemedicine platform: First results of general practitioners' usage, facilitators and barriers in the Local Health Authority Roma 1.

Background: Telemedical approaches represent a valuable tool for the management of coronavirus disease 2019 patients, allowing daily clinical assessment, monitoring of vital parameters, remote visits, and prescription of treatment or hospitalization in case of clinical worsening. This cross-sectional study aims to evaluate the use, barriers and facilitators of the "Lazio ADVICE" telemedical platform, a regional system for remote assistance for coronavirus disease 2019 patients at home, according to General Practitioners and Family Pediatricians of the Local Health Authority Roma 1, during the coronavirus disease 2019 pandemic. Methods: An interview-based survey was performed between December 2020 and January 2021. The survey investigated the demographic information of General Practitioner and Family Pediatricians, the knowledge of the platform, frequency of utilization, usefulness, strengths and weaknesses, and hypothesis of future implementation proposed. Results: We interviewed 214 physicians and 89 (41.6%) were classified as users and 125 (58.4%) as non-users. Older age and working in District 1, 14 and 15 (vs. District 13) significantly reduced the probability of using the platform physician. Among the 89 users, 19 (21.3%) used the platform every day or even several times a day, 40 (44.9%) several times a week but less than one access per day, 30 (33.7%) used the platform several times a month up to one entry per week. Most of them (92.3%) consider the platform useful. Barriers were poor integration with software and work routine (76.4%), and usability issues (53.9%). Among the 125 non-users, 14 (11.2%) didn't know the existence of the platform, 60 (48.0%) never tried it and 51 (40.8%) tried to use it. Reported reasons for the interruption of use were not very user-friendly (45.1%), perceived useless (37.3%), non-optimal functioning (23.5%), and lack of time (19.6%). Conclusion: The pandemic accelerated the implementation of telemedicine services around Lazio Region, starting a positive and continuous exchange of experiences, activities and best practices among physicians.

New Roles for Old Friends: Involvement of the Innate Immune System in Tumor Progression.

The association between the immune system and tumor progression has attracted much interest in the research community in recent years [...].

Neutrophil Extracellular Traps and Cancer: Trapping Our Attention with Their Involvement in Ovarian Cancer.

Neutrophils, the most abundant circulating leukocytes, play a well-known role in defense against pathogens through phagocytosis and degranulation. However, a new mechanism involving the release of neutrophil extracellular traps (NETs) composed of DNA, histones, calprotectin, myeloperoxidase, and elastase, among others, has been described. The so-called NETosis process can occur through three different mechanisms: suicidal, vital, and mitochondrial NETosis. Apart from their role in immune defense, neutrophils and NETs have been involved in physiopathological conditions, highlighting immunothrombosis and cancer. Notably, neutrophils can either promote or inhibit tumor growth in the tumor microenvironment depending on cytokine signaling and epigenetic modifications. Several neutrophils' pro-tumor strategies involving NETs have been documented, including pre-metastatic niche formation, increased survival, inhibition of the immune response, and resistance to oncologic therapies. In this review, we focus on ovarian cancer (OC), which remains the second most incidental but the most lethal gynecologic malignancy, partly due to the presence of metastasis, often omental, at diagnosis and the resistance to treatment. We deepen the state-of-the-art on the participation of NETs in OC metastasis establishment and progression and their involvement in resistance to chemo-, immuno-, and radiotherapies. Finally, we review the current literature on NETs in OC as diagnostic and/or prognostic markers, and their contribution to disease progression at early and advanced stages. The panoramic view provided in this article might pave the way for enhanced diagnostic and therapeutic strategies to improve the prognosis of cancer patients and, specifically, OC patients.

Special Issue "miRNAs in the Era of Personalized Medicine: From Biomarkers to Therapeutics 2.0".

Personalized medicine has become a new paradigm in the management of a variety of diseases [...].

Do Degree Programs Affect Health Profession Students' Attitudes and Opinions Toward Vaccinations? An Italian Multicenter Study.

Background: Healthcare workers' attitudes toward vaccination have been widely described in the literature, but a restricted amount of studies assessed healthcare students' knowledge, attitudes, and opinions on this issue. This study aimed to estimate the influence of a degree course on knowledge and immunization behavior among healthcare students and to compare medical students with students from other health profession degree programs to identify possible differences. Methods: A multicenter, cross-sectional study was performed in 2018 in 14 Italian Universities (3,131 students were interviewed). A validated questionnaire was used to assess knowledge, attitudes, and opinions toward vaccinations, with a specific focus on influenza vaccine and attitudes toward mandatory vaccination policies. Statistical software STATA® 14 was used. Results: Significant differences were recorded between medical students and other healthcare students. The intention to get vaccinated against influenza during the next season and having been vaccinated in the previous season was higher in the medical group (p < 0.001). In the group of students of other health professions, we registered a lower probability of identifying themselves as a high-risk group for contracting infectious diseases as a consequence of their profession and health status (aOR 0.49; CI95%: 0.40-0.60) and an increased likelihood of defining their level of knowledge on vaccine-preventable diseases and related vaccinations as "insufficient/sufficient/fair" (aOR 1.31; CI95%: 1.11-1.56). Conclusions: Results show several differences between medical students and students of other health professions when it comes to vaccination knowledge, attitudes, and perceptions, as well as a general low tendency to be vaccinated against influenza.

EVI1 Promotes the Proliferation and Invasive Properties of Human Head and Neck Squamous Cell Carcinoma Cells.

Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor prognosis. So far, the EGFR inhibitor cetuximab is the only approved targeted therapy. A deeper understanding of the molecular and genetic basis of HNSCC is needed to identify additional targets for rationally designed, personalized therapeutics. The transcription factor EVI1, the major product of the MECOM locus, is an oncoprotein with roles in both hematological and solid tumors. In HNSCC, high EVI1 expression was associated with an increased propensity to form lymph node metastases, but its effects in this tumor entity have not yet been determined experimentally. We therefore overexpressed or knocked down EVI1 in several HNSCC cell lines and determined the impact of these manipulations on parameters relevant to tumor growth and invasiveness, and on gene expression patterns. Our results revealed that EVI1 promoted the proliferation and migration of HNSCC cells. Furthermore, it augmented tumor spheroid formation and the ability of tumor spheroids to displace an endothelial cell layer. Finally, EVI1 altered the expression of numerous genes in HNSCC cells, which were enriched for Gene Ontology terms related to its cellular functions. In summary, EVI1 represents a novel oncogene in HNSCC that contributes to cellular proliferation and invasiveness.

Organisational Model and Coverage of At-Home COVID-19 Vaccination in an Italian Urban Context.

The COVID-19 pandemic called for a reorganisation of the methods for providing health services. The aim of this paper is to describe the organisational model implemented by one of Rome's Local Health Units (LHU), ASL Roma 1, for the "at-home COVID-19 vaccination campaign" dedicated to a target population and to outline data related to vaccination coverage stratified by health districts. A cross-sectional study was designed to describe the strategies implemented by LHU to deliver at-home vaccination programmes. People eligible for the at-home vaccination programme included patients living in the area of the LHU, being assisted by the district home care centre or not transportable or individuals with social situations that make traveling difficult. Priority for vaccination was given to (I) age > 80 years, (II) ventilated patients with no age limit, (III) very seriously disabled people with no age limit. Patients' data were acquired from regional and LHU databases. From 5 February until the 16 May, 6127 people got at least one dose of Pfizer-Biontech Comirnaty® vaccine, while 5278 (86.14%) completed the necessary two doses. The highest number of vaccines was administered during the first week of April, reaching 1296 doses overall. The number of vaccines administered were similar across the districts. The average number of people vaccinated at home was 6 per 1000 inhabitants in the LHU. This model proved to be extremely complex but effective, reaching satisfying results in terms of vaccination coverage.

Effect of urolithins A and B on ectopic endometrial growth in a murine model of endometriosis.

Endometriosis is an often painful disease in reproductive-aged women, in which endometrial-like tissue grows outside the uterine cavity. Since the limited current therapeutic alternatives fail in alleviating the symptoms and based on our previous research in in vitro models using the same compounds as the ones used in the present study, we aimed to evaluate the effects of urolithins A (UA) and B (UB) on the growth and survival of endometriotic-like lesions in a murine model of endometriosis. Female BALB/C mice were surgically induced with endometriosis and treated with 2.5 mg kg-1 day-1 intraperitoneal UA or UB. The mice were monitored daily and weighed and the estrous stage was determined. After 28 days of treatment, lesions were counted, measured, excised, and fixed. Both urolithins proved not to affect the estrous cycle or body weight of the mice. UA completely prevented endometriotic-like lesions, while UB diminished the implant volume (p < 0.05). Treatment also reduced epithelial and stromal cell proliferation within the implants (p < 0.001 and p < 0.01, respectively) and apoptosis was enhanced (p < 0.05 and p < 0.01, respectively). These results are promising and reveal that urolithins A and B, separately, have a beneficial effect on the overall endometriotic growth without affecting the body weight or estrous cycle.

The Impact of Digital Patient Portals on Health Outcomes, System Efficiency, and Patient Attitudes: Updated Systematic Literature Review.

BACKGROUND: Patient portals are becoming increasingly popular worldwide even though their impact on individual health and health system efficiency is still unclear. OBJECTIVE: The aim of this systematic review was to summarize evidence on the impact of patient portals on health outcomes and health care efficiency, and to examine user characteristics, attitudes, and satisfaction. METHODS: We searched the PubMed and Web of Science databases for articles published from January 1, 2013, to October 31, 2019. Eligible studies were primary studies reporting on the impact of patient portal adoption in relation to health outcomes, health care efficiency, and patient attitudes and satisfaction. We excluded studies where portals were not accessible for patients and pilot studies, with the exception of articles evaluating patient attitudes. RESULTS: Overall, 3456 records were screened, and 47 articles were included. Among them, 11 studies addressed health outcomes reporting positive results, such as better monitoring of health status, improved patient-doctor interaction, and improved quality of care. Fifteen studies evaluated the impact of digital patient portals on the utilization of health services with mixed results. Patient characteristics were described in 32 studies, and it was reported that the utilization rate usually increases with age and female gender. Finally, 30 studies described attitudes and defined the main barriers (concerns about privacy and data security, and lack of time) and facilitators (access to clinical data and laboratory results) to the use of a portal. CONCLUSIONS: Evidence regarding health outcomes is generally favorable, and patient portals have the potential to enhance the doctor-patient relationship, improve health status awareness, and increase adherence to therapy. It is still unclear whether the use of patient portals improves health service utilization and efficiency.

Tibial brown tumor as a presentation of primary hyperparathyroidism / [Tumor pardo tibial como forma de presentación de un hiperparatiroidismo primario]

Cystic fibrous osteitis is a complication of a very evolved hyperparathyroidism. Because the determination of calcium, parathyroid hormone and vitamin D have become routine studies, this bone complication is uncommon in western countries. However, it should be considered in the differential diagnosis of hypercalcemia and lytic bone lesions. The treatment is to suppress the excess parathyroid hormone by parathyroidectomy and osteosynthesis in pathological fracture. We present the case of a female patient with primary hyperparathyroidism and a brown tumor in the right tibia.

La osteítis fibrosa quística es la complicación de un hiperparatiroidismo muy evolucionado. Debido a que la determinación del calcio, hormona paratiroides y vitamina D han pasado a ser estudios rutinarios, esta complicación ósea es infrecuente en los países occidentales. Sin embargo, debe ser considerada en el diagnóstico diferencial de hipercalcemia y lesiones óseas líticas. El tratamiento de esta entidad va dirigido a suprimir el exceso de hormona paratiroides mediante la paratiroidectomia y osteosíntesis en los casos de fracturas patológicas. Se presenta el caso de una paciente con hiperparatiroidismo primario y un tumor pardo en la tibia derecha.

Increasing HPV Vaccination Uptake among Adolescents: A Systematic Review.

Human Papillomavirus (HPV) vaccination is a well-known fundamental strategy in the prevention of cervical cancer, as it is always caused by HPV infection. In fact, primary prevention of the infection corresponds to primary prevention of HPV-related cancers and other diseases. Since an effective prevention at the population level is the final goal, it is mandatory for healthcare systems to achieve a high HPV vaccination coverage among the adolescents to reduce the circulation of the virus and the burden of HPV-related diseases. This research identified, through a systematic literature review, 38 papers on strategies adopted to increase HPV vaccination coverage among adolescents. The evaluated strategies targeted adolescents/parents and/or healthcare providers and could be grouped in three main types: (1) reminder-based, (2) education, information, and communication activities, and (3) multicomponent strategies. Several types of strategy, such as those relied only on reminders and integrating different interventions, showed a positive impact on vaccination coverage. Nonetheless, the heterogeneity of the interventions suggests the importance to adapt such strategies to the specific national/local contexts to maximize vaccination coverage.

The impact of tumor board on cancer care: evidence from an umbrella review.

BACKGROUND: Tumor Boards (TBs) are Multidisciplinary Team (MDT) meetings in which different specialists work together closely sharing clinical decisions in cancer care. The composition is variable, depending on the type of tumor discussed. As an organizational tool, MDTs are thought to optimize patient outcomes and to improve care performance. The aim of the study was to perform an umbrella review summarizing the available evidence on the impact of TBs on healthcare outcomes and processes. METHODS: Pubmed and Web of Science databases were investigated along with a search through citations. The only study design included was systematic review. Only reviews published after 1997 concerning TBs and performed in hospital settings were considered. Two researchers synthetized the studies and assessed their quality through the AMSTAR2 tool. RESULTS: Five systematic reviews published between 2008 and 2017 were retrieved. One review was focused on gastrointestinal cancers and included 16 studies; another one was centered on lung cancer and included 16 studies; the remaining three studies considered a wide range of tumors and included 27, 37 and 51 studies each. The main characteristics about format and members and the definition of TBs were collected. The decisions taken during TBs led to changes in diagnosis (probability to receive a more accurate assessment and staging), treatment (usually more appropriate) and survival (not unanimous improvement shown). Other outcomes less highlighted were quality of life, satisfaction and waiting times. CONCLUSIONS: The study showed that the multidisciplinary approach is the best way to deliver the complex care needed by cancer patients; however, it is a challenge that requires organizational and cultural changes and must be led by competent health managers who can improve teamwork within their organizations. Further studies are needed to reinforce existing literature concerning health outcomes. Evidence on the impact of TBs on clinical practices is still lacking for many aspects of cancer care. Further studies should aim to evaluate the impact on survival rates, quality of life and patient satisfaction. Regular studies should be carried out and new process indicators should be defined to assess the impact and the performance of TBs more consistently.

Strategies to Increase Flu Vaccination Coverage among Healthcare Workers: A 4 Years Study in a Large Italian Teaching Hospital.

Flu vaccination is recommended among healthcare workers (HCWs). The low vaccination coverage registered in our hospital among HCWs called for new engaging approaches to improve flu vaccination coverage. The aim of this study was to evaluate the efficacy of different strategies implemented during the last four years (2015-2019). A quasi-experimental study was conducted, involving almost 4000 HCWs each year. Starting from the 2015-2016 campaign, new evidence-based strategies were progressively implemented. At the end of each campaign, an evaluation of the vaccination coverage rate reached was performed. Moreover, during the last three campaigns, differences in coverage among job category, wards involved or not in on-site vaccination (OSV) intervention, age classes and gender were analyzed. An increasing flu vaccination coverage rate was registered, from 6% in 2015-2016 to almost 22% at the end of 2018-2019. The overall number of vaccinated HCWs increased, especially at younger ages. OSV strategy always leads to better results, and physicians always show a higher vaccination coverage than nurses and other HCWs. The implemented strategies were effective in achieving higher flu vaccination coverage among HCWs in our hospital and therefore can be considered valuable examples of good prevention practices in hospital settings.

Seasonal influenza vaccination among health-care workers: the impact of different tailored programs in four University hospitals in Rome.

Seasonal influenza vaccination (SIV) of health-care workers (HCWs) is recommended in most countries to protect them and their patients from infection. Although SIV can reduce the risk of influenza complications among vulnerable patients, vaccination uptake is generally unsatisfactory. The present study aimed to assess the impact of different programs in promoting SIV uptake among HCWs during the season 2017/2018 in four teaching hospitals in Rome. A multicentric cross-sectional study was carried out, in order to describe the four different campaigns and to assess their impact by identifying and developing a set of indicators that provide information about the vaccination services, the percentage of invited HCWs, the vaccinators' workforce and the vaccination coverage rates.The hospitals organized different strategies: Hospital 1, 3 and 4 organized educational courses for HCWs and actively invited every single HCW through e-mail. All the hospitals organized a dedicated unit for influenza vaccination, and Hospital 1 added on-site vaccination sessions that required a large number of staff. Hospital 1 and hospital 4 registered a comparable vaccination coverage rate, 12.97% and 12.76%, respectively, while it was 6.88% in Hospital 2 and 4.23% in Hospital 3. Our indicators demonstrated to be effective and useful for analyzing the different SIV campaigns. The results suggest that the best practice to promote SIV among HCWs should include multiple approaches. Among those, an easy access to the vaccination site seems to play a key role in determining a higher vaccination coverage.

Cost-consequence analysis of influenza vaccination among the staff of a large teaching hospital in Rome, Italy: A pilot study.

Flu vaccination, as well as being effective to prevent seasonal influenza, decreases staff illness and absenteeism and reduces costs resulting from loss of productivity. Despite the effectiveness of flu vaccination, the seasonal coverage among healthcare workers is usually low. The aim of this retrospective observational study was to analyze the vaccination coverage rate among all employees (healthcare workers and administrative staff) of a large teaching hospital in Rome during the 2017-2018 influenza season, to perform a cost-consequence analysis of influenza vaccination (by evaluating the absenteeism due to illness in the epidemic period), and to assess the impact of vaccination in terms of both costs and sick days. The flu vaccination coverage rate was 9.8% among 4631 healthcare workers and 852 administrative employees. The human capital approach estimated a loss of productivity equal to 297.06 € for each vaccinated worker and 517.22 € for each unvaccinated worker (cost-outcome ratio: 120.07 €/sick day). Applying the friction cost method, a loss of productivity equal to 237.65 € for each vaccinated worker and 413.78 € for each unvaccinated worker (cost-outcome ratio: 104.19 €/sick day) was found. These results confirm the benefits of the flu vaccination for the society and the company. This allowed the management to grant one hour of permission to the flu-vaccinated workers in the following annual vaccination campaign (2018-2019).