Pro-active monitoring and social interventions at community level mitigate the impact of coronavirus (COVID-19) epidemic on older adults' mortality in Italy: A retrospective cohort analysis.

BACKGROUND: The COVID-19 epidemic in Italy has severely affected people aged more than 80, especially socially isolated. Aim of this paper is to assess whether a social and health program reduced mortality associated to the epidemic. METHODS: An observational retrospective cohort analysis of deaths recorded among >80 years in three Italian cities has been carried out to compare death rate of the general population and "Long Live the Elderly!" (LLE) program. Parametric and non-parametric tests have been performed to assess differences of means between the two populations. A multivariable analysis to assess the impact of covariates on weekly mortality has been carried out by setting up a linear mixed model. RESULTS: The total number of services delivered to the LLE population (including phone calls and home visits) was 34,528, 1 every 20 day per person on average, one every 15 days during March and April. From January to April 2019, the same population received one service every 41 days on average, without differences between January-February and March-April. The January-April 2020 cumulative crude death rate was 34.8‰ (9,718 deaths out of 279,249 individuals; CI95%: 34.1-35.5) and 28.9‰ (166 deaths out of 5,727 individuals; CI95%:24.7-33.7) for the general population and the LLE sample respectively. The general population weekly death rate increased after the 11th calendar week that was not the case among the LLE program participants (p<0.001). The Standardized Mortality Ratio was 0.83; (CI95%: 0.71-0.97). Mortality adjusted for age, gender, COVID-19 weekly incidence and prevalence of people living in nursing homes was lower in the LLE program than in the general population (p<0.001). CONCLUSIONS: LLE program is likely to limit mortality associated with COVID-19. Further studies are needed to establish whether it is due to the impact of social care that allows a better clients' adherence to the recommendations of physical distancing or to an improved surveillance of older adults that prevents negative outcomes associated with COVID-19.

Impact of COVID-19 on older adults and role of long-term care facilities during early stages of epidemic in Italy.

Older adults are the main victims of the novel COVID-19 coronavirus outbreak and elderly in Long Term Care Facilities (LTCFs) are severely hit in terms of mortality. This paper presents a quantitative study of the impact of COVID-19 outbreak in Italy during first stages of the epidemic, focusing on the effects on mortality increase among older adults over 80 and its correlation with LTCFs. The study of growth patterns shows a power-law scaling regime for the first stage of the pandemic with an uneven behaviour among different regions as well as for the overall mortality increase according to the different impact of COVID-19. However, COVID-19 incidence rate does not fully explain the differences of mortality impact in older adults among different regions. We define a quantitative correlation between mortality in older adults and the number of people in LTCFs confirming the tremendous impact of COVID-19 on LTCFs. In addition a correlation between LTCFs and undiagnosed cases as well as effects of health system dysfunction is also observed. Our results confirm that LTCFs did not play a protective role on older adults during the pandemic, but the higher the number of elderly people living in LTCFs the greater the increase of both general and COVID-19 related mortality. We also observed that the handling of the crises in LTCFs hampered an efficient tracing of COVID-19 spread and promoted the increase of deaths not directly attributed to SARS-CoV-2.

[The importance of flu vaccination during CoViD time]. / L'importanza della vaccinazione anti influenzale ai tempi della CoViD.

In the next months, the risk of coinfection with f lu virus and Sars-CoV-2 is high. Despite the number of studies dealing with the consequences of the interaction between the two viruses, the impact of this coexistence on human health is still uncertain. However, achieving high f lu vaccination coverage would mean avoiding hospital overload due to hospitalizations for f lu complications and facilitating a timely differential diagnosis that allows a quick and appropriate treatment of CoViD-19 cases. These are two valid reasons for actively promoting f lu vaccination, particularly this year when the risk of a "twindemic" determined by f lu and CoViD-19 is high. In Italy this year, for the first time, f lu vaccination is offered free of charge also to people aged 60 to 64, expanding individuals entitled to free vaccination. Furthermore, it is strongly recommended to healthcare workers and to elderly who live in residential or long-term care facilities.

[Routine vaccinations during SARS-CoV-2 epidemics]. / Le vaccinazioni di routine ai tempi del SARS-CoV-2.

The circulation of SARS-CoV-2 required the deplacement of resources from routine preventive activities to pandemic-related interventions. The vaccination services have been adapted to the individual territorial realities on the basis of virus circulation and restrictive measures put in place. The reduction of coverage with the consequent accumulation of susceptible subjects increases the risk of vaccine-preventable diseases' epidemics. Catch-up programs and strategies to optimize sessions, such as carrying out co-administrations, are in place on the national territory in order to reduce the risk.

Healthcare Workers Training Courses on Vaccinations: A Flexible Format Easily Adaptable to Different Healthcare Settings.

Since 2017, Italy has expanded the compulsory vaccination from 4 to 10 for those aged 0 to 16 years. Because of the great organizational effort required for the immunization services, minor attention was given to the vaccinations not included among the mandatory ones. This situation led to a real difficulty in harmonizing the vaccination procedures even inside a single region. In the Lazio region, the Laboratory of Vaccinology of the University of Rome Tor Vergata established a working group to create a new training model for healthcare professionals. The course program proposed an update of three vaccinations which are not mandatory but actively offered. It included the same part of scientific updating and a variable part based on local experiences. A specific anonymous questionnaire on knowledge and attitude was administered. The study aimed to propose a general format of training courses for vaccination centers adaptable to the individual local health units (ASLs) and to evaluate through questionnaires. The results show differences in knowledge and attitudes toward non-mandatory vaccinations among the ASLs of Lazio, confirming the usefulness of a support to make knowledge and procedures homogeneous. This model could be adapted to any healthcare setting and exported to other services.

[Vaccines: from the identification of the microorganism to marketing. How long does it take?] / Vaccini: dall'identificazione del microrganismo alla commercializzazione. Quanto tempo ci vuole?

The development of a vaccine, particularly one that can help against the recent pandemic, is a topic that has recently attracted public opinion. More than ninety vaccines are currently being developed against Sars-Cov2 by universities and companies around the world. They are protein-based vaccines, viral vector vaccines, DNA or RNA vaccines and inactivated or attenuated viral vaccines. The development of a vaccine starts from the identification and characterization of the microorganism that causes the disease. The second step is the preclinical phase. Then, there is the phase of clinical experimentation, which allows to study the posology, efficacy and safety of the vaccine, on an increasingly larger sample. In the European Union, vaccines are authorized through two procedures (EU and national) based on the quality, safety and efficacy requirements defined by the European and international guidelines. Timing of realization, authorization and marketing of new vaccines can be shortened in cases of particular need, through an accelerated evaluation known as "Priority Medicines". In this period, it is crucial not to neglect current vaccinations. In fact, during the pandemic period, many countries postponed vaccination campaigns against many vaccine-preventable diseases, causing a marked decrease in routine immunizations in childhood.

[Tuberculosis: an ever present disease but difficult to prevent]. / Tubercolosi patologia sempre attuale e difficile da prevenire.

Tuberculosis (TB) is an infectious and contagious disease caused by Mycobacterium tuberculosis, commonly called Koch's bacillus. TB is spread by air and is present all over the world. Not everyone who become infected develop the disease; the immune system can cope with the infection and the bacterium can remain dormant for years. Despite advances in therapy and prevention, TB remains one of the top 10 causes of death worldwide. Over 9 million new cases and over 1 million deaths occur each year. Since 1921 BCG has been the only authorized vaccine. More than ten experimental vaccines are currently in different stages of development. Depending on the type, they are divided into vaccines consisting of: live attenuated, inactivated mycobacteria and subunits. According to their purpose they can be divided in: vaccines aimed at preventing infection, vaccines aimed at preventing disease, vaccines aimed at preventing recurrence and therapeutic vaccines. Hopefully, these numerous attempts to develop new vaccination approaches will lead to obtain products with greater immunogenicity and efficacy.

[Adverse reactions after repeated doses of anti-tetanus vaccine: scientific evidences]. / Reazioni avverse dopo dosi ravvicinate di vaccino anti-tetanico nell'adulto: una ricerca sulle evidenze scientifiche.

The possible risk of hyperimmunization after tetanus vaccination is currently discussed after the National Vaccine Prevention Plan 2017-2019 confirmed the recommendation of a booster dose every ten years. Due to the ubiquitous nature of tetanus spores and the inability to obtain herd-immunity through vaccination, efforts to reduce the incidence of tetanus aim at eliminating the disease. The only way to prevent infection is vaccination followed by recommended periodic booster doses. Between 2012 and 2016, Italy notified 45% (252/564) of all cases reported by the 26 EU Member States, most of them in the over 65 age group, generally women in the rural areas. The recommendation of the antipertussis vaccine, combined with anti-tetanus, in pregnancy and the indications for antitetanic prophylaxis by vaccination or specific immunoglobulins in emergency setting, gives rise to doubts about the risk of hyperimmunization. Studies generally agree on the safety of diphtheria-tetanus-pertussis combined vaccines during the third trimester of pregnancy, and the time elapsed since the previous tetanus vaccination seems not to be related to significant differences in the incidence of adverse events or obstetrical complications. In the emergency wards, given the relatively high incidence of tetanus in Italy, the risk/benefit ratio often leads to prefer vaccination to no-intervention. The administration of tetanus immunoglobulins in subjects not vaccinated in the last 10 years seems justified by the epidemiology of tetanus in Italy.

[Anti-pneumococcus, anti-herpes-zoster and anti-papillomavirus vaccinations: experience in programming continuing education courses in local health units in Rome]. / Vaccinazioni anti-pneumococco, anti-herpes-zoster e anti­ papillomavirus: esperienza nella programmazione di corsi di formazione nelle asl di Roma.

The National Vaccine Prevention Plan considers the recommendations for immune prophylaxis in all ages of life. However, compulsory vaccination introduced in 2017 focused the attention on improving global vaccination coverage in infants and children, giving less attention to adult/elderly vaccinations. The immunization of this population is necessary considering the change in the age structure of the population, whose average life expectancy is increasing. Aim of this work was the organization of continuing education courses about anti-Pneumococcus, anti-Herpes-Zoster and anti-Papillomavirus vaccinations to offer an update of knowledge and to discuss the attitudes of health professionals in vaccination centers of the Local Health Units in Rome.

[Anti-flu Vaccine: tailor made solutions in large-scale distribution]. / Vaccino anti-influenzale: scelte sartoriali nella grande distribuzione.

Influenza is a public health problem with a strong impact from an epidemiological, clinical and economic point of view. Many factors contribute: ubiquity and contagiousness of the disease, antigenic variability of the viruses and the possibility of serious complications. Influenza rarely causes complications in healthy subjects. On the contrary complications can occur and be severe in people with fragile conditions. More susceptible to infection are: children, elderly, pregnant women, people with chronic conditions or undergoing immunosuppressive therapies. Vaccine is an important preventive measure. It allows to protect both the vaccinated person and those at risk. Thanks to the presence of diversified vaccines, we can offer targeted prevention. Vaccine innovations also involved production methods, allowing GPs to choose a quadrivalent cell-derived in addition to the quadrivalent egg-derived and the trivalent vaccine. Age, existing pathologies and immune system reactivity are fundamental elements guiding the customized choice of GPs. Recent years innovations concerning the increased immunogenicity (adjuvated and high-dose vaccines) and the protection against a greater number of strains (quadrivalent vaccine) in addition to new production methods (cell derived vaccine) allow us to trust in further possibilities for the future.

[Old outbreaks and new vaccines: Italy facing Ebola]. / Vecchie epidemie e nuovi vaccini: l'Italia di fronte al problema Ebola.

Zaire is the name of the most deadly Ebola Virus (ZEBOV), which caused many outbreaks in past years and is the causative agent of the most recent one. In July 2019, Ebola was declared a public health emergency of international concern. After this declaration, the steps required to prequalify and approve the r VSV ZEBOV vaccine followed each other quickly. Nowadays in Europe the risk of an outbreak is low. However, secondary cases in USA and Spain have alerted public opinion. Italy is not involved except for the assistance to its citizens infected in countries at risk mainly in contexts of humanitarian aid. In epidemic areas the situation deserves close monitoring, as shown by the interest of the WHO, FDA and EMA. Last year the Italian Ministry of Health issued four circulars on this subject to update epidemic data and procedures and to remember precautions. The live attenuated vaccine in use now shows encouraging results; however, the need to evaluate further vaccines remains to guarantee efficacy, safety and adequate quantities.

[Vaccines and sport: risk perception among athletes]. / I vaccini in ambito sportivo: percezione del rischio tra gli atleti.

Infection prevention is a key issue in both general population and in categories at risk, among which the athletes. There are risk factors related to the sporting practice performed at every level, from the amateur to the elite athletes. The control of the vaccination schedule and the empowerment of the sportsman in this area should be carried out both by the General Practitioner or the Pediatrician and by the federations to which the athletes belong. There is a need for guidelines and it is necessary to inform the athletes. This study was performed to evaluate the attitude of groups of athletes regarding infectious diseases and vaccination and confirms the lack of attention towards immunization in sports. Protocols for sport medical examinations, indeed, do not require controls on the state of vaccination and the offer of specific vaccines. It is therefore important the role that scientific societies are taking on in recommending immune prophylaxis for sportsmen.

[Vaccine co-administration in clinical practice]. / Somministrazione contemporanea dei vaccini nella pratica clinica.

Vaccines are biological products designed to induce a protective immune response, mimicking natural infection without the development of disease and / or complications. Combined vaccine administration and vaccines co-administration is a safe and effective practice, the benefits of which outweigh the disadvantages. The operators should assess individual variations for the completion of the vaccination schedule, which may be necessary in clinical practice, case by case. Often there are myths to dispel, such as fears about the overload of the immune system, the remora to do more injections in the same session, excessive reactogenicity and some false contraindications. The operators, in order to resolve their doubt in performing non-routine co-administrations, can rely on the Summary of Product Characteristics (SPC) of the individual vaccines and on the new available evidence.

[Bacterial lysates: history and availability]. / Storia e diffusione dei lisati batterici utilizzati come "vaccini".

The use of bacterial lysates (BLs) can be traced back to the end of the nineteenth century, and they are currently available in several countries across all continents. Over the last few decades, BLs have been used, both in pediatric patients and in adults, mainly for the prevention and treatment of bacterial infections of the respiratory tract. BLs are produced from bacterial cultures that undergo cell lysis with two different methods: mechanical lysis and chemical lysis. The in vivo mechanism of action is still not fully understood, and the main hypotheses focus on mucosal immunity modulation. We searched PubMed for relevant papers on the use of BLs for the prevention and treatment of chronic obstructive pulmonary disease and recurrent respiratory infections both in adult and in pediatric patients. We retrieved 169 articles and after screening and selection, we analyzed 13 RCTs focusing on adult patients and 8 on pediatric patients. The outcomes assessed were mainly about the efficacy of BLs on exacerbations, hospitalizations, antibiotic treatment, fever, number of episodes and days of absence from work or school. Many aspects of BLs are still not well understood and the quality of available studies is not satisfactory; in order to place BLs within the scope of Public Health, further good quality studies are needed, keeping in mind the necessity to respond to the needs of patients for whom no alternative effective treatments are available.

[The Italian Immunization Plan 2017: analysis and starting point for the Regional Plans]. / Il nuovo Piano Nazionale Prevenzione Vaccinale 2017-2019: analisi e punto di partenza per i piani regionali.

The National Immunization Plan 2017-2019 has been approved on January 2017. This official document contains the new Italian guidelines to improve vaccination coverage in the country. We conducted an accurate and critical analysis of the document, highlighting its key points and critical issues, in order to offer an practical tool for writing the Regional Plans. The new immunization schedule and the establishment of a restricted panel for the vaccine vigilance are the most significant innovations of the Plan. The Plan addresses also the issues of mandatory vaccination and of penalties for physicians who advise against vaccinations. Together with the presence of qualifying aspects as information about the ethical value and the benefits of vaccination, the Plan contains other interesting proposals, such as the introduction of a computerized vaccination register and the targeted use of new technologies to reach the population extensively. The Plan is set up as a conceptually rich tool, suitable for the development of regional operational plans.

[HPV vaccination: active offer in an Italian region]. / Offerta attiva della vaccinazione anti-HPV nella Regione Lazio.

Human Papillomavirus is responsible for 4.8% of cancers, and is the main cause of cervical cancer. Cervical cancer can be reduced by mean of secondary prevention (PAP-test, HPV-DNA test), while through primary prevention (anti-HPV vaccine) the incidence of other HPV-attributable cancers can also be reduced. In Italy, anti-HPV vaccination is part of the immunization schedule in girls since 2008, and in 2017 it was extended to boys. However, vaccine coverage is decreasing nationwide. This study aims to examine anti-HPV vaccination practices in Health care services of Lazio Region, Italy. Questionnaires were sent or administered directly to those in charge of vaccinations. Data, collected from 11/12 (92%) Lazio Local Health Units and from 116 vaccination centers, show a remarkable diversity in the offer: 41% of the centers open only 1-2 days/week, 42% only in the morning, and only 7% are open on Saturday. Vaccination is available by reservation only in 62% of the centers, while vaccines are not administered to ≥18 years subjects in 33%; 93% of the centers call actively the girls in the target cohort, while 70% and 94% recall the patients who had not received the first or the second dose of vaccine, respectively. Collaboration with family physicians and/or pediatricians was declared by 80% of the centers. Vaccine coverage could probably be improved by addressing the highlighted critical issues and applying best practices widely.

[Vaccines: benefits have been forgotten]. / Vaccini, dimenticati i perché a loro favore.

The increased use of vaccination has led to a significant decrease or even to the disappearance of serious infectious diseases. Currently, vaccines are often evaluated by their potential side effects while ignoring the benefits. This happens because of memory loss. The memory of the damage caused by vaccine-preventable diseases has been lost. This paper illustrates the epidemiology of the major vaccine-preventable diseases and the risk of reintroduction of many pathologies in case the vaccine coverage continues to decrease.

[Vaccines: history and stories between reality and imagination]. / La Storia e le storie sui vaccini. Un piano tra veridicità e fantasia.

Vaccinations and the controversy around them always go in parallel. We identified four categories blending in various amounts of truth and imagination: history, myths, shams and frauds. Over the years, they have alternated and sometimes transformed into one another. This sharp separation into categories is certainly academic and forced. In fact, the line between these aspects is not clear enough to allow a rigid and well-defined division. Our work starts from the category containing the most truthfulness: history, and goes on to analyze two categories that add fantasy to facts: myths and shams (or better, "old wives' tales"). The history deals with the topics of variolation and the first anti-vaccine activists' disputes. Myths that arose around immunization include immune overload, homeoprophylaxis, and excessive hygiene. In this context, immunization itself risked becoming a myth, being considered not amenable to improvements. In the category of old wives' tales we find rumors about the presence in the vaccines of considerable quantities of supposedly toxic components such as aluminum, squalene, Thimerosal and nanoparticles, as well as the existence of secret techniques of vaccine preparation that involve unethical procedures. The last category, fraud, is the poorest in both truth and fantasy but it is still hard to confront. The most famous fraud is the supposed link between vaccines and autism. In this frame, disinformation is certainly a fertile substrate for the emergence both of elements close to reality and of very imaginative ones. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and increasing the risk of vaccine-preventable disease outbreaks and epidemics. The role of communication in immunization is essential to its success, especially taking into account the deep transformations the world of information is going through. The great multitude of voices seem to carry the same weight, but it is not so in science. Web searches are influenced by the filter bubble phenomenon, which contributes to the radicalization of people's opinion through cognitive isolation. A new, more effective strategy of communication is required in order to regain the trust of populations in immunization in a context characterized by the presence of groups impervious to scientific evidence.

[Rare adverse events following immunization: coincidence]. / Eventi avversi rari successivi a vaccinazione: casualità o causalità?

The high standards of safety and effectiveness of vaccines have allowed them to get a prominent role in disease prevention and health protection. However, like any other intervention, vaccination is not free from risks. Rare adverse events occur after immunization in less than one in a thousand individuals and can be linked to vaccination by causality or coincidence. These events are reported on the SmPC (Summary of Product Characteristics). We have first divided the rare adverse events in local and generalized, and then we have analyzed them according to the type of vaccine linked to the event. Communication of the benefits of vaccines, that are surely greater than their risks, must take place in a conscious and scientific way, in order to avoid vaccinations being perceived as an imposition, instead of the great opportunity for everyone that they are.

[Haemophilus influenzae type b in Italy--after thirty years of vaccination may we lower our guard?]. / Haemophilus influenzae tipo b a trent'anni dal primo vaccino, possiamo abbassare la guardia?

Haemophilus influenzae b (Hib) is responsible for meningitis, systemic infections and acute respiratory illness, especially in children. The use of the conjugate vaccines against Hib reduced the incidence of the disease worldwide. In Italy, after the decrease resulted from vaccination, the disease may reappear due to the reduction in vaccination coverage, the presence of infections in adults and vaccine failures.