How should vaccination services be planned, organized, and managed? Results from a survey on the Italian vaccination services.

BACKGROUND: Quality improvement is an increasingly recognized approach to maximize service effectiveness and minimize costs in public health. However, the Italian law never provided for the institutional accreditation of vaccination services. Furthermore, a recently approved law added six more compulsory vaccinations to the original four, which has led to a considerable increase in vaccination efforts, without any previous resources evaluation. The aim of the study was to investigate structural, organizational and managerial characteristics of the Italian vaccination services, in order to suggest the adoption of adequate quality standards. STUDY DESIGN: A survey involving the representatives of the Italian Regions and Autonomous Provinces was performed between September 2017 and September 2018. METHODS: An online questionnaire, including 26 items, designed to evaluate the structural, organizational and managerial characteristics of vaccination services was administered. The correlation between the number of vaccination centres and the coverage for each region was used to evaluate the performance of the vaccination services. RESULTS: Respondents from seven Regions, totaling >15,000,000 inhabitants, answered the questionnaire. Overall, each vaccination service was potentially accessed by an average of 519 children aged zero to 24 months, with a ß-coefficient of -0.87 (p = 0.01) for infant vaccination coverage in 2016. Eighty-five percent of vaccination services were provided with architectural features to accommodate the disabled but only 49% provided reserved parking lots. An average of 0.4 physicians and 0.6 other healthcare workers per 10,000 inhabitants were employed in vaccination services, with complete computerization in 74% of them. CONCLUSION: The inverse relation between vaccination services' spatial accessibility and vaccination coverage suggests that distance and accessibility of vaccination services should be considered in planning. This survey constitutes a baseline data for Italian vaccination services that could be useful for decision makers in establishing minimum requirements to provide high-quality preventive healthcare service.

Increasing incidence of Clostridium difficile infections: results from a 5-year retrospective study in a large teaching hospital in the Italian region with the oldest population.

Limited information is available on the incidence of Clostridium difficile infections (CDIs) in Italian hospitals. In this study, we assessed the changes in the incidence of CDI over a 5-year period in a teaching hospital in Liguria, the Italian region with the oldest population. Secondary endpoints were the development of severe CDI and 30-day mortality. The annual incidence of CDI/10000 patient-days significantly increased from 0·54 in 2010 to 3·04 in 2014 (χ 2 for trend, P < 0·001). The median age of patients with CDI was 81 years. As many as 81% and 89% of these patients had comorbid conditions and previous exposure to antibiotics, respectively. In the multivariate analysis of risk factors for severe CDI, previous therapy with histamine 2 blockers and low serum albumin were associated with severe CDI, while diabetes appeared to be protective. In the multivariate model of risk factors for 30-day mortality, high leukocyte count, low serum albumin, and increased serum creatinine were unfavourably associated with outcome. Strict adherence to infection control measures was of utmost importance to counteract the increasing incidence of CDI in our hospital, particularly because of the advanced age of the patients and their very high frequency of chronic conditions and use of antibiotics, which readily predispose them to the development of CDI.

Available influenza vaccines: immunization strategies, history and new tools for fighting the disease.

The main public health strategy for containing influenza-related disease is annual vaccination, which is recommended for the elderly and others belonging to risk-factor categories, who present the highest morbidity and mortality, as reported by the World Health Organization (WHO) Recommendations. The availability of different influenza vaccine formulations makes the choice of the best immunization strategy a challenge for stakeholders and public health experts. Heterogeneity in at-risk categories included in national influenza vaccine recommendations still exists, in particular among European countries. Broader consensus is expected, which should positively impact on influenza vaccination coverage. The availability of quadrivalent vaccines, containing both influenza B lineages, offers the potential to improve protection by overcoming the drawbacks of wrongly predicting which B lineage will predominate in a given year.

Influenza vaccination in the elderly: why are the overall benefits still hotly debated?

The exact magnitude of the benefit of influenza vaccine among elderly individuals is subject of considerable debated. Existing vaccine effectiveness estimates come mostly from observational studies, which may be biased because of difficulties in identifying and adjusting for confounders. In this paper, we examine the potential sources of bias in observational studies of influenza vaccine effectiveness in the elderly and we discuss available evidence regarding the efficacy and effectiveness of licensed influenza vaccines. Although several methodological criticisms among the available analyses on seasonal vaccines for elderly were identified, overall seasonal influenza vaccines showed relevant efficacy/effectiveness in reducing the risk of influenza and its complications in the elderly, considering different measure of outcome.

Pneumococcal vaccination strategies in adult population: perspectives with the pneumococcal 13 - valent polysaccharide conjugate vaccine.

Streptococcus pneumoniae (Sp) is a leading cause of infection in people of all ages worldwide, determining a significant impact because of its relatively high incidence rate, the associated economic costs, and the high case-fatality rates. More attention has to be paid for elderly and people with one or more risk factors, in order to reduce health costs and pneumococcal hospital admissions. Moreover, the increasing incidence of antibiotic-resistant Sp strains is a source of concern for its relevant clinical importance in health-care settings. At present, the 23-valent polysaccharide (PPV23) vaccine has shown some limits in terms of protection in the elderly population and against invasive diseases, among adults affected with chronic diseases, non-bacteriemic pneumonias and with immune suppression, in particular in adults with HIV. In December 2011, FDA licensed the 13-valent pneumococcal conjugate vaccine (PCV13) for prevention of pneumonia and invasive diseases (IPDs) in adults aged ≥50 years. The same decision was concomitantly assumed in Europe by EMA. PCV13 has shown superior results both in terms of immunogenicity and of adequate stimulation of a stable and long-lasting immunological memory. European recommendations for PCV13 vaccination in adults are still heterogeneous between Countries. The availability of PCV13 for adults offer a new and promising tool against Sp IPDs and non-IPDs, especially in elderly and at risk populations.

Generation of iPSC lines derived from skin fibroblasts of two healthy controls using non-transmissible form of Sendai Virus.

We established two iPSC lines starting from skin fibroblasts of two healthy individuals using Sendai-virus-based technique. The obtained iPSCs were characterized showing same STR profile as starting fibroblasts, normal karyotype, loss of stemness vectors, expression of stemness markers, both through real-time PCR and immunofluorescence, (OCT4, SOX2, TRA-1-60, NANOG and SSEA4) and in vitro differentiation into three germ layers.

HPV related diseases in males: a heavy vaccine-preventable burden.

Human Papillomavirus (HPV) has a significant impact in male's health, as cause of clinical manifestations ranging from genital warts to several cancers of the anogenital and aero-digestive tract. HPV types which most frequently affect men are 6, 11, 16 and 18, included in the HPV quadrivalent vaccine, recently approved for use in males by Food and Drug Administration (FDA) and European Medicines Agency (EMA). Although several data about the safety and efficacy of quadrivalent vaccine are available, the implementation of proper immunization plans dedicate to male's population cannot ignore the knowledge of the characteristics of the disease in men, which in some aspects should be clarify, in particular clearance of type-specific HPV infections and transmission dynamics. Purpose of this review is to summarise the main information about the burden and the natural history of the HPV related disease in males.

Influenza vaccination in HIV-positive subjects: latest evidence and future perspective.

Annual influenza vaccination is recommended for persons with human immunodeficiency virus (HIV) infection. Recent reports indicate that immunizations may increase IIeplication in infected individuals. Generally, vaccination against influenza is well tolerated in both children and adult individuals with HNIVand does not induce significant changes in viral load and CD4+ cell counts. The observed increase in viral replication is usually transient and a clear, measurable progression of the underlying HIV disease is hard to be determined. Several studies reported immunogenicity data in HIV+ population, by comparing diferfent influenza vaccines, adjuvanted or not, and different administration routes. Data are encouraging because an adequate immune response is shown, although split/subunit vaccines do not elicite an efficient immune response in these subjects. New strategies have been evaluated to increase the immune response in immunocompromised patients.The aim of this review is to evaluate tolerability, safety, immunogenicity and efficacy of vaccines actually approved for human use and to consider latest evidence and future perspective in HIV positive subjects.

Generation of an iPSC line from skin fibroblasts of a patient with Joubert syndrome carrying the homozygous loss of function variant c.787dupC in the AHI1 gene.

We produced an iPSC line from a patient with Joubert syndrome carrying the homozygous c.787dupC variant in the AHI1 gene. The iPSC line was obtained by reprogramming skin fibroblasts, mycoplasma-free, using Sendai-virus-based technique. Characterization of iPSCs showed the same Short Tandem Repeats profile than fibroblasts, normal karyotype, expression of staminal markers (OCT4, SOX2, SSEA4 and NANOG) and ability to differentiate into three germ layers in vitro.

Impact of influenza during the post-pandemic season: epidemiological picture from syndromic and virological surveillance.

INTRODUCTION: Following the observation that 1 or 2 pandemic peak due to the circulation ofAHINlv had occurred in most countries and in most World Health Organization (WHO) Regions, WHO declared on August 10"h, 2010 that the world was moving into the post-pandemic period, whose surveillance presents considerable interest both from epidemiological and clinical point of view. We described the epidemiological picture emerged from syndromic and virological surveillance during the post-pandemic season in Liguria, Italy. MATERIALS AND METHODS: An Emergency Department Syndrome surveillance system, based on data collected at "San Martino" and IRCCS "G. Gaslini" Liguria Regional Reference University Hospitals for adults and children is active since July 2007. Monitored syndromes include "Influenza-Like Illness" (ILl) and "Low Respiratory Tract Infections" (LRTI). The Ligurian Regional Reference laboratory for Influenza virological surveillance and diagnosis offers rapid detection of influenza viruses by real-time and block RT-PCR, viral culture and genetic characterization by entire sequence analysis of haemagglutinin- and neuraminidase-coding regions in accordance with the international standards established by the global laboratory network. RESULTS AND DISCUSSION: The integration of syndromic surveillance system and laboratory surveillance for rapid detection and characterization of the disease responsible agent represented a specific and sensitive tool for influenza surveillance. The post-pandemic season was characterized by early onset and by the heaviest impacts for ILI and LRTI among the recent epidemic seasons. In contrast to the picture observed during the pandemic season, the 2010/11 winter was characterized by the intensive circulation of pandemic AH1N1v coupled with sustained activity due to influenza B and Respiratory Syncytial Virus (RSV). Antigenic and molecular characterization of influenza strains confirmed the good matching between circulating and 2010/11 vaccine viruses.

Epidemiological and molecular approaches for management of a measles outbreak in Liguria, Italy.

Since March 2010 a measles outbreak has been occurred in Genoa, Liguria, an administrative Region in Northern Italy. Epidemiological and molecular data on the outbreak, obtained from the passive mandatory notification system, the laboratory surveillance and an innovative syndrome surveillance system, were investigated. Overall 39 cases were reported in the urban area. Information about demography, vaccination status, hospitalization and geographic distribution of measles cases are available. 19 cases (48.7%) were laboratory-confirmed and were characterized by sequence analysis: 18 strains belonged to genotype D8, so identifying a new measles variant within the Liguria population. Adopted control measures seem to have limited viral circulation. The outbreak allowed to test the efficacy of the 3 surveillance systems active in Liguria, highlighting their advantages and some important limitations. More efforts are needed to collect and integrate any epidemiological and virological available data in order to better describe the local measles transmission dynamics.

Novel PTEN mutations in neurodevelopmental disorders and macrocephaly.

Somatic mutations of the phosphatase and tensin (PTEN) gene have been frequently detected in many types of human cancer. However, germline mutations can determine multiple hamartoma syndromes and, as more recently ascertained, syndromes clinically characterized by autism associated with macrocephaly. To determine whether germline mutations of PTEN may lead to different phenotypes, we screened all the nine exons of the PTEN gene in 40 patients with neurodevelopmental disorders, with or without features of autism spectrum disorder, associated with macrocephaly. Three novel de novo missense mutations were found (p.H118P, p.Y176C, p.N276S) in two severely mentally retarded patients with autism and in a subject with neurodevelopmental disorders without autistic features. Our results provide evidence that PTEN germline mutations may sustain a more wide phenotypical spectrum than previously suggested.

[A cross-sectional survey on childhood immunization coverage and reasons of non-compliance in Lazio Region, Italy (2007)]. / Indagine campionaria sulle coperture vaccinali in età pe- diatrica e sui motivi di mancata vaccinazione nella regione Lazio (2007).

During 2007, Laziosanità conducted a cross-sectional survey on childhood immunization coverage in Lazio Region. The survey, implemented in collaboration with the 12 LHUs of the Region, aimed at assessing immunization coverage among children, with 24 months of age or older, at regional and district level. In addition, the survey assessed reliability of the routine surveillance system and immunization records at peripheral level. Finally, delay in immunization schedule, and major reasons for non-compliance, as reported by the mothers, were analyzed. The survey results allowed to identify weakness in the routine surveillance system, low coverage levels for specific LHUs, and strategies for improvement of immunization coverage.

[Quality of post-discharge growth in small for gestational age preterm infants: an explorative study]. / Qualità della crescita post-dimissione in prematuri nati piccoli per età gestazionale: studio esplorativo.

OBJECTIVES: The Preterm newborns, especially if born small for gestational age (SGA), appear to be at risk for developing post-natal growth failure and an altered body composition. Nutrition-related growth during a critical window in infancy may affect the development of metabolic syndrome in adult life. Aim of the present study was to test the hypothesis that the post-discharge period is critical for programming the catch up growth and the later development of metabolic syndrome in small for gestational-age infants fed either standard or enriched formula. METHODS: A clinic randomized explorative study was conducted. Twenty-seven preterm SGA infants (gestational age < or = 33 weeks; birth weight < or = 1500 g) underwent assessment of growth and body composition by means of an air displacement system at 36 weeks, 15 days and 1 months adjusted age. SGA infants were randomized to receive standard formula (Kcal: 67/100 ml, proteins: 1,4 g/100 ml) or enriched formula (Kcal: 75/100 ml, proteins: 2 g/100 ml) after discharge. RESULTS: No differences in weight, fat mass, length and head circumference were found in SGA infants fed standard formula as compared to those fed enriched formula at 15 day or 1 months adjusted age. CONCLUSIONS: This explorative study suggests that in SGA infants growth, both in terms of quantity and quality, is not influenced by different nutritional management during the early post-discharge period.

Detection of influenza A(H1N1)pdm09 virus in a patient travelling from Shanghai to Italy in July 2018: an uncommon clinical presentation in a non-seasonal period.

Influenza is one of the most common infectious diseases in travellers, especially in those returning from subtropical and tropical regions. In late June 2018 an influenza A(H1N1)pdm09 virus infection was diagnosed in a 36-years-old man, returned from a travel in Shanghai and hospitalized at the Ospedale Policlinico San Martino, Genoa, Italy, with a diagnosis of fever and an uncommon clinical presentation characterised by a persistent leukopenia. Phylogenetic analysis revealed a closeness with influenza A(H1N1)pdm09 strains circulating in the US in May-June 2018. Prompt recognition of influenza infection led to a proper case management, demonstrating the crucial role of the continuous influenza surveillance programme.

Vaccination coverage in healthcare workers: a multicenter cross-sectional study in Italy.

INTRODUCTION: In recent years, a phenomenon known as "vaccine hesitancy" has spread throughout the world, even among health workers, determining a reduction in vaccination coverage (VC).A study aimed at evaluating VC among healthcare workers (HCWs) in 10 Italian cities (L'Aquila, Genoa, Milan, Palermo, Sassari, Catanzaro, Ferrara, Catania, Naples, Messina) was performed. MATERIALS AND METHODS: Annex 3 of the Presidential Decree n. 445 of 28 December 2000 was used to collect information on the vaccination status of HCWs. The mean and standard deviation (SD) were calculated with regard to the quantitative variable (age), while absolute and relative frequencies were obtained for categorical data (sex, professional profile, working sector, vaccination status). The connection between VC and the categorical variables was evaluated by chi-square method (statistical significance at p < 0.05). The statistical analyses were performed by SPSS and Stata software. RESULTS: A total of 3,454 HCWs participated in the project: 1,236 males and 2,218 females.The sample comprised: physicians (26.9%), trainee physicians (16.1%), nurses (17.2%) and other professional categories (9.8%). Low VC was generally recorded. Higher VC was found with regard to polio, hepatitis B, tetanus and diphtheria, while coverage was very low for measles, mumps, rubella, pertussis, chickenpox and influenza (20-30%). CONCLUSIONS: This study revealed low VC rates among HCWs for all the vaccinations. Measures to increase VC are therefore necessary in order to prevent HCWs from becoming a source of transmission of infections with high morbidity and/or mortality both within hospitals and outside.

Influence of protein and energy intakes on body composition of formula-fed preterm infants after term.

The aim of the present study was to evaluate changes in body composition in 48 preterm infants in relation to protein and energy intakes from term up to 3 months of corrected age, using air displacement plethysmography. Protein intake (grams per kilogram per day) was negatively associated with percentage of fat mass at 1 month of corrected age. The high-protein-intake group showed greater gain in lean body mass gain than did the low-protein-intake group. This finding suggests that during the first month of corrected age, high protein intake results in a significantly different weight gain composition.

Emergency department syndromic surveillance system for early detection of 5 syndromes: a pilot project in a reference teaching hospital in Genoa, Italy.

Early detection is fundamental for achieving effective control of infectious disease outbreaks. We described the development of a local chief complaint emergency department (ED)-based syndromic surveillance system to improve public health response in Genoa, Italy. The five syndromes under investigation by the syndromic surveillance system were influenza-like illness (ILI), low-respiratory tract illness (LRTI), not-haemorrhagic gastroenteritis, acute hepatitis, fever-with-rash (maculo-papular or vescicular) syndrome. Syndrome coding, data capture, transmission and processing, statistical analysis to assess indicators of disease activity and alert thresholds, and signal response were operatively described. Preliminary results on ILI syndromic surveillance showed that new system allowed the activation of the alert state with a specificity of 90.3% and a sensitivity of 72.9% in predicting epidemiological relevant events, such as > or = 10 accesses to ED for ILI in 3 days. The new syndromic surveillance system allowed to alert the public health institutions 2.5 days before than the local surveillance system based on sentinel physicians and paediatricians, permitting the early activation of the necessary measures for the containment and for burden reduction of the epidemic event. It is noteworthy that the syndromic surveillance epidemic cut-off was overcome once before and 4 times after influenza outbreak detected by sentinel-based surveillance system: all episodes were contemporary with Respiratory Syncytial Virus and Parainfluenza Virus circulation, as detected by regional reference laboratory.

[Quality of growth in preterm infants assessed at term equivalent age: a pilot study]. / E possibile mimare nel neonato pretermine la composizione corporea fetale? Uno studio pilota.

BACKGROUND: The American Academy of Pediatrics (AAP) recommends that preterm infants' growth duplicates fetal growth rates and that body composition replicates in utero body composition. Aim ofthe study was to compare the total body fat mass between preterm infants assessed at term and full-term newborns. METHODS: A prospective observational study was conducted. Forty-five preterm infants (mean (SD) gestational age: 30,1 (2.3) weeks; birth weight: 1125 (280) g), and 40 full term (mean (SD) 38.5 (1.2) weeks, 3203 (385) g, breast fed infants underwent assessment of growth and body composition by means of an air displacement system at term adjusted-age and on day 3 of life, respectively. A T test was used to compare % fat mass between preterm and term infants. RESULTS: Weight, length and head circumference were smaller in the preterm group assessed at term adjusted-age as compared to the term group. Mean (SD) percentage of fat mass in preterm infants was significantly higher as compared to term infants [14.5 (4.3) vs 7,6 (3.6), P < 0.0001]. CONCLUSIONS: Our data demonstrate that preterm infants are at risk of developing an increased adiposity in addition to postnatal growth retardation.

[Body composition in small for gestational age newborns]. / Composizione corporea in neonati piccoli per età gestazionale.

OBJECTIVES: Aim of the present study was to test the hypothesis that the body composition of small for gestational age preterm infants, assessed at term equivalent age, was different as compared to that of small for gestational age full-term newborns. METHODS: Growth parameters and body composition, assessed by means of an air displacement pediatric plethysmography system, was measured in 120 newborns (67 preterm and 53 full-term). RESULTS: Similar weight was found in preterm and full-term newborns at term equivalent age and at birth, respectively. On the contrary, percentage of total body fat mass was significantly higher in preterm newborns as compared to full-term newborns (14.3 +/- 4.7% vs. 5.7 +/- 3.8% respectively, P < 0.05). In the preterm group gestational age was negatively associated with total fat mass at term equivalent age. CONCLUSIONS. The preterm newborns, especially if born small for gestational age, appear to be at risk for developing an altered body composition, which is a risk factor for the development of the metabolic syndrome in adult life. Preterm infants, born small for gestational age, appear to develop a quantity of fat mass higher than the adipose tissue they would have accumulated if they had completed their intrauterine gestation. The gestational age and the nutritional management in the early postnatal life could play a key role in affecting the body composition in these vulnerable infants.