The recommended lifetime immunization schedule from the board of vaccination calendar for life in Italy: A continuing example of impact on public health policies.

The Vaccination Calendar for Life is an alliance of scientific and professional societies of public health physicians, paediatricians and general practitioners in Italy which provides a periodical update on the ideal, scientifically driven vaccination calendar throughout lifetime. Since 2012, the Lifetime Immunization Schedule has represented a benchmark for Regional and National Authorities to set up the updated list of vaccines provided actively and free of charge to infants, children, adolescents, adults and the elderly by inclusion in the Triennial National Vaccination Plan (TNVP), and in the Essential Levels of Care (LEA). The impact of the different editions of the Lifetime Immunization Schedule on the TNVP was deep, representing the inspiring source for the present vaccination policy. The 2019 edition called for more attention to pregnant women immunization; risk groups vaccination; uniform high coverage with the MMRV vaccine; extension of Meningococcal B vaccination also at adolescent age; use of quadrivalent conjugate meningococcal vaccine also at 1 year of life; progressive decrease of the age of free-of-charge offer of influenza to ≥ 60 and then to ≥ 50 year-old population; implementation of flu immunization ages 6 months-6 years; HPV vaccination also offered to 25-year old women at the time of the first screening (gender neutral immunization already offered); sequential PCV13-PPV23 pneumococcal vaccination in 65 year-old subjects; increased coverage with rotavirus vaccine in infants and zoster vaccine in the elderly.

Economic burden of HPV9-related diseases: a real-world cost analysis from Italy.

INTRODUCTION: The objectives of this study were to estimate the economic burden of HPV in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections. METHODS: A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis. RESULTS: In 2018, the total annual direct costs were €542.7 million, with a range of €346.7-€782.0 million. These costs could increase considering innovative therapies for cancer treatment (range €16.2-€37.5 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was €329.5 million, accounting for 61% of the total annual burden of HPV-related diseases in Italy. Of this amount, €135.9 million (41%) was related to men, accounting for 64% of the costs associated with non-cervical conditions. CONCLUSIONS: The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.

Application of socio-economic-health deprivation index, analysis of mortality and influenza vaccination coverage in the elderly population of Tuscany.

OBJECTIVE: The aim of this paper is to describe the results obtained from the application of a specific local deprivation index, to general and cause-specific mortality and influenza vaccination coverage among elderly people in the municipality of Florence. METHODS: General and cause-specific mortality data (2009-2013) and influenza vaccination coverage data (2015/16 and 2016/17) were collected for subjects aged ≥ 65 years residing in the municipality of Florence (Tuscany), at the 2011 Census section level. A Socio-Economic and Health Deprivation Index (SEHDI) was constructed and validated by means of socio-economic indicators and mortality ratios. RESULTS: Half of the population of Florence belonged to the medium deprivation group; about 25% fell into the two most deprived groups, and the remaining 25% were deemed to be wealthy. Elderly people mostly belonged to the high deprivation group. All-cause mortality and cause-specific mortality (cancer and respiratory diseases) reached their highest values in the high deprivation group. Influenza vaccination coverage (VC) was 54.7% in the 2015/16 and 2016/17 seasons, combined. VC showed a linear rising trend as deprivation increased and appeared to be correlated with different factors in the different deprivation groups. CONCLUSIONS: As socio-economic deprivation plays an important role in health choices, application of the SEHDI enables us to identify the characteristics of the main sub-groups of the population with low adherence to influenza vaccination. The results of the present study should be communicated to General Practitioners, in order to help them to promote influenza vaccination among their patients.

Effectiveness of HPV vaccination in women reaching screening age in Italy.

BACKGROUND AND OBJECTIVES: A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. STUDY DESIGN: During 2010-2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. RESULTS: Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p=0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p<0.01 and 2.1% vs 6.5%, p=0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p<0.01 and 0.6% vs 6.7%, p-value<0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p<0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. CONCLUSIONS: Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.

The role of the general practitioner in the screening and clinical management of chronic viral hepatitis in six EU countries.

INTRODUCTION: Chronic viral hepatitis is still a major public health concern in the EU. In order to halt the progression of the disease and to prevent onward transmission, timely recognition and accurate clinical management are crucial. The aim of the present study was to investigate the role of the general practitioner (GP) in the screening of persons at risk and in the clinical management of chronic viral hepatitis patients in six EU countries. METHODS: An online survey among GPs and secondary-care specialists was conducted in the UK, Germany, the Netherlands, Hungary, Italy and Spain. In the GP survey, we used a four-point Likert scale to find out how commonly risk groups are screened. In both surveys, we measured GPs involvement in monitoring clinical indicators in patients undergoing antiviral treatment, and explored whether patients in four clinical scenarios are referred back to primary care. RESULTS: Between five and 10 experts per professional group were surveyed, except for Spain (GPs: n = 2; Specialists: n = 4) and, in the case of the GP survey, Hungary (GPs: n = 1) and Germany (GPs: n = 4). Migrants are variably or not routinely screened for hepatitis B/C in the majority of cases. The majority of GPs reported that hepatitis B/C screening was routinely offered to people who inject drugs. In Hungary, Italy and in the Netherlands, screening sex workers is not a regular practice. As to whether GPs offer screening to men who have sex with men, responses varied; in Germany, the Netherlands and Italy, screening was "variably" or "commonly" implemented, while in Hungary the practice seems to be sporadic. In the UK, screening for hepatitis B seems to be common practice among GPs, while hepatitis C testing is only occasionally offered to this risk group. Most GPs (> 44%) in all countries except Hungary reported that hepatitis B/C screening was very commonly offered to HIV patients. The role of GPs in monitoring hepatitis cases and the referral of cases back to GPs by specialists varied both within and between countries. GPs are unlikely to monitor clinical outcomes other than side effects in patients undergoing treatment. Patients who have had a sustained virological response are usually referred back to GPs, whereas patients undergoing antiviral treatment and those who do not respond to treatment are rarely referred back. CONCLUSIONS: The GP's decision to offer screening to risk groups often seems to be an individual choice of the healthcare professional. Raising GPs' awareness of the disease, for example through the adoption of effective strategies for the dissemination and implementation of the existing guidelines for general practice, is strongly needed. The role of GPs and specialists involved in the management of chronically infected patients should also be clarified, as opinions sometimes differ markedly even within each professional group.

Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study.

The aim of the present study was to evaluate the effectiveness of the combined administration of myo-inositol and α-lipoic acid in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI), who had previously undergone intracytoplasmic sperm injection (ICSI) and received myo-inositol alone. Thirty-six of 65 normal-weight patients affected by PCOS who did not achieve pregnancy and one patient who had a spontaneous abortion were re-enrolled and given a cycle of treatment with myo-inositol and α-lipoic acid. For all female partners of the treated couples, the endocrine-metabolic and ultrasound parameters, ovarian volume, oocyte and embryo quality, and pregnancy rates were assessed before and after three months of treatment and compared with those of previous in vitro fertilization (IVF) cycle(s). After supplementation of myo-inositol with α-lipoic acid, insulin levels, BMI and ovarian volume were significantly reduced compared with myo-inositol alone. No differences were found in the fertilization and cleavage rate or in the mean number of transferred embryos between the two different treatments, whereas the number of grade 1 embryos was significantly increased, with a significant reduction in the number of grade 2 embryos treated with myo-inositol plus α-lipoic acid. Clinical pregnancy was not significantly different with a trend for a higher percentage for of myo-inositol and α-lipoic acid compared to the myo-inositol alone group. Our preliminary data suggest that the supplementation of myo-inositol and α-lipoic acid in PCOS patients undergoing an IVF cycle can help to improve their reproductive outcome and also their metabolic profiles, opening potential for their use in long-term prevention of PCOS.

Sexual behavior, use of contraceptive methods and risk factors for HPV infections of students living in central Italy: implications for vaccination strategies.

The most frequent risk factors related to the infection/persistence of HPV in the population are an early start of sexual activity, the number of sexual partners, smoking, and the utilization of some contraceptive methods. In Italy, HPV vaccine is offered free of charge to all 12-year-old female adolescents, with a possible extension to other age groups according to Regional policies. In order to value the suitability of the current HPV vaccination strategies in Italy, an epidemiological study on sexual habits in adolescents and young adults was organized. An anonymous questionnaire on sexual behavior and risk factors for HPV infection was administered to 2300 students aged 13-24 years attending secondary schools and universities in Tuscany during 2008-09. About 12% of the sample declared to be foreign citizen. The results highlight the early start of sexual activity among young students. Particularly, more than half of the interviewed students declared to be already sexually active. The mean and the median age of the first sexual intercourse was 15.4 +/- 1.4 years and 15 years (25th and 75th percentiles = 14-16), respectively. More than 77% of students at age 16 years declared they already had the first sexual intercourse, compared with 0.3% of those <12 years. Generally, females aged 13-16-years, if sexually active, had sexual contacts with a single partner. Most students declared to know common contraceptive methods (male condom and contraceptive pill). However, only half of them declared a regular use of male condom. These data confirm the importance of vaccination against HPV for young females before their sexual debut. In addition, the current multi-cohort strategy of HPV vaccination in Tuscany (free of charge in the age range 12-16 years) allows also to catch up those girls that have not yet had their first sexual experiences before 16 years (21.5% according to our study) but also to those girls already sexually active, who very rarely are already infected by all vaccine types at 16 years. Our results also show the importance of sexual health education and of promotion of correct behaviours in schools.

[Methodological aspects of clinical and economic impact of vaccine interventions and HTA. Focus on HPV vaccination]. / Aspetti metodologici della valutazione di impatto clinico ed economico negli interventi vaccinali in HTA. Focus sulla vaccinazione anti-HPV.

The aim of the present study is to analyze the methodological and technical aspects of Health Technology Assessment (HTA) as a tool for the clinical and economic impact of vaccine interventions, describe and comment the main studies at the national level, with a particular focus on HPV vaccination. The work was conducted in 3 phases: a) revision of the scientific literature, strictly linked to methodologies adopted in different studies on economic evaluations on HPV vaccines and analysis of Guidelines for building models for the economic assessment; b) analysis of the peculiarities and critical elements of economic evaluations in the field of vaccinology, from the clinical and epidemiological point of view, as well as the recognition of lack of knowledge on HPV infection dynamics; c) a comparative analysis of the two italian studies and of the results coming from them. Many differences between studies were found. Nevertheless, there is a general agreement on the economic profile of HPV vaccination for adolescent girls, if compared with the actual practice on the prevention of cervical carcinoma (pap-test screening). All the models showed a significant impact in terms of reduction of the incidence of cervical carcinoma and related mortality, in the long run, as well as a reduction of pre-cancer lesions and abnormal Pap tests. HTA approach has been recently recognized as a tool for decision making in vaccinology, and its methodologies and procedures are currently debated by public health experts. There is a strong need to continue the work in improving the model techniques of economic evaluations concerning HPV vaccination, as well as the adoption of homogeneous methods and standards, with the aim of helping the decision process in the field of Public Health.

Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus.

BACKGROUND AND OBJECTIVE: Patients with cortical malformations often have intractable seizures and are candidates for epilepsy surgery. Within an unselected series of patients with various forms of cortical malformation, nine patients with multilobar polymicrogyria had electrical status epilepticus during sleep (ESES) accompanied by infrequent focal motor seizures. Eight patients also had intractable atonic drop attack seizures. Because ESES usually is accompanied by a good long-term seizure prognosis, the objective of this study was to examine ESES outcome among patients with a structural lesion that is usually highly epileptogenic and has a low seizure remission trend. METHODS: The nine patients had follow-up periods lasting 4 to 19 years. All underwent brain MRI, serial sleep EEG recordings, and cognitive testing during and after ESES. RESULTS: ESES and drop attack seizures appeared between the ages of 2 and 5 years (mean, 4 years) and ceased between the ages of 5 and 12 years (mean, 8 years). At the last visit patients were 8 to 23 years of age (mean, 14.5 years) and were either seizure free or had very infrequent focal motor seizures during sleep. Three patients were free from antiepileptic drugs. In no patient was definite cognitive deterioration apparent after ESES in comparison with earlier evaluations. CONCLUSIONS: Age-related secondary bilateral synchrony underlying ESES may be facilitated in multilobar polymicrogyria. The good seizure outcome contrasts with that usually found in the presence of cortical malformations. For children with polymicrogyria and drop attack seizures, surgical treatment of the epilepsy should be considered cautiously, and sleep EEG recordings should be performed systematically.

Success stories in the implementation of universal hepatitis B vaccination: an update on Italy.

Compulsory universal vaccination against hepatitis B was introduced in 1991 in Italy for all newborns and 12-year-olds. Despite the decreasing circulation of the virus noted in the late-1980s, it was clear that only universal immunization would control hepatitis B infection and limit the transmission of the virus. Data collected during the first six years after vaccination was implemented show the success of the strategy. Over 90% of infants in the country and adolescents living in north-central Italy were immunized. Since 1995, the decrease in acute cases of hepatitis B has accelerated in the age groups 0-14 and 15-24, particularly in two regions of the north; during the same period, no comparable decrease in incidence was seen in older age groups. Monitoring coverage of vaccination and incidence of acute disease and seroepidemiological studies will continue and should show a rapid progression towards the elimination of HBV circulation in the country.

Bilateral periventricular nodular heterotopia with mental retardation and syndactyly in boys: a new X-linked mental retardation syndrome.

Bilateral periventricular nodular heterotopia (BPNH) is a recently recognized malformation of neuronal migration, and perhaps proliferation, in which nodular masses of gray matter line the walls of the lateral ventricles. Most affected individuals have epilepsy and normal intelligence with no other congenital anomalies. A striking skew of the sex ratio has been observed because 31 of 38 probands have been female, and one gene associated with BPNH was recently mapped to chromosome Xq28. We report three unrelated boys with a new multiple congenital anomaly-mental retardation syndrome that consists of BPNH, cerebellar hypoplasia, severe mental retardation, epilepsy, and syndactyly. Variable abnormalities included focal or regional cortical dysplasia, cataracts, and hypospadius. We hypothesize that this syndrome involves the same Xq28 locus as isolated BPNH, and we review the expanding number of syndromes associated with BPNH.