HPV vaccination and allocative efficiency: regional analysis of the costs and benefits with the bivalent AS04-adjuvanted vaccine, from the perspective of public health, for the prevention of cervical cancer and its pre-cancerous lesions

Introduction: by means of the decisions on whether to introduce the HPV vaccination, Public Health has already established the importance of associating the vaccination strategy to the policy of secondary prevention. The screening + vaccination strategy is more effective than the two methods taken individually. In support of this combined strategy and in order to make available per each region concrete elements for their regional planning, an assessment has been made, which also takes into account the effect of cross-protection regarding high-risk strains not contained in both vaccines, bivalent and quadrivalent, and more frequently responsible for pre-cancerous lesions and cervical cancer (CCU). This analysis evaluates the costs and benefits of screening + vaccination strategy in a 12-year-old female cohort. Furthermore, the paper provides results that may be useful to assess the opportunity to extend the vaccination to a second cohort of 24-25-year-old women. The analysis is preceded by a brief summary of CCU epidemiology available data, public health policies that give precise guidelines for vaccination strategies and analytical tools suitable to support public policy makers to efficiently allocate resources. Methods: two different models were used for two regional analyses.The vaccines may have different sustained- and cross-protection levels against non-vaccine oncogenic HPV-types. In the first analysis, a prevalence-based model estimated the potential net difference in HPV-related lesions (abnormal pap smear, cervical intraepithelial neoplasia (CIN), cervical cancer (CC) and genital warts (GW)) and associated costs generated by the two vaccines. Vaccine efficacy rates were based on published data for each vaccine. Lifetime vaccine efficacy was assumed. Results are reported over one year after reaching a steady state. Incidence and treatment costs were obtained from Italian and European sources. We also performed a cost-effectiveness analysis with a Markov model for each Italian region, previously described and successfully adapted to the national scenario. The analysis compares the HPV vaccination of a single cohort (12-year-old females) with a multiple cohort (12- + 25-year-old girls). Resource use was based on a standard therapeutic path applied to all regions. However we quantified the impact of the so-called "decentralization progress" by collecting regional data on: pap test coverage, tariffs for treatments, and cost of the vaccination course. Results: the results are set out in 21 regional reports. Conclusions: in the Italian scenario, characterized by decentralization and local autonomy, a further level of detail is essential in order to describe the specific local settings and implications of a new health intervention. The results show that the vaccination on a multiple cohort is more effective than a single cohort. Indeed, a major number of pre-cancerous lesions, cases of cancer, and related deaths are avoided. In a period of sharp decline in the health budget, investment in prevention seems to be the most reasonable choice in view of avoiding in the medium term pre-cancerous and cancerous lesions generating a significant expense. Our analysis places the extent of HPV vaccination among the measures that the regional decision-makers should put in place to maximize the efficiency of scarce resource

CMS DT Chambers: Optimized Measurement of Cosmic Rays Crossing Time in absence of Magnetic Field

Two spare drift chambers produced in the I.N.F.N. Legnaro Laboratory (Padova, Italy) for the barrel muon spectrometer of the LHC CMS experiment have been extensively tested using cosmic-ray muons. A fitting algorithm was developed to optimize the determination of the time of passage of the particle. A timing resolution of $\approx$2~ns has been obtained. The algorithm permits the measurement of the track reconstruction precision of the chambers by using cosmic-ray data with the same accuracy obtained using high-energy test-beam data

Detection and genotyping of human Papillomavirus in urine samples from unvaccinated male and female adolescents in Italy

The introduction of vaccination against Human Papillomavirus (HPV) in adolescent girls in 2006 has focused virological surveillance on this age group. As few studies have evaluated HPV infections in young populations, further data are needed in order to improve and extend prophylactic policy and to monitor epidemiological changes. The present study aimed at evaluating overall and type-specific HPV prevalence in both female and male adolescents in Italy. HPV DNA detection and genotyping was performed on urine samples collected from 870 unvaccinated adolescents (369 females, 501 males, 11-18 years of age) in five cities in Italy. Following DNA extraction by means of a commercial kit (NucliSENS®-miniMAG®, bioMérieux), the L1 gene fragment was PCR amplified and genotyped by restriction fragment length polymorphism analysis. HPV DNA was detected in 1.5% of all samples, and in 3% and 0.4% of samples from females and males, respectively. In approximately 70% of HPV DNA positive adolescents, the infection was due to a single genotype, with 88.9% of genotypes belonging to the HR-clade. The only two HPV-positive boys (14 and 18 years old) had HPV-70 genotype. Only one of the 11 HPV-infected girls was in the 11-14 age-group. HPV prevalence was 4.2% in girls aged 15-18 years and 60% of infections were due to vaccine types HPV-16 or HPV-6/-11. This is one of the few studies, the first conducted in Italy, on HPV infection in adolescents. Urine testing is the easier way of detecting HPV infection in younger populations. Our data revealed a very low HPV prevalence, and no infections were observed in the 12-year-old vaccine target population. The majority of infections were seen in females aged 15-18 years. Overall, more than 50% and 30% of the potentially persistent HPV infections detected in this group could have been prevented by the quadrivalent and the bivalent vaccines, respectively

Positivity to p-ANCA in patients with status epilepticus

BACKGROUND: Status epilepticus (SE) may occur in the setting of several internal or neurologic diseases. Anti-neutrophilic cytoplasmic antibodies (ANCA) are a group of Ig that may be observed in patients with different autoimmune disorders but are particularly associated with systemic vasculitis named ANCA-associated-vasculities (AAV). We herein report 3 patients with SE and positivity to p-ANCA. CASE PRESENTATION: One patient had a catastrophic evolution and died 5 months after disease onset. The other two patients had a good outcome and remained seizure-free at 30 months and 5 years of follow-up respectively. CONCLUSION: This report highlights the importance of considering ANCA dosage in patients with SE of unclear origin

Do the omeprazole family compounds exert a protective effect against influenza-like illness?

BACKGROUND: Infections by influenza viruses place a heavy burden on public health and economies worldwide. Although vaccines are the best weapons against influenza, antiviral drugs could offer an opportunity to alleviate the burden of influenza. Since omeprazole family compounds block the “proton pump”, we hypothesized that they could interfere with the mechanism of fusion of the virus envelope and endosomal membrane, thereby hindering the M2 proton pump mechanism of influenza viruses. METHODS: A matched case-control study was performed in 2010-2011 in Italy. Cases were subjects aged over 18 years with a diagnosis of Influenza-like Illness (ILI); 254 case-control pairs were recruited. A multivariable conditional logistic regression analysis was used to assess the association between the prevention of ILI and the administration of omeprazole family compounds. The interaction between omeprazole family compounds and influenza vaccination was also examined. RESULTS: After control for potential confounders, subjects treated with omeprazole family compounds displayed a lower risk of catching ILI (OR(adj) = 0.29, 95% CI: 0.15-0.52). The risk of ILI in unvaccinated non-OFC users was about six times than that in vaccinated OFC users. CONCLUSIONS: Although confirmation is necessary, these results suggest that omeprazole family compounds could be profitably used in the prevention of ILI

Measurement of Drift Velocity in the CMS Barrel Muon Chambers at the CMS Magnet Test Cosmic Challenge

This note reports the results of the analysis performed on the data collected by the CMS Barrel Muon system during the Magnet Test-Cosmic Challenge, aimed to study the Drift Tube chambers behavior at the nominal value of the CMS magnetic field. In particular, the analysis is devoted to the study of the drift velocity in the various equipped regions of the apparatus. It is shown that the drift velocity is significantly affected by the presence of a residual magnetic field in the chamber volume only in the innermost stations, MB1, of Wheel+2; where the maximal variation inside the chamber is of 4 percent, which does not prevent a good functionality of the DT trigger even in this most critical region

Computational methods for resting-state EEG of patients with disorders of consciousness

Patients who survive brain injuries may develop Disorders of Consciousness (DOC) such as Coma, Vegetative State (VS) or Minimally Conscious State (MCS). Unfortunately, the rate of misdiagnosis between VS and MCS due to clinical judgment is high. Therefore, diagnostic decision support systems aiming to correct any differentiation between VS and MCS are essential for the characterization of an adequate treatment and an effective prognosis. In recent decades, there has been a growing interest in the new EEG computational techniques. We have reviewed how resting-state EEG is computationally analyzed to support differential diagnosis between VS and MCS in view of applicability of these methods in clinical practice. The studies available so far have used different techniques and analyses; it is therefore hard to draw general conclusions. Studies using a discriminant analysis with a combination of various factors and reporting a cut-off are among the most interesting ones for a future clinical application

Marche

In Marche region 68% of women (aged 24-64) are screened regularly, meaning every 3 years. The analysis on cross-protective activity exercised by bivalent and quadrivalent vaccines shows that the bivalent vaccine could prevent more pre-cancerous lesions and cases of cervicocarcinoma than quadrivalent, and that the latter could prevent genital warts that are not prevented by bivalent. The major number of cases avoided by the bivalent make it possible to fully offset the cost savings related to warts associated with the quadrivalent vaccine. Furthermore, a cost-effectiveness analysis shows that, considering regional tariffs, the multiple cohort (12-year-old + 25-year-old women) vaccination strategy with a 90% coverage could prevent 18 cases of cervicocarcinoma and 8 related deaths more than the vaccination of only 12-year-old girls, and thus proves to be cost-effective (10,700 €/QALY)

Tobacco smoking among students in an urban area in Northern Italy

Introduction. Tobacco smoking, which usually begins in teen- age, is one of the most important lifestyle risk factors for chronic diseases and a major public health problem worldwide. The aims of the study were to determine the prevalence of tobacco smoking and the mean age of initiation among adolescents in Genoa (Italy) and to identify some socio-demographic predictors that could be associated with the onset of smoking. Materials and methods. 2,301 randomly selected students (14- 19 years old) in Genoa completed an ad hoc questionnaire. The Kaplan-Meier method was used to evaluate the instantaneous risk of experimenting with smoking. A multivariate logistic regression model was used to determine whether current or previous smoking status was associated with socio-demographic characteristics. Results. 59.5% of respondents had tried smoking, while 35.6% defined themselves as current smokers. No difference in current smoking prevalence emerged between males and females (35.2% and 35.9%, respectively, p = 0.83). The mean age on initiation was 13.5 years for males and 13.9 years for females. The instantaneous probability of trying smoking changed with age, reaching a maximum at 14 years. Subjects who tried smoking before this age were more inclined to con- tinue smoking. The probability of being a current smoker was significantly higher among students from unmarried-parent families and those attend- ing vocational and technical secondary schools. Conclusions. There is a great need for the activation of new health promotion interventions and enforcement of those already existing, in order to raise awareness of the damage caused by smoking among adolescents, especially those belonging to high- risk groups

Tolerability of new antiepileptic drugs:a network meta-analysis

Objective: The objective of this study was to perform a comparative assessment of tolerability of all licensed new antiepileptic drugs (AEDs) through a network meta-analysis (NMA) including all placebo-controlled double-blind clinical trials (RCTs) in all conditions in which these drugs have been tested. Methods: NMA with a frequentist approach was used to compare proportions of patients withdrawing because of adverse events (AEs). Analyses were conducted for all therapeutic doses pooled and specifically for high therapeutic doses. Patients treated with non-therapeutic doses of each drug were excluded. Results: A total of 195 RCTs were included in the current analysis, comprising a total of 28,013 patients treated with AEDs and 17,908 patients treated with placebo. RCTs included in the analysis were 8 for brivaracetam; 5 for eslicarbazepine; 22 for gabapentin; 7 for lacosamide; 14 for levetiracetam; 14 for lamotrigine; 6 for oxcarbazepine; 9 for perampanel; 50 for pregabalin; 5 for tiagabine; 36 for topiramate; 7 for zonisamide; 4 for gabapentin-extended formulation (ER); 2 each for levetiracetam-ER, lamotrigine-ER, and topiramate-ER; and 1 each for oxcarbazepine-ER and pregabalin-ER. Brivaracetam, gabapentin, gabapentin-ER, and levetiracetam had a significantly lower withdrawal rate compared to several other AEDs, while eslicarbazepine, lacosamide, oxcarbazepine, and topiramate had a higher withdrawal rate. Perampanel, lamotrigine, pregabalin, tiagabine, and zonisamide showed an intermediate pattern of tolerability. Additional analysis has been conducted through selection of highly recommended doses for each drug. This analysis has roughly confirmed results of head to head comparisons of the all-dose analysis, with some exceptions. A further analysis has been conducted after exclusion of RCTs in which patients were allocated to the therapeutic dose of the experimental drug without titration, and it failed to show clinically important differences. Significance: Relevant differences in short-term tolerability of AEDs have been observed between AEDs. Brivaracetam, gabapentin, and levetiracetam show the best tolerability profile while other AEDs are at higher risk for intolerable adverse effects