IntroductionHerpes zoster (HZ) chiefly affects older individuals and the immunocompromised and may lead to persistent pain, postherpetic neuralgia (PHN), and other complications.MethodsFrom 2012–2015, we conducted a prospective observational cohort study of adults ≥50 years with HZ presenting in primary care in Spain (NCT01521286). We estimated HZ incidence rates (IR) per 1,000 person-years (PY) over a 12-month period, and prospectively followed up a broader patient cohort; assessing pain severity using the ‘Zoster Brief Pain Inventory (ZBPI) and PHN development (defined as ZBPI ‘worst pain’ ≥3 at Day 90).ResultsHZ IR in adults ≥50 years was 4.88/1,000 PY (95% confidence interval [CI]: 4.44–5.35), similar for both genders. Incidence increased with age, from 2.54 (95% CI: 1.84–3.41) in 50–54-year-olds to 6.40/1,000 PY (95% CI: 4.86–8.28) in 75–79-year-olds. In 545 HZ patients followed prospectively, the proportion of HZ patients with PHN was 4.59% (95% CI: 2.99–6.70); and 11.79% (95% CI: 7.78–16.91) in those 212 patients with available ZBPI scores at Day 90. The proportion of patients developing PHN increased with increasing age. Mean ZBPI ‘worst pain’ scores in patients not developing PHN showed a marked decline between Day 0–30 (from 5.4 to 1.6) and none at Day 90; in patients with PHN this score remained high (>5.5) up to Day 150. Other complications were observed in 10.3% of patients.ConclusionsHZ presents a considerable burden in adults aged ≥50 years in Spain, with an IR of ~5/1,000 PY. HZ and PHN risk increased with age.

Herpes zoster (HZ) mainly affects older adults and immunocompromised individuals and is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain lasting for months or years. This study (ClinicalTrials.gov Identifier: NCT01772160) aimed to estimate the HZ incidence and the proportion of HZ patients with PHN in the Italian population aged 50 years or older. From 2013 to 2016, HZ-patients were recruited when presenting with acute HZ at 75 reporting general practitioners in Italy, covering 43,875 persons aged >= 50 years. PHN was defined as 'worst pain' rated >= 3 on the Zoster Brief Pain Inventory persisting or appearing over 90 days after rash onset. The overall HZ incidence rate per 1000 person-years (PY) was estimated as 6.46 (95% confidence interval [CI]: 5.99-6.95), increasing with age to 9.12/1000 PY (95% CI: 7.50-10.99) in 75-79 year-olds. Among 391 HZ-patients who completed the study, the overall proportion with PHN was 10.23% (95% CI: 7.41-13.67) and the highest proportion was 15.56% (95% CI: 6.49-29.46) for the 75-79 year-olds. Among the 128 patients (32.7%) who reported at least one pre-existing medical condition, 35.9% reported diabetes mellitus and 32.0% reported emotional problems, stress or depression. The study confirms previous findings that HZ and PHN cause an important clinical burden in older Italian adults. It also confirmed the age-related increasing risk of HZ and PHN.

BACKGROUND:We estimated the relative efficacy and safety of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials. METHODS:A systematic literature review evaluated two different HZ vaccines: adjuvanted recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (incidence of HZ and postherpetic neuralgia [PHN]) and safety (serious adverse events [SAE] and reactogenicity [injection-site reactions, systemic reaction]) outcomes. Primary analyses included frequentist NMAs with fixed effects for efficacy outcomes, due to limited data availability, and both fixed and random effects for safety and reactogenicity outcomes. As age is a known effect modifier of vaccine efficacy (VE), VE analyses were stratified by age. RESULTS:RZV demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VERZV = 0.92 (95% confidence interval [95%CI]: 0.88, 0.94), VEZVL = 0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VERZV = 0.91 (95%CI: 0.87, 0.94), VEZVL = 0.37 (95%CI: 0.25, 0.48)). Similarly, RZV demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VERZV = 0.89 (95%CI: 0.70, 0.96), VEZVL = 0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VERZV = 0.89 (95%CI: 0.69, 0.96), VEZVL = 0.67 (95%CI: 0.44, 0.80)). RZV was associated with significantly more injection-site and systemic reactions compared to most formulations of ZVL and placebo, however definitions and data collection procedures differed across the included studies. There were no statistically significant differences found between RZV and any formulation of ZVL or placebo for SAEs. CONCLUSION:RZV is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA, compared with ZVL. As anticipated with an adjuvanted vaccine, RZV results in more reactogenicity following immunization. No differences in SAEs were found between RZV and ZVL.

Cost-effectiveness analyses (CEAs) are increasingly requested by Health Care Authorities to take rational decisions on resource allocation. Single endpoint observations (EOs), used as inputs for CEAs may vary considerably depending on available sources. When comparing vaccines, the selected source for vaccine effectiveness/efficacy(VE)-inputs has a significant impact on CEA-outcomes (CEAOs). Probabilistic approaches, addressing values within a plausible VE-range instead of single EOs are gaining importance to manage parameter uncertainties and to outbalance interpretations of CEAOs. The aim of this study is to understand the importance of input-uncertainties according to different sources, when comparing non-typeable Haemophilus influenzae protein D (PHiD-CV) and 13-valent pneumococcal conjugate vaccines (PCV13). Plausible VE-ranges for serotype (ST)3, ST19A, non-typeable Haemophilus influenzae (NTHi ; only against acute otitis media) and net herd protection were based on 95%CI from controlled efficacy/effectiveness studies. A published static Markov model comparing both vaccines for Canada was adapted to use EOs or uniform probabilistic VE-estimations (UPVs) within their plausible ranges. Endpoints: 1.5%-discounted averages and percentiles 2.5 and 97.5 (%ile2.5;%ile97.5) for incremental direct costs (ΔDC, k€) and Quality-Adjusted-Life-Years (ΔQALYs), excluding(excl.) and including(incl.) a probabilistic sensitivity analysis (PSA) for other inputs. Presented are ΔDC(%ile2.5;%ile97.5); ΔQALYs(%ile2.5;%ile97.5) using EOs: -23,521(na ;na); 365(na ;na) excl.PSA and -23,569(-25,354;-21,976); 384(-176;1,036) incl.PSA, using UPV (excl.PSA) for VE_ST3: -23,534(-23,574;-23,495); 367(361;373), for VE_ST19A: -23,524(-23,604;-23,444); 365(352;378), for VE_Herd: -23,531(-24,115:-22,942); 367(264;470), for VE_NTHi: -23,073(-25,124;-20,973); 203(-555;943) and using UPVs for all_4_VEs: -23,078(-25,259;-20,959); 216(-563;966) excl.PSA and -23,111(-25,765;-20,596); 219(-678;1,189) incl.PSA. This study allowed to understand the importance of the choice of VE-assumptions for CEAs: overall CEAO was not significantly impacted by the choice of VE against ST3 and ST19A and for herd effect. Varying VE against NTHi however affected the variability of CEAO the most. PHiD-CV remained dominant over PCV13 independently of using EOs or UPVs.

SUMMARY Invasive group A streptococcal (iGAS) infections cause severe disease and death, especially in residents of long-term care facilities (LTCFs). In order to inform iGAS prevention, we compared the risk of iGAS in LTCF residents and community residents. We identified LTCF residents among cases of iGAS from national surveillance (2009–2010) using postcode matching, and cases of hospital-acquired infections via hospital admission records. We used Poisson regression to calculate incidence rate ratios (IRR) and logistic regression to explore factors associated with case fatality rate (CFR). A total of 2741 laboratory-confirmed iGAS cases were matched to a hospital admission: 156 (6%) were defined as hospital-acquired. Out of the total cases, 96 (3·5%) were LTCF residents. Compared with community residents, LTCF residents over 75 years of age had a higher risk of iGAS infection (IRR = 1·7; 95% CI 1·3–2·1) and CFR (OR = 2·3; 95% CI 1·3–3·8). Amongst community-acquired cases, the risk of iGAS in LTCF residents between 75 and 84 years of age doubled (IRR = 2·7; 95% CI 1·8–3·9) compared with their community counterparts. The CFR among community-acquired cases was higher in LTCF residents than community residents (21% vs. 11%). Age remained associated with death in our final model. Our study showed that, even controlling for age, LTCF residents have a higher risk of acquiring and dying from iGAS. Whilst existing co-morbidities may explain this, it is reasonable to assume that the institutional setting may facilitate transmission. Therefore, cases in LTCF require prompt investigation together with a better understanding of factors contributing to the acquisition of infection.

Head-to-head clinical efficacy randomized controlled trials (RCTs) for vaccines are often unfeasible due to logistical and/or ethical constraints and comparative real-world effectiveness studies are methodologically challenging. Without direct efficacy or effectiveness comparisons, relative risk/benefit of vaccines can be challenging to assess. While network meta-analyses (NMAs) have been used extensively to estimate the comparative efficacy and safety of therapeutic interventions, the application of this method to compare vaccines is rare. To our knowledge, there is only one published vaccine NMA which compares the relative effectiveness of rotavirus vaccines. We discuss how NMAs can be used to evaluate the relative efficacy and safety of vaccines within a specific disease area; using vaccines to prevent herpes zoster (HZ) as another case example. NMA methodology can be applied to indirectly compare vaccines; however, issues such as waning immunity, indirect vaccine effect, changing epidemiology over time, and seasonality of the disease of interest pose unique challenges. Detailed feasibility assessments should be undertaken to systematically determine if NMA is appropriate from a methodological and clinical perspective. This requires close collaboration between methodologists and clinical experts. Recently, a comparison of vaccines for HZ was deemed feasible, in particular due to availability of evidence studied in large, well-designed RCTs, and due to the epidemiology of HZ. Key challenges faced included variations in effect modifiers such as patient age, follow-up duration, and outcome definitions. It was possible to leverage existing NMA guidance to provide credible and reliable estimates of the relative effect of HZ vaccines that have not been studied in head-to-head efficacy trials. NMAs provide a method to indirectly compare different medical interventions, including vaccines, in the absence of head-to-head data. With RCT data and real world evidence, NMAs can contribute to inform vaccine recommendations and public health decision making.

To perform a systematic literature review (SLR) of efficacy and reactogenicity/safety of vaccines for herpes zoster in adults ≥ 50 years of age based on evidence from randomized controlled trials. A systematic search was performed in May 2017 using predefined terms in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials in addition to manual searches of relevant non-indexed conferences. Standard SLR methodology was used to select relevant publications using predefined Population, Intervention, Comparators, and Study Design (PICOS) criteria. Quality was assessed at the trial level using the Cochrane Risk of Bias tool. Key outcomes extracted included efficacy (against herpes zoster (HZ), post-herpetic neuralgia, and other HZ complications, as well as HZ burden of illness mean score) and reactogenicity/safety (injection site/local reactions, systemic/general reactions, vaccine-associated systemic/general reactions, total discontinuations, and serious adverse events). Of 1,290 unique publications retrieved for screening, 25 publications (associated with 21 unique trials and 108,678 patients) were included. There were 21 full texts and four conference abstracts all published between 1998 and 2017. Only two HZ vaccines were evaluated in the included studies: the candidate HZ adjuvanted subunit vaccine and Zoster Vaccine Live, although various routes of administration, formulations, doses, and schedules were assessed. Eight included articles (representing four trials and one sub-study) reported efficacy outcomes of interest, while 23 articles (representing 20 trials) reported reactogenicity/safety outcomes of interest. This SLR provides a comprehensive overview of the literature reporting on the efficacy and reactogenicity/safety of HZ vaccines. Vaccines against HZ demonstrated favourable benefit risk profile. Given no head-to-head efficacy studies were identified, the relative merits of the individual formulations should be explored. Further investigation is needed to examine the appropriateness and feasibility of combining the extracted outcomes using meta-analysis or network meta-analysis and to define the best methodology to be used.

Introduction : Le département de l’Isère a réalisé une étude sur la couverture vaccinale et les lieux de vaccination des enfants scolarisés en Isère. L’objectif de cet article est de présenter la méthode, originale et robuste, utilisée dans cette étude. Nous décrirons également la participation à l’étude. Méthodes : Une étude transversale a été réalisée chez les enfants de quatre ans en 2010/2011 à l’occasion des bilans de santé en école maternelle. Cent écoles ont été tirées au sort selon un plan de sondage complexe. Les carnets de vaccination de tous les élèves examinés en bilan ont été photographiés. Les données ont été apurées et redressées. La participation des enfants à l’étude a été étudiée en distinguant les motifs d’exclusion liés au mode de recueil des données ou propre aux bilans de santé. Les facteurs étudiés concernaient les caractéristiques intrinsèques des écoles et des données d’organisation des bilans. Résultats : Sur 100 écoles enquêtées, 2588 élèves ont été inclus dans l’étude pour un taux de participation de 85,1 %. Parmi les élèves sélectionnés, 9,6 % étaient exclus pour des motifs propres aux bilans et 5,3 % pour des motifs spécifiques à l’étude. La participation était meilleure pour les élèves examinés par une équipe de Protection maternelle et infantile (PMI) spécialisée dans les bilans. Il s’agit du seul facteur qui semble jouer sur la participation classique des élèves au bilan de santé en école maternelle. Discussion : Ce résultat est probablement généralisable aux autres missions de la PMI, et apporte un élément important pour l’organisation des activités de la PMI.

INTRODUCTION:The Isère department has carried out a study on vaccination programmes and sites of vaccination among schoolchildren in Isère. The objective of this article is to present the original and robust method used in the study. We also describe the participation rate in the study.METHODS:A cross-sectional study was conducted among 4-year-old children in 2010/2011 during nursery school checkups. One hundred schools were randomly selected according to a complex sampling plan. The vaccination records of all children examined at checkups were photographed and data were cleared and adjusted. The participation of children in the study was investigated by distinguishing the reasons for exclusion from the study due to the mode of data collection and due to factors specific to the checkups. The factors studied concerned the intrinsic characteristics of the schools as well as data on organisation of the checkups. A total of 2,588 children from the 100 schools surveyed were included in the study, corresponding to a participation rate of 85.1%.RESULTS:9.6% of the children selected were excluded for reasons specific to the checkups and 5.3% for reasons related to the study. Participation was higher for children examined by a team from the Maternal and Child Protection Unit (PMI: Protection maternelle et infantile), specialised in checkups. This was the only factor that appeared to impact the typical attendance of children at in nursery school health checkups.DISCUSSION:This result can probably be generalised to the other tasks of the PMI and provides important information for the future organisation of the PMI's activities.

In January-March 2013 in England, confirmed measles cases increased in children aged 10-16 years. In April-September 2013, the National Health System and Public Health England launched a national measles-mumps-rubella (MMR) campaign based on data from Child Health Information Systems (CHIS) estimating that approximately 8% in this age group were unvaccinated. We estimated coverage at baseline, and, of those unvaccinated (target), the proportion vaccinated up to 20/08/2013 (mid-point) to inform further public health action. We selected a sample of 6644 children aged 10-16 years using multistage sampling from those reported unvaccinated in CHIS at baseline and validated their records against GP records. We adjusted the CHIS MMR vaccine coverage estimates correcting by the proportion of vaccinated children obtained through sample validation. We validated 5179/6644 (78%) of the sample records. Coverage at baseline was estimated as 94.7% (95% confidence intervals, CI: 93.5-96.0%), lower in London (86.9%, 95%CI: 83.0-90.9%) than outside (96.1%, 95%CI 95.5-96.8%). The campaign reached 10.8% (95%CI: 7.0-14.6%) of the target population, lower in London (7.1%, 95%CI: 4.9-9.3) than in the rest of England (11.4%, 95%CI: 7.0-15.9%). Coverage increased by 0.5% up to 95.3% (95% CI: 94.1-96.4%) but an estimated 210,000 10-16 year old children remained unvaccinated nationally. Baseline MMR coverage was higher than previously reported and was estimated to have reached the 95% campaign objective at midpoint. Eleven per cent of the target population were vaccinated during the campaign, and may be underestimated, especially in London. No further national campaigns are needed but targeted local vaccination activities should be considered.

On 22 March 2013, 150 of 1,255 students (13–17 years) and staff at a school in London reported gastrointestinal symptoms; onset peaked 8 to 12 hours after a lunch served in the school on 21 March. We performed a retrospective cohort study of all students and staff. We defined cases as school attenders on 20 and 21 March with onset of gastrointestinal symptoms between 20 and 23 March. We tested food, environmental and stool samples of cases for common pathogens and bacterial toxins. We administered an online questionnaire via email, encouraging the use of smartphones to respond, to measure risk of illness for food items eaten at school on 20 and 21 March. Survey response was 45%. Adjusted risk ratios were generated in a multivariable analysis. Those who ate chicken balti on 21 March were 19.3 times more likely to become ill (95% confidence interval: 7.3–50.9). Clostridium perfringens was detected in all 19 stool samples collected. Within eight school hours of its launch, 412 of 561 (73%) responders had completed the survey. Hygienic standards in the kitchen were satisfactory. The investigation was done rapidly due to smartphone technology and we recommend considering this technology in future outbreaks.

INTRODUCTION:A few number of literature specifically addresses vaccination uptake among Public Health Residents (PHRs). Influenza vaccine attitudes and risk perceptions of PHRs across Italy were studied, contributing to literature on influenza vaccination uptake predictors, in particular among young physicians. METHODS:An online survey was conducted in 25 Schools of Public Health in Italy in 2011-2012. Results were analysed using prevalence and logistic regression methods. RESULTS:A total of 365 Italian public health residents were included in the study. Vaccination uptake was confirmed by 22.2 and 33.2% of PHRs in 2010-2011 and 2011-2012, respectively. For the 2010-2011 influenza season, vaccination was associated with male sex (adj-OR 3.43; 95% CI = 1.5-7.84) and vaccination history (adj-OR 29.44; 95% CI = 6.4-135.04). For the 2011-2012 season, vaccination was significantly associated with having had between one and three influenza vaccinations in the previous five years (adj-OR 11.56; 95% CI = 6.44-20.75) or more than three (adj-OR 13643; 95% CI = 30.8-604.7) and with individual participation in general population vaccination campaigns (adj-OR 1.85; 95% CI = 1.01-3.41). DISCUSSION:Italian residents in public health have no confidence and a low personal risk perception about vaccinations therefore taking no measures to protect patients, general population and themselves. Annual influenza vaccination acceptance is associated with influenza vaccine uptake in the previous years and personal involvement in general population vaccination campaigns. These factors should be considered for the design of future campaigns targeting public health residents.

Measles is a highly contagious and potentially fatal disease. Europe is far from the 95% coverage rates necessary for elimination of the disease, although a safe and cost-effective vaccine is available. We reviewed the literature on studies carried out in European countries from January 1991 to September 2011 on knowledge, attitudes and practices of health professionals towards measles vaccination and on how health professionals have an impact on parental vaccination choices. Both quantitative and qualitative studies were considered: a total of 28 eligible articles were retrieved. Healthcare workers are considered by parents as a primary and trustworthy source of information on childhood vaccination. Gaps in knowledge and poor communication from healthcare workers are detrimental to high immunisation rates. Correct and transparent information for parents plays a key role in parental decisions on whether to have their children vaccinated. Healthcare workers' knowledge of and positive attitudes towards measles-mumps-rubella (MMR) vaccination are crucial to meeting the measles elimination goal. An effort should be made to overcome potential communication barriers and to strengthen vaccine education among healthcare professionals.

L’articolo si concentra sull’opera per nastro magnetico “La voce dall’Inferno”. Inizialmente concepita come opera radiofonica, composta da Edoardo Torricella e Salvatore Sciarrino, vuole presentare attraverso le sonorità possibili con l’elettronica un approccio al mondo dei dannati che ne risvegli i rumori e le voci, l’acustica del luogo e le presenze. Su questi elementi si concentrerà anche il mio articolo, partendo dallo studio di un otologo sulla Commedia, ci si sposterà a questioni filosofiche ed estetiche che riguardano il rapporto tra la voce e lo spazio, tra la voce e il rumore e l’utilizzo dell’elettronica applicata alla voce. In modo particolare però si cercherà di concentrare l’attenzione, attraverso l’ascolto dell’opera, su di una tematica: come la voce influisca sulla percezione emotiva dell’ambiente sonoro. My essay focuses on the work for tape “La voce dall’Inferno”. Initially conceived as a radio opera, composed by Edoardo Torricella e Salvatore Sciarrino, “La voce dall’Inferno” wants to show through the sounds the world of damned with their noises, voices and their presence in that place. The electronic sounds and the possibilities open by record, freezing, generator and synthesis play an important role in the development and the aesthetic of the opera. On this elements will focus my article. We’ll move to philosophical and aesthetic issues that concern the relationship between voice and space, voice and noise, and the use of electronic instruments. In particular try to focus on a theme by listening to the opera: how the voice influences the emotional perception of the soundscape.