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BACKGROUND: We previously demonstrated that a hand hygiene program, including hand sanitizer and educational measures, for day care center (DCC) staff, children, and parents was more effective than a soap-and-water program, with initial observation, in preventing respiratory infections (RIs) in children attending DCCs. We analyzed the cost-effectiveness of these programs in preventing RIs. METHODS: A cluster, randomized, controlled and open study of 911 children aged 0 to 3 years, attending 24 DCCs in Almeria. Two intervention groups of DCC-families performed educational measures and hand hygiene, one with soap-and-water (SWG) and another with hand sanitizer (HSG). The control group (CG) followed usual hand-washing procedures. RI episodes, including symptoms, treatments, medical contacts, complementary analyses, and DCC absenteeism days, were reported by parents. A Bayesian cost-effectiveness model was developed. RESULTS: There were 5201 RI episodes registered. The adjusted mean societal costs of RIs per child per study period were CG: €522.25 (95% confidence interval [CI]: 437.10 to 622.46); HSG: €374.53 (95% CI: 314.90 to 443.07); SWG: €494.51 (95% CI: 419.21 to 585.27). The indirect costs constituted between 35.7% to 43.6% of the total costs. Children belonging to the HSG had an average of 1.39 fewer RI episodes than the CG and 0.93 less than the SWG. It represents a saving of societal cost mean per child per study period of €147.72 and €119.15, respectively. The HSG intervention was dominant versus SWG and CG. CONCLUSIONS: Hand hygiene programs that include hand sanitizer and educational measures for DCC staff, children, and parents are more effective and cost less than a program with soap and water and initial observation in children attending DCCs.

Bronchiolitis has a high morbidity in children under 2 years old. Respiratory syncytial virus (RSV) is the most common pathogen causing the disease. At present, there is only a costly humanized monoclonal RSV-specific antibody to prevent RSV. However, different immunization strategies are being developed. Hence, evaluation and comparison of their impact is important for policymakers. The analysis of the disease with a Bayesian stochastic compartmental model provided an improved and more natural description of its dynamics. However, the consideration of different age groups is still needed, since disease transmission greatly varies with age. In this work, we propose a multivariate age-structured stochastic model to understand bronchiolitis dynamics in children younger than 2 years of age considering high-quality data from the Valencia health system integrated database. Our modeling approach combines ideas from compartmental models and Bayesian hierarchical Poisson models in a novel way. Finally, we develop an extension of the model that simulates the effect of potential newborn immunization scenarios on the burden of disease. We provide an app tool that estimates the expected reduction in bronchiolitis episodes for a range of different values of uptake and effectiveness.

Background Several immunisation candidates against RSV are in late-stage clinical trials. To evaluate the benefits of a potential vaccination programme, both economic and health benefits will be needed. Health benefits are usually measured in Health-related Quality of Life (HRQoL) loss using standardised questionnaires. However, there are no RSV-specific questionnaires validated for children under 2 years, in whom most RSV episodes occur. Therefore, HRQoL estimates are taken from literature or inadequate tools. We determined HRQoL loss and direct costs due to an RSV episode in children younger than 2 years and their caregivers during a month of follow up, using a new questionnaire administered online. Methods An observational prospective multicentre surveillance study was conducted in children aged younger than two years. Children were recruited from 8 primary care centres and 1 hospital in the Valencia region and Catalonia (Spain). RSV-positive cases were obtained by immunochromatographic test. HRQoL was assessed using a new ad-hoc 38 item-questionnaire developed. Parents of infected children completed 4 questionnaires at four timepoints (day 0, 7, 14 and 30) after diagnosis. Results 117 children were enrolled in the study and 86 (73.5%) were RSV + . Median (interquartile range; IQR) scores were 0.52 (0.42-0.68), 0.65 (0.49-0.79), 0.82 (0.68-0.97) and 0.94 (0.81-1), for days 0, 7, 14 and 30, respectively. Compared to total recovery (Q30), HRQoL loss was 37.5%, 31.5% and 8.9% on days 0, 7 and 14 since diagnosis of the disease. The total median cost per patient (including treatments) was euro598.8 (IQR: 359.63-2425.85). Conclusions RSV had almost 40% impact on HRQoL during the first week since onset of symptoms and the median cost per episode and patient was about euro600. These results represent a substantial input for health-economic evaluations of future RSV-related interventions such as vaccination.

Background: Several studies have shown a substantial impact of Rotavirus (RV) vaccination on the burden of RV and all-cause acute gastroenteritis (AGE). However, the results of most impact studies could be confused by a dynamic and complex space-time process. Therefore, there is a need to analyse the impact of RV vaccination on RV and AGE hospitalisations in a space-time framework to detect geographical-time patterns while avoiding the potential confusion caused by population inequalities in the impact estimations. Methods: A retrospective population-based study using real-world data from the Valencia Region was performed among children aged less than 3years old in the period 2005-2016. A Bayesian spatio-temporal model was constructed to analyse RV and AGE hospitalisations and to estimate the vaccination impact measured in averted hospitalisations. Results: We found important spatio-temporal patterns in RV and AGE hospitalisations, RV vaccination coverage and in their associated adverted hospitalisations. Overall, similar to 1866 hospital admissions for RV were averted by RV vaccination during 2007-2016. Despite the low-medium vaccine coverage (similar to 50%) in 2015-2016, relevant 36 and 20% reductions were estimated in RV and AGE hospitalisations respectively. Conclusions The introduction of the RV vaccines has substantially reduced the number of RV hospitalisations, averting similar to 1866 admissions during 2007-2016 which were space and time dependent. This study improves the methodologies commonly used to estimate the RV vaccine impact and their interpretation.

BackgroundEstimate the incidence of herpes zoster (HZ), its complications and healthcare utilization rates in adults (>= 18-years-old) with a wide range of immunocompromised (IC) conditions compared to IC-free cohort.MethodA population-based retrospective study using the Valencia healthcare Integrated Databases (VID) (2009-2014). HZ and IC were defined using ICD-9 codes in primary care (PC) and hospitalization registers. Incidence rates (IR), risk of HZ, HZ-recurrence, HZ-complications and healthcare utilization rates were estimated in the IC-cohort compared to IC-free.ResultsThe study population consisted of 4,382,590 subjects, of which 578,873 were IC (13%). IR (in 1000 persons-year) of HZ overall, in IC and in IC-free cohort was 5.02, 9.15 and 4.65, respectively. IR of HZ increased with age in both cohorts and it was higher for all IC conditions studied, reaching up to twelvefold in subjects with stem cell transplantation. IC subjects had 51% higher risk of developing HZ, 25% higher HZ-recurrence and the risk of HZ-complications was 2.37 times higher than in IC-free. HZ-related healthcare utilization was higher in the IC-cohort than in IC-free (number of hospitalizations 2.93 times greater, hospital stays 12% longer, 66% more HZ-specialist visits, 2% more PC visits, sick leaves 18% longer and 20% higher antiviral dispensation).ConclusionsPatients suffering from all the IC conditions studied are at higher risk of developing HZ, HZ-recurrence and post-herpetic complications, which implies a substantial morbidity and a high consumption of resources. These results should be considered for vaccine policy implementation.

Introduction: Mother-to-child transmission (MTCT) is relevant in the global epidemiology of human immunodeficiency virus (HIV), as it represents the main route of infection in children. The study objectives were to determine the rate of HIV-MTCT and its epidemiological trend between the Spanish-born and immigrant population in Catalonia in the period 2000-2014. Methods: A prospective observational study of mother-child pairs exposed to HIV, treated in 12 hospitals in Catalonia in the period 2000-2014. HIV-MTCT rate was estimated using a Bayesian logistic regression model. R and WinBUGS statistical software were used. Results: The analysis included 909 pregnant women, 1,009 pregnancies, and 1,032 children. Data on maternal origin was obtained in 79.4% of women, of whom 32.7% were immigrants, with 53.0% of these from sub-Saharan Africa. The overall HIV-MTCT rate was 1.4% (14/1,023; 95% CI; 0.8-2.3). The risk of MTCT-HIV was 10-fold lower in women with good virological control (P=.01), which was achieved by two-thirds of them. The proportion of immigrants was significantly higher in the period 2008-2014 (P

Objectives: To estimate the incidence and burden of postherpetic neuralgia (PHN) and to investigate risk factors for PHN in the Valencia Region of Spain. Methods: Data were extracted from population and healthcare databases from the Valencia Region (2009-2014). Herpes zoster (HZ) and PHN were defined using ICD-9 codes and drug prescriptions in people aged >= 50 years. The risk of HZ patients for developing PHN and potential risk factors (diabetes mellitus, COPD and heart failure) were investigated. A survival analysis was developed to estimate the cumulative hazard of developing HZ and PHN between ages 50-90 years. Results: From a total of 2,289,485 subjects, 87,086 cases of HZ were registered, 13,658 (15.7%) of whom developed PHN. PHN risk was higher in women and increased sharply with age and comorbidities as diabetes mellitus, COPD and heart failure. The cumulative risk of developing HZ between ages 50-90 years was 31.7% (95% Cl: 31.3-32.1) and 6.9 (95% Cl: 6.7-7.1) for PHN. Conclusions: PHN risk was higher in women and increased with age and comorbidities. At least 32% and 7% of people will develop HZ and PHN, respectively, between ages 50-90 years. These results should be considered for vaccine policy implementation. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Background: Rotavirus vaccines are available in Spain from 2007. They are recommended by the Spanish Pediatric Association, but not funded by the National Health System (NHS) and its coverage rate reached 40-50%. The hospitalization rate reduction of rotavirus caused gastroenteritis (RVAGE) directly attributable to vaccination remains unclear due to the large differences described in published studies, ranging from 14 to 44.5% in children

Objectives: To assess the effectiveness of the HPV vaccines in preventing genital warts in young women. Design: Population-based study using health databases. Setting: Valencian Community (Spain). Participants: All girls and women aged 14-19 years who were registered in the Valencian Community between January 2009 and December 2014 (n = 279,787). Main outcome measures: Incident cases of genital warts were defined as the first activation of diagnosis code ICD-9-CM 078.11 (Condyloma acuminatum) in primary care and outpatient clinics during the study period. Results: There were 612 cases of genital warts. The overall incidence rate was 75.8/100,000 person-years (95% CrI 69.7-81.8). There was a decrease in genital warts when female candidates to be vaccinated with quadrivalent HPV vaccine reached the age of 18 (in 2012), compared to previous years. Incidence of genital warts in unvaccinated women and those who received the bivalent vaccine was higher than in girls and women who received the quadrivalent HPV vaccine. The effectiveness of a three-dose regimen of the quadrivalent HPV vaccine was 77% (95 Crl: 66-85%), whereas that of a single dose was 61% (95 Crl: 2087%). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine. Conclusions: Three doses of the quadrivalent HPV vaccine were effective against genital warts in our population. Moreover, with low vaccine coverage the incidence of genital warts decreased only in the vaccinated. (C) 2017 Elsevier Ltd. All rights reserved.

Objective: To describe Acute Otitis Media (AOM) in children aged 4 years or less and antibiotic prescription for AOM in vaccinated and not vaccinated with Pneumococcal Conjugate Vaccine (PCV).Methods: Retrospective cohort of children 2 months to 5 years of age, born between 2008 and 2013 in Valencia. Data was obtained from the Valencian health electronic databases (covering over 95% of the population). All databases were linked through a unique personal identification number. AOM diagnoses (CIE-9 381 and 382) and antibiotic prescriptions were retrieved from the primary care databases. A child was considered vaccinated when at least one dose of the vaccine was registered prior to diagnosis, and completely vaccinated if received two doses at age 6 months and a booster after 12 months of age.Results: From a cohort of 480.558 children, 382.853 cases of OMA were diagnosed in 217.063 children (45,17% of the study cohort). 60,2% of the children received at least one dose of PVC vaccine (44,7% completed vaccination). 53,33% of the completely vaccinated were diagnosed of AOM and 36,23% in non-vaccinated. Antibiotic was prescribed in 74,33% of the AOM episodes, with no difference between vaccinated and non-vaccinated. Amoxicillin-clavulanate was the most prescribed antibiotic (31,02%) with no difference between vaccination groups. No change in the antibiotic prescription occurred by calendar year.Conclusions: There are both a high incidence of AOM diagnosis in children aged 4 years or less in Valencia and a clear inappropriate antibiotic prescription for AOM. These drive to a lack of impact of PCV vaccination in antibiotic prescriptions.

Background: Although rotavirus vaccines have been licensed in Spain for over 8 years, they are not funded by its public health systems. The analysis of their effectiveness in the Valencia Region could better inform decisions about potential inclusion in the official immunization schedule. Our aim was to assess the effectiveness of Rotarix (R) (RV1) and RotaTeq (R) (RV5) against rotavirus hospitalizations. Methods: We conducted a retrospective cohort study using the region's health care databases, among resident children aged

Oxidative stress is associated with alterations in arachidonic acid (AA) metabolism. The present work was performed to assess the effect of the oxidant tert-butyl hydroperoxide on the release of AA from rat hepatocytes, and the possible preventive actions of estrogens on this effect. The exposure of [14C]-prelabeled cells to tertbutyl hydroperoxide produced the mobilization of [14C]-AA from hepatocyte lipids, both an intracellular [14C]-AA accumulation and an increased release of [14C]-products into the medium being observed. The formation of lysophospholipids was also enhanced significantly in the presence of the oxidant, thus suggesting the involvement of phospholipase A2 (E.C. 3.1.1.4) in the hepatocyte response to tert-butyl hydroperoxide. Estradiol and 2-hydroxyestradiol (25-100 microM) added in vitro to cell suspensions prevented significantly the oxidant- mediated stimulation of AA release, this effect probably being caused by the estrogen inhibitory actions against cellular lipid peroxidation.

The in vitro addition of 17 beta-estradiol (0-100 microM) to isolated rat hepatocytes efficiently prevented cellular lipid oxidation induced by the Fe(III)/ADP complex. 17 beta-estradiol was found to be less effective than its metabolic derivative 2-hydroxyestradiol. The presence of specific inhibitors of cytochrome P450 activity significantly diminished the antioxidant capacity of estradiol. These observations support the hypothesis that estradiol, in the micromolar range, inhibits iron-induced lipid peroxidation in liver cells by diverting reducing equivalents from the peroxidative process to its own metabolism.

The regulatory properties of the divalent metal ions Mg2+, Ca2+ and Mn2+ on the activity and kinetic behaviour of rat liver microsomal cholesterol esterase were studied in vitro. Mg2+ and Ca2+ exhibited similar concentration and preincubation time-dependent increases in esterase activity, with maximal stimulation at a concentration of 2 mM. However, Mn2+ had no effect at this concentration but displayed a potent inhibitory effect at concentrations above 20 mM. Activation of cholesterol esterase by Mg2+ and Ca2+ was selective in relation to i) the changes that cations produced in the enzyme kinetic constants, and ii) the chelating agents that reversed the metal ion-induced activation. Hence, the maximum rate of cholesterol ester hydrolysis doubled in the presence of Mg2+ and activation was reversed by EDTA, whereas a significant decrease in the apparent Km for cholesterol oleate was found when Ca2+ was added and this effect was blocked by ATP and EGTA. Both cations were able to reactivate cholesterol ester hydrolase activity in metal-depleted microsomes.

The basal activity of neutral cholesterol esterase (CEase) in isolated hepatocytes from fed rats showed a characteristic variation during incubation with an initial rise at 30 min and subsequent significant decrease at 2 h. Addition of estradiol (10(-4)M) not only prevented this decrease but also caused an early increase in the activity of the enzyme (125% above basal value) after 60 min of incubation. The simultaneous addition of dibutyryl cyclic AMP (db-cAMP) (10(-5)M) blocked the induction, whereas the cyclic nucleotide alone inhibited significantly the esterase activity. When hepatocyte suspensions were incubated in the presence of different fatty acids (oleate, myristate and laurate, initial concentration 1 mM) for a period of 1 h, a reduction in the CEase activity was observed. The present results suggest that the activity of rat liver neutral CEase may be under both direct and indirect hormonal control.