Effectiveness of self-financed rotavirus vaccines on acute gastroenteritis primary care episodes using real-world data in Spain: a propensity score-matched analysis of cohort study.

The objective of this study was to estimate, by a novel spatiotemporal approach in an environment of non-funded rotavirus (RV) vaccines, the RV vaccine effectiveness (VE) to prevent acute gastroenteritis primary care (AGE-PC)-attended episodes, demonstrating how indirect protection leads to underestimation of direct VE under high vaccine coverage (VC). This population-based retrospective cohort study used electronic healthcare registries including all children 2 months-5 years old, born from 2009 to 2018 in the Valencia Region (Spain). Direct RV VE preventing AGE-PC episodes was estimated using propensity score matching and Poisson regressions stratified by VC, adjusted by age and calendar season. Indirect VE was estimated by Poisson regression comparing AGE-PC rates in unvaccinated children among the different VC levels. A total of 563,442 children were included for the RV VC estimation; of them, 360,576 were included in the birth-cohort for VE analysis. RV VC showed strong variability among districts and seasons, rising on average from 21% in 2009/2010 to 55% in 2017/2018. The highest direct VE was found in vaccinated children from districts with 0-30% RV VC (16.4%) and the lowest in those from districts with ≥ 70% RV VC (9.7%). The indirect protection in unvaccinated children raised from 6 to 16.6% for those living with 20-30% and ≥ 70% VC, respectively. CONCLUSION: Considering that RV is the causative agent in 20% of AGE cases, a direct effectiveness of 82% preventing AGE-PC episodes due to RV could be deduced using a novel spatiotemporal approach. A reduction of 17% of AGE-PC episodes in unvaccinated was observed in areas with VC over 70% because of indirect protection. WHAT IS KNOWN: • The effectiveness of RV vaccines preventing hospitalizations due to RV-acute gastroenteritis (RV-AGE) has been extensively studied. However, RV also burdens the primary care (PC) setting, and data on vaccine effectiveness (VE) in preventing AGE-PC visits are scarce. • The RV vaccine distribution in Spain (non-funded), with large differences in vaccine coverage (VC) among healthcare districts, provides an ideal scenario to assess the actual VE in preventing AGE-PC consultations, including the direct and indirect protection. WHAT IS NEW: • A direct effectiveness of 82% preventing AGE-PC episodes due to RV could be deduced using a novel spatiotemporal approach. A reduction of 17% of AGE-PC episodes in unvaccinated was observed in areas with high VC because of indirect protection. • These findings, together with existing data on the impact on hospitalizations due to RV-AGE, offer valuable insights for implementing vaccination initiatives in countries that have not yet commenced such programs.

Child Care Center Hand Hygiene Programs' Cost-Effectiveness in Preventing Respiratory Infections.

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.

Herpes zoster risk and burden of disease in immunocompromised populations: a population-based study using health system integrated databases, 2009-2014.

BACKGROUND: Estimate 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. METHOD: A 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. RESULTS: The 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). CONCLUSIONS: Patients 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.

Spatio-temporal impact of self-financed rotavirus vaccination on rotavirus and acute gastroenteritis hospitalisations in the Valencia region, Spain.

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 3 years 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, ~ 1866 hospital admissions for RV were averted by RV vaccination during 2007-2016. Despite the low-medium vaccine coverage (~ 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 ~ 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.

Risk and impact of herpes zoster among COPD patients: a population-based study, 2009-2014.

BACKGROUND: The objective of this study was to assess the incidence of Herpes Zoster (HZ) among patients with chronic obstructive pulmonary disease (COPD) and the impact of HZ on the underlying COPD. METHODS: A retrospective cohort of all subjects older than 49 years was followed up between 2009 and 2014 using population and health databases of Valencia Region (Spain). HZ and COPD were identified using ICD-9 codes, differentiating COPD patients with inhaled corticosteroids prescriptions (COPD-ICS). The incidence of HZ was compared among 3 groups [non-COPD, COPD and COPD-ICS populations] and use of healthcare resource due to HZ for 6 months following HZ diagnosis through different statistical generalized linear models (GLM). We also compared resources consumption due to COPD before and after HZ. RESULTS: The cohort consisted of 2,289,485 subjects, including 161,317 COPD patients of which 29,708 were COPD-ICS. HZ incidence rates were 11 (95% confidence interval [CI]: 10.7-11.4) and 13 (95% CI: 12.3-13.8) cases/1000 persons-year for COPD and COPD-ICS populations respectively. Incidence increased with age in all groups. The risk of HZ rose by 45 and 61% among COPD and COPD-ICS patients respectively compared to non-COPD (95% credible intervals [CrI]: 1.41-1.5 and 1.52-1.71 respectively). COPD patients consumed more resources due to their HZ than non-COPD. There was no statistically significant impact of the HZ on the resources consumed due to COPD during the 6 months post-HZ compared to the 6 months pre-HZ. CONCLUSIONS: The presence of COPD increases the risk, severity and impact of zoster episodes.

Long-term impact of self-financed rotavirus vaccines on rotavirus-associated hospitalizations and costs in the Valencia Region, Spain.

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 <5 years of age, even with similar vaccination coverage. These results could be partly explained by variability in hospitalization policies, different study designs and the timeframe of observation. In addition, the direct economic impact of the reduction of hospitalizations has never been estimated. Therefore, there is a need to analyze the long-term impact of rotavirus vaccines on RVAGE and all cause gastroenteritis (AGE) hospitalizations and the national health system associated costs, minimizing potential confounders or biases. METHODS: A population-based, ecological study using the hospital discharge registry's Minimum Basic Data Set (MBDS) and the vaccine register (SIV) was performed, among Valencia Region's children <5 years old, during 2002 - 2015. RVAGE and AGE hospitalization risk was analyzed by vaccine coverage and adjusted by the total hospitalization rate for all causes to avoid external biases. The impact of AGE-associated health care utilization in prevaccine (2003-2006) versus postvaccine (2008-2014) years was also assessed. RESULTS: After vaccines licensure, the incidence of RVAGE-associated hospitalizations decreased markedly. A general vaccine coverage-related reduction in RVAGE or AGE-hospitalizations risk was observed in all age groups. Compared with unvaccinated children, RVAGE hospitalization risk decreased by 67% (95% CI: 55-67), 71% (95% CI: 58-81) and 68% (95% CI: 18-92) in children 0, 1 and 4 years of age, respectively, with a vaccination coverage between 40 and 42%. Overall, the hospital related costs were reduced around EUR 6 Mill per 105 children in 7 years. CONCLUSIONS: Despite the low-medium vaccine coverage, the introduction of rotavirus vaccines had a specific coverage-related response impact in the hospitalizations for RVAGE and AGE in children <5 years and their use substantially reduced hospital related costs. The model used reassures that the estimated impact is due to the vaccination and not to other external factors.

Effectiveness of rotavirus vaccines, licensed but not funded, against rotavirus hospitalizations in the Valencia Region, Spain.

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® (RV1) and RotaTeq® (RV5) against rotavirus hospitalizations. METHODS: We conducted a retrospective cohort study using the region's health care databases, among resident children aged <3 years covered by the National Health System, during January 2007-June 2012. We compared two cohorts of vaccinated children: the first included children who received at least one dose of a rotavirus vaccine, and the second included children who were not vaccinated with rotavirus vaccines but received at least one dose of a pneumococcal vaccine, another licensed but non-funded vaccine. The main outcome was rotavirus hospitalization, either laboratory-confirmed (confirmed) or codified as rotavirus (probable). Rotavirus vaccine effectiveness (RVE) by vaccine brand was assessed using Cox proportional hazards models. RESULTS: The study included 78,281 rotavirus and 96,643 pneumococcal vaccinees. Adjusted RVE against probable or confirmed rotavirus hospitalizations was 86% (95% CI: 78-91%) and 88% (95% CI: 81-92%) for a complete series of RV1 and RV5 respectively. CONCLUSIONS: Both rotavirus vaccines were over 85% effective against rotavirus hospitalization among young children. The high effectiveness shown argues in favor of their inclusion in the official schedule. Additional information on rotavirus vaccine safety, duration of protection, and benefit-risk will also be needed to inform such deliberations.