Age-specific vaccination coverage estimates for influenza, human papillomavirus and measles containing vaccines from seven population-based healthcare databases from four EU countries – The ADVANCE project

Background: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public–private collaboration aiming to develop and test a system for rapid benefit-risk monitoring of vaccines using existing healthcare databases in Europe. We estimated vaccine coverage from electronic healthcare databases as part of a fit-for-purpose assessment for vaccine benefit-risk studies. Methods: A retrospective dynamic cohort study was conducted through a distributed network approach. Coverage with measles-vaccine for birth year 2006, human papillomavirus (HPV)-vaccine for birth years 1990–2000 and influenza-vaccine for birth years 1920–1950 was estimated using period-prevalence and inverse probability weighting methods. Seven databases from four countries participated: Italy (Pedianet, Val Padana), Spain (BIFAP, SIDIAP), UK (RCGP-RSC, THIN), Denmark (SSI/AUH). Database access providers extracted the data, transformed it into a common structure and ran an R-script locally. The created output tables were shared and pooled at a central server. Results: The total study population comprised 274,616 persons for measles-vaccine, 2,011,666 persons for HPV-vaccine and 14,904,033 persons for influenza-vaccine. Measles-vaccine coverage varied from 84.3% (Denmark) to 96.5% (Italy, Val Padana) for the first dose and from 82.8% (Italy, Val Padana) to 90.9% (UK) for the second dose at the age of 7 years. The HPV-vaccine coverage, aggregated over birth years 1997–2000, ranged from 60% (UK) to 88.3% (Denmark) at the age of 15 years. The influenza-vaccine coverage for the influenza seasons from 2009 to 2015 for persons aged 65 years and more was roughly stable around 43% in Denmark and around 68% in the UK while a decrease from 58 to 50% was observed in Catalonia (Spain). Conclusions: We obtained detailed, age-specific coverage estimates though a common procedure. We discussed between database comparability and comparability to published national estimates

ADVANCE system testing: Can safety studies be conducted using electronic healthcare data? An example using pertussis vaccination

Introduction: The Accelerated Development of Vaccine benefit-risk Collaboration in Europe (ADVANCE) public-private collaboration, aimed to develop and test a system for rapid benefit-risk monitoring of vaccines using healthcare databases in Europe. The objective of this proof-of-concept (POC) study was to test the feasibility of the ADVANCE system to generate incidence rates (IRs) per 1000 person-years and incidence rate ratios (IRRs) for risks associated with whole cell- (wP) and acellular- (aP) pertussis vaccines, occurring in event-specific risk windows in children prior to their pre-school-entry booster. Methods: The study population comprised almost 5.1 million children aged 1 month to <6 years vaccinated with wP or aP vaccines during the study period from 1 January 1990 to 31 December 2015. Data from two Danish hospital (H) databases (AUH and SSI) and five primary care (PC) databases from, UK (THIN and RCGP RSC), Spain (SIDIAP and BIFAP) and Italy (Pedianet) were analysed. Database-specific IRRs between risk vs. non-risk periods were estimated in a self-controlled case series study and pooled using random-effects meta-analyses. Results: The overall IRs were: fever, 58.2 (95% CI: 58.1; 58.3), 96.9 (96.7; 97.1) for PC DBs and 8.56 (8.5; 8.6) for H DBs; convulsions, 7.6 (95% CI: 7.6; 7.7), 3.55 (3.5; 3.6) for PC and 12.87 (12.8; 13) for H; persistent crying, 3.9 (95% CI: 3.8; 3.9) for PC, injection-site reactions, 2.2 (95% CI 2.1; 2.2) for PC, hypotonic hypo-responsive episode (HHE), 0.4 (95% CI: 0.4; 0.4), 0.6 (0.6; 0.6) for PC and 0.2 (0.2; 0.3) for H; and somnolence: 0.3 (95% CI: 0.3; 0.3) for PC. The pooled IRRs for persistent crying, fever, and ISR, adjusted for age and healthy vaccinee period were higher after wP vs. aP vaccination, and lower for convulsions, for all doses. The IRR for HHE was slightly lower for wP than aP, while wP was associated with somnolence only for dose 1 and dose 3 compared with aP. Conclusions: The estimated IRs and IRRs were comparable with published data, therefore demonstrating that the ADVANCE system was able to combine several European healthcare databases to assess vaccine safety data for wP and aP vaccination

Quantifying outcome misclassification in multi-database studies: The case study of pertussis in the ADVANCE project

Background: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines using European healthcare databases. Event misclassification can result in biased estimates. Using different algorithms for identifying cases of Bordetella pertussis (BorPer) infection as a test case, we aimed to describe a strategy to quantify event misclassification, when manual chart review is not feasible. Methods: Four participating databases retrieved data from primary care (PC) setting: BIFAP: (Spain), THIN and RCGP RSC (UK) and PEDIANET (Italy); SIDIAP (Spain) retrieved data from both PC and hospital settings. BorPer algorithms were defined by healthcare setting, data domain (diagnoses, drugs, or laboratory tests) and concept sets (specific or unspecified pertussis). Algorithm- and database-specific BorPer incidence rates (IRs) were estimated in children aged 0–14 years enrolled in 2012 and 2014 and followed up until the end of each calendar year and compared with IRs of confirmed pertussis from the ECDC surveillance system (TESSy). Novel formulas were used to approximate validity indices, based on a small set of assumptions. They were applied to approximately estimate positive predictive value (PPV) and sensitivity in SIDIAP. Results: The number of cases and the estimated BorPer IRs per 100,000 person-years in PC, using data representing 3,173,268 person-years, were 0 (IR = 0.0), 21 (IR = 4.3), 21 (IR = 5.1), 79 (IR = 5.7), and 2 (IR = 2.3) in BIFAP, SIDIAP, THIN, RCGP RSC and PEDIANET respectively. The IRs for combined specific/unspecified pertussis were higher than TESSy, suggesting that some false positives had been included. In SIDIAP the estimated IR was 45.0 when discharge diagnoses were included. The sensitivity and PPV of combined PC specific and unspecific diagnoses for BorPer cases in SIDIAP were approximately 85% and 72%, respectively. Conclusion: Retrieving BorPer cases using only specific concepts has low sensitivity in PC databases, while including cases retrieved by unspecified concepts introduces false positives, which were approximately estimated to be 28% in one database. The share of cases that cannot be retrieved from a PC database because they are only seen in hospital was approximately estimated to be 15% in one database. This study demonstrated that quantifying the impact of different event-finding algorithms across databases and benchmarking with disease surveillance data can provide approximate estimates of algorithm validity

ADVANCE database characterisation and fit for purpose assessment for multi-country studies on the coverage, benefits and risks of pertussis vaccinations

Introduction: The public-private ADVANCE consortium (Accelerated development of vaccine benefit-risk collaboration in Europe) aimed to assess if electronic healthcare databases can provide fit-for purpose data for collaborative, distributed studies and monitoring of vaccine coverage, benefits and risks of vaccines. Objective: To evaluate if European healthcare databases can be used to estimate vaccine coverage, benefit and/or risk using pertussis-containing vaccines as an example. Methods: Characterisation was conducted using open-source Java-based (Jerboa) software and R scripts. We obtained: (i) The general characteristics of the database and data source (meta-data) and (ii) a detailed description of the database population (size, representatively of age/sex of national population, rounding of birth dates, delay between birth and database entry), vaccinations (number of vaccine doses, recording of doses, pattern of doses by age and coverage) and events of interest (diagnosis codes, incidence rates). A total of nine databases (primary care, regional/national record linkage) provided data on events (pertussis, pneumonia, death, fever, convulsions, injection site reactions, hypotonic hypo-responsive episode, persistent crying) and vaccines (acellular pertussis and whole cell pertussis) related to the pertussis proof of concept studies. Results: The databases contained data for a total population of 44 million individuals. Seven databases had recorded doses of vaccines. The pertussis coverage estimates were similar to those reported by the World Health Organisation (WHO). Incidence rates of ev

Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European population

Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.info:eu-repo/semantics/publishedVersio

Biodiversity and benthic megafaunal communities inhabiting the Formigas Bank (NE Azores)

The Formigas Bank is an offshore seamount located in the easternmost part of the Azores archipelago (northeast Atlantic). It rises from abyssal depths to the surface, including a small set of islets. The bank holds multiple nature conservation designations, including a Natura 2000 Special Area of Conservation, an OSPAR Marine Protected Area, a RAMSAR site and a Nature Reserve declared under the Azores network of protected areas. The protection is based on the presence of sublittoral biotopes of high conservation interest, and importance as feeding grounds, spawning and nursery areas for many marine species, including fish, cetaceans and turtles. Although some information exists on the sublittoral communities occurring on the seamount summit (e.g., infralittoral Cystoseira and Laminaria beds, circalittoral hydrarian and sponge gardens, rich pelagic fauna), virtually no information was available on the deep-sea communities inhabiting the seamount flanks. Therefore, during the MEDWAVES cruise, the flanks of the Formigas bank have been surveyed using multibeam sonar, an ROV and oceanographic profiles, with the objective to characterise deep-sea biodiversity and megafaunal communities as well as the environment where they occur. This communication will present results from the video annotations of the ten dives made on the seamount slopes between ~500m and ~1,500 m depth. Diverse communities of sedentary suspension-feeding organisms were observed, with more than 20 cold-water coral species (mainly octocorals) being recorded, as well as many different sponge morphotypes. Dense coral garden habitats and sponge grounds were identified on several occasions, confirming the presence of vulnerable marine ecosystems (VMEs) and of ecologically or biologically significant areas (EBSAs). Differences in the abundance and composition of these habitats between the northern and southern dive transects are interpreted as reflecting substrate and geomorphological differences, as well as the potential influence of the Mediterranean Outflow Water (MOW). The new knowledge on deep-sea megafaunal communities reinforces the importance of this seamount as an area of high conservation interest

ADVANCE system testing: Estimating the incidence of adverse events following pertussis vaccination in healthcare databases with incomplete exposure data

The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public–private collaboration aiming to develop and test a system for rapid vaccine benefit-risk monitoring using existing European healthcare databases. Incidence rate (IR) estimates of vaccination-associated adverse events that are needed to model vaccination risks can be calculated from existing healthcare databases when vaccination (exposure) data are available. We assessed different methods to derive IRs in risk periods following vaccination when exposure data are missing in one database, using estimated IRs and IRRs from other databases for febrile seizures, fever and persistent crying. IRs were estimated for children aged 0–5 years in outcome-specific risk and non-risk periods following the first dose of acellular pertussis (aP) vaccination in four primary care databases and one hospital database. We compared derived and observed IRs in each database using three methods: 1) multiplication of non-risk period IR for database i by IR ratio (IRR) obtained from meta-analysis of IRRs estimated using the self-controlled case-series method, from databases other than i; 2) same method as 1, but multiplying with background IR; and 3) meta-analyses of observed IRs from databases other than i. IRs for febrile seizures were lower in primary care databases than the hosp

Vulnerable marine ecosystems and biological features of Gazul mud volcano (Gulf of Cádiz): A contribution towards a potential "Gulf of Cádiz" EBSA

The Gulf of Cádiz (GoC) represents an area of socioeconomic and scientific importance for oceanographic, geological and biological processes. An interesting feature of the GoC is the presence of a large amount of mud volcanoes (MVs) and diapirs that display different seepage, seabed types, oceanographic settings and biological communities. Detailed exploration of some MVs is still needed for detecting Vulnerable Marine ecosystems (VMEs) that seem to be rare in other areas of the GoC, improving the current knowledge on its biodiversity and ecological attributes. During different expeditions (MEDWAVES-ATLAS, INDEMARES-CHICA 0610 & 0412 and ISUNEPCA 0616) carried out in different years, biological samples and videos were obtained in Gazul MV (Spanish Margin of the GoC). The study of those samples and videos has revealed the presence of several ecologically important VMEs (e.g. 3 species of reef framework-forming corals, coral gardens including solitary scleractinians, gorgonians and antipatharians, as well as deep-sea sponge aggregations and chemosynthesis-related structures) and a large number of species occurring in this MV, including new records for the European margin, threatened species and non-previously described species. The combination of different environmental and anthropogenic factors allowed the present-day persistence of these VMEs in the GoC. Some of Gazul MV biological and ecological attributes fit several criteria of the Convention on Biological Diversity for EBSA description (e.g. 1,3,4,6) that, together with those of other areas of the GoC, may contribute to the future potential nomination of an EBSA in this area of the NE Atlantic

Actualización de la base de datos arqueomagnética de Iberia y nuevas curvas de variación paleosecular para los últimos 3000 años

Trabajo presentado en la X Reunión de la Comisión de Paleomagnetismo de la Sociedad Geológica de España, celebrada del 14 al 17 de septiembre de 2017 en el valle del río Grío, Zaragoza (España)En este trabajo se presenta una actualización de la base de datos direccional de Iberia para los últimos 3000 años (Gómez-Paccard et al., 2006) y el primer catálogo de intensidad para este periodo. En direcciones, la base de datos ha aumentado en más de un 80%, incluyendo más de 10 resultados direccionales no publicados hasta la fecha. En intensidades, este estudio representa un aumento de más del 50% en la cantidad de datos de calidad disponibles (si nos referimos al primer milenio a.C., se cuadruplica el número de datos), entendiendo datos de calidad como aquellos que cumplen los siguientes criterios: a) que el número de especímenes empleados para la determinación de la paleointensidad sea igual o superior a 4; b) que el protocolo empleado sea Thellier (Thellier y Thellier, 1959) o derivados; c) que la anisotropía de la imanación termorremanente haya sido investigada y corregida. Toda esta información ha permitido desarrollar nuevas curvas de variación paleosecular de declinación, inclinación e intensidad de Iberia para los tres últimos milenios. Se ha empleado el método bootstrap (Thébault y Gallet, 2010) incluyendo la jerarquía asociada a la información estratigráfica cuando estaba disponible. Las nuevas curvas direccionales no presentan grandes diferencias con las anteriormente publicadas (Fig. 1), aunque se incrementa su precisión. En intensidad las principales diferencias aparecen en el primer milenio a.C. y en el posible doble máximo en torno a 600-800 años d.C, que no es recogido por esta curva. Las nuevas curvas de variación paleosecular suponen una mejora en las posibilidades de la datación arqueomagnética en la península ibéricaPeer reviewe

Incidence Rates of Autoimmune Diseases in European Healthcare Databases: A Contribution of the ADVANCE Project

Introduction: The public–private ADVANCE collaboration developed and tested a system to generate evidence on vaccine benefits and risks using European electronic healthcare databases. In the safety of vaccines, background incidence rates are key to allow proper monitoring and assessment. The goals of this study were to compute age-, sex-, and calendar-year stratified incidence rates of nine autoimmune diseases in seven European healthcare databases from four countries and to assess validity by comparing with published data. Methods: Event rates were calculated for the following outcomes: acute disseminated encephalomyelitis, Bell’s palsy, Guillain–Barré syndrome, immune thrombocytopenia purpura, Kawasaki disease, optic neuritis, narcolepsy, systemic lupus erythematosus, and transverse myelitis. Cases were identified by diagnosis codes. Participating organizations/databases originated from Denmark, Italy, Spain, and the UK. The source population comprised all persons registered, with at least 1 year of data prior to the study start, or follow-up from birth. Stratified incidence rates were computed per database over the period 2003 to 2014. Results: Between 2003 and 2014, 148,947 incident cases of nine autoimmune diseases were identified. Crude incidence rates were highest for Bell’s palsy [23.8/100,000 person-years (PYs), 95% confidence interval (CI) 23.6–24.1] and lowest for Kawasaki disease (0.7/100,000 PYs, 95% CI 0.6–0.7). Specific patterns were observed by sex, age, calendar time, and data sources. Rates were comparable with published estimates. Conclusion: A range of autoimmune events could be identified in the ADVANCE system. Estimation of rates indicated consistency across selected European healthcare databases, as well as consistency with US published data