Disease misclassification in electronic healthcare database studies: Deriving validity indices-A contribution from the ADVANCE project.

There is a strong and continuously growing interest in using large electronic healthcare databases to study health outcomes and the effects of pharmaceutical products. However, concerns regarding disease misclassification (i.e.

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.

ADVANCE: Towards near real-time monitoring of vaccination coverage, benefits and risks using European electronic health record databases.

Background: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private partnership aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines using European electronic health record (eHR) databases. This proof-of-concept study aimed to test the feasibility of near real-time (NRT) monitoring of vaccination coverage, benefits and risks based on multiple European eHR databases, using acellular pertussis vaccination in children aged <6 years as test case.

Methods: A qualitative feasibility assessment on NRT monitoring was carried out using a survey and face-to-face discussion with ADVANCE data partners.

ADVANCE system testing: Benefit-risk analysis of a marketed vaccine using multi-criteria decision analysis and individual-level state transition modelling.

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 electronic health record (eHR) databases in Europe. Proof-of-concept studies were designed to assess the proposed processes and system for generating the required evidence to perform B/R assessment and near-real time monitoring of vaccines. We aimed to test B/R methodologies for vaccines, using the comparison of the B/R profiles of whole-cell (wP) and acellular pertussis (aP) vaccine formulations in children as an example.

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.

Bias due to differential and non-differential disease- and exposure misclassification in studies of vaccine effectiveness.

Background: Studies of vaccine effectiveness (VE) rely on accurate identification of vaccination and cases of vaccine-preventable disease. In practice, diagnostic tests, clinical case definitions and vaccination records often present inaccuracies, leading to biased VE estimates. Previous studies investigated the impact of non-differential disease misclassification on VE estimation.

Benefit-Risk Monitoring of Vaccines Using an Interactive Dashboard: A Methodological Proposal from the ADVANCE Project.

Introduction: New vaccines are launched based on their benefit-risk (B/R) profile anticipated from clinical development. Proactive post-marketing surveillance is necessary to assess whether the vaccination uptake and the B/R profile are as expected and, ultimately, whether further public health or regulatory actions are needed. There are several, typically not integrated, facets of post-marketing vaccine surveillance: the surveillance of vaccination coverage, vaccine safety, effectiveness and impact.

Methodology for computing the burden of disease of adverse events following immunization.

Purpose: Composite disease burden measures such as disability-adjusted life-years (DALY) have been widely used to quantify the population-level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden.

Methods: We developed a practical methodological framework, explicitly describing all steps involved: acquisition of relative or absolute risks and background event incidence rates, selection of disability weights and durations, and computation of the years lived with disability (YLD) measure, with appropriate estimation of uncertainty.

Comparative long-term trend analysis of daily weather conditions with daily pollen concentrations in Brussels, Belgium.

A clear rise in seasonal and annual temperatures, a gradual increase of total radiation, and a relative trend of change in seasonal precipitation have been observed for the last four decades in Brussels (Belgium). These local modifications may have a direct and indirect public health impact by altering the timing and intensity of allergenic pollen seasons. In this study, we assessed the statistical correlations (Spearman's test) between pollen concentration and meteorological conditions by using long-term daily datasets of 11 pollen types (8 trees and 3 herbaceous plants) and 10 meteorological parameters observed in Brussels between 1982 and 2015.

Thyroid Cancer Incidence around the Belgian Nuclear Sites, 2000-2014.

The present study investigates whether there is an excess incidence of thyroid cancer among people living in the vicinity of the nuclear sites in Belgium. Adjusted Rate Ratios were obtained from Poisson regressions for proximity areas of varying sizes. In addition, focused hypothesis tests and generalized additive models were performed to test the hypothesis of a gradient in thyroid cancer incidence with increasing levels of surrogate exposures.

Biomarkers in patients admitted to the emergency department after exposure to acrylonitrile in a major railway incident involving bulk chemical material.

Background: A railway incident with victims of exposure to the cyanogenic substance acrylonitrile (ACN).

Aims: We retrospectively (i)built an inventory of the clinical characteristics of individuals admitted to surrounding emergency departments (ED's) and (ii)studied the correlation between N-2-cyanoethylvaline (CEV), a biomarker used in a population study for evaluating exposure to ACN, with lactate and thiocyanate (SCN), biomarkers determined during emergency care.

Results: 438 patients from 11 ED's were included and presented with known symptoms of ACN poisoning but also with concern about the risks.

Childhood leukaemia near nuclear sites in Belgium, 2002-2008.

This paper describes an ecological study investigating whether there is an excess incidence of acute leukaemia among children aged 0-14 years living in the vicinity of the nuclear sites in Belgium. Poisson regression modelling was carried out for proximity areas of varying sizes. In addition, the hypothesis of a gradient in leukaemia incidence with increasing levels of surrogate exposures was explored by means of focused hypothesis tests and generalized additive models.

Nicotine Dependence and Urinary Nicotine, Cotinine and Hydroxycotinine Levels in Daily Smokers.

Introduction: Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerström Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual FTND items.

Methods: Urine samples and questionnaire data of 239 daily smokers were obtained.