Arthritis and arthralgia as an adverse event following immunization: A systematic literature review.

BACKGROUND: Arthritis and arthralgia are reported as adverse events following immunization with various vaccines. OBJECTIVE: To better understand current knowledge of arthritis and arthralgia as an adverse event following immunization. METHODS: A systematic literature review of Pubmed, Embase, and Cochrane Library was conducted. Data extraction was performed by two independent reviewers. No restrictions on dates were imposed and all types of vaccine studies with primary data were reviewed. RESULTS: Of 343 included studies, there were 206 clinical trials, 90 observational studies, and 47 case reports. Influenza was the most commonly studied vaccine (n = 91, 24.4%). Of the 155 (45.2%) studies addressing causality assessment, 84 studies (54.2%) revealed the assessment method. Only seven clinical trials and 12 observational studies reported a measure of association. Four of these studies examined worsening of arthritic conditions in patients with pre-existing disease. Rigorous assessment of causality was not performed in most studies and many observational studies were prone to bias. CONCLUSIONS: The current evidence linking vaccination to incident arthritis or worsening of arthritic conditions is too heterogeneous and incomplete to infer a causal association. Recommendations for future studies include use of consistent, standardized case definitions and causality assessments, better control of confounding and minimization of bias, and inclusion of measures of associations.

Spontaneous reports of vasculitis as an adverse event following immunization: A descriptive analysis across three international databases.

BACKGROUND: Vasculitides have been reported as adverse events following immunization (AEFI) following various vaccines. We describe reports of vasculitis to three international spontaneous reporting systems. METHODS: All spontaneous reports of vasculitis following immunization between January 2003 and June 2014 were retrieved from Eudravigilance (EV), the Vaccine Adverse Event Reporting System (VAERS), and VigiBase®. A Standard MedDRA Query (SMQ) for vasculitis was used and vaccine types were categorized using the Anatomical Therapeutic Chemical classification system. We performed a descriptive analysis by source, sex, age, country, time to onset, vaccine, and type of vasculitis. RESULTS: We retrieved 1797 reports of vasculitis in EV, 1171 in VAERS, and 2606 in VigiBase®. Vasculitis was predominantly reported in children aged 1-17 years, and less frequently in the elderly (>65 years). The generic term "vasculitis" was the most frequently reported AEFI in this category across the three databases (range 21.9% to 27.5% of all reported vasculitis for vaccines). For the more specific terms, Henoch-Schoenlein Purpura (HSP) was most frequently reported, (19.1% on average), followed by Kawasaki disease (KD) (16.1% on average) and polymyalgia rheumatica (PMR) (9.2% on average). Less frequently reported subtypes were cutaneous vasculitis (CuV), vasculitis of the central nervous system (CNS-V), and Behcet's syndrome (BS). HSP, PMR and CuV were more frequently reported with influenza vaccines: on average in 29.3% for HSP reports, 61.5% for PMR reports and in 39.2% for CuV reports. KD was reported with pneumococcal vaccines in 32.0% of KD reports and with rotavirus vaccines in more than 20% of KD reports. BS was most frequently reported after hepatitis and HPV vaccines and CNS-V after HPV vaccines. CONCLUSION: Similar reporting patterns of vasculitides were observed in different databases. Implementation of standardized case definitions for specific vasculitides could improve overall data quality and comparability of reports.

Reference set for performance testing of pediatric vaccine safety signal detection methods and systems.

BACKGROUND: Safety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources. METHODS: The study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement. RESULTS: We selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC. CONCLUSION: A reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.

Vasculitis as an adverse event following immunization - Systematic literature review.

BACKGROUND: Several types of vasculitis have been observed and reported in temporal association with the administration of various vaccines. A systematic review of current evidence is lacking. OBJECTIVE: This systematic literature review aimed to assess available evidence and current reporting practice of vasculitides as adverse events following immunization (AEFI). METHODS: We reviewed the literature from 1st January 1994 to 30th June 2014. This review comprises randomized controlled trials, observational studies, case series, case reports, reviews and comments regardless of vaccine and target population. RESULTS: The initial search resulted in the identification of 6656 articles. Of these, 157 articles were assessed for eligibility and 75 studies were considered for analysis, including 6 retrospective/observational studies, 2 randomized controlled trials, 7 reviews, 11 case series, 46 case reports and 3 comments. Most of the larger, higher quality studies found no causal association between vaccination and subsequent development of vasculitis, including several studies on Kawasaki disease and Henoch-Schönlein purpura (IgA vasculitis). Smaller case series reported a few cases of vasculitis following BCG and vaccines against influenza and hepatitis. Only 24% of the articles reported using a case definition of vasculitis. CONCLUSIONS: Existing literature does not allow establishing a causative link between vaccination and vasculitides. Further investigations were strengthened by the use of standardized case definitions and methods for data collection, analysis and presentation to improve data comparability and interpretation of vasculitis cases following immunization.

Epidemiology, co-morbidities, and medication use of patients with Alzheimer's disease or vascular dementia in the UK.

Epidemiologic studies on age-specific incidence rates (IRs) separating Alzheimer's disease (AD) and vascular dementia (VaD) in the UK are scarce. We sought to assess IRs of AD and VaD in the UK and to compare co-morbidities and medication use between patients with AD, VaD, or without dementia. We identified cases aged ≥65 years with an incident diagnosis of AD or VaD between 1998 and 2008 using the General Practice Research Database (GPRD). We assessed IRs, stratified by age and gender, matched one dementia-free control patient to each demented patient, and analyzed co-morbidities and medication use. We identified 7,086 AD and 4,438 VaD cases. Overall, the IR of AD was 1.59/1,000 person-years (py) (95% CI 1.55-1.62) and the IR of VaD 0.99/1,000 py (95% CI 0.96-1.02). For AD, IRs were higher for women than for men, but not for VaD. Except for orthostatic hypotension, the prevalence of all cardiovascular (CV) co-morbidities and exposure to CV drugs was lower in patients with AD than in corresponding controls, whereas the opposite was true for VaD. The lower prevalence of CV diseases in patients with AD may be a true finding or the result of a channeling effect, i.e., the possibility that demented patients with CV diseases may be more likely diagnosed with VaD than AD.