Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

The human gut microbiome in early-onset type 1 diabetes from the TEDDY study

Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors1, including complex genetic elements2, patient exposures3 and the gut microbiome4. Viral infections5 and broader gut dysbioses6 have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts7,8 and a T1D mouse model9, these data support the protective effects of short-chain fatty acids in early-onset human T1D.Peer reviewe

Development of a self-administered early inflammatory arthritis detection tool

<p>Abstract</p> <p>Background</p> <p>Barriers to care limit the potential benefits of pharmacological intervention for inflammatory arthritis. A self-administered questionnaire for early inflammatory arthritis (EIA) detection may complement contemporary triage interventions to further reduce delays to rheumatologic care. The objective of this study was to develop a self-administered EIA detection tool for implementation in pre-primary care settings.</p> <p>Methods</p> <p>A core set of dimensions and constructs for EIA detection were systematically derived from the literature and augmented by investigative team arbitration. Identified constructs were formulated into lay language questions suitable for self-administration. A three-round Delphi consensus panel of EIA experts and stakeholders evaluated the relevance of each question to EIA detection and suggested additional items. Questions accepted by less than 70% of respondents in rounds one or two were eliminated. In round three, questions accepted by at least 80% of the panel were selected for the tool.</p> <p>Results</p> <p>Of 584 citations identified, data were extracted from 47 eligible articles. Upon arbitration of the literature synthesis, 30 constructs encompassing 13 dimensions were formulated into lay language questions and posed to the Delphi panel. A total of 181 EIA experts and stakeholders participated on the Delphi panel: round one, 60; round two, 59; and, round three, 169; 48 participated in all three rounds. The panel evaluated the 30 questions derived from the literature synthesis, suggested five additional items, and eliminated a total of 24. The eleven-question instrument developed captured dimensions of articular pain, swelling, and stiffness, distribution of joint involvement, function, and diagnostic and family history.</p> <p>Conclusions</p> <p>An eleven-question, EIA detection tool suitable for self-administration was developed to screen subjects with six to 52 weeks of musculoskeletal complaints. Psychometric and performance property testing of the tool is ongoing.</p