Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials.

OBJECTIVES: (1) To assess if co-administration of four-component meningococcal serogroup B vaccine (4CMenB) and other routine vaccines caused an interaction increasing the risk and/or severity of adverse events following immunisation (AEFI) compared with administration at separate visits and (2) to estimate the risk of AEFI recurrence. DESIGN: Risk-interval design SETTING: Three randomised controlled trials conducted in Europe. PARTICIPANTS: A total of 5026 healthy 2-month-old to 15-month-old infants. INTERVENTIONS: 4CMenB and routine vaccines (hexavalent combined diphtheria-tetanus-acellular pertussis-inactivated polio-Haemophilus influenzae type b-hepatitis B vaccine+seven-valent pneumococcal conjugate vaccine or measles-mumps-rubella-varicella vaccine) administered concomitantly or separately 1 month apart, in regular (2, 4, 6 and 12 months), accelerated (2, 3, 4 and 12 months) or delayed (two doses of 4CMenB at ≥12 months of age) schedules. OUTCOME MEASURES: Primary: Fever (≥38°C) during the first 48 hours post immunisation. Secondary: crying, change in eating habits, diarrhoea, irritability and tenderness at the 4CMenB injection site. RESULTS: Compared with separate administration, concomitant administration decreased the overall incidence of fever (≥38°C), 86% versus 75%, and other systemic AEFIs but increased the incidence of 4CMenB injection site tenderness, 55% versus 66%, moderate/severe fevers (≥39°C), 13% versus 18%, and long-lasting (>1 day) fevers, 23% versus 33%. Co-administration reduced AEFI risk by 4%-49% with the greatest impact among infants with prior AEFI(s). Fever recurrence risk was proportional to the number of prior fever events: 79% at dose 2 with one prior episode; 44% and 74% at dose 3 with one and two prior episodes, respectively; and 29%, 45% and 60% at dose 4 with one, two and three prior episodes, respectively. Severity was not increased at recurrence and a similar pattern of recurrence risk proportional to the number of prior events was observed for other AEFIs. CONCLUSIONS: The cumulative risk of AEFI is reduced with concomitant versus separate administration of 4CMenB and routine infant vaccines. Infants with a prior AEFI are at higher risk of the same AEFI at subsequent immunisations, but severity with recurrence is usually not increased. TRIALS REGISTRATION NUMBER: NCT00657709, NCT00847145, NCT00721396 and NCT02712177; Pre-results.

Cardiac complications after stroke: protocol for a systematic review and meta-analysis.

INTRODUCTION: Stroke is the second most common cause of death after ischaemic heart diseases and the third leading cause of disability worldwide. The contribution of cardiac complications to the mortality of patients with stroke is variable across studies, ranging from 12.5% to 22.7%. Many of these cardiac complications are preventable, and early recognition and adequate management guided by appropriate up-to-date knowledge of their relative incidence and fatality can help to improve patients' outcomes. This systematic review aims to summarise the available data on the burden of cardiac complications after stroke. METHODS AND ANALYSIS: This review will include all cross-sectional, case-control and cohort studies and clinical trials published between 1 January 1950 and 31 December 2017, involving adults and/or children, and reporting on the prevalence, the incidence and/or the mortality of cardiac complications after stroke. Two reviewers will independently screen titles and abstracts of records retrieved from PubMed, Excerpta Medica Database, ISI Web of Science and the Cumulative Index to Nursing and Allied Health Literature for eligibility, and then assess the risk of bias and quality of reporting to select the studies which will be included. All authors will contribute to the retrieval of full texts of eligible records and data extraction. Heterogeneity across studies will be evaluated by the χ2 test on Cochran's Q statistic. Study-specific estimates of the prevalence, incidence and mortality of cardiac complications after stroke across studies will be pooled through random-effect or fixed-effect meta-analysis depending on the source of the heterogeneity, after stabilising the variance of individual studies using the Freeman-Tukey double arcsine transformation. Visual analysis of funnel plots and Egger's test will be done to detect small-study effect. ETHICS AND DISSEMINATION: This review and meta-analysis will be based on published data and will therefore not require a specific ethical clearance. The results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42018082551.

Risk of Recurrence of Adverse Events Following Immunization: A Systematic Review.

CONTEXT: Reimmunizing patients who had an adverse event following immunization (AEFI) is sometimes a challenge because there are limited data on the risk and severity of AEFI recurrence. OBJECTIVE: To summarize the literature on the risk of AEFI recurrence. DATA SOURCES: PubMed, Embase, and Cochrane library. STUDY SELECTION: We included articles in English or French published before September 30, 2016. Articles were selected if they estimated the risk of AEFI recurrence in at least 5 individuals. Studies with experimental vaccines were excluded. DATA EXTRACTION: Data on study design, setting, population, vaccines, and AEFI recurrence were extracted. RESULTS: Twenty-nine articles were included. Among patients with a history of hypotonic hyporesponsive episode (n = 398), anaphylaxis (n = 133), or seizures (n = 60) who were reimmunized, events recurred in 0% to 0.8%. Allergic-like events recurred in 30 of 594 reimmunized patients. Fever recurred in 0% to 84% of 836 reimmunized patients, depending on the vaccine and dose number. Among children with extensive limb swelling after the fourth dose of diphtheria-tetanus-acellular pertussis vaccine, recurrence was higher when the fifth dose was given withthe full-antigen formulation (78%) compared with the reduced-antigen formulation (53%, P = .02) LIMITATIONS: Many studies, included few patients, and those with severe AEFIs were often not reimmunized. CONCLUSIONS: Despite vaccines being administered to millions of people annually, there are few studies in which researchers evaluated AEFI recurrence. Published studies suggest that reimmunization is usually safe. However in these studies, severe cases were often not reimmunized.