Observational safety study of specific outcomes after trivalent cell culture seasonal influenza vaccination (Optaflu® ) among adults in THIN database of electronic UK primary healthcare records.

PURPOSE: To investigate the safety of trivalent seasonal influenza vaccine (TIVc) (Optaflu® ), the first cell culture seasonal trivalent influenza vaccine available in Europe. METHODS: Codes and unstructured text in adult electronic healthcare records (The Health Improvement Network) were searched for a TIVc brand name or batch number and possible outcomes within a 3 month pre- to 6 month post-TIVc exposure study period (2012-2015). The outcomes were severe allergic reactions, Bell's palsy, convulsions, demyelination, paresthesia, noninfectious encephalitis, neuritis (optic and brachial), vasculitis, inflammatory bowel disease, and thrombocytopenia. Risk periods were defined based on biologically plausible time frame postvaccination when an outcome caused by the vaccine might be expected to occur. Possible outcomes were adjudicated against outcome specific case definitions and a date of onset assigned by using electronic and other medical records. Observed (risk period) to expected (outside risk and preexposure periods) rate ratios, postexposure incidence, and plots of time from exposure to outcome were reported. RESULTS: Sixteen of 1011 events from 4578 exposures fulfilled a primary case definition and had a date of onset during the study period. Three were in observed time. The observed-to-expected rate ratios were (3.3, 95% CI 0.3, 31.7) for convulsions and (1.5, 95% CI 0.2, 14.9) for thrombocytopenia with 1 outcome each in observed time. There was 1 incident inflammatory bowel disease in observed, but none in expected, time. CONCLUSION: The small sample size restricts interpretation; however, no hypothesis of an increased risk of a study outcome was generated. Adjudication of events against case definitions to reduce misclassification of onset and outcomes allowed use of precise risk periods. KEY POINTS This observational study did not generate a hypothesis of an association between the first cell-culture seasonal influenza vaccination available in the European Union and any of the study outcomes (severe allergic reactions, Bell's palsy, convulsions, demyelination, paresthesia, noninfectious encephalitis, neuritis [optic and brachial], vasculitis, inflammatory bowel disease [IBD], and thrombocytopenia). The small sample size limits interpretation of the results. The review of each possible outcome identified from electronic healthcare records against case definitions was included to minimize misclassification of time and outcomes and allow the use of precise risk-periods in an observed-to-expected within cohort analysis. Plots of time from exposure to outcome were included to assess the risk windows.

Update on systemic vasculitides.

Management of systemic vasculitis has been revolutionised over the last decade with the introduction of targeted biological agents. With an increase in both the prevalence and the recognition of vasculitis as well as the high cost of these agents, it is important to ensure their most optimal utilisation. The goals of vasculitis therapy include the induction and maintenance of remissions, preventing relapses, reducing the toxicity of therapy with the aim of reducing morbidity and mortality as well as improving the quality of life of those afflicted. This review focuses on the recent advances in the diagnosis, surveillance and treatment of these conditions.

IgE deficiency may indicate underlying hypogammaglobulinaemia?

Low serum immunoglobulin E (IgE) (<2 kU/L) found during allergy investigations may be a marker for other immunodeficiency states, in particular common variable immunodeficiency. The latter is characterised by recurrent infections, mainly respiratory, resulting in structural lung damage making early diagnosis important. We looked through 4013 samples retrospectively over a 12-month period to identify samples with IgE<2 kU/L. We identified 74/4013 (1.84%) with serum IgE levels<2 kU/L. Only 20 samples had serum immunoglobulin quantification and serum electrophoresis requested. Three of these samples were from the same patient, 10/18 (56%) had one or more classes of immunoglobulin above/below reference range for age and two of these had new diagnosis of immunodeficiency. Serum IgE<2 kU/L can be a marker for hypogammaglobulinaemia or common variable immunodeficiency. As early diagnosis is important to reduce morbidity and mortality, very low serum IgE should trigger further investigation­that is, serum protein electrophoresis and immunoglobulin quantification.

Practical management of lupus nephritis in pregnancy and the puerperium.

Pregnancy represents a major challenge in the management of patients with systemic lupus erythematosus, with substantial risks to both mother and baby. Over the past 40 years there have been major improvements in outcomes. This partly relates to the discovery of the antiphospholipid syndrome, which has transformed management of lupus pregnancy, but also due to more effective drugs and better obstetric practice. Despite these advances, significant maternal and fetal morbidity may still occur in patients with lupus nephritis, and there remain ongoing challenges in order to improve outcomes further. In this article we focus on the challenges facing lupus nephritis patients considering pregnancy, and discuss how we approach practical management issues in relation to the current literature.