The physical health and quality of life of patients with X-linked agammaglobulinaemia in England and Wales

Ph. D. Thesis.Background Patients with X-linked agammaglobulinaemia (XLA) have absent peripheral circulating Blymphocytes and agammaglobulinaemia caused by defects in BTK. Treatment consists of life-long immunoglobulin replacement therapy. This only contains the IgG isotype containing little or no IgA or IgM. Patients may still, therefore, experience recurrent infections and complications. Novel therapies are potentially available, most notably gene therapy and newborn screening. I aimed to examine the clinical health outcomes and quality of life for patients with XLA in England and Wales to evaluate current practices and the potential role for novel therapies. Methods This is a retrospective, longitudinal observational study of patients with a definite diagnosis of XLA (BTK mutation or absent BTK expression), in England and Wales. Retrospective clinical data were collected from patients’ records, including conversion of lung function results to Z-scores. Patients and/or their families were invited to complete questionnaires on their health-related quality of life (HRQoL) and psychological health. Results were compared against UK norms and UK patients with cystic fibrosis. Results Fifty-four patients were enrolled in the study (21 children, 33 adults). Median age at diagnosis was 2.59 years with no statistically significant improvement seen since 1990. Twenty-two patients (44%) had evidence of bronchiectasis on high-resolution computerised tomography. Patients with bronchiectasis were diagnosed with XLA significantly later than patients without bronchiectasis. Neither infection incidence nor IgG trough levels were associated with an increased risk of bronchiectasis. In the absence of bronchiectasis, XLA patients had normal HRQoL results. HRQoL was strongly correlated with respiratory symptoms and lung function. Conclusions Recurrent respiratory tract infections and bronchiectasis remain a major burden for this cohort despite modern therapy. In the absence of bronchiectasis, patients have a normal HRQoL. Curative therapy, such as gene therapy or bone marrow transplantation, may provide the only option for improving outcomes in XLABubble Foundation, Jeffrey Modell Foundation, UKPI

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome