Development and validation of a respiratory syncytial virus multiplex immunoassay.

PURPOSE: Respiratory syncytial virus (RSV) is one of the leading causes of severe respiratory disease in infants and adults. While vaccines and monoclonal therapeutic antibodies either are or will shortly become available, correlates of protection remain unclear. For this purpose, we developed an RSV multiplex immunoassay that analyses antibody titers toward the post-F, Nucleoprotein, and a diverse mix of G proteins. METHODS: A bead-based multiplex RSV immunoassay was developed, technically validated to standard FDA bioanalytical guidelines, and clinically validated using samples from human challenge studies. RSV antibody titers were then investigated in children aged under 2 and a population-based cohort. RESULTS: Technical and clinical validation showed outstanding performance, while methodological developments enabled identification of the subtype of previous infections through use of the diverse G proteins for approximately 50% of samples. As a proof of concept to show the suitability of the assay in serosurveillance studies, we then evaluated titer decay and age-dependent antibody responses within population cohorts. CONCLUSION: Overall, the developed assay shows robust performance, is scalable, provides additional information on infection subtype, and is therefore ideally suited to be used in future population cohort studies.

Are patients with newly diagnosed breast cancer getting appropriate DEXA scans? A District General Hospital experience.

Breast cancer patients are often at high risk of fragility fractures partly due to adjuvant endocrine therapy such as aromatase inhibitors and chemotherapy. Baseline dual energy X-ray absorptiometry (DEXA) scanning is recommended as a standard of care in identifying patients who are at risk so they can be commenced on bone protective therapy. NICE guideline 80 - "Early and locally advanced breast cancer"[1] states that patients with early invasive breast cancer should have a baseline DEXA scan to assess BMD before the commencement of aromatase inhibitor treatment; if patients have treatment-induced menopause or are starting ovarian ablation/suppression therapy. We have audited the performance of a DGH against these guidelines with a target of 100% concordance. During a one year period (April 2012-April 2013), 100 patients with a new diagnosis of breast cancer were selected at random from the hospital coding database. 100 patients were chosen as this was a convenient sample size. We gathered information for these patients using electronic records, letters, and imaging. This showed a poor compliance of 38% against NICE guidelines. This in turn means that patients with low BMD at diagnosis of breast cancer are being under diagnosed and under treated, resulting in increased potential morbidity associated with fragility fractures. The interventions that resulted from this audit were: dissemination of these results to surgical and oncology departments, posters summarising the guidelines put up in breast clinics, and breast MDTs to discuss the need for DEXA scans for patients with breast cancer. A re-audit was performed for patients diagnosed with early, invasive breast cancer in January 2014 where a compliance of 90% was achieved. This represents a huge improvement in compliance from the baseline measure of 38%. In order to show that this improvement could be sustained, two further cycles were performed in February and March 2014, where the compliance was 92% and 100% respectively. Therefore the improvement in compliance was not only maintained but in fact the compliance increased even further during subsequent cycles. Hence we have achieved a large improvement in the quality of assessment of bone quality in breast cancer patients. Moreover, we have demonstrated the importance of the dissemination of information and education within a multidisciplinary setting.