When the Cause Is Not Crystal Clear A 55-year-old woman with a history of chronic renal insufficiency presented to the emergency department with recurrent falls, dizziness, and lethargy over a peri...

Background The use of monoclonal antibodies in various settings has been linked to the development of progressive multifocal leukoencephalopathy (PML). Whilst this association is well-described with agents such as rituximab and natalizumab, the literature describing the occurrence of PML with ofatumumab therapy (especially in a haematology setting) is sparse. This case aims to draw attention to the above association with a particular focus on the mechanisms by which B-cell-depleting therapy can precipitate PML during the treatment of haematological malignancy. Case presentation A 68-year-old Caucasian man presented with acute-on-subacute confusion and reduced mobility. He had a history of chronic lymphocytic leukaemia for which he had completed six cycles of ofatumumab and chlorambucil 2 months prior to presentation. Biochemistry, physical examination and imaging were unremarkable on admission. Subsequent neurological examination demonstrated diminished reflexes and an extensor right plantar, while magnetic resonance imaging (MRI) assessment revealed white matter hyperintensities in the frontal lobes with restricted diffusion surrounding these areas. Cerebrospinal fluid (CSF) analysis demonstrated normal cell counts and chemistry but detected John Cunningham virus (JCV) via polymerase chain reaction (PCR), with a quantitative value of 41,850 gEg/ml. CSF immunophenotyping excluded malignant processes. A diagnosis of PML was confirmed, and with the support of palliative care, the patient was discharged to a hospice for ongoing care with the family's agreement. Conclusion PML remains a rare complication of ofatumumab treatment. Nevertheless, clinicians should maintain a certain level of suspicion for this risk, especially in the context of patients presenting with clinical syndromes of encephalopathy and focal neurologic deficits. Furthermore, research to better our understanding of the manifold links between B-cell function and JCV regulation could provide valuable information for use in the future prevention and treatment of PML.

Introduction Intravenous fluids are one of the most commonly prescribed drugs in the hospital setting and yet the practice continues to fall short of National Institute for Health and Care Excellence (NICE) guidelines, with significant gaps in staff knowledge exposing patients to heightened morbidity and mortality. Aim Following the 2013 publishing of updated NICE guidelines on intravenous fluid prescribing, an intravenous fluid team was formed within the Royal Liverpool University Hospital (RLUH). Their role has been (and continues to be) to overhaul the culture of suboptimal intravenous fluid prescribing within the hospital and, ultimately, to improve patient outcomes. A framework to engender this change has been developed and is offered as an example to other Trusts within which improvement of guideline-compliant intravenous fluid prescribing remains stagnant. Method There have been three principal stages of the project to this point which are best demonstrated in a chronological manner. The period of 2010–2014 allowed for assessment of the issue of intravenous fluid prescribing and analysis of its causes through serial audits and a staff-wide survey. From 2015, there has been implementation of several measures (educative, managerial, administrative and technological) within the hospital to foster reproducible and positive change with regards to intravenous fluid prescribing. Finally, between 2016 and 2017, three cycles of a rolling audit based on NICE guidelines have been completed to allow measurement of improvement in intravenous fluid prescribing practice. Conclusion Results have demonstrated a significant improvement in the appropriateness of the intravenous maintenance and replacement fluids prescribed in the hospital since the March 2016 audit. Moreover, a 29-fold increase has been observed in the use of 4% dextrose/0.18% sodium chloride as maintenance fluid (gold standard as per NICE guidelines) since the staff-wide survey of 2015. Despite progress however, adherence to NICE guidelines remains below the recommended 100% and therefore further work remains to be done.