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Introduction Pneumococcal disease (PD) significantly contributes to morbidity and mortality, carrying substantial economic and public health burden. This article is a targeted review of evidence for pneumococcal vaccination in the UK, the definitions of groups at particular risk of PD and vaccine effectiveness. Areas covered Relevant evidence focusing on UK data from surveillance systems, randomized controlled trials, observational studies and publicly available government documents is collated and reviewed. Selected global data are included where appropriate. Expert opinion National vaccination programs have reduced the incidence of vaccine-type PD, despite the rising prominence of non-vaccine serotypes in the UK. The introduction of higher-valency conjugate vaccines provides an opportunity to improve protection against PD for adults in risk groups. Several incentives are in place to encourage general practitioners to vaccinate risk groups, but uptake is low-suboptimal particularly among at-risk individuals. Wider awareness and understanding among the public and healthcare professionals may increase vaccination uptake and coverage. National strategies targeting organizational factors are urgently needed to achieve optimal access to vaccines. Finally, identifying new risk factors and approaches to risk assessment for PD are crucial to ensure those at risk of PD can benefit from pneumococcal vaccination.

Abstract Myeloma patients presenting with renal failure continue to have a poor prognosis despite significant advances in anti‐myeloma therapy. MERIT was a randomised clinical trial (RCT), set up to evaluate if mechanical reduction of elevated free light chain levels (FLC) would result in clinical benefit. Completion of the planned seven plasma exchanges (PEs) in the first 14 days failed to show, for the exchange group, a greater reduction in FLC or any improvement in dialysis independence at 100 days or subsequently. To improve prognosis for these patients requires earlier diagnosis and prompt anti‐myeloma therapy with effectiveness guided by frequent FLC monitoring.

Monoclonal gammopathy (MG) is a frequently detected clonal B-cell or plasma-cell disorder. Importantly, every multiple myeloma (MM) case is preceded by MG. Although clinical algorithms now allow earlier treatment of patients with biomarkers of malignancy before MM-induced tissue damage (CRAB) occurs, most patients are still diagnosed late. It is important to revisit how MG should be managed in clinical practice and whether screening is required. As the prevalence of MG and other medical co-morbidities both rise with increasing age, the degree of contribution of MG to disease states other than malignant progression is often unclear. This can lead to monitoring lapses and under recognition of the organ dysfunction that can occur with monoclonal gammopathy of clinical significance (MGCS). Therefore, models of progression to MM and/or MGCS require further refinement. While MG is currently detected incidentally, a case for screening has been made with ongoing studies in this area. Screening has the potential benefit of earlier detection and prevention of both MGCS and delayed MM presentations, but important drawbacks include the psychosocial impact on individuals and resource burden on healthcare services. MG terminology should transition alongside our increasing understanding of the condition and genomic characterization that have already begun to revise the MG nomenclature. The biology of MG has been poorly understood and is often inferred from the biology of MM, which is unhelpful. We review the literature and case for MG screening in this paper. In particular, we highlight areas that require focus to establish screening for MG.

Introduction Multiple myeloma is a plasma cell malignancy that accounts for 1%–2% of newly diagnosed cancers.At diagnosis, approximately 20% of patients can be identified, using cytogenetics, to have inferior survival (high-risk). Additionally, standard-risk patients, with detectable disease (minimal residual disease (MRD)-positive) postautologus stem cell transplant (ASCT), fare worse compared with those who do not (MRD-negative). Research is required to determine whether a risk-adapted approach post-ASCT could further improve patient outcomes.Methods RADAR is a UK, multicentre, risk-adapted, response-guided, open-label, randomised controlled trial for transplant-eligible newly diagnosed multiple myeloma patients, using combinations of lenalidomide (R), cyclophosphamide (Cy), bortezomib (Bor), dexamethasone (D) and isatuximab (Isa).Participants receive RCyBorD(x4) induction therapy, followed by high-dose melphalan and ASCT. Post-ASCT, there are three pathways as follows:A phase III discontinuation design to assess de-escalating therapy in standard-risk MRD-negative patients. Participants receive 12 cycles of Isa maintenance. Those who remain MRD-negative are randomised to either continue or stop treatment.A phase II/III multiarm multistage design to test treatment strategies for treatment escalation in standard-risk MRD-positive patients. Participants are randomised to either; R, RBorD(x4) +R, RIsa, or RBorIsaD(x4) + RIsa.A phase II design to assess the activity of intensive treatment strategies in high-risk patients. Participants are randomised to RBorD(x4) +R or RBorIsaD(x4) + RIsa.1400 participants will be registered to allow for 500, 450 and 172 participants in each pathway. Randomisations are equal and treatment is given until disease progression or intolerance.Ethics and dissemination Ethical approval was granted by the London–Central Research Ethics Committee (20/LO/0238) and capacity and capability confirmed by the appropriate local research and development department for each participating centre prior to opening recruitment. Participant informed consent is required before trial registration and reconfirmed post-ASCT. Results will be disseminated by conference presentations and peer-reviewed publications.Trial registration number ISCRTN46841867.

Objectives: To determine the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody status amongst healthcare workers (HCWs) working through the first wave of the Coronavirus (COVID-19) pandemic in 2020. To examine the association of seroprevalence and self-reported COVID-19 symptoms with occupation, sex, and ethnicity; and how these factors were associated with physical and mental wellbeing. Design: Single-centre cohort study. Setting: Large public hospital in the United Kingdom. Intervention: All HCWs who had been tested for anti-SARS-CoV-2 immunoglobulin (Ig) G nucleocapsid antibody in summer 2020 were asked to complete an electronic survey focusing on their physical and mental health in Winter 2020–21. This survey was comprised of the Short Form 12v2, Physical Component Summary (PCS), Mental Component Summary (MCS), and Generalised Anxiety Disorder 7-item (GAD-7) questionnaires. Results: 7604/9781 (77.7%) HCWs were antibody tested, of which 1082 completed the full survey. Antibody testing was conducted between 17/06/20–30/07/20, during which time our seroprevalence rate was 28% (299/1082). Of those self-reporting COVID-19 symptoms, 51% (201/395) were antibody positive. Antibody-positive participants had lower PCS scores (p = 0.016), indicating poorer physical health. Lower PCS scores were also found in those deemed high risk for COVID-19 by their GP (p = 0.001), and those aged >44 years (p = 0.009). Antibody-negative participants had lower MCS scores (p = 0.044), indicating poorer mental health. Those who self-reported COVID-19 symptoms had lower PCS scores (p=

Variable responses to vaccination are of historical and current concern, particularly among vulnerable groups. Biochemical and behavioural methods of improving vaccination response have been examined. There is some evidence that vaccinating in the morning could enhance vaccine responses, however, this has consistently been shown in thymus-dependent vaccinations, such as influenza. The present analysis of data from two observational studies of the association between psychosocial factors and vaccination response. These data included response to a thymus-independent vaccination - pneumococcal polysaccharide vaccine, examined morning versus afternoon vaccine administration in 75 healthy young adults and 61 parents, including 32 caregivers of a child with a development disability and 29 control parents. In both datasets, timing of vaccination was not related to antibody response. This suggests that effects of time of day may be limited to thymus-dependent vaccinations although replication in a large randomised controlled trial using other thymus-dependent vaccinations is required.

Autologous stem cell transplant (ASCT) remains the standard of care for consolidation after induction therapy for eligible patients with newly diagnosed myeloma. In recent clinical trials comparing ASCT to delayed ASCT, patients aged over 65 were excluded. In real-world practice stem cell transplants are not restricted to those aged under 65 and clinicians decide on transplant eligibility based on a patient’s fitness rather than a strict age cut-off. Data from the UK NCRI Myeloma XI trial, a large phase III randomized controlled trial with pathways for transplant-eligible and -ineligible patients, were used in an exploratory analysis to examine the efficacy and toxicity of ASCT in older patients including an analysis using an age-matched population to compare outcomes for patients receiving similar induction therapy with or without ASCT. Older patients within the transplant-eligible pathway were less likely to undergo stem cell harvest at the end of induction than younger patients and of those patients undergoing ASCT there was a reduction in progression-free survival associated with increasing age. ASCT in older patients was well tolerated with no difference in morbidity or mortality between patients aged

Abstract Background There is a paucity of data on paediatric kidney disease in developing countries such as Malawi. Descriptive research on kidney disease is essential to improving patient outcomes. Methods We conducted a cross-sectional study at a tertiary hospital in Malawi from 2012 to 2013. Children under 14 years with proteinuric kidney disease were enrolled from paediatric wards and outpatient clinics at Queen Elizabeth Central Hospital (QECH). Demographic, clinical and laboratory data were collected from patients at enrolment and at 3 months review at which point clinical status and disease outcome were ascertained. Results Thirty-four (22 male) patients were studied, mean age 8.54 (SD = 3.62 years). Glomerular disease (n = 25, 68%) was the most common presumed renal lesion at presentation. Nephritic syndrome (10) was characterised by a lower baseline complement C3 than nephrotic syndrome (p = 0.0027). Seven (47%) cases of nephrotic syndrome achieved complete remission. Eight (80%) cases of nephritic syndrome improved with supportive therapy. Nineteen (56%) patients presented with clinically significant renal damage with eGFR

We previously reported the safety and efficacy of low dose BaP [Bezafibrate (Bez) and Medroxyprogesterone acetate (MPA)] in 20 acute myeloid leukaemia (AML) patients for whom chemotherapy was not an option. This study provided evidence that BaP had anti-AML activity and improved haemopoiesis; absence of haematological toxicity allowed continuous daily administration. Similarly a previous trial in endemic Burkitt lymphoma demonstrated anti-B cell lymphoma activity of low and high dose BaP again in the absence of toxicity.We conducted a study to further evaluate the safety and activity of high dose BaP therapy in adults with AML (and high risk Myelodysplastic Syndromes (MDS)), chronic lymphocytic leukaemia (CLL) or B-cell Non-Hodgkin Lymphoma (BHNL). Eighteen patients were recruited to the study over 20 months, 16 AML/MDS, 1 CLL, and 1 BNHL. Although MPA was well tolerated throughout the study, only 2 patients were able to tolerate Bez treatment for their whole trial duration, indicating that Bez escalation is not feasible in the setting of adult AML/MDS. Thus there has been no obvious benefit in improved haemopoiesis or overt anti-leukaemia activity from the attempts to escalate BaP dose over previous published studies. Since current therapeutic options in MDS are restricted it may be now of value to continue to evaluate low dose BaP based approaches in low risk MDS rather than AML/high risk MDS. Furthermore, screening of low dose BaP against libraries of other already available dugs may identify an addition to BaP that augments the anti-neoplastic efficacy without significant toxicity. Keywords: Clinical trials, Myeloid leukaemia, Lymphoid malignancies, Therapy, Bezafibrate, Progesterone

Diagnosis of myelodysplastic syndrome can be difficult especially in cases with a low blast count and a normal karyotype. Flow cytometry has been used to distinguish myelodysplastic syndrome from non-clonal cytopenias. No one single simple flow cytometric parameter has been proposed to be diagnostic of myelodysplastic syndrome. We have studied samples from 100 myelodysplastic syndrome patients and as control samples; 70 non-clonal cytopenias, 5 subjects with normal hematology, 31 patients with acute myeloid leukemia and 11 with chronic myelomonocytic leukemia or myeloproliferative disorder. We show that reduced relative mean fluorescence of CD38 below a threshold value on CD34+ cells diagnosed low-grade myelodysplastic syndrome with 95% sensitivity (95% confidence interval, 87–99%) and 92% specificity (95% confidence interval, 82–97%). This simple flow cytometric test may be of value in the routine clinical diagnosis of myelodysplastic syndrome, especially in cases with a low blast count and normal karyotype.