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AimsThe population prevalence of cardiomyopathies and the natural history of symptomatic heart failure (HF) and arrhythmia across cardiomyopathy phenotypes is poorly understood. Study aims were to estimate the population-diagnosed prevalence of cardiomyopathies and describe the temporal relationship between a diagnosis of cardiomyopathy with HF and arrhythmia.MethodsPeople with cardiomyopathy (n=4116) were identified from linked electronic health records (~9 million individuals; 2000–2018) and categorised into hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM) and cardiac amyloidosis (CA). Cardiomyopathy point prevalence, rates of symptomatic HF and arrhythmia and timing relative to a diagnosis of cardiomyopathy were determined.ResultsIn 2018, DCM was the most common cardiomyopathy. DCM and HCM were twice as common among men, with the reverse trend for ARVC. Between 2010 and 2018, prevalence increased for ARVC by 180% and HCM by 9%. At diagnosis, more patients with CA (66%), DCM (56%) and RCM (62%) had pre-existing HF compared with ARVC (29%) and HCM (27%). Among those free of HF at diagnosis of cardiomyopathy, annualised HF incidence was greatest in CA and DCM. Diagnoses of all cardiomyopathies clustered around the time of HF onset.ConclusionsThe recorded prevalence of all cardiomyopathies increased over the past decade. Recognition of CA is generally preceded by HF, whereas individuals with ARVC or HCM more often developed HF after their cardiomyopathy diagnosis suggesting a more indolent course or better asymptomatic recognition. The clustering of HF and cardiomyopathy diagnoses suggests opportunities for presymptomatic or earlier diagnosis.

Panobinostat (a pan histone deacetylase inhibitor) is approved in combination with bortezomib and dexamethasone for patients with relapsed multiple myeloma who have received two or more previous lines of therapy. We aimed to improve the safety of this combination and investigate efficacy by incorporating low-dose thalidomide, using sub-cutaneous weekly bortezomib, and determining the maximum tolerated dose of panobinostat in this regimen.

Although an Observed Structured Clinical Examination (OSCE) has been used to evaluate patient interaction and general knowledge competencies of third-year students during their required surgical clerkships, whether surgical clerkship experience predicts satisfactory performance with a surgical patient in an OSCE environment has not been investigated.

The article discusses Tappan Square as a paradigm of changing vision of Oberlin, Ohio. The town has been the site of several transformations of its founders' original concept of utopia for its one hundred and fifty year history. In the first half of Oberlin's history, the building of utopia in this town reflected an architecturally unified college and town. The second half, Oberlin College attempted to project its reputation as a respectable institution in the form of an academic campus clearly separate, but not antagonistic to, from the town.

Introduction and methods:Myeloma is a cancer with one of the longest pathways to diagnosis. This may be due to the non-specific nature of presenting symptoms and its' relative rarity. Early diagnosis initiatives have focused on the role of the primary physician. Despite concern that patients referred to non-haematology specialists may experience long diagnostic intervals, data remain sparse on pathways within hospital care. The TEAMM trial is a double-blind, placebo controlled multicentre UK trial of supportive care, investigating levofloxacin prophylaxis for 12 weeks from diagnosis to reduce infection, versus the risk of healthcare associated infection. Data were collected from patients within 14 days of starting anti-myeloma treatment, including symptoms attributable to myeloma, visits to their primary physician, first hospital department visited for these symptoms, and first visit to a haematologist, with corresponding dates. The relationship between diagnostic time intervals and the number of CRAB (hyperCalcaemia, Renal disease, Anaemia, Bone disease) features and ISS (International Staging System) were analysed by pathway into hospital care using the chi-square test for categorical variables or Wilcoxon/Kruskal-Wallis test for continuous variables as appropriate.

Williams: Novartis: Honoraria; Janssen: Honoraria, Other: Travel support, Speakers Bureau; Celgene: Honoraria, Other: Travel support, Speakers Bureau; Takeda: Honoraria, Other: Travel support, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Yong:Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor; Janssen: Research Funding. Cook:Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Glycomimetics: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Jenner:Amgen: Consultancy, Honoraria, Other: Travel support; Takeda: Consultancy, Honoraria, Other: Travel support; Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Morgan:Univ of AR for Medical Sciences: Employment; Bristol Meyers: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Davies:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.

Introduction: Histone deacetylase inhibitors (HDACis) have demonstrated clinical efficacy in multiple myeloma, particularly in combination with proteasome inhibitors. CHR-3996 is a class 1 selective HDACi with potent anti-myeloma activity in vitro. Aminopeptidase inhibitors act downstream of the proteasome and prevent breakdown of proteasome generated peptides into amino acids. Synergistic cytotoxicity was observed in vitro when CHR-3996 was combined with the aminopeptidase inhibitor, tosedostat through rapid activation of NFkB followed by increased expression of the repressors IκBα, A20, CYLD, BIRC3. The MUK-three study was designed to translate these pre-clinical findings into a phase 1 clinical trial. This dose escalation study aimed to determine the maximum tolerated dose, safety and preliminary activity of CHR-3996 administered in combination with Tosedostat for patients with relapsed, refractory MM. Here we present the final study results.

Yong: Autolous: Consultancy; Novartis: Consultancy; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS: Honoraria. Off Label Use: Carfilzomib with cyclophosphamide and dexamethasone as therapy in relapsed myeloma. Ramasamy:Celgene: Honoraria; Amgen: Honoraria; Takeda Millenium: Honoraria. Cavenagh:Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Owen:Celgene: Honoraria, Research Funding; Janssen: Honoraria. Kaiser:Chugai: Consultancy; Janssen: Honoraria; BristolMyerSquibb: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Williams:Amgen: Honoraria; Janssen: Honoraria.

Introduction. Carfilzomib-containing doublet and triplet regimens demonstrate high response rates both in the relapsed and frontline settings and will soon enter the treatment pathways for multiple myeloma (MM). While the phase 3 studies, ENDEAVOUR and ASPIRE provide information on combinations with dexamethasone with or without lenalidomide, there are limited data on other combinations, especially with alkylating agents.

Abstract 2074

Around 75% of myeloma patients have evidence of myeloma bone disease at diagnosis and most develop it at some point. Bisphosphonates - pamidronate, sodium clodronate and zoledronic acid - have revolutionised the treatment of myeloma bone disease and form a significant part of the myeloma treatment pathway. It is therefore important to understand patient perspectives of and preferences for this important treatment.To understand the information patients receive from clinicians and the impact this has on their understanding of bisphosphonates, to establish what patient preferences are for how and where they receive bisphosphonates and to determine whether patients are satisfied with the level of decision-making input they have about their bisphosphonate treatment.Patients were asked to complete a 36 question survey, devised by Myeloma UK, which was available in paper copy and online. 606 patients responded to the survey of which 95.3% had received bisphosphonates. When asked about the information they were given by their clinicians when prescribed bisphosphonates, 81.7% received a verbal explanation, 23.7% received written information and 2.7% received details of a website/helpline. 30.6% used a product leaflet and 30.1% sourced a patient organisation information sheet. 80% of patients thought the information was ‘easy to understand’. When asked why they had been prescribed bisphosphonates, patients accurately reported that it was ‘to strengthen the bones’ (82.5%), ‘to delay the progression of myeloma’ (28.7%) and ‘to prevent/reduce high levels of calcium in the blood’ (15.7%). 16.6% of patients wrongly thought that bisphosphonates were prescribed ‘to heal the bones’ and 5.8% had no understanding of bisphosphonates.51.7% of patients received their current or last bisphosphonates ‘by monthly infusion in hospital’ and 39.1% ‘by tablet form at home’. 9.2% stated ‘other’ referring to more flexible methods of prescribing. When asked how they would prefer to receive their bisphosphonates, 46.5% selected ‘by regular visits for infusion in hospital’ and 41.1% ‘by daily tablets taken at home’. Patients who preferred to receive bisphosphonates ‘by regular visits for infusion in hospital’ reported this was due to ‘confidence in quality of care in hospital’ (80.7%), ‘there is medical support on hand’ (54.4%), ‘it keeps a check on my myeloma’ (64.9%), ‘I prefer monthly rather than daily treatment’ (52.1%) and ‘I can get my blood tests done at the same time' (59.1%). Patients who preferred to receive bisphosphonates by ‘daily tablets taken at home’, reported this was due to ‘convenience’ (93.3%), ‘ease’ (71.4%), ‘it reduces hospital visits' (61.6%) and allows them to ‘avoid infusions’ (37.9%).On a scale of (1) no input and (5) full input, patients gave the level of decision-making input they had over how and where to receive bisphosphonates an average rating of 2.1 – 64.6% rated (1), 6.2% rated (2), 4.9% rated (3), 2.8% rated (4), 21.5% rated (5). When asked if they were satisfied with this level of input, 79.5% of patients were satisfied, 20.3% would have preferred more input and 0.2% less.Patients who received information about bisphosphonates were generally satisfied it was good quality and helped them understand why they were prescribed bisphosphonates. A significant proportion of patients did not receive a verbal explanation and/or did not receive written information from a clinician or source information themselves, which explains the high percentage of patients who did not understand why they had been prescribed bisphosphonates.Patients have different and individual preferences for how and where they want to receive bisphosphonates. Patients were polarised between their preferences for receiving their bisphosphonates intravenously or by tablet form and when responses were cross-referenced, their preferences were approximately correlated with their most recent bisphosphonate. The survey also shows approximately 1 in 5 patients would have preferred more decision-making input on their choice of bisphosphonate treatment.In the UK, there is variation in uptake of oral and intravenous bisphosphonates despite evidence showing improved efficacy of intravenous zoledronic acid over oral sodium clodronate. Further investigation is warranted to determine the link between patient's preferences and uptake of different bisphosphonates.Low: Novartis UK Limited: Research Funding. Morgan:Novartis UK Limited: Research Funding.