This investigation of patients' and carers' experiences of NS identifies numerous strategies for improving patient education, support and pre-hospital management, all of which may reduce pre-hospital delays and consequently decrease morbidity and mortality from NS.

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms.

Rachel T Clarke, 1 academic foundation doctor; Tom Jenyon, 2 medical education fellow; Victoria van Hamel Parsons, 3 medical student; Andrew J King, 1 specialist registrar, haematology

Venous thromboembolism (VTE) is a recognised complication of sickle cell disease (SCD), long considered to be a hypercoagulable state. While there is a good understanding of arterial thrombosis in SCD, the nature of VTE in SCD is less well-characterised. In this retrospective cohort study, we found that the incidence of VTE in our patient cohort was higher than in the non-SCD black population; patients of all SCD genotypes with VTE had significantly elevated steady-state platelet counts compared to those without. Recent hospitalisation (typically with acute sickle pain) was the commonest precipitating risk factor. These findings suggest consideration of longer VTE prophylaxis for acute hospital admissions in SCD.

Purulent pericarditis due to Neisseria meningitidis without meningeal infection is rare, only ten cases having been reported (Solheim et al, 1977;Thompson et al, 1977). This case is of additional interest because the patient developed and recovered from acute renal failure after surgical drainage of a pericardial effusion causing tamponade. Case historyA 33-year-old woman presented with severe retrosternal chest pain and dyspnoea after a one-week period of non-specific malaise without meningitic symptoms. There was no relevant medical history.The only abnormal findings and investigations on admission were a temperature of 38 4'C and white cell count of 25 9X 10'/l (87% neutrophils). The pain radiated to the right hypochondrium, and the next day she became shocked and was transferred to this hospital with a presumptive diagnosis of pulmonary embolus.On arrival her systolic blood pressure was 70 mmHg. Her neck veins were distended and there was tenderness and rigidity in the right hypochondrium; the heart sounds were normal. Chest radiography showed a prominent right pulmonary artery but the electrocardiogram was not diagnostic. An echocardiogram showed pericardial fluid. It seemed unlikely that she would tolerate invasive investigations, and she underwent emergency sternotomy with a view to pulmonary embolectomy. The operative findings were of pericardial tamponade, with 400 ml of pus and fibrinous exudate in the pericardium. This was evacuated and a pericardial drain inserted. There was a short episode of ventricular fibrillation while the chest was being closed but resuscitation was performed rapidly. Postoperative blood pressure was 80/60 mmHg, and urine output exceeded 150 ml/hour for six hours. Antibiotic treatment with gentamicin, benzylpenicillin, and flucloxacillin was started, and mechanical ventilation with 7 cm of positive end-expiratory pressure was carried out.By the next day the patient had developed oliguric acute renal failure, and haemodialysis was performed on the third day after operation. There was heavy proteinuria (4,35 g/l), and the urinary sodium concentration was 52-5 mmol/l; the urine contained red blood cells but no casts.For the next three days coagulation studies were consistent with disseminated intravascular coagulation, which was treated with fresh frozen plasma, small doses of vitamin K, and the heparin (2000-3000 IU) needed for haemodialysis.Tracheostomy was performed on the sixth postoperative day; the patient was haemodynamically stable, an echocardiogram showed a small amount of pericardial fluid, and lung function was satisfactory after withdrawal of positive end-expiratory pressure. The infecting organism was characterised as N meningitidis group W135, and treatment with benzylpenicillin alone was continued. Lumbar puncture was performed; the cerebrospinal fluid was normal.She was extubated on the 12th postoperative day but needed haemodialysis for a further two weeks. At that time the echocardiogram showed a small amount of fluid in the pericardium, and the electrocardiogra...

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Introduction: The national Venous Thromboembolism (VTE) Prevention Programme in England was launched in 2010 and incorporates standardised guidance on risk assessment (RA) and thromboprophylaxis (TP) with a requirement for root cause analysis of all episodes of hospital associated thrombosis (HAT), defined as any VTE occurring whilst an inpatient or within 90 days of discharge. We previously reported findings of root cause analysis for HAT over 2010 - 2012, demonstrating that achieving a 90% risk assessment rate resulted in a significant reduction in the incidence of HAT. We update our findings on the impact of implementation of the national programme on the incidence of HAT, proportion of potentially preventable HAT episodes, and mortality from hospital-associated pulmonary embolism (PE). As appropriate TP only reduces the risk of VTE by two-thirds, we also looked at risk factors for TP failure. Methods: We examined HAT data collected from the root cause analysis programme at King's College Hospital from April 2011 to March 2015. Further data were gathered through retrospective review of patient notes. VTE risk factors for HAT attributed to TP failure were compared to a "non-HAT" group, (patients who received appropriate TP and did not develop HAT) drawn from VTE prevention audit data from 2013-2014. Episodes of HAT that developed following inadequate prescription or administration of either anticoagulant or mechanical TP were deemed as "potentially preventable" episodes. Results: Across the four-year study period there were 725 episodes of HAT, giving an incidence of 3.28 episodes per 1000 hospital admissions. There was no significant change in incidence from 2011-2015. The median age of the cohort was 64 years (IQR = 27 years). 56.7% (n = 411) of the HAT episodes were deep vein thromboses, of which 54.7% (n = 225) involved the proximal vasculature. PE accounted for 41.7% (n = 302) episodes, of which 10.9% (n = 33) were fatal events. HAT developed following medical, surgical or obstetric admission in 43.3% (n = 314), 54.6% (n = 396) and 2.1% (n = 15) respectively. VTE risk factors were present in 97.9% (n = 710) of patients with HAT with concomitant bleeding risk factors in 37.1% (n = 269). Consistently, the most common outcome of root cause analysis was TP failure (47.6% overall, n = 345) with no significant trend across the study period; 19.7% (n = 143) of episodes were attributed to inadequate anticoagulant TP, 26.1% (n = 189) to contraindication to anticoagulant TP, 4.4% (n = 32) to contraindication to all forms of TP, and 2.2% (n = 16) episodes were unexpected (HAT occurring in a patient without identifiable VTE risk factors). There has been a significant reduction in the proportion of potentially preventable HAT episodes from 38.2% (n = 66) in 2011-2012 to 20.3% (n = 39) in 2014-2015 (p < 0.001). Furthermore, the proportion of fatal PE reduced over the study period from 16.0% (n = 12) of HAT in 2011-2012 to 6.3% (n = 5) of HAT in 2014-2015 (p = 0.049). The audit of VTE prevention practice over 2013/14 included 515 patients, of which 423 (82.1%) received appropriate TP and did not develop HAT. Compared to this group, patients with HAT attributed to TP failure had more risk factors (3.1 vs. 2.7, p < 0.002), were more likely to be over 60 years of age (59.4% vs. 42.3%, p = 0.01), or to have had orthopaedic surgery(6.7% vs. 1.8%, p = 0.001). Discussion: Implementation of a comprehensive VTE prevention programme incorporating root cause analysis of HAT has led to a significant fall in the proportion of HAT that were potentially preventable with a corresponding reduction in mortality attributed to PE. However, there has been no change in the overall incidence of HAT with a rise in cases associated with TP failure. Further research is required to optimise TP in high VTE risk groups. Disclosures Arya: Bayer plc: Research Funding.

ObjectivesRegular intravenous immunoglobulin (IVIg) is commonly used for autoimmune neurological conditions. In our hospital, 388 patients received 203,571 grams of IVIg in 2014/15 amounting to 3127 patient-days. Given potential side effects, cost and impact to patients, we reconfigured our service to improve clinical assessment prior to IVIg administration and reduce waiting times.MethodsWe mapped a typical patient journey and minimised processes that did not add value. Through workshops with juniors, consultants, nurses, managers and pharmacists we identified drivers for delays and suboptimal assessments, and raised awareness of the issue. Finally, we trialed a clerking proforma with prompts for risk factors and a junior doctor-led ‘2-Step IVIG clinic’ for IVIg day admissions.ResultsWe audited 62 patients over 12 weeks. Following our interventions, mean waiting time from arrival to IVIg administration was reduced from 71.2 (median 55, IQR 5–160) to 20.7 minutes (median 20, IQR 5–30). Pre-IVIG clinical assessment was also improved with 100% of patients assessed for thromboembolism (from 45.5%), infection (from 90.9%) and comorbidities (from 72.7%).ConclusionOur project highlights the importance of a multidisciplinary approach, allowing us to implement significant changes in the unit's structure, reduce unnecessary waiting times and ensure safe administration of IVIg.