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Abstracts of the Warwick Undergraduate Medical Research Conference 2011

On 1 October 2011 the Warwick Medical School, University of Warwick, hosted the Warwick Undergraduate Medical Research Conference to showcase undergraduate medical research. Some papers were presented orally, others as posters; selected abstracts may be found below.

 

CONTENTS

Oral presentations: Audits

Improving Emergency Department pain scoring in a district general hospital

N. Britton1 and Dr J. Harden2
1University of Aberdeen, 2Wishaw General Hospital

Failed discharges in the Emergency Admissions Unit (EAU); A Service Evaluation

S. Jaspal
University of Birmingham

 

Oral presentations: Case Reports

Therapeutic Knee Arthroscopy under Local Anaesthesia: A Case Report

E. Watts1, J. Davies2, C. Hickson1
1Warwick Medical School, 2University of Toronto, Canada

 

Posters

Radiological and clinical evaluation of the midterm results of Pinnacle® uncemented acetabular cups

J. Khan and J. Bellevue de Sylva
University of Liverpool

Postoperative nausea and vomiting (PONV) in the Post-anaesthetic care unit (PACU)

M. Shumbusho
Warwick Medical School

Administration of Intravenous Antibiotics in the Management of Neutropenic Sepsis

R. Aiyer and J. Bharya
University of Birmingham Medical School

How well do we screen for diabetes in patients presenting with Acute Coronary Syndrome?

S. Jaspal
University of Birmingham

Elective resection of a right-sided retroperitoneal liposarcoma

Olivia Chu
Warwick Medical School

Caffeine: poison or potion?

N. D. Gollop
Cardiff University

Does multiple modality treatment infer a better outcome than single modality treatment? Does chemotherapy improve survival outcome?

K. Khan-Mahmood and G. Alusi
Barts and the London School of Medicine and Dentistry

The potential role of OX40/CD30 as organisers of inflammatory infiltrates in a novel model of tertiary lymphoid neogenesis in murine salivary glands

P. Rankin and M. Chung
University of Birmingham

Differences in the program of lymphatic and vascular vessel formation in a novel model of ectopic lymphoneogenesis in salivary glands

M. Chung and P. Rankin
University of Birmingham

The effect of a family history of major depression on the outcome of electroconvulsive therapy

C. Smith
Cardiff University

Are partially activated non-dividing effector cells (PANDEs) tolerant or anergic T-cells?

A. Baheerathan
University of Leicester

Producing and evaluating a novel lentiviral vector for β-thalassaemia Gene therapy

Y. Bokinni, Dr V. Kao, Dr M. García-Gómez and Dr M. Antoniou
King's College London

Exploring the extent of communication surrounding the transition to palliative care in patients with heart failure

E. Green, C. Gardiner, C. Ingleton and M. Gott
University of Sheffield

 

ABSTRACTS

Oral presentations: Audits


Improving Emergency Department pain scoring in a district general hospital

N. Britton1and Dr J. Harden2
1University of Aberdeen, 2Wishaw General Hospital

Background and Aims

Pain is commonly under-recognised, under-treated and there is often a delay in treatment. An audit was carried out to assess whether interventions had improved the recording of pain scores and management of pain in Wishaw General Hospital Emergency Department (ED). The data collected was compared with standards set out by the College of Emergency Medicine to gauge how effective interventions had been.

Methods

Data was collected retrospectively for patients attending the ED on two randomly allocated dates in February 2010 and again in July 2011. Exclusion criteria included children, direct speciality referrals, patients treated in out-of-hours GP and patients attending clinics.

Results

The initial audit showed sub-optimal pain score recording and administration of analgesia. Following the introduction of a more robust triage system, the re-audit demonstrated an 8% increase (13% to 21%) in the number of patients with a pain score recorded. A 5% increase was also noted in the number of patients who received analgesia. However, the average time taken to receive analgesia had increased by 50% compared to the first cycle audit.

Conclusion and Implications

Although some aspects of pain management have improved following re-audit, other areas continue to fall below standards. We explain how simple interventions may be used to improve future results.


Failed discharges in the Emergency Admissions Unit (EAU); A Service Evaluation

S. Jaspal
University of Birmingham

Background

Failed discharges are a measure of service efficacy. The number of hospital readmissions has increased by 110,000 over the last 10 years. It has been suggested that this increase is due to hospital staff wanting to discharge patients as soon as possible to free up hospital beds more quickly. This implies a level of sub-optimal care. New legislation is set to introduce a system where hospitals will not be paid for readmissions that could have been prevented.

Method

Retrospective service evaluation, looking at the number of failed discharges in the Emergency Assessment Unit (EAU) of Wolverhampton New Cross Hospital. A failed discharge was defined as a patient readmitted to the EAU within 30 days of their discharge from the EAU. Patient notes were looked at to determine the number of failed discharges. The failed discharge was then categorised as avoidable or unavoidable, depending on the reason for the failed discharge.

Results

198 patients were included in this service evaluation. 9 of the 198 patients were identified as failed discharges. 2 of the 9 failed discharges were classed as avoidable, and the reasons for both failed discharges were due to a lack of social support for the patient and patient's family.

Conclusions

The Wolverhampton New Cross EAU has a low rate of failed discharges (4.55%). However, by improving the social support for patients and their families, where this support is offered at an earlier stage, this rate could be lowered further.

 

Oral Presentations: Case reports


Therapeutic Knee Arthroscopy under Local Anaesthesia: A Case Report

E. Watts1, J. Davies2, C. Hickson1
1Warwick Medical School, 2University of Toronto, Canada

Introduction

A 55-year-old British male presented to an orthopaedics outpatient appointment with right-sided knee pain. He described a long history of localised pain over the medial margin following a twisting injury 6 months ago. The patient gave a short history of swelling and instability in the knee joint, but denied any history of catching or locking. He had a BMI of 55 (wt. 160 kg) and was currently being treated for hypercholesterolemia, hypertension (168/91), atrial fibrillation and non-insulin dependent diabetes.

Examination

The patient had a normally aligned knee joint with localised tenderness over the medial joint space. Due to the large circumference of his thigh, leg and knee, the presence of oedema could not be accurately assessed. Special tests (e.g. Lachmann's, McMurray's) could also not be performed. MRI showed a medial meniscal tear involving the posterior horn. He was scheduled for an arthroscopic meniscal repair pending anaesthetic review.

Anaesthetic review concluded that the patient was unfit for general anaesthetic, due to his high BMI and significant co-morbidities. The patient also refused spinal anaesthesia. After further discussions with the patient, he elected to have the arthroscopic meniscal repair under local anaesthesia.

Treatment

The patient's right knee was injected with 80mL of 1% lignocaine and adrenaline diluted to 120 mL with saline over the standard antero-medial and antero-lateral portal sites, and into the knee joint. No tourniquet was used. The degenerate posterior horn tears were debrided to stabilise the joint margins. The patient reported a slight instance of pain during meniscal debridement and instrument induction, but described the overall experience of the procedure as pain-free.

Conclusion

Local anesthesia for knee arthroscopy should be considered a safe alternative in all patients requiring spinal anaesthesia. Systematic review studies have found that it is well tolerated and cost effective; with 95% of patients agreeing that they would have the same procedure under local anesthesia in the future.

 

Posters


Radiological and clinical evaluation of the midterm results of Pinnacle® uncemented acetabular cups

J. Khan and J. Bellevue de Sylva
University of Liverpool

Introduction

Total Hip Arthroplasty utilises many forms of artificial implants which inevitably have varying rates of success. Prostheses vary greatly in design areas such as bearing surface, head size and method of fixation to name a few. The only way to assess accurately how an implant performs is by monitoring it post-operatively; some implant designs have been shown by similar studies to have unacceptable failure rates. The surgeon requires accurate and reliable data on all forms of modern hip prostheses in order to make the best clinical decision, and to ensure the procedure yields the best results possible.

Aim

We aimed to contribute to the knowledge base by providing midterm clinical and radiological performance measures, taken from the radiographs and clinical assessment of a sample of 241 hips fitted with the DePuy Pinnacle®Cup at Broadgreen hospital, with a minimum 5-year follow-up (range 5-9 years, mean 7.2 years).

Methods

A single surgeon series was used for sample selection of patients with an operation date between February 2002 and September 2004. Baseline measurements such as BMI and Charnley classification were recorded from patient notes whilst Harris hip score (HHS) was measured pre-operatively and post-operatively at every follow-up clinic visit. TraumaCad software was used to take measurements of cup version and inclination.

Results

An average increase of 44.57 was found in HHS (95% CI 41.79 – 47.35). The mean cup inclination was 48.9° with a range of 30° - 67°. Mean cup version was 11.43° with a range of 0° - 33°. The revision rate for any reason was 5.4%. There was no evidence of loosening noted in any surviving cups on radiological assessment.

Conclusion/Recommendations

The Pinnacle®cup has displayed a low incidence of failure after 5 years with a clear improvement in HHS. Based upon these promising midterm results we recommend use of the Pinnacle® cup in patients of a similar demographic. We recommend continued auditing at 5-year intervals to gain long term outcomes.


Postoperative nausea and vomiting (PONV) in the Post-anaesthetic care unit (PACU)

M. Shumbusho
Warwick Medical School

This is a re-audit that was done to see if there has been an improvement in the incidence of PONV in PACU.

Aims

To establish current anti-emetic practice in surgical procedures at the University Hospital Coventry & Warwickshire (UHCW); to quantify scale of PONV in PACU at UHCW in 2010; to examine audit adherence to departmental PONV guidelines.

Method

This was a prospective survey over a period of 4 weeks in July/August 2010, carried out in the PACUs at UHCW and St Cross Hospital, Rugby. Data collection was done with a proforma and tick-box system. Only surgical cases that required general anaesthesia (GA) were included in audit. The PONV Criteria was 1) No Nausea or Vomiting, 2) Nausea only, or 3) Vomited.

The audit standard was that 100% of patients should receive care that followed departmental guidelines; 100% of high-risk patients should receive prophylactic anti-emetics; 100% of patients should prescribed anti-emetics for the treatment of established PONV as per the guidelines; and that 0% of low-risk patients should receive prophylactic anti-emetics.

Results

A total of 178 patients were audited but 15 were excluded, so analysis was carried out on 163 patients: 98 females and 64 males. 94% (154/163) patients experienced no PONV, while only 6% (9/163) suffered PONV even though 74% (120/163) were in medium- to high-risk groups for PONV. 7.3% (12/163) patients required anti-emetic Rx in PACU for PONV.

Ondansetron and Dexamethasone were the two most commonly used prophylactic anti-emetics, whereas Cyclizine, Ondansetron & Buccastem were the most commonly prescribed treatment of PONV. IM Prochlorperazine was prescribed to only 1.2% (2/163) patients.

Conclusion

The incidence of PONV in PACU at 6% is low and reflects good departmental clinical practice. It has also improved from 8% in the 2007 PONV audit results. However, departmental guidelines need to be reviewed to reflect current departmental practice. Current guidelines state that treatment of PONV should commence with Cyclizine 50 mg IM or IV and if PONV still isn't controlled to give Prochlorperazine 12.5mg IM or 25mg PR 8 hourly for 24 hours. If this still doesn't control it Ondansetron 4mg IV as a single dose should be the last resort.


Administration of Intravenous Antibiotics in the Management of Neutropenic Sepsis

R. Aiyer and J. Bharya
University of Birmingham Medical School

Introduction

Febrile neutropenic sepsis is a serious complication of chemotherapy. Despite the number of different care protocols that exist, one of the problems includes the time taken to administer IV antibiotics to patients presenting with chemotherapy-induced neutropenia. Selected hospitals have a Patient Group Direction (PGD) in place which allows nurses to deliver the first dose of antibiotic without waiting for a medically authorised prescription, which could potentially save lives.

Method

This study explores the management of 61 subjects who were admitted into the Queen Elizabeth Hospital presenting with symptoms such as pain, pyrexia, rigors, sore mouth and general malaise and compared the use of PGD to it non-use.

Results

Of the 61 patients who were administered antibiotics, 20 were specifically reviewed. 13 patients were administered antibiotics in a time lapse of >1hr. In the whole study 7 PGDs were used and allowed for the patient to be treated within an average time of 37 minutes compared to 163 minutes (2hr43min) for the other patients.

Discussion

In the last few months of undertaking this audit, the majority of patients received their treatment within an hour. However, it is obvious that there were 13 patients who had delayed treatments (>1hour). On the other hand, the 7 patients who benefited from the use of PGD received the antibiotics on average 126 minutes quicker.


How well do we screen for diabetes in patients presenting with Acute Coronary Syndrome?

S. Jaspal
University of Birmingham

Background

Acute coronary syndrome (ACS) covers a range of acute myocardial states. Diabetes is associated with increased risk of mortality after an ACS. Elevated blood glucose at hospital admission for ACS is a strong indicator of poorer prognosis and glycaemic control decreases after an ACS. Therefore, recommended guidelines suggest that all patients admitted with an ACS have a laboratory glucose measurement.

Method

The angiography list was used to identify possible patients that may have been previously or currently admitted for an ACS. The hospital 'iCare' portal, an electronic system with access to patient notes, was then utilised to identify those who had been admitted for an ACS. 'iCare' was utilised to determine the diabetic status of the patient and to ascertain blood test results. The blood test results under scrutiny were laboratory glucose and HbA1c.

Results

21 of 40 patients (52.5%) admitted with an ACS had laboratory blood glucose measured during their admission to the hospital. No new diabetics were identified. 5 previously known diabetics were included in the audit; 3 had their HbA1c measured, whilst none had laboratory glucose measurements.

Conclusions

With only 52.5% of ACS patients having a formal laboratory glucose measurement during their hospital admission, we are not currently measuring laboratory glucose measurements as often as recommended. Screening for diabetes in ACS patients is not optimum. There is much scope for improvement.


Elective resection of a right-sided retroperitoneal liposarcoma

Olivia Chu
Warwick Medical School

Background

Liposarcoma was first described by Virchow in the 1860s; it is now recognised as the most common of soft tissue sarcomas, which are relatively rare in relation to other types of cancer. Liposarcomas normally occur in middle age, showing a slight predominance toward men. Most cases arise de novo, frequently arising from deep-seated stroma of the extremities. The most recent World Health Organization classification of soft tissue tumours recognizes 5 categories of liposarcomas, from well differentiated to pleomorphic.

Case description

We describe the case of a 62-year-old female from the West Midlands who reported 6 weeks history of "pulling" discomfort in the right upper quadrant of the abdomen with associated post-prandial pain. A firm abdominal mass was noticed and was reported to have enlarged over weeks. CT investigation found a large right-sided retroperitoneal liposarcomas. The lady was admitted for elective resection of the mass.

Clinical outcome

An en bloc resection was achieved; after careful inspection no macroscopic malignancy was found. A tumour of 4.2kg was excised along with a right nephrectomy, a right hemicolectomy, and a sliver of liver resected. Histological investigation showed a grade 3 dedifferentiated liposarcomas with no evidence of lymphovascular invasion.

Learning points

Liposarcomas tend to originate in stromal tissues rather than adipose tissue; retroperitoneal liposarcomas should be considered when abdominal mass is reported without significant systemic symptoms; surgical management in this instance would prevent further dedifferentiation and improve survival rate.


Caffeine: poison or potion?

N. D. Gollop
Cardiff University

Introduction

In health and disease apoptosis is a complex and important mode of controlled cell death. Caffeine (3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6,-dione) is a central nervous system stimulant which can be used socially and in medicine to increase sympathetic activity. Recent data has shown that high doses of caffeine may induce apoptosis in pathological skin cells.

Aim

To observe the effects of increasing concentrations of caffeine on rates of apoptosis in two novel cell lines.

Method

Caffeine was applied at varying concentrations (5mM-60mM) to non-adherent and adherent ARPE-19 (a human retinal pigment epithelial cell line) and MDCKii (Madin-Darby canine kidney II) cell lines. The effect of the stimulant was recorded and assessed by the use of direct imaging, lactate dehydrogenous (LDH) assays, and DAPI (4',6-diamidino-2-phenylindole) staining and fluorescence microscopy.

Results

At 24 hours, the induction of apoptosis was apparent in both cell lines from concentrations of 5mM. The MDCKii cell line completed apoptosis at 20mM and the ARPE-19 cell line at 60mM. At 48 hours, induction and completion was seen in both cell lines at 5mM. The adherent cells showed greater resilience to apoptosis throughout. LDH levels correlated with visual findings.

Conclusion

As caffeine concentrations and exposure time increased, the rate and effect of apoptosis also increased.

The results create many questions about the use of caffeine. With the average cup of coffee containing between 1.74mM and 3.81mM of caffeine, could excessive use have harmful, long-term apoptotic effects? Alternatively, could caffeine have an anti-cancer application, killing pathological cells by design?


Does multiple modality treatment infer a better outcome than single modality treatment? Does chemotherapy improve survival outcome?

K. Khan-Mahmood and G. Alusi
Barts and the London School of Medicine and Dentistry

Method

Patient data was extracted from the NHS database using EPR viewer to produce a cohort of 273 patients with oral cavity and oropharyngeal squamous cell carcinoma. They were examined with regard to a number of factors and outcomes with comparisons being made. The cohort was then divided into early- and late-stage cancers using T staging. Within each group the same factors and outcomes were investigated, after which early and late cancers were compared together. Statistical analysis was carried out using the SPSS program to produce Kaplan Meier plots to examine survival outcome between the various treatment modalities and outcomes in regards to T and cancer staging.

Results

This study highlighted that out of the deceased group of patients, the majority (72.8%) died within 2 years of treatment, regardless of cancer site, stage or treatment modality (all inclusive). When multiple and single modality treatments were investigated in terms of survival outcome, T staging and cancer staging produced differing results. This is significant as the two staging systems are linked and yet produced differing results. There were too many variables in this study, with not enough data within each comparison set to come to a statistically significant conclusion for each comparison made in order to answer the objectives set out at the beginning of the study. Results were inconclusive as to which treatment modality inferred the best outcome, mimicking the literature.

Conclusions

It was difficult to ascertain a clear-cut conclusion as to whether multiple modality treatment had a better outcome compared to single modality treatment, with equal survival and mortality figures being found for both treatment modalities. A possible reason for this could be the sample size being too small. Grouping carcinomas as early and late made comparisons easier and highlighted that it is very difficult to examine single versus multiple modality and outcome, as single modality treatment can be very different for early stage carcinomas and late stage carcinomas and doesn't necessarily infer a worse prognosis. A clear conclusion can be made into the link between staging and mortality, showing that as staging increases, mortality increases and prognosis becomes worse. Comparing survival and mortality within the whole cohort, showed that out of the patients who were deceased, the majority of deaths occurred within 2 years of patients undergoing treatment. This is of clinical significance in terms of prognostic value and survival time of patients with oral cavity and oropharyngeal squamous cell carcinoma. Further work is needed on a larger number of patients to confirm these findings. Due to time constraints and the complexity of interaction between variables it is extremely difficult to assess whether the introduction of chemotherapy has made a difference in survival outcome. This study raises more questions that require further investigation, using a larger sample size.


The potential role of OX40/CD30 as organisers of inflammatory infiltrates in a novel model of tertiary lymphoid neogenesis in murine salivary glands

P. Rankin and M. Chung
University of Birmingham

Introduction

Formation of organised lymphoid structures is a hallmark feature of chronic autoimmune diseases. In secondary lymphoid organs organisation is acquired via tight leucocyte/stromal cell interaction. Co-stimulatory molecules such as OX40 and CD30 play a key role in this process. We aimed to evaluate the effects that lack of OX40 and CD30 play on the formation of tertiary lymphoid structures in a novel model of murine salivary gland inflammation.

Methods

Ectopic lymphoneogenesis was induced cannulating murine salivary glands of OX40/CD30 KO and WT mice with 10^8 p.f.u. of luciferase-expressing adenovirus. Mice were culled at various time points post-cannulation and samples were stained for lymphoid cell markers using immunofluorescence. Aggregate area and degree of organisation in terms of segregation was established by two independent observers on electronically acquired images, using ImageJ software.

Results

Day 8 post–cannulation samples were characterized by large aggregates that only showed segregation in 40% of the foci, while day 15 foci, though characterised by smaller dimension displayed higher level of lymphoid organisation in terms of segregation and formation of follicular dendritic cell networks. By day 23 foci found were smaller and displayed features of involution of the structural organization (only 27% segregation). OX40/CD30 KO mice showed smaller, fewer infiltrates with less segregation at all time points.

Discussion

Our data show that the degree of segregation of the lymphoid aggregates into B cell T cell areas was higher in wild type mice compared to OX40/CD30 KO making OX40/CD30 a potential therapeutic target in chronic inflammation.


Differences in the program of lymphatic and vascular vessel formation in a novel model of ectopic lymphoneogenesis in salivary glands

M. Chung and P. Rankin
University of Birmingham

Introduction

In secondary lymphoid organs, the balance between input and output of leucocytes is regulated by coordinated expansion of endothelial and lymphatic vascular beds. Whether this happens at site of inflammation, where tertiary lymphoneogenesis occurs, is unknown. In this study we aimed to dissect the relationship between the angiogenic and lymphangiogenic programs during the dynamic formation of ectopic lymphoid aggregates.

Methods

Ectopic lymphoneogenesis was induced cannulating WT murine salivary glands with 10^8 p.f.u. of luciferase-expressing adenovirus. Mice were culled at various time points post-cannulation (p.c.). FACS analysis of digested tissues was performed to quantify numbers of vascular and lymphatic endothelial cells. Samples were stained for lymphatic vessel cell markers (Lyve) using immunofluorescence (IF). Numbers and area coverage of lymphatic vessels were assessed using ImageJ software.

Results

Data obtained by FACS analysis of salivary gland tissues showed that the percentage coverage of vascular endothelial cells (CD31+GP38-) remains relatively stable throughout the inflammatory process. In contrast, the percentage of lymphatic endothelial cells (CD45-EPCAM-CD31+GP38+) showed an increase at day 5 p.c., followed by a significant decrease at days 10 to 15 and a subsequent increase from day 18 onwards. IF analysis demonstrated that while the first increase is mainly due to proliferation of many small Lyve + vessels, the latest lymphatic expansion is linked to the significant enlargement of a smaller number of vessels.

Discussion

This work suggest that lymphatic endothelium undergo dramatic changes in shape and dimension during the inflammatory process, that are likely to be determined by the inflammatory infiltrate in different disease stages.


The effect of a family history of major depression on the outcome of electroconvulsive therapy

C. Smith
Cardiff University

Background and aims

Electroconvulsive therapy is an effective treatment for major depression; however, few predictors of response have been established. I aim to examine whether a family history of unipolar or bipolar depression is a predictor of response, remission and relapse rates after electroconvulsive therapy in patients with unipolar or bipolar depression.

Methods

I used data on 121 patients treated at Whitchurch hospital, Cardiff. Prior to treatment, it was established whether patients had a family history of unipolar or bipolar depression. Patients were then administered ECT and outcome measures were compared using independent t-tests, regression analysis and Kaplan-Meier survival curves.

Results

A high proportion of patients had a family history, and these patients had a significantly earlier age of onset of depression. Presence of psychosis and increasing age significantly increase ECT efficacy, however family history does not predict outcomes. There was a non-significant trend for patients with a family history to have longer remissions.

Conclusions

Family history does not seem to predict ECT efficacy. A larger sample size is needed to explore trends fully, which may prove that the time to relapse is significantly.


Are partially activated non-dividing effector cells (PANDEs) tolerant or anergic T-cells?

A. Baheerathan
University of Leicester

The effector functions of activated T-cells are diverse and include cytokine production, proliferation, cytolysis and intracellular signalling events; it has been shown that T-cell activation is not "all or nothing" response and thus, these effector functions can be dissociated from one another. The phenomenon of activation in the absence of proliferation has been demonstrated both in CFSE-based proliferation studies as well as in certain pathological settings. Yet despite being

demonstrated in a pathological context, very little is known about cells that exhibit this phenotype. Thus, the aim of our project was to further characterise this cell population and elucidate the mechanisms that underlie their lack of proliferation.

Our first aim was to identify the activating reagent (out of anti-CD3/CD28 dynabeads, SEB and PHA at varying concentrations) that generated the highest proportion of partially-activated non dividing effector cells (PANDEs) from CD4+ T-cells that were activated and left in cell culture for 6days. Following our finding that anti-CD3/CD28 dynabeads (1/10 dilution) was the best method to obtain PANDEs in-vitro, we then identified that a significantly higher proportion of PANDEs were formed in an RO+ memory phenotype.

Another target of this project was to identify whether PANDEs exert other effector functions; using intra-cytoplasmic cytokine staining and flow cytometric acquisition, we were able to show that PANDEs are cytokine-producing cells. We also showed using reverse-transcriptase PCR that PANDEs express significantly higher levels of the transcription factor FOXO1; down-regulation of this transcription factor has shown to be critical in allowing the clonal expansion of T-effector cells.

PANDEs are a cell-population that predominate in the RO+ cell-line, are capable of cytokine production and express higher levels of the transcription factor FOXO1. Further research must focus on whether PANDEs remain resistant to proliferation on secondary activation and whether they are present at a higher percentage in active auto-immune inflammatory disease (as implied by current literature). Our research so far, combined with findings from studies that identify PANDEs in a pathological context, justify further research on this cell type.


Producing and evaluating a novel lentiviral vector for β-thalassaemia Gene therapy

Y. Bokinni, Dr V. Kao, Dr M. García-Gómez and Dr M. Antoniou
King's College London

Introduction

β-thalassaemia, a single gene disorder affecting the β-globin gene, results in the formation of defective haemoglobin A. Treatment presently incorporates regular blood transfusions and currently the only option for a 'cure' is with hematopoietic stem cell (HSC) transplantation. Fewer than 30% of affected individuals have HLA compatible siblings, and in light of the characteristic dilemmas surrounding HSC transplantation, β-thalassaemia has become a target for gene based therapies. The approach essentially involves the use of recombinant HIV viruses, known as lentiviral vectors (LV) in mediating gene delivery.

Method

Antoniou's group have recently devised a number of "GLOBE" constructs with the inclusion of regions physiologically present within the endogenous human β -globin gene, previously deemed insignificant, and therefore, omitted from all known published constructs to date. The inclusion of a full β-globin 2nd intron (850bp) has been added, yielding the latest generation of LV, GLOBE 4. The aim of this project was to conduct a comparative expression analysis between the GLOBE-2 (control) and GLOBE-4 vectors to evaluate whether the inclusion of the full 2nd intron allows (i) efficient LV production (in contrast with previous findings observed with gammaretroviral vectors) and (ii) increases β-globin mRNA levels. Lentiviral vectors were produced via cell transfection, and subsequently used to transduce our HSC model, the murine erythroleukemia cell (MEL). The quantity of vector derived human β-globin expression was quantified via qPCR and RT-qPCR analysis to determine the level of expression per LV copy.

Results

Average viral titres obtained for the GLOBE- 2 and GLOBE-4 constructs were 7.2x107and 5x107viral particles (vp)/ml respectively, incurring a 31% variance despite a 600bp difference in size. The relative amounts of β-globin expression adjusted to level of expression per vector copy were 0.869 (± 0.21) and 0.061 (±0.07) for GLOBE 4 and 2, thus revealing a 93% greater level of expression for the novel GLOBE 4 construct.

Conclusion

The results obtained suggest that LV production is not severely negatively affected by the inclusion of the full 2nd intron (a finding not published to date), and that its presence may indeed significantly increase mature human β-globin mRNA levels.


Exploring the extent of communication surrounding the transition to palliative care in patients with heart failure

E. Green, C. Gardiner, C. Ingleton and M. Gott
University of Sheffield

Background

The End of Life Care Strategy for England recognises the importance of a timely transition to palliative care (PC) within the context of heart failure (HF). There is evidence that communication around this issue is poor, limiting the capacity of patients and their families to make fully-informed care choices.

Method

The three phases of the study constituted 1) a literature review; 2) interviews (n = 7) and focus groups (n = 3) with 24 HCPs specialising in cardiology and PC; and 3) quantitative questionnaires completed by hospital in-patients with HF (n = 8), and various HCPs involved in their care. The qualitative data were analysed using the principles of thematic analysis. Quantitative data are presented descriptively and comparisons are drawn between data sources.

Results

The literature review identified 19 relevant papers, from which a number of barriers to effective communication about transitions emerged: 1) the unpredictable trajectory of heart failure and resultant prognostic ambiguity; 2) the uncertainty of HCPs regarding patient preferences; and 3) low levels of confidence in dealing with end of life issues due to inadequate education. The data obtained from HCPs supported these findings, and a limited concurrence between palliative medicine and cardiology specialists regarding the communication of prognosis and access to PC services for HF patients was also identified.

Conclusion

There is currently no consensus outlining an ideal format for end of life communication within the context of HF. In addition, there is a need for both established prognostic guidelines and further education to develop communication skills.