Investigating the functional and molecular impact of BTK inhibition on mTOR kinase signalling in CLL cells
Vidhya Chauhan1, Emilio Cosimo2 and Alison Michie3
1Medical Student, University of Glasgow, UK
2Postdoctoral Research Associate, University of Glasgow, UK
3Reader in Molecular Lymphopoiesis, University of Glasgow, UK
Aims: Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the western world and is currently incurable, being refractory to first line immunochemotherapeutic agents. Consequently, the demand for the development of novel therapies targeting the signals of the cytoprotective CLL tumour microenvironment (TME) is increasing. This laboratory-based research study aims to define how Bruton Tyrosine Kinase (BTK) inhibition, using the novel drug ibrutinib, effects mTOR kinase signalling in CLL cells.
Methods: This study utilised flow cytometry, western blotting, and quantitative real-time PCR techniques to assess the impact of Ibrutinib on mTOR kinase signalling in primary CLL patient samples. CLL cells were cultured in vitro for both short- and long-term periods (48 h and 11–14 days, respectively) under survival and proliferation inducing conditions, to mimic the CLL tumour microenvironment of lymphoid organs.
Results: Compared to untreated cells, ibrutinib significantly reduced CLL cell viability, inducing apoptosis in BCR stimulated cells (95% CI 2.60–10.50; p = 0.013). Moreover, in these pro-survival conditions, ibrutinib reduced phosphorylation of the mTOR targets Akt and S6 as well as decreased transcriptional levels of Mcl-1, FOXO1 and Cyclin D2, key regulators of CLL cell proliferation and survival. By contrast, in short- and long-term stromal co-cultures, ibrutinib did not overcome the CD40L-, IL-4-, and IL-21-mediated pro-survival and pro-proliferative signals.
Conclusion: Clinical trials have shown ibrutinib to be an effective novel therapy in the treatment of CLL. This study supports current evidence and exemplifies ibrutinib’s ability to overcome BCR-mediated pro-survival signalling. However, in order to overcome pivotal cytoprotective signals produced within the TME and chemoresistance, ibrutinib may be best utilised in combination with other drugs.
An audit of referrals for 24-h Holter monitoring and its diagnostic yield
Yuan Ye Beh1, Subbashini S Chandran1, Andy McConnell2 and Jonathan Affolter3
1Medical Student, University of Aberdeen, UK
2Electrophysiologist, University of Aberdeen, UK
3Consultant Cardiologist, University of Aberdeen, UK
Background: Despite local guidelines, currently, there are no national referral guidelines on Holter monitoring in the UK. Its diagnostic yield often remains poor. Investigation into its use may save medical resources and improve waiting time.
Aim: To quantify the level of appropriate referrals for 24-h Holter monitoring in a general population.
Methods: We selected 254 patients referred to the Aberdeen Royal Infirmary (ARI) Cardiology Department for Holter monitoring in September 2014. The results of the Holter monitoring were divided into four categories: Symptomatic & Abnormal Rhythm (YSYR), Symptomatic & Normal Rhythm (YSNR), Asymptomatic & Abnormal Rhythm (NSYR), Asymptomatic & Normal Rhythm (NSNR). Among the four groups, YSYR and YSNR were considered useful results (for diagnosis and reassurance). Subsequently, we matched the results to their referral sources and reasons.
Results: Referral sources were widespread. Useful results (YSYR and YSNR) accounted for only 20.1% of all Holter referrals. The NSNR group took up the biggest proportion (72.5%). Palpitations remained the most common reasons of request (55.5%). Most episodes occurred less than three times weekly.
Limitation: The frequency of symptoms was not stated in some referrals.
Conclusion: Many referrals for 24-h Holter monitoring in ARI Cardiology Department were considered inappropriate and might contribute to the low yield of useful results. Holter referrals should have a heightened threshold, or be restricted to cardiac departments. Other diagnostic tools (e.g. patient-activated event recorder) should be considered as the mainstay of monitoring for other referrals.
Does an elevated 72-hour peak post operative C-reactive protein (CRP) serum concentration predict postoperative complications in major head and neck cancer operations? A retrospective study
SJJ Touyz1, B Langley1, N Syyed2, C MacIver3, C Wales3 and J McMahon3
1Medical Student MbCHb4, University of Glasgow Medical School, UK
2StR3, in Oral maxillofacial surgery (OMFS), Southern General Hospital, UK
3Consultant in OMFS, Southern General Hospital, UK
Background: Head and neck (H&N) cancers usually require major surgical resections with reconstructions. Postoperative wound and pulmonary complications frequently occur. Complication severity is classified by Clavien–Dindo grading. C-Reactive protein (CRP) is a quantifiable marker of systemic inflammatory response syndrome (SIRS). Previous colorectal surgery studies linked elevated postoperative CRP with wound complication and severity.
Aim: To investigate associations between peak postoperative CRP and postoperative complications following major H&N surgery, including: (i)severity, (ii)wound and (iii) pulmonary complications.
Methods: A total of 378 patients’ clinical data were prospectively analysed. Complications were classified using Clavien–Dindo grading. t-Tests and receiver operating curves were used for analysis.
Results: There is strong statistical association and accuracy between elevated postoperative CRP and predicting pulmonary complications. No statistical associations were found between elevated postoperative CRP and complication severity or wound complications.
Conclusions: H&N patients with pulmonary complications demonstrate significantly elevated postoperative CRP. Measuring postoperative CRP for the magnitude of postoperative SIRS is consequently an important predictor of postoperative pulmonary complications. This may target perioperative care packages prior to clinical presentation of pulmonary complications. Unlike colorectal studies, no associations were found between postoperative CRP and postoperative complication severity or wound complications. This suggests that postoperative CRP does not predict postoperative complication severity for H&N surgery. Accordingly, the Clavien–Dindo grading may need modification for H&N patients.
Use of zebrafish as a model organism to discover novel therapeutics
Mohammed I Murtaza
Medical Student, University of Glasgow, UK
Although in vitro screens have been highly useful in identifying modifiers of well-understood processes, their success is restricted in processes that are poorly understood because knowledge of the pathway and drug target is a pre-requisite rather than an aim. Large-scale phenotype-based in vivo screens for drug discovery have been limited by ethical and practical factors, often being laborious and expensive. Zebrafish provides a means to bridge the gap between cell culture assays, lacking physiological context and screening in mammalian models that suffer from low throughput. The attributes that make zebrafish an attractive model organism also make it ideal for drug discovery. Despite being an amniote model, it is devoid of strict regulations for animal experiments enabling their use in high throughput screening (HTS) economically, facilitated by their high fecundity. Over the past decade, zebrafish has established itself as a good model for human diseases and an assay system for small molecule screening. It accelerates drug discovery by combining several processes of drug development such as disease modelling, target identification, lead discovery and toxicology. A brief review of zebrafish as a model organism is followed by in-depth discussion of several assays undertaken on developmental, behavioural, cardiac and other zebrafish functions to discover novel compounds of therapeutic potential. Identification of the novel GS4012 compound as a chemical suppressor of congenital disease phenotype through in vivo HTS is one such example of how zebrafish can be used to discover novel drug leads.
Evaluation of patients undergoing MAGIC protocol chemotherapy and curative resection for gastric cancer from 2008 to 2012
Laura Osborne1, Grant Fullarton2, Carol Craig2, Matthew Forshaw2, Colin MacKay2, James Going3, Oliver Cram4, Stuart Ballantyne4, Derek Grose4, David McIntosh4, Jeff Evans4 and Janet Graham4
1University of Glasgow, UK
2Department of Surgery, Glasgow Royal Infirmary, UK
3Department of Pathology, New South Glasgow Hospital, UK
4Beatson West of Scotland Cancer Centre, UK
Background: Gastric cancer has historically been managed by surgically; however, perioperative chemotherapy, as detailed in the MAGIC trial, has been shown to improve outcome. This protocol consists of three cycles of epirubicin, cisplatin, and 5-flurouracil chemotherapy before and after surgery.
Aims: In this study, we aimed to assess impact of completing all cycles of chemotherapy on overall survival (OS), and assess whether CT response to pre-operative chemotherapy correlated with patient outcome.
Method: We compiled a retrospective database of 78 patients diagnosed with gastric tumours who underwent pre-operative chemotherapy followed by surgery at The Beatson West of Scotland Cancer Centre and Glasgow Royal Infirmary from January 2008 to December 2012. Kaplan meier survival analysis was used to compare OS and progression-free survival between patients completing all chemotherapy and those not completing chemotherapy.
Results: Thirty-seven patients completed all six cycles of chemotherapy; 34 patients did not complete all cycles of chemotherapy; and seven patients were found to have disease which had progressed at staging laparoscopy and did not undergo radical surgery and post-operative chemotherapy. There was an improvement in survival seen in the complete therapy group, but this was not statistically significant (p = 0.159). There was a statistically significant (p = 0.001) difference in PFS between the two groups. CT response was not found to correlate with outcome (p = 0.725).
Conclusion: We demonstrated a statistically significant improvement in progression-free survival in patients completing treatment compared with the incomplete group. We did not find CT response to be a reliable predictor of outcome.
Evaluation of computed tomography in diagnosis of acute appendicitis
Tricia Yeoh
Medical Student, University of Glasgow and Department of Radiology, Queen Elizabeth University Hospital, UK
Background: Appendicitis is the one of the most common causes of the acute abdomen in the UK. Recent studies have emphasised that obtaining an accurate diagnosis is more important than a quick diagnosis. Computed-tomography (CT) is the most accurate imaging modality and has been increasingly used. The negative appendectomy rate has also been shown to drop with the use of this modality. Thus, it is pertinent to ensure that local practices meet set standards.
Aim: To determine the effectiveness of CT in the diagnosis of acute appendicitis.
Method: Retrospective audit of patients at the Queen Elizabeth University Hospital and the Glasgow Royal Infirmary from 1 March 2015 to 1 September 2015. Inclusion criteria are patients with suspected appendicitis who had a pre-operative CT, appendectomy and histopathology.
Results: Out of 70 appendectomies included, 65 were positive (primary acute appendicitis), 2 were negative (histologically normal) while 3 had other pathology. The positive predictive value and the sensitivity were both 95.4% while the negative appendectomy rate is 2.9%. Twenty-four patients had a perforation of the appendix. The sensitivity of CT at diagnosing a perforated appendix from a non-perforated appendix is 75%. The average reporting time of the CT is 47 min.
Conclusion: Overall, the utility of CT met the standard set by medical literature. The average reporting time fell short of the standard but was deemed acceptable. Learning points were suggested.
What is the best approach to preventing congenital toxoplasmosis in the UK?
Sasha Reeve1 and Winnie Dhaliwal2
1Medical Student, University of St Andrews, UK
2Teaching Fellow, University of St Andrews, UK
Background: Toxoplasma gondii is a parasite that causes toxoplasmosis; primary infection during pregnancy can affect the foetus and lead to life-threatening congenital toxoplasmosis. Currently there is no vaccine available and present global practice involves public education and screening. Due to the potentially severe clinical consequences of lack of treatment, it is important to raise awareness of this parasite and to identify infected individuals at an early stage. Current NICE recommendations are that routine serological screening should not be offered as the risks of screening could outweigh any potential benefits. This was last reviewed in 2011 and a reassessment may be necessary in view of demographic changes.
Aim: The objective of this dissertation is to answer the question, “What is the best approach to preventing congenital toxoplasmosis in the UK?”
Methods: A systematic search of online databases including PubMed, Embase and Medline was undertaken. After application of my exclusion and inclusion criteria, 11 articles remained and were critically analysed with regards to prevention methods practiced in various European countries.
Results: Most papers regarding antenatal and neonatal screening did not provide sufficient evidence for valid conclusions. Primary prevention methods proved to be effective in areas of high seroprevalence. Multi-ethnic populations may have a relatively high seroprevalence and more parasite-associated risk factors, thus individual risk assessment of non-native patients in the UK is reasonable.
Conclusion: The guidelines for toxoplasmosis screening appear to be justified. However, greater action could be taken to ensure adherence to primary prevention methods, thereby reducing cases of congenital toxoplasmosis.
Is there an increase in expression of autophagy-related proteins in the dorsal root ganglion after sciatic nerve crush injury?
EA Logan1 and MR Andrews2
1Medical Student, University of St. Andrews School of Medicine, UK
2Lecturer in Anatomy, School of Medicine, University of St. Andrews, UK
Background: Autophagy is a catabolic cellular process whereby expired cytoplasmic proteins and organelles are sequestered into a double membrane structure, the autophagosome, and subsequently degraded by lysosomes. Although autophagic activity has been found to be upregulated after spinal cord injury (SCI), the regenerative value of this is yet undetermined.
Aim: We proposed to determine whether expression of autophagy-related proteins in the dorsal root ganglion (DRG) is increased after peripheral nerve injury, and thereby in a model of successful nerve regeneration.
Methods: Specifically, we investigated whether expression of the autophagic proteins LC3, p62 and TNF receptor-associated factor 6 binding protein (T6BP) is increased in the DRGs of rats that have suffered unilateral sciatic nerve crush injury. Immunohistochemistry and western blot analyses were used to analyse both the uninjured and injured DRGs at four separate time points and to determine protein levels.
Results: The DRGs housing the cell bodies of injured primary neurons exhibited greater activating transcription factor 3 (ATF-3) staining, thereby confirming that these neurons were under stress. Immunohistochemical analysis of LC3 was inconclusive due to the highly suspected presence of lipofuscin. Immunohistochemical analysis of p62 was suggestive of no increased expression post-injury. Furthermore, analysis of the western blots suggested no increased expression of LC3-II or T6BP in response to injury.
Conclusion: Although the results are suggestive of no increased expression of autophagy-related proteins in the DRG after SCI, further investigation for expression of these proteins at the site of injury will provide insights into autophagy’s role in post-SCI regeneration.
A peer-led paediatric mock OSCE: medical students’ perceptions
Lisa Murphy1, Stephanie Potts1, Alexander Fletcher12 and Louise Murchison3
1Medical Student, University of Glasgow, UK
2Paediatric Registrar (ST1), University of Glasgow, UK
3Academic Clinical Fellow in Paediatric Surgery, University of Glasgow, UK
Background: The peer-led mock OSCE (PLMO) can be a valuable way of improving medical students clinical skills without draining faculty resources. These types of sessions are held regularly, with little insight into the best methods of ensuring that they are giving effective teaching.
Aims: To explore how students perceive the feedback from peer-examiners in a PLMO setting, and to identify the best methods of reflective learning in these settings.
Methods: An 8 station PLMO, with post-OSCE teaching, was delivered to final year medical students at the University of Glasgow three weeks before their summative paediatric OSCE. Pre- and post-PLMO questionnaires explored students’ views on reflective learning and their perception of the PLMO.
Results: Responders stated that PLMO increased their OSCE confidence (98%) and clinical skills (90%). All responders valued the post-PLMO feedback session. Responders perceived personal peer-feedback as more useful than marking schemes as reflection tools for improving both clinical competency (9.1 vs 8.3, P < 0.05) and OSCE performance (9.1 vs 8.3, P = 0.007).
Conclusion: Our PLMO subjectively improves paediatric clinical skill and OSCE-confidence, with the next step for this research to be an evaluation of the results of the summative paediatric OSCE in our cohort of PLMO attenders compared to the rest of the year. Real-time practice and personalised feedback were convincingly described as benefits, and appear to be the two key factors contributing to paediatric PLMO success.
Profiling the neuroinflammatory response to trypanosome infection in C57Bl6 mice
Neil Ramsay
Faculty of Veterinary medicine, Institute of Comparative Medicine, University of Glasgow, UK
Human Africa Trypanosomiasis (HAT) is a fatal (if untreated) parasitic infection, with 10,000 cases reported annually. Research has focused on the use of murine models to better understand its pathological features, especially in the late CNS stage where treatment is limited. The project aims to compare the neuroinflammatory profile of two common murine strains used in HAT research; CD-1 and C57Bl6. These profiles consisted of measurement of blood brain barrier (BBB) damage using MRI scanning, neuropathological scoring of coronal H + E stained brain sections as well assessment of the expression of neuroinflammatory mediators including Cxcl9, Cxcl10, Cxcl11, Cxcr3 and Ifn-γ using end-point RT-PCR. Analysis was completed using uninfected controls with measurements at 7, 14, 21 and 28 days post infection (d.p.i.), with the disease progressing to the CNS stage between 14 and 21 d.p.i. Statistical analysis showed significant difference between strains for percentage signal change generated from contrast enhancement maps (P = 0.031), with the difference between strains at 21 d.p.i. far starker (P = <0.0001). However, comparison between strains with regards to neuropathological score showed no significant difference between strains (P = 0.0603). All neuroinflammatory markers investigated showed significant differences in expression levels comparing uninfected controls to 28 d.p.i (matching with expected patterns in the literature), with the exception of Cxcl11 (P = 0.117). This is thought to be due to a mutation in C57Bl6 causing Cxcl11 to be less active. Both strains mirrored the expected pathological progression of the disease; however, the decreased BBB damage in C57Bl6 at 21 d.p.i. may indicate a resistance to infection compared to CD-1, without a relative lag in neuropathology. The evidence indicates differences between the standard CD-1 strain and C57Bl6. The model should be better characterised in this strain before knockout models based on this line can be used. It may indicate that caution should be applied regarding insights into HAT pathogenesis which have been gained through use of knockout models as mice strain appears to influence pathogenesis.
Is resurfacing arthroplasty an effective treatment for active patients with degenerative hip disease?
Jasmine Latter1 and James Robb2
1Medical Student, University of Glasgow, UK
2MD FRCS, Honorary Senior Lecturer, University of St Andrews, UK
Background: Hip procedures account for nearly half of all operations in the UK. Resurfacing is a metal-on-metal bearing surface hip arthroplasty for the treatment of degenerative hip diseases, such as osteoarthritis. Concerns regarding the effects of metal ion concentrations in patients have brought the efficacy of resurfacing into question.
Aims: To determine if resurfacing arthroplasty is an effective treatment for active patients with degenerative hip disease.
Methods: Critical literature review using PubMed. A literature search was conducted using the search terms ‘metal-on-metal’ AND ‘hip’ AND ‘resurfacing’. Inclusion and exclusion criteria were applied. Studies included were written in English, had a minimum of 50 patients with minimum five years of follow-up (or mean of 5 years for metal ion levels) and of selected study designs (RCTs, cohorts). Patients were adolescents or adults with primary metal-on-metal resurfacing hip implants. Outcome measures were survival rates, revision rates, functional outcomes and metal ion concentrations. Follow-up was medium to long term.
Results: Nineteen studies were included (18 cohort studies and one randomised control trial). Survival rates with various end-points and functional outcomes consistently illustrated superior outcomes in males and patients with larger femoral heads. Overall, revision rates were very low, but there was a greater incidence of revisions in females. The correlation between metal ion concentrations, implant wear and tissue destruction is inconclusive. Increased ion levels were associated with more revisions but not definitively.
Conclusion: Resurfacing arthroplasty is an effective treatment for males and large femoral head sizes with superior survival and functional outcomes; however, this treatment should be avoided in females and patients with small femoral components. Determining long-term effects of metal ions requires further research.
The prevalence of frailty, cognitive impairment and delirium in an older acute surgical population
AJ Connelly1, S Ullah2 and SJ Moug3
1Medical Student, Undergraduate Medical School, University of Glasgow, UK
2Surgical Registrar, Department of Colorectal Surgery, Royal Alexandra Hospital, UK
3Consultant Surgeon and Honorary Clinical Senior Lecturer, University of Glasgow, UK and Royal Alexandra Hospital, UK
Background: Surgery on older patients is becoming increasingly common, even in the acute setting. However, there are limited data regarding the prevalence of frailty, cognitive impairment, and delirium in these patients; information that can have important implications for patient care, surgical outcomes and informed consent. With this in mind, this study assessed the prevalence of frailty, cognitive impairment, and delirium in patients aged 65 years and over who had been recently admitted to a surgical acute receiving ward, and how those prevalences varied with several demographic and medical factors. Surgical outcomes (including length of hospital stay, readmission to hospital, and mortality at both 30 and 90 days) will be followed up in the future.
Methods: Acute surgical patients over 65 years of age who had been admitted for less than 24 h, who had not yet had surgery and who could complete the questionnaires, were assessed using three tools – a 7-point clinical frailty score derived from the Canadian Study of Health and Ageing (CSHA), a Montreal Cognitive Assessment (MoCA) test for cognitive impairment and a Confusion Assessment Method (CAM) evaluation for delirium. The patients’ age, gender, postcode (and thus Scottish Index of Multiple Deprivation (SIMD) score), number of medications and number of co-morbidities were also determined.
Results: Forty-one patients were included with an average age of 76.8 years, of whom 22 (53.7%) were men. About 31.7% were mildly, moderately or severely frail; 78.0% had some cognitive impairment (defined as <26 out of 30; the mean score was 20.7, median 21, and range 10–28); and none were suffering from delirium. Both frailty and cognitive impairment increased somewhat with age, number of medications, and each other, but not with gender, SIMD score or number of co-morbidities.
Conclusions: A high proportion of older people admitted with an acute surgical problem had evidence of frailty and cognitive impairment, with many patients suffering from both. The three tools used were quick, easy and seemingly accurate ways to assess these features.
Making effective use of Cinacalcet in patients with renal faliure
Hirushi S Jayasekera
Medical Student, University of Glasgow, NHS, UK
Background: Cinacalcet is a calcimimetic used in patients with hyperparathyroidism secondary to renal failure.
Aims: First, to evaluate the impact of Cinacalcet initiation on parathyroid hormone (PTH) levels and bone biochemistry. Second, to assess whether NICE guidelines are followed within practice. Lastly, to propose data-based solutions to bridge any gaps in clinical practice.
Method: As a retrospective study, 70 patients previously/currently on Cinacalcet with secondary hyperparathyroidism were identified from the database of the Glasgow Renal and Transplant Unit. Their bone profiles were recorded at intervals of 1, 3, 6 and 12 months post-Cinacalcet initiation. Twelve doctors from the Unit completed a questionnaire based on the NICE guidelines. Results were collated and graphs drawn.
Results: There was a statistically significant negative relationship between time spent post-Cinacalcet administration and PTH levels; r(3) = 0.03, P < 0.05. PTH levels fell by 46% within a year; adjusted calcium and alkaline phosphatase levels decreased by 0.5% and 20%, respectively, and phosphate levels increased by 2%. Using NICE criteria, 75% of the patients were either prescribed Cinacalcet too early/without their PTH being monitored. 50% of the doctors are unaware of the Cinacalcet guidelines.
Conclusion: Cinacalcet decreased PTH levels, but NICE guidelines were not followed. Suggested solutions included linking patient databases to automated email-reminders of blood tests, and ‘mandatory bloods’ to improve monitoring. An educational lecture updating staff on current guidelines could help standardise prescribing of Cinacalcet.
Balancing the risk: antidepressant use in Pregnancy. A review of prescribing practice in the West of Scotland, 2012–2014
Lynsey Carthew
Medical Student, Inverclyde Royal Hospital, University of Glasgow, Greenock, Scotland
It is estimated that approximately 15% of women of women of child bearing age meet the DSM IV criteria for depression. This review examined the benefit–risk ratio, in prescribing antidepressants in the perinatal period. Part 1 examined current guidelines in Scotland and reviewed the literature surrounding both risk and benefit to both mothers and new-borns. Part 2 involved a more in depth look at current prescribing practice pregnant women in Inverclyde, Scotland between 2012 and 2014. In this time, 89 women presented to Inverclyde Royal Hospital’s Maternal Psychiatry Specialist team. Particularly, the cases of two women prescribed Paroxetine, were considered to illustrate the different challenges in treating women with depression in pregnancy, and highlight the reasons a physician may choose to either initiate or continue Paroxetine in pregnancy, despite its slightly unfavourable profile in pregnancy. This review highlights the complexities of antidepressant prescribing in pregnancy, and compares current practice in the West of Scotland to guidelines and the literature to enable readers to understand risk–benefit prescribing in pregnancy. This review aimed to allow readers to draw a useful link between theoretical literature and prescribing guidelines and practical treatment decisions in pregnant women. It also highlighted the need for more large-scale reviews of antidepressant prescribing practice in pregnancy, to enable doctors to make informed choices regarding treatment and examine their rationale for treatment decisions in this group.
Polypharmacy and medication reviews in rheumatology
C Scott1, E Twynam-Perkins1, J Hunter2 and W Pasha3
1Medical Student, Glasgow University, UK
2Consultant Rheumatologist, Glasgow University, UK
3Rheumatology Trainee, Glasgow University, UK
Background: Complex problems require multiple prescriptions. Problematic polypharmacy leads to lack of efficacy or harm (physical or psychological). QOF demands medication review for medicines taken >15 months. The King’s Fund report1 suggested a hospital visit to provide a coordinated approach to medicines rationalisation. This survey explores the extent of the problem and patients’ views.
Methods: A total of 173 unselected new, return, out and day patients helped with a questionnaire survey exploring patients’ medicines and review processes.
Results: Patient population: 33% male; mean age 58 (range 24–86); 39% had Rheumatoid Arthritis, 15% Psoriatic Arthritis, 13% Osteoarthritis, other groups <10%. Co-morbidities included hypertension (33%), other cardiovascular diseases (25%), gastrointestinal diseases (16%), hypothyroidism (12%), diabetes (10%) and others each <10%. Patients took 0–23 different medicines (mean 7). It was found that 67% took more than four medicines, 21% more than nine (cf. 6% in Scottish population2); 34% of >64-year-olds took more than nine medicines. 63% recognised sometimes missing medicines. Also, 37% were aware of prior medicines review, usually in primary care, and 55% of the remainder thought medicines review worthwhile. When predictive factors (gender, age, co-morbidities, duration of rheumatic disease and number of medicines) were explored, only those on more than nine medicines favoured medicines review significantly more often (P = 0.038).
Conclusion: Rheumatology patients take more medicines than the general population. There is a perceived need for medicines review, with patients favouring GP input (60%) more than a hospital clinic (30%), nurse-led (2%) or pharmacist-led (5%) review.
Analysis of the Scottish burn population and development of mortality modelling tools
V Armour1 and C Gilhooly2
1Medical Student, Glasgow Royal Infirmary, University of Glasgow, UK
2Consultant Intensivist and Anaesthetist, Glasgow Royal Infirmary, University of Glasgow, UK
Scoring tools have been used to predict mortality after burn injury for many years. Despite this, no scoring tools have been developed in the Scottish burn population. The aim of this project was to use two model development techniques to create a model for mortality prediction in the Scottish burn population. This study included all patients admitted to Scottish Burns Units, from 2012 to 2014. Data were collected by the Care of Burns in Scotland Network (COBIS). Mortality modelling was undertaken by multiple logistic regression (MLR) and artificial neural networking (ANN). Anonymised patient data were analysed via SPSS (Version 22; SPSS, Inc, IBM, Chicago, IL, USA). Ethical approval was not required for this project as it is part of the core plan of COBIS. Over a three-year period, 1391 patients were admitted. Mean total burn surface area (TBSA) was 4.8% (IQR 1-89%) and the most prevalent cause of burns was scald. Twenty-four deaths occurred over the three-year period. The final MLR model produced had an area under the receiver operating characteristic curve (AUROC) of 0.738 and was as follows:
Logit(mortality) = 0.084age + 0.125TBSA − 10.426
The final ANN gave an AUROC value of 0.971. TBSA and age were the most important independent variables in the ANN. Despite minimal use in burns mortality prediction, ANN appears to be superior to the traditional MLR approach. Increasing use of technology in clinical practice could allow ANN’s to become more common place for event prediction in all areas of medicine.
Identification of a novel biomarker of IKKα-dependent NF-κB signalling in oestrogen receptor (ER)-positive breast cancer
Kelvin KW Cheng1, Lindsay Bennett2 and Joanne Edwards3
1Medical Student, School of Medicine, University of Glasgow, UK
2Post-doctorate researcher, MRC Centre of Regenerative Medicine, SCRM Building, University of Edinburgh, UK
3Senior Lecturer (Experimental Therapeutics), Unit of Experimental Therapeutics, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences-University of Glasgow, UK
Background: Although studies showed that higher cytoplasmic IKKα levels are associated with reduced recurrence-free survival in ER-positive tumours, the examination of non-canonical pathway signalling in response to higher IKKα levels could not be performed due to the lack of selective markers.
Aim: To identify selective markers of IKKα-dependent non-canonical NF-κB signalling.
Methods: MCF7 (ER-positive breast cancer cell line) cells were treated with varying combinations of IKKα siRNA and lymphotoxin (LTx). Expression of IKKα and phospho-p100 were evaluated using immunoblots. Taqman Low Density Arrays (TLDA) were used to identify differentially expressed genes. The selected genes were validated using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).
Results: Western blots showed successful silencing of IKKα but failed to detect phospho-p100. Using TLDA, TNFAIP2 and CDK1 showed significant changes in gene expression but failed to reach statistical significance. Eight genes were chosen for qRT-PCR validation, but TNFAIP2 was the only gene to have shown significant changes in gene expression on validation. TNFAIP2 expression increased by 1.6 folds (P = 0.369) with LTx activation. Comparing samples that were treated with LTx and IKKα silencing against samples treated only with LTx showed significant reductions in TNFAIP2 by 1.54 folds (P = 0.535). When samples treated with LTx were compared against samples treated with IKKα silencing, there was a significant decrease in gene expression by 2.5 folds (P = 0.009).
Conclusion: We provide preliminary evidence of TNFAIP2 as a potential biomarker of IKKα-dependent non-canonical NF-κB signalling in ER-positive breast cancer. TNFAIP2 expression increases and decreases with IKKα silencing and LTx treatment, respectively.
The health of asylum seekers and refugees in Glasgow: a qualitative study
Shona Mackinnon
Medical Student, University of Glasgow, UK
Background: Asylum seekers and refugees are a vulnerable group, often the subject of intense prejudice, stigmatisation and misconception.
Aims: The purpose of the research was to gain an understanding of the health-related issues in this population and to use this to consider ways in which students could help.
Methods: A range of unstructured and semi-structured interviews were conducted with asylum seekers and refugees themselves and with members of the community who interact with this group, including healthcare professionals and volunteers.
Results: Mental health was found to be the single biggest health issue, resulting from past experiences as well as current stresses. Most commonly people experienced low mood and depression. There was significant deficiency in mental health service provisions, with people in some cases waiting over nine months for counselling, and charity groups also being severely overstretched. In terms of accessing health services, almost everyone interviewed was registered with a GP and able to make an appointment. Most were aware of the emergency telephone number 999, though almost no one knew about the NHS24 advice line. Furthermore, many individuals reported facing language barriers, despite rights to an interpreter, and people were unaware of their financial aid entitlements. The management of chronic disease was found to pose significant logistical challenges, often requiring long-term follow-up and referral to specialist services, though attendance at these appointments was low.
Conclusions and Outcomes: The health needs of asylum seekers and refugees are complex and wide-ranging. Two student volunteering schemes have been established to help address these issues.
The clinical relevance of axillary node staging in delivering adjuvant treatment in patients aged over 70 with breast cancer
Fernando Loo1, Alison K Lannigan2 and Juliette Murray2
1Medical Student, University of Glasgow, UK
2Consultant Surgeon, Breast Unit, Wishaw General Hospital, UK
Background: Axillary node staging is used to guide post-operative adjuvant treatments, but evidence for its use in people over 70 years of age is sparse.
Aims: To evaluate the relevance of axillary node staging in determining adjuvant treatment for patients over 70 years of age.
Methods: Data were collected prospectively about surgery, nodal status and adjuvant treatment plans. The extent to which axillary nodal status determined the adjuvant treatment actually delivered was calculated and this was compared to current recommendations.
Results: A total of 312 patients, mean age 77 (range 70–93 years) were included, of whom 166 patients (53.2%) underwent a mastectomy; 154 (92.8%) had axillary surgery; 73 (47.4%) were node positive; 5 (6.8%) node positive patients had a sentinel lymph node biopsy (SLNB) only; 8 patients (11.0%) had radiotherapy post-SLNB; 11 patients (15.1%) had SLNB then axillary clearance; and 47 patients (64.4%) had axillary clearance at outset. Seventeen (37.0%) patients with 1–3 positive nodes and eight (29.6%) with ≥4 positive nodes received chemotherapy. Also, 146 patients (46.8%) underwent conservation surgery (BCS); 125 (85.6%) had axillary surgery; 22 (17.6%) were node positive; 6 (27.3%) node positive patients had a SLNB only; 2 patients (9.1%) had radiotherapy post-SLNB; 5 patients (22.7%) had SLNB then axillary clearance; and 9 patients (40.9%)had axillary clearance. Also, six (35.3%) patients with 1–3 positive nodes and three (60.0%) patients with ≥4 positive nodes received chemotherapy.
Conclusion: Current algorithms recommend adjuvant radiotherapy and chemotherapy following positive node staging. However, in this age group, many patients do not have any further treatment due to comorbidity. Thus, the influence of axillary node staging on adjuvant treatment options is less for patients aged over 70.
