Posters and speed presentations
A novel mechanism for drug evasion in solid tumours
Allon Hazan, Muhammad M Rahman, Joanne Selway, Dimalee Heerath, Margharita Tamassa, Mike Philpott
Centre for Cell biology and Cutaneous Research, Queen Mary, University of London
Introduction: The Hedgehog signalling pathway is a key driver of cancer growth, particularly in the prostate, brain, basal cell carcinoma and lung cancer. A key member of the hedgehog pathway is the protein Smoothened, which when over-activated promotes tumour growth. As such, many drugs such as Cyclopamine target Smoothened, and prevent it driving cell division. Smoothened is thought of as a trans-membrane protein, and drugs actively inhibit cell-surface binding. However, many drugs are poorly effective. We therefore hypothesised that an unknown mechanism bypasses conventional drug mechanisms.
Results: By using novel antibody based methods, and by utilising cell-fractionalisation, we found that rather just being located at the cell surface, Smoothened, also has an additional isoform (cleaved product) which is located in the cell’s nucleus, and appears to have functional properties. This isoform is 32KdA in size, and is found more frequently in cancer cells than in normal tissue. This novel cleavage product represents the first noted expression of a 7-transmembrane protein in the nucleus of a cell. Notably, we also found a highly conserved sequence of amino-acids tail-end of the Smoothened protein which is highly indicative of a nuclear-localisation sequence. Indeed, this sequence is present in all vertebrates suggesting a role in development which is hijacked by cancer cells to promote cell division.
Conclusion: We have observed a novel protein cleavage product of Smoothened which accounts for poor drug response by directly entering the nucleus to drive cell growth.
Routine HIV testing in an Inner City Emergency Department
L.J. Hunter, C. Lojo Rial , Larbalestier , J. Paparello,
Emergency Department, Guy's & St Thomas' NHS Foundation Trust, Department of Sexual Health & HIV , Guy's & St Thomas' NHS Foundation Trust, London.
Introduction: The National Institute of Clinical Excellence (NICE) and the Royal College of Emergency Medicine recommend that adults should be tested for HIV in endemic areas with a prevalence >0.2%. It is estimated that approximately 25% of those living with HIV are unaware of their diagnosis. Late diagnosis is associated with a ten-fold increased risk of death in the following year,1 and increased risk of onwards HIV transmission. In July 2015 we commenced a pilot project to assess the feasibility of routine HIV testing within a busy inner city ED.
Methods: Adult patient had an HIV test performed if they required venepuncture during their A&E attendance. Tests were ordered using a pre-configured blood order set including a pre-selected HIV test. Patients were informed of the intention to test all attendances and were able to opt out if desired. Positive or equivocal results were followed up by our HIV team.
Results: Over 36 weeks, 64% of ED attendances (19,569/30,461) were tested for HIV. Our prevalence was 0.9% (n=172) and of those 0.3% were not aware of their positive HIV status (n=68). Thirteen patients were not currently engaged in services, although aware of their diagnosis. Median age was 36(18-61). Patients who tested positive were predominantly male (84%) and Caucasian (59%) (37% BME, 4% Asian).50% of patients who tested positive self- identified as heterosexual, and 50% as MSM (men who have sex with men). A significant number (54%) of newly diagnosed patients had previously attended our emergency department prior to routine HIV testing. 23% of new diagnoses required an acute admission.
Conclusion: The Emergency Department provides a suitable environment for opportunistic HIV testing in areas of high prevalence. We have maintained testing rates of > 65 % of our ED attendances, achieved early diagnosis and treatment engagement in patients who were unaware of their HIV status. In addition, we have identified a number of patients who had been lost to follow-up and have now re-engaged in care.
A plasma-based DNA methylation assay differentiates malignant from non-malignant lung disease
Dr. Yasmin Buchaeckert,
Epigenomics AG, Berlin, Germany
Introduction: Low-dose computed tomography (LDCT) is a commonly-used method for lung cancer (LC) screening. Patients with positive findings from LDCT are referred for diagnostic bronchoscopy, frequently resulting in a large number of false positive findings. Non-invasive diagnostic tools may contribute to further assess the risk of lung cancer for patients with positive LDCT findings prior to undergoing invasive bronchoscopy. Here, we report on a panel of two DNA methylation markers, SHOX2 and PTGER4, with the potential to differentiate malignant from non-malignant lung disease.
Material and Methods: We developed a triplex real-time PCR to assess the level of methylated DNA of genes SHOX2 and PTGER4 in bisulfite converted DNA with ACTB as internal control from 3,5 ml plasma. In a case-control design 149 specimens from lung cancer patients and age-matched healthy individuals were evaluated. The diagnostic performance was compared to the results from a previously conducted training study on 151 specimens.
Data and Results: Including 59 LC subjects into the training study, the marker panel performed with very high sensitivity (78 – 95%) at reasonable rates of false positives (5 – 36%). In a marker validation study including 149 patients, a total of 49 LC cases and 100 clinical controls were tested. At a set specificity of 95% sensitivity was 67 %. At a set sensitivity of 95% specificity was 62%. Sensitivity was consistently high across major histological subtypes and stages.
Conclusions: The combined analysis of the DNA methylation markers SHOX2 and PTGER4 can be used to detect lung cancer in plasma samples with very high sensitivity at reasonable false positive rates. These findings were observed in a training study and confirmed in a marker validation study. The marker panel serves as the basis for a lung cancer diagnostic blood-test which may ultimately show clinical utility as a follow-up test for current imaging techniques by reducing the false positive rate of these methods.
Should Schwartz Center Rounds® be incorporated in the medical school curriculum: a quantitative and qualitative exploration of student views
Faye Gishen1, Deborah Gill1, Sophia Whitman2, Steven Walker2, Rhiannon Barker3
1University College London; 2St Gilesmedical, London, U; 3Point of Care Foundation
Background: Medicine is recognised as stressful profession. Medical students experience stress from early on in their training.1 It has been shown that the wellbeing of staff impacts upon the wellbeing of patients2. Schwartz Center Rounds (SCRs) were introduced in the US in 1997 to enhance communication and compassion in a multidisciplinary forum3,4. SCRs have since been adopted in hospitals around the UK and were mentioned in the Francis report as helping to foster compassion in healthcare5. It is not known whether SCRs could enhance training for medical students.
Aim: To seek the views of medical students as part of an exploration into the value and optimum format/timing of incorporating SCRs into the medical school curriculum.
Methods: Two SCRs were piloted at University College London Medical School (UCLMS): students at the start of Year 5 and students near the end Year 6 were invited to attend. The sessions were based upon the format currently used in hospitals whereby a panel of healthcare professionals present a series of cases, followed by an open discussion involving the audience, facilitated by two trained clinicians. At the end of the session, students were invited to complete a questionnaire (Year 5 electronic; Year 6 paper-based with space for comments) adapted from a nationally used SCR tool. A facilitated focus group was organised comprising 7 students from both academic years. The session was transcribed and reviewed using qualitative analysis.
Results: Feedback was obtained from 77% (258/334) of Year 5, compared with 37% (126/343) of year 6 students. 79% of students attending said they would attend a future SCR and 63% considered that the SCR should be integrated into the UCLMS curriculum. Mean rating for the SCR out of 5 (highest) was 3.5 for Year 5 students and 3.3 for Year 6 students. There was a difference between the two groups as to whether they had ever worried about compassion fatigue (Year 5: 69% vs Year 6: 87% p = 0.02). A summary of responses to further questions can be seen in Table 1.
Analysis of the focus group transcript confirmed that the SCR was well received. Although students reported some discomfort in contributing to the discussion in front of a large audience, the SCR fostered helpful discussions afterwards. Students expressed that the SCR may help them process their emotions when faced with stressful situations at work in the future.
Conclusion: Most students found that taking part in a SCR was beneficial and should be incorporated into the curriculum. Further consideration is required around timing and format to optimise attendance and participation. Training of staff and costs present practical issues regarding embedding and sustaining such Rounds into the medical school culture.
Barikana, A (2007). "Stress in Medical Students.". Journal of Medical Education 11 (1): 41–44.
Raleigh VS, Hussey D, Seccombe I, Qi R. Do associations between staff and inpatient feedback have the potential for improving patient experience? An analysis of surveys in NHS acute trusts in England. Qual Saf Healthcare 2009;18:347–354
The Mid Staffordshire NHS Foundation Trust Public Inquiry - Chaired by Robert Francis QC http://www.england.nhs.uk/tag/francis-report/
The development of the Research RegistryÒ: a global research registry to increase compliance with the Declaration of Helsinki 2013
Mr Daniyal J Jafree
University College London Medical School
Background: Previously, the registration of research has focused on clinical trials. However, many study types remain poorly registered, despite a mandate from the Declaration of Helsinki 2013 to register all studies involving human participants. Our aim was to develop a global registry to increase registration of research studies, including those that are not possible to register on existing registries.
Material and Methods: A new global research registry was launched in February 2015, the Research RegistryÒ (www.researchregistry.com). This allows prospective or retrospective registration of any study involving human participants. In addition to monitoring the demographics of registrations, we also sent a survey to the first 1000 registrants to obtain user feedback.
Results: To date, the Research RegistryÒ has received over 1300 registrations from over 80 countries, with over 4 million patients enrolled. A wide range of study types has been received, including: first-in-man case reports, observational and interventional studies. Retrospective cohort studies are the most commonly registered study type. The greatest proportion of registrations were made as a mandatory requirement of journal submission, not during the study planning period. User feedback has identified the most important elements of registration to be its awareness, time, cost and ease.
Conclusion: The Research RegistryÒ has established itself as a new registry, with clear focus on areas not well represented in existing registries. Going forward, our plan is to continue developing the platform in line with user feedback, by optimising the Research RegistryÒ to increase the convenience of registration.
Performance review of TEMS (Transanal Endoscopic MicroSurgery)/TAMIS(TransAnal Minimally Invasive Surgery) for excision of rectal lesions in a District General Hospital
A P Shanmuganandan, B Pereira, MRS Siddiqui, N Farkas, S Mohamed, AM Abulafi
Introduction: Bowel cancer screening programs have meant rectal cancers often are detected early. Existing treatments such as Total Mesorectal Excision (TME) carry significant morbidity and mortality. Alternative surgical options such as Transanal Endoscopic Micro-Surgery (TEMS) and TransAnal Minimally Invasive Surgery (TAMIS) may offer safer organ and function preserving therapy. Our study reviews a single centre experience with TEMS and TAMIS procedures managing rectal lesions.
Methods: Retrospective analysis of patients who underwent TEMS/TAMIS procedures from August 2011-August 2016.
Results: 43 patients underwent transanal excision using TEMS (KARL-Storz) or single port TAMIS (Covidien) kits. All patients went through the colorectal MDT with standardized MRI reporting. Average age was 70yrs (range=40-87). Mean hospital stay was 2.8 days. Complications; 1 had post-operative bleeding that required repeat surgery; 1 developed a pre-sacral collection that necessitated antibiotics.
10 patients had tubulo-villous adenoma with high-grade dysplasia, 7 had invasive adenocarcinoma (4=T1SM1, 2=T1SM2, 1=T1SM3) and 1 had neuroendocrine tumor, others demonstrated benign dysplasia. All cancers had R0excision. The patient with T1SM3 and another with T1SM2 underwent adjuvant chemoradiation. All patients had flexible sigmoidoscopy at 3 months. 4 had recurrent benign polyps (2 underwent endoscopic resections, 2 repeat TEMS) with no cancer recurrence. No pain or continence disturbances were reported. Mean follow-up is currently 12.5 months.
Conclusion: TEMS/TAMIS excision offers a safe surgical option preserving organ and function in carefully selected early rectal lesions. Prospective randomised controlled trials comparing TEMS/TAMIS with TME incorporating longer-term follow-up are needed to confirm its place in the surgical armamentarium for early rectal cancers.
INTERACTIVE POSTER SESSIONS
An innovative technique for breast cancer detection
Hartmut Gemmeke, T Hopp, M Zapf, N Ruiter.
Karlsruhe Institute of Technology, Germany
Breast cancer is one of the most common and fatal cancerous diseases among women. If breast cancer is diagnosed early, patients have a good prognosis. Our ultrasound technique promises to localize breast cancer before it poses a risk: without breast compression, without contrast agent and without radiation.
Our 3D-Ultrasound-Computertomography (3D-USCT) surrounds the breast in a water bath with several thousand ultrasound transducers. The patient lies prone on the patient bed with one breast suspended in the measuring aperture. During the measurement one transducer emits ultrasound waves at a centre frequency of 2.5 MHz and all others receive the scattered and transmitted signals. By the iterative data taking of all sender-receiver combinations (50 GB raw data per breast within 6 min) the data contains all information about refraction, scattering, attenuation, and diffraction. From the once acquired raw data three modalities can be reconstructed: reflection-, speed-of-sound- and attenuation-tomography. Especially the transmission tomography allows identifying tumours by generating quantitative speed-of-sound and attenuation images.
The reached position resolution is for reflection tomography approx. 0.24 mm, for attenuation 12 mm and speed-of-sound 5 mm. The latter two may be improved by a wave-approach under development. For image reconstruction computationally intensive algorithms need to be applied. The algorithms could be considerably accelerated by the use of a dedicated GPU-cluster. The high-resolution reflection images can now be obtained within 16 min.
A Systematic review and Meta-Analysis on the role of music in reducing anxiety and discomfort during Flexible Sigmoidoscopy
AP Shanmuganandan, MRS Siddiqui, N Farkas, R Thomas, S Mohamed,AM Abulafi
Introduction: The use of flexible sigmoidoscopy is becoming more prevalent in bowel cancer screening, although uptake remains low. A meta-analysis of studies investigating the role of music in reducing anxiety and discomfort in patients undergoing screening flexible sigmoidoscopy was performed.
Methods: A systematic review of comparative studies up to August 2016 were identified from MEDLINE, the Cochrane Controlled Trials Register (1960–2016) and EMBASE (1991–2016). Further searches were conducted using article bibliographies and conference abstracts. Medical subject headings used included, sigmoidoscopy, music, endoscopy and anxiety.
Adult studies reporting the effect of music on anxiety or pain after flexible sigmoidoscopy were included. Two authors extracted outcome data independently using outcome measures defined a priori. Quality assessment was performed using risk of bias tables.
Results: Data of 138 patients from 3 studies was analyzed using open metaanalyst. Patients who listened to music during flexible sigmoidoscopy had less anxiety compared to those without music [Random effects; SMD: 6.68(3.84,9.52), S.E=1.45, p<0.001]. No statistical heterogeneity identified (Q=6.68, df=1, p=0.719, I2=0). Patients who listened to music during flexible sigmoidoscopy had less pain compared to those without music [Random effects; SMD:1.13(0.52,1.75), S.E=0.31,p<0.001]. No statistical heterogeneity identified (p=0.528, I2=0). Patients who listened to music during flexible sigmoidoscopy found it more useful compared to those without music [RR:0.61(0.46,0.80),p<0.001]. No statistical heterogeneity identified (p=0.318, I2=0).
Conclusions: Music was deemed a helpful intervention when undergoing flexible sigmoidoscopy and appears to reduce anxiety and pain. Music can potentially improve patient experience and screening test uptake. Further studies may consolidate our findings.
Streamlining the investigation of abdominal pain in the emergency department
Chelsea & Westminster Hospitals London
Assessment of women of childbearing age presenting with lower abdominal pain to the Emergency Department (ED) can be problematic1. Streamlining of investigations in accordance with appropriate guidance can improve the patient journey, help with flow through the ED and aid in swift diagnosis.
Standards of care issued by the Royal College of Surgeons of England, for investigating women of child bearing age presenting with abdominal pain to the surgical take, highlight that all females of childbearing age should be investigated with a urine or serum bhcg level3. This completed audit cycle reveals a 10% improvement in compliance with these standards following interventional input. This demonstrates an example of simple innovative change in an established process that has lead to improved patient care.
Atypical leg symptoms (ALS): does routine measurement of the ankle brachial pressure index (ABPI) in primary care benefit patients?
Christine Oesterling1, Amun Kalia1, Thomas Chetcuti1, Steven Walker2
1, Eastmead Surgery, Greenford, Middlesex; 2, St Giles Medical, London, UK
Aims/objectives: To investigate whether routine measurement of ABPI in patients with ALS and no skin changes helps management, increases satisfaction and reduces referral.
Content of presentation: Thirty-five consecutive patients (Male 15), mean age 64 years (range: 39-88) with ALS underwent clinical review and ABPI by the same doctor. Presentation included pain, cold feet, cramps, irritations and concerns regarding circulation. Prior to testing referral was considered necessary in 10, not required in 22 and unclear in 3. ABPI changed the referral decision in 11 (31%) and confirmed the decision in 24 (69%). During the 30 month study period 10 (29%) patients were referred (9 vascular, 1 neurology). Since testing 16/35 (46%) could be contacted by phone (mean interval 18months, range 2-28). Fifteen of 16 (94%) appreciated that their symptoms were quickly and conveniently assessed. Eight of 11 (73%) with normal results were reassured by their test results and in 8/11 symptoms have since resolved.
Relevance: NICE recommends measuring ABPI where PAD is suspected. In busy practice, PAD is often not considered where the history is unclear. Patients with ALS may be referred unnecessarily, whilst others with PAD may miss the opportunity of early treatment.
Outcome/Conclusion APBI helps management of ALS by detecting unexpected PAD, reassures patients and avoids or confirms the need for referral.
Discussion: This limited study suggests that ABPI should be more widely used in ALS. It can be quickly and conveniently performed and is appreciated by patients. An unexpected result may lead to review of the history and clinical findings.
An analysis of the perceived barriers to research registration – surveying registered studies in a global research registry.
UCL Medical School, London
Introduction: Progress to increase research registration, as mandated by the Declaration of Helsinki, is hindered by a lack of understanding of the perceived barriers to registration. In this survey-based study, we sought to gain insights into these barriers from users of a global research registry, the Research RegistryÒ (www.researchregistry.com).
Methods: A survey was emailed to authors of the first 1000 registrations to the Research RegistryÒ, and all the registrations to the systematic review section. Multiple choice and free-text answers were analysed using descriptive statistics and thematic analysis respectively.
Results: From 674 contactable participants, 120 (17.8%) completed the survey. Participants declared the most commonly registered study type to be observational (76.6%). 17.5% of participants made their registrations during the planning of the study, whereas 47.5% registered at the time of journal submission, or after the peer-review process. 49.0% of participants declared that they had previously performed unregistered research. The most common motive for registration was the mandatory requirement of journal submission. The most important elements of a registration were stated as: ease, low cost and short duration. The most commonly perceived barriers to research registration were: awareness, cost and time.
Conclusion: We demonstrate that the Declaration of Helsinki 2013, which encourages the prospective registration of all research study types, is not being met. The perceived barriers to registration focus on convenience, particularly: cost, ease and duration of registration. As such, registries can improve compliance to registration by applying a user-centric approach, and by focusing on improving the convenience of registration.
The first 500 registrations to the Research Registry: advancing registration of under-registered study types.
UCL Medical School, London
Introduction: Emphasis of research registration has been placed on clinical trials, despite the Declaration of Helsinki 2013 mandating the registration of all research studies involving human participants. In response, Research Registry® (www.researchregistry.com) was launched in February 2015, enabling prospective or retrospective registration any study type. In this study, we describe the first 500 registrations to the Research Registry®.
Methods: Since February 2015, data of registrations to the Research Registry® have been collected, including: country of origin, type of studies registered and data curation activity. Inappropriate registrations were identified and removed from the database or modified as required. A quality score was assigned for each registration, based on Bradford-Hill’s criteria on what a research study should convey. Changes in quality scores over time were assessed.
Results: From 500 registrations received from 57 different countries, over 1.7 million patients were enrolled. The most common study types were retrospective cohort studies (37.2%), case series (14.8%) and first-in-man case reports (10.4%). Retrospective data curation identified 80 studies that were initially registered as the incorrect study type, and were subsequently correct. A significant improvement in quality score for registrations was observed over the 9-month period (p < 0.0001).
Conclusion: Since its conception, Research Registry® has established itself as a new registry that is free, easy to use. Research Registry® enables the registration of any study type, including those which are currently under-registered. We intend to continue developing Research Registry® in a user-centric manner, and to further promote the registry to advance the cause of registration.
Epi proColon, a coorectal cancer screening test based on methylated SEPT9 DNA in plasma
Epigenomics AG, Berlin, Germany
Screening for colorectal cancer is limited by acceptance of currently recommended methods. The development of a simple blood based alternative would help to improve participation in screening. There is a large body of literature describing the occurrence of tumor DNA in the plasma of patients with a variety of cancers, including colorectal cancer. In previous studies we characterized DNA methylation biomarkers in colorectal cancer and reported on the methylation status of SEPT9 DNA as a marker for this disease.
The aim of this research was the development of a test system for the detection of methylated SEPT9 DNA in blood plasma as a marker for colorectal cancer.
We developed a pre-analytics system based on magnetic particle capture of DNA for the extraction of cell free DNA from plasma, and the subsequent bisulfite treatment of this DNA for the analysis of the methylation status of the target SEPT9 promoter sequence. Follow bisulfite treatment, we introduced a magnetic particle based DNA purification procedure, from which purified bisulfite converted DNA is eluted as template for PCR. We developed a PCR methodology for specific amplification of the methylated target DNA based on suppression of amplification of the non-methylated DNA, allowing determination of the methylation status of the SEPT9 sequence.
The test was developed and demonstrated highly sensitive and specific analytical performance. It was clinically validated in a number of studies .
We have developed a highly sensitive and specific blood based screening test for colorectal cancer. We believe that this test provides an additional choice to the menu of colorectal cancer screening options that will result in increased participation in colorectal cancer screening.
Czech-ing out rapid diagnostic testing in Prague
1. Visit urban and rural general practices in Prague observing consultation over a 2 week period.
2. Analyse differences in primary healthcare provision between host and home country, through tutorials with host doctors.
3. Write a formal report on observed findings proposing change to UK general practice.
Poster content: Epidemiology relevant to Czech general practice will be displayed focusing on patient population and set up of health care provision. The duties of a Czech general practitioner will be incorporated, concentrating on their role as ‘investigators of disease’ being the first point of access to health care for patients. The use of Czech rapid diagnostic tests in primary care will be explored.
Relevance: Investigating the successes of general practice in another European country, identified through analysis of observed consultation, is useful to improve the provision of primary care in the UK particularly in the area of disease detection.
Outcomes: An understanding of how the Czech Republic, a country with comparable patient demographic to the UK, uses rapid diagnostic tests (RDTs) to investigate coryzal symptoms and manage consultation expectation effectively. Warfarin dose titration is assisted with INR RDTs in Czech practice with instantly available FOB results with RDT use.
Discussion: The use of CRP RDTs in primary care may help differentiate virulent infection from that to be managed conservatively, whilst alleviating patient concern. Providing general practices with instant results for INR and FOB, haematological sequelae of anticoagulation and FOB can be detected with the effect of loss to follow up diminished.
Is there a link between undergraduate teaching and clinical practice in delivering palliative care and how might deficits be addressed?
Iain Lawrie and Steven Walker
The Pennine Acute Hospitals NHS Trust, University of Manchester, St Gilesmedical London
Background and purpose: PC has gained prominence in an effort to deliver quality care for people with end of life needs.1 Non-specialist doctors provide the majority of such care.2 Limited research suggests lack of preparedness and confidence for this role.3 Similarly, weaknesses may exist in PC teaching at some medical schools.4 Two parallel studies explore this further.
Methodology: A survey of General Practitioners (GPs) and Hospital Doctors (HDs) examined education, knowledge and confidence in managing patients with PC needs. A second study surveyed UK medical school PC course organisers, focusing on teaching and organisation. Results were analysed for common themes.
Results: Most GPs and HDs regularly saw patients with PC needs, and viewed PC positively. Self-assessment of competences was mixed. Participation in postgraduate PC education was low. Attending conferences does not change practice. Clinical attachments, shadowing opportunities, e-learning and textbooks are more likely to be beneficial.
Undergraduates receive increased PC teaching time with greater curriculum integration and wider use of assessment however variability and areas of weakness exist. Concerns expressed include insufficient placements, teachers and funding. Doubts existed whether courses deliver quality training, adequately prepare doctors to care for PC patients, or fulfil General Medical Council requirements.
Discussion and Conclusion: PC teaching at medical school may be insufficient to equip doctors to care for patients with PC needs. There is a need for increased postgraduate training for non-specialists. To be effective, such training should be learner-centred, involve clinical scenarios and experiential learning, and recognition of barriers to PC education.