Leeds Teaching Hospitals NHS Trust Research Articles

Development of an integrated electronic platform for patient self-report and management of adverse events during cancer treatment

Significant adverse events (AE) during cancer therapy disrupt treatment and escalate to emergency admissions. Approaches to improve the timeliness and accuracy of AE reporting may improve safety and reduce health service costs. Reporting AE via patient reported outcomes (PROs), can improve clinician-patient communication and making data available to clinicians in 'real-time' using electronic PROs (ePROs) could potentially transform clinical practice by providing easily accessible records to guide treatment decisions. This manuscript describes the development of eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is a National Institute for Health Research-funded programme, a system for patients to self-report and manage AE online during and after cancer treatment. A multidisciplinary team of IT experts, staff and patients developed using agile principles a secure web application interface (QStore) between an existing online questionnaire builder (QTool) displaying real-time ePRO data to clinicians in the electronic patient record at Leeds Teaching Hospitals NHS Trust. Hierarchical algorithms were developed corresponding to Common Terminology Criteria for Adverse Events grading using the QTool question dependency function. Patient advocates (N = 9), patients (N = 13), and staff (N = 19) usability tested the system reporting combinations of AE. The eRAPID system allows patients to report AE from home on PC, tablet or any web enabled device securely during treatment. The system generates immediate self-management advice for low or moderate AE and for severe AE advice to contact the hospital immediately. Clinicians can view patient AE data in the electronic patient record and receive email notifications when patients report severe AE. Evaluation of the system in a randomised controlled trial in breast, gynaecological and colorectal cancer patients undergoing systemic therapy is currently underway. To adapt eRAPID for different treatment groups, pilot studies are being undertaken with patients receiving pelvic radiotherapy and upper gastrointestinal surgery. ISRCTN88520246.

The junior doctor body - engaging trainees in leadership, management and quality improvement at Leeds Teaching Hospitals NHS Trust.

To engage trainees in leadership, management and quality improvement at Leeds Teaching Hospitals NHS Trust. We approached the chief medical officer at Leeds Teaching Hospitals NHS Trust with a proposal to engage more trainees in leadership, management and quality improvement activities within the trust. These were met with universal approval at a senior management meeting on 24 November 2015. We designed terms of reference and person specifications by January 2016. We invited applications by 8 …

The junior doctor body – engaging trainees in leadership, management and quality improvement at Leeds Teaching Hospitals NHS Trust

To engage trainees in leadership, management and quality improvement at Leeds Teaching Hospitals NHS Trust. We approached the chief medical officer at Leeds Teaching Hospitals NHS Trust with a proposal to engage more trainees in leadership, management and quality improvement activities within the trust. These were met with universal approval at a senior management meeting on 24 November 2015. We designed terms of reference and person specifications by January 2016. We invited applications by 8 …

An introduction to the quality improvement training programme at Leeds Teaching Hospitals NHS Trust

To produce a quality improvement training programme that is available to all employees at Leeds Teaching Hospitals NHS Trust. We designed an introduction to quality improvement training programme, based on the Institute for Healthcare Improvement’s Model for Improvement and the Lens of Profound Knowledge. These sessions …

An analysis of the relationship between serum cortisol and serum sodium in routine clinical patients

ObjectivesAdrenal insufficiency is an uncommon cause of hyponatraemia that should not be overlooked due to the severe consequences of an Addisonian crisis. Using the laboratory database of a large teaching hospital, we have explored the relationship between serum sodium and serum cortisol, and have estimated the frequency of hypoadrenalism in severely hyponatraemic patients. Design and methodsData were gathered over a 23 month period from the Laboratory Information Management System at the Leeds Teaching Hospitals NHS Trust for instances where serum sodium and cortisol had been measured on a single sample. Data were also gathered over the same time period for all patients with severe hyponatraemia (serum sodium ≤120mmol/L) in order to determine the frequency of cortisol requesting and the incidence of adrenal insufficiency. ResultsAnalysis of the data (n=3268 patients) revealed a trend showing higher cortisol concentrations in patients who were severely hypo- or hypernatraemic. The median cortisol concentration for patients with sodium ≤110mmol/L was 856nmol/L, and there was a gradual decrease in cortisol over the sodium range ≤110–150mmol/L (Rs =−0.323, p<0.0001). Patients with sodium ≥151mmol/L had a median cortisol of 725nmol/L. 42% of the 978 patients with serum sodium ≤120mmol/L had serum cortisol measured within two weeks, of whom 1.7% were diagnosed with adrenal insufficiency. ConclusionsThis dataset shows rising cortisol in response to hypo- or hypernatraemia, in keeping with the stress response to illness. The data show that adrenal insufficiency is a rare cause of hyponatraemia which may be overlooked.

Transoral laser resection or radiotherapy? Patient choice in the treatment of early laryngeal cancer: a prospective observational cohort study

The choices made by patients offered treatment for early laryngeal cancer with radiotherapy or transoral laser resection were reviewed. A prospective review was conducted of all patients diagnosed and treated for early laryngeal carcinoma from December 2002 to September 2009 at the Leeds Teaching Hospitals NHS Trust. A total of 209 patients with tumour stage T1 or T2 laryngeal cancer were treated; each new patient suitable for radiotherapy or transoral laser resection was seen jointly by the clinical (radiation) oncologist and head and neck surgeon, and offered the choice of treatment. Of the patients, 47.4 per cent were given a choice between radiotherapy and transoral laser resection; 51.2 per cent were advised to have radiotherapy, and there were no records for the remaining 1.4 per cent. From those given the choice, 59.6 per cent chose transoral laser resection (p < 0.02 (t-test)) and 35.4 per cent chose radiotherapy. When given the choice, a statistically significant majority of patients choose transoral laser resection rather than radiotherapy.

Would the introduction of the Index of Orthognathic Functional Treatment Need (IOFTN) affect referrals and acceptance of people for orthognathic treatment?

Introduction The Index of Orthognathic Functional Treatment Need (IOFTN) was developed to measure functional difficulties arising from malocclusions related to facial deformity. The IOFTN is not currently being used to determine suitability for orthognathic treatment, however, it is a useful aid for assessing and referring patients and takes into account functional and facial appearance. This paper aims to evaluate the potential impact of introduction of the IOFTN on the future provision of orthognathic services.Methods Two methods were used to consider the impact of the IOFTN on orthognathic provision. Firstly, a local retrospective audit was undertaken in Leeds Teaching Hospital NHS Trust involving thirty consecutively treated patients, for whom full records were retrieved. Data was collected using a standardised data caption form. Local standards were agreed concerning the need for treatment. Secondly, a systematic search of published studies was completed to assess evidence from across the UK.Results The audit standard, that is, 90% of patients treated with orthognathic surgery should be categorised as grade 4 (great need) or 5 (very great need) using the IOFTN, was fulfilled. The most common reason for seeking treatment related to dental and facial aesthetics and no patients were treated for speech or TMJ problems alone. The systematic review searches identified four suitable records for inclusion in the review, including two audits and two retrospective studies undertaken in secondary care settings across England and Scotland. These studies showed that at least 86% of all participants scored 4 or 5 using the IOFTN.Conclusions The findings from the audit and literature review indicate that referrals from general dentists and acceptance for orthognathic treatment in secondary care is unlikely to be significantly affected by introduction of the IOFTN. Referring dentists may find the IOFTN a useful prompt for determining whether people are suitable for orthognathic treatment.

Gaining biomarker insights from existing stage II colorectal cancer (CRC) patient cohorts in the United Kingdom: Using real-world data to guide treatment decisions.

614 Background: Trial data, while valuable, does not reflect the importance of a biomarker or treatment in the general population as trials generally exclude patients (pts) due to age or comorbidities. We used merged large population datasets to validate a linked anonymized stage II CRC pt cohort as representative of the population to identify the prognostic and predictive value of deficient mismatch repair (MMR) and a new biomarker Ga-interacting vesicle-associated protein (GIV). Methods: English national data on stage II CRC pts surgically treated from 2001-2015, n = 92,147, were analyzed for survival and clinicopathological parameters. Anonymized data were then linked to pathology and a subset of 405 unselected pts surgically treated from 1990-2003 at the Leeds Teaching Hospitals NHS Trust. These were investigated for 5 antibodies. 4 identified deficient MMR status and one was a new marker; GIV. Results: Population data vs the cohort of 405 pts showed a median age of 73 vs 74 yrs, M:F 55%:45% vs. 53%:47%. These are older than seen in most clinical trials and more reflective of the general stage II CRC population. The median survivals of 108 vs 92 months are as expected based on relative time periods covered. 374 patients yielded valid MMR status on immunohistochemistry (92%); 17% were dMMR and 83% were proficient. dMMR vs pMMR pts did not differ in age (median age 75 vs 74.5) or distribution of T3 (69% vs 66%), but were more likely to be female (71% vs 42%), sited in the right colon (76% vs 30%) and poorly differentiated (42% vs 8%). 11% of dMMR and 8% of pMMR received adjuvant chemotherapy in this cohort. GIV scoring status was also evaluated (405): 30% (121) were negative, 65% (264) positive and 5% (20) were not scored. Survival and risk scores by MMR and GIV status will be presented. Conclusions: Population based data has been created to validate the representativeness of a stage II biomarker cohort. This approach using large, population based data-sets provides opportunities to understand the generalizability of biomarker cohorts. The creation and expansion of such cohorts will more effectively validate existing and new biomarkers and treatments in real-world populations.

Citrate anticoagulation in the ICU: the Leeds experience.

Continuous renal replacement therapy (CRRT) is widely used in the management of critically ill patients with acute kidney injury. It requires effective anticoagulation of the extracorporeal blood circuit. Although heparin is the most commonly prescribed anticoagulant, there are issues associated with heparin, and there has been increasing interest in regional citrate anticoagulation as an alternative. In 2013, The Leeds Teaching Hospitals NHS Trust switched from heparin to citrate anticoagulant for CRRT in intensive care units (ICUs) across the Trust. This article examines the reasons for the switch, the implementation of citrate and the impact of this quality-improvement project in terms of patient outcome data and feedback from the ICU nursing team.

Alcoholic liver disease on the intensive care unit - Outcomes and prognostication.

Hospital admissions with decompensated chronic alcoholic liver disease have been increasing, leading to increased pressure on intensive care unit services. We aimed to determine the outcome and prognostic factors for patients with alcoholic liver disease requiring admission to intensive care unit. This was a retrospective study over 5 years (January 2006-December 2010) of all intensive care unit admissions with alcoholic liver disease to either of the two Leeds Teaching Hospitals NHS Trust general intensive care units. A detailed case note review was conducted based on a pre-established proforma. Eighty-two patients included. Primary outcome was hospital mortality. The overall intensive care unit and hospital mortality were 46% and 67%, respectively. Hospital mortality in patients successfully discharged from intensive care unit with the intent of recovery remained high at 21%. Variceal bleed was the only indicator that had a mortality <60%. Factors which suggested a poor outcome included sepsis (86% mortality) and hepato-renal syndrome (86% mortality). A Sequential Organ Failure Assessment score of greater than 10 on intensive care unit admission was associated with 97% hospital mortality. Sequential Organ Failure Assessment score increased from a mean of 10.9-12.5 in those that did not survive hospital. Patients with first alcoholic liver disease related admission had poorer outcomes. These results are similar to previous studies with no significant improvement in outcomes. Alcoholic liver disease is not a contra-indication to intensive care unit admission but assessment of the individual patient is required. The most appropriate objective factors to guide prognostication are the presenting intensive care unit diagnosis and Sequential Organ Failure Assessment score. First presentation of alcoholic liver disease is not a positive prognostic indicator.

17 Is maternal blood pressure during pregnancy associated with infant arterial stiffness?

Introduction In adults, arterial stiffness measured by pulse wave velocity (PWV) is regarded as a predictor of cardiovascular disease [1]. This association is less well established in infants, however. Infant and childhood vascular development is dependent on several factors related to the pregnancy, including maternal blood pressure (BP) with one study finding an inverse relationship between BP and neonatal aortic PWV at 1–3days [2]. Objective To assess the association between maternal BP in pregnancy and infant brachio-femoral PWV at age 2–6weeks. Methods The Baby VIP study recruited mother-baby pairs from postnatal wards at Leeds Teaching Hospitals NHS Trust. PWV was measured non-invasively in 284 babies at a home visit 2–6weeks after recruitment using the Vicorder device. Maternal BP at booking and at 36weeks gestation, along with other co-variables, were collected from delivery and antenatal notes. Multivariable linear regression models were used to link maternal systolic and diastolic BPs, and BP change from booking to 36weeks with PWV. Results At booking, the mean maternal systolic BP was 112mmHg (standard deviation (s.d) 12) and diastolic BP was 67mmHg (s.d 10). At 36weeks gestation, mean maternal systolic BP was 116.3mmHg (s.d 15) and diastolic BP was 70.8mmHg (s.d 12). Mean infant PWV was 6.7m/s (s.d 1.3). PWV was not significantly associated with hypertension in pregnancy (at booking or at 36weeks) in univariate analysis, where hypertension was defined as systolic BP⩾140mmHg or diastolic BP⩾90mmHg, or a rise in systolic BP of ⩾30mmHg or rise in diastolic BP of ⩾15mmHg from booking to 36weeks ( p >0.05). There was no association between infant PWV and maternal systolic BP at 36 weeks assessed as a continuous variable (regression co-efficient 0.003m/s, 95% confidence intervals (CI) −0.01, 0.01, p =0.6) adjusted for pregnancy factors including maternal age, ethnicity, history of gestational diabetes, pre-eclampsia, anaemia, BMI and infant factors including baby's age, position, whether sleep or awake at the time of measurement, and prematurity. There was no association between infant PWV and a ⩾30mmHg rise in systolic BP at 36 weeks from booking (adjusted regression co-efficient −0.4m/s, 95% CI −1.1, 0.41, p =0.4). Conclusions This study has shown that there is no evidence of any associations between infant PWV and hypertension or maternal BP during pregnancy. We demonstrate the feasibility and acceptability of using PWV in early infancy. However, further studies are required to determine the predictors of infant PWV, the significance and long term implications of PWV measurements in infants.

PTU-128 Prevalence and Management of Irritable Bowel Syndrome Seen in Colorectal Surgery and Gastroenterology Clinics

Introduction Irritable bowel syndrome (IBS) in the UK accounts for a large proportion of patients seen in secondary care. Pathways to the diagnosis of IBS are not standardised, and patients are often reviewed outside a luminal Gastroenterology service. We examined the burden of IBS in both Colorectal Surgery and Gastroenterology clinics. Methods All patients seen with IBS in either Gastroenterology (GE) or Colorectal Surgery (CS) clinics over a 1 month period January to February 2014 at Leeds Teaching Hospitals NHS Trust were identified. The following data were retrospectively recorded: age/sex of the patient, investigations prior to diagnosis, number of visits to that speciality clinic, number and type of medications prescribed, and final placement of the patient. We compared management of patients in both settings using a Chi-squared test. Results There were a total of 76 patients with IBS seen in CS clinics (mean age 49.6 years, 39 (51.3%) female) and 57 patients in GE clinics (mean age 39.1 years, 39 (68.4%) female). The number and type of investigations requested prior to diagnosis are detailed in Table 1. In CS clinics, colonic imaging (colonoscopy, sigmoidoscopy or barium enema) was requested in 70 (92.1%) patients, compared with 39 (68.4%) patients in GE clinics (P = 0.001). Cross-sectional imaging was utilised in 36 (47.4%) patients in CS clinics, compared with 19 (33.3%) patients in GE clinics (P = 0.15). Serological testing for coeliac disease was not performed in 22 (29.9%) patients in CS clinics, and 5 (8.8%) patients in GE clinics (P = 0.008). For the CS clinic patients the mean number of visits was 2.7 (range 1–14) with 22 (28.95%) patients offered prescribed therapy. In the GE clinic patients the mean number of visits was 2.5 (range 1–5), with 43 (75.4%) patients offered prescribed therapy (P Conclusion These data highlight the need for a more consistent referral process, and a more specialised approach to the management of this patient group. This should be based on current guidelines for the management of IBS using evidence-based treatments and with easy access to dietetic, psychological, and specialist nurse support. Disclosure of Interest None Declared

Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour.

Background:Colorectal cancer (CRC) is a major cause of mortality and morbidity. The impact of inflammatory biomarkers (C-reactive protein etc.) on CRC is increasingly studied including systemic neutrophil-to-lymphocyte ratio (NLR) as they seem to predict outcome.Methods:All patients who underwent curative resection for CRC from 2000 to 2004 at Leeds Teaching Hospitals NHS Trust had pre-operative NLR calculated. Demographic, histopathological and survival data were collected. Tissue microarrays were created and stained to determine the mismatch repair (MMR) protein status of each tumour. Local lymphocytic response to the tumour was assessed and graded.Results:About 358 patients were eligible. Of these 88 had an NLR ⩾5, which predicted lower overall survival and greater disease recurrence. A high NLR is associated with higher pT- and pN-stage and a greater incidence of extramural venous invasion. MMR protein status was not associated with NLR. A pronounced lymphocytic reaction at the invasive margin (IM) indicated a better prognosis and was associated with a lower NLR.Conclusion:Neutrophil-to-lymphocyte ratio predicts disease-free and overall survival and is associated with a more aggressive tumour phenotype. The lymphocytic response to tumour at the IM is associated with NLR however dMMR is not. Neutrophil-to-lymphocyte ratio is a cheap, easy-to-access test that predicts outcome in CRC.

PTU-312 Patients referred straight to test for suspected upper gastro intestinal malignancy and normal endoscopy need further investigation: Abstract PTU-312 Table 1

Introduction Straight to Test (STT) Oesophagogastroduodenoscopy (OGD) is a referral pathway for General Practitioners (GP) for suspected cancer (red flag) symptoms of the Upper Gastrointestinal (UGI) tract. Pathways vary between organisations, many of which discharge patients following a normal OGD. Here we report the outcome of further investigation of patients with a normal upper endoscopy. Method Data were gathered retrospectively from STT referrals over a 3 month period (January – March 2012) at Leeds Teaching Hospitals NHS Trust, UK. Patients with simple dyspepsia and a normal OGD were discharged; those with weight loss underwent CT scan and clinic review. Electronic records were reviewed for further investigations and outcomes. Data were compared to a similar audit in 2009 in the same hospital. Results Of 298 STT endoscopy referrals 16 were excluded, due to failure to attend for OGD (8) or incomplete or inappropriate procedure (8). 282 patients underwent STT OGD; age range: 20 to 91 yrs, mean: 66 yrs, 44% males. In comparison, in the previous audit 200 patients were referred over a 6 month period. Presenting symptoms included: dysphagia 114 (40%), dyspepsia 98 (34%) and unintentional weight loss 91 (32%). UGI and non-UGI cancer was identified in 17 (6.02%) and 16 (5.67%) of patients, respectively; the corresponding figures from the 2009 audit were 13 (6.5%) and 7 (4.0%). Of the 17 identified UGI cancers, 9 (52.9%) were oesophageal, 7 (41.2%) gastric and 1 (5.9%) gastro-oesophageal junction. Other findings included peptic ulcer 20 (7.1%) and oesophagitis 10 (3.5%). Patients with a normal OGD and alarm symptoms (84) underwent further investigation, usually CT (65). The 16 cancers identified outside the UGI tract were pancreatic (3), lung (3), lymphoma (2), CLL (1), renal (2), ampullary (1), liver- HCC (1), parathyroid (1), colorectal (1) and ovarian (1). The positive predictive value (PPV) of individual symptoms is shown in the table; the PPV of dysphagia plus weight loss for UGI cancer was 23.07%. Conclusion Since 2009, suspected UGI cancer referrals have tripled, yet detection of UGI and non-UGI malignancy combined remains over 10%. UGI malignancy was identified in 1 in 4 patients presenting with the combination of dysphagia and weight loss. For patients referred with suspected UGI cancer and no significant finding on endoscopy, further targeted investigation is recommended. Disclosure of interest None Declared.

PTU-009 The utility of routine chromoendoscopy for detection of dysplastic lesions during surveillance colonoscopy in patients with colonic inflammatory bowel disease. does research translate to clinical practice?

Introduction Dysplasia in colonic inflammatory bowel disease (IBD) is often multifocal and flat. Chromoendoscopy (CE) has been shown in prospective studies to improve dysplasia detection rates by improving the ability to detect subtle mucosal changes. 1 The utility of CE in dysplasia detection in patients with IBD during routine clinical practice has not been reported so far. We aimed to compare the yield of dysplastic lesions detected by CE with standard white light endoscopy (WLE). Method Retrospective cohort study of patients with long standing (>7 years) colonic IBD undergoing surveillance colonoscopy at Leeds Teaching Hospital NHS Trust between January 2012 to December 2013. Details of diagnosis, duration of disease and outcomes of the colonoscopy were collected from the endoscopy database, electronic patient records and patient notes. Results There were 120 colonoscopies in the CE group and 220 colonoscopies in the WLE group. The groups were well matched for all demographic variables. 27 dysplastic lesions were detected in 20 patients in the CE group and 9 dysplastic lesions were detected in 6 patients in the WLE group. All the lesions were detected on targeted biopsy and harboured low grade dysplasia. The adjusted prevalence ratio (on a per patient basis) for detecting any dysplastic lesion was 4.6 (95% CI 1.6–13.7) in favour of CE. Conclusion CE colonoscopy improves detection of dysplastic lesions during surveillance colonoscopy of patients with colonic IBD even in routine clinical practice, confirming data from prospective trials. CE should be the standard of care for all IBD surveillance procedures as advocated by both BSG and ECCO guidelines. Disclosure of interest None Declared. Reference Subramanian V, Mannath J, Ragunath K, et al . Meta-analysis: the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Aliment Pharmacol Ther. 2011;33(3):304–12

PTH-018 Predicting survival in palliative oesophageal stent insertion

<h3>Introduction</h3> Self-expanding metal stents (SEMS) are an important treatment modality in palliation of malignant dysphagia, either alone or in addition to chemotherapy or radiotherapy. However, the optimal timing of stent insertion remains uncertain when considering prognosis in advanced malignancy. We present a large single centre experience of patients undergoing SEMS insertion for malignant dysphagia. The aim was to identify risk factors associated with overall and 30 day mortality post-oesophageal stenting. <h3>Method</h3> All patients receiving an oesophageal stent for palliation of dysphagia in primary oesophageal malignancy between January 2009 and December 2013 in Leeds Teaching Hospitals NHS Trust were included. All devices used were Niti S double covered stents inserted by four experienced practitioners using a combined endoscopic and fluoroscopic procedure. Demographics, tumour site and stage, performance status, Charlson co-morbidity index, dysphagia score, previous oncological therapies and serum albumin and CRP in the week prior to stent insertion were retrieved from electronic patient records. Kaplan-Meier survival estimates and Cox proportional hazards regression were performed to identify risk factors predictive of mortality. <h3>Results</h3> Among 259 patients (mean age 70.3 (range 32 to 99)), the median post-stent survival was 100 days (95% CI, 87 to 116). 51 patients (20%) died within 30 days of the stenting procedure and 10 patients (4%) died within 7 days. 35 patients (14%) required repeat stenting for tumour overgrowth, stricture or stent migration; the median time to re-stent was 137 days (95% CI, 99 to 175). Serum CRP &gt; 50 was an independent predictor of 30 day mortality (hazard ratio [HR], 3.7; 95% CI, 1.7 to 8.0). Overall post-stent mortality was associated with CRP &gt; 50 (HR, 2.3; 95% CI, 1.6 to 3.2) and albumin &lt; 30 (HR, 1.9; 95% CI, 1.1 to 3.1). <h3>Conclusion</h3> Our 30 day mortality of 20% is consistent with data published elsewhere (13¹–25%²), but this study identifies the association of elevated CRP with short-term mortality. This may reflect advanced disease or concurrent infection (such as aspiration pneumonia) and may be a useful guide to optimising timing of stent insertion. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Homs MY, Steyerberg EW, Eijkenboom WM, <i>et al</i>. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Lancet 2004;364(9444):1497–504 van Heel NC, Haringsma J, Boot H, <i>et al</i>. Comparison of 2 expandable stents for malignant esophageal disease: a randomized controlled trial. Gastrointestinal Endoscopy;76(1):52–8

P116. Effects of trastuzumab treatment on the patterns of survival and metastasis in Her-2 positive breast cancers

P116. Effects of trastuzumab treatment on the patterns of survival and metastasis in Her-2 positive breast cancers

P114. Acellular dermal matrix versus latissimus dorsi breast reconstruction: An investigation of the costs

P114. Acellular dermal matrix versus latissimus dorsi breast reconstruction: An investigation of the costs

Issue Highlights

Issue Highlights

Can rapid integrated polymerase chain reaction-based diagnostics for gastrointestinal pathogens improve routine hospital infection control practice? A diagnostic study.

Every year approximately 5000-9000 patients are admitted to a hospital with diarrhoea, which in up to 90% of cases has a non-infectious cause. As a result, single rooms are 'blocked' by patients with non-infectious diarrhoea, while patients with infectious diarrhoea are still in open bays because of a lack of free side rooms. A rapid test for differentiating infectious from non-infectious diarrhoea could be very beneficial for patients. To evaluate MassCode multiplex polymerase chain reaction (PCR) for the simultaneous diagnosis of multiple enteropathogens directly from stool, in terms of sensitivity/specificity to detect four common important enteropathogens: Clostridium difficile, Campylobacter spp., Salmonella spp. and norovirus. A retrospective study of fixed numbers of samples positive for C. difficile (n = 200), Campylobacter spp. (n = 200), Salmonella spp. (n = 100) and norovirus (n = 200) plus samples negative for all these pathogens (n = 300). Samples were sourced from NHS microbiology laboratories in Oxford and Leeds where initial diagnostic testing was performed according to Public Health England methodology. Researchers carrying out MassCode assays were blind to this information. A questionnaire survey, examining current practice for infection control teams and microbiology laboratories managing infectious diarrhoea, was also carried out. MassCode assays were carried out at Oxford University Hospitals NHS Trust. Further multiplex assays, carried out using Luminex, were run on the same set of samples at Leeds Teaching Hospitals NHS Trust. The questionnaire was completed by various NHS trusts. Sensitivity and specificity to detect C. difficile, Campylobacter spp., Salmonella spp., and norovirus. Nucleic acids were extracted from 948 clinical samples using an optimised protocol (200 Campylobacter spp., 199 C. difficile, 60 S. enterica, 199 norovirus and 295 negative samples; some samples contained more than one pathogen). Using the MassCode assay, sensitivities for each organism compared with standard microbiological testing ranged from 43% to 94% and specificities from 95% to 98%, with particularly poor performance for S. enterica. Relatively large numbers of unexpected positives not confirmed with quantitative PCR were also observed, particularly for S. enterica, Giardia lamblia and Cryptosporidium spp. As the results indicated that S. enterica detection might provide generic challenges to other multiplex assays for gastrointestinal pathogens, the Luminex xTag(®) gastrointestinal assay was also run blinded on the same extracts (937/948 remaining) and on re-extracted samples (839/948 with sufficient material). For Campylobacter spp., C. difficile and norovirus, high sensitivities (> 92%) and specificities (> 96%) were observed. For S. enterica, on the original MassCode/Oxford extracts, Luminex sensitivity compared with standard microbiological testing was 84% [95% confidence interval (CI) 73% to 93%], but this dropped to 46% on a fresh extract, very similar to MassCode, with a corresponding increase in specificity from 92% to 99%. Overall agreement on the per-sample diagnosis compared with combined microbiology plus PCR for the main four/all pathogens was 85.6%/64.7%, 87.0%/82.9% and 89.8%/86.8% for the MassCode assay, Luminex assay/MassCode extract and Luminex assay/fresh extract, respectively. Luminex assay results from fresh extracts implied that 5% of samples did not represent infectious diarrhoea, even though enteropathogens were genuinely present. Managing infectious diarrhoea was a significant burden for infection control teams (taking 21% of their time) and better diagnostics were identified as having major potential benefits for patients. Overall, the Luminex xTag gastrointestinal panel showed similar or superior sensitivity and specificity to the MassCode assay. However, on fresh extracts, this test had low sensitivity to detect a key enteric pathogen, S. enterica; making it an unrealistic option for most microbiology laboratories. Extraction efficiency appears to be a major obstacle for nucleic acid-based tests for this organism, and possibly the whole Enterobacteriaceae family. To improve workflows in service microbiology laboratories, to reduce workload for infection control practitioners, and to improve outcomes for NHS patients, further research on deoxyribonucleic acid-based multiplex gastrointestinal diagnostics is urgently needed. The Health Technology Assessment programme of the National Institute for Health Research.