Prospective Multicenter Evaluation Research Articles

French multicentre prospective evaluation of radiofrequency ablation in the management of haemorrhoidal disease

PurposeThe aim of this study was to evaluate the efficacy and safety of radiofrequency ablation (RFA) in the management of haemorrhoidal disease with 1 year’s follow-up.MethodThis prospective multicentre study assessed RFA (Rafaelo©) in outpatients with grade II–III haemorrhoids. RFA was performed in the operating room under locoregional or general anaesthesia. Primary endpoint was the evolution of a quality-of-life score adapted to the haemorrhoid pathology (HEMO-FISS-QoL) 3 months after surgery. Secondary endpoints were evolution of symptoms (prolapsus, bleeding, pain, itching, anal discomfort), complications, postoperative pain and medical leave.ResultsA total of 129 patients (69% men, median age 49 years) were operated on in 16 French centres. Median HEMO-FISS-QoL score dropped significantly from 17.4/100 to 0/100 (p < 0.0001) at 3 months. At 3 months, the rate of patients reporting bleeding (21% vs. 84%, p < 0.001), prolapse (34% vs. 91.3%, p < 0.001) and anal discomfort (0/10 vs. 5/10, p < 0.0001) decreased significantly. Median medical leave was 4 days [1–14]. Postoperative pain was 4/10, 1/10, 0/10 and 0/10 at weeks 1, 2, 3 and 4. Seven patients (5.4%) were reoperated on by haemorrhoidectomy for relapse, and three for complications. Reported complications were haemorrhage (3), dysuria (3), abscess (2), anal fissure (1), external haemorrhoidal thrombosis (10), pain requiring morphine (11). Degree of satisfaction was high (+ 5 at 3 months on a − 5/+ 5 scale).ConclusionRFA is associated with an improvement in quality of life and symptoms with a good safety profile. As expected for minimally invasive surgery, postoperative pain is minor with short medical leave.Clinical trial registration and dateClinical trial NCT04229784 (18/01/2020).

Informing ENT training bootcamps - Operating Out-of-hours: A Multicentre Prospective Evaluation.

ENT specialty trainees are invited to national bootcamps to prepare for critical events to which they may have never been exposed. Here, we evaluate the frequency of out-of-hours ENT operations and the level of supervision provided to inform aspiring trainees and the national bootcamps. Information on all ENT operations performed out-of-hours was prospectively recorded by trainees in Kent, Surrey and Sussex over seven months. There was a 100 per cent response rate. The trainee was the most senior surgeon present for 48.4 per cent of out-of-hours operations. Four of the six most frequently performed out-of-hours operations are not included in the ENT indicator procedures, and two are not included in the national ENT bootcamps. Trainees should be aware of the most common procedures they may be expected to perform out-of-hours. Training in these should be provided prior to the commencement of specialty training. The audit design can be replicated across surgical specialties.

ORthopaedic trauma hospital outcomes - Patient operative delays (ORTHOPOD) Study: The management of day-case orthopaedic trauma in the United Kingdom

IntroductionORTHOPOD: Day Case Trauma is a multicentre prospective service evaluation of day-case trauma surgery across four countries. It is an epidemiological assessment of injury burden, patient pathways, theatre capacity, time to surgery and cancellation. It is the first evaluation of day-case trauma processes and system performance at nationwide scale. MethodsData was prospectively recorded through a collaborative approach. Arm one captured weekly caseload burden and operating theatre capacity. Arm two detailed patient and injury demographics, and time to surgery for specific injury groups. Patients scheduled for surgery between 22/08/22 and 16/10/22 and operated on before 31/10/22, were included. For this analysis, hand and spine injuries were excluded. ResultsData was obtained from 86 Data Access Groups (70 in England, 2 in Wales, 10 in Scotland and 4 in Northern Ireland). After exclusions, 709 weeks worth of data representing 23,138 operative cases were analysed. Day-case trauma patients (DCTP) accounted for 29.1% of overall trauma burden and utilised 25.7% of general trauma list capacity. They were predominantly adults aged 18 to 59 (56.7%) with upper limb Injuries (65.7%). Across the four nations, the median number of day-case trauma lists (DCTL) available per week was 0 (IQR 1). 6 of 84 (7.1%) hospitals had at least five DCTLs per week. Rates of cancellation (13.2% day-case; 11.9% inpatient) and escalation to elective operating lists (9.1% day-case; 3.4% inpatient) were higher in DCTPs. For equivalent injuries, DCTPs waited longer for surgery. Distal radius and ankle fractures had median times to surgery within national recommendations: 3 days and 6 days respectively. Outpatient route to surgery was varied. Dominant pathways (>50% patients listed at that episode) in England and Wales were uncommon but the most frequently seen was listing patients in the emergency department, 16 of 80 hospitals (20%). ConclusionThere is significant mismatch in DCTP management and resource availability. There is also considerable variation in DCTP route to surgery. Suitable DCTL patients are often managed as inpatients. Improving day-case trauma services reduces the burden on general trauma lists and this study demonstrates there is considerable scope for service and pathway development and improved patient experience.

Patient-reported Satisfaction and Regret Following Focal Therapy for Prostate Cancer: A Prospective Multicenter Evaluation

BackgroundSeveral reports are available regarding the treatment decision regret of patients receiving conventional treatments for localized prostate cancer (PCa); yet data on patients undergoing focal therapy (FT) are sparse. ObjectiveTo evaluate the treatment decision satisfaction and regret among patients who underwent FT for PCa with high-intensity focused ultrasound (HIFU) or cryoablation (CRYO). Design, setting, and participantsWe identified consecutive patients who underwent HIFU or CRYO FT as the primary treatment for localized PCa at three US institutions. A survey with validated questionnaires, including the five-question Decision Regret Scale (DRS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF-5), was mailed to the patients. The regret score was calculated based on the five items of the DRS, and regret was defined as a DRS score of >25. Outcome measurements and statistical analysisMultivariable logistic regression models were applied to assess the predictors of treatment decision regret. Results and limitationsOf 236 patients, 143 (61%) responded to the survey. Baseline characteristics were similar between responders and nonresponders. During a median (interquartile range) follow-up of 43 (26–68) mo, the treatment decision regret rate was 19.6%. On a multivariable analysis, higher prostate-specific antigen (PSA) at nadir after FT (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.1–2, p = 0.009), presence of PCa on follow-up biopsy (OR 3.98, 95% CI 1.5–10.6, p = 0.006), higher post-FT IPSS (OR 1.18, 95% CI 1.01–1.37, p = 0.03), and newly diagnosed impotence (OR 6.67, 95% CI 1.57–27, p = 0.03) were independent predictors of treatment regret. The type of energy treatment (HIFU/CRYO) was not a predictor of regret/satisfaction. Limitations include retrospective abstraction. ConclusionsFT for localized PCa is well accepted by the patients, with a low regret rate. Higher PSA at nadir, presence of cancer on follow-up biopsy, bothersome postoperative urinary symptoms, and impotence after FT were independent predictors of treatment decision regret. Patient summaryIn this report, we looked at the factors affecting satisfaction and regret in patients with prostate cancer undergoing focal therapy. We found that focal therapy is well accepted by the patients, while presence of cancer on follow-up biopsy as well as bothersome urinary symptoms and sexual dysfunction can predict treatment decision regret.

29 Bridge for Meth: Multi-Center Prospective Evaluation of Emergency Department Initiation of Mirtazapine for Problematic Methamphetamine Use

To describe the characteristics and clinical outcomes among ED patients treated with mirtazapine for problematic methamphetamine use at 6 EDs participating in the CA Bridge, Centers of Excellence Program (COE).

241 Multicenter Prospective Evaluation of Out-of-Hospital Cardiac Arrest Patients Using Transesophageal Echocardiography: A Preliminary Analysis from The Resuscitative TEE Collaborative Registry

Transesophageal echocardiography (TEE) has been proposed as a tool that is ideally suited to image patients during cardiac arrest resuscitation. Providing continuous imaging of the heart during cardiopulmonary resuscitation (CPR), TEE can help identify reversible pathologies and optimize the quality of chest compressions. We performed a preliminary analysis of data collected by the Resuscitative TEE Collaborative Registry, a multicenter, prospective, observational study evaluating the use of TEE during out-of-hospital cardiac arrest (OHCA).

A multi-centre prospective evaluation of THEIA™ to detect diabetic retinopathy (DR) and diabetic macular oedema (DMO) in the New Zealand screening program

PurposeTo validate the potential application of THEIA™ as clinical decision making assistant in a national screening program.MethodsA total of 900 patients were recruited from either an urban large eye hospital, or a semi-rural optometrist led screening provider, as they were attending their appointment as part of New Zealand Diabetic Eye Screening Programme. The de-identified images were independently graded by three senior specialists, and final results were aggregated using New Zealand grading scheme, which was then converted to referable/non-referable and Healthy/mild/more than mild/sight threatening categories.ResultsTHEIA™ managed to grade all images obtained during the study. Comparing the adjudicated images from the specialist grading team, “ground truth”, with the grading by the AI platform in detecting “sight threatening” disease, at the patient level THEIA™ achieved 100% imageability, 100% [98.49–100.00%] sensitivity and [97.02–99.16%] specificity, and negative predictive value of 100%. In other words, THEIA™ did not miss any patients with “more than mild” or “sight threatening” disease. The level of agreement between the clinicians and the aggregated results was (k value: 0.9881, 0.9557, and 0.9175), and the level of agreement between THEIA™ and the aggregated labels was (k value: 0.9515).ConclusionThis multi-centre prospective trial showed that THEIA™ did not miss referable disease when screening for diabetic retinopathy and maculopathy. It also had a very high level of granularity in reporting the disease level. As THEIA™ has been tested on a variety of cameras, operating in a range of clinics (rural/urban, ophthalmologist-led\\optometrist-led), we believe that it will be a suitable addition to a public diabetic screening program.

Diagnostic stewardship for blood cultures in the emergency department: A multicenter validation and prospective evaluation of a machine learning prediction tool.

SummaryBackgroundOveruse of blood cultures (BCs) in emergency departments (EDs) leads to low yields and high numbers of contaminated cultures, accompanied by increased diagnostics, antibiotic usage, prolonged hospitalization, and mortality. We aimed to simplify and validate a recently developed machine learning model to help safely withhold BC testing in low-risk patients.MethodsWe extracted data from the electronic health records (EHR) for 44.123 unique ED visits with BC sampling in the Amsterdam UMC (locations VUMC and AMC; the Netherlands), Zaans Medical Center (ZMC; the Netherlands), and Beth Israel Deaconess Medical Center (BIDMC; United States) in periods between 2011 and 2021. We trained a machine learning model on the VUMC data to predict blood culture outcomes and validated it in the AMC, ZMC, and BIDMC with subsequent real-time prospective evaluation in the VUMC.FindingsThe model had an Area Under the Receiver Operating Characteristics curve (AUROC) of 0.81 (95%-CI = 0.78–0.83) in the VUMC test set. The most important predictors were temperature, creatinine, and C-reactive protein. The AUROCs in the validation cohorts were 0.80 (AMC; 0.78–0.82), 0.76 (ZMC; 0.74–0.78), and 0.75 (BIDMC; 0.74–0.76). During real-time prospective evaluation in the EHR of the VUMC, it reached an AUROC of 0.76 (0.71–0.81) among 590 patients with BC draws in the ED. The prospective evaluation showed that the model can be used to safely withhold blood culture analyses in at least 30% of patients in the ED.InterpretationWe developed a machine learning model to predict blood culture outcomes in the ED, which retained its performance during external validation and real-time prospective evaluation. Our model can identify patients at low risk of having a positive blood culture. Using the model in practice can significantly reduce the number of blood culture analyses and thus avoid the hidden costs of false-positive culture results.FundingThis research project was funded by the Amsterdam Public Health – Quality of Care program and the Dutch “Doen of Laten” project (project number: 839205002).

A multicenter prospective evaluation of owner medication adherence for feline cardiovascular disease in the referral setting

ObjectiveThe aim of this paper is to evaluate owners' chronic medication adherence for management of feline cardiovascular disease in the small animal referral setting. Animals, materials and methodsA questionnaire-based study of owners at five multispecialty, small animal referral centers was conducted. Owners completed a written survey evaluating demographics, degree of medication adherence, and difficulties encountered for medication adherence. Owners were free to decline participation in the study. ResultsFifty-four questionnaires were available for review. The most common diagnosis was hypertrophic cardiomyopathy (n = 31, 57.4%). Clopidogrel was the most cited medication that was difficult to administer consistently (n = 13, 24.0%) although twenty owners (37.0%) reported no difficulty consistently administering medications. “Taste of medication” (n = 14, 25.9%) was the most reported reason for difficulty medicating their cat, and most owners (n = 36, 66.7%) stated twice daily was the highest frequency of heart medications they feel they can consistently administer. Fifty owners (92.6%) met the criteria for medication adherence. ConclusionsChronic medication adherence in this study population was high. Clopidogrel was the most difficult medication to consistently administer, and twice a day dosing was the highest frequency of medication administration most owners could achieve. Cardiologists should be aware of these factors when determining optimal treatment protocols for the management of cardiovascular disease in cats.

Activated clotting time in inpatient diagnostic and interventional settings

Monitoring for the anticoagulant effect of unfractionated (UFH) at the point of care using activated clotting time in real time is vital where risk of thrombosis is high. Although monitoring UFH effect is a routine and important task, changing from one ACT instrument type or technology to another must be preceded by a clinical and statistical evaluation to determine the suitability and repeatability and establish normal and treatable ranges of this newer instrument. In this multi-center prospective evaluation we tested 1236 paired ACT+ samples, and 463 paired ACT-LR samples (1699 total) from enrolled study subjects. Clinical settings included CVOR cardiopulmonary bypass, at the beside in extracorporeal life support (ELS), the Cardiac Catheterization Lab (CCL) during diagnostic studies and percutaneous coronary interventions (PCI), interventional radiology procedures and EP interventions. This study found more consistent clinical performance from the GEM Hemochron 100 as compared to the current clinical model, the Hemochron Signature Elite. The bias of GEM Hemochron 100 for ACT+ and ACT-LR was greatest in the setting of the CVOR where ACT levels were high. ACT-LR measurements by the GEM Hemochron 100 were comparable to the SE when performed in settings of CCL, ECM, EP and ICU. Results obtained for both ACT-LR and ACT+ in all clinical settings in this study using the GEM Hemochron 100 are as accurate and more repeatable as those with the current clinically available Signature Elite.

Standardised protocol for a prospective cross-sectional multicentre clinical utility evaluation of two dual point-of-care tests in non-clinical settings for the screening of HIV and syphilis in men who have sex with men

IntroductionPoint-of-care dual tests (POCTs) for simultaneously detecting antibodies to HIV and syphilis (dual HIV-syphilis POCTs) have been developed recently and show encouraging performance compared with the reference tests in laboratory-based...

Evaluation of an automated artificial intelligence (AI)/ natural language processing (NLP) engine to match patients (pts) with advanced solid cancers to biomarker-driven early phase (EP) clinical trials.

e13513 Background: The increasing complexity of precision medicine in oncology creates significant challenges in identification of pts for biomarker-driven clinical trials. Worldwide expansion of genomic testing will identify more pts with potentially actionable alterations, but the manual task of matching pts to clinical trials requires laborious interpretation of fragmented medical information and knowledge of suitable trial eligibility criteria. Inspirata’s Trial Navigator (TN) solution uses AI and NLP to automatically extract relevant information from both patient medical records and trial protocols to identify appropriate trials. We conducted a retrospective study to evaluate the ability of TN to match pts referred to the Guy’s Hospital EP trials unit. Methods: Anonymised referral letters and genomic reports for pts referred from Jan 2019 to Dec 2020 were used. A subset was used to train TN to extract relevant variables for matching against eligibility criteria for all UK Experimental Cancer Medicine Centre (ECMC) Network trials open within 160 km of Guy’s Hospital at the time of referral, favouring biomarker-matched studies. Finally, TN was tasked with finding 5 ECMC trial matches for 40 referred pts. Matches were scored for eligibility and tumour and/ or biomarker suitability using a quality index (QI): 0, ineligible; 1, generic match; 2, tumour match; 3, biomarker match; 4, tumour and biomarker match. Results: Of 40 pts, most common tumour groups included gastrointestinal (55%), HNSCC (20%) and gynae (10%). TN was able to correctly identify at least 1 suitable trial (median = 4) for 39/40 pts (97%). Selection biomarkers were available for 27 pts, of whom 21 (78%) were matched to at least one appropriate biomarker-directed trial, 5 (12%) were matched to biomarker-agnostic trials and one was not correctly matched due to exclusion for progressive CNS metastases. Of 13 pts without biomarker information, 11 (84%) were matched to at least 1 tumour-appropriate trial and 2 to tumour-agnostic trials. Of all 200 trial matches, 134 (67%) were appropriately matched, of which 80 (59%) were external to Guy’s Cancer centre. Conclusions: TN successfully matched 90% of these preselected cancer pts to an appropriate biomarker- or tumour-directed trial, indicating potential to improve access and recruitment to early phase cancer trials, including those external to the primary treating site with which referrers may not be familiar. A prospective multicentre evaluation of TN is warranted to further define improvements in trial recruitment and efficiency.[Table: see text]

Neoadjuvant Prehabilitation Therapy for Locally Advanced Non–Small-Cell Lung Cancer: Optimizing Outcomes Throughout the Trajectory of Care

BackgroundPrehabilitation is well established for improving outcomes in cancer surgery. Combining prehabilitation with neoadjuvant treatments may provide an opportunity to rapidly initiate cancer-directed therapy while improving functional status in preparation for local consolidation. In this proof-of-concept study, we analyzed non–small-cell lung cancer patients who underwent simultaneous prehabilitation and neoadjuvant therapy. Patients and MethodsWe retrospectively analyzed all patients who underwent neoadjuvant treatment for non–small-cell lung cancer followed by curative intent surgery between 2015 and 2021. Patients who were screened for the prehabilitation program were identified. The screening included assessment of physical performance, nutritional status, and signs of anxiety and depression. ResultsWe identified a total of 141 patients who underwent neoadjuvant therapy. Twenty patients were screened to undergo a prehabilitation program. Four patients did not complete the exercise program (1 surgical intervention too soon, 1 drop-out after the first session, and 2 patients were deemed fit without intervention). The postoperative median length of stay was 2 days (range 1-18). Patients improved their 6-minute-walk test despite undergoing neoadjuvant treatment by a mean of 33 meters (± 50, P = .1). Self-reported functional status (DASI) showed significant improvement by a mean of 10 points (± 11, P = .03), and HADS-anxiety-score was significantly reduced after the prehabilitation program by a mean of 1.5 points (± 1, P = .005). ConclusionNeoadjuvant prehabilitation therapy is feasible and associated with encouraging results. The performance of all measures remains a logistic challenge. With multimodal strategies for lung cancer treatment becoming key to optimal outcomes, neoadjuvant prehabilitation therapy is a concept worthy of prospective multi-center evaluation.

A prospective multi-centre study assessing the safety and effectiveness following the implementation of an accelerated chest pain pathway using point-of-care troponin for use in New Zealand rural hospital and primary care settings.

AimsMost rural hospitals and general practices in New Zealand (NZ) are reliant on point-of-care troponin. A rural accelerated chest pain pathway (RACPP), combining an electrocardiogram (ECG), a structured risk score (Emergency Department Assessment of Chest Pain Score), and serial point-of-care troponin, was designed for use in rural hospital and primary care settings across NZ. The aim of this study was to evaluate the safety and effectiveness of the RACPP.Methods and resultsA prospective multi-centre evaluation following implementation of the RACPP was undertaken from 1 July 2018 to 31 December 2020 in rural hospitals, rural and urban general practices, and urgent care clinics. The primary outcome measure was the presence of 30-day major adverse cardiac events (MACEs) in low-risk patients. The secondary outcome was the percentage of patients classified as low-risk that avoided transfer or were eligible for early discharge. There were 1205 patients enrolled in the study. 132 patients were excluded. Of the 1073 patients included in the primary analysis, 474 (44.0%) patients were identified as low-risk. There were no [95% confidence interval (CI): 0–0.3%] MACE within 30 days of the presentation among low-risk patients. Most of these patients (91.8%) were discharged without admission to hospital. Almost all patients who presented to general practice (99%) and urgent care clinics (97.6%) were discharged to home directly.ConclusionThe RACPP is safe and effective at excluding MACEs in NZ rural hospital and primary care settings, where it can identify a group of low-risk patients who can be safely discharged home without transfer to hospital.

Diaphragm pacing in spinal cord injury can significantly decrease mechanical ventilation in multicenter prospective evaluation.

Cervical spinal cord injury (SCI) can lead to dependence on mechanical ventilation (MV) with significant morbidity and mortality. The diaphragm pacing system (DPS) was developed as an alternative to MV. We conducted a prospective single-arm study of DPS in MV-dependent patients with high SCI and intact phrenic nerves. Following device acclimation, pacing effectiveness to provide ventilation was evaluated. The primary endpoint was the number who could use DPS to breathe for 4 continuous hours without MV. Secondary endpoints included the number of patients that could use DPS 24h/day free of MV and the ability of DPS to maintain clinically acceptable tidal volume (Vt). In addition, we conducted a meta-analysis that included the prospective study along with data from four recently published studies to evaluate DPS hourly use. Fifty-three patients were implanted in the prospective study. Most were male (77.4%) with a median time from injury to treatment of 28.3 (IQR: 12.1, 83.3) months. Four- and 24-h use occurred in 96.2% (95% CI: 87.0%, 99.5%) and 58.5% (95% CI: 44.1%, 74.9%), respectively. Four and 24-h results in the meta-analysis cohort (n=196) exhibited similar results 92.2% (95% CI: 82.6%, 96.7%) and 52.7% (95% CI: 36.2%, 68.6%) using DPS for 4 and 24h, respectively. DPS use significantly exceeded the calculated basal tidal volume requirements by a mean of 48.4% (95% CI: 37.0, 59.9%; p<0.001). This study demonstrates that in most ventilator-dependent patients, diaphragm pacing can effectively supplement or completely replace the need for MV and support basal metabolic requirements.

A Prospective Multicenter Evaluation of Initial Treatment Choice in Metastatic Renal Cell Carcinoma Prior to the Immunotherapy Era: The MaRCC Registry Experience.

The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations. Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest in the clinical trial group (50.3 [35.8-not reached] months) versus pazopanib (39.0 [29.7-50.9] months) and sunitinib 26.2 [19.9-61.5] months). Non-clear cell RCC (21.5% of patients) was associated with worse median OS than clear cell RCC (18.0 vs. 47.3 months). Differences in baseline characteristics, treatment starting dose, and relative dose exposure among treatment groups suggest selection bias. Survey results revealed a de-emphasis on quality of life, toxicity, and patient preference compared with efficacy in treatment selection. The MaRCC Registry gives insights into real-world first-line treatment selection, outcomes, and physician rationale regarding initial treatment selection prior to the immunotherapy era. Differences in outcomes between clinical trial and off-study patients reflect the difficulty in translating trial results to real-world patients, and emphasize the need to broaden clinical trial eligibility. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed regarding these endpoints.

ScotCap - A large observational cohort study.

AimThe aim of this work was to evaluate the performance of colon capsule endoscopy (CCE) in a lower gastrointestinal diagnostic care pathway.MethodThis large multicentre prospective clinical evaluation recruited symptomatic patients (patients requiring investigation of symptoms suggestive of colorectal pathology) and surveillance patients (patients due to undergo surveillance colonoscopy). Patients aged 18 years or over were invited to participate and undergo CCE by a secondary‐care clinician if they met the referral criteria for a colonoscopy. The primary outcome was the test completion rate (visualization of the whole colon and rectum). We also measured the need for further tests after CCE.ResultsA total of 733 patients were invited to take part in this evaluation, with 509 patients undergoing CCE. Of these, 316 were symptomatic patients and 193 were surveillance patients. Two hundred and twenty‐eight of the 316 symptomatic patients (72%) and 137 of the 193 surveillance patients (71%) had a complete test. It was found that 118/316 (37%) of symptomatic patients required no further test following CCE, while 103/316 (33%) and 81/316 (26%) required a colonoscopy and flexible sigmoidoscopy, respectively. Fifty‐three of the 193 surveillance patients (28%) required no further test following CCE, while 104/193 (54%) and 30/193 (16%) required a colonoscopy and flexible sigmoidoscopy, respectively. No patient in this evaluation was diagnosed with colorectal cancer. Two patients experienced serious adverse events – one capsule retention with obstruction and one hospital admission with dehydration due to the bowel preparation.ConclusionCCE is a safe, well‐tolerated diagnostic test which can reduce the proportion of patients requiring colonoscopy, but the test completion rate needs to be improved to match that of lower gastrointestinal endoscopy.

Multi-centre prospective cohort study of diaphragmatic defect phenotype and repair in neonates with congenital diaphragmatic hernia: ‘The Defect Study’

Abstract Defect size and closure technique in neonates with congenital diaphragmatic hernia (CDH) has long-term consequences for morbidity in survivors. Although subjective operative reporting of the defect size has been standardized, objective evaluation is lacking. There is no reported optimum closure technique related to the size and position of the diaphragmatic defect. We aim to objectively describe diaphragmatic defects and repair methods, at the time of neonatal CDH repair, through a prospective multi-centre service evaluation project. We will evaluate all neonates born with CDH surviving to diaphragmatic repair. All specialist paediatric surgical centres in the UK, Ireland and New Zealand will be invited to participate. Non-identifiable patient data will be collected over a 24-month period using a REDCap database. Diaphragmatic defects and hemidiaphragm measurements will be recorded intra-operatively alongside standardized defect reporting. Closure technique and 1-year outcomes will be captured. Demographics and peri-operative data will be reported as median (interquartile range), mean (standard deviation) or categorical variables. Defect measurement will be calculated as an ellipse with area displayed as a histogram. Patch usage will be compared to the defect area using univariate logistic regression analysis. Univariate logistic regression analysis will also be used to assess for the association between peri-operative variables and complications. Where possible, a multi-variate regression analysis will be performed. Centres will register the project as service evaluation at each participating hospital site. The results will be submitted to an international peer reviewed journal and will be disseminated via appropriate international forums and through patient support networks (CDH-UK).

Multicenter Prospective Evaluation of Diagnostic Potential of Flow Cytometric Aberrancies in Myelodysplastic Syndromes

Background: Myelodysplastic syndromes (MDS) are considered clonal diseases and are diagnosed according to WHO by cytomorphology and cytogenetics. The diagnostic potential of flow cytometric aberrancies has not yet been comprehensively evaluated.Aim: Multicenter prospective evaluation of diagnostic potential of flow cytometric aberrancies predefined according to European LeukemiaNet (ELN).Methods: 1682 patients undergoing diagnostics for suspected MDS according to WHO 2016 criteria were analyzed in parallel by flow cytometry according to ELN recommendations.Results: Median age was 72 years (18-97). MDS, MPN-RS-T or CMML were confirmed by cytomophology in 1029 (61%) cases, 653 (39%) were non-MDS. IPSS-R data was available in 857 (51%). An overall flow cytometric readout was available in 1679 (99.8%). 1001 (60%) were in agreement with MDS while 678 (40%) were not. Flow cytometric readout significantly correlated with cytomorphologic diagnosis (p<0.001): 850 (51%) were positive by both methods (flow+/cyto+), 502 (30%) were flow-/cyto-, 176 (10%) were flow-/cyto+ and 151 (9%) flow+/cyto-. The rate of flow+ was higher in high-risk MDS (MDS-EB1/2, 92%) and CMML (89%) compared to low-risk MDS (76%). Accordingly, regarding IPSS-R highest frequency of flow+ was found in very high risk (96%) and lowest one in very low risk group (64%).Non-MDS cases had a fewer myeloid progenitor cells (MPC) (mean±SD, 0.8±0.9%) compared to low-risk MDS (1.7±2.3%, p<0.001), high-risk MDS (6.3±5.0%, p<0.001) and CMML (1.9±2.6%, p<0.001). In particular, MPC >3% was strongly associated with MDS/CMML (286/293, 98%, p<0.001). Antigen expression aberrancies in MPC were more frequent in cases with MDS or CMML than in non-MDS cases but differed between entities with lower frequencies in low-risk MDS cases (table 1).Neutrophil aberrancies were found more frequently in neoplastic cases than in non-MDS cases (table 1). Again, frequencies of aberrations were higher for high-risk MDS as compared to low-risk MDS while this was not the case for CMML showing frequencies rather similar to low-risk MDS.Frequencies of aberrancies in monocytes revealed a similar figure as in neutrophils with higher rates in neoplastic cases but clearly significant numbers positive in non-MDS cases. Interestingly, frequencies were not higher in high-risk MDS as compared to low-risk MDS. As anticipated, frequencies were highest in CMML (table 1).Regarding erythroid cells only an aberrant percentage of them and aberrant CD71 expression were found in a reasonable number of cases. Importantly, rates of positivity were rather high in non-MDS cases which did not differ from CMML cases (table 1).In order to identify the diagnostic value of each individual aberrancy multivariate analyses were performed in the three subgroups, low-risk MDS, high-risk MDS and CMML, as well as in the total cohort. In low-risk MDS ten aberrancies were independently related to MDS (table 2). Five of these aberrancies were found in MPCs, two each in neutrophils and monocytes and one in erythroid cells. In high-risk MDS 11 aberrancies were independently related to MDS (table 2). Eight were found in MPCs, two in neutrophils, none in monocytes and one in erythroid cells. In CMML 12 aberrancies were independently related to CMML (table 2). Four were found in MPCs, neutrophils and monocytes, respectively, and none in erythroid cells. Considering all these three groups together and all aberrancies identified significantly related to MDS/CMML in at least one group in univariate analysis, multivariate analysis identified 12 aberrancies independently related to MDS/CMML (table 2). Six were found in MPCs, two in neutrophils, three in monocytes and one in erythroid cells.Taking into consideration only aberrancies independently associated with MDS/CMML, three such aberrancies resulted in an 80% agreement with the cytomorphologic diagnosis of MDS/CMML, i.e. 20% concordantly negative and 60% concordantly positive. Importantly, this applies without need of at least two cell compartments being affected as specified in the ELN recommendations.Conclusions: This multicenter prospective evaluation confirms the diagnostic potential of flow cytometric aberrancies. A core set of 17 markers identified as independently related to a diagnosis of MDS/CMML is suggested mandatory for flow cytometric evaluation of suspected MDS. An MPC count >3% should be considered indicative of MDS/CMML. [Display omitted] DisclosuresKern: MLL Munich Leukemia Laboratory: Other: Part ownership. Eidenschink Brodersen: Hematologics, Inc.: Current Employment, Other: Equity Ownership. Van de Loosdrecht: Celgene: Consultancy, Research Funding; Amgen: Consultancy; Roche: Consultancy; Novartis: Consultancy; Alexion: Consultancy.

At risk child: a contemporary analysis of injured children in London and the South East of England: a prospective, multicentre cohort study

BackgroundInjury is a leading health burden in children yet relatively little is reported about the contemporary risks they face. Current national registry data may under-represent the true burden of injury...