Low Probability Patients Research Articles

Integrating Pre-test Probability and Point-of-Care Ultrasound (POCUS) in the Emergency Department (ED) Diagnosis of Small Bowel Obstruction (SBO).

Introduction A computed tomography (CT) scan and point-of-care ultrasound (POCUS) are commonly employed for diagnosing small bowel obstructions (SBOs). Prior studies demonstrated that POCUS has 90-95% sensitivity and specificity compared with CT scanning, which is the gold standard. Unlike other imaging modalities (in which the ordering and performing clinician are not the same), POCUS-performing/interpreting sonologists must recognize the risk of confirmation bias in the POCUS application. Per Bayesian analysis, the likelihood of a diagnosis being true following a diagnostic test is based on the ordering clinician's pre-test probability and the test characteristics (sensitivity and specificity, from which positive and negative likelihood ratios can be calculated). Consequently, establishing pre-test probability is important in informing downstream diagnostic or therapeutic interventions, as pre-test probability influences post-test odds. Little research has been done on the role of POCUS sonologist's pre-test probability and actual POCUS results regarding SBO. This study assessed the role of POCUS, integrating pre-test probability and POCUS results to determine post-test odds. Methods One hundred six patients were recruited on a convenience basis and underwent POCUS and CT between April 2017 and December 2022. All sonographers were credentialed in POCUS. POCUS sonologists' pre-test probabilities and POCUS and CT results were captured, which were compared. Sensitivity, specificity, LR+, and LR- were calculated, and correlations were made between pre-test probability and POCUS and CT results. Results POCUS exhibited a sensitivity of 92% and specificity of 90%, with a corresponding positive likelihood ratio (LR+) of 9.3 and a negative likelihood ratio (LR-) of 0.09 for diagnosing SBO. Among patients with a high pre-test probability of SBO, a negative ultrasound yielded post-test odds of 0.4%, whereas a positive POCUS yielded post-test odds of 39.6%. Among patients with a low pre-test probability, a negative POCUS resulted in post-test odds of 0%, while a positive POCUS led to post-test odds of 2.1%, yielding a number needed to scan (NNS) of ~50 to identify a patient with an SBO on CT. Conclusion This study confirmed POCUS's sensitivity and specificity of ~90-95% and a corresponding LR+ of 9.2 and LR- of 0.9. Pre-test probability substantially affected post-test odds. Patients with a high pre-test probability and a positive POCUS had post-test odds of 39.6 and should have a confirmatory CT, while those with a negative POCUS have very low post-test odds and very likely will not benefit from CT. Patients with low pre-test probability and a positive POCUS have post-test odds of 2.1%, similar to the Wells Score and HEART score; such patients may not benefit from a CT, though clinicians should use their judgment/discretion. Patients with a low pre-test probability and a negative POCUS have post-test odds of 0% and should not have a CT. Among low pre-test probability patients, the NNS was ~50 to identify patients with an SBO on CT.

Validation of the myocardial-ischaemic-injury-index machine learning algorithm to guide the diagnosis of myocardial infarction in a heterogenous population: a prespecified exploratory analysis

SummaryBackgroundDiagnostic pathways for myocardial infarction rely on fixed troponin thresholds, which do not recognise that troponin varies by age, sex, and time within individuals. To overcome this limitation, we recently introduced a machine learning algorithm that predicts the likelihood of myocardial infarction. Our aim was to evaluate whether this algorithm performs well in routine clinical practice and predicts subsequent events.MethodsThe myocardial-ischaemic-injury-index (MI3) algorithm was validated in a prespecified exploratory analysis using data from a multi-centre randomised trial done in Scotland, UK that included consecutive patients with suspected acute coronary syndrome undergoing serial high-sensitivity cardiac troponin I measurement. Patients with ST-segment elevation myocardial infarction were excluded. MI3 incorporates age, sex, and two troponin measurements to compute a value (0–100) reflecting an individual's likelihood of myocardial infarction during the index visit and estimates diagnostic performance metrics (including area under the receiver-operating-characteristic curve, and the sensitivity, specificity, negative predictive value, and positive predictive value) at the computed score. Model performance for an index diagnosis of myocardial infarction (type 1 or type 4b), and for subsequent myocardial infarction or cardiovascular death at 1 year was determined using the previously defined low-probability threshold (1·6) and high-probability MI3 threshold (49·7). The trial is registered with ClinicalTrials.gov, NCT01852123.FindingsIn total, 20 761 patients (64 years [SD 16], 9597 [46%] women) enrolled between June 10, 2013, and March 3, 2016, were included from the High-STEACS trial cohort, of whom 3272 (15·8%) had myocardial infarction. MI3 had an area under the receiver-operating-characteristic curve of 0·949 (95% CI 0·946–0·952) identifying 12 983 (62·5%) patients as low-probability for myocardial infarction at the pre-specified threshold (MI3 score <1·6; sensitivity 99·3% [95% CI 99·0–99·6], negative predictive value 99·8% [99·8–99·9]), and 2961 (14·3%) as high-probability at the pre-specified threshold (MI3 score ≥49·7; specificity 95·0% [94·6–95·3], positive predictive value 70·4% [68·7–72·0]). At 1 year, subsequent myocardial infarction or cardiovascular death occurred more often in high-probability patients than low-probability patients (520 [17·6%] of 2961 vs 197 [1·5%] of 12 983], p<0·0001).InterpretationIn consecutive patients undergoing serial cardiac troponin measurement for suspected acute coronary syndrome, the MI3 algorithm accurately estimated the likelihood of myocardial infarction and predicted subsequent adverse cardiovascular events. By providing individual probabilities the MI3 algorithm could improve the diagnosis and assessment of risk in patients with suspected acute coronary syndrome.FundingMedical Research Council, British Heart Foundation, National Institute for Health Research, and NHSX.

National adherence to the ASGE-SAGES guidelines for managing suspected choledocholithiasis: An EAST multicenter study.

The American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons provide guidelines for managing suspected common bile duct (CBD) stones. We sought to evaluate adherence to the guidelines among patients with choledocholithiasis and/or acute biliary pancreatitis (ABP) and to evaluate the ability of these guidelines to predict choledocholithiasis. We prospectively identified patients undergoing same-admission cholecystectomy for choledocholithiasis and/or ABP from 2016 to 2019 at 12 United States medical centers. Predictors of suspected CBD stones were very strong (CBD stone on ultrasound; bilirubin >4 mg/dL), strong (CBD > 6 mm; bilirubin ≥1.8 to ≤4 mg/dL), or moderate (abnormal liver function tests other than bilirubin; age >55 years; ABP). Patients were grouped by probability of CBD stones: high (any very strong or both strong predictors), low (no predictors), or intermediate (any other predictor combination). The management of each probability group was compared with the recommended management in the guidelines. The cohort was comprised of 844 patients. High-probability patients had 64.3% (n = 238/370) deviation from guidelines, intermediate-probability patients had 29% (n = 132/455) deviation, and low-probability patients had 78.9% (n = 15/19) deviation. Acute biliary pancreatitis increased the odds of deviation for the high- (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.06-2.8; p = 0.03) and intermediate-probability groups (OR, 1.6; 95% CI, 1.07-2.42; p = 0.02). Age older than 55 years (OR, 2.19; 95% CI, 1.4-3.43; p < 0.001) also increased the odds of deviation for the intermediate group. A CBD greater than 6 mm predicted choledocholithiasis in the high (adjusted OR (aOR), 2.16; 95% CI, 1.17-3.97; p = 0.01) and intermediate group (aOR, 2.78; 95% CI, 1.59-4.86; p < 0.001). Any very strong predictor (aOR, 2.43; 95% CI, 1.76-3.37; p < 0.0001) and both strong predictors predicted choledocholithiasis (aOR, 2; 95% CI, 1.35-2.96; p < 0.001). Almost 45% of patients with suspected CBD stones were managed discordantly from the American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons guidelines. We believe these guidelines warrant revision to better reflect the ability of the clinical variables at predicting choledocholithiasis. Therapeutic/Care Management; Level IV.

Diagnostic Value of Neutrophil Lymphocyte Ratio and D-Dimer as Biological Markers of Deep Vein Thrombosis in Patients Presenting with Unilateral Limb Edema.

IntroductionPatients with deep vein thrombosis (DVT) pose high morbidity and mortality risk thus needing fast and accurate diagnosis. Wells clinical prediction scores with D-dimer testing are traditionally used to rule out patients with low probability of DVT. However, D-dimer testing has a few limitations regarding its relatively low specificity. Neutrophil-lymphocyte ratio (NLR), a marker of inflammation, was found to increase in DVT. Hence, we aimed to evaluate the role of NLR for DVT diagnosis.MethodsData were collected from medical records of patients with suspected DVT at Cipto Mangunkusumo National General Hospital during January–December 2014. Diagnosis of DVT was conducted using lower limb ultrasonography. Diagnostic values for NLR, D-dimer, and NLR + D-dimer were determined by receiver operating characteristic (ROC) analysis to obtain area under the curve (AUC), sensitivity, specificity, negative predictive value, and positive predictive values. Sensitivity and specificity analyses of NLR and D-dimer were also conducted based on Wells score and divided into groups of low and high probability of DVT.ResultsThe AUC values for NLR, D-dimer, and NLR + D-dimer were 72.6%, 70.4%, and 76.1%, respectively. The optimal cut-off value determined for NLR was 5.12 with sensitivity of 67.7%, specificity of 67.9%, PPV of 68.85%, and NPV of 64.91% in differentiating subjects with and without DVT. This study also found that D-dimer had sensitivity of 69.4%, specificity of 71.4%, PPV of 72.88%, and NPV of 67.8%. Meanwhile, the NLR + D-dimer combination had sensitivity of 66.1% and specificity of 72.6%. Multivariate analysis showed that NLR (OR: 2.636; 95% CI: 1.144–6.076; p: 0.023) and D-dimer (OR: 4.175; 95% CI: 1.810–9.633; p: 0.001) were associated with DVT.ConclusionNLR value has wider AUC than D-Dimer and is relatively easier to obtain and does not require specific assay, thus enabling rapid evaluation of symptomatic patients suspected of having DVT. Adding NLR to D-dimer increased AUC to detect DVT. Therefore, NLR could serve as a complementary diagnostic tool for D-dimer to exclude DVT, especially in low clinical probability patients.

A73 PERFORMANCE OF ASGE AND ESGE CRITERIA FOR RISK STRATIFICATION FOR CHOLEDOCHOLITHIASIS IN A REAL-WORLD SETTING

Abstract Background Choledocholithiasis (CDL) is a common clinical entity and can lead to serious complications, such as pancreatitis or ascending cholangitis. Endoscopic retrograde cholangio-pancreatography (ERCP) is generally the first-line procedure for definitive management of CDL. ERCP has well-established adverse events. Given the risks, patients can be stratified by likelihood of finding CDL on ERCP, thus potentially avoiding an unnecessary procedure in low probability patients. There are three commonly used criteria for this – the American Society for Gastrointestinal Endoscopy (ASGE) 2010 criteria, the ASGE 2019 criteria, and the European Society of Gastrointestinal Endoscopy (ESGE) 2019 criteria. These criteria use a mixture of biliary imaging, clinical condition, and liver biochemistry to stratify patients into low, intermediate, and high probability for CDL. Aims To test the performance characteristics of the ASGE 2010, ASGE 2019, and ESGE 2019 criteria for probability of CDL on a real-world sample. Methods We identified all adult patients who had ERCP done at our local centre for suspected CDL between 2012/01/01 and 2018/10/07. A sample of 1000 cases were chosen. We obtained the patients’ pre-procedural liver biochemistries, pre-procedural imaging in the preceding 6 months, and their ERCP reports. We used a semi-automated algorithm to determine confirmation of CDL. We inferred clinical gallstone pancreatitis using the surrogate of serum lipase at or greater than three times upper limit of normal. We could not capture clinical ascending cholangitis from the collected data. We stratified each patient according to the three guidelines and calculated their performance characteristics. Results After manually reviewing visits with incomplete ERCP or repeat ERCP, we analyzed 879 ERCP visits. There were 622 with stone or sludge found on ERCP. The performance characteristics of the high-probability and intermediate-probability criteria of the three guidelines are listed in the table below. Conclusions Our results for the 2010 ASGE guidelines high probability patients are in keeping with previous validation studies. There have been only one validation study each of the 2019 ASGE guidelines and the 2019 ESGE guidelines, and our results are different in sensitivity and negative predictive value. Future directions in refining these risk stratification tools are needed, and our project in ongoing in assessing the additional value of trends in liver biochemistry. Funding Agencies None

Potential overdiagnosis of long QT syndrome using exercise stress and QT stand testing in children and adolescents with a low probability of disease.

Long QT syndrome (LQTS) is a dangerous arrhythmia disorder that often presents in childhood and adolescence. The exercise stress test (EST) and QT-stand test may unmask QT interval prolongation at key heart rate transition points in LQTS, but their utility in children is debated. To determine if the QT-stand test or EST can differentiate children with a low probability of LQTS from those with confirmed LQTS. This retrospective study compares the corrected QT intervals (QTc) of children (<19 years) during the QT-stand test and EST. Patients were divided into three groups for comparison: confirmed LQTS (n = 14), low probability of LQTS (n = 14), and a control population (n = 9). Using the Bazett formula, confirmed LQTS patients had longer QTc intervals than controls when supine, standing, and at 3-4 min of recovery (p ≤ .01). Patients with a low probability of LQTS had longer QTc duration upon standing (p = .018) and at 1 min of recovery (p = .016) versus controls. There were no significant QTc differences at any transition point between low probability and confirmed LQTS. Using the Fridericia formula, differences in QTc between low probability and confirmed LQTS were also absent at the transition points examined, except at 1 min into exercise, where low probability patients had shorter QTc intervals (437 vs. 460 ms, p = .029). The diagnostic utility of the QT stand test and EST remainsunclear in pediatric LQTS. The formula used for heart rate correction may influence accuracy, and dynamic T-U wave morphology changes may confound interpretation in low probability situations.

Validation of a machine learned model to predict the diagnosis of myocardial infarction

Abstract Introduction The myocardial-ischemic-injury-index (MI3) is a promising machine learned algorithm that predicts the likelihood of myocardial infarction in patients with suspected acute coronary syndrome. Whether this algorithm performs well in unselected patients or predicts recurrent events is unknown. Methods In an observational analysis from a multi-centre randomised trial, we included all patients with suspected acute coronary syndrome and serial high-sensitivity cardiac troponin I measurements without ST-segment elevation myocardial infarction. Using gradient boosting, MI3 incorporates age, sex, and two troponin measurements to compute a value (0–100) reflecting an individual's likelihood of myocardial infarction, and estimates the negative predictive value (NPV) and positive predictive value (PPV). Model performance for an index diagnosis of myocardial infarction, and for subsequent myocardial infarction or cardiovascular death at one year was determined using previously defined low- and high-probability thresholds (1.6 and 49.7, respectively). Results In total 20,761 of 48,282 (43%) patients (64±16 years, 46% women) were eligible of whom 3,278 (15.8%) had myocardial infarction. MI3 was well discriminated with an area under the receiver-operating-characteristic curve of 0.949 (95% confidence interval 0.946–0.952) identifying 12,983 (62.5%) patients as low-probability (sensitivity 99.3% [99.0–99.6%], NPV 99.8% [99.8–99.9%]), and 2,961 (14.3%) as high-probability (specificity 95.0% [94.7–95.3%], PPV 70.4% [69–71.9%]). At one year, subsequent myocardial infarction or cardiovascular death occurred more often in high-probability compared to low-probability patients (17.6% [520/2,961] versus 1.5% [197/12,983], P&amp;lt;0.001). Conclusions In unselected consecutive patients with suspected acute coronary syndrome, the MI3 algorithm accurately estimates the likelihood of myocardial infarction and predicts probability of subsequent adverse cardiovascular events. Performance of MI3 at example thresholds Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Medical Research Council

Prediction of cerebral venous thrombosis with a new clinical score and D-dimer levels.

To investigate prediction of cerebral venous thrombosis (CVT) by clinical variables and D-dimer levels. This prospective multicenter study included consecutive patients with clinically possible CVT. On admission, patients underwent clinical examination, blood sampling for D-dimers measuring (ELISA test), and magnetic resonance/CT venography. Predictive value of clinical variables and D-dimers for CVT was calculated. A clinical score to stratify patients into groups with low, moderate, or high CVT risk was established with multivariate logistic regression. CVT was confirmed in 26.2% (94 of 359) of patients by neuroimaging. The optimal estimate of clinical probability was based on 6 variables: seizure(s) at presentation (4 points), known thrombophilia (4 points), oral contraception (2 points), duration of symptoms >6 days (2 points), worst headache ever (1 point), and focal neurologic deficit at presentation (1 point) (area under the curve [AUC] 0.889). We defined 0 to 2 points as low CVT probability (negative predictive value [NPV] 94.1%). Of the 186 (51.8%) patients who had a low probability score, 11 (5.9%) had CVT. The frequency of CVT was 28.3% (34 of 120) in patients with a moderate (3-5 points) and 92.5% (49 of 53) in patients with a high (6-12 points) probability score. All low CVT probability patients with CVT had D-dimers >500 μg/L. Predictive value of D-dimers for CVT for >675 μg/L (best cutoff) vs >500 μg/L was as follows: sensitivity 77.7%, specificity, 77%, NPV 90.7%, and accuracy 77.2% vs sensitivity 89.4%, specificity 66.4%, NPV 94.6%, and accuracy 72.4%, respectively. Adding the clinical score to D-dimers >500 μg/L resulted in the best CVT prediction score explored (at the cutoff ≥6 points: sensitivity 83%/specificity 86.8%/NPV 93.5%/accuracy 84.4%/AUC 0.937). The proposed new clinical score in combination with D-dimers may be helpful for predicting CVT as a pretest score; none of the patients with CVT showed low clinical probability for CVT and D-dimers <500 μg/L. NCT00924859.

Systematic review and meta-analysis of outcomes in patients with suspected deep vein thrombosis

AbstractAfter deep vein thrombosis (DVT) is diagnosed, prompt evaluation and therapeutic intervention are of paramount importance for improvement in patient-important outcomes. We systematically reviewed patient-important outcomes in patients with suspected DVT, including mortality, incidence of pulmonary embolism (PE) and DVT, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, Ovid Medline, Embase for eligible studies, references lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Nine studies with 5126 patients were included for lower extremity DVT. Three studies with 500 patients were included for upper extremity DVT. Among patients with lower extremity DVT, 0.85% (95% confidence interval [CI], 0% to 2.10%) and 0% developed recurrent DVT and PE, respectively, at 3 months. Among patients with upper extremity DVT, 0.49% (95% CI, 0% to 1.16%) and 1.98% (95% CI, 0.62% to 3.33%) developed recurrent DVT and PE, respectively, at 3 months. No major bleeding events were reported for those anticoagulated, which is lower than in other systematic reviews. For both upper and lower extremity DVT, low pretest probability patients with a negative D-dimer had a comparable incidence of VTE at 3 months (∼1%) as patients with a negative ultrasound (US). At higher pretest probabilities, negative US testing with or without serial US appears to be the safer option. In this review, we summarized the outcomes of patients evaluated by various diagnostic pathways. In most instances, there was significant limitation due to small population size or lack of direct evidence of effects of using a specific pathway. This systematic review was registered at PROSPERO as CRD42018100502.

Leveraging real world data and AIML to inform smart patient care in oncology.

e20002 Background: Identifying optimal therapy options can help maximize treatment outcomes. Finding ways to help improve treatment decision is of great value to achieve better patient care. With the availability of robust patient real world data and the application of state of the art Artificial Intelligence and Machine Learning (AIML) technology, new opportunities have emerged for a broad spectrum of research needs from oncology R&amp;D to commercialization. To illustrate the above advancements, this study identified patients diagnosed with CLL who may progress to next line of treatment in the near future (e.g. future 3 months). More importantly, we can identify treatment patterns which are more effective in treating different types of CLL patients. Methods: This study includes multiple steps which have already been analyzed for feasibility: 1. Collect CLL patients. IQVIA's real world data contains ~60,000 active CLL treated patients. ~2,000 patients have progressed line of treatment in 3 month. 2. Define patients into positive and negative cohorts based on those who have/have not advanced to line L2+. 3. Determine patient profiles based on treatment regimens, symptoms, lab tests, doctor visits, hospital visits, and co-morbidity, etc. 4. Select patient and treatment features to fit an AIML predictive model. 5. Test different algorithms to achieve best model results and validate model performance. 6. Score and classify CLL patients into high and low probability based on the predictive model. 7. Match patients based on feature importance and compare regimens between positive and negative cohort. Results: Model accuracy is above 90%. Top clinical features are calculated for each patient. Optimum treatment patterns between high and low probability patients are identified, with controlling patient key features. Conclusions: Conclusions from this study is expected to yield deeper insight into more tailored treatments by patient type. CLL patients started with oral therapy(targeting) have better response than other treatments.

LO55: Comparison of the age-adjusted D-dimer, clinical probability-adjusted D-dimer, and Wells rule with D-dimer for diagnosing deep vein thrombosis in the emergency department.

Introduction: Diagnosing deep vein thrombosis (DVT) is of critical importance because of its associated morbidity and mortality. Diagnosing DVT can be challenging in the Emergency Department (ED) due to inconsistent adherence to, and utilization of the Wells rule. Both the age-adjusted and clinical probability adjusted D-dimer have been shown to decrease ultrasound (US) utilization rates. We aimed to compare the safety and efficacy of the Wells score with D-dimer to the age-adjusted and clinical probability-adjusted D-dimer in Canadian ED patients tested for DVT. Methods: This was a health records review of ED patients investigated for DVT at two EDs over a two-year period. Inclusion criteria were ED physician ordered duplex ultrasonography or D-dimer for investigation of lower limb DVT. Patients under the age of 18 were excluded. DVT was considered to be present during the ED visit if DVT was diagnosed on duplex ultrasonography and was treated for acute DVT, or if the patient was subsequently diagnosed with pulmonary embolism (PE) or DVT during the next 30 days. Trained researchers extracted anonymized data. The Wells D-dimer, age-adjusted D-dimer, and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of duplex ultrasonography imaging and the false negative rate was calculated for each rule. Results: Between April 1st 2013 and March 31st 2015, there were 1,198 patients tested for DVT. Of the low and moderate clinical pretest probability patients (Wells score ≤ 2), only 436 had a D-Dimer test and were eligible for our analysis. The average age of the patients was 59, 56% were female, and 4% had a malignancy. 207/436 patients (47.4%, 95%CI 42.8-52.2%) would have had US imaging for DVT if the age-adjusted D-dimer rule was used. 214/436 patients (49.1%, 95%CI 44.4-53.8%) would have had imaging for DVT if the clinical probability-adjusted D-dimer was used. If the Wells rule was used with the standard D-dimer cutoff of 500, 241/436 patients (55.2%, 95%CI 50.6-59.9%) would have had imaging for DVT. The false-negative rate for the Wells rule was 1.5% (95%CI 0.5-4.4%). The false-negative rate for the age-adjusted D-dimer rule was 1.3% (95%CI 0.4-3.8%). The false-negative rate for the clinical-probability adjusted D-Dimer was 1.8% (95%CI 0.7-4.5%). Conclusion: In comparison with the approach of the Wells score and D-dimer, both the age-adjusted and clinical probability-adjusted D-dimer diagnostic strategies could reduce the proportion of patients who require US imaging.

A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease

SummaryBackgroundA clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn’s disease.AimTo assess the utility of this CDST for predicting exposure‐efficacy and disease outcomes.MethodsUsing data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST‐defined response groups (low, intermediate and high).ResultsA linear relationship existed between CDST‐defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST‐defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high‐probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the high‐intermediate and low‐probability groups within GETAID were no longer significant when including low‐probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low‐ to intermediate‐probability vs high‐probability patients (adjusted HR 2.06, 95% CI 1.33‐3.21).ConclusionsWe further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure‐efficacy relationships and rapidity of onset of action and could be used to help identify patients who would most benefit from interval shortening and those most likely to require surgery while on active therapy.

Safety of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions: A single-center experience of 214 patients

Endoscopic ultrasound-guided ethanol ablation (EUS-EA) for pancreatic cystic lesions (PCLs) has been used in recent years as a feasible treatment modality for low malignant probability PCLs or patients considered high-risk for surgery. The present study aimed to confirm the safety of EUS-EA and to find predictive factors for adverse event (AE). A retrospective review was performed from the prospectively maintained database of patients who underwent EUS-EA for PCLs from June 2006 to April 2018 at Seoul National University Hospital. The primary outcomes of the study were the rates of AEs and severe AEs by EUS-EA. The secondary outcome was the predictive factors of AEs including acute pancreatitis and abdominal pain. A total of 214 patients were evaluated and the diagnoses of PCLs according to cystic fluid analysis and clinical features were as follows: serous cystic neoplasm (32.2%), mucinous cystic neoplasm (26.6%), branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) (29.4%), and pseudocyst (11.7%). Three patients (1.4%) experienced severe AEs. Overall, AEs occurred in 71 (33.2%) patients. BD-IPMN (OR: 2.87; 95% CI: 1.05-7.84; P = 0.040), multilocular cysts (OR: 3.59; 95% CI: 1.09-11.85; P = 0.036), suspected ethanol leakage during procedure (OR: 10.68; 95% CI: 1.98-57.53; P = 0.006), and sticky cystic fluid (OR: 3.83; 95% CI: 1.20-12.24; P = 0.024) were predictive factors for post-procedural acute pancreatitis. PCLs of uncinate process (OR: 2.99; 95% CI: 1.22-7.35; P = 0.017) and PCLs with exophytic portion (OR: 3.70; 95% CI: 1.96-7.01; P<0.001) were predictive factors for post-procedural abdominal pain. EUS-EA is a safe procedure with a very low rate of severe AEs. It seems possible to predict the AEs according to the features of the procedure and PCLs.

Pre-test probability prediction in patients with a low to intermediate probability of coronary artery disease: a prospective study with a fractional flow reserve endpoint

European and North American guidelines currently recommend pre-test probability (PTP) stratification based on simple probability models in patients with suspected coronary artery disease (CAD). However, no unequivocal recommendation has yet been established. We aimed to compare the ability of risk factors and different PTP stratification models to predict haemodynamically obstructive CAD with fractional flow reserve (FFR) as reference in low to intermediate probability patients. We prospectively included 1675 patients with low to intermediate risk who had been referred to coronary computed tomography angiography (CTA). Patients with coronary stenosis were subsequently investigated by invasive coronary angiography (ICA) with FFR measurement if indicated. Discrimination and calibration were assessed for four models: the updated Diamond-Forrester (UDF), the CAD Consortium Basic, the Clinical, and the Clinical + Coronary artery calcium score (CACS). At coronary CTA, 24% of patients were diagnosed with a suspected stenosis and 10% had haemodynamically obstructive CAD at the ICA. Calibration for all CAD Consortium models increased compared with the UDF score. However, all models overestimated the probability of haemodynamically obstructive CAD. Discrimination increased by area under the receiver operating curve from 67% to 86% for UDF vs. CAD Consortium Clinical + CACS. The proportion of low-probability patients (pre-test score < 15%) was for the UDF, CAD Consortium Basic, Clinical, and Clinical + CACS: 14%, 58%, 51%, and 66%, respectively. The corresponding negative predictive values were 97%, 94%, 95%, and 98%, respectively. CAD Consortium models improve PTP stratification compared with the UDF score, mainly due to superior calibration in low to intermediate probability patients. Adding the coronary calcium score to the models substantially increases discrimination. NCT02264717.

Prevalence of Pulmonary Embolism in Patients Presenting With Syncope.

Prevalence of Pulmonary Embolism in Patients Presenting With Syncope.

Serial Biomarker Monitoring Early after HCT Identifies Different Risks for Relapse and Graft-Vs-Host Disease

Relapse of malignancy and lethal graft versus host disease (GVHD) are the principal causes of failure of allogeneic hematopoietic cell transplant (HCT). Recently we have shown that at seven days after HCT an algorithm using two serum biomarkers (ST2 and REG3α) can predict severe GVHD (Hartwell et al. JCI Insight 2017). We determined whether serial testing (in the first month following HCT) of patients with low probability biomarkers would improve the predictive accuracy of the algorithm and identify patients with different risks of relapse and lethal GVHD. Patients who received an HCT at 18 centers in the Mount Sinai Acute GVHD International Consortium (MAGIC) for hematologic malignancy and who supplied three blood samples were divided into a training set and validation set with equal numbers of lethal GVHD events, which was defined as death from GVHD or infection during treatment for GVHD. Patients in the training set (n=702) underwent HCT from January 1, 2006 until June 30, 2015, whereas patients in the validation set (n=906) underwent HCT from July 1, 2015 to May 1, 2017. Serum samples were analyzed using the previously published algorithm of two biomarkers up to three times (day 7, day 14, day 28 or GVHD onset, if onset occurred within the first 28 days). The algorithm generates a predicted probability of lethal GVHD between 0 and 1 for each patient. Patients were categorized as either low probability (LP) or high probability (HP) for lethal GVHD. HP thresholds of 0.20 and 0.16 were used to classify patients with and without GVHD symptoms, respectively (once categorized as HP, patients remained in that category and were not retested). All results were similar between training and validation sets, and we present here the validation set results. Serial testing identified 28% of patients as HP with a three-fold greater cumulative incidence of lethal GVHD at one year (13% vs 4%, p Early development of GVHD (by day 28) is a risk factor for lethal GVHD. Therefore, we next plotted RFS (dashed line), relapse (solid line), and lethal GVHD (dotted line) rates in patients who developed GVHD by day 28. 25% of patients with GVHD were categorized as HP and had a cumulative incidence of lethal GVHD more than four times higher (28%) than that of relapse (6%); however the risks were reversed for the 75% of patients who were LP, where relapse (15%) occurred twice as often as lethal GVHD (7%) (Figure 3B). In patients who did not develop GVHD in the first month, this reversal of risks was even more dramatic. Approximately half (53%) of the entire validation cohort did not develop GVHD by day 28 and was LP at all three evaluations. These patients had an exceptionally low risk of lethal GVHD and thus they relapsed (25%) much more often than they died from GVHD (3%). When malignancies were classified according to risk for relapse by the disease risk index (DRI) (Figure 3C), the probability of relapse was three fold higher than lethal GVHD in malignancies with a low DRI (12%), six fold higher for intermediate DRI (20%), and eleven fold higher for high/very high DRI (33%). We conclude that a serial monitoring strategy using GVHD biomarkers for one month after HCT is able to identify two groups of patients with very different risks of lethal GVHD and relapse. For these patients, the intensity of immunosuppression after day 28 could be tailored according to the probabilities of developing lethal GVHD and relapse in the context of clinical trials. Disclosures Aziz:Doris Duke Charitable Foundation: Research Funding. Ayuk:Therakos (Mallinckrodt): Honoraria; Novartis: Honoraria; Celgene: Consultancy; Gilead: Consultancy. Chen:REGiMMUNE: Consultancy; Incyte: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Magenta Therapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy. Merli:Neovii Biotech: Honoraria; AMGEN: Honoraria. Roesler:Sanofi: Other: Travel, Accommodations, Expenses; Amgen: Equity Ownership; Jazz Pharmaceuticals: Other: Travel, Accommodations, Expenses; Immunomedics: Equity Ownership; Biogen: Equity Ownership; Merck: Consultancy; Pfizer: Consultancy. Kitko:Novartis: Consultancy, Honoraria; Mallinckrodt: Honoraria, Other: Travel, Accommodations, Expenses. Qayed:Novartis: Consultancy. Wolfl:Bristol-myers Squibb: Equity Ownership; Novartis: Equity Ownership; Taheda: Equity Ownership; Juno: Equity Ownership; Neovii: Other: Travel, Accommodations, Expenses. Mielke:Celgene: Speakers Bureau; DGHO: Speakers Bureau; EHA: Speakers Bureau; Kiadis Pharma: Speakers Bureau; Miltenyi: Speakers Bureau. Wudhikarn:Takeda Oncology: Other: Travel, Accommodations, Expenses. Nakamura:Celgene: Honoraria; Molmed: Honoraria; Merck: Consultancy; Pharmacyclics: Consultancy; Atara: Consultancy; Jazz Pharmaceuticals: Consultancy. Pulsipher:CSL Behring: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Adaptive Biotech: Consultancy, Research Funding; Amgen: Honoraria. Reshef:Pfizer: Consultancy; Atara Biotherapeutics: Consultancy; Kite Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy. Levine:Therakos: Consultancy; Novartis: Consultancy; Bluebird: Consultancy; Incyte: Consultancy; Kamada: Research Funding; Viracor: Patents & Royalties. Ferrara:Incyte: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Xenikos: Consultancy, Other: Travel, Accommodations, Expenses; Kamada: Consultancy, Research Funding; Viracor: Consultancy, Patents & Royalties.

Comparison of the age-adjusted and clinical probability-adjusted D-dimer to exclude pulmonary embolism in the ED

BackgroundDiagnosing pulmonary embolism (PE) in the emergency department (ED) can be challenging because its signs and symptoms are non-specific. ObjectiveWe compared the efficacy and safety of using age-adjusted D-dimer interpretation, clinical probability-adjusted D-dimer interpretation and standard D-dimer approach to exclude PE in ED patients. Design/methodsWe performed a health records review at two emergency departments over a two-year period. We reviewed all cases where patients had a D-dimer ordered to test for PE or underwent CT or VQ scanning for PE. PE was considered to be present during the emergency department visit if PE was diagnosed on CT or VQ (subsegmental level or above), or if the patient was subsequently found to have PE or deep vein thrombosis during the next 30 days. We applied the three D-dimer approaches to the low and moderate probability patients. The primary outcome was exclusion of PE with each rule. Secondary objective was to estimate the negative predictive value (NPV) for each rule. Results1163 emergency patients were tested for PE and 1075 patients were eligible for inclusion in our analysis. PE was excluded in 70.4% (95% CI 67.6–73.0%), 80.3% (95% CI 77.9–82.6%) and 68.9%; (95% CI 65.7–71.3%) with the age-adjusted, clinical probability-adjusted and standard D-dimer approach. The NPVs were 99.7% (95% CI 99.0–99.9%), 99.1% (95% CI 98.3–99.5%) and 100% (95% CI 99.4–100.0%) respectively. ConclusionThe clinical probability-adjusted rule appears to exclude PE in a greater proportion of patients, with a very small reduction in the negative predictive value.

Clinical Utility of Cxbladder Monitor for Patients with a History of Urothelial Carcinoma: A Physician-Patient Real-World Clinical Data Analysis.

IntroductionInternational guidelines advocate regular surveillance of patients following urothelial carcinoma (UC). A validated molecular diagnostic non-invasive urine test, Cxbladder Monitor, correctly identifies patients with a UC history who have low-probability of recurrence. The present study assesses the clinical utility of Cxbladder Monitor in reducing the number and frequency of urologic procedures ordered without missing detection of recurrent UC.MethodsData from 828 physician–patient assessments were generated from 18 participant physicians who each evaluated the same real-world clinical case data for 30 patients undergoing surveillance for recurrent UC. Each physician ordered tests and procedures and their timing, following review of the patient’s demographic data, pre-existing conditions, risk factors and clinical history before and after disclosure of Cxbladder Monitor results. Changes in the number, type and timing of procedures ordered were assessed.ResultsThe addition of Cxbladder Monitor significantly reduced the overall number of tests ordered by 38.7%, including flexible cystoscopy by 43%, for patients whose Cxbladder Monitor result was low-probability. When the result was elevated-probability, the number of procedures ordered, including cystoscopy, was increased consistent with the increased risk of recurrent UC. Importantly, based on the tests ordered by each physician for each of the patients, all cases of recurrent UC would have been detected.ConclusionThe increase in clinical utility of Cxbladder Monitor for the management of patients undergoing surveillance for recurrent UC was shown to be driven by the reduction in procedures ordered for low-probability patients and for the more invasive procedures ordered for elevated-probability patients. In this study, the total number of procedures ordered, including the number of cystoscopies, was reduced especially in patients with low-probability of UC. The invasive procedures were ordered in a more targeted fashion for elevated-probability patients, without compromising the detection of recurrent UC.Clinicaltrials.gov IdentifierNCT02700659.FundingPacific Edge Limited.Electronic supplementary materialThe online version of this article (10.1007/s40487-018-0059-5) contains supplementary material, which is available to authorized users.

The declining frequency of inducible myocardial ischemia during stress echocardiography over 27 consecutive years (1983–2009)

BackgroundPrevious studies have suggested a decline in positivity of stress cardiac imaging, suggesting the need for developing better strategies for test selection to achieve acceptable cost-effectiveness balance. The aim of this retrospective study was to assess the rate of positivity of stress echocardiography (SE) over 27 consecutive years. MethodsWe assessed the rate of SE positivity in 2007 patients without previous myocardial infarction or coronary revascularization who performed SE in a tertiary care referral center from 1983 to 2009. SE was performed with dipyridamole (1427), dobutamine (136) or exercise (444). ResultsThere was a progressive decline over time in the rate of SE positivity from 42% (1983–1991) to 22% (2001–2009), with a relative increase of patients with low pre-test probability of disease (from 5% to 27%). The percentage of patients studied with SE under anti-ischemic therapy increased markedly (from 8% in the first to 61% in the last nine years). ConclusionOver 27 consecutive years, we observed a steady decline in SE positivity rate (with >5-fold increase of low probability patients), with almost 8-fold increase in anti-ischemic therapy at testing. We probably need refined criteria of referral for testing and/or better ways to titrate the negative response beyond wall motion abnormalities during SE.

Diagnostic value of respiratory polygraphy in patients with low probability of obstructive sleep apnea syndrome

Introduction and objectivePolysomnography (PSG) is the gold standard technic for the diagnosis of obstructive sleep apnea syndrome (OSAS). It is an expensive, complex and not always available technic, meaning that respiratory polygraphy (RP) has become usual. Although RP is not validated in low probability patients, Spanish guidelines recommend conservative treatment in patients with negative RP. We intended to study the prevalence and severity of OSAS through PSG in a sample of patients with low probability and negative RP. Material and methodsRetrospective, observational, descriptive and analytic study of low probability OSAS patients with negative RP in whom a PSG was performed. Anthropometric, clinical and sleep data were collected. ResultsEighty-two patients were included. After PSG, a greater number of hypopneas (137.8±70.1 vs. 51.2±38.4 [p<0.05]) and apnea hypopnea index (27.8±15.6 vs. 11.7±7.1 [p<0.05]) was observed, as well as an increment in OSAS prevalence of 17%, which was 35% in severe OSAS. In mild OSAS, there was a decrement of 41%. ConclusionAccording with the results of this study, RP significantly underestimates the prevalence and severity of OSAS in low probability patients. While it is necessary to adequately stratify the OSAS probability in order to correctly indicate diagnosis tests, we recommend performing a PSG in low probability patients with negative RP.