How Much Overtesting Is Needed to Safely Exclude a Diagnosis? A Different Perspective on Triage Testing Using Bayes' Theorem.
ABSTRACT: Ruling out disease often requires expensive or potentially harmful confirmation testing. For such testing, a less invasive triage test is often used. Intuitively, few negative confirmatory tests suggest success of this approach. However, if negative confirmation tests become too rare, too many disease cases could have been missed. It is therefore important to know how many negative tests are needed to safely exclude a diagnosis. We quantified this relationship using Bayes' theorem, and applied this to the example of pulmonary embolism (PE), for which triage is done with a Clinical Decision Rule (CDR) and D-dimer testing, and CT-angiography (CTA) is the confirmation test. For a maximum proportion of missed PEs of 1% in triage-negative patients, we calculate a 67% 'mandatory minimum' proportion of negative CTA scans. To achieve this, the proportion of patients with PE undergoing triage testing should be appropriately low, in this case no higher than 24%. Pre-test probability, triage test characteristics, the proportion of negative confirmation tests, and the number of missed diagnoses are mathematically entangled. The proportion of negative confirmation tests--not too high, but definitely not too low either--could be a quality benchmark for diagnostic processes.
Project description:OBJECTIVES:To evaluate the efficiency and safety of emergency department (ED) coronary computed tomography angiography (CTA) during a 3-year clinical experience. METHODS:Single-center registry of coronary CTA in consecutive ED patients with suspicion of acute coronary syndrome (ACS). The primary outcome was efficiency of coronary CTA defined as the length of hospitalization. Secondary endpoints of safety were defined as the rate of downstream testing, normalcy rates of invasive coronary angiography (ICA), absence of missed ACS, and major adverse cardiac events (MACE) during follow-up, and index radiation exposure. RESULTS:One thousand twenty two consecutive patients were referred for clinical coronary CTA with suspicion of ACS. Overall, median time to discharge home was 10.5 (5.7-24.1) hours. Patient disposition was 42.7 % direct discharge from the ED, 43.2 % discharge from emergency unit, and 14.1 % hospital admission. ACS rate during index hospitalization was 9.1 %. One hundred ninety two patients underwent additional diagnostic imaging and 77 underwent ICA. The positive predictive value of CTA compared to ICA was 78.9 % (95 %-CI 68.1-87.5 %). Median CT radiation exposure was 4.0 (2.5-5.8) mSv. No ACS was missed; MACE at follow-up after negative CTA was 0.2 %. CONCLUSIONS:Coronary CTA in an experienced tertiary care setting allows for efficient and safe management of patients with suspicion for ACS. KEY POINTS:• ED Coronary CTA using advanced systems is associated with low radiation exposure. • Negative coronary CTA is associated with low rates of MACE. • CTA in ED patients enables short median time to discharge home. • CTA strategy is characterized by few downstream tests including unnecessary ICA.
Project description:Background:Proteins in the urine of women with preeclampsia (PE) bind Congo Red dye (urine congophilia). We sought to determine the diagnostic performance of a paper-based point-of-care test detecting urine congophilia for rapid triage and diagnosis of PE. Methods:Prospective cohort study conducted in 346 consecutive pregnant women evaluated for PE in the Labour and Delivery triage unit at our institution. The Congo Red Dot (CRD) Paper Test (index test) was performed on fresh urine samples. The CRD Paper Test results were compared to an expert adjudicated diagnosis in each case. The accuracy of the CRD Paper Test was also compared to urine and serum analytes (placental growth factor and soluble fms-like tyrosine kinase-1) previously proposed as diagnostic aids for PE. Findings:During the first triage visit, 32% (112/346) of women received a clinical diagnosis of PE. Yet, 63% (217/346) were admitted for in-patient diagnostic work-up or delivery. The CRD Paper Test was positive in 25% (86/346) of the cases. Adjudication confirmed PE in 28% (96/346) of all cases. The CRD Paper Test outperformed measured serum and urine markers (80·2% sensitivity, 89·2% specificity, 92·1% negative predictive value, 86·7% accuracy). The pre-test, positive and negative post-test probabilities were 27·7%, 74·0%, and 8·0%, respectively. Of women who were discharged undelivered, 38% (133/346) had at least one additional triage visit and the interval between the last negative and first positive CRD Paper Test was 12 (interquartile range, [5-34]) days. Interpretation:The CRD Paper Test is a simple, non-invasive, "sample-in/answer-out" point-of-care clinical tool for rapid identification of PE. Funding:Saving Lives at Birth Program and NICHD.
Project description:Although risk stratification is an important goal of cardiac noninvasive tests (NITs), few contemporary data exist on the prognostic value of different NITs according to patient sex.The goal of this study was to compare the results and prognostic information derived from anatomic versus stress testing in stable men and women with suspected coronary artery disease.In 8,966 patients tested at randomization (4,500 to computed tomography angiography [CTA], 52% female; 4,466 to stress testing, 53% female), we assessed the relationship between sex and NIT results and between sex and a composite of death, myocardial infarction, or unstable angina hospitalization.In women, a positive CTA (?70% stenosis) was less likely than a positive stress test result (8% vs. 12%; adjusted odds ratio: 0.67). Compared with negative test results, a positive CTA was more strongly associated with subsequent clinical events than a positive stress test result (CTA-adjusted hazard ratio of 5.86 vs. stress-adjusted hazard ratio of 2.27; adjusted p = 0.028). Men were more likely to have a positive CTA than a positive stress test result (16% vs. 14%; adjusted odds ratio: 1.23). Compared with negative test results, a positive CTA was less strongly associated with subsequent clinical events than a positive stress test result in men, although this difference was not statistically significant (adjusted p = 0.168). Negative CTA and stress test results were equally likely to predict an event in both sexes. A significant interaction between sex, NIT type, and test result (p = 0.01) suggests that sex and NIT type jointly influence the relationship between test result and clinical events.The prognostic value of an NIT result varies according to test type and patient sex. Women seem to derive more prognostic information from a CTA, whereas men tend to derive similar prognostic value from both test types.
Project description:Importance:Triage tests enhance the efficiency cervical cancer screening based on human papillomavirus (HPV), but the best approach for maximizing programmatic effectiveness is still uncertain, particularly in a real-world scenario. Objective:To compare the clinical performance of 6 triage strategies based on liquid-based cytology (LBC) and HPV-16 and HPV-18 genotyping individually or in combination as sequential triage tests to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher among women with high-risk HPV. Design, Setting, and Participants:This diagnostic study of routine cervical cancer screening was conducted at 100 primary health centers in Tlaxcala, Mexico. Women aged 30 to 64 years were recruited from August 1, 2013, to February 24, 2016, as part of the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage study. Six triage scenarios for referral to colposcopy were examined: (1) LBC testing that found atypical squamous cells of undetermined significance (ASC-US) or worse, (2) positive results in HPV-16 genotyping, (3) positive results in HPV-18 genotyping, (4) positive results in HPV-16/HPV-18 genotyping, (5) positive results in HPV-16 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse, and (6) positive results in HPV-16/HPV-18 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse. Data were analyzed from October 2017 to August 2018. Exposures:Liquid-based cytological testing with simultaneous HPV-16 and HPV-18 genotyping. Women whose HPV genotyping results were positive for HPV-16 or HPV-18 or whose LBC results found ASC-US or worse and a random set of negative and normal results were referred to colposcopy with histologic analysis used for disease confirmation. Main Outcomes and Measures:Clinical performance of each test strategy for detection of CIN grade 2 or higher. Secondary outcomes included resource utilization of each triage scenario, measured by the number of tests performed, the referral rate for colposcopy, and the numbers of colposcopies per CIN grade 2 or higher detected. Results:A total of 36?212 women (median [interquartile range] age, 40 [35-47] years) were screened, and 4051 women (11.2%) had high-risk HPV. Of these women, 1109 (24.6%) were found to have HPV-16, HPV-18, or ASC-US or worse. Further histologic testing detected CIN grade 2 or higher in 110 of 788 women (14.0%) who underwent follow-up colposcopy. Sensitivity and specificity for 3 main triage strategies were 42.9% and 74.0% for LBC; 58.3% and 54.4% for HPV-16/HPV-18 genotyping; and 86.6% and 34.0% for HPV-16/HPV-18 genotyping with reflex LBC. The referral rate to colposcopy was 29% for HPV-16/HPV-18 with reflex LBC, which was 2-fold higher than the referral rate of 12% for LBC. Conclusions and Relevance:Triage of women with high-risk HPV with HPV-16/HPV-18 genotyping with reflex LBC was significantly associated with improvement in detection of CIN grade 2 or higher compared with LBC alone. The benefit of disease prevented may outweigh the cost of increasing requirements for colposcopy services in settings with limited adherence to follow-up after a positive screening result.
Project description:PURPOSE:To compare patient outcomes following magnetic resonance angiography (MRA) versus computed tomographic angiography (CTA) ordered for suspected pulmonary embolism (PE). METHODS:In this IRB-approved, single-center, retrospective, case-control study, we reviewed the medical records of all patients evaluated for PE with MRA during a 5-year period along with age- and sex-matched controls evaluated with CTA. Only the first instance of PE evaluation during the study period was included. After application of our exclusion criteria to both study arms, the analysis included 1173 subjects. The primary endpoint was major adverse PE-related event (MAPE), which we defined as major bleeding, venous thromboembolism, or death during the 6 months following the index imaging test (MRA or CTA), obtained through medical record review. Logistic regression, chi-square test for independence, and Fisher's exact test were used with a p?<?0.05 threshold. RESULTS:The overall 6-month MAPE rate following MRA (5.4%) was lower than following CTA (13.6%, p?<?0.01). Amongst outpatients, the MAPE rate was lower for MRA (3.7%) than for CTA (8.0%, p?=?0.01). Accounting for age, sex, referral source, BMI, and Wells' score, patients were less likely to suffer MAPE than those who underwent CTA, with an odds ratio of 0.44 [0.24, 0.80]. Technical success rate did not differ significantly between MRA (92.6%) and CTA (90.5%) groups (p?=?0.41). CONCLUSION:Within the inherent limitations of a retrospective case-controlled analysis, we observed that the rate of MAPE was lower (more favorable) for patients following pulmonary MRA for the primary evaluation of suspected PE than following CTA.
Project description:BACKGROUND:Coronary computed tomography angiography (CTA) and functional testing strategies for stable chest pain yield similar outcomes; one aspect that may guide test choice is safety. METHODS:We compared test safety (test complications, incidental findings, and effective radiation dose) between CTA and functional testing as-tested in PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain). In the subgroup whose physicians intended nuclear stress over other functional tests if randomized to the functional arm, we compared radiation dose of CTA versus nuclear stress and identified characteristics associated with dose. RESULTS:Of 9470 patients, none had major and <1% had minor complications (CTA: 0.8% [37/4633] vs. functional: 0.6% [27/4837]). CTA identified more incidental findings (11.6% [539/4633] vs. 0.7% [34/4837], p < 0.001), most commonly pulmonary nodules (9.4%, 437/4633). CTA had similar 90-day cumulative radiation dose to functional testing. However, in the subgroup whose physicians intended nuclear stress (CTA 3147; nuclear 3203), CTA had lower median index test (8.8 vs. 12.6 mSv, p < 0.001) and 90-day cumulative (11.6 vs. 13.1 mSv, p < 0.001) dose, independent of patient characteristics. The lowest nuclear doses employed 1-day Tc-99m protocols (12.2 mSv). The lowest CTA doses were at sites performing ?500 CTAs/year (6.9 mSv) and with advanced (latest available) CT scanners (5.5 mSv). CONCLUSION:Complications were negligibly rare for both CTA and functional testing. CTA detects more incidental findings. Compared to nuclear stress testing, CTA's lower radiation dose, independent of patient characteristics, makes it an attractive test choice. Radiation dose varies with imaging protocol, indicating opportunities to further reduce dose. (ClinicalTrials.gov number, NCT01174550).
Project description:<h4>Background</h4>In the United States, functional stress testing is the primary imaging modality for patients with stable symptoms suspected to represent coronary artery disease (CAD). Coronary computed tomography angiography (CTA) is excellent at identifying anatomic coronary artery disease (CAD). The application of computational fluid dynamics to coronary CTA allows fractional flow reserve (FFR) to be calculated noninvasively (FFR<sub>CT</sub>). The relationship of noninvasive stress testing to coronary CTA and FFR<sub>CT</sub> in real-world clinical practice has not been studied.<h4>Methods</h4>We evaluated 206 consecutive patients at Loyola University Chicago with suspected CAD who underwent noninvasive stress testing followed by coronary CTA and FFR<sub>CT</sub> when indicated. Patients were categorized by stress test results (positive, negative, indeterminate, and equivocal). Duke treadmill score (DTS), METS, exercise duration, and chest pain with exercise were analyzed. Lesions ? 50%stenosis were considered positive by coronary CTA. FFR<sub>CT</sub> < 0.80 was considered diagnostic of ischemia.<h4>Results</h4>Two hundred and six patients had paired noninvasive stress test and coronary CTA/FFR<sub>CT</sub> results. The median time from stress test to coronary CTA was 49 days. Average patient age was 60.3 years, and 42% were male. Of the 206 stress tests, 75% were exercise (70% echocardiographic, 26% nuclear, and 4% EKG). There were no associations of stress test results with CAD > 50% or FFR<sub>CT</sub> < 0.80 (<i>p</i> = 0.927 and <i>p</i> = 0.910, respectively). Of those with a positive stress test, only 30% (3/10) had CAD > 50% and only 50% (5/10) had FFR<sub>CT</sub> < 0.80. Chest pain with exercise did not correlate with CAD > 50% or FFR<sub>CT</sub> < 0.80 (<i>p</i> = 0.66 and <i>p</i> = 0.12, respectively). There were no significant correlations between METS, DTS, or exercise duration and FFR<sub>CT</sub> (<i>r</i> = 0.093, <i>p</i> = 0.274; <i>r</i> = 0.012, <i>p</i> = 0.883; and <i>r</i> = 0.034, <i>p</i> = 0.680; respectively).<h4>Conclusion</h4>Noninvasive stress testing, functional capacity, chest pain with exercise, and DTS are not associated with anatomic or functional CAD using a diagnostic strategy of coronary CTA and FFR<sub>CT</sub>.
Project description:Duplex ultrasound is routinely used to evaluate suspected deep venous thrombosis after total joint arthroplasty. When there is a clinical suspicion for a pulmonary embolism, a chest angiogram (chest CTA) is concomitantly obtained.Two questions were addressed: First, for the population of patients who receive duplex ultrasound after total joint arthroplasty, what is the rate of positive results? Second, for these patients, how many of these also undergo chest CTA for clinical suspicion of pulmonary embolus and how many of these tests are positive? Furthermore, what is the correlation between duplex ultrasound results and chest CTA results?A retrospective chart review was conducted of total joint replacement patients in 2011 at a single institution. Inclusion criteria were adult patients who underwent a postoperative duplex ultrasonography for clinical suspicion of deep venous thrombosis (DVT). Demographic data, result of duplex scan, clinical indications for obtaining the duplex scan, and DVT prophylaxis used were recorded. Additionally, if a chest CTA was obtained for clinical suspicion for pulmonary embolus, results and clinical indication for obtaining the test were recorded. The rate of positive results for duplex ultrasonography and chest CTA was computed and correlated based on clinical indications.Two hundred ninety-five patients underwent duplex ultrasonography of which only 0.7% were positive for a DVT. One hundred three patients underwent a chest CTA for clinical suspicion of a pulmonary embolism (PE) of which 26 revealed a pulmonary embolus, none of which had a positive duplex ultrasound.Postoperative duplex scans have a low rate of positive results. A substantial number of patients with negative duplex results subsequently underwent chest CTA for clinical suspicion for which a pulmonary embolus was found, presumably resulting from a DVT despite negative duplex ultrasound result. A negative duplex ultrasonography should not rule out the presence of a DVT which can embolize to the lungs and thus should not preclude further workup when clinical suspicion exists for a pulmonary embolus.
Project description:The non-invasive Cxbladder urine test system has demonstrated clinical utility in ruling out urothelial carcinoma (UC) in patients with asymptomatic microscopic hematuria (AMH), suggesting that the number of invasive diagnostic tests, including cystoscopy, used in this patient population may be reduced by Cxbladder testing prior to conducting a full urological work-up. The aim of this study was to demonstrate the enhanced clinical utility of communicating objective information on diagnostic decisions made by individual physicians on individual patients with AMH.Three hundred ninety-six physician-patient decisions were generated from twelve participant physicians evaluating real world case notes from the same 33 patients presenting with AMH. Each physician reviewed and recommended diagnostic tests and procedures based on each patient's referral data and then re-evaluated their clinical recommendation following disclosure of the non-invasive Cxbladder urine test result. Changes assessed were the total number of requested diagnostic procedures and the number of invasive procedures, including cystoscopy, following addition of information from Cxbladder in the Triage and Triage and Detect modalities.Physicians made significant changes to their diagnostic behavior for patients with AMH when presented with Cxbladder test results, including a reduction in the number of total and invasive procedures including cystoscopy for individuals identified as having a low probability of UC. The intensity of investigation was targeted and increased, including use of total procedures and cystoscopy, for patients identified by Cxbladder tests as having a high probability of UC: urologists increased the level of investigation for both total procedures and invasive procedures. The outcome resulted in patients with a high risk of UC receiving appropriate guideline-recommended invasive diagnostic tests. Patients who tested negative were offered fewer and significantly less invasive procedures. This change in physician behavior results in an increased clinical and patient utility, lower risk of missed UC and invasive test-related harm incidents.This study demonstrated the potential for increased clinical resolution and significantly enhanced patient management, when physicians consider Cxbladder test results in their clinical evaluation. The change in physician behavior led to more appropriate diagnostic procedure selection and resource allocation to the benefit of both patients and healthcare systems.
Project description:Testing for high-risk human papillomavirus DNA (HPV test) has gained increasing acceptance as an alternative method to cytology in cervical cancer screening. Compared to cytology, HPV test has a higher sensitivity for the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), but this could lead to a large colposcopy burden. Genotyping for HPV16/18 has been recommended in triaging HPV-positive women. This study was aimed to evaluate the screening performance of HPV testing and the role of genotyping triage in Northern Thailand.A population-based cervical screening program was performed in Chiang Mai (Northern Thailand) using cytology (conventional Pap test) and HPV test (Hybrid Capture 2). Women who had abnormal cytology or were HPV-positive were referred for colposcopy. Cervical samples from these women were genotyped using the Linear Array assay.Of 5,456 women, 2.0% had abnormal Pap test results and 6.5% tested positive with Hybrid Capture 2. Of 5,433 women eligible for analysis, 355 with any positive test had histologic confirmation and 57 of these had histologic HSIL+. The sensitivity for histologic HSIL+ detection was 64.9% for Pap test and 100% for Hybrid Capture 2, but the ratio of colposcopy per detection of each HSIL+ was more than two-fold higher with Hybrid Capture 2 than Pap test (5.9 versus 2.8). Genotyping results were available in 316 samples. HPV52, HPV16, and HPV58 were the three most common genotypes among women with histologic HSIL+. Performance of genotyping triage using HPV16/18/52/58 was superior to that of HPV16/18, with a higher sensitivity (85.7% versus 28.6%) and negative predictive value (94.2% versus 83.9%).In Northern Thailand, HPV testing with genotyping triage shows better screening performance than cervical cytology alone. In this region, the addition of genotyping for HPV52/58 to HPV16/18 is deemed necessary in triaging women with positive HPV test.