Prospective Diagnostic Accuracy Study Research Articles

Diagnostic Accuracy of an Integrated AI Tool to Estimate Gestational Age From Blind Ultrasound Sweeps

Accurate assessment of gestational age (GA) is essential to good pregnancy care but often requires ultrasonography, which may not be available in low-resource settings. This study developed a deep learning artificial intelligence (AI) model to estimate GA from blind ultrasonography sweeps and incorporated it into the software of a low-cost, battery-powered device. To evaluate GA estimation accuracy of an AI-enabled ultrasonography tool when used by novice users with no prior training in sonography. This prospective diagnostic accuracy study enrolled 400 individuals with viable, single, nonanomalous, first-trimester pregnancies in Lusaka, Zambia, and Chapel Hill, North Carolina. Credentialed sonographers established the "ground truth" GA via transvaginal crown-rump length measurement. At random follow-up visits throughout gestation, including a primary evaluation window from 14 0/7 weeks' to 27 6/7 weeks' gestation, novice users obtained blind sweeps of the maternal abdomen using the AI-enabled device (index test) and credentialed sonographers performed fetal biometry with a high-specification machine (study standard). The primary outcome was the mean absolute error (MAE) of the index test and study standard, which was calculated by comparing each method's estimate to the previously established GA and considered equivalent if the difference fell within a prespecified margin of ±2 days. In the primary evaluation window, the AI-enabled device met criteria for equivalence to the study standard, with an MAE (SE) of 3.2 (0.1) days vs 3.0 (0.1) days (difference, 0.2 days [95% CI, -0.1 to 0.5]). Additionally, the percentage of assessments within 7 days of the ground truth GA was comparable (90.7% for the index test vs 92.5% for the study standard). Performance was consistent in prespecified subgroups, including the Zambia and North Carolina cohorts and those with high body mass index. Between 14 and 27 weeks' gestation, novice users with no prior training in ultrasonography estimated GA as accurately with the low-cost, point-of-care AI tool as credentialed sonographers performing standard biometry on high-specification machines. These findings have immediate implications for obstetrical care in low-resource settings, advancing the World Health Organization goal of ultrasonography estimation of GA for all pregnant people. ClinicalTrials.gov Identifier: NCT05433519.

Ultrasound is an accurate imaging modality for diagnosing hip luxation in dogs presenting with hind limb lameness.

To determine the accuracy of ultrasound for diagnosing hip luxation in dogs presenting for hind limb lameness. 24 client-owned dogs presenting with pelvic limb lameness and concern for hip luxation were enrolled in this prospective diagnostic accuracy study from April 1, 2021, to July 1, 2022. An experienced ultrasonographer and a novice ultrasonographer, both masked to the diagnoses, performed hip ultrasonography using a point-of-care ultrasound machine. The experienced evaluator also performed a more comprehensive ultrasonography with a high-end ultrasound machine to characterize concurrent pelvis and hip disease. Pelvic radiographs served as the criterion standard for the diagnosis of hip luxation. Ultrasonographic diagnosis of hip luxation demonstrated high accuracy, ranging from 84.2% to 100% for detecting the presence of luxation and 80.6% to 98.1% for diagnosing the direction of luxation for the novice and experienced evaluators, respectively, with substantial interevaluator agreement (κ = 0.722). Compared to radiographs, ultrasound accurately diagnosed the presence of osteoarthrosis with almost perfect agreement (κ = 0.913) and the presence of fractures of the femoral head/neck and the nonaxial portions of the pelvis with substantial intermodality agreement (κ = 0.775). In 36% of patients, ultrasound identified injury to soft tissue structures that contribute to hip stability, including the gluteal muscles, gemelli, and joint capsule. Ultrasound can be utilized to accurately diagnose the presence of hip luxation and document concurrent hip and pelvic disease. Applications include the use of ultrasonography as part of a routine point-of-care protocol to catalogue injuries in patients with acute trauma and in mobile practice or remote settings where radiography is not readily available.

Comparative evaluation of CT and MRI in the preoperative staging of colon cancer

The aim of this study is to compare the diagnostic performance of magnetic resonance imaging (MRI) against computed tomography (CT) in various aspects of local staging in colon cancer patients. This study was a prospective single arm diagnostic accuracy study. All consecutive adult patients with confirmed colon cancer that met the current criteria for surgical resection were considered as eligible. Diagnostic performance assessment included T (T1/T2 vs T3/T4 and < T3ab vs > T3cd) and N (N positive) staging, serosa and retroperitoneal surgical margin (RSM) involvement and extramural vascular invasion (EMVI). Imaging was based on a 3 Tesla MRI system and the evaluation of all sequences (T1, T2 and diffusion-weighted imaging-DWI series) by two independent readers. CT scan was performed in a 128 row multidetector (MD) CT scanner (slice thickness: 1 mm) with intravenous contrast. Pathology report was considered as the gold standard for local staging. Sensitivity (SE), specificity (SP), and area under the curve (AUC) were calculated for both observers. MRI displayed a higher diagnostic performance over CT in terms of T1/T2 vs T3/T4 (SE: 100% vs 83.9%, SP: 96.6% vs 81%, AUC: 0.825 vs 0.983, p < 0.001), N positive (p < 0.001) and EMVI (p = 0.023) assessment. An excellent performance of MRI was noted in the T3ab vs T3cd (CT AUCReader1: 0.636, AUCReader2: 0.55 vs MRI AUCReader1: 0.829 AUCReader2 0.846, p = 0.01) and RSM invasion diagnosis. In contrast to these, MRI did not perform well in the identification of serosa invasion. MRI had a higher diagnostic yield than CT in several local staging parameters.

Utility of an in-line somatic cell count sensor for selecting cows for dry-cow therapy

Minimizing the use of antimicrobials at the end of lactation (dry cow therapy, DCT) requires categorization of cows as likely infected or uninfected. While microbiology is the gold standard for such categorization, the costs of doing so mean that indirect tests such as somatic cell count (SCC) are commonly used. An in-line SCC sensor (SenseHub In Line Somatic Cell Count, in-line SCC) is commercially available but its utility to differentiate cows eligible for dry cow therapy has not been assessed. This prospective diagnostic accuracy study was undertaken to define the sensitivity (Se) and specificity (Sp) of SenseHub SCC against cow-composite milk samples submitted for conventional microbiology. A secondary objective was to assess the utility of SenseHub SCC compared with the maximum (max DHI SCC) or last (last DHI SCC) SCC determined from cow-composite milk samples collected as part of routine herd production recording at monthly intervals throughout lactation. Cows (n = 1,544) from 4 spring-calving, predominantly pasture-fed dairy herds from 3 regions of New Zealand had cow-composite milk samples collected following aseptic teat end preparation immediately before or after the final milking of lactation. These samples were submitted for routine microbiology. The microbiology data from approximately half the cows (n = 770; training data set) were randomly selected after blocking for intramammary infection (IMI) status within herd and these data were used to determine the optimal predictor for indicating IMI from the in-line SCC data by maximizing the area under the receiver operator curve (AUC). The average of the in-line SCC over the final 12 weeks of lactation (in-line 12wSCC) was found to be the best predictor and used for further analyses. The Se and Sp of the in-line SCC for any IMI or for a major pathogen IMI (defined as presence of Staphylococcus aureus, Streptococcus dysgalactiae or Streptococcus uberis) was calculated using the test data set (n = 774). The AUC for the maximum and last DHI SCC were compared with that of the in-line 12wSCC. The cow-level prevalence of any IMI or a major IMI across the entire population was 50.6% and 14.2%, respectively. At a cutpoint of 150,000 cells/mL, Se and Sp of the in-line 12wSCC for any IMI was 0.68 (95%CI 0.64-0.72) and 0.71 (95% CI 0.65-76), respectively, and the Se and Sp for a major pathogen IMI was 0.89 (95%CI 0.82-0.95) and 0.51 (95% CI 0.47-0.55), respectively. The AUC for a major pathogen IMI was 0.82 (95% CI 0.79-0.86), 0.82 (95% CI 0.78-0.86) and 0.84 (95% CI 0.90-0.97) for in-line 12wSCC, max DHI SCC and last DHI SCC, respectively. These AUC did not differ and the AUC for the in-line 12wSCC was non-inferior to that of the last and maximum HT SCC (both P < 0.001). It was concluded that the in-line 12wSCC had an AUC, Se and Sp not different from DHI SCC data and hence this test has utility in selecting cows for different dry cow therapy treatments.

Evaluation of the passive mast cell activation test for identifying allergens in perioperative anaphylaxis: a study protocol for a prospective diagnostic accuracy study

IntroductionPerioperative anaphylaxis (POA) can lead to significant complications. Therefore, accurate identification of allergens for POA patients is critical to ensure the safety of future surgical and anaesthetic procedures. Existing perioperative...

Prospective Validation of Glial Fibrillary Acidic Protein, d ‐Dimer, and Clinical Scales for Acute Large‐Vessel Occlusion Ischemic Stroke Detection

Background Large‐vessel occlusion (LVO) ischemic stroke is responsible for significant morbidity and mortality. We have previously described a novel tool for acute LVO detection that combines blood‐based biomarkers (glial fibrillary acidic protein and d ‐dimer) with stroke severity scales to achieve high accuracy. Accordingly, the present study sought to prospectively validate cutoff values that we had previously established for biomarkers and scales. Methods The TIME (Testing for Identification Markers of Stroke) trial was designed as a prospective observational diagnostic accuracy study. All ambulance‐identified stroke code activations &lt;18 hours from symptom onset were recruited at Brandon Regional Hospital (Brandon, FL) between May 2021 and August 2022. Previously determined cutoff concentrations of plasma glial fibrillary acidic protein (213 pg/mL) and d ‐dimer (600 ng/mL) were used in combination with prehospital stroke scales to detect LVO. We compared rates of LVO detection against a reference standard using computed tomography/magnetic resonance angiography. Results A total of 382 patients with suspected stroke were recruited. The final cohort was composed of 323 patients with suspected stroke with the following distribution: LVO ischemic stroke (n = 29, 9%), non‐LVO ischemic stroke (n = 48, 15%), hemorrhagic stroke (n = 13, 4%), transient ischemic attack (n = 12, 3.9%), and stroke mimics (n = 220, 68.1%). Combining blood‐based biomarkers (glial fibrillary acidic protein and d ‐dimer) with the scale field assessment stroke triage for emergency destination yielded the best performance for LVO detection, with specificity of 94% and sensitivity of 71%. Performance was found to be higher in a subanalysis focusing on patients presenting &lt;6 hours from symptom onset, with 93% specificity and 81% sensitivity. Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage. Conclusion The present work prospectively validated the potential utility of previously defined glial fibrillary acidic protein and d ‐dimer cutoff levels (ie, 213 pg/mL and 600 ng/mL, respectively), demonstrating their value for discrimination of LVO stroke from differential diagnoses during code stroke workups. (ClinicalTrials.gov number, NCT04292600.)

Signs and symptoms of serious illness in adults with acute abdominal pain presenting to ambulatory care: a systematic review.

Acute abdominal pain is a common complaint, caused by a variety of conditions, ranging from acutely life-threatening to benign and self-limiting with symptom overlap complicating diagnosis. Signs and symptoms may be valuable when assessing a patient to guide clinical work. Summarising evidence on the accuracy of signs and symptoms for diagnosing serious illness in adults with acute abdominal pain in an ambulatory care setting. We performed a systematic review, searching for prospective diagnostic accuracy studies who included adults presenting with acute abdominal pain to an ambulatory care setting. Six databases and guideline registers were searched, using a comprehensive search strategy. We assessed the risk of bias, calculated descriptive statistics and measures of diagnostic accuracy. Results were pooled when at least four studies were available. Out of 18,923 unique studies, 16 studies with moderate to high-risk bias were included. Fourteen clinical features met our criteria, including systolic blood pressure <100 mmHg (LR +7.01), shock index >0.85, uterine cervical motion tenderness (LR +5.62 and LR- 8.60) and a self-assessment questionnaire score >70 (LR +12.20) or <25 (LR- 0.19). Clinical diagnosis made by the clinician had the best rule-in ability (LR +24.6). We identified 14 signs and symptoms that can influence the likelihood of a serious illness, including pain characteristics, systemic signs, gynaecological signs and clinician's overall assessment. The risk of bias was moderate to high, leading to uncertainty, preventing us from making firm conclusions. This highlights the need for better research in this setting.

68Ga-FAPI-04 positron emission tomography/CT and laparoscopy for the diagnosis of occult peritoneal metastasis in newly diagnosed locally advanced gastric cancer: study protocol of a single-centre prospective cohort study

IntroductionAccurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly...

Right Ventricular “Bubble Time” to Identify Patients With Right Ventricular Dysfunction

ObjectiveWe propose a novel method of evaluating right ventricular (RV) dysfunction in the emergency department (ED) using RV “bubble time” – the duration of time bubbles from a saline flush are visualized in the RV on echocardiography. The objective was to identify the optimal cutoff value for RV bubble time that differentiates patients with RV dysfunction and report on its diagnostic test characteristics. MethodsThis prospective diagnostic accuracy study enrolled a convenience sample of hemodynamically stable ED patients. A sonographer administered a 10-milliliter saline flush into patient’s intravenous catheter, performed a bedside echocardiogram, and measured RV bubble time. Subsequently, the patient underwent a comprehensive cardiologist-interpreted echocardiogram with 36 hours, which served as the gold standard. Patients with RV strain or enlargement on the latter echocardiogram were considered to have RV dysfunction. Bubble time was evaluated by a second provider, blinded to the initial results, who reviewed the ultrasound clips. The primary outcome measure was the optimal cutoff value of RV bubble time that identifies patients with and without RV dysfunction. ResultsOf 196 patients, median age was 67 and half were female, with 69 (35.2%) having RV dysfunction. Median RV bubble time among patients with RV dysfunction was 62 seconds (interquartile range (IQR): 52, 93) compared with 21 seconds (IQR: 12, 32) among patients without (p<0.0001). The optimal cutoff value of RV bubble time for identifying patients with RV dysfunction was ≥40 seconds, with a sensitivity of 0.97 (95% CI: 0.93, 1.00) and specificity of 0.87 (95% CI: 0.82, 0.93). ConclusionIn ED patients, an RV bubble time of ≥40 seconds had high sensitivity in identifying patients with RV dysfunction, while an RV bubble time of <40 seconds had good specificity in identifying patients without RV dysfunction. These findings warrant further investigation in undifferentiated patient population and by emergency physicians without advanced ultrasound training.

Prospective diagnostic accuracy study of history taking and physical examination for adults with vertigo in general practice: study protocol

IntroductionVertigo is a prevalent and burdensome symptom. More than 80% of patients with vertigo are primarily treated by their general practitioner (GP) and are never referred to a medical specialist....

Ultra-high-resolution CT vs. invasive angiography for detecting hemodynamically significant coronary artery disease: Rationale and methods of the CORE-PRECISION multicenter study

BackgroundDirect coronary arterial evaluation via computed tomography (CT) angiography is the most accurate noninvasive test for the diagnosis of coronary artery disease (CAD). However, diagnostic accuracy is limited in the setting of severe coronary calcification or stents. Ultra-high-resolution CT (UHR-CT) may overcome this limitation, but no rigorous study has tested this hypothesis. MethodsThe CORE-PRECISION is an international, multicenter, prospective diagnostic accuracy study testing the non-inferiority of UHR-CT compared to invasive coronary angiography (ICA) for identifying patients with hemodynamically significant CAD. The study will enroll 150 patients with history of CAD, defined as prior documentation of lumen obstruction, stenting, or a calcium score ≥400, who will undergo UHR-CT before clinically prompted ICA. Assessment of hemodynamically significant CAD by UHR-CT and ICA will follow clinical standards. The reference standard will be the quantitative flow ratio (QFR) with <0.8 defined as abnormal. All data will be analyzed in independent core laboratories. ResultsThe primary outcome will be the comparative diagnostic accuracy of UHR-CT vs. ICA for detecting hemodynamically significant CAD on a patient level. Secondary analyses will focus on vessel level diagnostic accuracy, quantitative stenosis analysis, automated contour detection, in-depth plaque analysis, and others. ConclusionCORE-PRECISION aims to investigate if UHR-CT is non-inferior to ICA for detecting hemodynamically significant CAD in high-risk patients, including those with severe coronary calcification or stents. We anticipate this study to provide valuable insights into the utility of UHR-CT in this challenging population and for its potential to establish a new standard for CAD assessment.

Granulocytes in cerebrospinal fluid of adults suspected of a central nervous system infection: a prospective study of diagnostic accuracy.

Cerebrospinal fluid (CSF) granulocytes are associated with bacterial meningitis, but information on its diagnostic value is limited and primarily based on retrospective studies. Therefore, we assessed the diagnostic accuracy of CSF granulocytes. We analyzed CSF granulocytes (index test) from all consecutive patients in two prospective cohort studies in the Netherlands. Both studies included patients ≥ 16years, suspected of a central nervous system (CNS) infection, who underwent a diagnostic lumbar puncture. All episodes with elevated CSF leukocytes (≥ 5 cells per mm3) were selected and categorized by clinical diagnosis (reference standard). Of 1261 episodes, 625 (50%) had elevated CSF leukocytes and 541 (87%) were included. 117 of 541 (22%) were diagnosed with bacterial meningitis, 144 (27%) with viral meningoencephalitis, 49 (9%) with other CNS infections, 76 (14%) with CNS autoimmune disorders, 93 (17%) with other neurological diseases and 62 (11%) with systemic diseases. The area under the curve to discriminate bacterial meningitis from other diagnoses was 0.97 (95% confidence interval [CI] 0.95-0.98) for CSF granulocyte count and 0.93 (95% CI 0.91-0.96) for CSF granulocyte percentage. CSF granulocyte predominance occurred in all diagnostic categories. A cutoff at 50% CSF granulocytes gave a sensitivity of 94% (95% CI 90-98), specificity of 80% (95% CI 76-84), negative predictive value of 98% (95% CI 97-99) and positive predictive value of 57% (95% CI 52-62). CSF granulocytes have a high diagnostic accuracy for bacterial meningitis in patients suspected of a CNS infection. CSF granulocyte predominance occurred in all diagnostic categories, limiting its value in clinical practice.

TOAST stroke subtype classification in clinical practice: implications for the Get With The Guidelines-Stroke nationwide registry.

The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) is the most commonly used ischemic stroke subtype classification system worldwide and a required field in the US National Get With The Guidelines-Stroke (GWTG-Stroke) registry. However, stroke diagnostics have advanced substantially since the TOAST classification was designed 30 years ago, potentially making it difficult to apply reliably. In this prospective diagnostic accuracy study, we analyzed consecutive ischemic stroke patients admitted to a Comprehensive Stroke Center between July-October 2021. Clinical practice TOAST classification diagnoses rendered by the stroke team in the electronic medical record (EMR) at discharge were retrieved from GWTG-Stroke registry and compared to a reference ("gold") standard diagnosis derived from agreement between two expert raters after review of the EMR and patient imaging. Among 49 patients; age was 72.3 years (±12.1), 53% female, and presenting NIHSS median 3 (IQR 1-11). Work-up included: brain imaging in 100%; cardiac rhythm assessment in 100%; cervical/cerebral vessel imaging in 98%; TTE ± TEE in 92%; and TCD emboli evaluation in 51%. Reference standard diagnoses were: LAA-6%, SVD-14%, CE-39%, OTH-10%, UND-M (more than one cause)-20%, and UND-C (cryptogenic)-10%. GWTG-Stroke TOAST diagnoses agreed with reference standard diagnoses in 30/49 (61%). Among the 6 subtype diagnoses, specificity was generally high (84.8%-97.7%), but sensitivity suboptimal for LAA (33%), OTH (60%), UND-M (10%), and UND-C (20%). Positive predictive value was suboptimal for 5 of the 6 subtypes: LAA (13%), SVD (58%), OTH (75%), UND-M (50%), and UND-C (50%). Clinical practice TOAST classification subtype diagnoses entered into the GWTG-Stroke registry were accurate in only 61% of patients, a performance rate that, if similarly present at other centers, would hamper the ability of the national registry to provide dependable insights into subtype-related care. Development of an updated ischemic stroke subtype classification system, with algorithmic logic embedded in electronic medical records, is desirable.

It was not possible to detect BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma: A diagnostic accuracy study.

The objective of this study is to evaluate the diagnostic accuracy of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma. This is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma-based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of BRAF V600E mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild-type BRAF lesions were included. The participants underwent plasma circulating cell-free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele-specific TaqMan™ real-time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated. Twelve patients with conventional ameloblastoma were included. BRAF V600E mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma-based liquid biopsy circulating cell-free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%. Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.

Performance of a stool-based quantitative PCR assay for the diagnosis of tuberculosis in adolescents and adults: a multinational, prospective diagnostic accuracy study

Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens. We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR test with the current diagnostic standard for Mycobacterium tuberculosis DNA detection from sputum and stool, Xpert-MTB/RIF Ultra (Xpert Ultra). Sputum, stool, and urine samples were provided by a cohort of participants, aged 10 years or older, diagnosed with tuberculosis. Participants with tuberculosis (cases) were enrolled within 72 h of treatment initiation for tuberculosis diagnosed clinically or following laboratory confirmation. Participants without tuberculosis (controls) consisted of household contacts of the cases who did not develop tuberculosis during a 6-month follow-up. The performance was compared with a robust composite microbiological reference standard (CMRS). The cohort of adolescents and adults (n=408) included 268 participants with confirmed or clinical tuberculosis (cases), 147 (55%) of whom were living with HIV, and 140 participants (controls) without tuberculosis. The sensitivity of the novel stool qPCR was 93·7% (95% CI 87·4-97·4) compared with participants with detectable growth on M tuberculosis culture, and 88·1% (81·3-93·0) compared with sputum Xpert Ultra. The stool qPCR had an equivalent sensitivity as sputum Xpert Ultra (94·8%, 89·1-98·1) compared with culture. Compared with the CMRS, the sensitivity of the stool qPCR was higher than the current standard for tuberculosis diagnostics on stool, Xpert Ultra (80·4%, 73·4-86·2 vs 73·5%, 66·0-80·1; p=0·025 on paired comparison). The qPCR also identified 17-21% additional tuberculosis cases compared to sputum Xpert Ultra or sputum culture. In controls without tuberculosis, the specificity of the stool qPCR was 96·9% (92·2-99·1). In this study, a novel qPCR for the diagnosis of tuberculosis from stool specimens had a higher accuracy in adolescents and adults than the current diagnostic PCR gold standard on stool, Xpert-MTB/RIF Ultra, and equivalent sensitivity to Xpert-MTB/RIF Ultra on sputum. National Institutes of Health (NIH) Allergy and Infectious Diseases, and NIH Fogarty International Center.

Diagnostic performance of Mycoplasmopsis bovis antibody ELISA tests on bulk tank milk from dairy herds

BackgroundTesting of bulk tank milk (BTM) for Mycoplasmopsis bovis (previously Mycoplasma bovis) antibodies is increasingly popular. However the performance of some commercially available tests is unknown, and cutoff values possibly need to be adjusted in light of the purpose. Therefore, the aim of this study was to compare the diagnostic performance of three commercially available M. bovis antibody ELISAs on BTM, and to explore optimal cutoff values for screening purposes. A prospective diagnostic test accuracy study was performed on 156 BTM samples from Belgian and Swiss dairy farms using Bayesian Latent Class Analysis. Samples were initially classified using manufacturer cutoff values, followed by generated values.ResultsFollowing the manufacturer’s guidelines, sensitivity of 91.4%, 25.6%, 69.2%, and specificity of 67.2%, 96.8%, 85.8% were observed for ID-screen, Bio K432, and Bio K302, respectively. Optimization of cutoffs resulted in a sensitivity of 89.0%, 82.0%, and 85.5%, and a specificity of 83.4%, 75.1%, 77.2%, respectively.ConclusionsThe ID-screen showed the highest diagnostic performance after optimization of cutoff values, and could be useful for screening. Both Bio-X tests may be of value for diagnostic or confirmation purposes due to their high specificity.

Stata tip 154: Computing power and sample size for prospective diagnostic accuracy studies using Stata’s official power commands

Stata tip 154: Computing power and sample size for prospective diagnostic accuracy studies using Stata’s official power commands

Evaluation of Less Invasive Sampling Tools for the Diagnosis of Cutaneous Leishmaniasis.

Diagnosis of cutaneous leishmaniasis (CL) usually relies on invasive samples, but it is unclear whether more patient-friendly tools are good alternatives for diverse lesions when used with polymerase chain reaction (PCR). Patients with suspected CL were enrolled consecutively in a prospective diagnostic accuracy study. We compared dental broach, tape disc, and microbiopsy samples with PCR as index tests, using PCR with skin slit samples as reference test. Subsequently, we constructed a composite reference test including microscopy, the 3 index tests and skin slit PCR, and we compared these same tests with the composite reference test. We assessed diagnostic accuracy parameters with 95% confidence intervals for all comparisons. Among 344 included patients, 282 (82.0%) had CL diagnosed, and 62 (18.0%) CL absence, by skin slit PCR. The sensitivity and specificity by PCR were 89.0% (95% confidence interval, 84.8%-92.1%) and 58.1% (45.7%-69.5%), respectively, for dental broach, 96.1% (93.2%-97.8%) and 27.4% (17.9%-39.6%) for tape disc, and 74.8% (66.3%-81.7%) and 72.7% (51.8%-86.8%) for microbiopsy. Several reference test-negative patients were consistently positive with the index tests. Using the composite reference test, dental broach, and skin slit had similar diagnostic performance. Dental broach seems a less invasive but similarly accurate alternative to skin slit for diagnosing CL when using PCR. Tape discs lack specificity and seem unsuitable for CL diagnosis without cutoff. Reference tests for CL are problematic, since using a single reference test is likely to miss true cases, while composite reference tests are often biased and impractical as they require multiple tests.

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: A prospective study of diagnostic accuracy

ObjectivesWe evaluated the diagnostic accuracy of cerebrospinal fluid (CSF) inflammatory markers for diagnosing bacterial meningitis in neonates with sepsis and/or meningitis. MethodsCases were identified from a prospective multicenter study including patients aged 0-3 months with Group B Streptococcal (GBS) or Escherichia coli culture positive sepsis/meningitis. CSF CXCL10, MDC, IL-6, IL-8, IL-10, TNF- α, MIF, IL-1RA, CXCL13, IL-1β, CRP and procalcitonin concentrations were measured with Luminex technology. ResultsIn 61/373 patients (17%) residual CSF from the lumbar puncture was available, of whom 16 (26%) had definitive meningitis, 15 (25%) probable meningitis and 30 (49%) had sepsis. All biomarkers were detectable in CSF and showed significantly higher concentrations in definitive meningitis versus sepsis patients and six biomarkers in probable meningitis versus sepsis patients. Discrimination between definitive meningitis and sepsis was excellent for IL-1RA (area under the receiver operating characteristic curve [AUC] 0.93), TNF-α (AUC 0.92), CXCL10 (AUC 0.90), IL-1β (AUC 0.92), IL-6 (AUC 0.94), IL-10 (AUC 0.93) and a combination of IL-1RA, TNF-α, CXCL-10 and CSF leukocyte count (AUC 0.95). CSF leukocyte count remained the predictor with the highest diagnostic accuracy (AUC 0.96). ConclusionCSF inflammatory markers can be used to differentiate between neonatal sepsis and meningitis.

Point of care thoracic ultrasound versus chest computed tomography in the approach of febrile neutropenia patients: A diagnostic accuracy cohort study.

Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study. Consecutive patients with febrile neutropenia who underwent CT (Computerized Tomography) underwent TUS evaluation within 24h of CT. Both studies were performed by an expert who was blinded to the clinical information and results of the alternative imaging modalities. 34 patients met the inclusion criteria. The median age was 39.9 years (±17 standard deviation). TUS as a diagnostic test had a sensitivity of 92.9% and specificity of 83.3%, negative predictive value of 71.4%, and positive predictive value of 96.3%. Substantial between-method agreement was demonstrated with a kappa of 0.71 (P = .001) between the TUS and chest CT findings. We obtained a kappa of 1 (P = .001) for the final diagnosis of Pleural Effusion (PE). We concluded that TUS is a promising screening test for immunocompromised individuals. The results showed good diagnostic performance of TUS compared to CT for the detection of pulmonary findings highly suggestive of pathology with high accuracy and reproducibility.