Prospective Diagnostic Accuracy Study Research Articles

The 4AT scale for rapid detection of delirium in emergency department triage.

To assess the diagnostic accuracy and time impact of the 4AT scale in emergency department triage. A Prospective diagnostic accuracy study was carried out. People aged ≥65 years presenting to the emergency department from 1 November 2021 to 30 June 2022 were included. Nurses opportunistically screened eligible patients using the 4AT scale during triage according to the Manchester Triage System Francesc de Borja Hospital emergency department, Gandía (Spain). Accuracy was compared with medical diagnosis of delirium. Time (seconds) spent in triage with and without screening was assessed. The study included 370 patients (55.1% men, mean age 81.8 years), of whom 58.4% (n = 216) were screened. A final diagnosis of delirium was made in 41.4% of those screened. The most frequently used presentational flow charts and discriminators were 'behaving strangely' (15%) and 'rapid onset' (33.3%). The highest accuracy was obtained for a score of 3 points or more (sensitivity 85.1%; specificity 66.9%; positive predictive value 52.8%; negative predictive value 71.7%). No significant differences were found in the time spent in triage according to the performance of screening. A score of 3 points or more on the 4AT scale enables rapid detection of delirium in emergency department triage, without consuming more time than conventional triage.

Pleural fluid carbohydrate antigen 72-4 and malignant pleural effusion: a diagnostic test accuracy study.

The prognosis of malignant pleural effusion (MPE) is poor. A timely and accurate diagnosis is the prerequisite for managing MPE patients. Carbohydrate antigen 72-4 (CA72-4) is a diagnostic tool for MPE. We aimed to evaluate the diagnostic accuracy of pleural fluid CA72-4 for MPE. A prospective, preregistered, and double-blind diagnostic test accuracy study. We prospectively enrolled participants with undiagnosed pleural effusions from two centers in China (Hohhot and Changshu). CA72-4 concentration in pleural fluid was measured by electrochemiluminescence. Its diagnostic accuracy for MPE was evaluated by a receiver operating characteristic (ROC) curve. The net benefit of CA72-4 was determined by a decision curve analysis (DCA). In all, 153 participants were enrolled in the Hohhot cohort, and 58 were enrolled in the Changshu cohort. In both cohorts, MPE patients had significantly higher CA72-4 levels than benign pleural effusion (BPE) patients. At a cutoff value of 8 U/mL, pleural fluid CA72-4 had a sensitivity, specificity, and area under the ROC curve (AUC) of 0.46, 1.00, and 0.79, respectively, in the Hohhot cohort. In the Changshu cohort, CA72-4 had a sensitivity, specificity, and AUC of 0.27, 0.94, and 0.86, respectively. DCA revealed the relatively high net benefit of CA72-4 determination. In patients with negative cytology, the AUC of CA72-4 was 0.67. Pleural fluid CA72-4 helps differentiate MPE and BPE in patients with undiagnosed pleural effusions.

Modified Thermodilution for Simultaneous Cardiac Output and Recirculation Assessment in Veno-venous Extracorporeal Membrane Oxygenation: A Prospective Diagnostic Accuracy Study.

Thermodilution is unreliable in veno-venous extracorporeal membrane oxygenation (VV-ECMO). Systemic oxygenation depends on recirculation fractions and ratios of extracorporeal membrane oxygenation (ECMO) flow to cardiac output. In a prospective in vitro simulation, this study assessed the diagnostic accuracy of a modified thermodilution technique for recirculation and cardiac output. The hypothesis was that this method provided clinically acceptable precision and accuracy for cardiac output and recirculation. Two ECMO circuits ran in parallel: one representing a VV-ECMO and the second representing native heart, lung, and circulation. Both circuits shared the right atrium. Extra limbs for recirculation and pulmonary shunt were added. This study simulated ECMO flows from 1 to 2.5 l/min and cardiac outputs from 2.5 to 3.5 l/min with recirculation fractions (0 to 80%) and pulmonary shunts. Thermistors in both ECMO limbs and the pulmonary artery measured the temperature changes induced by cold bolus injections into the arterial ECMO limb. Recirculation fractions were calculated from the ratio of the areas under the temperature curve (AUCs) in the ECMO limbs and from partitioning of the bolus volume (flow based). With known partitioning of bolus volumes between ECMO and pulmonary artery, cardiac output was calculated. High-precision ultrasonic flow probes served as reference for Bland-Altman plots and linear mixed-effect models. Accuracy and precision for both the recirculation fraction based on AUC (bias, -5.4%; limits of agreement, -18.6 to 7.9%) and flow based (bias, -5.9%; limits of agreement, -18.8 to 7.0%) are clinically acceptable. Calculated cardiac output for all recirculation fractions was accurate but imprecise (RecirculationAUC: bias 0.56 l/min; limits of agreement, -2.27 to 3.4 l/min; and RecirculationFLOW: bias 0.48 l/min; limits of agreement, -2.22 to 3.19 l/min). Recirculation fraction increased bias and decreased precision. Adapted thermodilution for VV-ECMO allows simultaneous measurement of recirculation fraction and cardiac output and may help optimize patient management with severe respiratory failure.

Diagnostic accuracy of the upper limb neurodynamic test 1 using neurodynamic sequencing in diagnosis of carpal tunnel syndrome

BackgroundThe upper limb neurodynamic test 1 is used in the diagnosis of median nerve neuropathies such as carpal tunnel syndrome but its diagnostic validity remains limited. Neurodynamic sequencing has been suggested to increase the specificity of the neurodynamic tests, however, to date, information on the diagnostic accuracy of this variation in neurodynamic testing is required. ObjectivesThe aim of this study was to analyze the diagnostic validity of the local sequence of ULNT1 (LS-ULNT1) (i.e. a sequence that begins at the joint where the problem is (wrist) and progressively moves joints further away from it), in the diagnosis of CTS. A secondary aim was to describe the location of sensory responses to this modified neurodynamic test sequence. DesignA prospective diagnostic accuracy study was designed. MethodNerve conduction studies were used as the gold standard. The LS-ULNT1 was performed in 58 consecutive patients (17 men, 44 women) with suspected CTS. ResultsSensitivity of the LS-ULNT1 was 65.7% (CI 48.0–80.9%) and the specificity was 95.7% (CI 78.1–99.9%). The positive and negative likelihood ratios were >5 and < 0.5, respectively, indicating the ability of the test to generate small but sometimes important changes in post-test probability. ConclusionsThe overall results of this study showed that the LS-ULNT1 could be useful in confirming the diagnosis of CTS. The test demonstrated high specificity and the +LR indicated the ability of the test to generate changes in posttest probability, especially with a positive LS-ULNT1 result.

Diagnostic accuracy of a point-of-care antigen test for SARS-CoV-2 and influenza in a primary care population (RAPTOR-C19)

ObjectivesLimited evidence exists for the diagnostic performance of point-of-care tests for SARS-CoV-2 and influenza in community healthcare. We carried out a prospective diagnostic accuracy study of the LumiraDx™ SARS-CoV-2 and influenza A or B assay in primary care. MethodsTotal of 913 adults and children with symptoms of current SARS-CoV-2 infection were recruited from 18 UK primary care practices during a period when Omicron was the predominant COVID variant of concern (June 2022 to December 2022). Trained health care staff performed the index test, with diagnostic accuracy parameters estimated for SARS-CoV-2 and influenza against real-time reverse-transcription PCR (rtRT-PCR). Results151/887 participants were SARS-CoV-2 rtRT-PCR positive, 109 positive for Influenza A, 6 for Influenza B. Index test sensitivity for SARS-CoV-2 was 80.8% (122 of the 151, 95% CI, 73.6–86.7%) and specificity 98.9% (728 of the 736, 95% CI, 97.9–99.5%). For influenza A, sensitivity was 61.5% (67 of the 109, 95% CI, 51.7–70.6%) and specificity 99.4% (771 of the 776, 95% CI, 98.5–99.8%). Sensitivity to detect SARS-CoV-2 and influenza dropped sharply at rtRT-PCR cycle thresholds (Ct) > 30. DiscussionsThe LumiraDx™ SARS-CoV-2 and influenza A/B assay had moderate sensitivity for SARS-CoV-2 in symptomatic patients in primary care, with lower performance with high rtRT-PCR Ct. Negative results in this patient group cannot definitively rule out SARS-CoV-2 or influenza.

Higher Sensitivity of Xpert MTB/RIF Ultra Over Tuberculosis Culture for the Diagnosis of Spinal Tuberculosis With Open or Computed Tomography-Guided Biopsies.

Diagnostic specimens for spinal tuberculosis (STB) are mostly collected via open surgery. Percutaneous computed tomography (CT)-guided biopsies are used in times of limited surgical availability. However, poor diagnostic accuracy of Mycobacterium tuberculosis (Mtb) culture has been reported with this method, due to limited sample volume and the paucibacillary nature of STB. We evaluated Xpert MTB/RIF Ultra on open and CT-guided biopsies as compared with the gold standard Mtb culture and histopathology. We conducted a prospective diagnostic accuracy study of Xpert Ultra, as compared with tuberculosis culture and histopathology, in adults with signs and symptoms of STB at a tertiary academic hospital in South Africa from November 2020 to December 2021. Diagnostic testing was performed on 31 patients with available samples. Xpert Ultra had a sensitivity of 94.7% (95% CI, 75.3%-99.7%) and specificity of 100% (95% CI, 75.7%-100.0%) against a reference standard of Mtb culture and histopathology. Xpert Ultra had high diagnostic accuracy in open and CT-guided biopsy samples with sensitivity and specificity of 100% and 100% (open) and 89% and 100% (CT), respectively. Mtb culture had limited specificity for CT-guided biopsies (43%; 95% CI, 15.8%-74.9%). HIV-1 coinfection did not affect Mtb abundance measures by Xpert Ultra or culture. Xpert Ultra was also superior to culture for STB diagnosis in patients concurrently treated for pulmonary tuberculosis. Xpert Ultra detected more STB cases than culture for CT-guided biopsy samples. There was also no difference in sensitivity for open biopsies, irrespective of HIV-1 status, making it an important tool for rapid diagnosis, especially during times or in locations where open surgery is not possible or concurrent pulmonary tuberculosis treatment is initiated.

Pleural fluid soluble Fas ligand and tuberculous pleural effusion: a prospective diagnostic test accuracy study.

The diagnosis of tuberculous pleural effusion (TPE) is challenging for pulmonologists. Adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin-27 (IL-27) have some limitations for diagnosing TPE. Soluble Fas ligand (sFasL) had a high diagnostic value for TPE. However, it remains unknown: (I) whether sFasL has an additional diagnostic value to the traditional markers (e.g., ADA); (II) whether sFasL provides a net benefit in patients with undiagnosed pleural effusion; (III) factors affecting the diagnostic accuracy of sFasL for TPE. This study aimed to evaluate the additional diagnostic value and benefit of pleural fluid sFasL for TPE. We prospectively enrolled 211 patients with undiagnosed pleural effusion. The concentration of sFasL in pleural fluid was measured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy and net benefit of sFasL and ADA for TPE were analyzed by a receiver operating characteristic (ROC) curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discriminant improvement (IDI). The area under the ROC curves (AUCs) of sFasL and ADA were 0.74 (95% CI: 0.65-0.83) and 0.80 (95% CI: 0.71-0.90), respectively. The decision curve of sFasL revealed net benefit. The continuous NRI and IDI of sFasL were 0.36 (0.00-0.72, P=0.05) and 0.02 (-0.01-0.06, P=0.18), respectively. Pleural fluid sFasL has moderate diagnostic accuracy for TPE.

Active close contact investigation of tuberculosis through computer-aided detection and stool Xpert MTB/RIF among people living in Oromia Region, Ethiopia (CADOOL Study): protocol for a prospective, cross-sectional study

IntroductionPulmonary tuberculosis (TB) is an infectious disease with high incidence in low-income countries (LICs); it remains one of the infectious diseases with the highest mortality in the world, especially in...

Use of airway pressure-based indices to detect high and low inspiratory effort during pressure support ventilation: a diagnostic accuracy study

BackgroundAssessment of the patient’s respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (Paw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation.MethodsIn this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative Paw generated during the first 100 ms (P0.1) and the maximal negative swing of Paw (∆Pocc) were measured. After an end-inspiratory airway occlusion, Paw reached a plateau, and the magnitude of change in plateau from peak Paw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (Pmus) and Pmus–time product per minute (PTPmus/min) were used as the reference standard for the patient’s effort. High and low effort was defined as Pmus > 10 and < 5 cmH2O, or PTPmus/min > 200 and < 50 cmH2O s min−1, respectively.ResultsA total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective Pmus and PTPmus/min criterion. The receiver operating characteristic area of the three Paw-based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83–0.96), specificity (0.74–0.88), and positive (0.80–0.91) and negative predictive values (0.78–0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using Pmus and PTPmus/min criterion, respectively. High receiver operating characteristic areas of the three Paw-based indices by the two criteria were found (0.93–0.95). A high sensitivity (0.80–1.00) and negative predictive value (0.97–1.00) were found with a low positive predictive value (0.23–0.64).ConclusionsBy performing simple airway occlusion maneuvers, the Paw-based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort.

Host biomarkers and combinatorial scores for the detection of serious and invasive bacterial infection in pediatric patients with fever without source.

Improved tools are required to detect bacterial infection in children with fever without source (FWS), especially when younger than 3 years old. The aim of the present study was to investigate the diagnostic accuracy of a host signature combining for the first time two viral-induced biomarkers, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon γ-induced protein-10 (IP-10), with a bacterial-induced one, C-reactive protein (CRP), to reliably predict bacterial infection in children with fever without source (FWS) and to compare its performance to routine individual biomarkers (CRP, procalcitonin (PCT), white blood cell and absolute neutrophil counts, TRAIL, and IP-10) and to the Labscore. This was a prospective diagnostic accuracy study conducted in a single tertiary center in children aged less than 3 years old presenting with FWS. Reference standard etiology (bacterial or viral) was assigned by a panel of three independent experts. Diagnostic accuracy (AUC, sensitivity, specificity) of host individual biomarkers and combinatorial scores was evaluated in comparison to reference standard outcomes (expert panel adjudication and microbiological diagnosis). 241 patients were included. 68 of them (28%) were diagnosed with a bacterial infection and 5 (2%) with invasive bacterial infection (IBI). Labscore, ImmunoXpert, and CRP attained the highest AUC values for the detection of bacterial infection, respectively 0.854 (0.804-0.905), 0.827 (0.764-0.890), and 0.807 (0.744-0.869). Labscore and ImmunoXpert outperformed the other single biomarkers with higher sensitivity and/or specificity and showed comparable performance to one another although slightly reduced sensitivity in children < 90 days of age. Labscore and ImmunoXpert demonstrate high diagnostic accuracy for safely discriminating bacterial infection in children with FWS aged under and over 90 days, supporting their adoption in the assessment of febrile patients.

Layer-specific circumferential strain using fast strain-encoded cardiac magnetic resonance imaging in acute myocardial injury - a prospective study of diagnostic and prognostic accuracy

Abstract Background In patients presenting acutely with chest pain or shortness of breath, an acute myocardial injury diagnosed through modern troponin assays is common. Yet, a differential diagnosis is often demanding and must weigh the timely treatment of an ischemic cause against the risk of an invasive procedure without intervention. Modern cardiac magnetic resonance (CMR) strain sequences such as fast-SENC (fSENC) might support clinical decision-making in identifying predictors of myocardial dysfunction (1). Furthermore, their resolution should be able to differentiate epicardial from endocardial function impairment. This study sought to assess a layer-specific strain approach's diagnostic and prognostic accuracy using circumferential strain. Methods In this board-approved prospective observational study, patients from the emergency department fulfilling rule-in criteria for NSTEMI according to current guidelines received an ultra-fast fSENC CMR independently of standard care (2,3). fSENC was acquired in a single heartbeat acquisition, and global/segmental circumferential strain (GCS) as well as dysfunctional segments were measured. GCS was measured in two layers (epicardial/endocardial = GCSepi/GCSendo). Patients were followed up for two years for the occurrence of cardiovascular death and divided into groups according to their final diagnosis upon discharge. Results 64 patients (51 male) were included, consisting of 25 with NSTEMI, 16 with myocarditis and 23 with other causes of myocardial injury (OMI). GCS was reduced in all patients but with no significant difference between groups (NSTEMI: -14.3±3.8; myocarditis: 15.9±4.6; OMI: 13.9±3.8; p&amp;gt;0.05). GCSendo (-16.3±4.0) was generally lower than GCSepi (-12.5±3.1) in all groups (p &amp;lt; 0.001), but did not differ between groups (p&amp;gt;0.05). Overall, 2-year mortality was low (4.7%). Nevertheless, GCSendo predicted outcome (p = 0.03), unlike GCS. 2-year survival in patients with normal GCS (&amp;gt;-17%) and ≤5 dysfunctional segments was 100.0%. Conclusions Layer-specific circumferential strain is a significant predictor of prognosis. Endo- and epicardial strain is reduced in all types of myocardial injury. For the identification of underlying pathology however, layer-specific circumferential strain did not add incremental value.

Transoral Ultrasound in the Outpatient Clinic for the Diagnostic Work-Up of Oropharyngeal Cancer: A Feasibility Study.

Magnetic resonance imaging (MRI) is the preferred imaging modality for oropharyngeal cancers (OPCs), but it has difficulties distinguishing between small OPCs and unilateral tonsil hypertrophy. We hypothesized that surgeon-performed transoral ultrasound (US) could be used to accurately detect T-stage OPCs. We performed a single-center prospective diagnostic accuracy study including patients with suspected or biopsy-verified OPCs during outpatient appointments. All patients were offered transoral US and MRI. If transoral US could not be tolerated by the patient, transcervical US was performed. The primary outcome was the diagnostic accuracy of detecting OPCs with US compared to MRI, using histopathology as the reference standard. The secondary outcome was comparing the primary tumor diameters between US and MRI blinded to each other. Out of the 26 patients included in the study, 21 (81%) had OPCs. Transoral US could be performed in 21/21 and 1/5 patients with suspected palatine and lingual tonsil OPCs, respectively. Overall, US diagnostic accuracy was 92%, compared to 81% with MRI (p = 0.37). US and MRI had a high correlation between tumor diameters in the anteroposterior diameter (R = 0.80, p < 0.001), corresponding to the depth axis on US. In conclusion, this small study showed the promise and feasibility of transoral US to improve the initial clinical evaluations of patients with suspected OPCs.

Role of creatine phosphokinase as a diagnostic marker in tubal ectopic pregnancy.

Ectopic pregnancy (EP) is still one of the leading preventable causes of maternal morbidity and mortality in the first trimester. Amidst the use of sensitive assays for β-HCG and high-definition ultrasonography for the identification of EP, the search for a more reliable and sensitive marker remains a challenge till date. Our aim was to determine the validity of creatine phosphokinase (CPK) and its isoenzyme (CPK-MB) in the prediction of tubal EP. A prospective and comparative diagnostic accuracy study was conducted among 105 pregnant women in the first trimester who met the eligibility criteria in the Department of Obstetrics and Gynecology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS). The study included 35 patients each with tubal EP (EP), abortive intrauterine pregnancy (AP), and normal intrauterine pregnancy (NP). CPK, CPK-MB, and β-HCG were measured among all the participants, and the participants were followed up longitudinally. A total of 105 pregnant women were included. The mean CPK and CPK-MB levels were significantly higher among the women with EP when compared to NP (P < 0.05) and AP (P < 0.05) women; however, there was no significant difference between the NP and AP groups (P > 0.05). Moreover, the receiver operating characteristic (ROC) curve showed that both CPK and CPK-MB were good predictors of EP, with CPK (area under the curve [AUC] = 0.764) being a better predictor than CPK-MB (AUC: 0.650) in the diagnosis of EP. Early diagnosis of EP allows appropriate and timely management, which would not only reduce mortality and morbidity associated with the condition but also enable preservation of fertility and improve future pregnancy outcome. Hence, the need of the hour is a reliable biochemical diagnostic marker for EP, such as CPK.

Evaluation of kit-based loop-mediated isothermal amplification (TB-LAMP) assay in the diagnosis of tubercular lymphadenitis

Background. The rapid and accurate diagnosis of tubercular lymphadenitis remains a challenging task today. The World Health Organization (WHO) endorsed the LoopAMP MTBC kit (TB-LAMP) as a replacement for sputum smear microscopy in the diagnosis of pulmonary tuberculosis (PTB). However, no prospective diagnostic accuracy study of TB-LAMP for tubercular lymphadenitis in adults has been performed yet. The current study evaluated the diagnostic performance of TB-LAMP in tubercular lymphadenitis (LNTB). Methods. In a prospective observational study conducted at a tertiary care hospital in India, 90 subjects (age &gt;18 years) suspected of LNTB were recruited consecutively and followed up for 6 months between January 2019 and December 2020. Samples were processed for microscopy, culture, GeneXpert, histopathology and TB-LAMP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TB-LAMP against the composite reference standard (CRS) and culture were determined. Results. TB-LAMP showed a sensitivity of 83.78 % (95 % CI, 73.76–90.47) and a specificity of 81.25 % (95 % CI, 56.99–93.41), respectively, against the CRS. The PPV and NPV were 95.38 % (95 % CI, 87.29–98.42) and 52.00 % (95 % CI, 33.50–69.97), respectively. TB-LAMP showed a sensitivity of 88.89 % (95 % CI, 71.94–96.15) and a specificity of 36.17 % (95 % CI, 23.97–50.46), respectively, against culture. The PPV and NPV were 44.44 % (95 % CI, 32–57.62) and 85 % (95 % CI, 63.96–94.76), respectively. Conclusion. TB-LAMP can be used instead of conventional microscopy for the diagnosis of TB in lymph node specimens at primary healthcare centres. It provides rapid and cost-effective diagnosis of LNTB in resource-limited settings due to good sensitivity and NPV.

Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries

Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8-68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7-48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4-34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5-94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7-84·3) compared with those without HIV (61·0%, 51·6-69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF).

Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study.

Variable pharmacokinetics of rifampin in tuberculosis (TB) treatment can lead to poor outcomes. Urine spectrophotometry is simpler and more accessible than recommended serum-based drug monitoring, but its optimal efficacy in predicting serum rifampin underexposure in adults with TB remains uncertain. Adult TB patients in New Jersey and Virginia receiving rifampin-containing regimens were enrolled. Serum and urine samples were collected over 24 h. Rifampin serum concentrations were measured using validated liquid chromatography-tandem mass spectrometry, and total exposure (area under the concentration-time curve) over 24 h (AUC0-24) was determined through noncompartmental analysis. The Sunahara method was used to extract total rifamycins, and rifampin urine excretion was measured by spectrophotometry. An analysis of 58 eligible participants, including 15 (26%) with type 2 diabetes mellitus, demonstrated that urine spectrophotometry accurately identified subtarget rifampin AUC0-24 at 0-4, 0-8, and 0-24 h. The area under the receiver operator characteristic curve (AUC ROC) values were 0.80 (95% CI 0.67-0.90), 0.84 (95% CI 0.72-0.94), and 0.83 (95% CI 0.72-0.93), respectively. These values were comparable to the AUC ROC of 2 h serum concentrations commonly used for therapeutic monitoring (0.82 [95% CI 0.71-0.92], P = 0.6). Diabetes status did not significantly affect the AUC ROCs for urine in predicting subtarget rifampin serum exposure (P = 0.67-0.92). Spectrophotometric measurement of urine rifampin excretion within the first 4 or 8 h after dosing is a simple and cost-effective test that accurately predicts rifampin underexposure. This test provides critical information for optimizing tuberculosis treatment outcomes by facilitating appropriate dose adjustments.

Preoperative Assessment of Perianal Fistulas with Combined Magnetic Resonance and Tridimensional Endoanal Ultrasound: A Prospective Study.

we designed a prospective study of diagnostic accuracy that compared pelvic MRI and 3D-EAUS with pelvic MRI alone in the preoperative evaluation and postoperative outcomes of patients with perianal fistulas. the sample size was 72 patients and this was divided into two imaging groups. MRI alone was performed on the first group. Both MRI and 3D-EAUS were performed in parallel on the second group. Surgical exploration took place after two weeks and was the standard reference. Park's classification, the presence of a concomitant abscess or a secondary tract, and the location of the internal opening were recorded. All patients were re-evaluated for complete fistula healing and fecal incontinence six months postoperatively. All of the collected data were subjected to statistical analysis. the MRI group included 36 patients with 42 fistulas. The MRI + 3D-EAUS group included 36 patients with 46 fistulas. The adjusted sensitivity and negative predictive value were 1.00 for most fistula types in the group that underwent combined imaging. The adjusted specificity improved for intersphincteric fistulas in the same group. The adjusted balanced accuracy improved for all fistula types except rectovaginal. The combination of imaging methods showed improved diagnostic accuracy only in the detection of a secondary tract. The healing rate at six months was 100%. Fecal incontinence at six months did not present a statistically significant difference between the two groups (Fisher's exact test p-value > 0.9). Patients with complex perianal fistulas had a statistically significant higher probability of undergoing a second surgery (x2 test p-value = 0.019). the combination of pelvic MRI and 3D-EAUS showed improved metrics of diagnostic accuracy and should be used in the preoperative evaluation of all patients with perianal fistulas, especially those with complex types.

Can Non-Invasive Spectrophotometric Hemoglobin Replace Laboratory Hemoglobin Concentrations for Preoperative Anemia Screening? A Diagnostic Test Accuracy Study.

Preoperative assessment of hemoglobin concentration in blood is important to diagnose anemia. The primary aim of this prospective diagnostic test accuracy study was to monitor non-invasive spectrophotometric hemoglobin (SpHb, g/dL) concentrations among adults prior to elective surgery and to investigate the correlation and agreement of SpHb with laboratory hemoglobin (Hb, g/dl). A secondary aim was to identify the anemia cut-off values for SpHb based on the World Health Organization (WHO) definitions for anemia. This study included 151 consecutive patients (age ≥ 18 year) presenting for preoperative evaluation prior to scheduled elective general or orthopedic surgery. Results identified the mean ± SD of SpHb at 11.43 ± 2.01 g/dL, which underestimated the mean laboratory Hb (12.64 ± 2.29 g/dL, p < 0.001). A bias mean difference (SpHb-Hb) of -1.21 g/dL, with a SD of 1.76, was reported. This bias (SpHb-Hb) was inversely correlated with the mean Hb concentrations. A positive correlation existed between SpHb and Hb, with a good degree of reliability and a significant Intra Class Correlation (ICC). SpHb diagnosed anemia in 32.3% and 60.3% of males and females, respectively. The SpHb cut-off values to identify anemia were 11.3 and 10.2 g/dL for males and females, respectively, with a sensitivity of 83.3% for males and only 62.9% for females. The specificity for males and females were 81% and 91.3%, respectively. SpHb sensitivity allows for anemia diagnosis among males, but not females. However, the specificity allows SpHb to rule out anemia for both.

Transcranial Color-Coded Sonography With Angle Correction As a Screening Tool for Raised Intracranial Pressure.

Transcranial Doppler (TCD) has been evaluated as a noninvasive intracranial pressure (ICP) assessment tool. Correction for insonation angle, a potential source of error, with transcranial color-coded sonography (TCCS) has not previously been reported while evaluating ICP with TCD. Our objective was to study the accuracy of TCCS for detection of ICP elevation, with and without the use of angle correction. Prospective study of diagnostic accuracy. Academic neurocritical care unit. Consecutive adults with invasive ICP monitors. Ultrasound assessment with TCCS. End-diastolic velocity (EDV), time-averaged peak velocity (TAPV), and pulsatility index (PI) were measured in the bilateral middle cerebral arteries with and without angle correction. Concomitant mean arterial pressure (MAP) and ICP were recorded. Estimated cerebral perfusion pressure (CPP) was calculated as estimated CPP (CPPe) = MAP × (EDV/TAPV) + 14, and estimated ICP (ICPe) = MAP-CPPe. Sixty patients were enrolled and 55 underwent TCCS. Receiver operating characteristic curve analysis of ICPe for detection of invasive ICP greater than 22 mm Hg revealed area under the curve (AUC) 0.51 (0.37-0.64) without angle correction and 0.73 (0.58-0.84) with angle correction. The optimal threshold without angle correction was ICPe greater than 18 mm Hg with sensitivity 71% (29-96%) and specificity 28% (16-43%). With angle correction, the optimal threshold was ICPe greater than 21 mm Hg with sensitivity 100% (54-100%) and specificity 30% (17-46%). The AUC for PI was 0.61 (0.47-0.74) without angle correction and 0.70 (0.55-0.92) with angle correction. Angle correction improved the accuracy of TCCS for detection of elevated ICP. Sensitivity was high, as appropriate for a screening tool, but specificity remained low.

Identification of patients at high risk for brain death using an automated digital screening tool: a prospective diagnostic accuracy study

BackgroundAn automated digital screening tool (DETECT) has been developed to aid in the early identification of patients who are at risk of developing brain death during critical care.MethodsThis prospective diagnostic accuracy study included consecutive patients ≥ 18 years admitted to neurocritical care for primary or secondary acute brain injury. The DETECT screening tool searched routinely monitored patient data in the electronic medical records every 12 h for a combination of coma and absence of bilateral pupillary light reflexes. In parallel, daily neurological assessment was performed by expert neurointensivists in all patients blinded to the index test results. The primary target condition was the eventual diagnosis of brain death. Estimates of diagnostic accuracy along with their 95%-confidence intervals were calculated to assess the screening performance of DETECT.ResultsDuring the 12-month study period, 414 patients underwent neurological assessment, with 8 (1.9%) confirmed cases of brain death. DETECT identified 54 positive patients and sent 281 notifications including 227 repeat notifications. The screening tool had a sensitivity of 100% (95% CI 63.1–100%) in identifying patients who eventually developed brain death, with no false negatives. The mean time from notification to confirmed diagnosis of brain death was 3.6 ± 3.2 days. Specificity was 88.7% (95% CI 85.2–91.6%), with 46 false positives. The overall accuracy of DETECT for confirmed brain death was 88.9% (95% CI 85.5–91.8%).ConclusionsOur findings suggest that an automated digital screening tool that utilizes routinely monitored clinical data may aid in the early identification of patients at risk of developing brain death.