Real-world diagnostic accuracy of lipoarabinomannan in three non-sputum biospecimens for pulmonary tuberculosis disease.

BACKGROUND: Development of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV. METHODS: We conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4-20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard. FINDINGS: Urine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4-20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells <200 cells/mm3. Urine LAM by S4-20 achieved diagnostic sensitivity of 62% (95% CI: 53%-70%) and specificity of 99% (95% CI: 96%-100%). Plasma and serum LAM by FIND 28 showed similar sensitivity (70%, 95% CI: 62%-78%) and comparable specificities (90%, 95% CI: 82%-97%; 94%, 95% CI: 88%-99%). Diagnostic sensitivity of urine LAM by S4-20 was higher among participants without HIV (41%, 95% CI: 24%-61%) compared to HIV-positive participants with CD4 ≥200 cells/mm3 (20%, 95% CI: 8%-39%). INTERPRETATION: Detection of LAM was achievable in non-sputum specimens for pulmonary TB, but additional analyte concentration or signal amplification may be required to achieve diagnostic accuracy targets. FUNDING: Bill and Melinda Gates Foundation.

Impact of an Automated Closed-Loop Communication and Tracking Tool on the Rate of Recommendations for Additional Imaging in Thoracic Radiology Reports.

OBJECTIVE: Assess the effects of feedback reports and implementing a closed-loop communication system on rates of recommendations for additional imaging (RAIs) in thoracic radiology reports. METHODS: In this retrospective, institutional review board-approved study at an academic quaternary care hospital, we analyzed 176,498 thoracic radiology reports during a pre-intervention (baseline) period from April 1, 2018, to November 30, 2018; a feedback report only period from December 1, 2018, to September 30, 2019; and a closed-loop communication system plus feedback report (IT intervention) period from October 1, 2019, to December 31, 2020, promoting explicit documentation of rationale, time frame, and imaging modality for RAI, defined as complete RAI. A previously validated natural language processing tool was used to classify reports with an RAI. Primary outcome of rate of RAI was compared using a control chart. Multivariable logistic regression determined factors associated with likelihood of RAI. We also estimated the completeness of RAI in reports comparing IT intervention to baseline using χ2 statistic. RESULTS: The natural language processing tool classified 3.2% (5,682 of 176,498) reports as having an RAI; 3.5% (1,783 of 51,323) during the pre-intervention period, 3.8% (2,147 of 56,722) during the feedback report only period (odds ratio: 1.1, P = .03), and 2.6% (1,752 of 68,453) during the IT intervention period (odds ratio: 0.60, P < .001). In subanalysis, the proportion of incomplete RAI decreased from 84.0% (79 of 94) during the pre-intervention period to 48.5% (47 of 97) during the IT intervention period (P < .001). DISCUSSION: Feedback reports alone increased RAI rates, and an IT intervention promoting documentation of complete RAI in addition to feedback reports led to significant reductions in RAI rate, incomplete RAI, and improved overall completeness of the radiology recommendations.

Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study.

BACKGROUND: Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing. METHODS: We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by viral growth in culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by positive viral growth in culture. RESULTS: Among 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, virus growth and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with culture positivity (relative risk=7.61, 95% CI: 3.01-19.22), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, the presence of N antigen remained strongly associated (adjusted relative risk=7.66, 95% CI: 3.96-14.82) with culture positivity, regardless of COVID-19 symptoms. CONCLUSIONS: Most adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset. N antigen testing is a strong predictor of viral infectiousness and may be a more suitable biomarker, rather than absence of symptoms or viral RNA, to discontinue isolation within two weeks from symptom onset.

Adoption of a diagnostic certainty scale in abdominal imaging: 2-year experience at an academic institution.

PURPOSE: Assess use of a diagnostic certainty scale (CS) for abdominal imaging reports and identify factors associated with greater adoption. METHODS: This retrospective, Institutional Review Board-exempt study was conducted at an academic health system. Abdominal radiology reports containing diagnostic certainty phrases (DCPs) generated 4/1/2019-3/31/2021 were identified by a natural language processing tool. Reports containing DCPs were subdivided into those with/without a CS inserted at the end. Primary outcome was monthly CS use rate in reports containing DCPs. Secondary outcomes were assessment of factors associated with CS use, and usage of recommended DCPs over time. Chi-square test was used to compare proportions; univariable and multivariable regression assessed impact of other variables. RESULTS: DCPs were used in 81,281/124,501 reports (65.3%). One-month post-implementation, 82/2310 (3.6%) of reports with DCPs contained the CS, increasing to 1862/4644 (40.1%) by study completion (p < 0.001). Multivariable analysis demonstrated reports containing recommended DCPs were more likely to have the CS (Odds Ratio [OR] 4.5; p < 0.001). Using CT as a reference, CS use was lower for ultrasound (OR 0.73; p < 0.001) and X-ray (OR 0.38; p < 0.001). There was substantial inter-radiologist variation in CS use (OR 0.01-26.3, multiple p values). CONCLUSION: DCPs are very common in abdominal imaging reports and can be further clarified with CS use. Although voluntary CS adoption increased 13-fold over 2 years, > 50% of reports with DCPs lacked the CS at study's end. More stringent interventions, including embedding the scale in report templates, are likely needed to reduce inter-radiologist variation and decrease ambiguity in conveying diagnostic certainty to referring providers and patients.

Radiologists' Contribution to Variation in Detecting Clinically Significant Prostate Cancer in Men With Prostate MRI.

OBJECTIVE: Assess radiologists' contribution to variation in clinically significant prostate cancer (csPCa) detection in patients with elevated prostate-specific antigen (PSA) and multiparametric MRI (mpMRI). METHODS: This institutional review board-approved, retrospective cohort study was performed at a tertiary, academic, National Cancer Institute-designated Comprehensive Cancer Center with a multidisciplinary prostate cancer program. Men undergoing mpMRI examinations from January 1, 2015, to December 31, 2019, with elevated PSA (≥4 ng/mL) and biopsy within 6 months pre- or post-MRI or prostatectomy within 6 months post-mpMRI were included. Univariate and multivariable hierarchical logistic regression assessed impact of patient, provider, mpMRI examination, mpMRI report, and pathology factors on the diagnosis of Grade Group ≥ 2 csPCa. RESULTS: Study cohort included 960 MRIs in 928 men, mean age 64.0 years (SD ± 7.4), and 59.8% (555 of 928) had csPCa. Interpreting radiologist was not significant individually (P > .999) or combined with mpMRI ordering physician and physician performing biopsy or prostatectomy (P = .41). Prostate Imaging Reporting and Data System (PI-RADS) category 2 (odds ratio [OR] 0.18, P = .04), PI-RADS category 4 (OR 2.52, P < .001), and PI-RADS category 5 (OR 4.99, P < .001) assessment compared with no focal lesion; PSA density of 0.1 to 0.15 ng/mL/cc (OR 2.46, P < .001), 0.15 to 0.2 ng/mL/cc (OR 2.77, P < .001), or ≥0.2 ng/mL/cc (OR 4.52, P < .001); private insurance (reference = Medicare, OR 0.52, P = .001), and unambiguous extraprostatic extension on mpMRI (OR 2.94, P = .01) were independently associated with csPCa. PI-RADS 3 assessment (OR 1.18, P = .56), age (OR 0.99, P = .39), and African American race (OR 0.90, P = .75) were not. DISCUSSION: Although there is known in-practice variation in radiologists' interpretation of mpMRI, in our multidisciplinary prostate cancer program we found no significant radiologist-attributable variation in csPCa detection.