Adverse Events Associated with Intra-Arterial Administration of Gadolinium-Based Contrast Agents: A Systematic Review and Meta-Analysis.

PURPOSE: To determine the risk of immediate hypersensitivity reactions (HRs), contrast-associated acute kidney injury (CA-AKI), nephrogenic systemic fibrosis (NSF), and gadolinium retention associated with use of intra-arterial gadolinium-based contrast agents (GBCAs). MATERIALS AND METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from 1988 (GBCAs approved for clinical use) to March 2021 for studies reporting adverse events associated with intra-arterial administration of GBCAs. The number of adverse events and GBCA administrations were used to calculate incidence in individual studies, and results across studies were pooled using random-effects meta-analysis. RESULTS: There were 72 studies (patients = 1,221) that reported on HR, 59 studies (patients = 1,142) that reported on CA-AKI, and 6 studies (patients = 291) that reported on NSF. No studies reported gadolinium retention as an outcome. Based on 5 events and 1,451 GBCA administrations, the incidence of HR per 100 administrations was 0.95 (95% CI, 0.52-1.51). Based on 90 events and 1,318 GBCA administrations, the incidence of CA-AKI per 100 administrations was 5.94 (95% CI, 3.92-8.34). Based on 7 events and 361 GBCA administrations, the incidence of NSF per 100 Group I GBCA administrations was 4.72 (95% CI, 0.35-13.70). There were no unconfounded NSF events after Group II GBCA administration. CONCLUSIONS: HRs to intra-arterial administration of GBCAs are rare, with no serious reactions. Limited data demonstrate a higher-than-expected rate of CA-AKI; however, multiple confounding factors were noted. Thus, any causative link of CA-AKI to GBCA remains controversial. Also, severe physiologic reactions (including life-threatening arrhythmias) during coronary angiography have been reported.

Proportion of malignancy in Bosniak classification of cystic renal masses version 2019 (v2019) classes: systematic review and meta-analysis.

OBJECTIVES: Determine the proportion of malignancy within Bosniak v2019 classes. METHODS: MEDLINE and EMBASE were searched. Eligible studies contained patients with cystic renal masses undergoing CT or MRI renal protocol examinations with pathology confirmation, applying Bosniak v2019. Proportion of malignancy was estimated within Bosniak v2019 class. Risk of bias was assessed using QUADAS-2. RESULTS: We included 471 patients with 480 cystic renal masses. No class I malignant masses were observed. Pooled proportion of malignancy were class II, 12% (6/51, 95% CI 5-24%); class IIF, 46% (37/85, 95% CI 28-66%); class III, 79% (138/173, 95% CI 68-88%); and class IV, 84% (114/135, 95% CI 77-90%). Proportion of malignancy differed between Bosniak v2019 II-IV classes (p = 0.004). Four studies reported the proportion of malignancy by wall/septa feature. The pooled proportion of malignancy with 95% CI were class III thick smooth wall/septa, 77% (41/56, 95% CI 53-91%); class III obtuse protrusion ≤ 3 mm (irregularity), 83% (97/117, 95% CI 75-89%); and class IV nodule with acute angulation, 86% (50/58, 95% CI 75-93%) or obtuse angulation ≥ 4 mm, 83%, (64/77, 95% CI 73-90%). Subgroup analysis by wall/septa feature was limited by sample size; however, no differences were found comparing class III masses with irregularity to class IV masses (p = 0.74) or between class IV masses by acute versus obtuse angles (p = 0.62). CONCLUSION: Preliminary data suggest Bosniak v2019 class IIF masses have higher proportion of malignancy compared to the original classification, controlling for pathologic reference standard. There are no differences in proportion of malignancy comparing class III masses with irregularities to class IV masses with acute or obtuse nodules. KEY POINTS: • The proportion of malignancy in Bosniak v2019 class IIF cystic masses is 46% (37 malignant/85 total IIF masses, 95% confidence intervals (CI) 28-66%). • The proportion of malignancy in Bosniak v2019 class III cystic masses is 79% (138/173, 95% CI 68-88%) and in Bosniak v2019 class IV cystic masses is 84% (114/135, 95% CI 77-90%). • Class III cystic masses with irregularities had similar proportion of malignancy (83%, 97/117, 95% CI 75-89%) compared to Bosniak class IV masses (84%, 114/135, 95% CI 77-90%) overall (p = 0.74) with no difference within class IV masses by acute versus obtuse angulation (p = 0.62).

Direct Comparison of Diagnostic Accuracy of Fast Kilovoltage Switching Dual-Energy Computed Tomography and Magnetic Resonance Imaging for Detection of Enhancement in Renal Masses.

PURPOSE: The aim of the study was to compare diagnostic accuracy of dual-energy computed tomography (DECT) and magnetic resonance imaging (MRI) to detect enhancement in renal masses. METHODS: Adults renal masses of 10 mm or greater with both fast kilovoltage potential switching DECT and contrast-enhanced MRI performed within 12 months were retrospectively included. Two blinded radiologists independently evaluated for enhancement subjectively (5-point Likert scales) and quantitatively (signal intensity ratio ≥15% for MRI, iodine concentration ≥1.2 or ≥2.0 mg/mL for DECT). Per-lesion diagnostic accuracy, with histologic reference standard for solid masses, was expressed as the area under the receiver operator curve (AUC) for each index test. Differences were evaluated for statistical significance using the DeLong test. RESULTS: We included 24 patients with 41 masses: 17 solid renal masses and 24 Bosniak 1 or 2 cysts. There was no significant difference in diagnostic accuracy comparing subjective enhancement by MRI and using iodine overlay DECT for reader 1 (AUC 0.99 vs 0.99, P = 0.38) or reader 2 (AUC 1.00 vs 0.94, P = 0.12) Interobserver agreement was κ = 0.61 for DECT and κ = 0.71 for MRI. There was no significant difference either in accuracy between quantitative assessment using signal intensity ratio or iodine concentration for reader 1 (AUC 0.94 vs 0.94, P = 0.88) or reader 2 (AUC 0.97 vs 0.92, P = 0.16). False-negative results in both subjective and quantitative assessment were nearly exclusively seen in papillary renal cell carcinoma, occurring with both DECT and MRI. CONCLUSIONS: We detected no significant differences in accuracy for detecting enhancement in renal masses comparing MRI and DECT. Our results require further investigation in larger sample sizes, but suggest that DECT may be comparable to MRI for detection of enhancement in renal masses.

Association of Accuracy, Conclusions, and Reporting Completeness With Acceptance by Radiology Conferences and Journals.

BACKGROUND: Preferential publication of studies with positive findings can lead to overestimation of diagnostic test accuracy (i.e. publication bias). Understanding the contribution of the editorial process to publication bias could inform interventions to optimize the evidence guiding clinical decisions. PURPOSE/HYPOTHESIS: To evaluate whether accuracy estimates, abstract conclusion positivity, and completeness of abstract reporting are associated with acceptance to radiology conferences and journals. STUDY TYPE: Meta-research. POPULATION: Abstracts submitted to radiology conferences (European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and International Society for Magnetic Resonance in Medicine (ISMRM)) from 2008 to 2018 and manuscripts submitted to radiology journals (Radiology, Journal of Magnetic Resonance Imaging [JMRI]) from 2017 to 2018. Primary clinical studies evaluating sensitivity and specificity of a diagnostic imaging test in humans with available editorial decisions were included. ASSESSMENT: Primary variables (Youden's index [YI > 0.8 vs. <0.8], abstract conclusion positivity [positive vs. neutral/negative], number of reported items on the Standards for Reporting of Diagnostic Accuracy Studies [STARD] for Abstract guideline) and confounding variables (prospective vs. retrospective/unreported, sample size, study duration, interobserver agreement assessment, subspecialty, modality) were extracted. STATISTICAL TESTS: Multivariable logistic regression to obtain adjusted odds ratio (OR) as a measure of the association between the primary variables and acceptance by radiology conferences and journals; 95% confidence intervals (CIs) and P-values were obtained; the threshold for statistical significance was P < 0.05. RESULTS: A total of 1000 conference abstracts (500 ESGAR and 500 ISMRM) and 1000 journal manuscripts (505 Radiology and 495 JMRI) were included. Conference abstract acceptance was not significantly associated with YI (adjusted OR = 0.97 for YI > 0.8; CI = 0.70-1.35), conclusion positivity (OR = 1.21 for positive conclusions; CI = 0.75-1.90) or STARD for Abstracts adherence (OR = 0.96 per unit increase in reported items; CI = 0.82-1.18). Manuscripts with positive abstract conclusions were less likely to be accepted by radiology journals (OR = 0.45; CI = 0.24-0.86), while YI (OR = 0.85; CI = 0.56-1.29) and STARD for Abstracts adherence (OR = 1.06; CI = 0.87-1.30) showed no significant association. Positive conclusions were present in 86.7% of submitted conference abstracts and 90.2% of journal manuscripts. DATA CONCLUSION: Diagnostic test accuracy studies with positive findings were not preferentially accepted by the evaluated radiology conferences or journals. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Evaluation of class II cystic renal masses proposed in Bosniak classification version 2019: a systematic review of supporting evidence.

PURPOSE: The Bosniak classification of cystic renal masses version 2019 (v.2019) includes an expanded number of types of masses in class II; such masses are considered benign in clinical practice. Data supporting these additions have not been well-documented. We aim to determine the proportion of malignant or probably malignant renal masses among the types added to Bosniak v.2019 class II. METHODS: Multiple databases were searched for studies evaluating the proportion of malignant or probably malignant renal masses among new Bosniak v.2019 class II types, four for CT and two for MRI. Risk of bias and applicability was assessed using the QUADAS-2 tool. RESULTS: Ten studies (2068 renal masses) met inclusion criteria. Among the four added class II types at CT, the proportion of malignancy among (1) 'homogeneous hyperattenuating (≥ 70 HU) masses at unenhanced CT' was 0% (0/32) in three studies; (2) 'homogeneous masses - 9 to 20 HU at unenhanced CT' was 0% (0/1454) in two studies, and (3) 'homogeneous masses 21 to 30 HU at portal-venous phase CT' was 0% (0/454) in four studies. Masses that are homogeneous, have low attenuation, and are too small to characterize on CT had no supportive evidence. Among the two added class II types at MRI, the proportion of malignancy among (1) 'homogeneous masses markedly hyperintense at unenhanced T2-weighted MR imaging (similar to CSF) was 0% (0/72) in one study, and (2) 'homogeneous masses markedly hyperintense at T1-weighted MR imaging (~ 2.5 × renal parenchyma signal intensity)' was 0% (0/32) and 5% (2/37) in two studies. Nine studies were at risk of bias within at least one QUADAS-2 domain. CONCLUSION: The addition of six types of cystic renal masses to Class II in the Bosniak v.2019 proposal may be justified but based on limited evidence, with no evidence for 'homogeneous low attenuation masses that are too small to characterize' on CT, and thus considering them benign is in part based on expert opinion. Protocol Registration: PROSERO CRD42020196408.

Content Analysis and Characterization of Medical Tweets During the Early Covid-19 Pandemic.

Objective The novel coronavirus disease 2019 (Covid-19) has infected millions worldwide and impacted the lives of many folds more. Many clinicians share new Covid-19-related resources, research, and ideas within the online Free Open Access to Medical Education (FOAM) community of practice. This study provides a detailed content and contributor analysis of Covid-19-related tweets among the FOAM community during the first months of the pandemic. Design, Setting, and Participants In this social media content analysis study, Twitter was searched from November 1, 2019, to March 21, 2020, for English tweets discussing Covid-19 in the FOAM community. Tweets were classified into one of 13 pre-specified content categories: original research, editorials, FOAM resource, public health, podcast or video, learned experience, refuting false information, policy discussion, emotional impact, blatantly false information, other Covid-19, and non-Covid-19. Further analysis of linked original research and FOAM resources was performed. One-thousand (1000) randomly selected contributor profiles and those deemed to have contributed false information were analyzed. Results The search yielded 8541 original tweets from 4104 contributors. The number of tweets in each content category were: 1557 other Covid-19 (18.2%), 1190 emotional impact (13.9%), 1122 FOAM resources (13.1%), 1111 policy discussion (13.0%), 928 advice (10.9%), 873 learned experience (10.2%), 424 non-Covid-19 (5.0%), 410 podcast or video (4.8%), 304 editorials (3.6%), 275 original research (3.2%), 245 public health (2.9%), 83 refuting false information (1.0%), and 19 blatantly false (0.2%). Conclusions Early in the Covid-19 pandemic, the FOAM community used Twitter to share Covid-19 learned experiences, online resources, crowd-sourced advice, and research and to discuss the emotional impact of Covid-19. Twitter also provided a forum for post-publication peer review of new research. Sharing blatantly false information within this community was infrequent. This study highlights several potential benefits from engaging with the FOAM community on Twitter.

Completeness of reporting for systematic reviews of point-of-care ultrasound: a meta-research study.

OBJECTIVES: Systematic reviews are often considered among the highest quality of evidence. Completely reported systematic reviews, however, are required so readers can assess for generalisability of the research to practice and risk of bias. The objective of this study was to assess the completeness of reporting for systematic reviews assessing the diagnostic accuracy of point-of-care ultrasound (POCUS) using the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Diagnostic Test Accuracy (PRISMA-DTA) checklist that was published in 2018. DESIGN AND SETTING: In this meta-research study, MEDLINE, EMBASE and Cochrane Library databases were searched, with no date restriction, on March 1st, 2020 for systematic reviews assessing the diagnostic accuracy of POCUS. Adherence to PRISMA-DTA for the main text and abstract was scored independently and in duplicate using a modified checklist. Prespecified subgroup analyses were performed. MAIN OUTCOME MEASURES: The primary outcome was the mean PRISMA-DTA checklist adherence for the full-text and abstract. RESULTS: A total of 71 studies published from 2008 to 2020 met the inclusion criteria. The overall adherence for the full-text was moderate: 19.8 out of 26.0 items (76%) and for the abstract was 7.0 out of 11.0 items (64%). Although many items in the PRISMA-DTA checklist were frequently reported, several were r infrequently reported (<33% of studies), including item 5 (protocol registration), item D2 (minimally acceptable test accuracy) and item 14 (variability in target condition, index test and reference standards). Subgroup analyses showed a higher PRISMA-DTA mean adherence (SD) for high impact journals (20.9 (2.52) vs 18.9 (1.95); p<0.001), studies including supplemental materials (20.6 (2.48) vs 18.9 (2.28); p=0.004), studies citing adherence to PRISMA reporting guidelines (20.4 (1.95) vs 19.0 (3.00); p=0.038) and studies published in journals endorsing PRISMA guidelines (20.2 (2.47) vs 18.6 (2.37); p=0.025). There was variable adherence based on journal of publication (p=0.006), but not for study population (adult vs paediatric vs mixed) (p=0.62), year of publication (p=0.94), body region (p=0.78) or country (p=0.40). There was no variability in abstract adherence based on whether the abstract was structured with subheadings or not (p=0.25). A Spearman's correlation found moderate correlation between higher word counts and abstractand full-text adherence (R=0.45, p<0.001 and R=0.38, p=0.001), respectively. CONCLUSIONS: Overall, the reporting of POCUS diagnostic accuracy systematic reviews and meta-analyses was moderate. We identified deficits in several key areas including the preregistration of systematic reviews in an online repository, handling of multiple definitions of target conditions, index tests and reference standards and specifying minimally acceptable test accuracy. Prospective registration of reviews and detailed reporting as per PRISMA-DTA during the research process could improve reporting completeness. At an editorial level, word count and supplemental material limitations may impede reporting completeness, whereas endorsement of reporting guidelines on journal websites could improve reporting.

Barriers to reporting guideline adherence in point-of-care ultrasound research: a cross-sectional survey of authors and journal editors.

OBJECTIVE: Although the literature supporting the use of point-of-care ultrasound (POCUS) continues to grow, incomplete reporting of primary diagnostic accuracy studies has previously been identified as a barrier to translating research into practice and to performing unbiased systematic reviews. This study assesses POCUS investigator and journal editor attitudes towards barriers to adhering to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 guidelines. DESIGN, SETTING, PARTICIPANTS: Two separate surveys using a 5-point Likert scale were sent to POCUS study investigators and journal editors to assess for knowledge, attitude and behavioural barriers to the complete reporting of POCUS research. Respondents were identified based on a previous study assessing STARD 2015 adherence for POCUS studies published in emergency medicine, anaesthesia and critical care journals. Responses were anonymously linked to STARD 2015 adherence data from the previous study. Written responses were thematically grouped into the following categories: knowledge, attitude and behavioural barriers to quality reporting, or other. Likert response items are reported as median with IQRs. MAIN OUTCOME MEASURES: The primary outcome was the median Likert score for the investigator and editor surveys assessing knowledge, attitude and behavioural beliefs about barriers to adhering to the STARD 2015 guidelines. RESULTS: The investigator survey response rate was 18/69 (26%) and the editor response rate was 5/21 (24%). Most investigator respondents were emergency medicine practitioners (13/21, 62%). Two-thirds of investigators were aware of the STARD 2015 guidelines (12/18, 67%) and overall agreed that incomplete reporting limits generalisability and the ability to detect risk of bias (median 4 (4, 5)). Investigators felt that the STARD 2015 guidelines were useful, easy to find and easy to use (median 4 (4, 4.25); median 4 (4, 4.25) and median 4 (3, 4), respectively). There was a shared opinion held by investigators and editors that the peer review process be primarily responsible for ensuring complete research reporting (median 4 (3, 4) and median 4 (3.75, 4), respectively). Three of 18 authors (17%) felt that the English publication language of STARD 2015 was a barrier to adherence. CONCLUSIONS: Although investigators and editors recognise the importance of completely reported research, reporting quality is still a core issue for POCUS research. The shared opinion held by investigators and editors that the peer review process be primarily responsible for reporting quality is potentially problematic; we view completely reported research as an integral part of the research process that investigators are responsible for, with the peer review process serving as another additional layer of quality control. Endorsement of reporting guidelines by journals, auditing reporting guideline adherence during the peer review process and translation of STARD 2015 guidelines into additional languages may improve reporting completeness for the acute POCUS literature. TRIAL REGISTRATION NUMBER: Open Science Framework Registry (https://osf.io/5pzxs/).

Diagnostic accuracy of dual-energy CT for the detection of bone marrow edema in the appendicular skeleton: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis evaluated the diagnostic accuracy of dual-energy CT (DECT) for detecting bone marrow edema (BME) in the appendicular skeleton. METHODS: A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and gray literature from inception through January 31, 2020, was performed. Original articles with > 10 patients evaluating the accuracy of DECT for detecting BME in the appendicular skeleton with a reference standard of MRI and/or clinical follow-up were included. Study details were independently extracted by two reviewers. Meta-analysis was performed using a bivariate random-effects model with multivariable meta-regression. Risk of bias (RoB) was evaluated with QUADAS-2. RESULTS: Twenty studies evaluating 790 patients for BME in the appendicular skeleton were included in analysis. The summary sensitivity, specificity, and AUC values for BME in the appendicular skeleton were 86% (95% confidence interval [CI] 82-89%), 93% (95% CI 90-95%), and 0.95, respectively. Quantitative analysis had a higher sensitivity than qualitative analysis on meta-regression (p = 0.01), but no difference in specificity (p = 0.28). No other covariates contributed to variability in accuracy (etiology (trauma vs non-trauma); location (upper vs lower extremity); and RoB). Studies demonstrated generally low or unclear RoB and applicability. Eight studies included index tests with high RoB when quantitative assessments used a retrospective cut-off value. CONCLUSIONS: DECT demonstrates a higher specificity than sensitivity and AUC > 0.9. In scenarios where MRI availability is limited or contraindicated, DECT could be an alternative to MRI for detecting BME in the appendicular skeleton. However, limitations in sources of variability and RoB warrant continued study. KEY POINTS: • Twenty studies evaluating 790 patients for bone marrow edema in the appendicular skeleton with dual-energy CT were included in analysis. • The summary sensitivity, specificity, and AUC values for detecting bone marrow in the appendicular skeleton were 86% (95% confidence interval [CI] 82-89%), 93% (95% CI 90-95%), and 0.95, respectively. • In scenarios where MRI availability is limited or is contraindicated, DECT could be an alternative to MRI for detecting bone marrow edema in the appendicular skeleton.

Safety of Off-Label Use of Ferumoxtyol as a Contrast Agent for MRI: A Systematic Review and Meta-Analysis of Adverse Events.

BACKGROUND: Ferumoxytol has been studied as an alternative to gadolinium-based MRI contrast agents, but regulatory body warnings currently limit its use. PURPOSE: Estimate the adverse event rate in patients undergoing MRI with ferumoxytol as a contrast agent. STUDY TYPE: Systematic review. POPULATION: Thirty-nine studies including 5411 ferumoxytol administrations in 4336 patients. ASSESSMENT: Multiple databases were searched for studies using ferumoxytol as an off-label MRI contrast agent in any patient population as of April 2020. Studies were eligible for inclusion if they reported the number and severity of adverse events (classified by American College of Radiology [ACR] severity of acute reactions). Risk of bias was assessed using the ROBINS-I tool. STATISTICAL TESTS: The proportion of administrations with adverse events was calculated using random effects meta-analysis of proportions. RESULTS: No deaths related to ferumoxytol administration were reported. Sixteen studies reported immediate adverse events in 3849 patients undergoing 4901 ferumoxytol administrations. Ninety-seven immediate adverse events were reported and the pooled adverse event proportion for immediate adverse events was 0.02 (95% confidence interval [CI] 0.02-0.02). Twenty-three studies reported time-unspecified adverse events in 487 patients undergoing 510 ferumoxytol administrations. Five time-unspecified adverse events were reported; the pooled adverse event proportion for time-unspecified adverse events was 0.01 (95% CI 0.00-0.04). 88% of adverse events were mild (90/102), 11% (11/102) were moderate, and 1% (1/102) was severe. Sixteen studies were at low risk of bias, 23 studies were at serious risk of bias. Subgroup analysis by patient population revealed no significant variability (adult vs. pediatric). No studies evaluated the use of ferumoxytol as an alternative to patients who had a prior hypersensitivity reaction to gadolinium-based contrast agents (GBCAs). DATA CONCLUSION: The overall adverse event rate for off-label ferumoxytol use as an MRI contrast agent is 2%, with rare severe reactions and no deaths. To date, there are no studies evaluating the safety of ferumoxytol as an alternative to GBCAs in patients with a prior hypersensitivity reaction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 5.

Empiric Switching of Gadolinium-Based Contrast Agents in Patients With History of Previous Immediate Hypersensitivity Reaction to GBCA: A Prospective Single-Center, Single-Arm Efficacy Trial.

BACKGROUND: Breakthrough hypersensitivity reactions (HRs) to gadolinium-based contrast agent (GBCA) occur in 40% of patients despite corticosteroid premedication. Other strategies to reduce HRs are not well studied. OBJECTIVE: The aim of this study was to prospectively evaluate HR rate to GBCA among patients with history of HR to GBCA, empirically given an alternative GBCA prior to repeat administration. MATERIALS AND METHODS: From September 2019 to September 2020, patients with prior HR to GBCA received 13-hour oral corticosteroid and diphenhydramine premedication prescription with switching of GBCA to gadoterate (previously unavailable at our institution before September 2019). Power analysis (α error, 0.05; ß error, 0.80) determined 21 patients were required. Patients were evaluated under a quality assurance waiver from the institutional review board. A radiologist documented the nature of initial HR and inciting GBCA, premedication received, incidence, and severity of breakthrough HR. RESULTS: After exclusions, we evaluated 26 patients with mild (92.3% [24/26]) or moderate (7.7% [2/26]) HR to gadobutrol (53.8% [14/26]), gadoxetate (3.8% [1/26]), and gadopentetate (3.8% [1/26]). In 38.5% (10/26), inciting GBCA was unknown but was likely gadobutrol or gadopentetate based on availability. There were 22 females. The mean patient age was 52.1 ± 15.8 years.From 27 gadoterate administrations, 59.3% (16/27) patients received corticosteroid and diphenhydramine premedication, 11.1% (3/27) received only diphenhydramine, and 29.6% (8/27) with no premedication.Hypersensitivity reaction rate after empiric switching to gadoterate was 3.7% (1 mild reaction; 95% confidence interval [CI], 0.09%-18.9%) overall with no difference in patients with (6.3% [1/16]; 95% CI, 0.15%-28.7%) or without (0%; [0/11] upper bound 95% CI, 25.0%) corticosteroid premedication. CONCLUSIONS: In this prospective single-arm study, empirically switching GBCA to gadoterate in patients with prior HR to GBCA substantially reduced the expected rate of subsequent HRs in patients with and without the use of corticosteroid premedication. IMPLICATIONS FOR PATIENT CARE: Empirically switching GBCAs, with or without the use of corticosteroid premedication, can substantially reduce the rate of hypersensitivity breakthrough reactions.

Reporting Bias in Imaging Diagnostic Test Accuracy Studies: Are Studies With Positive Conclusions or Titles Submitted and Published Faster?

OBJECTIVE: The purpose of this study is to evaluate whether imaging diagnostic test accuracy (DTA) studies with positive conclusions or titles have a shorter time to publication than those with nonpositive (i.e., negative or neutral) conclusions or titles. MATERIALS AND METHODS: We included primary imaging DTA studies from systematic reviews published in 2015. The conclusion and title of each study were extracted, and their positivity was classified independently in duplicate. The time from study completion to publication was extracted and calculated. A Cox regression model was used to evaluate associations of conclusion and title positivity with time to publication, with adjustment made for potentially confounding variables. RESULTS: A total of 774 imaging DTA studies were included; time from study completion to publication could be calculated for 516 studies. The median time from completion to publication was 18 months (interquartile range, 13-26 months) for the 413 studies with positive conclusions, 23 months (interquartile range, 16-33 months) for the 63 studies with neutral conclusions, and 25 months (interquartile range, 15-38 months) for the 40 studies with negative conclusions. A positive conclusion was associated with a shorter time from study completion to publication compared with a non-positive conclusion (hazard ratio, 1.31; 95% CI, 1.02-1.68). Of all included studies, 39 (5%) had positive titles, 731 (94%) had neutral titles, and 4 (< 1%) had negative titles. Positive titles were not significantly associated with a shorter time to study publication (hazard ratio, 1.12; 95% CI, 0.75-1.69). CONCLUSION: Positive conclusions (but not titles) were associated with a shorter time from study completion to publication. This finding may contribute to an overrepresentation of positive results in the imaging DTA literature.

Blinding practices during acute point-of-care ultrasound research: the BLIND-US meta-research study.

OBJECTIVES: Point-of-care ultrasound (POCUS) diagnostic accuracy research has significant variation in blinding practices. This study characterises the blinding practices during acute POCUS research to determine whether research methodology adequately reflects POCUS use in routine clinical practice. DESIGN, SETTINGS AND PARTICIPANTS: A search for POCUS diagnostic accuracy studies published in Emergency Medicine, Anaesthesia and Critical Care journals from January 2016 to January 2020 was performed. Studies were included if they were primary diagnostic accuracy studies. The study year, journal impact factor, population, hospital area, body region, study design, blinding of the POCUS interpreter to clinical information, whether the person performing the POCUS scan was the same person interpreting the scan, and whether the study reported incremental diagnostic yield were extracted in duplicate by two authors. Descriptive statistics were provided and prespecified subgroup analysis was performed. MAIN OUTCOME MEASURES: The primary outcome was the number of studies that blinded the POCUS interpreter to at least some part of the clinical information. Secondary outcomes included whether the person performing the POCUS scan was the same person interpreting it and whether the study reported incremental diagnostic yield. RESULTS: 520 abstracts were screened with 97 studies included. The POCUS interpreter was blinded to clinical information in 37 studies (38.1%), not blinded in 34 studies (35.1%) and not reported in 26 studies (26.8%). The POCUS interpreter was the same person obtaining the images in 72 studies (74.2%), different in 14 studies (14.4%) and not reported in 11 studies (11.3%). Only four studies (4.1%) reported incremental diagnostic yield for POCUS. Inter-rater reliability was moderate (k=0.64). Subgroup analysis based on impact factor, body region, hospital area, patient population and study design did not show significant differences after completing pairwise comparisons. CONCLUSIONS: Although blinding the POCUS interpreter to clinical information may be done in a perceived attempt to limit bias, this may result in accuracy estimates that do not reflect routine clinical practice. Similarly, having a different clinician perform and interpret the POCUS scan significantly limits generalisability to practice as it does not truly reflect 'point-of-care' ultrasound at all. Reporting incremental diagnostic yield from implementing POCUS into a diagnostic pathway better reflects the value of POCUS; however, this methodology was infrequently used. TRIAL REGISTRATION NUMBER: The study protocol was registered on Open Science Framework (https://osf.io/h5fe7/).

Thoracic imaging tests for the diagnosis of COVID-19.

BACKGROUND: The respiratory illness caused by SARS-CoV-2 infection continues to present diagnostic challenges. Early research showed thoracic (chest) imaging to be sensitive but not specific in the diagnosis of coronavirus disease 2019 (COVID-19). However, this is a rapidly developing field and these findings need to be re-evaluated in the light of new research. This is the first update of this 'living systematic review'. This update focuses on people suspected of having COVID-19 and excludes studies with only confirmed COVID-19 participants. OBJECTIVES: To evaluate the diagnostic accuracy of thoracic imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected COVID-19. SEARCH METHODS: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID-19 publications through to 22 June 2020. We did not apply any language restrictions. SELECTION CRITERIA: We included studies of all designs that recruited participants of any age group suspected to have COVID-19, and which reported estimates of test accuracy, or provided data from which estimates could be computed. When studies used a variety of reference standards, we retained the classification of participants as COVID-19 positive or negative as used in the study. DATA COLLECTION AND ANALYSIS: We screened studies, extracted data, and assessed the risk of bias and applicability concerns using the QUADAS-2 domain-list independently, in duplicate. We categorised included studies into three groups based on classification of index test results: studies that reported specific criteria for index test positivity (group 1); studies that did not report specific criteria, but had the test reader(s) explicitly classify the imaging test result as either COVID-19 positive or negative (group 2); and studies that reported an overview of index test findings, without explicitly classifying the imaging test as either COVID-19 positive or negative (group 3). We presented the results of estimated sensitivity and specificity using paired forest plots, and summarised in tables. We used a bivariate meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS: We included 34 studies: 30 were cross-sectional studies with 8491 participants suspected of COVID-19, of which 4575 (54%) had a final diagnosis of COVID-19; four were case-control studies with 848 cases and controls in total, of which 464 (55%) had a final diagnosis of COVID-19. Chest CT was evaluated in 31 studies (8014 participants, 4224 (53%) cases), chest X-ray in three studies (1243 participants, 784 (63%) cases), and ultrasound of the lungs in one study (100 participants, 31 (31%) cases). Twenty-six per cent (9/34) of all studies were available only as preprints. Nineteen studies were conducted in Asia, 10 in Europe, four in North America and one in Australia. Sixteen studies included only adults, 15 studies included both adults and children and one included only children. Two studies did not report the ages of participants. Twenty-four studies included inpatients, four studies included outpatients, while the remaining six studies were conducted in unclear settings. The majority of included studies had a high or unclear risk of bias with respect to participant selection, index test, reference standard, and participant flow. For chest CT in suspected COVID-19 participants (31 studies, 8014 participants, 4224 (53%) cases) the sensitivity ranged from 57.4% to 100%, and specificity ranged from 0% to 96.0%. The pooled sensitivity of chest CT in suspected COVID-19 participants was 89.9% (95% CI 85.7 to 92.9) and the pooled specificity was 61.1% (95% CI 42.3 to 77.1). Sensitivity analyses showed that when the studies from China were excluded, the studies from other countries demonstrated higher specificity compared to the overall included studies. When studies that did not classify index tests as positive or negative for COVID-19 (group 3) were excluded, the remaining studies (groups 1 and 2) demonstrated higher specificity compared to the overall included studies. Sensitivity analyses limited to cross-sectional studies, or studies where at least two reverse transcriptase polymerase chain reaction (RT-PCR) tests were conducted if the first was negative, did not substantively alter the accuracy estimates. We did not identify publication status as a source of heterogeneity. For chest X-ray in suspected COVID-19 participants (3 studies, 1243 participants, 784 (63%) cases) the sensitivity ranged from 56.9% to 89.0% and specificity from 11.1% to 88.9%. The sensitivity and specificity of ultrasound of the lungs in suspected COVID-19 participants (1 study, 100 participants, 31 (31%) cases) were 96.8% and 62.3%, respectively. We could not perform a meta-analysis for chest X-ray or ultrasound due to the limited number of included studies. AUTHORS' CONCLUSIONS: Our findings indicate that chest CT is sensitive and moderately specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may have limited capability in differentiating SARS-CoV-2 infection from other causes of respiratory illness. However, we are limited in our confidence in these results due to the poor study quality and the heterogeneity of included studies. Because of limited data, accuracy estimates of chest X-ray and ultrasound of the lungs for the diagnosis of suspected COVID-19 cases should be carefully interpreted. Future diagnostic accuracy studies should pre-define positive imaging findings, include direct comparisons of the various modalities of interest on the same participant population, and implement improved reporting practices. Planned updates of this review will aim to: increase precision around the accuracy estimates for chest CT (ideally with low risk of bias studies); obtain further data to inform accuracy of chest X-rays and ultrasound; and obtain data to further fulfil secondary objectives (e.g. 'threshold' effects, comparing accuracy estimates across different imaging modalities) to inform the utility of imaging along different diagnostic pathways.

Thoracic imaging tests for the diagnosis of COVID-19.

BACKGROUND: The diagnosis of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents major challenges. Reverse transcriptase polymerase chain reaction (RT-PCR) testing is used to diagnose a current infection, but its utility as a reference standard is constrained by sampling errors, limited sensitivity (71% to 98%), and dependence on the timing of specimen collection. Chest imaging tests are being used in the diagnosis of COVID-19 disease, or when RT-PCR testing is unavailable. OBJECTIVES: To determine the diagnostic accuracy of chest imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected or confirmed COVID-19. SEARCH METHODS: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, and The Stephen B. Thacker CDC Library. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 5 May 2020. SELECTION CRITERIA: We included studies of all designs that produce estimates of test accuracy or provide data from which estimates can be computed. We included two types of cross-sectional designs: a) where all patients suspected of the target condition enter the study through the same route and b) where it is not clear up front who has and who does not have the target condition, or where the patients with the target condition are recruited in a different way or from a different population from the patients without the target condition. When studies used a variety of reference standards, we included all of them. DATA COLLECTION AND ANALYSIS: We screened studies and extracted data independently, in duplicate. We also assessed the risk of bias and applicability concerns independently, in duplicate, using the QUADAS-2 checklist and presented the results of estimated sensitivity and specificity, using paired forest plots, and summarised in tables. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS: We included 84 studies, falling into two categories: studies with participants with confirmed diagnoses of COVID-19 at the time of recruitment (71 studies with 6331 participants) and studies with participants suspected of COVID-19 (13 studies with 1948 participants, including three case-control studies with 549 cases and controls). Chest CT was evaluated in 78 studies (8105 participants), chest X-ray in nine studies (682 COVID-19 cases), and chest ultrasound in two studies (32 COVID-19 cases). All evaluations of chest X-ray and ultrasound were conducted in studies with confirmed diagnoses only. Twenty-five per cent (21/84) of all studies were available only as preprints, 15/71 studies in the confirmed cases group and 6/13 of the studies in the suspected group. Among 71 studies that included confirmed cases, 41 studies had included symptomatic cases only, 25 studies had included cases regardless of their symptoms, five studies had included asymptomatic cases only, three of which included a combination of confirmed and suspected cases. Seventy studies were conducted in Asia, 2 in Europe, 2 in North America and one in South America. Fifty-one studies included inpatients while the remaining 24 studies were conducted in mixed or unclear settings. Risk of bias was high in most studies, mainly due to concerns about selection of participants and applicability. Among the 13 studies that included suspected cases, nine studies were conducted in Asia, and one in Europe. Seven studies included inpatients while the remaining three studies were conducted in mixed or unclear settings. In studies that included confirmed cases the pooled sensitivity of chest CT was 93.1% (95%CI: 90.2 - 95.0 (65 studies, 5759 cases); and for X-ray 82.1% (95%CI: 62.5 to 92.7 (9 studies, 682 cases). Heterogeneity judged by visual assessment of the ROC plots was considerable. Two studies evaluated the diagnostic accuracy of point-of-care ultrasound and both reported zero false negatives (with 10 and 22 participants having undergone ultrasound, respectively). These studies only reported True Positive and False Negative data, therefore it was not possible to pool and derive estimates of specificity. In studies that included suspected cases, the pooled sensitivity of CT was 86.2% (95%CI: 71.9 to 93.8 (13 studies, 2346 participants) and specificity was 18.1% (95%CI: 3.71 to 55.8). Heterogeneity judged by visual assessment of the forest plots was high. Chest CT may give approximately the same proportion of positive results for patients with and without a SARS-CoV-2 infection: the chances of getting a positive CT result are 86% (95% CI: 72 to 94) in patient with a SARS-CoV-2 infection and 82% (95% CI: 44 to 96) in patients without. AUTHORS' CONCLUSIONS: The uncertainty resulting from the poor study quality and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results. Our findings indicate that chest CT is sensitive but not specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may not be capable of differentiating SARS-CoV-2 infection from other causes of respiratory illness. This low specificity could also be the result of the poor sensitivity of the reference standard (RT-PCR), as CT could potentially be more sensitive than RT-PCR in some cases. Because of limited data, accuracy estimates of chest X-ray and ultrasound of the lungs for the diagnosis of COVID-19 should be carefully interpreted. Future diagnostic accuracy studies should avoid cases-only studies and pre-define positive imaging findings. Planned updates of this review will aim to: increase precision around the accuracy estimates for CT (ideally with low risk of bias studies); obtain further data to inform accuracy of chest X rays and ultrasound; and continue to search for studies that fulfil secondary objectives to inform the utility of imaging along different diagnostic pathways.

Breakthrough Hypersensitivity Reactions to Gadolinium-based Contrast Agents and Strategies to Decrease Subsequent Reaction Rates: A Systematic Review and Meta-Analysis.

Background Hypersensitivity reactions to gadolinium-based contrast agents (GBCAs) that occur despite corticosteroid premedication (breakthrough reactions) are not well understood. Purpose To determine the GBCA breakthrough reaction rate overall and according to GBCA class and to determine the effect of using an alternative GBCA or allergy skin testing on the risk of a breakthrough reaction. Materials and Methods In this systematic review and meta-analysis, MEDLINE (from 1946 to 2019), Embase (from 1947 to 2019), and the Cochrane Central Register of Controlled Trials (2019 only) were searched for patients with a breakthrough reaction to a GBCA who were undergoing repeat GBCA administration. Breakthrough reaction rates were determined with random-effects modeling and meta-regression. Secondary analyses of GBCA class, switching to an alternative GBCA, and allergy skin testing were assessed. Quality Assessment of Diagnostic Accuracy Studies 2 was used to determine risk of bias and applicability. Percentages are meta-regression results and do not directly reflect raw data. Results Of the 148 identified studies, 23 were included, encompassing 120 patients and 130 GBCA administrations. The overall breakthrough reaction rate was 39% (95% confidence interval [CI]: 30%, 49%; 37 of 103 administrations). Breakthrough reaction rates for macrocyclic (36%; 95% CI: 25%, 48%; 23 of 64 administrations) and protein-binding linear (31%; 95% CI: 1%, 94%; [one of seven administrations) GBCAs did not differ (P = .90). There were insufficient analyzable data for gadodiamide, gadoversetamide, and gadopentetate. Hypersensitivity reaction rate after switching GBCAs was 50% (95% CI: 21%, 79%; three of nine administrations) with and 71% (95% CI: 21%, 95%; four of five administrations) without corticosteroid premedication, which did not differ (P = .82 and P = .17, respectively) from the observed rate when using corticosteroid premedication and the same GBCA (36%; 95% CI: 26%, 48%; 37 of 84 administrations). Hypersensitivity reaction rate after allergy skin testing (17%; 95% CI: 7%, 29%; zero of 21 studies) did not differ when compared with use of the same agent with corticosteroid premedication (P = .10). Meta-analysis limitations were the small number of patients and the high risk of bias. Conclusion Patients with a prior hypersensitivity reaction to a gadolinium-based contrast agent (GBCA) often had breakthrough reactions. The effect of switching to an alternative GBCA or using allergy skin testing to decrease reaction risk lacked enough available data for meaningful comparisons. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Prince in this issue.

Overinterpretation of Research Findings: Evaluation of "Spin" in Systematic Reviews of Diagnostic Accuracy Studies in High-Impact Factor Journals.

BACKGROUND: To compare the frequency of "spin" in systematic reviews of diagnostic accuracy studies in high-impact journals with the frequency a previously assessed series of reviews. METHODS: Medline was searched from January 2010 to January 2019. Systematic reviews of diagnostic accuracy studies were included if they reported a meta-analysis and were published in a journal with an impact factor >5. Two investigators independently scored each included systematic review for positivity of conclusions and for actual and potential overinterpretation practices. RESULTS: Of 137 included systematic reviews, actual overinterpretation was present in ≥1 form in the abstract in 63 (46%) and in the full-text report in 52 (38%); 108 (79%) contained a form of potential overinterpretation. Compared with the previously assessed series (reviews published 2015-2016), reviews in this series were less likely to contain ≥1 form of actual overinterpretation in the abstract and full-text report or ≥1 form of potential overinterpretation (P < 0.001 for all comparisons). The significance of these comparisons did not persist for actual overinterpretation in sensitivity analysis in which Cochrane systematic reviews were removed. Reviews published in the Cochrane Database of Systematic Reviews were less likely to contain actual overinterpretation in the abstract or the full-text report than reviews in other high-impact journals (P < 0.001 for both comparisons). CONCLUSIONS: Reviews of diagnostic accuracy studies in high-impact journals are less likely to contain overinterpretation or spin. This difference is largely due to the reviews published in the Cochrane Database of Systematic Reviews, which contain spin less often than reviews published in other high-impact journals.

Adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) 2015 Guidelines in Acute Point-of-Care Ultrasound Research.

Importance: Incomplete reporting of diagnostic accuracy research impairs assessment of risk of bias and limits generalizability. Point-of-care ultrasound has become an important diagnostic tool for acute care physicians, but studies assessing its use are of varying methodological quality. Objective: To assess adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) 2015 guidelines in the literature on acute care point-of-care ultrasound. Evidence Review: MEDLINE was searched to identify diagnostic accuracy studies assessing point-of-care ultrasound published in critical care, emergency medicine, or anesthesia journals from 2016 to 2019. Studies were evaluated for adherence to the STARD 2015 guidelines, with the following variables analyzed: journal, country, STARD citation, STARD-adopting journal, impact factor, patient population, use of supplemental material, and body region. Data analysis was performed in November 2019. Findings: Seventy-four studies were included in this systematic review for assessment. Overall adherence to STARD was moderate, with 66% (mean [SD], 19.7 [2.9] of 30 items) of STARD items reported. Items pertaining to imaging specifications, patient population, and readers of the index test were frequently reported (>66% of studies). Items pertaining to blinding of readers to clinical data and to the index or reference standard, analysis of heterogeneity, indeterminate and missing data, and time intervals between index and reference test were either moderately (33%-66%) or infrequently (<33%) reported. Studies in STARD-adopting journals (mean [SD], 20.5 [2.9] items in adopting journals vs 18.6 [2.3] items in nonadopting journals; P = .002) and studies citing STARD (mean [SD], 21.3 [0.9] items in citing studies vs 19.5 [2.9] items in nonciting studies; P = .01) reported more items. Variation by country and journal of publication were identified. No differences in STARD adherence were identified by body region imaged (mean [SD], abdominal, 20.0 [2.5] items; head and neck, 17.8 [1.6] items; musculoskeletal, 19.2 [3.1] items; thoracic, 20.2 [2.8] items; and other or procedural, 19.8 [2.7] items; P = .29), study design (mean [SD], prospective, 19.7 [2.9] items; retrospective, 19.7 [1.8] items; P > .99), patient population (mean [SD], pediatric, 20.0 [3.1] items; adult, 20.2 [2.7] items; mixed, 17.9 [1.9] items; P = .09), use of supplementary materials (mean [SD], yes, 19.2 [3.0] items; no, 19.7 [2.8] items; P = .91), or journal impact factor (mean [SD], higher impact factor, 20.3 [3.1] items; lower impact factor, 19.1 [2.4] items; P = .08). Conclusions and Relevance: Overall, the literature on acute care point-of-care ultrasound showed moderate adherence to the STARD 2015 guidelines, with more complete reporting found in studies citing STARD and those published in STARD-adopting journals. This study has established a current baseline for reporting; however, future studies are required to understand barriers to complete reporting and to develop strategies to mitigate them.