Timely diagnosis of influenza can help clinical management.
To examine the accuracy of rapid influenza diagnostic tests (RIDTs) in adults and children with influenza-like illness and evaluate factors ...associated with higher accuracy.
PubMed and EMBASE through December 2011; BIOSIS and Web of Science through March 2010; and citations of articles, guidelines, reviews, and manufacturers.
Studies that compared RIDTs with a reference standard of either reverse transcriptase polymerase chain reaction (first choice) or viral culture.
Reviewers abstracted study data by using a standardized form and assessed quality by using Quality Assessment of Diagnostic Accuracy Studies criteria.
159 studies evaluated 26 RIDTs, and 35% were conducted during the H1N1 pandemic. Failure to report whether results were assessed in a blinded manner and the basis for patient recruitment were important quality concerns. The pooled sensitivity and specificity were 62.3% (95% CI, 57.9% to 66.6%) and 98.2% (CI, 97.5% to 98.7%), respectively. The positive and negative likelihood ratios were 34.5 (CI, 23.8 to 45.2) and 0.38 (CI, 0.34 to 0.43), respectively. Sensitivity estimates were highly heterogeneous, which was partially explained by lower sensitivity in adults (53.9% CI, 47.9% to 59.8%) than in children (66.6% CI, 61.6% to 71.7%) and a higher sensitivity for influenza A (64.6% CI, 59.0% to 70.1%) than for influenza B (52.2% CI, 45.0% to 59.3%).
Incomplete reporting limited the ability to assess the effect of important factors, such as specimen type and duration of influenza symptoms, on diagnostic accuracy.
Influenza can be ruled in but not ruled out through the use of RIDTs. Sensitivity varies across populations, but it is higher in children than in adults and for influenza A than for influenza B.
Canadian Institutes of Health Research.
In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was ...developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
Systematic reviews of diagnostic test accuracy Leeflang, Mariska M G; Deeks, Jonathan J; Gatsonis, Constantine ...
Annals of internal medicine,
12/2008, Volume:
149, Issue:
12
Journal Article
Peer reviewed
Open access
More and more systematic reviews of diagnostic test accuracy studies are being published, but they can be methodologically challenging. In this paper, the authors present some of the recent ...developments in the methodology for conducting systematic reviews of diagnostic test accuracy studies. Restrictive electronic search filters are discouraged, as is the use of summary quality scores. Methods for meta-analysis should take into account the paired nature of the estimates and their dependence on threshold. Authors of these reviews are advised to use the hierarchical summary receiver-operating characteristic or the bivariate model for the data analysis. Challenges that remain are the poor reporting of original diagnostic test accuracy studies and difficulties with the interpretation of the results of diagnostic test accuracy research.
Systematic reviews that "compare" the accuracy of 2 or more tests often include different sets of studies for each test.
To investigate the availability of direct comparative studies of test accuracy ...and to assess whether summary estimates of accuracy differ between meta-analyses of noncomparative and comparative studies.
Systematic reviews in any language from the Database of Abstracts of Reviews of Effects and the Cochrane Database of Systematic Reviews from 1994 to October 2012.
1 of 2 assessors selected reviews that evaluated at least 2 tests and identified meta-analyses that included both noncomparative studies and comparative studies.
1 of 3 assessors extracted data about review and study characteristics and test performance.
248 reviews compared test accuracy; of the 6915 studies, 2113 (31%) were comparative. Thirty-six reviews (with 52 meta-analyses) had adequate studies to compare results of noncomparative and comparative studies by using a hierarchical summary receiver-operating characteristic meta-regression model for each test comparison. In 10 meta-analyses, noncomparative studies ranked tests in the opposite order of comparative studies. A total of 25 meta-analyses showed more than a 2-fold discrepancy in the relative diagnostic odds ratio between noncomparative and comparative studies. Differences in accuracy estimates between noncomparative and comparative studies were greater than expected by chance (P < 0.001).
A paucity of comparative studies limited exploration of direction in bias.
Evidence derived from noncomparative studies often differs from that derived from comparative studies. Robustly designed studies in which all patients receive all tests or are randomly assigned to receive one or other of the tests should be more routinely undertaken and are preferred for evidence to guide test selection.
National Institute for Health Research (United Kingdom).
Systematic reviews of diagnostic test accuracy synthesize data from primary diagnostic studies that have evaluated the accuracy of 1 or more index tests against a reference standard, provide ...estimates of test performance, allow comparisons of the accuracy of different tests, and facilitate the identification of sources of variability in test accuracy.
To develop the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagnostic test accuracy guideline as a stand-alone extension of the PRISMA statement. Modifications to the PRISMA statement reflect the specific requirements for reporting of systematic reviews and meta-analyses of diagnostic test accuracy studies and the abstracts for these reviews.
Established standards from the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network were followed for the development of the guideline. The original PRISMA statement was used as a framework on which to modify and add items. A group of 24 multidisciplinary experts used a systematic review of articles on existing reporting guidelines and methods, a 3-round Delphi process, a consensus meeting, pilot testing, and iterative refinement to develop the PRISMA diagnostic test accuracy guideline. The final version of the PRISMA diagnostic test accuracy guideline checklist was approved by the group.
The systematic review (produced 64 items) and the Delphi process (provided feedback on 7 proposed items; 1 item was later split into 2 items) identified 71 potentially relevant items for consideration. The Delphi process reduced these to 60 items that were discussed at the consensus meeting. Following the meeting, pilot testing and iterative feedback were used to generate the 27-item PRISMA diagnostic test accuracy checklist. To reflect specific or optimal contemporary systematic review methods for diagnostic test accuracy, 8 of the 27 original PRISMA items were left unchanged, 17 were modified, 2 were added, and 2 were omitted.
The 27-item PRISMA diagnostic test accuracy checklist provides specific guidance for reporting of systematic reviews. The PRISMA diagnostic test accuracy guideline can facilitate the transparent reporting of reviews, and may assist in the evaluation of validity and applicability, enhance replicability of reviews, and make the results from systematic reviews of diagnostic test accuracy studies more useful.
Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require ...intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing.
To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia.
On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions.
Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19.
Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias.
We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present. Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies. We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups.
The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify or ...rule out current infection, identify people in need of care escalation, or to test for past infection and immune response. Point-of-care antigen and molecular tests to detect current SARS-CoV-2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to laboratory-based diagnostic methods, with the aim of reducing household and community transmission.
To assess the diagnostic accuracy of point-of-care antigen and molecular-based tests to determine if a person presenting in the community or in primary or secondary care has current SARS-CoV-2 infection.
On 25 May 2020 we undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions.
We included studies of people with suspected current SARS-CoV-2 infection, known to have, or not to have SARS-CoV-2 infection, or where tests were used to screen for infection. We included test accuracy studies of any design that evaluated antigen or molecular tests suitable for a point-of-care setting (minimal equipment, sample preparation, and biosafety requirements, with results available within two hours of sample collection). We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction (RT-PCR) tests and established clinical diagnostic criteria).
Two review authors independently screened studies and resolved any disagreements by discussion with a third review author. One review author independently extracted study characteristics, which were checked by a second review author. Two review authors independently extracted 2x2 contingency table data and assessed risk of bias and applicability of the studies using the QUADAS-2 tool. We present sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots. We pooled data using the bivariate hierarchical model separately for antigen and molecular-based tests, with simplifications when few studies were available. We tabulated available data by test manufacturer.
We included 22 publications reporting on a total of 18 study cohorts with 3198 unique samples, of which 1775 had confirmed SARS-CoV-2 infection. Ten studies took place in North America, two in South America, four in Europe, one in China and one was conducted internationally. We identified data for eight commercial tests (four antigen and four molecular) and one in-house antigen test. Five of the studies included were only available as preprints. We did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies. We judged patient selection to be at high risk of bias in 50% of the studies because of deliberate over-sampling of samples with confirmed COVID-19 infection and unclear in seven out of 18 studies because of poor reporting. Sixteen (89%) studies used only a single, negative RT-PCR to confirm the absence of COVID-19 infection, risking missing infection. There was a lack of information on blinding of index test (n = 11), and around participant exclusions from analyses (n = 10). We did not observe differences in methodological quality between antigen and molecular test evaluations. Antigen tests Sensitivity varied considerably across studies (from 0% to 94%): the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%; based on 8 evaluations in 5 studies on 943 samples). Data for individual antigen tests were limited with no more than two studies for any test. Rapid molecular assays Sensitivity showed less variation compared to antigen tests (from 68% to 100%), average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%) based on 13 evaluations in 11 studies of on 2255 samples. Predicted values based on a hypothetical cohort of 1000 people with suspected COVID-19 infection (with a prevalence of 10%) result in 105 positive test results including 10 false positives (positive predictive value 90%), and 895 negative results including 5 false negatives (negative predictive value 99%). Individual tests We calculated pooled results of individual tests for ID NOW (Abbott Laboratories) (5 evaluations) and Xpert Xpress (Cepheid Inc) (6 evaluations). Summary sensitivity for the Xpert Xpress assay (99.4%, 95% CI 98.0% to 99.8%) was 22.6 (95% CI 18.8 to 26.3) percentage points higher than that of ID NOW (76.8%, (95% CI 72.9% to 80.3%), whilst the specificity of Xpert Xpress (96.8%, 95% CI 90.6% to 99.0%) was marginally lower than ID NOW (99.6%, 95% CI 98.4% to 99.9%; a difference of -2.8% (95% CI -6.4 to 0.8)) AUTHORS' CONCLUSIONS: This review identifies early-stage evaluations of point-of-care tests for detecting SARS-CoV-2 infection, largely based on remnant laboratory samples. The findings currently have limited applicability, as we are uncertain whether tests will perform in the same way in clinical practice, and according to symptoms of COVID-19, duration of symptoms, or in asymptomatic people. Rapid tests have the potential to be used to inform triage of RT-PCR use, allowing earlier detection of those testing positive, but the evidence currently is not strong enough to determine how useful they are in clinical practice. Prospective and comparative evaluations of rapid tests for COVID-19 infection in clinically relevant settings are urgently needed. Studies should recruit consecutive series of eligible participants, including both those presenting for testing due to symptoms and asymptomatic people who may have come into contact with confirmed cases. Studies should clearly describe symptomatic status and document time from symptom onset or time since exposure. Point-of-care tests must be conducted on samples according to manufacturer instructions for use and be conducted at the point of care. Any future research study report should conform to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline.
Compression ultrasonography (CUS) is the first-line imaging test in the diagnostic management of suspected deep vein thrombosis (DVT) of the lower extremity. Three CUS strategies are used in clinical ...practice. However, their relative diagnostic accuracy is uncertain.
This systematic review and meta-analysis aimed to summarize and compare the diagnostic accuracy of single limited, serial limited, and whole-leg CUS for DVT.
MEDLINE, Embase, and CENTRAL were searched from January 1st, 1989 to July 23rd, 2019 for studies assessing at least one of the CUS strategies in adults with suspected DVT of the lower extremity, using clinical follow-up for venous thromboembolism or contrast venography as the reference standard. Study selection, data extraction, and risk of bias assessment were performed in duplicate by independent authors. A bivariate random-effects model was used to compute diagnostic accuracy summary estimates.
Forty studies (n = 21,250) were included. The venous thromboembolic event rate after a negative CUS (failure rate) of single limited (1.4%; 95% CI, 0.83-2.5), serial limited (1.9%; 95% CI, 1.4-2.5), and whole-leg CUS (1.0%; 95% CI, 0.6-1.6) did not differ significantly. The proportion of positive results was lower with single limited CUS, as was DVT prevalence in this group.
The failure rates of single limited, serial limited, and whole-leg CUS for DVT appeared to be quite comparable. The relative failure rate of single limited CUS remains uncertain, as the DVT prevalence was lower in these studies. Therefore, this CUS strategy may only be safe in a selected group of low-risk patients. Preference for one of the strategies may be based on pretest probability assessment, feasibility, expertise, and perceived clinical relevance of isolated distal DVT.
COVID-19 has been arguably the most important public health concern worldwide in 2020, and efforts are now escalating to suppress or eliminate its spread. In this study we undertook a meta-analysis ...to estimate the global and regional seroprevalence rates in humans of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to assess whether seroprevalence is associated with geographical, climatic and/or sociodemographic factors.
We systematically reviewed PubMed, Scopus, Embase, medRxiv and bioRxiv databases for preprints or peer-reviewed articles (up to 14 August 2020). Study eligibility criteria were population-based studies describing the prevalence of anti-SARS-CoV-2 (IgG and/or IgM) serum antibodies. Participants were people from different socioeconomic and ethnic backgrounds (from the general population), whose prior COVID-19 status was unknown and who were tested for the presence of anti-SARS-CoV-2 serum antibodies. We used a random-effects model to estimate pooled seroprevalence, and then extrapolated the findings to the global population (for 2020). Subgroup and meta-regression analyses explored potential sources of heterogeneity in the data, and relationships between seroprevalence and sociodemographic, geographical and/or climatic factors.
In total, 47 studies involving 399 265 people from 23 countries met the inclusion criteria. Heterogeneity (I2 = 99.4%, p < 0.001) was seen among studies; SARS-CoV-2 seroprevalence in the general population varied from 0.37% to 22.1%, with a pooled estimate of 3.38% (95%CI 3.05–3.72%; 15 879/399 265). On a regional level, seroprevalence varied from 1.45% (0.95–1.94%, South America) to 5.27% (3.97–6.57%, Northern Europe), although some variation appeared to relate to the serological assay used. The findings suggested an association of seroprevalence with income levels, human development indices, geographic latitudes and/or climate. Extrapolating to the 2020 world population, we estimated that 263.5 million individuals had been exposed or infected at the time of this study.
This study showed that SARS-CoV-2 seroprevalence varied markedly among geographic regions, as might be expected early in a pandemic. Longitudinal surveys to continually monitor seroprevalence around the globe will be critical to support prevention and control efforts, and might indicate levels of endemic stability or instability in particular countries and regions.
Invasive aspergillosis is the most common life-threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither be too invasive nor too great ...a burden for the already weakened patient. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) seems to have the potential to meet both requirements.
To obtain summary estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of invasive aspergillosis.
We searched MEDLINE, EMBASE and Web of Science with both MeSH terms and text words for both aspergillosis and the sandwich ELISA. We checked the reference lists of included studies and review articles for additional studies. We conducted the searches in February 2014.
We included cross-sectional studies, case-control designs and consecutive series of patients assessing the diagnostic accuracy of galactomannan detection for the diagnosis of invasive aspergillosis in patients with neutropenia or patients whose neutrophils are functionally compromised. The reference standard was composed of the criteria given by the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG).
Two review authors independently assessed quality and extracted data. We carried out meta-analysis using the bivariate method. We investigated sources of heterogeneity by adding potential sources of heterogeneity to the model as covariates.
We included 54 studies in the review (50 in the meta-analyses), containing 5660 patients, of whom 586 had proven or probable invasive aspergillosis. When using an optical density index (ODI) of 0.5 as a cut-off value, the sensitivity of the test was 82% (73% to 90%) and the specificity was 81% (72% to 90%). At a cut-off value of 1.0 ODI, the sensitivity was 72% (65% to 80%) and the specificity was 88% (84% to 92%). At a cut-off value of 1.5 ODI, the sensitivity was 61% (47% to 75%) and the specificity was 93% (89% to 97%). None of the potential sources of heterogeneity had a statistically significant effect on either sensitivity or specificity.
If we used the test at a cut-off value of 0.5 ODI in a population of 100 patients with a disease prevalence of 9% (overall median prevalence), two patients who have invasive aspergillosis would be missed (sensitivity 82%, 18% false negatives), and 17 patients would be treated unnecessarily or referred unnecessarily for further testing (specificity 81%, 19% false negatives). If we used the test at a cut-off value of 1.5 in the same population, that would mean that four invasive aspergillosis patients would be missed (sensitivity 61%, 39% false negatives), and six patients would be treated or referred for further testing unnecessarily (specificity 93%, 7% false negatives). These numbers should, however, be interpreted with caution because the results were very heterogeneous.
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