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Research Synthesis Methods May 2021Comparative accuracy studies evaluate the relative performance of two or more diagnostic tests. As any other form of research, such studies should be reported in an... (Review)
Review
Comparative accuracy studies evaluate the relative performance of two or more diagnostic tests. As any other form of research, such studies should be reported in an informative manner, to allow replication and to be useful for decision-making. In this study we aimed to assess whether and how components of test comparisons were reported in comparative accuracy studies. We evaluated 100 comparative accuracy studies, published in 2015, 2016 or 2017, randomly sampled from 238 comparative accuracy systematic reviews. We extracted information on 20 reporting items, pertaining to the identification of the test comparison, its validity, and the actual results of the comparison. About a third of the studies (n = 36) did not report the comparison as a study objective or hypothesis. Although most studies (n = 86) reported how participants had been allocated to index tests, we could often not evaluate whether test interpreters had been blinded to the results of other index tests (n = 40; among 59 applicable studies), nor could we identify the sequence of index tests (n = 52; among 90 applicable studies) or the methods for comparing measures of accuracy (n = 59). Two-by-four table data (revealing the agreement between index tests) were only reported by 9 of 90 paired comparative studies. More than half of the studies (n = 64) did not provide measures of statistical imprecision for comparative accuracy. Our findings suggest that components of test comparisons are frequently missing or incompletely described in comparative accuracy studies included in systematic reviews. Explicit guidance for reporting comparative accuracy studies may facilitate the production of full and informative study reports.
Topics: Diagnostic Tests, Routine; Humans; Systematic Reviews as Topic
PubMed: 33217225
DOI: 10.1002/jrsm.1469 -
Clinical Microbiology and Infection :... Jun 2020Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management... (Review)
Review
BACKGROUND
Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management guidelines agree on the need for CSF molecular testing in combination with other direct and indirect biological testing, both in CSF and blood. Multiplex molecular tests have been developed to reduce turnaround times and facilitate the diagnostic approach.
OBJECTIVES
We aim to discuss the role of multiplex molecular panels in the management of CNS infections.
SOURCES
The MEDLINE database and the grey literature have been searched for relevant articles.
CONTENT
New molecular multiplex panels are being developed to simultaneously detect a large array of neuropathogens in CSF. Although one of these assays has been US Food and Drug Administration-approved, extensive analytical and clinical validation is still missing, and suboptimal performance related issues have been raised. Its use has been associated with decreased costs, reduced length of hospital stay and reduced antiviral therapy administration in retrospective, industry-sponsored studies. The pros and cons of this multiplex syndromic approach are discussed in this narrative review.
IMPLICATIONS
Molecular multiplex CNS infection diagnosis panels have been developed and present several attractive features, including ease of use and low turnaround time. However, suboptimal analytical performances render these tests difficult to use without additional confirmatory tests. Such panels are not comprehensive nor adapted to all situations, depending on the epidemiological or clinical context. Overall, available data in the literature currently do not support the use of a multiplex PCR panel in clinical routine as a 'stand-alone' molecular assay. Except in restricted laboratory capacity settings where such easy-to-use multiplex panels offer the diagnostic means that would otherwise not be available, the stepwise testing approach remains a more rational option. Serological testing both in blood and CSF should not be neglected, but it represents essential complementary tools regarding some neuropathogens.
Topics: Central Nervous System Infections; Diagnostic Tests, Routine; Encephalitis; Humans; Meningitis; Molecular Diagnostic Techniques; Retrospective Studies
PubMed: 31899336
DOI: 10.1016/j.cmi.2019.12.013 -
Statistics in Medicine Jul 2022The development of a new diagnostic test ideally follows a sequence of stages which, among other aims, evaluate technical performance. This includes an analytical...
The development of a new diagnostic test ideally follows a sequence of stages which, among other aims, evaluate technical performance. This includes an analytical validity study, a diagnostic accuracy study, and an interventional clinical utility study. In this article, we propose a novel Bayesian approach to sample size determination for the diagnostic accuracy study, which takes advantage of information available from the analytical validity stage. We utilize assurance to calculate the required sample size based on the target width of a posterior probability interval and can choose to use or disregard the data from the analytical validity study when subsequently inferring measures of test accuracy. Sensitivity analyses are performed to assess the robustness of the proposed sample size to the choice of prior, and prior-data conflict is evaluated by comparing the data to the prior predictive distributions. We illustrate the proposed approach using a motivating real-life application involving a diagnostic test for ventilator associated pneumonia. Finally, we compare the properties of the approach against commonly used alternatives. The results show that, when suitable prior information is available, the assurance-based approach can reduce the required sample size when compared to alternative approaches.
Topics: Bayes Theorem; Diagnostic Tests, Routine; Humans; Reproducibility of Results; Sample Size
PubMed: 35403239
DOI: 10.1002/sim.9393 -
Trends in Molecular Medicine Dec 2020Children suffering from infectious diseases, both bacterial and viral, are often treated with empirical antibiotics. Keeping in mind both the menace of microorganisms... (Review)
Review
Children suffering from infectious diseases, both bacterial and viral, are often treated with empirical antibiotics. Keeping in mind both the menace of microorganisms and antibiotic toxicity, it is imperative to develop point-of-care testing (POCT) to discriminate bacterial from viral infections, and to define indications for antibiotic treatment. This article reviews potential protein biomarkers and host-derived gene expression signatures for differentiating between bacterial and viral infections in children, and focuses on emerging multiplex POCT devices for the simultaneous detection of sets of protein biomarkers or streamlined gene expression signatures that may provide rapid and cost-effective pathogen-discriminating tools.
Topics: Age Factors; Bacterial Infections; Biomarkers; Child; Diagnosis, Differential; Diagnostic Tests, Routine; Host-Pathogen Interactions; Humans; Point-of-Care Testing; Virus Diseases
PubMed: 33008730
DOI: 10.1016/j.molmed.2020.09.004 -
Journal of Clinical Virology : the... Aug 2021In 2018, a bi-partisan proposed draft legislation called the Verifying Accurate, Leading-edge IVCT Development (VALID) Act was released by Representative Larry Bucshon... (Review)
Review
In 2018, a bi-partisan proposed draft legislation called the Verifying Accurate, Leading-edge IVCT Development (VALID) Act was released by Representative Larry Bucshon (Republican-Indiana) and Diana DeGette, (Democrat-Colorado). The VALID Act attempts to create a new framework for the oversight and regulations of both laboratory-developed testing procedures (commonly known as laboratory-developed tests) and In vitro diagnostic tests by the U.S. Food and Drug Administration. The potential impact of this new law if passed may be significant for clinical laboratories in terms of diagnostic test development and implementation. In this report, we review the background and key information that every clinical virologist should know about the VALID Act.
Topics: Clinical Laboratory Services; Colorado; Diagnostic Tests, Routine; Humans; Laboratories; United States; United States Food and Drug Administration
PubMed: 34243115
DOI: 10.1016/j.jcv.2021.104875 -
American Journal of Obstetrics &... Jan 2022
Topics: COVID-19; Diagnostic Tests, Routine; Humans; RNA, Viral; SARS-CoV-2
PubMed: 34656735
DOI: 10.1016/j.ajogmf.2021.100514 -
The Journal of Thoracic and... Jun 2020
Topics: Diagnostic Tests, Routine; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac
PubMed: 31471083
DOI: 10.1016/j.jtcvs.2019.07.041 -
Turkish Journal of Haematology :... Nov 2019Thrombotic microangiopathies (TMAs) are multiple disease entities with different etiopathogeneses, characterized by thrombocytopenia, microangiopathic hemolytic anemia... (Review)
Review
Thrombotic microangiopathies (TMAs) are multiple disease entities with different etiopathogeneses, characterized by thrombocytopenia, microangiopathic hemolytic anemia (MAHA) with schistocytosis, variable symptoms including fever, and multi-organ failure such as mild renal impairment and neurological deficits. The two paradigms of TMAs are represented on one hand by acquired thrombotic thrombocytopenic purpura (TTP) and on the other by hemolytic uremic syndrome (HUS). The differential diagnosis between these two paradigmatic forms of TMA is based on the presence of either frank renal failure in HUS or a severe deficiency (<10%) of the zinc-protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in TTP. ADAMTS13 is an enzyme involved in the proteolytic processing of von Willebrand factor (vWF), and its deficiency results in formation of high-molecular-weight vWF-rich microthrombi in the environment of the microvasculature. The presence of these ultra-large vWF multimers in the microcirculation can recruit platelets, promoting multi-organ ischemic lesions. The presence of ADAMTS13 activity at >10% could rule out the presence of a TTP form. However, it is often difficult to differentiate either a TTP or HUS clinical scenario presenting with typical symptoms of TMA. There are in fact several additional diagnoses that should be considered in patients with ADAMTS13 activity of >10%. Widespread inflammation with endothelial damage and adverse reactions to drugs play a central role in the pathogenesis of several forms of TMA, and in these cases, the differential diagnosis should be directed at the underlying disease. Hence, a correct etiologic diagnosis of TMA should involve a critical illness, cancer-associated TMA, drug-induced TMA, and hematopoietic transplant-associated TMA. A complete assessment of all the possible etiologies for TMA symptoms, including acquired or congenital TTP, will allow for a more accurate diagnosis and application of a more appropriate treatment.
Topics: Diagnostic Tests, Routine; Humans; Thrombotic Microangiopathies
PubMed: 31337190
DOI: 10.4274/tjh.galenos.2019.2019.0165 -
Emergency Medicine Journal : EMJ Jul 2019In this two-part series on sources of bias in studies of diagnostic test performance, we outline common errors and optimal conditions during three study phases: patient...
In this two-part series on sources of bias in studies of diagnostic test performance, we outline common errors and optimal conditions during three study phases: patient selection, interpretation of the index test and disease verification by a gold standard. Here in part 1, biases associated with suboptimal participant selection are discussed through the lens of partial verification bias and spectrum bias, both of which increase the proportion of participants who are the 'sickest of the sick' or the 'wellest of the well.' Especially through retrospective methodology, partial verification introduces bias by including patients who are test positive by a gold standard, since patients with a positive index test are more likely to go on to further gold standard testing. Spectrum bias is frequently introduced through case-control design, dropping of indeterminate results or convenience sampling. After reading part 1, the informed clinician should be better able to judge the quality of a diagnostic test study, its inherent limitations and whether its results could be generalisable to their practice. Part 2 will describe how interpretation of the index test and disease verification by a gold standard can contribute to diagnostic test bias.
Topics: Bias; Diagnostic Tests, Routine; Humans; Patient Selection; Research Design; Retrospective Studies
PubMed: 31302605
DOI: 10.1136/emermed-2019-208446 -
Clinical Microbiology and Infection :... Feb 2021Rapid diagnostic tests (RDTs) for infectious diseases, with a turnaround time of less than 2 hours, are promising tools that could improve patient care, antimicrobial... (Review)
Review
BACKGROUND
Rapid diagnostic tests (RDTs) for infectious diseases, with a turnaround time of less than 2 hours, are promising tools that could improve patient care, antimicrobial stewardship and infection prevention in the emergency department (ED) setting. Numerous RDTs have been developed, although not necessarily for the ED environment. Their successful implementation in the ED relies on their performance and impact on patient management.
OBJECTIVES
The aim of this narrative review was to provide an overview of currently available RDTs for infectious diseases in the ED.
SOURCES
PubMed was searched through August 2019 for available studies on RDTs for infectious diseases. Inclusion criteria included: commercial tests approved by the US Food and Drug Administration (FDA) or Conformité Européenne (CE) in vitro diagnostic devices with data on clinical samples, ability to run on fully automated systems and result delivery within 2 hours.
CONTENT
A nonexhaustive list of representative commercially available FDA- or CE-approved assays was categorized by clinical syndrome: pharyngitis and upper respiratory tract infection, lower respiratory tract infection, gastrointestinal infection, meningitis and encephalitis, fever in returning travellers and sexually transmitted infection, including HIV. The performance of tests was described on the basis of clinical validation studies. Further, their impact on clinical outcomes and anti-infective use was discussed with a focus on ED-based studies.
IMPLICATIONS
Clinicians should be familiar with the distinctive features of each RDT and individual performance characteristics for each target. Their integration into ED work flow should be preplanned considering local constraints of given settings. Additional clinical studies are needed to further evaluate their clinical effectiveness and cost-effectiveness.
Topics: Automation, Laboratory; Communicable Diseases; Diagnostic Test Approval; Diagnostic Tests, Routine; Emergency Service, Hospital; Europe; Humans; Reagent Kits, Diagnostic; United States; United States Food and Drug Administration
PubMed: 32120036
DOI: 10.1016/j.cmi.2020.02.024