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The Journal of Applied Laboratory... Sep 2020Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly expanding number of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease.
CONTENT
PubMed (Medline), Scopus, and Web of Science were searched until March 22, 2020, for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesized, and we conducted random-effects meta-analysis, and determined mean difference (MD) and standard mean difference at the biomarker level for disease severity. Risk of bias and applicability concerns were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2.
SUMMARY
45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD, 1.28 ×109/L), neutrophil count (MD, 1.49 ×109/L), C-reactive protein (MD, 49.2 mg/L), lactate dehydrogenase (MD, 196 U/L), D-dimer (standardized MD, 0.58), and aspartate aminotransferase (MD, 8.5 U/L); all p < 0.001. Furthermore, low lymphocyte count (MD -0.32 × 109/L), platelet count (MD -22.4 × 109/L), and hemoglobin (MD, -4.1 g/L); all p < 0.001 were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.
Topics: Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Diagnostic Tests, Routine; Humans; Outcome Assessment, Health Care; Pandemics; Patient Selection; Pneumonia, Viral; Reference Standards; SARS-CoV-2
PubMed: 32573713
DOI: 10.1093/jalm/jfaa098 -
Journal of Medical Virology Dec 2021To control the spread of the coronavirus disease 2019 (COVID-19) epidemics, it is necessary to have easy-to-use, reliable diagnostic tests available. The nasopharyngeal...
To control the spread of the coronavirus disease 2019 (COVID-19) epidemics, it is necessary to have easy-to-use, reliable diagnostic tests available. The nasopharyngeal sampling method being often uncomfortable, nasal sampling could prove to be a viable alternative to the reference sampling method. We performed a multicentre, prospective validation study of the COVID-VIRO® test, using a nasal swab sampling method, in a point-of-care setting. In addition, we performed a multicentre, prospective, and usability study to validate the use of the rapid antigen nasal diagnostic test by laypersons. In March 2021, 239 asymptomatic and symptomatic patients were included in the validation study. Compared with reverse-transcription polymerase chain reaction on nasopharyngeal samples, the sensitivity and specificity of the COVID-VIRO® Antigen test combined with a nasal sampling method were evaluated as 96.88% and 100%, respectively. A total of 101 individuals were included in the usability study. Among these, 99% of the participants rated the instructions material as good, 98% of the subjects executed the test procedure well, and 98% of the participants were able to correctly interpret the test results. This study validates the relevance of COVID-VIRO® as a diagnostic tool from nasal specimens as well as its usability in the general population. COVID-VIRO® diagnostic performances and ease of use make it suitable for widespread utilization.
Topics: Adult; Antigens, Viral; COVID-19 Testing; Diagnostic Tests, Routine; Humans; Male; Point-of-Care Testing; Prospective Studies; SARS-CoV-2; Self-Testing; Sensitivity and Specificity
PubMed: 34331707
DOI: 10.1002/jmv.27249 -
Analytical Methods : Advancing Methods... Jan 2021Infections and sepsis represent a growing global burden. There is a widespread clinical need for a rapid, high-throughput and sensitive technique for the diagnosis of... (Review)
Review
Infections and sepsis represent a growing global burden. There is a widespread clinical need for a rapid, high-throughput and sensitive technique for the diagnosis of infections and detection of invading pathogens and the presence of sepsis. Current diagnostic methods primarily consist of laboratory-based haematology, biochemistry and microbiology that are time consuming, labour- and resource-intensive, and prone to both false positive and false negative results. Current methods are insufficient for the increasing demands on healthcare systems, causing delays in diagnosis and initiation of treatment, due to the intrinsic time delay in sample preparation, measurement, and analysis. Vibrational spectroscopic techniques can overcome these limitations by providing a rapid, label-free and low-cost method for blood analysis, with limited sample preparation required, potentially revolutionising clinical diagnostics by producing actionable results that enable early diagnosis, leading to improved patient outcomes. This review will discuss the challenges associated with the diagnosis of infections and sepsis, primarily within the UK healthcare system. We will consider the clinical potential of spectroscopic point-of-care technologies to enable blood analysis in the primary-care setting.
Topics: Diagnostic Tests, Routine; Humans; Point-of-Care Systems; Sepsis
PubMed: 33284291
DOI: 10.1039/d0ay01991g -
Annals of Emergency Medicine Jun 2020
Review
Topics: Alberta; Awareness; Clinical Decision-Making; Diagnostic Tests, Routine; Electronic Health Records; Emergency Medicine; History, 19th Century; Humans; Medical Overuse; Patient Safety; Patient Satisfaction; Physicians; Practice Patterns, Physicians'; Triage; Uncertainty
PubMed: 31874767
DOI: 10.1016/j.annemergmed.2019.10.015 -
Journal of Clinical Epidemiology Apr 2021This study outlines the development of a new method (split component synthesis; SCS) for meta-analysis of diagnostic accuracy studies and assesses its performance...
OBJECTIVES
This study outlines the development of a new method (split component synthesis; SCS) for meta-analysis of diagnostic accuracy studies and assesses its performance against the commonly used bivariate random effects model.
METHODS
The SCS method summarizes the study-specific diagnostic odds ratio (on the ln(DOR) scale), which mainly reflects test discrimination rather than threshold effects, and then splits the summary ln(DOR) into its component parts, logit sensitivity (Se) and logit specificity (Sp). Performance of SCS estimator was assessed through simulation and compared against the bivariate random effects model estimator in terms of bias, mean squared error (MSE), and coverage probability across varying degrees of between-studies heterogeneity.
RESULTS
The SCS estimator for the DOR, Se, and Sp was less biased and had smaller MSE than the bivariate model estimator. Despite the wider width of the 95% confidence intervals under the bivariate model, the latter had a poorer coverage probability than that under the SCS method.
CONCLUSION
The SCS estimator outperforms the bivariate model estimator and thus represents an improvement in the approach to diagnostic meta-analyses. The SCS method is available to researchers through the diagma module in Stata and the SCSmeta function in R.
Topics: Clinical Trials as Topic; Computer Simulation; Data Accuracy; Diagnostic Tests, Routine; Humans; Meta-Analysis as Topic; Research Design; Sensitivity and Specificity
PubMed: 33333166
DOI: 10.1016/j.jclinepi.2020.12.015 -
Frontiers in Immunology 2021Dating to the discovery of the Lupus Erythematosus (LE) cell in 1948, there has been a dramatic growth in the discovery of unique autoantibodies and their cognate... (Review)
Review
Dating to the discovery of the Lupus Erythematosus (LE) cell in 1948, there has been a dramatic growth in the discovery of unique autoantibodies and their cognate targets, all of which has led to the availability and use of autoantibody testing for a broad spectrum of autoimmune diseases. Most studies of the sensitivity, specificity, commutability, and harmonization of autoantibody testing have focused on widely available, commercially developed and agency-certified autoantibody kits. However, this is only a small part of the spectrum of autoantibody tests that are provided through laboratories world-wide. This manuscript will review the wider spectrum of testing by exploring the innovation pathway that begins with autoantibody discovery followed by assessment of clinical relevance, accuracy, validation, and then consideration of regulatory requirements as an approved diagnostic test. Some tests are offered as "Research Use Only (RUO)", some as "Laboratory Developed Tests (LDT)", some enter Health Technology Assessment (HTA) pathways, while others are relegated to a "death valley" of autoantibody discovery and become "orphan" autoantibodies. Those that achieve regulatory approval are further threatened by the business world's "Darwinian Sea of Survival". As one example of the trappings of autoantibody progression or failure, it is reported that more than 200 different autoantibodies have been described in systemic lupus erythematosus (SLE), a small handful (~10%) of these have achieved regulatory approval and are widely available as commercial diagnostic kits, while a few others may be available as RUO or LDT assays. However, the vast majority (90%) are orphaned and languish in an autoantibody 'death valley'. This review proposes that it is important to keep an inventory of these "orphan autoantibodies" in 'death valley' because, with the increasing availability of multi-analyte arrays and artificial intelligence (MAAI), some can be rescued to achieve a useful role in clinical diagnostic especially in light of patient stratification and precision medicine.
Topics: Autoantibodies; Autoimmune Diseases; Biomarkers; Diagnostic Test Approval; Diagnostic Tests, Routine; Humans; Immunoassay; Translational Research, Biomedical
PubMed: 34122443
DOI: 10.3389/fimmu.2021.679613 -
Pain Research & Management 2021The study explored the clinical influence, effectiveness, limitations, and human comparison outcomes of machine learning in diagnosing (1) dental diseases, (2)...
PURPOSE
The study explored the clinical influence, effectiveness, limitations, and human comparison outcomes of machine learning in diagnosing (1) dental diseases, (2) periodontal diseases, (3) trauma and neuralgias, (4) cysts and tumors, (5) glandular disorders, and (6) bone and temporomandibular joint as possible causes of dental and orofacial pain.
METHOD
Scopus, PubMed, and Web of Science (all databases) were searched by 2 reviewers until 29 October 2020. Articles were screened and narratively synthesized according to PRISMA-DTA guidelines based on predefined eligibility criteria. Articles that made direct reference test comparisons to human clinicians were evaluated using the MI-CLAIM checklist. The risk of bias was assessed by JBI-DTA critical appraisal, and certainty of the evidence was evaluated using the GRADE approach. Information regarding the quantification method of dental pain and disease, the conditional characteristics of both training and test data cohort in the machine learning, diagnostic outcomes, and diagnostic test comparisons with clinicians, where applicable, were extracted.
RESULTS
34 eligible articles were found for data synthesis, of which 8 articles made direct reference comparisons to human clinicians. 7 papers scored over 13 (out of the evaluated 15 points) in the MI-CLAIM approach with all papers scoring 5+ (out of 7) in JBI-DTA appraisals. GRADE approach revealed serious risks of bias and inconsistencies with most studies containing more positive cases than their true prevalence in order to facilitate machine learning. Patient-perceived symptoms and clinical history were generally found to be less reliable than radiographs or histology for training accurate machine learning models. A low agreement level between clinicians training the models was suggested to have a negative impact on the prediction accuracy. Reference comparisons found nonspecialized clinicians with less than 3 years of experience to be disadvantaged against trained models.
CONCLUSION
Machine learning in dental and orofacial healthcare has shown respectable results in diagnosing diseases with symptomatic pain and with improved future iterations and can be used as a diagnostic aid in the clinics. The current review did not internally analyze the machine learning models and their respective algorithms, nor consider the confounding variables and factors responsible for shaping the orofacial disorders responsible for eliciting pain.
Topics: Algorithms; Artificial Intelligence; Diagnostic Tests, Routine; Facial Pain; Humans; Machine Learning; Pain Management
PubMed: 33986900
DOI: 10.1155/2021/6659133 -
The Journal of Pathology. Clinical... Apr 2020The human microbiome can play key roles in disease, and diagnostic testing will soon have the ability to examine these roles in the context of clinical applications.... (Review)
Review
The human microbiome can play key roles in disease, and diagnostic testing will soon have the ability to examine these roles in the context of clinical applications. Currently, most diagnostic testing in pathology applications focuses on a small number of disease-causing microbes and dismisses the whole microbial community that causes or is modulated by disease. Microbiome modifications have already provided clinically relevant insights in gut and oral diseases, such as irritable bowel disease, but there are currently limitations when clinically examining microbiomes outside of these body sites. This is critical, as the majority of microbial samples used in pathology originate from body sites that contain low concentrations of microbial DNA, including skin, tissue, blood, and urine. These samples, also known as low microbial biomass samples, are difficult to examine without careful consideration and precautions to mitigate contamination and biases. Here, we present the limitations when analysing low microbial biomass samples using current protocols and techniques and highlight the advantages that microbiome testing can offer diagnostics in the future, if the proper precautions are implemented. Specifically, we discuss the sources of contamination and biases that may result in false assessments for these sample types. Finally, we provide recommendations to mitigate contamination and biases from low microbial biomass samples during diagnostic testing, which will be especially important to effectively diagnose and treat patients using microbiome analyses.
Topics: Biomass; DNA, Bacterial; Diagnostic Tests, Routine; Gastrointestinal Microbiome; Humans; Microbiota; Sequence Analysis, DNA
PubMed: 31944633
DOI: 10.1002/cjp2.151 -
PLoS Neglected Tropical Diseases Aug 2019Because the success of deworming programs targeting soil-transmitted helminths (STHs) is evaluated through the periodically assessment of prevalence and infection... (Clinical Trial)
Clinical Trial
Diagnostic performance of a single and duplicate Kato-Katz, Mini-FLOTAC, FECPAKG2 and qPCR for the detection and quantification of soil-transmitted helminths in three endemic countries.
BACKGROUND
Because the success of deworming programs targeting soil-transmitted helminths (STHs) is evaluated through the periodically assessment of prevalence and infection intensities, the use of the correct diagnostic method is of utmost importance. The STH community has recently published for each phase of a deworming program the minimal criteria that a potential diagnostic method needs to meet, the so-called target product profiles (TPPs).
METHODOLOGY
We compared the diagnostic performance of a single Kato-Katz (reference method) with that of other microscopy-based methods (duplicate Kato-Katz, Mini-FLOTAC and FECPAKG2) and one DNA-based method (qPCR) for the detection and quantification of STH infections in three drug efficacy trials in Ethiopia, Lao PDR, and Tanzania. Furthermore, we evaluated a selection of minimal diagnostic criteria of the TPPs.
PRINCIPAL FINDINGS
All diagnostic methods showed a clinical sensitivity of ≥90% for all STH infections of moderate-to-heavy intensities. For infections of very low intensity, only qPCR resulted in a sensitivity that was superior to a single Kato-Katz for all STHs. Compared to the reference method, both Mini-FLOTAC and FECPAKG2 resulted in significantly lower fecal egg counts for some STHs, leading to a substantial underestimation of the infection intensity. For qPCR, there was a positive significant correlation between the egg counts of a single Kato-Katz and the DNA concentration.
CONCLUSIONS/SIGNIFICANCE
Our results indicate that the diagnostic performance of a single Kato-Katz is underestimated by the community and that diagnostic specific thresholds to classify intensity of infection are warranted for Mini-FLOTAC, FECPAKG2 and qPCR. When we strictly apply the TPPs, Kato-Katz is the only microscopy-based method that meets the minimal diagnostic criteria for application in the planning, monitoring and evaluation phase of an STH program. qPCR is the only method that could be considered in the phase that aims to seek confirmation for cessation of program.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03465488.
Topics: Adolescent; Animals; Brazil; Child; Diagnostic Tests, Routine; Ethiopia; Feces; Female; Helminthiasis; Helminths; Humans; Laos; Male; Microscopy; Molecular Diagnostic Techniques; Parasite Egg Count; Prevalence; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Soil; Tanzania; World Health Organization
PubMed: 31369558
DOI: 10.1371/journal.pntd.0007446 -
Malaria Journal Sep 2021The diagnosis of malaria, using microscopy or rapid diagnostic tests (RDTs), requires the collection of capillary blood. This procedure is relatively simple to perform...
BACKGROUND
The diagnosis of malaria, using microscopy or rapid diagnostic tests (RDTs), requires the collection of capillary blood. This procedure is relatively simple to perform but invasive and poses potential risks to patients and health workers, arising from the manipulation of potentially infectious bodily fluids. Less or non-invasive diagnostic tests, based on urine, saliva or requiring no sampling, have the potential to generate less discomfort for the patient and to offer simpler and less risky testing procedures that could be safely performed by untrained staff or even self-performed. To explore the potential acceptance and perceived value of such non-invasive tests, an online, international survey was conducted to gather feedback from National Malaria Control Programme (NMCP) representatives.
METHODS
An online survey comprising nineteen questions, available in English, French or Spanish, was emailed to 300 individuals who work with NMCPs in malaria-endemic countries. Answers were collected between November and December 2017; responses were qualitatively analysed to identify key themes and trends and quantitatively analysed to determine average values stratified by region.
RESULTS
Responses were received from 70 individuals, from 33 countries. Approximately half of the respondents (52 %) considered current blood-based tests for malaria to be minimally invasive and non-problematic in their setting. For these participants, non-invasive tests would only be of interest if they brought additional performance improvements, as compared with the performance of microscopy and RDTs. Most respondents were of the view that saliva-based (80 %) and urine-based (66 %) tests would be more readily acceptable among children than blood-based tests. Potential use-case scenarios of interest for both saliva- and urine-based tests were ease-of-testing by community health workers, additional surveillance, self-testing, and outbreak investigation. Many respondents (41 %) thought that if saliva-based tests retailed at <$0.50 per unit they could largely replace conventional RDTs, whereas only 25 % of respondents thought a similarly priced urine-based test would do so.
CONCLUSIONS
Although limited to NMCP stakeholders, this survey indicated that current tests for malaria, based on capillary blood, are generally perceived to be minimally invasive and non-problematic. Non-invasive tests, especially if saliva-based, would be welcome if they could match or out-perform the price and performance of current blood-based tests.
Topics: Diagnostic Tests, Routine; Health Knowledge, Attitudes, Practice; Humans; Malaria; Patient Acceptance of Health Care; Sensitivity and Specificity
PubMed: 34560899
DOI: 10.1186/s12936-021-03911-y