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American Journal of Epidemiology Jan 2021Health-care workers (HCWs) are at the frontline of response to coronavirus disease 2019 (COVID-19), being at a higher risk of acquiring the disease and, subsequently,... (Meta-Analysis)
Meta-Analysis
Health-care workers (HCWs) are at the frontline of response to coronavirus disease 2019 (COVID-19), being at a higher risk of acquiring the disease and, subsequently, exposing patients and others. Searches of 8 bibliographic databases were performed to systematically review the evidence on the prevalence, risk factors, clinical characteristics, and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs. A total of 97 studies (all published in 2020) met the inclusion criteria. The estimated prevalence of SARS-CoV-2 infection from HCWs' samples, using reverse transcription-polymerase chain reaction and the presence of antibodies, was 11% (95% confidence interval (CI): 7, 15) and 7% (95% CI: 4, 11), respectively. The most frequently affected personnel were nurses (48%, 95% CI: 41, 56), whereas most of the COVID-19-positive medical personnel were working in hospital nonemergency wards during screening (43%, 95% CI: 28, 59). Anosmia, fever, and myalgia were the only symptoms associated with HCW SARS-CoV-2 positivity. Among HCWs positive for COVID-19 by reverse transcription-polymerase chain reaction, 40% (95% CI: 17, 65) were asymptomatic at time of diagnosis. Finally, severe clinical complications developed in 5% (95% CI: 3, 8) of the COVID-19-positive HCWs, and 0.5% (95% CI: 0.02, 1.3) died. Health-care workers suffer a significant burden from COVID-19, with those working in hospital nonemergency wards and nurses being the most commonly infected personnel.
Topics: COVID-19; Global Health; Health Personnel; Humans; Prevalence; Risk Factors; SARS-CoV-2
PubMed: 32870978
DOI: 10.1093/aje/kwaa191 -
Clinical Infectious Diseases : An... Nov 2016We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive... (Meta-Analysis)
Meta-Analysis Review
Galactomannan, β-D-Glucan, and Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.
We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive fungal disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT.
Topics: Adolescent; Adult; Child; Child, Preschool; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Invasive Fungal Infections; Mannans; Neoplasms; Polymerase Chain Reaction; Young Adult; beta-Glucans
PubMed: 27567122
DOI: 10.1093/cid/ciw592 -
PloS One 2015We aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream infections through... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream infections through a systematic review and meta-analysis.
METHODS
A computerized literature search was conducted to identify studies that assessed the diagnostic value of 16S rRNA gene PCR test for bloodstream infections. Study quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence intervals (95% CI) for each study. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Statistical analysis was performed in Meta-DiSc 1.4 and Stata/SE 12.0 software.
RESULTS
Twenty-eight studies were included in our meta-analysis. Using random-effect model analysis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.87 (95% CI, 0.85-0.89), 0.94 (95% CI, 0.93-0.95), 12.65 (95% CI, 8.04-19.90), 0.14 (95% CI, 0.08-0.24), and 116.76 (95% CI, 52.02-262.05), respectively. The SROC curve indicated that the area under the curve (AUC) was 0.9690 and the maximum joint sensitivity and specificity (Q*) was 0.9183. In addition, heterogeneity was statistically significant but was not caused by the threshold effect.
CONCLUSION
Existing data suggest that 16S rRNA gene PCR test is a practical tool for the rapid screening of sepsis. Further prospective studies are needed to assess the diagnostic value of PCR amplification and DNA microarray hybridization of 16S rRNA gene in the future.
Topics: Bacteremia; Databases, Factual; Humans; Odds Ratio; Polymerase Chain Reaction; Publication Bias; RNA, Ribosomal, 16S; Reproducibility of Results; Sensitivity and Specificity; Sepsis
PubMed: 25996771
DOI: 10.1371/journal.pone.0127195 -
Journal of Clinical Virology : the... Nov 2021Timely and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial to reduce the risk of viral transmission. We... (Meta-Analysis)
Meta-Analysis
Comparing the diagnostic accuracy of rapid antigen detection tests to real time polymerase chain reaction in the diagnosis of SARS-CoV-2 infection: A systematic review and meta-analysis.
BACKGROUND
Timely and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial to reduce the risk of viral transmission. We investigated the diagnostic accuracy of rapid antigen detection tests (RADTs) in the diagnosis of SARS-CoV-2 infection.
METHODS
A systematic literature search was performed using Pubmed, Embase, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary receiver-operating characteristic curve (HSROC) of RADTs were pooled using meta-analysis. We used commercial and laboratory-developed reverse transcriptase-polymerase chain reaction (RT-PCR) as reference standards.
RESULTS
We identified 24 studies comprising 14,188 patients. The overall pooled sensitivity, specificity, and DOR of RADTs for diagnosis of SARS-CoV-2 were 0.68 (95%CI, 0.59 - 0.76), 0.99 (95%CI, 0.99 - 1.00), and 426.70 (95% CI, 168.37 - 1081.65), respectively. RADTs and RT-PCR had moderate agreement with an estimated pooled Cohen's kappa statistic of 0.75 (95%CI, 0.74-0.77), and area under the HSROC of 0.98 (95%CI, 0.96 - 0.99). The pooled sensitivity of RADTs was significantly increased in subjects with viral load of Ct-value ≤25 or in those within 5 days after symptom onset than it was in subjects with lower viral loads or longer symptom duration.
CONCLUSIONS
The overall sensitivity of RADTs was inferior to that of the RT-PCR assay. The RADTs were more sensitive for samples of Ct-value ≤ 25 and might be suitable for subjects in the community within 5 days of symptom onset.
Topics: COVID-19; Humans; Real-Time Polymerase Chain Reaction; Reference Standards; SARS-CoV-2; Sensitivity and Specificity
PubMed: 34560340
DOI: 10.1016/j.jcv.2021.104985 -
The Kaohsiung Journal of Medical... Feb 2018Broad-range bacterial rDNA polymerase chain reaction (PCR) followed by sequencing may be identified as the etiology of infective endocarditis (IE) from surgically... (Meta-Analysis)
Meta-Analysis Review
Broad-range bacterial rDNA polymerase chain reaction (PCR) followed by sequencing may be identified as the etiology of infective endocarditis (IE) from surgically removed valve tissue; therefore, we reviewed the value of molecular testing in identifying organisms' DNA in the studies conducted until 2016. We searched Google Scholar, Scopus, ScienceDirect, Cochrane, PubMed, and Medline electronic databases without any time limitations up to December 2016 for English studies reporting microorganisms involved in infective endocarditis microbiology using PCR and real-time PCR. Most studies were prospective. Eleven out of 12 studies used valve tissue samples and blood cultures while only 1 study used whole blood. Also, 10 studies used the molecular method of PCR while 2 studies used real-time PCR. Most studies used 16S rDNA gene as the target gene. The bacteria were identified as the most common microorganisms involved in infective endocarditis. Streptococcus spp. and Staphylococcus spp. were, by far, the most predominant bacteria detected. In all studies, PCR and real-time PCR identified more pathogens than blood and tissue cultures; moreover, the sensitivity and specificity of PCR and real-time PCR were more than cultures in most of the studies. The highest sensitivity and specificity were 96% and 100%, respectively. The gram positive bacteria were the most frequent cause of infective endocarditis. The molecular methods enjoy a greater sensitivity compared to the conventional blood culture methods; yet, they are applicable only to the valve tissue of the patients undergoing cardiac valve surgery.
Topics: Endocarditis, Bacterial; Humans; Real-Time Polymerase Chain Reaction; Reproducibility of Results
PubMed: 29413230
DOI: 10.1016/j.kjms.2017.09.011 -
PloS One 2020Wheezing is a major problem in children, and respiratory viruses are often believed to be the causative agent. While molecular detection tools enable identification of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Wheezing is a major problem in children, and respiratory viruses are often believed to be the causative agent. While molecular detection tools enable identification of respiratory viruses in wheezing children, it remains unclear if and how these viruses are associated with wheezing. The objective of this systematic review is to clarify the prevalence of different respiratory viruses in children with wheezing.
METHODS
We performed an electronic in Pubmed and Global Index Medicus on 01 July 2019 and manual search. We performed search of studies that have detected common respiratory viruses in children ≤18 years with wheezing. We included only studies using polymerase chain reaction (PCR) assays. Study data were extracted and the quality of articles assessed. We conducted sensitivity, subgroup, publication bias, and heterogeneity analyses using a random effects model.
RESULTS
The systematic review included 33 studies. Rhinovirus, with a prevalence of 35.6% (95% CI 24.6-47.3, I2 98.4%), and respiratory syncytial virus, at 31.0% (95% CI 19.9-43.3, I2 96.4%), were the most common viruses detected. The prevalence of other respiratory viruses was as follows: human bocavirus 8.1% (95% CI 5.3-11.3, I2 84.6%), human adenovirus 7.7% (95% CI 2.6-15.0, I2 91.0%), influenza virus6.5% (95% CI 2.2-12.6, I2 92.4%), human metapneumovirus5.8% (95% CI 3.4-8.8, I2 89.0%), enterovirus 4.3% (95% CI 0.1-12.9, I2 96.2%), human parainfluenza virus 3.8% (95% CI 1.5-6.9, I2 79.1%), and human coronavirus 2.2% (95% CI 0.6-4.4, I2 79.4%).
CONCLUSIONS
Our results suggest that rhinovirus and respiratory syncytial virus may contribute to the etiology of wheezing in children. While the clinical implications of molecular detection of respiratory viruses remains an interesting question, this study helps to illuminate the potential of role respiratory viruses in pediatric wheezing.
REVIEW REGISTRATION
PROSPERO, CRD42018115128.
Topics: Bocavirus; Child; Child, Preschool; Coronavirus; Humans; Orthomyxoviridae; Parainfluenza Virus 1, Human; Polymerase Chain Reaction; Respiratory Sounds; Respiratory System; Respiratory Tract Infections
PubMed: 33315873
DOI: 10.1371/journal.pone.0243735 -
Sao Paulo Medical Journal = Revista... Jan 2003Cutaneous melanoma presents significant morbidity and mortality. Nowadays, about 90% of them are diagnosed by clinical examination and most are localized melanomas.... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Cutaneous melanoma presents significant morbidity and mortality. Nowadays, about 90% of them are diagnosed by clinical examination and most are localized melanomas. Sentinel node biopsy has brought about a new and interesting approach towards localized cutaneous melanoma. The meaning of micrometastases in sentinel nodes diagnosed by the reverse transcriptase-polymerase chain reaction is not well established.
OBJECTIVE
To define the real value of micrometastases diagnosed by the reverse transcriptases polymerase chain reaction in relation to melanoma recurrence.
METHODS
Systematic literature review and meta-analysis. The Cochrane Library, Medline, Embase and Lilacs were the databases searched. We used the following key words: sentinel node and melanoma; sentinel node and reverse transcriptase-polymerase chain reaction; melanoma and reverse transcriptase-polymerase chain reaction. Cohort studies enrolling localized cutaneous melanoma patients who underwent sentinel node biopsy were selected. Sentinel node evaluations included hematoxylin and eosin, immunohistochemistry and reverse transcriptase-polymerase chain reaction.
RESULTS
Out of the 1,542 studies evaluated, four were eligible. The four studies, when combined, were statistically homogeneous. The sample totaled 450 patients grouped as follows: 163 with a sentinel node negative to hematoxylin eosin and immunohistochemistry and positive to the reverse transcriptase-polymerase chain reaction; 192 with a sentinel node negative to hematoxylin eosin, immunohistochemistry and the reverse transcriptase-polymerse chain reaction and 95 patients with a sentinel node positive to hematoxylin eosin and/or immunohistochemistry. We analyzed the first two groups. The meta-analysis for the random model showed an increased effect from a positive reverse transcriptase-polymerase chain reaction on the recurrence rate. A similar result occurred in the meta-analysis for the fixed effect model.
CONCLUSION
Patients with a positive reverse transcriptase-polymerase chain reaction had a greater recurrence rate than those with a negative reverse transcriptase-polymerase chain reaction. This suggests an important role for the reverse transcriptase-polymerase chain reaction in sentinel node examinations. In view of the small sample, a clinical trial could better evaluate this question.
Topics: Humans; Immunohistochemistry; Lymphatic Metastasis; Melanoma; Reverse Transcriptase Polymerase Chain Reaction; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 12751340
DOI: 10.1590/s1516-31802003000100006 -
Health Technology Assessment... May 2015There is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen... (Review)
Review
Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review.
BACKGROUND
There is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen deoxyribonucleic acid (DNA) in blood samples within a few hours. SeptiFast (Roche Diagnostics GmBH, Mannheim, Germany) is a multipathogen probe-based system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection. As background to this study, we report a systematic review of Phase III diagnostic accuracy studies of SeptiFast, which reveals uncertainty about its likely clinical utility based on widespread evidence of deficiencies in study design and reporting with a high risk of bias.
OBJECTIVE
Determine the accuracy of SeptiFast real-time PCR for the detection of health-care-associated bloodstream infection, against standard microbiological culture.
DESIGN
Prospective multicentre Phase III clinical diagnostic accuracy study using the standards for the reporting of diagnostic accuracy studies criteria.
SETTING
Critical care departments within NHS hospitals in the north-west of England.
PARTICIPANTS
Adult patients requiring blood culture (BC) when developing new signs of systemic inflammation.
MAIN OUTCOME MEASURES
SeptiFast real-time PCR results at species/genus level compared with microbiological culture in association with independent adjudication of infection. Metrics of diagnostic accuracy were derived including sensitivity, specificity, likelihood ratios and predictive values, with their 95% confidence intervals (CIs). Latent class analysis was used to explore the diagnostic performance of culture as a reference standard.
RESULTS
Of 1006 new patient episodes of systemic inflammation in 853 patients, 922 (92%) met the inclusion criteria and provided sufficient information for analysis. Index test assay failure occurred on 69 (7%) occasions. Adult patients had been exposed to a median of 8 days (interquartile range 4-16 days) of hospital care, had high levels of organ support activities and recent antibiotic exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to 88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled diagnostic metrics derived from our systematic review, our clinical study revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology in the diagnosis of bloodstream infection. However, latent class analysis indicates that BC has a low sensitivity, questioning its relevance as a reference test in this setting. Using this analysis approach, the sensitivity of the SeptiFast test was low but also appeared significantly better than BC. Blood samples identified as positive by either culture or SeptiFast real-time PCR were associated with a high probability (> 95%) of infection, indicating higher diagnostic rule-in utility than was apparent using conventional analyses of diagnostic accuracy.
CONCLUSION
SeptiFast real-time PCR on blood samples may have rapid rule-in utility for the diagnosis of health-care-associated bloodstream infection but the lack of sensitivity is a significant limiting factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in this setting are urgently required. Future work recommendations include technology developments to improve the efficiency of pathogen DNA extraction and the capacity to detect a much broader range of pathogens and drug resistance genes and the application of new statistical approaches able to more reliably assess test performance in situation where the reference standard (e.g. blood culture in the setting of high antimicrobial use) is prone to error.
STUDY REGISTRATION
The systematic review is registered as PROSPERO CRD42011001289.
FUNDING
The National Institute for Health Research Health Technology Assessment programme. Professor Daniel McAuley and Professor Gavin D Perkins contributed to the systematic review through their funded roles as codirectors of the Intensive Care Foundation (UK).
Topics: Bacteremia; Critical Care; Cross Infection; England; False Negative Reactions; False Positive Reactions; Humans; Prospective Studies; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; State Medicine; Technology Assessment, Biomedical; Time Factors
PubMed: 25961752
DOI: 10.3310/hta19350 -
Annals of Internal Medicine Sep 2017Rapid and accurate influenza diagnostics can improve patient care. (Meta-Analysis)
Meta-Analysis Review
Diagnostic Accuracy of Novel and Traditional Rapid Tests for Influenza Infection Compared With Reverse Transcriptase Polymerase Chain Reaction: A Systematic Review and Meta-analysis.
BACKGROUND
Rapid and accurate influenza diagnostics can improve patient care.
PURPOSE
To summarize and compare accuracy of traditional rapid influenza diagnostic tests (RIDTs), digital immunoassays (DIAs), and rapid nucleic acid amplification tests (NAATs) in children and adults with suspected influenza.
DATA SOURCES
6 databases from their inception through May 2017.
STUDY SELECTION
Studies in English, French, or Spanish comparing commercialized rapid tests (that is, providing results in <30 minutes) with reverse transcriptase polymerase chain reaction reference standard for influenza diagnosis.
DATA EXTRACTION
Data were extracted using a standardized form; quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) criteria.
DATA SYNTHESIS
162 studies were included (130 of RIDTs, 19 of DIAs, and 13 of NAATs). Pooled sensitivities for detecting influenza A from Bayesian bivariate random-effects models were 54.4% (95% credible interval [CrI], 48.9% to 59.8%) for RIDTs, 80.0% (CrI, 73.4% to 85.6%) for DIAs, and 91.6% (CrI, 84.9% to 95.9%) for NAATs. Those for detecting influenza B were 53.2% (CrI, 41.7% to 64.4%) for RIDTs, 76.8% (CrI, 65.4% to 85.4%) for DIAs, and 95.4% (CrI, 87.3% to 98.7%) for NAATs. Pooled specificities were uniformly high (>98%). Forty-six influenza A and 24 influenza B studies presented pediatric-specific data; 35 influenza A and 16 influenza B studies presented adult-specific data. Pooled sensitivities were higher in children by 12.1 to 31.8 percentage points, except for influenza A by rapid NAATs (2.7 percentage points). Pooled sensitivities favored industry-sponsored studies by 6.2 to 34.0 percentage points. Incomplete reporting frequently led to unclear risk of bias.
LIMITATIONS
Underreporting of clinical variables limited exploration of heterogeneity. Few NAAT studies reported adult-specific data, and none evaluated point-of-care testing. Many studies had unclear risk of bias.
CONCLUSION
Novel DIAs and rapid NAATs had markedly higher sensitivities for influenza A and B in both children and adults than did traditional RIDTs, with equally high specificities.
PRIMARY FUNDING SOURCE
Québec Health Research Fund and BD Diagnostic Systems.
Topics: Adult; Child; Diagnostic Tests, Routine; Humans; Immunoassay; Influenza, Human; Molecular Diagnostic Techniques; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 28869986
DOI: 10.7326/M17-0848 -
International Journal of Infectious... Sep 2020Diagnosis is a challenging issue for eliminating malaria. Loop-mediated isothermal amplification (LAMP) could be an alternative to conventional methods. This study aimed... (Comparative Study)
Comparative Study Meta-Analysis
Systematic review and meta-analysis of diagnostic accuracy of loop-mediated isothermal amplification (LAMP) methods compared with microscopy, polymerase chain reaction and rapid diagnostic tests for malaria diagnosis.
BACKGROUND
Diagnosis is a challenging issue for eliminating malaria. Loop-mediated isothermal amplification (LAMP) could be an alternative to conventional methods. This study aimed to evaluate the diagnostic accuracy of LAMP for malaria compared with microscopy, polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs).
METHODS AND DESIGN
MEDLINE, Web of Science and Scopus were searched from inception to 1 July 2019. Prospective and retrospective, randomised and non-randomised, mono-center and multi-center studies, including symptomatic or asymptomatic patients, that reported one LAMP method and one comparator (microscopy, RDT or PCR) were included. PROSPERO registration number: CRD42017075186.
RESULTS
Sixty-six studies published between 2006 and 2019 were included, leading to the analysis of 30,641 LAMP tests. The pooled sensitivity of LAMP remained between 96% and 98%, whichever the comparator. The pooled specificity of LAMP was around 95%, but was a little higher if the best PCR studies were considered. The AUC was found to be >0.98, whichever the subgroup of studies was considered. Diagnostic odds ratio (DOR) was found to be around 1000 for all subgroups, except for Plasmodium vivax.
CONCLUSION
This meta-analysis confirmed that the LAMP method is robust for diagnosing malaria, both in symptomatic and asymptomatic people. Thus, the impact of LAMP for controlling malaria is expected to be important.
Topics: Diagnostic Tests, Routine; Humans; Malaria; Microscopy; Nucleic Acid Amplification Techniques; Plasmodium; Polymerase Chain Reaction; Prospective Studies; Retrospective Studies; Sensitivity and Specificity
PubMed: 32659450
DOI: 10.1016/j.ijid.2020.07.009