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Journal of Medical Virology Dec 2022Nucleic acid molecular diagnostic technology plays an important role in the detection of severe fever with thrombocytopenia syndrome (SFTS). However, no relevant reports... (Meta-Analysis)
Meta-Analysis
Accuracy of reverse-transcription polymerase chain reaction and loop-mediated isothermal amplification in diagnosing severe fever with thrombocytopenia syndrome: A systematic review and meta-analysis.
Nucleic acid molecular diagnostic technology plays an important role in the detection of severe fever with thrombocytopenia syndrome (SFTS). However, no relevant reports have been published on the accuracy of reverse-transcription polymerase chain reaction (RT-PCR) and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) in the diagnosis of SFTS. Thus, we conducted a meta-analysis and systematic review to evaluate the accuracy of the two methods. On June 19, 2022, we comprehensively searched the PubMed, Embase, Cochrane Library, Web of Science, Scoups, Ovid, Proquest, China National Knowledge Infrastructure Database, Wan Fang Data, Traditional Chinese Medicine Database (Sinomed), VIP Database, and Reading Showing Database for articles on nucleic acid diagnostic techniques, such as RT-PCR and RT-LAMP, used to diagnose SFTS. Statistical analysis was performed using STATA 14.0 and Meta-Disc 1.4. Sixteen articles involving 2942 clinical blood samples were included in the analysis. RT-PCR and RT-LAMP were used as index tests, whereas RT-PCR or other detection methods were used as reference standards. The pooled values for the sensitivity, specificity, positive and negative likelihood ratios of the RT-PCR test were 0.97 (95% confidence interval [CI]: 0.92-0.99), 1.00 (95% CI: 0.98-1.00), 483.87 (95% CI: 58.04-4033.76), and 0.03 (95% CI:0.01-0.08), respectively. Those for the RT-LAMP test were 0.95 (95% CI: 0.91-0.97), 0.99 (95% CI: 0.93-1.00), 111.18 (95% CI: 13.96-885.27), and 0.05 (95% CI: 0.03-0.09), respectively. Both RT-PCR and RT-LAMP have high diagnostic value in SFTS and can be applied in different scenarios for laboratory confirmation or on-site screening.
Topics: Humans; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Nucleic Acids; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35968756
DOI: 10.1002/jmv.28068 -
Medical Journal of the Islamic Republic... 2022Tuberculosis is one of the oldest known diseases in humans, and early detection of tuberculosis is one of the main measures to decrease the spread of tuberculosis. In... (Review)
Review
An Evaluation of The Diagnostic Value of Sputum Smears Microscopy and Pcr Relative to Sputum Culture in The Diagnosis of Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis in Iran.
Tuberculosis is one of the oldest known diseases in humans, and early detection of tuberculosis is one of the main measures to decrease the spread of tuberculosis. In many parts of the world, including Iran, the diagnosis of tuberculosis is based on the detection of acid-fast bacillus in sputum smear microscopy and PCR. this study aimed to synthesize evidence on the diagnostic accuracy of sputum smear and PCR compared to sputum culture for the diagnosis of PT in Iranian patients. This systematic review and meta-analysis was conducted based on PRISMA guideline for systematic review and meta-analysis. Eligible studies were cross-sectional original diagnostic studies published in English and Persian in Iran which examined the sensitivity or specificity(study outcome) of sputum smear microscopy or PCR( as the test) relative to sputum culture (as the gold standard/comparator) among Iranian patients suspected of having tuberculosis( study population). Studies whose data were not complete or extractable were excluded. A total of 3518 subjects were evaluated from 15 eligible studies. The pooled sensitivity of sputum smear and PCR was 75.12 (95% CI: 66.68-83.56) and 88.02 (95% CI: 82.87-93.27), respectively. The specificity for sputum smear and PCR was 93.94 (95% CI: 91.26-96.63) and 91.82 (95% CI: 87.29-96.35) respectively. The sensitivity of both sputum smears was higher in studies published after 2010, and had higher quality. The specificity of sputum smear was a bit lower in studies published after2010 but higher in studies with higher quality. The specificity of PCR was higher in studies published after 2010 but higher in studies with higher quality. The increased sensitivity of sputum smear and PCR during recent years suggests the improvement of preparation and laboratory methods in recent years. However, the imperfect sensitivity of these tests highlights the need for a more accurate diagnostic method for the detection of pulmonary tuberculosis in Iran.
PubMed: 36447544
DOI: 10.47176/mjiri.36.112 -
Memorias Do Instituto Oswaldo Cruz Jan 2016Chronic Chagas disease diagnosis relies on laboratory tests due to its clinical characteristics. The aim of this research was to review commercial enzyme-linked... (Comparative Study)
Comparative Study Meta-Analysis Review
Chronic Chagas disease diagnosis relies on laboratory tests due to its clinical characteristics. The aim of this research was to review commercial enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) diagnostic test performance. Performance of commercial ELISA or PCR for the diagnosis of chronic Chagas disease were systematically searched in PubMed, Scopus, Embase, ISI Web, and LILACS through the bibliography from 1980-2014 and by contact with the manufacturers. The risk of bias was assessed with QUADAS-2. Heterogeneity was estimated with the I2 statistic. Accuracies provided by the manufacturers usually overestimate the accuracy provided by academia. The risk of bias is high in most tests and in most QUADAS dimensions. Heterogeneity is high in either sensitivity, specificity, or both. The evidence regarding commercial ELISA and ELISA-rec sensitivity and specificity indicates that there is overestimation. The current recommendation to use two simultaneous serological tests can be supported by the risk of bias analysis and the amount of heterogeneity but not by the observed accuracies. The usefulness of PCR tests are debatable and health care providers should not order them on a routine basis. PCR may be used in selected cases due to its potential to detect seronegative subjects.
Topics: Chagas Disease; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Humans; Polymerase Chain Reaction; Sensitivity and Specificity; Trypanosoma cruzi
PubMed: 26814640
DOI: 10.1590/0074-02760150296 -
The Bone & Joint Journal Mar 2022The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated... (Comparative Study)
Comparative Study Meta-Analysis
Synovial fluid calprotectin performs better than synovial fluid polymerase chain reaction and interleukin-6 in the diagnosis of periprosthetic joint infection : a systematic review and meta-analysis.
AIMS
The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI.
METHODS
We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified.
RESULTS
Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI.
CONCLUSION
Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: 2022;104-B(3):311-320.
Topics: Humans; Interleukin-6; Joint Prosthesis; Leukocyte L1 Antigen Complex; Polymerase Chain Reaction; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid
PubMed: 35227091
DOI: 10.1302/0301-620X.104B3.BJJ-2021-1320.R1 -
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 -
Life (Basel, Switzerland) Nov 2021The diagnosis of COVID-19 is made using reverse transcription polymerase chain reaction (RT-PCR) but its sensitivity varies from 20 to 100%. The presence of gustatory... (Review)
Review
Exploring the Clinical Utility of Gustatory Dysfunction (GD) as a Triage Symptom Prior to Reverse Transcription Polymerase Chain Reaction (RT-PCR) in the Diagnosis of COVID-19: A Meta-Analysis and Systematic Review.
BACKGROUND
The diagnosis of COVID-19 is made using reverse transcription polymerase chain reaction (RT-PCR) but its sensitivity varies from 20 to 100%. The presence of gustatory dysfunction (GD) in a patient with upper respiratory tract symptoms might increase the clinical suspicion of COVID-19.
AIMS
To perform a systematic review and meta-analysis to determine the pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-) and diagnostic odds ratio (DOR) of using GD as a triage symptom prior to RT-PCR.
METHODS
PubMed and Embase were searched up to 20 June 2021. Studies published in English were included if they compared the frequency of GD in COVID-19 adult patients (proven by RT-PCR) to COVID-19 negative controls in case control or cross-sectional studies. The Newcastle-Ottawa scale was used to assess the methodological quality of the included studies.
RESULTS
21,272 COVID-19 patients and 52,298 COVID-19 negative patients were included across 44 studies from 21 countries. All studies were of moderate to high risk of bias. Patients with GD were more likely to test positive for COVID-19: DOR 6.39 (4.86-8.40), LR+ 3.84 (3.04-4.84), LR- 0.67 (0.64-0.70), pooled sensitivity 0.37 (0.29-0.47) and pooled specificity 0.92 (0.89-0.94). While history/questionnaire-based assessments were predictive of RT-PCR positivity (DOR 6.62 (4.95-8.85)), gustatory testing was not (DOR 3.53 (0.98-12.7)). There was significant heterogeneity among the 44 studies (I = 92%, < 0.01).
CONCLUSIONS
GD is useful as a symptom to determine if a patient should undergo further testing, especially in resource-poor regions where COVID-19 testing is scarce. Patients with GD may be advised to quarantine while repeated testing is performed if the initial RT-PCR is negative.
FUNDING
None.
PubMed: 34947846
DOI: 10.3390/life11121315 -
Infectious Diseases and Therapy Mar 2019Capnocytophaga canimorsus infections are associated with dog bites, especially in asplenic or immunocompromised patients, and typically manifest as sepsis and/or...
INTRODUCTION
Capnocytophaga canimorsus infections are associated with dog bites, especially in asplenic or immunocompromised patients, and typically manifest as sepsis and/or bacteremia. Meningitis has been rarely described, and its diagnosis may be delayed due to poor or slow growth using traditional culture techniques. We provide our experience using polymerase chain reaction (PCR) to establish the diagnosis and perform a comprehensive review of C. canimorsus meningitis cases to provide summary data on the clinical manifestations, diagnosis, and outcomes of this unusual infection.
METHODS
A systematic review of the peer-reviewed English literature (PubMed, Embase, Ovid Medline) from January 1966 to March 2018 was conducted to identify cases of C. canimorsus meningitis. Data collected included demographics, risk factors, cerebrospinal fluid (CSF) findings, PCR results, treatments, and outcomes. Descriptive statistics are presented as numbers (percentages) and medians (ranges).
RESULTS
A total of 37 patients were reviewed with a median age of 63 years (12 days to 83 years) with a male predominance (76%). A relatively low proportion had an immunocompromised state (16% splenectomy and 5% steroid use); the most common risk factor was alcoholism (19%). Fifty-nine percent reported a dog bite (all within ≤ 14 days prior to presentation), while 22% reported a non-bite dog exposure, 3% reported cat bite, and 3% reported both dog and cat exposures; 11% reported no animal contact. CSF parameters included a median white count of 1024 cells/mm, 81% had neutrophilic predominance, median protein of 190 mg/dl, and median glucose CSF/serum ratio 0.23. In 54% of cases, blood cultures were positive for C. canimorsus (median, 4 days) and 70% had positive CSF cultures (median, 5 days). PCR established the diagnosis in eight (22%) cases. Antibiotic therapy was given for a median of 15 days (range, 7 to 42 days). Prognosis was overall favorable with only one (3%) death reported and adverse neurologic and/or physical sequelae in 19% of the survivors.
CONCLUSION
C. canimorsus meningitis is a rare but increasingly important clinical entity occurring in patients of all ages, typically after dog exposure. While classically considered an infection among immunocompromised patients, most cases have occurred in previously healthy, immunocompetent persons. Diagnosis may be rapidly established by PCR, and this test should be considered in culture-negative cases with associated exposures. Outcome was generally favorable after a median antibiotic duration of 15 days.
PubMed: 30706413
DOI: 10.1007/s40121-019-0233-6 -
European Urology Open Science Oct 2022Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are... (Review)
Review
CONTEXT
Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are culture-independent molecular methods available for commercial use to diagnose UTI.
OBJECTIVE
To systematically evaluate the evidence comparing the diagnostic and therapeutic values of molecular diagnostic methods to urine culture in the management of UTI in adults.
EVIDENCE ACQUISITION
We performed a critical review of Embase, Ovid, and PubMed in February 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Studies involving pregnant women, ureteral stones, ureteral stents, and percutaneous nephrostomy tubes were excluded. Risk of bias and methodological quality were assessed using the Cochrane risk of bias tool and Newcastle Ottawa Scale. Fifteen publications were selected for inclusion.
EVIDENCE SYNTHESIS
Included reports compared NGS (nine studies) and PCR (six studies) to urine culture. A meta-analysis of seven similar studies utilizing NGS demonstrates that NGS is more sensitive in the identification of urinary bacteria and detects greater species diversity per urine sample than culture. PCR protocols designed to detect a diverse range of microbes had increased sensitivity and species diversity compared with culture. Phenotypic and genotypic resistomes are concordant in approximately 85% of cases. There is insufficient evidence to compare patient symptomatic responses to antibiotic therapy guided by molecular testing versus standard susceptibility testing.
CONCLUSIONS
Moderately strong evidence exists that molecular diagnostics demonstrate increased sensitivity in detecting urinary bacteria at the expense of poor specificity in controls. Additional data comparing patient symptoms and cure rates following antibiotic selection directed by molecular methods compared with culture are needed to elucidate their place in UTI care.
PATIENT SUMMARY
We compare culture-independent molecular methods with urine culture in the management of urinary tract infection. We found good evidence that molecular methods detect more bacteria than culture; however, the clinical implications to support their routine use are unclear.
PubMed: 36093322
DOI: 10.1016/j.euros.2022.08.009 -
The Saudi Dental Journal Mar 2022This systematic review aimed to evaluate the antiviral effect of mouthwashes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). (Review)
Review
OBJECTIVE
This systematic review aimed to evaluate the antiviral effect of mouthwashes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
MATERIAL AND METHODS
An electronic search was performed on PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ProQuest, and Google Scholar, and was complemented by a manual search. Both clinical and studies that focused on the antiviral effect of mouthwashes against SARS-CoV-2 were included. Risk of bias assessment was performed only on the clinical studies using the RoB-2 and ROBINS-I tools.
RESULTS
A total of 907 records were found; after initial selection by title and abstract, 33 full-text articles were selected to be evaluated for eligibility. Finally, a total of 27 studies were included for the qualitative synthesis, including 16 studies and 11 clinical trials. Antiviral effects were evaluated separately for the and clinical studies. In vitro studies included mouthwashes containing hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, essential oils, cetylpyridinium chloride, and other compounds; studies included mouthwashes containing hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, essential oils, chlorine dioxide, β-cyclodextrin-citrox, and sorbitol with xylitol. Povidone-iodine, cetylpyridinium chloride, and essential oils were effective , while hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, β-cyclodextrin-citrox, and sorbitol with xylitol were effective . Unclear or high risk of bias was found for almost all clinical studies, and only one study presented with a low risk of bias. No further quantitative analysis was performed.
CONCLUSION
Although povidone-iodine, cetylpyridinium chloride, and essential oils may be an alternative to reduce the viral load and , more studies are needed to determine the real antiviral effect of these different mouthwashes against SARS-CoV-2.This work was not funded. The protocol was registered in PROSPERO (identification number: CRD42021236134).
PubMed: 35125835
DOI: 10.1016/j.sdentj.2022.01.006 -
Journal of Plastic, Reconstructive &... Oct 2015Peripheral neuromas can result in an unbearable neuropathic pain and functional impairment. Their treatment is still challenging, and their optimal management is to be... (Review)
Review
Peripheral neuromas can result in an unbearable neuropathic pain and functional impairment. Their treatment is still challenging, and their optimal management is to be defined. Experimental research still plays a major role, but - although numerous neuroma models have been proposed on different animals - there is still no single model recognised as being the reference. Several models show advantages over the others in specific aspects of neuroma physiopathology, prevention or treatment, making it unlikely that a single model could be of reference. A reproducible and standardised model of peripheral neuroma would allow better comparison of results from different studies. We present a systematic review of the literature on experimental in vivo models, analysing advantages and disadvantages, specific features and indications, with the goal of providing suggestions to help their standardisation. Published models greatly differ in the animal and the nerve employed, the mechanisms of nerve injury and the evaluation methods. Specific experimental models exist for terminal neuromas and neuromas in continuity (NIC). The rat is the most widely employed animal, the rabbit being the second most popular model. NIC models are more actively researched, but it is more difficult to generate such studies in a reproducible manner. Nerve transection is considered the best method to cause terminal neuromas, whereas partial transection is the best method to cause NIC. Traditional histomorphology is the historical gold-standard evaluation method, but immunolabelling, reverse transcriptase-polymerase chain reaction (RT-PCR) and proteomics are gaining increasing popularity. Computerised gait analysis is the gold standard for motor-recovery evaluation, whereas mechanical testing of allodynia and hyperalgesia reproducibly assesses sensory recovery. This review summarises current knowledge on experimental neuroma models, and it provides a useful tool for defining experimental protocols. Furthermore, it could help future research to define standard experimental model(s) of peripheral neuromas, allowing better comparison of results and improvement of our understanding of such a complex disease.
Topics: Animals; Humans; Neoplasms, Experimental; Neuroma; Neurosurgical Procedures; Peripheral Nervous System Neoplasms
PubMed: 26113274
DOI: 10.1016/j.bjps.2015.05.013