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The Cochrane Database of Systematic... Sep 2015Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mould infection in immunocompromised people. Early diagnosis of IA and prompt... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mould infection in immunocompromised people. Early diagnosis of IA and prompt administration of appropriate antifungal treatment are critical to the survival of people with IA. Antifungal drugs can be given as prophylaxis or empirical therapy, instigated on the basis of a diagnostic strategy (the pre-emptive approach) or for treating established disease. Consequently there is an urgent need for research into both new diagnostic tools and drug treatment strategies. Newer methods such as polymerase chain reaction (PCR) to detect fungal nucleic acids are increasingly being investigated.
OBJECTIVES
To provide an overall summary of the diagnostic accuracy of PCR-based tests on blood specimens for the diagnosis of IA in immunocompromised people.
SEARCH METHODS
We searched MEDLINE (1946 to June 2015) and EMBASE (1980 to June 2015). We also searched LILACS, DARE, Health Technology Assessment, Web of Science and Scopus to June 2015. We checked the reference lists of all the studies identified by the above methods and contacted relevant authors and researchers in the field.
SELECTION CRITERIA
We included studies that: i) compared the results of blood PCR tests with the reference standard published by the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG); ii) reported data on false-positive, true-positive, false-negative and true-negative results of the diagnostic tests under investigation separately; and iii) evaluated the test(s) prospectively in cohorts of people from a relevant clinical population, defined as a group of individuals at high risk for invasive aspergillosis. Case-control studies were excluded from the analysis.
DATA COLLECTION AND ANALYSIS
Authors independently assessed quality and extracted data. For PCR assays, we evaluated the requirement for either one or two consecutive samples to be positive for diagnostic accuracy. We investigated heterogeneity by subgroup analyses. We plotted estimates of sensitivity and specificity from each study in receiver operating characteristics (ROC) space and constructed forest plots for visual examination of variation in test accuracy. We performed meta-analyses using the bivariate model to produce summary estimates of sensitivity and specificity.
MAIN RESULTS
Eighteen primary studies, corresponding to 19 cohorts and 22 data sets, published between 2000 and 2013 were included in the meta-analyses, with a median prevalence of IA (proven or probable) of 12.0% (range 2.5 to 30.8 %). The majority of people had received chemotherapy for a haematological malignancy or had undergone a hematopoietic stem cell transplant. Several PCR techniques were used among the included studies. The sensitivity and specificity of PCR for the diagnosis of IA varied according to the interpretative criteria used to define a test as positive. The mean sensitivity and specificity were 80.5% (95% CI; 73.0 to 86.3) and 78.5% (67.8 to 86.4) for a single positive test result, and 58.0% (36.5 to 76.8) and 96.2% (89.6 to 98.6) for two consecutive positive test results.
AUTHORS' CONCLUSIONS
PCR shows moderate diagnostic accuracy when used as screening tests for IA in high-risk patient groups. Importantly the sensitivity of the test confers a high negative predictive value (NPV) such that a negative test allows the diagnosis to be excluded. Consecutive positives show good specificity in diagnosis of IA and could be used to trigger radiological and other investigations or for pre-emptive therapy in the absence of specific radiological signs when the clinical suspicion of infection is high. When a single PCR positive test is used as diagnostic criterion for IA in a population of 100 people with a disease prevalence of 13.0% (overall mean prevalence), three people with IA would be missed (sensitivity 80.5%, 19.5% false negatives), and 19 people would be unnecessarily treated or referred for further tests (specificity of 78.5%, 21.5% false negatives). If we use the two positive test requirement in a population with the same disease prevalence, it would mean that six IA people would be missed (sensitivity 58.0%, 42.1% false negatives) and three people would be unnecessarily treated or referred for further tests (specificity of 96.2%, 3.8% false negatives). Galactamannan and PCR have good NPV for excluding disease but the low prevalence of disease limits the ability to rule in a diagnosis. The biomarkers are detecting different aspects of disease and the combination of both together is likely to be more useful.
Topics: Aspergillosis; Cohort Studies; Data Accuracy; False Negative Reactions; False Positive Reactions; Humans; Immunocompromised Host; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity
PubMed: 26343815
DOI: 10.1002/14651858.CD009551.pub2 -
Sensors (Basel, Switzerland) Jan 2023This systematic review describes and discusses three commercially available integrated systems for forensic DNA analysis, i.e., ParaDNA, RapidHIT, and ANDE. A variety of... (Review)
Review
This systematic review describes and discusses three commercially available integrated systems for forensic DNA analysis, i.e., ParaDNA, RapidHIT, and ANDE. A variety of aspects, such as performance, time-to-result, ease-of-use, portability, and costs (per analysis run) of these three (modified) rapid DNA analysis systems, are considered. Despite their advantages and developmental progress, major steps still have to be made before rapid systems can be broadly applied at crime scenes for full DNA profiling. Aspects in particular that need (further) improvement are portability, performance, the possibility to analyze a (wider) variety of (complex) forensic samples, and (cartridge) costs. Moreover, steps forward regarding ease-of-use and time-to-result will benefit the broader use of commercial rapid DNA systems. In fact, it would be a profit if rapid DNA systems could be used for full DNA profile generation as well as indicative analyses that can give direction to forensic investigators which will speed up investigations.
Topics: Forensic Genetics; Microsatellite Repeats; Polymerase Chain Reaction; DNA Fingerprinting; DNA
PubMed: 36772114
DOI: 10.3390/s23031075 -
Haematologica May 2017Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute... (Meta-Analysis)
Meta-Analysis Review
Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (hazard ratio=2.76 [1.90-4.00]), overall survival (hazard ratio=2.36 [1.73-3.22]), and cumulative incidence of relapse (hazard ratio=3.65 [2.53-5.27]), but not non-relapse mortality (hazard ratio=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than polymerase chain reaction-based detection (I=75.1% <0.1% for leukemia-free survival, 67.8% <0.1% for overall survival, and 22.1% <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation.
Topics: Acute Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Neoplasm Recurrence, Local; Neoplasm, Residual; Prognosis; Survival Analysis; Transplantation, Homologous
PubMed: 28126965
DOI: 10.3324/haematol.2016.159343 -
Journal of Pharmacy & Pharmaceutical... 2021To provide the latest evidence on the efficacy and safety of lopinavir/ritonavir compared to other treatment options for COVID-19. (Meta-Analysis)
Meta-Analysis
PURPOSE
To provide the latest evidence on the efficacy and safety of lopinavir/ritonavir compared to other treatment options for COVID-19.
METHODS
We searched PubMed, Cochran Library, Embase, Scopus, and Web of Science for the relevant records up to April 2021. Moreover, we scanned MedRxiv, Google Scholar, and clinical registry databases to identify additional records. We have used the Newcastle-Ottawa Scale and Cochrane risk of bias tools to assess the quality of studies. This Meta-analysis was conducted using RevMan software (version 5.3).
RESULTS
Fourteen studies were included. No significant difference was observed between lopinavir/ritonavir and non-antiviral treatment groups in terms of negative rate of PCR (polymerase chain reaction) on day 7 (risk ratio [RR]: 0.83; 95% CI: 0.63 to 1.09; P=0.17), and day 14 (RR: 0.93; 95% CI: 0.81 to 1.05; P=0.25), PCR negative conversion time (mean difference [MD]: 1.09; 95% CI: -0.10 to 2.29; P=0.07), secondary outcomes, and adverse events (P>0.05). There was no significant difference between lopinavir/ritonavir and chloroquine as well as lopinavir/ritonavir and hydroxychloroquine regarding the efficacy outcomes (P>0.05). However, lopinavir/ritonavir showed better efficacy than arbidol for the same outcomes (P<0.05). Lopinavir/ritonavir plus arbidol was effective compared to arbidol alone in terms of the negative rate of PCR on day 7 (P=0.02). However, this difference was not significant regarding other efficacy outcomes (P>0.05).
CONCLUSION
Lopinavir/ritonavir has no more treatment effects than other therapeutic agents used herein in COVID-19 patients.
Topics: COVID-19; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Hydroxychloroquine; Lopinavir; Randomized Controlled Trials as Topic; Retrospective Studies; Ritonavir; COVID-19 Drug Treatment
PubMed: 34048671
DOI: 10.18433/jpps31668 -
Genes Aug 2023Stem cells have been associated with self-renewing and plasticity and have been investigated in various odontogenic lesions in association with their pathogenesis and... (Review)
Review
BACKGROUND
Stem cells have been associated with self-renewing and plasticity and have been investigated in various odontogenic lesions in association with their pathogenesis and biological behavior. We aim to provide a systematic review of stem cell markers' expression in odontogenic tumors and cysts.
METHODS
The literature was searched through the MEDLINE/PubMed, EMBASE via OVID, Web of Science, and CINHAL via EBSCO databases for original studies evaluating stem cell markers' expression in different odontogenic tumors/cysts, or an odontogenic disease group and a control group. The studies' risk of bias (RoB) was assessed via a Joanna Briggs Institute Critical Appraisal Tool. Meta-analysis was conducted for markers evaluated in the same pair of odontogenic tumors/cysts in at least two studies.
RESULTS
29 studies reported the expression of stem cell markers, e.g., SOX2, OCT4, NANOG, CD44, ALDH1, BMI1, and CD105, in various odontogenic lesions, through immunohistochemistry/immunofluorescence, polymerase chain reaction, flow cytometry, microarrays, and RNA-sequencing. Low, moderate, and high RoBs were observed in seven, nine, and thirteen studies, respectively. Meta-analysis revealed a remarkable discriminative ability of SOX2 for ameloblastic carcinomas or odontogenic keratocysts over ameloblastomas.
CONCLUSION
Stem cells might be linked to the pathogenesis and clinical behavior of odontogenic pathologies and represent a potential target for future individualized therapies.
PubMed: 37761874
DOI: 10.3390/genes14091735 -
Annals of Medicine and Surgery (2012) Dec 2021As the COVID-19 pandemic rages on, reports on disparities in vaccine roll out alongside COVID-19 reinfection have been emerging. We conducted a systematic review to... (Review)
Review
BACKGROUND
As the COVID-19 pandemic rages on, reports on disparities in vaccine roll out alongside COVID-19 reinfection have been emerging. We conducted a systematic review to assess the determinants and disease spectrum of COVID-19 reinfection.
MATERIALS AND METHODS
A comprehensive search covering relevant databases was conducted for observational studies reporting Polymerase Chain Reaction (PCR) confirmed infection and reinfection cases. A quality assessment tool developed by the National Institute of Health (NIH) for the assessment of case series was utilized. Meta-analyses were performed using RevMan 5.3 for pooled proportions of findings in first infection and reinfection with a 95% confidence interval (CI).
RESULTS
Eighty-one studies reporting 577 cases were included from 22 countries. The mean age of patients was 46.2 ± 18.9 years and 179 (31.0%) cases of comorbidities were reported. The average time duration between first infection and reinfection was 63.6 ± 48.9 days. During first infection and reinfection, fever was the most common symptom (41.4% and 36.4%, respectively) whilst anti-viral therapy was the most common treatment regimen administered (44.5% and 43.0%, respectively). Comparable odds of symptomatic presentation and management were reported for the two infections. However, a higher Intensive Care Unit (ICU) admission rate was observed in reinfection compared to first infection (10 vs 3). Ten deaths were reported with respiratory failure being the most common cause of death (7/10 deaths).
CONCLUSION
Our findings support immunization practices given increased ICU admissions and mortality in reinfections. Our cohort serves as a guide for clinicians and authorities in devising an optimal strategy for controlling the pandemic. (249 words).
PubMed: 34900250
DOI: 10.1016/j.amsu.2021.103130 -
Diagnostics (Basel, Switzerland) Nov 2022The present systematic review and meta-analysis about the accuracy of diagnostic tests aim to describe the findings of literature over the last thirty years for the... (Review)
Review
The present systematic review and meta-analysis about the accuracy of diagnostic tests aim to describe the findings of literature over the last thirty years for the diagnosis of Chagas disease (CD). This work aimed to determine the accuracy of diagnostic techniques for CD in the disease's acute and chronic phases. The PubMed database was searched for studies published between 1990 and 2021 on CD diagnostics. Fifty-six published studies that met the criteria were analyzed and included in the meta-analysis, evaluating diagnostic accuracy through sensitivity and specificity. For Enzyme-Linked Immunosorbent Assay (ELISA), Fluorescent Antibody Technique (IFAT), Hemagglutination Test (HmT), Polymerase Chain Reaction (PCR), and Real-Time Polymerase Chain Reaction (qPCR) diagnosis methods, the sensitivity had a median of 99.0%, 78.0%, 75.0%, 76.0%, and 94.0%, respectively; while specificity presented a median of 99.0%, 99.0%, 99.0%, 98.0%, and 98.0%, respectively. This meta-analysis showed that ELISA and qPCR techniques had a higher performance compared to other methods of diagnosing CD in the chronic and acute phases, respectively. It was concluded utilizing the Area Under the Curve restricted to the false positive rates (AUC), that the ELISA diagnostic test presents the highest performance in diagnosing acute and chronic CD, compared to serological and molecular tests. Future studies focusing on new CD diagnostics approaches should be targeted.
PubMed: 36359595
DOI: 10.3390/diagnostics12112752 -
European Journal of Radiology Open 2023The optimal choice of protocol for diagnostic imaging in children with tuberculosis (TB) is a contemporary challenge due to the war in Ukraine, which potentially can... (Review)
Review
PURPOSE
The optimal choice of protocol for diagnostic imaging in children with tuberculosis (TB) is a contemporary challenge due to the war in Ukraine, which potentially can create a steep rise in TB cases in Western Europe. We aimed to gather all primary research comparing imaging modalities and their diagnostic accuracies for pulmonary findings in children with suspected or confirmed pulmonary tuberculosis (PTB).
METHOD
We searched the databases PubMed and Embase using pre-specified search terms, for English- and non-English published and un-published reports from the period 1972 to 2022. We retrieved reports via citation search in excluded literature reviews and systematic reviews. Studies were eligible if most of the study population was between 0 and 18 years of age with confirmed or suspected PTB, and study participants had described diagnostic images from two or more different imaging modalities.
RESULTS
A total of 15 studies investigated conventional chest X-Ray (CXR) and computed tomography (CT) in diagnosing PTB in children. Nine studies investigated the number of participants in where CT or CXR confirmed the diagnosis of TB, and all of them, including a total of 1244 patients, reported that findings compatible with TB were more frequently detected on CT than CXR. Only two studies did not include radiological findings as part of their diagnostic criteria for PTB, and combined they showed that CT diagnosed 54/54 (100 %) children with confirmed PTB, while CXR diagnosed 42/54 (78 %). Two studies compared magnetic resonance imaging (MRI) with CXR and showed that MRI diagnosed more children with PTB than CXR. One study reported a higher positive predictive value (PPV), sensitivity and specificity for PTB findings for MRI than CXR. One study compared CXR with high-kilovolt (high-kV) CXR, finding compatible sensitivity and specificity regarding confirmation of PTB. Two studies compared ultrasound (US) with CXR and found that US had a higher diagnostic yield and more often correctly identified consolidations, mediastinal LAP, and pleural effusion.
CONCLUSION
CT showed a higher diagnostic accuracy for PTB findings than CXR, MRI and US, and should be the imaging modality of first choice when available. MRI had a higher sensitivity and specificity than CXR for LAP, pleural effusion, and cavitation. US was complimentary in initial diagnostic work-up and follow up. A diagnostic strategy for PTB in children according to local availability and expertise is proposed, as no evidence from this systematic review shows otherwise, in acknowledgement of the expertise in high TB-burdened countries. CT can be performed when in doubt, due to the higher diagnostic yield.
PubMed: 36624819
DOI: 10.1016/j.ejro.2022.100472 -
Current Ophthalmology Reports 2020Studies have reported ocular involvement in the coronavirus disease 2019 (COVID-19), with SARS-CoV-2 having been detected in ocular swab samples. This has implicated the... (Review)
Review
PURPOSE OF REVIEW
Studies have reported ocular involvement in the coronavirus disease 2019 (COVID-19), with SARS-CoV-2 having been detected in ocular swab samples. This has implicated the eye as a portal of transmission. The aim of this systemic review is to summarise and discuss the current literature regarding ocular involvement of SARS-CoV-2 in COVID-19.
RECENT FINDINGS
In this systematic review, the prevalence of ocular symptoms and signs was low (from 0 to 31.58%) and conjunctivitis was a relatively rare occurrence. The rate of detection of SARS-CoV-2 in the ocular swab samples was low as well and this ranged from 0 to 11.11%. The development of ocular symptoms and signs was not always accompanied by the detection of SARS-CoV-2 in the ocular swab samples. The opposite was described as well. This may reflect issues related to the characteristics of SARS-CoV-2 and of the study design. Nonetheless, the nature of research in a pandemic is that conclusions can change as more information is obtained.
SUMMARY
Whilst the eye is unlikely to be a main transmission route, we need to consider the possibilities of conjunctivitis as a presenting complaint and of the eye playing a role in the transmission of SARS-CoV-2. Furthermore, we need to take the appropriate precautions in our practice. Further studies are needed to evaluate the viral tropism of SARS-CoV-2 and its role in the eyes.
PubMed: 33014631
DOI: 10.1007/s40135-020-00257-7 -
JAMA Network Open Oct 2022After a cluster of pediatric cases of hepatitis of unknown etiology were identified in Scotland in March 2022, the World Health Organization published an outbreak alert,...
IMPORTANCE
After a cluster of pediatric cases of hepatitis of unknown etiology were identified in Scotland in March 2022, the World Health Organization published an outbreak alert, and more than 1010 probable cases were reported. Some cases progressed to acute liver failure and required liver transplant. Although many patients had positive results for adenovirus on polymerase chain reaction testing from whole blood samples and/or reported recent COVID-19 infection (with or without seropositivity), the precise pathogenesis remains unclear despite the high potential morbidity of this condition.
OBJECTIVE
To summarize the currently available evidence regarding novel pediatric hepatitis of unknown etiology (or novel hepatitis), encompassing case numbers, testing, management, and outcomes.
EVIDENCE REVIEW
A rapid review of the literature from April 1, 2021, to August 30, 2022, aimed to identify all available published case series and case-control studies of novel hepatitis. The search included PubMed and references and citations of short-listed studies.
FINDINGS
A total of 22 available case series and case-control studies describing 1643 cases were identified, with 120 children (7.3%) receiving liver transplants and 24 deaths (1.5%). Outcome reporting and testing for adenovirus and SARS-CoV-2 was incomplete. Assessment of disease severity and management was mixed and results regarding testing for adenovirus and SARS-CoV-2 were inconsistent for both serological testing and testing of explant or biopsy liver samples. More recent studies suggest a more plausible role for adenovirus and/or adeno-associated virus 2.
CONCLUSIONS AND RELEVANCE
This systematic review without meta-analysis describes the challenge posed by hepatitis of unknown etiology in terms of investigation and management, with many cases progressing to acute liver failure. The lack of clarity regarding pathogenesis means that these children may be missing the potential for targeted therapies to improve outcomes and avert the need for transplant. Clinicians, immunologists, and epidemiologists must collaborate to investigate the pathogenesis of this novel hepatitis.
Topics: Humans; Child; SARS-CoV-2; COVID-19; Disease Outbreaks; Hepatitis; Liver Failure, Acute
PubMed: 36255724
DOI: 10.1001/jamanetworkopen.2022.37091