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The International Journal of... Aug 2003As Mycobacterium tuberculosis isolation rates in tuberculous effusions are relatively low, several biochemical and immunological markers have been proposed to diagnose... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
As Mycobacterium tuberculosis isolation rates in tuberculous effusions are relatively low, several biochemical and immunological markers have been proposed to diagnose tuberculous pleurisy including adenosine deaminase (ADA) and interferon-gamma (IFN-gamma). Here we summarise the literature on ADA and IFN-gamma as predictors of tuberculous pleurisy.
METHODS
After a systematic review of English language studies, we used summary receiver operating characteristic curve (SROC) analysis to determine the cumulative diagnostic accuracy of both markers and Bayes' theorem to calculate post-test probability of disease in settings with different prevalences of tuberculous pleurisy, assessed and reported the quality of primary studies.
RESULTS
From 1978 to November 2000, studies containing sufficient data for the determination of both sensitivity and specificity were 31 on ADA, including 4738 patients, and 13 on IFN-gamma, including 1189 patients. SROC curve yielded a maximum joint sensitivity and specificity of 93% for ADA and 96% for IFN-gamma. In the setting of tuberculous effusion prevalence of 5%, 25% and 85%, post-test probability of a negative ADA test were 0.4%, 2.4% and 24%, and 0.22%, 1.2% and 17% for a negative IFN-gamma test.
CONCLUSION
With the caveat that limitations in the design of the studies summarised here may distort estimates of test performance, ADA and IFN-gamma appear to be reasonably accurate at detecting TB pleurisy.
Topics: Adenosine Deaminase; Bayes Theorem; Biomarkers; Clinical Trials as Topic; Humans; Interferon-gamma; Mycobacterium tuberculosis; Predictive Value of Tests; ROC Curve; Tuberculosis, Pleural
PubMed: 12921155
DOI: No ID Found -
Orphanet Journal of Rare Diseases May 2023Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally... (Review)
Review
INTRODUCTION
Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally described as mimicker of polyarteritis nodosa, with immunodeficiency and early-onset stroke.
METHODS
A systematic review according to PRISMA approach, including all articles published before the 31st of August 2021 in Pubmed and EMBASE database was performed.
RESULTS
The search identified 90 publications describing 378 unique patients (55.8% male). To date 95unique mutations have been reported. The mean age at disease onset was 92.15 months (range 0-720 months), 32 (8.5%) showed an onset of the first signs/symptoms after 18 years old and 96 (25.4%) after 10 years old. The most frequent clinical characteristics described were cutaneous (67.9%), haematological manifestations (56.3%), recurrent fever (51.3%), neurological as stroke and polyneuropathy (51%), immunological abnormalities (42.3%), arthralgia/arthritis (35.4%), splenomegaly (30.6%), abdominal involvement (29.8%), hepatomegaly (23.5%), recurrent infections (18.5%), myalgia (17.9%), kidney involvement (17.7%) etc. Patients with skin manifestations were older than the others (101.1 months SD ± 116.5, vs. 75.3 SD ± 88.2, p 0.041), while those with a haematological involvement (64.1 months SD ± 75.6 vs. 133.1 SD ± 133.1, p < 0.001) and immunological involvement (73.03 months SD ± 96.9 vs. 103.2 SD ± 112.9, p 0.05) are younger than the others. We observed different correlations among the different clinical manifestations. The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) has improved the current history of the disease.
CONCLUSION
Due to this highly variable phenotype and age of presentation, patients with DADA2 may present to several type of specialists. Given the important morbidity and mortality, early diagnosis and treatment are mandatory.
Topics: Male; Female; Humans; Adenosine Deaminase; Intercellular Signaling Peptides and Proteins; Phenotype; Stroke; Mutation
PubMed: 37179309
DOI: 10.1186/s13023-023-02721-6 -
ACR Open Rheumatology Feb 2021The object of this study was to analyze the benefits and harms of different treatment options and to analyze test accuracy used in the evaluation of patients with...
OBJECTIVE
The object of this study was to analyze the benefits and harms of different treatment options and to analyze test accuracy used in the evaluation of patients with primary systemic polyarteritis nodosa (PAN).
METHODS
A systematic search of published English-language literature was performed in Ovid Medline, PubMed, Embase, and the Cochrane Library from the inception of each database through August 2019. Articles were screened for suitability in addressing patient, intervention, comparison, and outcome questions, with studies presenting the highest level of evidence given preference.
RESULTS
Of 137 articles selected for data abstraction, we analyzed 21 observational studies and seven randomized controlled trials (RCTs). The results showed indirect evidence that a deep skin biopsy provides good diagnostic accuracy. A combined nerve and muscle biopsy should be obtained for patients with PAN with peripheral neuropathy. Cyclophosphamide with high-dose glucocorticoids (GCs) is effective as an induction treatment for newly diagnosed active and severe PAN. GC monotherapy is adequate in the majority of patients with nonsevere PAN, although it has a high relapse rate with GC taper. There was insufficient data in determining the optimal duration of non-GC and GC maintenance therapy. Tumor necrosis factor inhibitors are effective treatment for patients with deficiency of adenosine deaminase 2 (DADA2) with stroke and vasculitis manifestations.
CONCLUSION
This comprehensive systematic review synthesizes and evaluates the harms and benefits of different treatment options and the accuracy of commonly used tests for the diagnosis of systemic PAN. Data for diagnosis and management of PAN and DADA2 are mostly limited to observational studies. More high-quality RCTs are needed.
PubMed: 33512781
DOI: 10.1002/acr2.11189 -
The International Journal of... Nov 2010To determine the accuracy of adenosine deaminase (ADA) measurements in the diagnosis of tuberculous meningitis (TBM). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the accuracy of adenosine deaminase (ADA) measurements in the diagnosis of tuberculous meningitis (TBM).
DESIGN
After a systematic review of English language studies, the sensitivity, specificity and accuracy of ADA concentrations in the diagnosis of cerebrospinal fluid (CSF) were evaluated using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance.
RESULTS
Ten studies met our inclusion criteria. The sensitivity of ADA in the diagnosis of TBM was 0.79 (95%CI 0.75-0.83), specificity 0.91 (95%CI 0.89-0.93), positive likelihood ratio 6.85 (95%CI 4.11-11.41), negative likelihood ratio 0.29 (95%CI 0.19-0.44) and diagnostic odds ratio 26.93 (95%CI 12.73-56.97).
CONCLUSION
Our data suggest that ADA in the CSF can be a sensitive and specific target and a critical criteria for the diagnosis of TBM.
Topics: Adenosine Deaminase; Humans; Likelihood Functions; Models, Statistical; ROC Curve; Sensitivity and Specificity; Tuberculosis, Meningeal
PubMed: 20937176
DOI: No ID Found -
Biomolecules Mar 2022RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination... (Review)
Review
RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination of Adenosine (A) to Inosine (I) or Cytidine (C) to Uridine (U) is the most common type of mammalian RNA editing. It occurs as a nuclear co- and/or post-transcriptional event catalyzed by ADARs (Adenosine deaminases acting on RNA) and APOBECs (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like genes). RNA editing may modify the structure, stability, and processing of a transcript. This review focuses on RNA editing in psychiatric, neurological, neurodegenerative (NDs), and autoimmune brain disorders in humans and rodent models. We discuss targeted studies that focus on RNA editing in specific neuron-enriched transcripts with well-established functions in neuronal activity, and transcriptome-wide studies, enabled by recent technological advances. We provide comparative editome analyses between human disease and corresponding animal models. Data suggest RNA editing to be an emerging mechanism in disease development, displaying common and disease-specific patterns. Commonly edited RNAs represent potential disease-associated targets for therapeutic and diagnostic values. Currently available data are primarily descriptive, calling for additional research to expand global editing profiles and to provide disease mechanistic insights. The potential use of RNA editing events as disease biomarkers and available tools for RNA editing identification, classification, ranking, and functional characterization that are being developed will enable comprehensive analyses for a better understanding of disease(s) pathogenesis and potential cures.
Topics: Adenosine; Adenosine Deaminase; Animals; Brain; Brain Diseases; Mammals; Neurodegenerative Diseases; RNA; RNA Editing
PubMed: 35327657
DOI: 10.3390/biom12030465 -
Journal of Clinical Gastroenterology Sep 2006Adenosine deaminase (ADA) levels are used for diagnosing tuberculosis in several locations and although many studies have evaluated ADA levels in ascitic fluid. These... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND GOALS
Adenosine deaminase (ADA) levels are used for diagnosing tuberculosis in several locations and although many studies have evaluated ADA levels in ascitic fluid. These studies have defined arbitrary cut-off points creating difficulties in the clinical application of the results. The goals of this study are: to determine the usefulness of ADA levels in ascitic fluid as a diagnostic test for peritoneal tuberculosis (PTB) and define the best cut-off point.
STUDY
A systematic review was done on the basis of 2 independent searches. We selected prospective studies that included consecutive patients. Diagnosis of PTB had to be confirmed by bacteriologic or histologic methods and ADA levels determined by the Giusti method. Inclusion/exclusion criteria were applied by 2 independent reviewers. A receiver operating characteristic curve was constructed to establish the optimal cut-off point and the likelihood ratios (LRs) estimated using fixed-effect pooled method.
RESULTS
Twelve prospective studies were found. Four of them met the inclusion criteria and were thus included in the meta-analysis. They included 264 patients, of which 50 (18.9%) had PTB. ADA levels showed high sensitivity (100%) and specificity (97%) using cut-off values from 36 to 40 IU/L. The included studies were homogeneous. Optimal cut-off point was determined at 39 IU/L, and LRs were 26.8 and 0.038 for values above and below this cut-off.
CONCLUSIONS
This study supports the proposition that ADA determination is a fast and discriminating test for diagnosing PTB with an optimal cut-off value of 39 IU/L.
Topics: Adenosine Deaminase; Ascitic Fluid; Clinical Enzyme Tests; Humans; Peritonitis, Tuberculous; Prospective Studies; ROC Curve; Sensitivity and Specificity
PubMed: 16940883
DOI: 10.1097/00004836-200609000-00009 -
Respiratory Medicine May 2008Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of adenosine deaminase (ADA) in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of adenosine deaminase (ADA) in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a meta-analysis to determine the accuracy of ADA measurements in the diagnosis of tuberculous pleurisy.
METHODS
After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of ADA concentration in the diagnosis of pleural effusion were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.
RESULTS
Sixty-three studies met our inclusion criteria. The summary estimates for ADA in the diagnosis of tuberculous pleurisy in the studies included were sensitivity 0.92 (95% confidence interval 0.90-0.93), specificity 0.90 (95% confidence interval 0.89-0.91), positive likelihood ratio 9.03 (95% confidence interval 7.19-11.35), negative likelihood ratio 0.10 (95% confidence interval 0.07-0.14), and diagnostic odds ratio 110.08 (95% confidence interval 69.96-173.20).
CONCLUSIONS
ADA determination is a relative sensitive and specific test for the diagnosis of tuberculous pleurisy. Measurement of ADA in pleural effusion is thus likely to be a useful diagnostic tool for tuberculous pleurisy. The results of ADA assays should be interpreted in parallel with clinical findings and the results of conventional tests.
Topics: Adenosine Deaminase; Biomarkers; Clinical Enzyme Tests; Humans; Mycobacterium tuberculosis; Odds Ratio; Pleural Effusion; ROC Curve; Sensitivity and Specificity; Tuberculosis, Pleural
PubMed: 18222681
DOI: 10.1016/j.rmed.2007.12.007 -
JAMA Jul 2007Pharmacotherapies that augment the incretin pathway have recently become available, but their role in the management of type 2 diabetes is not well defined. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Pharmacotherapies that augment the incretin pathway have recently become available, but their role in the management of type 2 diabetes is not well defined.
OBJECTIVE
To assess the efficacy and safety of incretin-based therapy in adults with type 2 diabetes based on randomized controlled trials published in peer-reviewed journals or as abstracts.
DATA SOURCES
We searched MEDLINE (1966-May 20, 2007) and the Cochrane Central Register of Controlled Trials (second quarter, 2007) for English-language randomized controlled trials involving an incretin mimetic (glucagonlike peptide 1 [GLP-1] analogue) or enhancer (dipeptidyl peptidase 4 [DPP4] inhibitor). We also searched prescribing information, relevant Web sites, reference lists and citation sections of recovered articles, and abstracts presented at recent conferences.
STUDY SELECTION
Randomized controlled trials were selected if they were at least 12 weeks in duration, compared incretin therapy with placebo or other diabetes medication, and reported hemoglobin A(1c) data in nonpregnant adults with type 2 diabetes.
DATA EXTRACTION
Two reviewers independently assessed trials for inclusion and extracted data. Differences were resolved by consensus. Meta-analyses were conducted for several efficacy and safety outcomes.
RESULTS
Of 355 potentially relevant articles identified, 51 were retrieved for detailed evaluation and 29 met the inclusion criteria. Incretins lowered hemoglobin A(1c) compared with placebo (weighted mean difference, -0.97% [95% confidence interval {CI}, -1.13% to -0.81%] for GLP-1 analogues and -0.74% [95% CI, -0.85% to -0.62%] for DPP4 inhibitors) and were noninferior to other hypoglycemic agents. Glucagonlike peptide 1 analogues resulted in weight loss (1.4 kg and 4.8 kg vs placebo and insulin, respectively) while DPP4 inhibitors were weight neutral. Glucagonlike peptide 1 analogues had more gastrointestinal side effects (risk ratio, 2.9 [95% CI, 2.0-4.2] for nausea and 3.2 [95% CI, 2.5-4.4] for vomiting). Dipeptidyl peptidase 4 inhibitors had an increased risk of infection (risk ratio, 1.2 [95% CI, 1.0-1.4] for nasopharyngitis and 1.5 [95% CI, 1.0-2.2] for urinary tract infection) and headache (risk ratio, 1.4 [95% CI, 1.1-1.7]). All but 3 trials had a 30-week or shorter duration; thus, long-term efficacy and safety could not be evaluated.
CONCLUSIONS
Incretin therapy offers an alternative option to currently available hypoglycemic agents for nonpregnant adults with type 2 diabetes, with modest efficacy and a favorable weight-change profile. Careful postmarketing surveillance for adverse effects, especially among the DPP4 inhibitors, and continued evaluation in longer-term studies and in clinical practice are required to determine the role of this new class among current pharmacotherapies for type 2 diabetes.
Topics: Adamantane; Adenosine Deaminase Inhibitors; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Glucagon-Like Peptide 1; Glycoproteins; Humans; Hypoglycemic Agents; Liraglutide; Nitriles; Peptides; Pyrazines; Pyrrolidines; Sitagliptin Phosphate; Triazoles; Venoms; Vildagliptin
PubMed: 17622601
DOI: 10.1001/jama.298.2.194 -
Clinical & Developmental Immunology 2012High HIV burden countries have experienced a high burden of pleural TB in HIV-infected patients. (Review)
Review
BACKGROUND
High HIV burden countries have experienced a high burden of pleural TB in HIV-infected patients.
OBJECTIVE
To review the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients.
METHODS
A literature search from 1950 to June 2011 in MEDLINE was conducted.
RESULTS
Two-hundred and ninety-nine studies were identified, of which 30 met the inclusion criteria. The immunopathogenesis as denoted by cells and cytokine profiles is distinctly different between HIV and HIV-uninfected pleural TB disease. Adenosine deaminase and interferon gamma are good markers of pleural TB disease even in HIV-infected patients. HIV-uninfected TB suspects with pleural effusions commonly have a low yield of TB organisms however the evidence suggests that in dually infected patients smear and cultures have a higher yield. The Gene Xpert MTB/RIF assay has significant potential to improve the diagnosis of pleural TB in HIV-positive patients.
CONCLUSIONS
Pleural TB in HIV-infected patients has a different immunopathogenesis than HIV-uninfected pleural TB and these findings in part support the differences noted in this systematic review. Research should focus on developing an interferon gamma-based point of care diagnostic test and expansion of the role of Gene Xpert in the diagnosis of pleural TB.
Topics: Adenosine Deaminase; Anti-HIV Agents; Antitubercular Agents; Bacterial Load; Biomarkers; CD4 Lymphocyte Count; Coinfection; HIV Infections; HIV-1; Humans; Interferon-gamma; Mycobacterium tuberculosis; Tuberculosis, Pleural; Viral Load
PubMed: 22474483
DOI: 10.1155/2012/842045 -
Sports Medicine (Auckland, N.Z.) May 2015'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic... (Review)
Review
BACKGROUND AND OBJECTIVE
'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic environment. In lowlanders who ascend to altitude, genetic factors may also contribute to the substantial interindividual variation in exercise performance noted at altitude. We performed a systematic literature review to identify genetic variants of possible influence on human hypoxic exercise performance, commenting on the strength of any identified associations.
CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW
All studies of the association of genetic factors with human hypoxic exercise performance, whether at sea level using 'nitrogen dilution of oxygen' (normobaric hypoxia), or at altitude or in low-pressure chambers (field or chamber hypobaric hypoxia, respectively) were sought for review.
SEARCH STRATEGY FOR IDENTIFICATION OF STUDIES
Two electronic databases were searched (Ovid MEDLINE, Embase) up to 31 January 2014. We also searched the reference lists of relevant articles for eligible studies. All studies published in English were included, as were studies in any language for which the abstract was available in English.
DATA COLLECTION AND ANALYSIS
Studies were selected and data extracted independently by two reviewers. Differences regarding study inclusion were resolved through discussion. The quality of each study was assessed using a scoring system based on published guidelines for conducting and reporting genetic association studies.
RESULTS
A total of 11 studies met all inclusion criteria and were included in the review. Subject numbers ranged from 20 to 1,931 and consisted of healthy individuals in all cases. The maximum altitude of exposure ranged from 2,690 to 8,848 m. The exercise performance phenotypes assessed were mountaineering performance (n = 5), running performance (n = 2), and maximum oxygen consumption ([Formula: see text]O2max) (n = 4). In total, 13 genetic polymorphisms were studied, four of which were associated with hypoxic exercise performance. The adenosine monophosphate deaminase (AMPD1) C34T (rs17602729), beta2-adrenergic receptor (ADRB2) Gly16Arg single nucleotide polymorphism (SNP) (rs1042713), and androgen receptor CAG repeat polymorphisms were associated with altitude performance in one study, and the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) (rs4646994) polymorphism was associated with performance in three studies. The median score achieved in the study quality analysis was 6 out of 10 for case-control studies, 8 out of 10 for cohort studies with a discrete outcome, 6 out of 9 for cohort studies with a continuous outcome, and 4.5 out of 8 for genetic admixture studies.
CONCLUSION
The small number of articles identified in the current review and the limited number of polymorphisms studied in total highlights that the influence of genetic factors on exercise performance in hypoxia has not been studied in depth, which precludes firm conclusions being drawn. Support for the association between the ACE-I allele and improved high-altitude performance was the strongest, with three studies identifying a relationship. Analysis of study quality highlights the need for future studies in this field to improve the conduct and reporting of genetic association studies.
Topics: AMP Deaminase; Actinin; Altitude Sickness; Athletic Performance; Exercise; Genetic Variation; Genotype; Humans; INDEL Mutation; Oxygen Consumption; Peptidyl-Dipeptidase A
PubMed: 25682119
DOI: 10.1007/s40279-015-0309-8