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BMJ Open Jun 2017To perform a meta-analysis to evaluate the diagnostic performance of the antiglycoprotein-2 (GP2) antibody for Crohn's disease (CD). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To perform a meta-analysis to evaluate the diagnostic performance of the antiglycoprotein-2 (GP2) antibody for Crohn's disease (CD).
METHODS
Three databases (EMBASE, ISI Web of Knowledge and PubMed) were systematically searched. There were 17 eligible studies included in the meta-analysis. A total of 2439 patients with CD and 3184 controls were involved in these studies. STATA V.11.2 and Meta-DiSc V.1.4 were used to perform the meta-analysis.
RESULTS
The area under the summary receiver operating characteristic curve was 0.68-0.72. The pooled diagnostic sensitivity of the anti-GP2 antibody ranged from 14% to 24%, and the specificity was 96%-98%.
CONCLUSIONS
The anti-GP2 antibody is a specific biomarker for CD, and further exploration of its prevalence among different clinical phenotypes of CD will provide a better understanding of its diagnostic performance.
Topics: Antibodies; Area Under Curve; Biomarkers; Crohn Disease; GPI-Linked Proteins; Humans; ROC Curve
PubMed: 28601823
DOI: 10.1136/bmjopen-2016-014843 -
Blood Advances Jun 2023Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis and is challenging to diagnose because...
Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis and is challenging to diagnose because of the complicated testing methods required. We performed a systematic review of all reported cases to better assess the clinical, immunohematologic, and therapeutic characteristics of PCH. We systematically analyzed PubMed, Medline, and EMBASE to identify all cases of PCH confirmed by Donath-Landsteiner (DL) testing. Three authors independently screened articles for inclusion, and systematically extracted epidemiologic, clinical, laboratory, treatment, and outcomes data. Discrepancies were adjudicated by a fourth author. We identified 230 cases, with median presentation hemoglobin of 6.5 g/dL and nadir of 5.5 g/dL. The most common direct antiglobulin test (DAT) result was the presence of complement and absence of immunoglobulin G (IgG) bound to red blood cells, although other findings were observed in one-third of cases. DL antibody class and specificity were reported for 71 patients, of which 83.1% were IgG anti-P. The use of corticosteroids is common, although we found no significant difference in the length of hospitalization for patients with and without steroid therapy. Recent reports have highlighted the use of complement inhibitors. Among patients with follow-up, 99% (213 of 216) were alive at the time of reporting. To our knowledge, this represents the largest compilation of PCH cases to date. We discovered that contemporary PCH most commonly occurs in children with a preceding viral infection, corticosteroid use is frequent (but potentially ineffective), and DAT results are more disparate than traditionally reported.
Topics: Child; Humans; Hemoglobinuria, Paroxysmal; Erythrocytes; Anemia, Hemolytic, Autoimmune; Adrenal Cortex Hormones; Immunoglobulin G
PubMed: 36716137
DOI: 10.1182/bloodadvances.2022009516 -
PLoS Neglected Tropical Diseases 2013Strongyloidiasis is frequently under diagnosed since many infections remain asymptomatic and conventional diagnostic tests based on parasitological examination are not... (Review)
Review
BACKGROUND
Strongyloidiasis is frequently under diagnosed since many infections remain asymptomatic and conventional diagnostic tests based on parasitological examination are not sufficiently sensitive. Serology is useful but is still only available in reference laboratories. The need for improved diagnostic tests in terms of sensitivity and specificity is clear, particularly in immunocompromised patients or candidates to immunosuppressive treatments. This review aims to evaluate both conventional and novel techniques for the diagnosis of strongyloidiasis as well as available cure markers for this parasitic infection.
METHODOLOGY/PRINCIPAL FINDINGS
The search strategy was based on the data-base sources MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS and was limited in the search string to articles published from 1960 to August 2012 and to English, Spanish, French, Portuguese and German languages. Case reports, case series and animal studies were excluded. 2003 potentially relevant citations were selected for retrieval, of which 1649 were selected for review of the abstract. 143 were eligible for final inclusion.
CONCLUSIONS
Sensitivity of microscopic-based techniques is not good enough, particularly in chronic infections. Furthermore, techniques such as Baermann or agar plate culture are cumbersome and time-consuming and several specimens should be collected on different days to improve the detection rate. Serology is a useful tool but it might overestimate the prevalence of disease due to cross-reactivity with other nematode infections and its difficulty distinguishing recent from past (and cured) infections. To evaluate treatment efficacy is still a major concern because direct parasitological methods might overestimate it and the serology has not yet been well evaluated; even if there is a decline in antibody titres after treatment, it is slow and it needs to be done at 6 to 12 months after treatment which can cause a substantial loss to follow-up in a clinical trial.
Topics: Animals; Clinical Laboratory Techniques; Drug Monitoring; Humans; Parasitology; Sensitivity and Specificity; Strongyloides; Strongyloidiasis
PubMed: 23350004
DOI: 10.1371/journal.pntd.0002002 -
International Journal of Rheumatic... May 2021To evaluate the diagnostic value of anti-citrullinated α-enolase peptide 1 (anti-CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic... (Meta-Analysis)
Meta-Analysis
AIM
To evaluate the diagnostic value of anti-citrullinated α-enolase peptide 1 (anti-CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic review and meta-analysis.
METHODS
The PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases were searched for relevant studies published until September 23, 2020. A bivariate mixed-effects model was used to calculate the diagnostic indices from primary data of eligible studies. We performed meta-regression and subgroup analysis to explore the sources of heterogeneity.
RESULTS
Twenty-four articles, with a total of 17 380 patients with RA and 7505 control participants, met the criteria for inclusion in the meta-analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratios for the anti-CEP 1 antibody were 44% (95% CI: 38%-51%), 97% (95% CI: 96%-98%), and 14.81 (95% CI: 10.66-20.57) and 0.57 (95% CI: 0.52-0.64), respectively. The pooled positive and negative predictive values were 0.96 (95% CI: 0.95-0.97) and 0.53 (95% CI: 0.43-0.63), respectively. The area under the summary receiver operating characteristic curve was 0.86. Meta-regression indicated that the anti-CEP 1 antibody detection method may be a source of heterogeneity. The subgroup analysis of the group in which the anti-CEP 1 antibody was detected by using a commercial enzyme-linked immunosorbent assay (ELISA) kit had a sensitivity of 59% (95% CI: 50%-68%) and a specificity of 93% (95% CI: 85%-97%).
CONCLUSIONS
The anti-CEP 1 antibody had moderate RA diagnostic value with relatively low sensitivity and high specificity. An ELISA may increase the RA diagnostic sensitivity.
Topics: Anti-Citrullinated Protein Antibodies; Antibodies; Arthritis, Rheumatoid; Biomarkers, Tumor; DNA-Binding Proteins; Enzyme-Linked Immunosorbent Assay; Genetic Predisposition to Disease; Humans; Peptides, Cyclic; Phosphopyruvate Hydratase; Sensitivity and Specificity; Tumor Suppressor Proteins
PubMed: 33713557
DOI: 10.1111/1756-185X.14093 -
F1000Research 2021Mass testing and adequate management are essential to terminate the spread of coronavirus disease 2019 (COVID-19). This testing is due to the possibility of...
Mass testing and adequate management are essential to terminate the spread of coronavirus disease 2019 (COVID-19). This testing is due to the possibility of unidentified cases, especially ones without COVID-19 related symptoms. This review aimed to examine the outcome of the existing studies on the ways of identifying COVID-19 cases, and determine the populations at risk, symptom and diagnostic test management of COVID-19. The articles reviewed were scientific publications on the PubMed, Science Direct, ProQuest, and Scopus databases. The keywords used to obtain the data were COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and case detection, case management or diagnostic test. We applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Population, Intervention, Control and Outcomes (PICO) approaches. A total of 21 articles from 13 countries met the inclusion criteria and were further analyzed qualitatively. However, 62% of the articles used a rapid antibody test for screening rather than a rapid antigen test. According to the rapid antigen test, 51.3% were positive, with men aged above 50 years recording the highest number of cases. Furthermore, 57.1% of patients were symptomatic, while diagnostic tests' sensitivity and specificity increased to 100% in 14 days after the onset. : Real-time polymerase chain reaction (RT-PCR) is recommended by the World Health Organization for detection of COVID-19. Suppose it is unavailable, the rapid antigen test is used as an alternative rather than the rapid antibody test. Diagnosis is expected to be confirmed using the PCR and serological assay to achieve an early diagnosis of COVID-19, according to disease progression, gradual rapid tests can be used, such as rapid antigen in an earlier week and antibody tests confirmed by RT-PCR and serological assay in the second week of COVID-19.
Topics: COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Humans; Male; SARS-CoV-2; Sensitivity and Specificity
PubMed: 35719313
DOI: 10.12688/f1000research.50929.3 -
BioMed Research International 2023Schistosomiasis is causing high morbidity and significant mortality in endemic areas. Kato-Katz stool examination and urine filtration techniques are the conventional... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Schistosomiasis is causing high morbidity and significant mortality in endemic areas. Kato-Katz stool examination and urine filtration techniques are the conventional methods for the detection of intestinal and urinary schistosomiasis. The most appropriate diagnostic tools for the detection of schistosomiasis especially in low-prevalence settings should be used. Therefore, this study is aimed at investigating the diagnostic accuracy of and diagnostic tools in sub-Saharan Africa.
METHODS
Electronic databases such as PubMed, PubMed Central/Medline, HINARI, Scopus, EMBASE, Science Direct, Google Scholar, and Cochrane Library were reviewed. The pooled estimates and heterogeneity were determined using Midas in Stata 14.0. The diagnostic accuracy of index tests was compared using the hierarchical summary of the receiver operating characteristic (HSROC) curve in Stata 14.0.
RESULTS
Twenty-four studies consisting of 12,370 individuals were tested to evaluate the accuracy of antigen, antibody, and molecular test methods for the detection of and . The pooled estimate of sensitivity and specificity of CCA was 88% (95% CI: 83-92) and 72 (95% CI: 62-80), respectively, when it is compared with parasitological stool examination for detection. On the other hand, ELISA showed a pooled estimate of sensitivity and specificity of 95% (95% CI: 93-96) and 35% (95% CI: 21-52), respectively, for the examination of using stool examination as a reference test. With regard to , the pooled estimate of sensitivity and specificity of polymerase chain reaction was 97% (95% CI: 78-100) and 94% (95% CI: 74-99), respectively. Moreover, the sensitivity and specificity of urine CCA vary between 41-80% and 55-91%, respectively, compared to urine microscopy.
CONCLUSION
The effort of schistosomiasis elimination requires accurate case identification especially in low-intensity infections. This study showed that CCA had the highest sensitivity and moderate specificity for the diagnosis of . Similarly, the sensitivity of ELISA was excellent, but its specificity was low. The diagnostic accuracy of PCR for the detection of was excellent compared to urine microscopic examination.
Topics: Humans; Animals; Microscopy; Schistosoma mansoni; Urinalysis; Africa South of the Sahara; Diagnostic Tests, Routine
PubMed: 37621699
DOI: 10.1155/2023/3769931 -
Health Technology Assessment... Oct 2022Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to...
BACKGROUND
Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma.
OBJECTIVES
The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care.
DESIGN
(1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives.
DATA SOURCES
For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE (National Library of Medicine, Bethesda, MD, USA), Embase (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform ( WHO ICTRP ) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews ( KSR ) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used.
REVIEW METHODS
For review 1, cohort and case-control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed.
RESULTS
People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5-2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents ( = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research.
LIMITATIONS
The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet.
CONCLUSIONS
Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia).
FUTURE WORK
Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42019115506 and CRD42020170766.
FUNDING
This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.
Topics: United States; Adult; Child; Male; Humans; Female; Celiac Disease; Longitudinal Studies; Prospective Studies; Skin Neoplasms; Immunoglobulin A; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 36321689
DOI: 10.3310/ZUCE8371 -
Przeglad Gastroenterologiczny 2015Keratins are proteins that form intermediate filaments of epithelial cell cytoskeleton. The utility of keratin expression determination is based on the fact that... (Review)
Review
Keratins are proteins that form intermediate filaments of epithelial cell cytoskeleton. The utility of keratin expression determination is based on the fact that epithelial cells acquire a specific pattern of keratin expression during differentiation and maturation, which reflects the specificity of the tissue and the degree of maturation, and generally remains stable during carcinogenesis. Determination of the pattern makes it possible to identify the origin of cells in diagnosing neoplastic lesions as well as in research on pathophysiology or the possibility to apply keratin-positive cell detection in the process of cancer staging and treatment planning. As keratins undergo degradation during apoptosis as caspase substrate the identification of the caspase-derived K18 fragment by the use of specific monoclonal antibody allows us to estimate the apoptosis/necrosis ratio, especially in liver pathology, e.g. nonalcoholic steatohepatitis, chronic hepatitis or graft-versus-host disease or in assessing response to antiviral or antitumour therapy.
PubMed: 26557935
DOI: 10.5114/pg.2015.51182 -
Recent Patents on Anti-cancer Drug... 2017Heat shock proteins (Hsp) are major chaperone molecules that have recently emerged as cancer therapeutic targets owing to their involvement in tumor cell proliferation,... (Review)
Review
BACKGROUND
Heat shock proteins (Hsp) are major chaperone molecules that have recently emerged as cancer therapeutic targets owing to their involvement in tumor cell proliferation, differentiation, invasion and metastasis. High levels of extracellular Hsp90 and Hsp70 have been closely associated with a wide range of human cancers. Accumulating evidence suggests that the pharmacological inhibition of these molecules can play a pivotal role in non-surgical cancer treatment. Efforts have been taken to develop monoclonal antibodies (mAbs) and antibody fragments targeting extracellular Hsp90 and Hsp70, alone or conjugated with standard anticancer agents, to control several types of cancer, such as breast, colon, prostate or melanoma.
OBJECTIVE
To provide an overview on the development of monoclonal antibodies and antibody fragments with capacity to bind Hsp90 and Hsp70, aiming at being used for cancer treatment.
METHODS
A systematic review was performed using European Patent Office and Google patents databases.
RESULTS
Based on the available literature and patents, we report the potential anticancer strategies based on these biological molecules.
CONCLUSIONS
Supported by the recent developments in this field, Hsp targeting antibodies therapy may emerge for clinical use in the future for cancer patients, namely as antibody-drug conjugates combining the specificity of these antibodies with the potency of cytotoxic drugs.
Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; Drug Delivery Systems; Heat-Shock Proteins; Humans; Neoplasms; Patents as Topic
PubMed: 27881057
DOI: 10.2174/1574892812666161123141516 -
Clinical Infectious Diseases : An... Jun 2020We reviewed relevant syphilis diagnostic literature and conducted a meta-analysis to address the question, "What is the sensitivity and specificity of the Syphilis... (Meta-Analysis)
Meta-Analysis
We reviewed relevant syphilis diagnostic literature and conducted a meta-analysis to address the question, "What is the sensitivity and specificity of the Syphilis Health Check, a rapid qualitative test for the detection of human antibodies to Treponema pallidum." The Syphilis Health Check is the only rapid syphilis test currently cleared by the Food and Drug Administration (FDA). We conducted a systematic review and a meta-analysis using Bayesian bivariate random-effects and fixed-effect models to create pooled estimates of sensitivity and specificity of the Syphilis Health Check. We identified 5 test evaluations published in the literature and 10 studies submitted to the FDA and for a Clinical Laboratory Improvement Amendments waiver application. The pooled sensitivity (95% CI) from the laboratory evaluations (n = 5) was 98.5% (92.1-100%), while pooled specificity was 95.9% (81.5-100.0%). The pooled sensitivity for prospective studies (n = 10) was 87.7% ( 71.8-97.2%), while pooled specificity was 96.7% (91.9-99.2%). Using nontreponemal supplemental testing, the sensitivity improved to a pooled sensitivity of 97.0% (94.8-98.6%). The Syphilis Health Check may provide accurate detection of treponemal antibody.
Topics: Antibodies, Bacterial; Bayes Theorem; Humans; Point-of-Care Systems; Prospective Studies; Sensitivity and Specificity; Syphilis; Syphilis Serodiagnosis; Treponema pallidum
PubMed: 32578863
DOI: 10.1093/cid/ciaa350