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The Journal of Maternal-fetal &... Oct 2021To assess the accuracy of the placental alpha microglobulin-1 (PAMG-1) to predict preterm birth (PB) in women with symptoms of PB through use of formal methods for... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the accuracy of the placental alpha microglobulin-1 (PAMG-1) to predict preterm birth (PB) in women with symptoms of PB through use of formal methods for systematic reviews and meta-analytic techniques.
METHODS
We performed a comprehensive search of medical bibliographic databases to identify observational studies that reported on the predictive accuracy of PAMG-1 for PB. Two investigators independently assessed studies, assessed quality of studies, and extracted data. Summary receiver operating characteristic (SROC) curves, pooled sensitivities, specificities, likelihood ratios (LR), and diagnostic odds ratio (DOR) were generated.
RESULTS
Seventeen studies involving 2590 women met the inclusion criteria. Meta-analysis of 15 studies (including 1906 women) revealed a pooled sensitivity of 66.2% (95% CI: 59.1, 72.7) and specificity of 96.1% (95% CI: 95.1, 97.0) with the SROC equal to 0.97 (95% CI: 0.95, 0.98) for prediction of delivery within 7 d of testing. The summary estimates were 15.26 (95% CI: 11.80, 19.75) for LR + and 0.31 (95% CI: 0.17, 0.55) for LR - for prediction of delivery within 7 d of testing. Pooled estimate of DOR for predicting delivery within 7 d of testing was 55.13 (95% CI: 35.32, 86.06). The sensitivity, specificity and the SROC of PAMG-1 pooled from 10 studies (including 1508 women) for prediction of delivery within 14 d of testing were 64.4% (95% CI: 56.8, 71.5), 96.9% (95% CI: 95.8, 97.7) and 0.97 (95% CI: 0.95, 0.98). The overall pooled LR + and LR - of PAMG-1 for predicting delivery within 14 d of testing among the included studies were 16.72 (95% CI: 12.03, 23.23) and 0.42.1 (95% CI: 0.31, 0.56), respectively. The pooled DOR of the PAMG-1 for prediction delivery within 14 d of testing was equal to 44.65 (95% CI: 26.30, 75.78).
CONCLUSION
Cervical PAMG-1 had a high accuracy to predict PB within 7 and 14 d of testing in symptomatic pregnant women.
Topics: Cervix Uteri; Female; Humans; Infant, Newborn; Obstetric Labor, Premature; Placenta; Predictive Value of Tests; Pregnancy; Premature Birth; Sensitivity and Specificity
PubMed: 31736399
DOI: 10.1080/14767058.2019.1685962 -
Health Technology Assessment... Mar 2019Preterm birth may result in short- and long-term health problems for the child. Accurate diagnoses of preterm births could prevent unnecessary (or ensure appropriate)...
BACKGROUND
Preterm birth may result in short- and long-term health problems for the child. Accurate diagnoses of preterm births could prevent unnecessary (or ensure appropriate) admissions into hospitals or transfers to specialist units.
OBJECTIVES
The purpose of this report is to assess the test accuracy, clinical effectiveness and cost-effectiveness of the diagnostic tests PartoSure™ (Parsagen Diagnostics Inc., Boston, MA, USA), Actim Partus (Medix Biochemica, Espoo, Finland) and the Rapid Fetal Fibronectin (fFN) 10Q Cassette Kit (Hologic, Inc., Marlborough, MA, USA) at thresholds ≠50 ng/ml [quantitative fFN (qfFN)] for women presenting with signs and symptoms of preterm labour relative to fFN at 50 ng/ml.
METHODS
Systematic reviews of the published literature were conducted for diagnostic test accuracy (DTA) studies of PartoSure, Actim Partus and qfFN for predicting preterm birth, the clinical effectiveness following treatment decisions informed by test results and economic evaluations of the tests. A model-based economic evaluation was also conducted to extrapolate long-term outcomes from the results of the diagnostic tests. The model followed the structure of the model that informed the 2015 National Institute for Health and Care Excellence guidelines on preterm labour diagnosis and treatment, but with antenatal steroids use, as opposed to tocolysis, driving health outcomes.
RESULTS
Twenty studies were identified evaluating DTA against the reference standard of delivery within 7 days and seven studies were identified evaluating DTA against the reference standard of delivery within 48 hours. Two studies assessed two of the index tests within the same population. One study demonstrated that depending on the threshold used, qfFN was more or less accurate than Actim Partus, whereas the other indicated little difference between PartoSure and Actim Partus. No study assessing qfFN and PartoSure in the same population was identified. The test accuracy results from the other included studies revealed a high level of uncertainty, primarily attributable to substantial methodological, clinical and statistical heterogeneity between studies. No study compared all three tests simultaneously. No clinical effectiveness studies evaluating any of the three biomarker tests were identified. One partial economic evaluation was identified for predicting preterm birth. It assessed the number needed to treat to prevent a respiratory distress syndrome case with a 'treat-all' strategy, relative to testing with qualitative fFN. Because of the lack of data, our de novo model involved the assumption that management of pregnant women fully adhered to the results of the tests. In the base-case analysis for a woman at 30 weeks' gestation, Actim Partus had lower health-care costs and fewer quality-adjusted life-years (QALYs) than qfFN at 50 ng/ml, reducing costs at a rate of £56,030 per QALY lost compared with qfFN at 50 ng/ml. PartoSure is less costly than Actim Partus while being equally effective, but this is based on diagnostic accuracy data from a small study. Treatment with qfFN at 200 ng/ml and 500 ng/ml resulted in lower cost savings per QALY lost relative to fFN at 50 ng/ml than treatment with Actim Partus. In contrast, qfFN at 10 ng/ml increased QALYs, by 0.002, and had a cost per QALY gained of £140,267 relative to fFN at 50 ng/ml. Similar qualitative results were obtained for women presenting at different gestational ages.
CONCLUSION
There is a high degree of uncertainty surrounding the test accuracy and cost-effectiveness results. We are aware of four ongoing UK trials, two of which plan to enrol > 1000 participants. The results of these trials may significantly alter the findings presented here.
STUDY REGISTRATION
The study is registered as PROSPERO CRD42017072696.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Biomarkers; Cost-Benefit Analysis; Female; Fibronectins; Humans; Infant, Newborn; Mass Screening; Obstetric Labor, Premature; Predictive Value of Tests; Pregnancy; Premature Birth; Respiratory Distress Syndrome, Newborn; Technology Assessment, Biomedical
PubMed: 30917097
DOI: 10.3310/hta23130 -
Cell Biochemistry and Biophysics Sep 2014Accumulating studies have evaluated the association of Alpha-2-Macroglobulin gene (A2M) 5 bp insertion/deletion (5 bp I/D, rs3832852) and Ile1000Val (rs669)... (Meta-Analysis)
Meta-Analysis Review
Influence of Alpha-2-Macroglobulin 5 bp I/D and Ile1000Val polymorphisms on the susceptibility of Alzheimer's disease: a systematic review and meta-analysis of 52 studies.
Accumulating studies have evaluated the association of Alpha-2-Macroglobulin gene (A2M) 5 bp insertion/deletion (5 bp I/D, rs3832852) and Ile1000Val (rs669) polymorphisms with Alzheimer's disease (AD) risk, but the results remain inconclusive. To investigate whether these two polymorphisms facilitate the susceptibility to AD, we conducted a comprehensive systematic review and meta-analysis. Databases of PubMed, Embase, Web of Science, Medline, CNKI, and Google Scholar were searched to get the genetic association studies. All statistical analyses were conducted with Review Manager 5.2 and STATA11.0. Fifty-two articles were included in the final meta-analysis. We performed meta-analysis of 39 studies involving 8,267 cases and 7,932 controls for the 5 bp I/D polymorphism and 27 studies involving 6,585 cases and 6,637 controls for the Ile/Val polymorphism. Overall results did not show significant association between these two polymorphisms and AD risk in dominant, recessive, and multiplicative genetic models. On the stratification analyses by ethnicity and APOE ε4 status with genotypes of polymorphism sites, similar negative associations were found. The meta-analysis suggests that there is no enough evidence for associations of A2M gene polymorphisms (5 bp I/D, Ile1000Val) with AD risk at present, even after stratification by ethnicity and APOE ε4 with genotypes of polymorphism sites. However, due to the heterogeneity in the meta-analysis, the results should be interpreted with caution.
Topics: Alzheimer Disease; Genetic Predisposition to Disease; Humans; INDEL Mutation; Polymorphism, Single Nucleotide; alpha-Macroglobulins
PubMed: 24756728
DOI: 10.1007/s12013-014-9950-3 -
Journal of Alzheimer's Disease : JAD 2014A blood-based protein biomarker, or set of protein biomarkers, that could predict onset and progression of Alzheimer's disease (AD) would have great utility; potentially... (Review)
Review
A blood-based protein biomarker, or set of protein biomarkers, that could predict onset and progression of Alzheimer's disease (AD) would have great utility; potentially clinically, but also for clinical trials and especially in the selection of subjects for preventative trials. We reviewed a comprehensive list of 21 published discovery or panel-based (> 100 proteins) blood proteomics studies of AD, which had identified a total of 163 candidate biomarkers. Few putative blood-based protein biomarkers replicate in independent studies but we found that some proteins do appear in multiple studies; for example, four candidate biomarkers are found to associate with AD-related phenotypes in five independent research cohorts in these 21 studies: α-1-antitrypsin, α-2-macroglobulin, apolipoprotein E, and complement C3. Using SomaLogic's SOMAscan proteomics technology, we were able to conduct a large-scale replication study for 94 of the 163 candidate biomarkers from these 21 published studies in plasma samples from 677 subjects from the AddNeuroMed (ANM) and the Alzheimer's Research UK/Maudsley BRC Dementia Case Registry at King's Health Partners (ARUK/DCR) research cohorts. Nine of the 94 previously reported candidates were found to associate with AD-related phenotypes (False Discovery Rate (FDR) q-value < 0.1). These proteins show sufficient replication to be considered for further investigation as a biomarker set. Overall, we show that there are some signs of a replicable signal in the range of proteins identified in previous studies and we are able to further replicate some of these. This suggests that AD pathology does affect the blood proteome with some consistency.
Topics: Alzheimer Disease; Biomarkers; Blood Proteins; Disease Progression; Humans; Proteome
PubMed: 24121966
DOI: 10.3233/JAD-130380 -
Obstetrics and Gynecology May 2007To systematically review evidence of the association between fibrinolytic defects and recurrent miscarriage. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review evidence of the association between fibrinolytic defects and recurrent miscarriage.
DATA SOURCES
MEDLINE, EMBASE, and references of retrieved articles (last update September 2006) were used.
METHODS OF STUDY SELECTION
Studies comparing the prevalence of fibrinolytic defects in patients with recurrent miscarriage and control women were reviewed. Of 111 potentially relevant studies, data from 14 were integrated with meta-analytic techniques and were presented as odds ratios (ORs).
TABULATION, INTEGRATION, AND RESULTS
Plasminogen activator inhibitor-1 4G/5G polymorphism (OR 1.65, 95% confidence interval [CI] 0.92-2.95) and increased plasminogen activator inhibitor activity were not significantly associated with recurrent miscarriage, although the latter showed profound heterogeneity across studies. Although factor XII C46T polymorphism is not associated with recurrent miscarriage (OR 1.07, 95% CI 0.52-2.22), factor XII deficiency is significantly associated (five studies, 1,096 women; OR 18.11, 95% CI 5.52-59.39), with minimal heterogeneity across studies. Factor XIII Val34Leu and Tyr204Phe polymorphisms were not associated with recurrent miscarriage (OR 1.24, 95% CI 0.46-3.34 and OR 2.61, 95% CI 0.45-15.16, respectively). There were no eligible studies found for the rest of the factors searched (urokinase-type plasminogen activator, tissue-type plasminogen activator, kallicrein, a2-antiplasmin, a2-macroglobulin, thrombin-activated thrombolysis inhibitor, and factor XI). Only a small minority of studies ascertained miscarriage according to specific criteria, and none of the studies provided equal examination for confounders in cases and controls.
CONCLUSION
Factor XII deficiency is associated with recurrent miscarriage. Data on the other factors either fail to show association or are quite limited.
Topics: Abortion, Habitual; Case-Control Studies; Child; Factor XII; Factor XII Deficiency; Factor XIII; Female; Fibrinolysis; Gestational Age; Humans; Odds Ratio; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Pregnancy
PubMed: 17470597
DOI: 10.1097/01.AOG.0000260873.94196.d6