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The Cochrane Database of Systematic... Nov 2015Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. However, no test can predict the severity of problems a person with Down's syndrome will have.
OBJECTIVES
The aim of this review was to estimate and compare the accuracy of first trimester serum markers for the detection of Down's syndrome in the antenatal period, both as individual markers and as combinations of markers. Accuracy is described by the proportion of fetuses with Down's syndrome detected by screening before birth (sensitivity or detection rate) and the proportion of women with a low risk (normal) screening test result who subsequently had a baby unaffected by Down's syndrome (specificity).
SEARCH METHODS
We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 25 August 2011), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (Archived 2007), Health Services Research Projects in Progress database (25 August 2011). We did forward citation searching ISI citation indices, Google Scholar and PubMed 'related articles'. We did not apply a diagnostic test search filter. We also searched reference lists and published review articles.
SELECTION CRITERIA
We included studies in which all women from a given population had one or more index test(s) compared to a reference standard (either chromosomal verification or macroscopic postnatal inspection). Both consecutive series and diagnostic case-control study designs were included. Randomised trials where individuals were randomised to different screening strategies and all verified using a reference standard were also eligible for inclusion. Studies in which test strategies were compared head-to-head either in the same women, or between randomised groups were identified for inclusion in separate comparisons of test strategies. We excluded studies if they included less than five Down's syndrome cases, or more than 20% of participants were not followed up.
DATA COLLECTION AND ANALYSIS
We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC meta-analytical methods or random-effects logistic regression methods to analyse test performance and compare test accuracy as appropriate. Analyses of studies allowing direct and indirect comparisons between tests were undertaken.
MAIN RESULTS
We included 56 studies (reported in 68 publications) involving 204,759 pregnancies (including 2113 with Down's syndrome). Studies were generally of good quality, although differential verification was common with invasive testing of only high-risk pregnancies. We evaluated 78 test combinations formed from combinations of 18 different tests, with or without maternal age; ADAM12 (a disintegrin and metalloprotease), AFP (alpha-fetoprotein), inhibin, PAPP-A (pregnancy-associated plasma protein A, ITA (invasive trophoblast antigen), free βhCG (beta human chorionic gonadotrophin), PlGF (placental growth factor), SP1 (Schwangerschafts protein 1), total hCG, progesterone, uE3 (unconjugated oestriol), GHBP (growth hormone binding protein), PGH (placental growth hormone), hyperglycosylated hCG, ProMBP (proform of eosinophil major basic protein), hPL (human placental lactogen), (free αhCG, and free ßhCG to AFP ratio. Direct comparisons between two or more tests were made in 27 studies.Meta-analysis of the nine best performing or frequently evaluated test combinations showed that a test strategy involving maternal age and a double marker combination of PAPP-A and free ßhCG significantly outperformed the individual markers (with or without maternal age) detecting about seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). Limited evidence suggested that marker combinations involving PAPP-A may be more sensitive than those without PAPP-A.
AUTHORS' CONCLUSIONS
Tests involving two markers in combination with maternal age, specifically PAPP-A, free βhCG and maternal age are significantly better than those involving single markers with and without age. They detect seven out of 10 Down's affected pregnancies for a fixed 5% FPR. The addition of further markers (triple tests) has not been shown to be statistically superior; the studies included are small with limited power to detect a difference.The screening blood tests themselves have no adverse effects for the woman, over and above the risks of a routine blood test. However some women who have a 'high risk' screening test result, and are given amniocentesis or chorionic villus sampling (CVS) have a risk of miscarrying a baby unaffected by Down's. Parents will need to weigh up this risk when deciding whether or not to have an amniocentesis or CVS following a 'high risk' screening test result.
Topics: ADAM Proteins; ADAM12 Protein; Biomarkers; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; Female; Humans; Maternal Age; Membrane Proteins; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Prenatal Diagnosis; alpha-Fetoproteins
PubMed: 26617074
DOI: 10.1002/14651858.CD011975 -
Frontiers in Genetics 2018This present research work reports the comparative analysis of the entire nucleotide sequence of mitochondrial genomes of and and phylogenetic analyses of their...
This present research work reports the comparative analysis of the entire nucleotide sequence of mitochondrial genomes of and and phylogenetic analyses of their protein-coding genes in order to establish their phylogenetic relationship within Cichlids. The mitochondrial genomes of and are 16,583 and 16,580 base pairs long, respectively, including 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA genes, and one control region (D-loop) which is 888 and 887 base pairs long, respectively, showing the same gene order and identical number of gene or regions with other well-elucidated mitogenomes of Cichlids. However, with exception of cytochrome-c oxidase subunit-1 () gene, all the identified PCGs were initiated by ATG-codons. Structurally, 11 tRNA genes in species and 9 tRNA genes in species, folded into typical clover-leaf secondary structure created by the regions of self-complementarity within tRNA. All the 22 tRNA genes in both species lack variable loop. Moreover, 28 genes which include 12-protein-coding genes are encoded on the H-strand and the remaining 9 genes including one protein-coding gene are encoded on the L-strand. Thirteen sequences of concatenated mitochondrial protein-coding genes were aligned using MUSCLE, and the phylogenetic analyses performed using maximum likelihood and Bayesian inference showed that and had a broad phylogenetic relationship. These results may be a useful tool in resolving higher-level relationships in organisms and a useful dataset for studying the evolution of the Cichlidae mitochondrial genome, since Cichlids are well-known model species in the study of evolutionary biology, because of their extreme morphological, biogeographical, parental care behavior for eggs and larvae and phylogenetic diversities.
PubMed: 30894873
DOI: 10.3389/fgene.2018.00651 -
Neuromodulation : Journal of the... Apr 2024Guanine nucleotide-binding protein alpha-activating activity polypeptide O (GNAO1) syndrome, a rare congenital monogenetic disorder, is characterized by a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Guanine nucleotide-binding protein alpha-activating activity polypeptide O (GNAO1) syndrome, a rare congenital monogenetic disorder, is characterized by a neurodevelopmental syndrome and the presence of dystonia. Dystonia can be very pronounced and even lead to a life-threatening status dystonicus. In a small number of pharmaco-refractory cases, deep brain stimulation (DBS) has been attempted to reduce dystonia. In this study, we summarize the current literature on outcome, safety, and outcome predictors of DBS for GNAO1-associated dystonia.
MATERIALS AND METHODS
We conducted a systematic review and meta-analysis on individual patient data. We included 18 studies describing 28 unique patients.
RESULTS
The mean age of onset of symptoms was 2.4 years (SD 3.8); 16 of 28 patients were male, and dystonia was nearly always generalized (20/22 patients). Symptoms were present before DBS for a median duration of 19.5 months, although highly variable, occurring between 3 and 168 months. The exact phenotype, genotype, and radiologic abnormalities varied and seemed to be of little importance in terms of DBS outcome. All studies described an improvement in dystonia. Our meta-analysis focused on pallidal DBS and found an absolute and relative improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) of 32.5 points (37.9%; motor part; p = 0.001) and 5.8 points (21.5%; disability part; p = 0.043) at last follow-up compared with preoperative state; 80% of patients were considered responders (BFMDRS-M reduction by ≥25%). Although worsening over time does occur, an improvement was still observed in patients after >10 years. All reported cases of status dystonicus resolved after DBS surgery. Skin erosion and infection were observed in 18% of patients.
CONCLUSION
Pallidal DBS can be efficacious and safe in GNAO1-associated dystonia.
Topics: Child, Preschool; Female; Humans; Male; Deep Brain Stimulation; Dystonia; Dystonic Disorders; Globus Pallidus; GTP-Binding Protein alpha Subunits, Gi-Go; Heredodegenerative Disorders, Nervous System; Treatment Outcome; Infant, Newborn; Infant; Child
PubMed: 37999699
DOI: 10.1016/j.neurom.2023.10.187 -
Journal of Athletic Training 2014Elevated levels of the astroglial protein S100B have been shown to predict sport-related concussion. However, S100B levels within an athlete can vary depending on the... (Review)
Review
OBJECTIVE
Elevated levels of the astroglial protein S100B have been shown to predict sport-related concussion. However, S100B levels within an athlete can vary depending on the type of physical activity (PA) engaged in and the methodologic approach used to measure them. Thus, appropriate reference values in the diagnosis of concussed athletes remain undefined. The purpose of our systematic literature review was to provide an overview of the current literature examining S100B measurement in the context of PA. The overall goal is to improve the use of the biomarker S100B in the context of sport-related concussion management.
DATA SOURCES
PubMed, SciVerse Scopus, SPORTDiscus, CINAHL, and Cochrane.
STUDY SELECTION
We selected articles that contained (1) research studies focusing exclusively on humans in which (2) either PA was used as an intervention or the test participants or athletes were involved in PA and (3) S100B was measured as a dependent variable.
DATA EXTRACTION
We identified 24 articles. Study variations included the mode of PA used as an intervention, sample types, sample-processing procedures, and analytic techniques.
DATA SYNTHESIS
Given the nonuniformity of the analytical methods used and the data samples collected, as well as differences in the types of PA investigated, we were not able to determine a single consistent reference value of S100B in the context of PA. Thus, a clear distinction between a concussed athlete and a healthy athlete based solely on the existing S100B cutoff value of 0.1 μg/L remains unclear. However, because of its high sensitivity and excellent negative predictive value, S100B measurement seems to have the potential to be a diagnostic adjunct for concussion in sports settings. We recommend that the interpretation of S100B values be based on congruent study designs to ensure measurement reliability and validity.
Topics: Athletic Injuries; Biomarkers; Brain Concussion; Humans; Predictive Value of Tests; Reference Values; Reproducibility of Results; S100 Calcium Binding Protein beta Subunit; Sports
PubMed: 25299445
DOI: 10.4085/1062-6050-49.3.33 -
BJOG : An International Journal of... Sep 2016Controversies about the performance of conventional prenatal screening using maternal serum and ultrasound markers (PSMSUM) in detecting Down syndrome (DS) have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Controversies about the performance of conventional prenatal screening using maternal serum and ultrasound markers (PSMSUM) in detecting Down syndrome (DS) have been raised as a result of a recently available noninvasive prenatal test based on cell-free fetal DNA sequencing.
OBJECTIVES
To evaluate the screening performance of PSMSUM in detecting DS in Chinese women.
SEARCH STRATEGY
An exhaustive literature search of MEDLINE, Embase, the Cochrane Library, ISI Web of Science and China BioMedical Disc.
SELECTION CRITERIA
Primary studies, published from January 2004 to November 2014, which examined the screening accuracy of PSMSUM in pregnant Chinese women, compared with a reference standard, either chromosomal verification or inspection of the newborn.
DATA COLLECTION AND ANALYSIS
Data were extracted as screening positive/negative results for Down and non-Down syndrome pregnancies, allowing estimation of sensitivities and specificities. Risks of bias within and across studies were assessed. Screening accuracy measures were pooled using a bivariate random effects regression model.
MAIN RESULTS
Seventy-eight studies, involving six categories of PSMSUM, were included. Second-trimester double serum [pooled sensitivity (SEN) = 0.80, pooled specificity (SPE) = 0.95] and triple-serum (pooled SEN = 0.79, pooled SPE = 0.96) screening were the predominant PSMSUM methods. The screening performances of these methods achieved the national standard but varied enormously across studies. First-trimester combined screening (pooled SEN = 0.92, pooled SPE = 0.93) and second-trimester quadruple serum screening (median SEN = 0.86, median SPE = 0.96) performed better, but were rarely used.
AUTHOR'S CONCLUSIONS
Second-trimester maternal serum screening has the potential to achieve satisfactory screening performance in middle- and low-income countries. The reported enormous range in screening performance of second-trimester PSMSUM calls for urgent implementation of methods for performance optimization.
TWEETABLE ABSTRACT
Meta-analysis results show good accuracy of maternal serum and ultrasound screening for trisomy 21 in Chinese women.
Topics: Asian People; Biomarkers; China; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; Female; Humans; Maternal Age; Maternal Serum Screening Tests; Pregnancy; Pregnancy-Associated Plasma Protein-A; Prenatal Diagnosis; Ultrasonography; alpha-Fetoproteins
PubMed: 27627591
DOI: 10.1111/1471-0528.14009 -
Frontiers in Endocrinology 2022It is currently controversial whether subclinical hyperthyroidism is associated with gene variants. We describe a man with subclinical hyperthyroidism and a gene...
BACKGROUND AND OBJECTIVES
It is currently controversial whether subclinical hyperthyroidism is associated with gene variants. We describe a man with subclinical hyperthyroidism and a gene variant who was diagnosed with Carney complex (CNC), and we performed a systematic review of published studies to assess the association between gene variants and the risk of subclinical hyperthyroidism.
DESIGN AND METHODS
The PubMed, EMBASE, OVID, Science Direct, and gray literature electronic databases were searched for articles published from January 2002 to May 2021 using predefined keywords and inclusion and exclusion criteria. Data on thyroid function from selected studies were extracted and analyzed.
RESULTS
We identified a CNC patient with a subclinical hyperthyroidism phenotype combined with multiple components and genetic sequenced data. In a subsequent systematic review, twenty selected studies (14 case studies and 6 series studies) enrolling 23 individuals were included in the final analysis. The patient's thyroid function data were qualitative in 11 cases and quantitative in 12 cases. The prevalence of subclinical hyperthyroidism in the CNC patients with a gene variant, including our patient, was markedly higher than that in the normal population (12.5% vs. 2%).
CONCLUSIONS
The findings of this systematic review provide helpful evidence that gene variants and subclinical hyperthyroidism are related and suggest that subclinical hyperthyroidism may be a neglected phenotype of gene variants and a novel component of CNC patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021197655.
Topics: Carney Complex; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; Humans; Hyperthyroidism; Phenotype
PubMed: 36213268
DOI: 10.3389/fendo.2022.951133 -
Medicine Jul 2016Inconsistent results have been reported about the risk stratification of patients with Brugada syndrome. We have summarized the evidence regarding the strength of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Inconsistent results have been reported about the risk stratification of patients with Brugada syndrome. We have summarized the evidence regarding the strength of association between 6 risk factors (family history of sudden cardiac death [SCD] or syncope, inducible ventricular arrhythmias on electrophysiology study [EPS], spontaneous type 1 Brugada electrocardiogram [ECG], male sex, family history of SCD, and sodium voltage-gated channel alpha subunit 5 [SCN5A] gene mutation) and subsequent cardiac events in Brugada syndrome patients.
METHODS
Pubmed, Ovid, Embase, and the Cochrane Library were searched for studies published between January 1992 and March 2016. Only prospective studies (27 studies, 4494 patients) that reported estimates with 95% confidence intervals (CIs) of cardiac events for the 6 risk factors were included.
RESULTS
Family history of SCD or syncope (risk ratio [RR] 4.97, 95% CI 3.96-6.23, P < 0.001), inducible ventricular arrhythmia on EPS (RR 3.56, 95% CI 1.30-9.74, P = 0.01), and spontaneous type 1 Brugada ECG (RR 4.07, 95% CI 2.23-7.41, P < 0.001) were associated with an increased risk of future cardiac events. Spontaneous type 1 Brugada ECG was associated with an elevated risk of future cardiac events in patients without a family history of SCD.
CONCLUSIONS
Inducible ventricular arrhythmias on EPS, spontaneous type 1 Brugada ECG, and family history of SCD or syncope indicate a high risk of future cardiac events in patients with Brugada syndrome. Spontaneous type 1 Brugada ECG significantly increased the risk of future cardiac events in patients without family history of SCD.
Topics: Brugada Syndrome; Electrocardiography; Genetic Predisposition to Disease; Humans; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Risk Assessment; Risk Factors; Sex Factors; Syncope; Ventricular Fibrillation
PubMed: 27472692
DOI: 10.1097/MD.0000000000004214 -
Scientific Reports Jun 2024To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We... (Meta-Analysis)
Meta-Analysis
To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science for studies on GC and HIF1A, covering studies published until January 31st, 2022. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for clinical characteristics based on high and low HIF1A protein levels. We used random-effects and fixed-effects meta-analysis methods to determine mean effect sizes of ORs and evaluated publication heterogeneity with τ, I, and Q values. Additionally, we generated funnel plots to inspect publication bias. Our meta-analysis included 20 publications with 3416 GC patients to estimate the association between high or low HIF1A expression and clinical characteristics. Positive HIF1A expression was significantly associated with T stage progression (OR: 2.46; 95% CI 1.81-3.36; P < 0.01), TNM stage progression (OR: 2.50; 95% CI 1.61-3.87; P < 0.01), lymph node metastasis (OR: 2.06; 95% CI 1.44-2.94; P < 0.01), undifferentiated status (OR: 1.83; 95% CI 1.45-2.32; P < 0.01), M stage progression (OR: 2.34; 95% CI 1.46-3.77; P < 0.01), Borrmann stage progression (OR: 1.48; 95% CI 1.02-2.15; P = 0.04), larger tumor size (OR: 1.27; 95% CI 1.06-1.52; P < 0.01), vascular invasion (OR: 1.94; 95% CI 1.38-2.72; P < 0.01), and higher vascular endothelial growth factor (VEGF) protein expression (OR: 2.61; 95% CI 1.79-3.80; P < 0.01) in our meta-analysis. GC Patients highly expressing HIF1A protein might be prone to tumor progression, poorly differentiated GC cell types, and a high VEGF expression.
Topics: Stomach Neoplasms; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lymphatic Metastasis; Biomarkers, Tumor; Neoplasm Staging; Vascular Endothelial Growth Factor A; Gene Expression Regulation, Neoplastic
PubMed: 38877062
DOI: 10.1038/s41598-024-63019-6 -
European Neuropsychopharmacology : the... Dec 2020The neurotrophin hypothesis indicates that neurotrophic factors are important for the pathophysiology of major depressive disorder (MDD), with alterations in peripheral... (Meta-Analysis)
Meta-Analysis
The neurotrophin hypothesis indicates that neurotrophic factors are important for the pathophysiology of major depressive disorder (MDD), with alterations in peripheral neurotrophin levels having potential clinical application for MDD. The present meta-analysis aimed to investigate the diagnostic value for MDD of peripheral neurotrophin levels in cross-sectional studies and the association between peripheral neurotrophin levels and the response to antidepressant treatment in longitudinal studies. Published studies in the PubMed and Web of Science databases were systematically searched up to February 2020. The search terms included depressive disorder, neurotrophic factor, serum/plasma and their synonyms. Human studies reporting on BDNF, GDNF, IGF-2, VEGF, NGF, FGF-2, and S100B levels in MDD patients were included. Data comparing MDD patients and healthy controls, and/or between responders and non-responders before and after antidepressant treatment were extracted. A random effects model was used to calculate standardized mean differences. A total of 177 original studies were identified, including 139 cross-sectional and 38 longitudinal studies. Significantly reduced BDNF and NGF levels and significantly elevated IGF-1, VEGF, and S100B levels were reported in MDD patients compared with healthy controls, while GDNF and FGF-2 levels were not significantly different. Furthermore, compared with non-responders, S100B levels at baseline and BDNF levels following treatment were significantly elevated in responders. In addition, there was a significantly elevated level of VEGF after treatment in responders only. In conclusions, alterations in peripheral neurotrophins levels were strongly associated with the biology and the treatment response of MDD. Further investigations are required to examine potential sources of heterogeneity.
Topics: Antidepressive Agents; Biomarkers; Brain-Derived Neurotrophic Factor; Cross-Sectional Studies; Depressive Disorder, Major; Humans; Insulin-Like Growth Factor I; Nerve Growth Factor; Nerve Growth Factors; S100 Calcium Binding Protein beta Subunit; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 32980240
DOI: 10.1016/j.euroneuro.2020.09.633 -
Journal of Neurotrauma Feb 2018This systematic review and meta-analysis aimed to determine the prognostic value of S-100β protein to identify patients with post-concussion symptoms after a mild... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed to determine the prognostic value of S-100β protein to identify patients with post-concussion symptoms after a mild traumatic brain injury (mTBI). A search strategy was submitted to seven databases from their inception to October 2016. Individual patient data were requested. Cohort studies evaluating the association between S-100β protein level and post-concussion symptoms assessed at least seven days after the mTBI were considered. Outcomes were dichotomized as persistent (≥3 months) or early (≥7 days <3 months). Our search strategy yielded 23,298 citations of which 29 studies including between seven and 223 patients (n = 2505) were included. Post-concussion syndrome (PCS) (16 studies) and neuropsychological symptoms (9 studies) were the most frequently assessed outcomes. The odds of having persistent PCS (odds ratio [OR] 0.62, 95% confidence interval [CI]: 0.34-1.12, p = 0.11, I 0% [n = five studies]) in patients with an elevated S-100β protein serum level were not significantly different from those of patients with normal values while the odds of having early PCS (OR 1.67, 95% CI: 0.98-2.85, p = 0.06, I 38% [n = five studies]) were close to statistical significance. Similarly, having an elevated S-100β protein serum level was not associated with the odds of returning to work at six months (OR 2.31, 95% CI: 0.50-10.64, p = 0.28, I 22% [n = two studies]). Overall risk of bias was considered moderate. Results suggest that the prognostic biomarker S-100β protein has a low clinical value to identify patients at risk of persistent post-concussion symptoms. Variability in injury to S-100ß protein sample time, mTBI populations, and outcomes assessed could potentially explain the lack of association and needs further evaluation.
Topics: Brain Concussion; Humans; Post-Concussion Syndrome; Prognosis; S100 Calcium Binding Protein beta Subunit
PubMed: 28969486
DOI: 10.1089/neu.2017.5013