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Genetics in Medicine : Official Journal... Nov 2019For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a... (Meta-Analysis)
Meta-Analysis
PURPOSE
For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs.
METHODS
We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians.
RESULTS
After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15-20%).
CONCLUSION
Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs.
Topics: Autism Spectrum Disorder; Developmental Disabilities; Diagnostic Tests, Routine; Exome; Genetic Testing; Humans; Intellectual Disability; Neurodevelopmental Disorders; Exome Sequencing
PubMed: 31182824
DOI: 10.1038/s41436-019-0554-6 -
Clinical Oral Investigations Nov 2021This systematic review and meta-analysis aimed to assess the diagnostic accuracy and reliability of commonly used caries detection methods for proximal caries... (Meta-Analysis)
Meta-Analysis Review
AIM
This systematic review and meta-analysis aimed to assess the diagnostic accuracy and reliability of commonly used caries detection methods for proximal caries diagnostics. Visual examination (VE), bitewing radiography (BWR), laser fluorescence (LF), and fibre-optic transillumination (FOTI) were considered in detail.
MATERIAL AND METHODS
PRISMA guidelines for the reporting of systematic reviews and meta-analyses were applied. The mnemonic PIRDS (problem, index test, reference test, diagnostic and study type) concept was used to guide the literature search. Next, studies that met the inclusion criteria were stepwise selected and evaluated for their quality with a risk of bias (RoB) assessment tool. Studies with low/moderate bias and sufficient reporting were considered for meta-analysis. The pooled sensitivity (SE), specificity (SP), diagnostic odds ratio (DOR), and area under the ROC curve (AUC) were calculated.
RESULTS
From 129 studies meeting the selection criteria, 31 in vitro studies and five clinical studies were finally included in the meta-analysis. The AUC values for in vitro VE amounted to 0.84 (caries detection) and 0.85 (dentin caries detection). BWR ranged in vitro from 0.55 to 0.82 (caries detection) and 0.81-0.92 (dentin caries detection). LF showed higher AUC values for overall caries detection (0.91) and dentin caries detection (0.83) than did other methods. Clinical data are limited.
CONCLUSION
The number of diagnostic studies with low/moderate RoB was found to be low and indicates a need for high-quality, well-designed caries diagnostic studies.
CLINICAL RELEVANCE
BWR and LF showed good diagnostic performance on proximal surfaces. However, because of the low number of includable clinical studies, these data should be interpreted with caution.
Topics: Dental Caries Susceptibility; Diagnostic Tests, Routine; Reproducibility of Results; Sensitivity and Specificity; Transillumination
PubMed: 34480645
DOI: 10.1007/s00784-021-04113-1 -
JAMA Network Open Nov 2023Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH).
OBJECTIVE
To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH.
DATA SOURCES
PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, ventriculomegaly, cerebral ventriculomegaly, primary ventriculomegaly, fetal ventriculomegaly, prenatal ventriculomegaly, molecular analysis, genetic cause, genetic etiology, genetic testing, exome sequencing, whole exome sequencing, genome sequencing, microarray, microarray analysis, and copy number variants.
STUDY SELECTION
Eligible studies included those with at least 10 probands with the defining feature of CH and/or severe cerebral ventriculomegaly that had undergone ES. Studies with fewer than 10 probands, studies of mild or moderate ventriculomegaly, and studies using genetic tests other than ES were excluded. A full-text review of 68 studies was conducted by 2 reviewers. Discrepancies were resolved by consensus.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guidelines were used by 2 reviewers to extract data. Data were synthesized using a random-effects model of single proportions. Data analysis occurred in April 2023.
MAIN OUTCOMES AND MEASURES
The primary outcome was pooled diagnostic yield. Additional diagnostic yields were estimated for specific subgroups on the basis of clinical features, syndromic presentation, and parental consanguinity. For each outcome, a 95% CI and estimate of interstudy heterogeneity (I2 statistic) was reported.
RESULTS
From 498 deduplicated and screened records, 9 studies with a total of 538 CH probands were selected for final inclusion. The overall diagnostic yield was 37.9% (95% CI, 20.0%-57.4%; I2 = 90.1). The yield was lower for isolated and/or nonsyndromic cases (21.3%; 95% CI, 12.8%-31.0%; I2 = 55.7). The yield was higher for probands with reported consanguinity (76.3%; 95% CI, 65.1%-86.1%; I2 = 0) than those without (16.2%; 95% CI, 12.2%-20.5%; I2 = 0).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of the diagnostic yield of ES in CH, the diagnostic yield was concordant with that of previous recommendations for other neurodevelopmental disorders, suggesting that ES should also be recommended as a routine diagnostic adjunct for patients with CH.
Topics: Female; Pregnancy; Humans; Autism Spectrum Disorder; Exome Sequencing; Pathology, Molecular; Patients; Hydrocephalus
PubMed: 37991765
DOI: 10.1001/jamanetworkopen.2023.43384 -
BMC Medicine Nov 2013Non-cardiovascular chest pain (NCCP) has a high healthcare cost, but insufficient guidelines exist for its diagnostic investigation. The objective of the present work... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-cardiovascular chest pain (NCCP) has a high healthcare cost, but insufficient guidelines exist for its diagnostic investigation. The objective of the present work was to identify important diagnostic indicators and their accuracy for specific and non-specific conditions underlying NCCP.
METHODS
A systematic review and meta-analysis were performed. In May 2012, six databases were searched. Hand and bibliography searches were also conducted. Studies evaluating a diagnostic test against a reference test in patients with NCCP were included. Exclusion criteria were having <30 patients per group, and evaluating diagnostic tests for acute cardiovascular disease. Diagnostic accuracy is given in likelihood ratios (LR): very good (LR+ >10, LR- <0.1); good (LR + 5 to 10, LR- 0.1 to 0.2); fair (LR + 2 to 5, LR- 0.2 to 0.5); or poor (LR + 1 to 2, LR- 0.5 to 1). Joined meta-analysis of the diagnostic test sensitivity and specificity was performed by applying a hierarchical Bayesian model.
RESULTS
Out of 6,316 records, 260 were reviewed in full text, and 28 were included: 20 investigating gastroesophageal reflux disorders (GERD), 3 musculoskeletal chest pain, and 5 psychiatric conditions. Study quality was good in 15 studies and moderate in 13. GERD diagnosis was more likely with typical GERD symptoms (LR + 2.70 and 2.75, LR- 0.42 and 0.78) than atypical GERD symptoms (LR + 0.49, LR- 2.71). GERD was also more likely with a positive response to a proton pump inhibitor (PPI) test (LR + 5.48, 7.13, and 8.56; LR- 0.24, 0.25, and 0.28); the posterior mean sensitivity and specificity of six studies were 0.89 (95% credible interval, 0.28 to 1) and 0.88 (95% credible interval, 0.26 to 1), respectively. Panic and anxiety screening scores can identify individuals requiring further testing for anxiety or panic disorders. Clinical findings in musculoskeletal pain either had a fair to moderate LR + and a poor LR- or vice versa.
CONCLUSIONS
In patients with NCCP, thorough clinical evaluation of the patient's history, symptoms, and clinical findings can indicate the most appropriate diagnostic tests. Treatment response to high-dose PPI treatment provides important information regarding GERD, and should be considered early. Panic and anxiety disorders are often undiagnosed and should be considered in the differential diagnosis of chest pain.
Topics: Chest Pain; Diagnostic Tests, Routine; Humans; Sensitivity and Specificity
PubMed: 24207111
DOI: 10.1186/1741-7015-11-239 -
Sexually Transmitted Infections Dec 2022Current rapid tests for syphilis and yaws can detect treponemal and non-treponemal antibodies. We aimed to critically appraise the literature for rapid diagnostic tests... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current rapid tests for syphilis and yaws can detect treponemal and non-treponemal antibodies. We aimed to critically appraise the literature for rapid diagnostic tests (RDTs) which can better distinguish an active infection of syphilis or yaws.
METHODS
We conducted a systematic review and meta-analysis, searching five databases between January 2010 and October 2021 (with an update in July 2022). A generalised linear mixed model was used to conduct a bivariate meta-analysis for the pooled sensitivity and specificity. Heterogeneity was assessed using the I statistic. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) to assess the risk of bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to evaluate the certainty of evidence.
RESULTS
We included 17 studies for meta-analyses. For syphilis, the pooled sensitivity and specificity of the treponemal component were 0.93 (95% CI: 0.86 to 0.97) and 0.98 (95% CI: 0.96 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.90 (95% CI: 0.82 to 0.95) and 0.97 (95% CI: 0.92 to 0.99), respectively. For yaws, the pooled sensitivity and specificity of the treponemal component were 0.86 (95% CI: 0.66 to 0.95) and 0.97 (95% CI: 0.94 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.80 (95% CI: 0.55 to 0.93) and 0.96 (95% CI: 0.92 to 0.98), respectively.
CONCLUSIONS
RDTs that can differentiate between active and previously treated infections could optimise management by providing same-day treatment and reducing unnecessary treatment.
PROSPERO REGISTRATION NUMBER
CRD42021279587.
Topics: Humans; Yaws; Syphilis; Diagnostic Tests, Routine; Sensitivity and Specificity
PubMed: 36180209
DOI: 10.1136/sextrans-2022-055546 -
Microvascular Research May 2023Up to 30 % of patients with psoriasis (PsO) develop psoriatic arthritis (PsA), and diagnosis can be difficult. Nailfold capillaroscopy (NC) is an easily applicable,... (Review)
Review
Up to 30 % of patients with psoriasis (PsO) develop psoriatic arthritis (PsA), and diagnosis can be difficult. Nailfold capillaroscopy (NC) is an easily applicable, non-invasive procedure to assess skin microcirculation. This systematic review investigates NC as diagnostic tool for PsO and PsA, including correlations between NC outcome measures to clinical and laboratory outcome measures. This systematic review was built on the PICO and PRISMA guidelines. In total 22 relevant studies were found Searching in the Web of Science, PubMed and Embase, latest update June 13th, 2022. The following NC outcome measures are found to be significantly more prevalent in PsO patients than healthy controls: reduced density, reduced length and more abnormal morphology. Likewise, in PsA patients, reduced density, more abnormal morphology, more microhaemorrhages and fewer hairpin shapes are found to be significantly more prevalent. Results were non-conclusive in terms of disease activity and duration with NC findings. Random-effects meta-analysis showed a significant reduction of density in PsO patients compared to healthy controls (studies: 6, n = 249; SMD = -0.91; 95 % CI [-1.41, -0.40], p = 0.0058, heterogeneity I=74 %, AUC = 0.740) and in PsA patients compared to healthy controls (studies: 5, n = 130; SMD = -1.22; 95 % CI [-2.38, -0.06], p = 0.0432, heterogeneity I=89 %, AUC = 0.806). No NC outcome measures were overall conclusive in differentiating PsO from PsA. Considering the conflicting results and small sample sizes further large-scale research on the identification of capillaroscopic changes in PsO and PsA and correlations with standardised clinical and laboratory outcome measures are necessary.
Topics: Humans; Arthritis, Psoriatic; Diagnostic Tests, Routine; Health Status; Microscopic Angioscopy; Psoriasis
PubMed: 36657709
DOI: 10.1016/j.mvr.2023.104476 -
PLoS Neglected Tropical Diseases Oct 2022To determine the diagnostic validity of the enzyme-linked immunosorbent assay (ELISA) and Rapid Diagnostic Tests (RDT) among individuals with suspected chronic Chagas... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the diagnostic validity of the enzyme-linked immunosorbent assay (ELISA) and Rapid Diagnostic Tests (RDT) among individuals with suspected chronic Chagas Disease (CD).
METHODOLOGY
A search was made for studies with ELISA and RDT assays validity estimates as eligibility criteria, published between 2010 and 2020 on PubMed, Web of Science, Scopus, and LILACS. This way, we extracted the data and assessed the risk of bias and applicability of the studies using the QUADAS-2 tool. The bivariate random effects model was also used to estimate the overall sensitivity and specificity through forest-plots, ROC space, and we visually assessed the heterogeneity between studies. Meta-regressions were made using subgroup analysis. We used Deeks' test to assess the risk of publication bias.
RESULTS
43 studies were included; 27 assessed ELISA tests; 14 assessed RDTs; and 2 assessed ELISA and RDTs, against different reference standards. 51.2 % of them used a non-comparative observational design, and 46.5 % a comparative clinical design ("case-control" type). High risk of bias was detected for patient screening and reference standard. The ELISA tests had a sensitivity of 99% (95% CI: 98-99) and a specificity of 98% (95% CI: 97-99); whereas the Rapid Diagnostic Tests (RDT) had values of 95% (95% CI: 94-97) and 97% (95% CI: 96-98), respectively. Deeks' test showed asymmetry on the ELISA assays.
CONCLUSIONS
ELISA and RDT tests have high validity for diagnosing chronic Chagas disease. The analysis of these two types of evidence in this systematic review and meta-analysis constitutes an input for their use. The limitations included the difficulty in extracting data due to the lack of information in the articles, and the comparative clinical-type design of some studies.
Topics: Humans; Diagnostic Tests, Routine; Sensitivity and Specificity; Chagas Disease; Enzyme-Linked Immunosorbent Assay; Reference Standards
PubMed: 36256676
DOI: 10.1371/journal.pntd.0010860 -
Tropical Medicine & International... Nov 2022To investigate the current status of the availability and affordability of specific essential medicines and diagnostics for diabetes in Africa. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the current status of the availability and affordability of specific essential medicines and diagnostics for diabetes in Africa.
METHODS
Systematic review and meta-analysis. Studies conducted in Africa that reported any information on the availability and affordability of short-acting, intermediate-acting, and premixed insulin, glibenclamide, metformin, blood glucose, glycated haemoglobin or HbA1c, and lipid profile tests were included. Random-effect model meta-analysis and descriptive statistics were performed to determine the pooled availability and affordability, respectively.
RESULTS
A total of 21 studies were included. The pooled availability of each drug was as follows: short-acting insulin 33.5% (95% CI: 17.8%-49.2%, I = 95.02%), intermediate-acting insulin 23.1% (95% CI: 6.3%-39.9%, I = 91.6%), premixed insulin 49.4% (95% CI: 24.9%-73.9%, I = 90.57%), glibenclamide 55.9% (95% CI: 43.8%-68.0%, I = 96.7%), and metformin 47.0% (95% CI: 34.6%-59.4%, I = 97.54%). Regarding diagnostic tests, for glucometers the pooled availability was 49.5% (95% CI: 37.9%-61.1%, I = 97.43%), for HbA1c 24.6% (95% CI: 3.1%-46.1%, I = 91.64), and for lipid profile tests 35.7% (95% CI: 19.4%-51.9%, I = 83.77%). The median (IQR) affordability in days' wages was 7 (4.7-7.5) for short-acting insulin, 4.4 (3.9-4.9) for intermediate-acting insulin, 7.1 (5.8-16.7) for premixed insulin, 0.7 (0.7-0.7) for glibenclamide, and 2.1 (1.8-2.8) for metformin.
CONCLUSION
The availability of the five essential medicines and three diagnostic tests for diabetes in Africa is suboptimal. The relatively high cost of insulin, HbA1c, and lipid profile tests is a significant barrier to optimal diabetes care. Pragmatic country-specific strategies are urgently needed to address these inequities in access and cost.
Topics: Humans; Diagnostic Tests, Routine; Glyburide; Glycated Hemoglobin; Health Services Accessibility; Drugs, Essential; Diabetes Mellitus; Costs and Cost Analysis; Insulin; Metformin; Insulin, Short-Acting; Lipids
PubMed: 36121433
DOI: 10.1111/tmi.13819 -
BMJ Open Feb 2018Health systems are currently subject to unprecedented financial strains. Inappropriate test use wastes finite health resources (overuse) and delays diagnoses and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Health systems are currently subject to unprecedented financial strains. Inappropriate test use wastes finite health resources (overuse) and delays diagnoses and treatment (underuse). As most patient care is provided in primary care, it represents an ideal setting to mitigate waste.
OBJECTIVE
To identify overuse and underuse of diagnostic tests in primary care.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES AND ELIGIBILITY CRITERIA
We searched MEDLINE and Embase from January 1999 to October 2017 for studies that measured the inappropriateness of any diagnostic test (measured against a national or international guideline) ordered for adult patients in primary care.
RESULTS
We included 357 171 patients from 63 studies in 15 countries. We extracted 103 measures of inappropriateness (41 underuse and 62 overuse) from included studies for 47 different diagnostic tests.The overall rate of inappropriate diagnostic test ordering varied substantially (0.2%-100%)%).17 tests were underused >50% of the time. Of these, echocardiography (n=4 measures) was consistently underused (between 54% and 89%, n=4). There was large variation in the rate of inappropriate underuse of pulmonary function tests (38%-78%, n=8).Eleven tests were inappropriately overused >50% of the time. Echocardiography was consistently overused (77%-92%), whereas inappropriate overuse of urinary cultures, upper endoscopy and colonoscopy varied widely, from 36% to 77% (n=3), 10%-54% (n=10) and 8%-52% (n=2), respectively.
CONCLUSIONS
There is marked variation in the appropriate use of diagnostic tests in primary care. Specifically, the use of echocardiography (both underuse and overuse) is consistently poor. There is substantial variation in the rate of inappropriate underuse of pulmonary function tests and the overuse of upper endoscopy, urinary cultures and colonoscopy.
PROSPERO REGISTRATION NUMBER
CRD42016048832.
Topics: Adult; Diagnostic Tests, Routine; Echocardiography; Endoscopy, Digestive System; Humans; Primary Health Care; Respiratory Function Tests; Unnecessary Procedures
PubMed: 29440142
DOI: 10.1136/bmjopen-2017-018557 -
European Clinical Respiratory Journal 2016To identify bronchoscopy-related complications and discomfort, meaningful complication rates, and predictors. (Review)
Review
OBJECTIVE
To identify bronchoscopy-related complications and discomfort, meaningful complication rates, and predictors.
METHOD
We conducted a systematic literature search in PubMed on 8 February 2016, using a search strategy including the PICO model, on complications and discomfort related to bronchoscopy and related sampling techniques.
RESULTS
The search yielded 1,707 hits, of which 45 publications were eligible for full review. Rates of mortality and severe complications were low. Other complications, for instance, hypoxaemia, bleeding, pneumothorax, and fever, were usually not related to patient characteristics or aspects of the procedure, and complication rates showed considerable ranges. Measures of patient discomfort differed considerably, and results were difficult to compare between different study populations.
CONCLUSION
More research on safety aspects of bronchoscopy is needed to conclude on complication rates and patient- and procedure-related predictors of complications and discomfort.
PubMed: 27839531
DOI: 10.3402/ecrj.v3.33324