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Clinical and Experimental Rheumatology Feb 2022Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance.
METHODS
We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate.
RESULTS
We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly.
CONCLUSIONS
The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.
Topics: Autoantibodies; Humans; Ligases; Syndrome
PubMed: 35225224
DOI: 10.55563/clinexprheumatol/8xj0b9 -
Autoimmunity Reviews Oct 2021To identify and assess the magnitude of effect of pregnancy outcome predictors in women with antiphospholipid syndrome (APS) by means of systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To identify and assess the magnitude of effect of pregnancy outcome predictors in women with antiphospholipid syndrome (APS) by means of systematic review and meta-analysis.
METHODS
PubMed and Embase were searched (13th June 2020) for studies reporting on pre-pregnancy risk factors of pregnancy outcomes in APS patients. Literature screening and data extraction were conducted by two reviewers independently, in a blinded standardized manner. Pooled univariate odds ratios (OR) were computed using a random effects model. Heterogeneity was assessed by I%.
RESULTS
The search yielded 3013 unique results; 27 records were included in this meta-analysis. Previous thrombosis was associated with a decreased live birth risk (OR 0.60, p < 0.01, I = 40%), increased neonatal mortality (OR 15.19, p < 0.01, I = 0%), an increased risk of antenatal or postpartum thrombosis (OR 6.26, p < 0.01, I = 0%) and an increased risk of delivering a small for gestational age neonate (SGA) (OR 2.60, p = 0.01, I = 0%). Patients with an APS laboratory category I (double or triple positivity) profile had a decreased live birth risk (OR 0.66, p < 0.01, I = 0%), an increased risk of SGA (OR 1.86, p = 0.01, I = 43%) and preterm birth (OR 1.35, p < 0.01, I = 49%). Triple positivity was associated with a decreased live birth risk (OR 0.33, p < 0.01, I = 68%), an increased risk of preeclampsia (OR 2.43, p = 0.02, I = 35%) and SGA (OR 2.47, p = 0.04, I = 61%). Patients with lupus anticoagulant positivity had an increased risk of preeclampsia (OR 2.10, p = 0.02, I = 48%), SGA (OR 1.78, p < 0.01, I = 0%) and preterm birth (OR 3.56, p = 0.01, I = 48%). Risk of bias assessment suggested considerable bias on study participation and statistical methods.
CONCLUSIONS
The results of this meta-analysis identified previous thrombosis, laboratory category I, triple positivity and lupus anticoagulant positivity as the most important predictors of adverse pregnancy outcomes. This up-to-date knowledge, can be used in preconception counseling and tailoring of obstetric care.
Topics: Antiphospholipid Syndrome; Female; Humans; Infant, Newborn; Lupus Coagulation Inhibitor; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth
PubMed: 34280554
DOI: 10.1016/j.autrev.2021.102901 -
International Journal of Geriatric... Feb 2018The Montreal Cognitive Assessment (MoCA; Nasreddine et al., 2005) is a cognitive screening tool that aims to differentiate healthy cognitive aging from Mild Cognitive... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The Montreal Cognitive Assessment (MoCA; Nasreddine et al., 2005) is a cognitive screening tool that aims to differentiate healthy cognitive aging from Mild Cognitive Impairment (MCI). Several validation studies have been conducted on the MoCA, in a variety of clinical populations. Some studies have indicated that the originally suggested cutoff score of 26/30 leads to an inflated rate of false positives, particularly for those of older age and/or lower education. We conducted a systematic review and meta-analysis of the literature to determine the diagnostic accuracy of the MoCA for differentiating healthy cognitive aging from possible MCI.
METHODS
Of the 304 studies identified, nine met inclusion criteria for the meta-analysis. These studies were assessed across a range of cutoff scores to determine the respective sensitivities, specificities, positive and negative predictive accuracies, likelihood ratios for positive and negative results, classification accuracies, and Youden indices.
RESULTS
Meta-analysis revealed a cutoff score of 23/30 yielded the best diagnostic accuracy across a range of parameters.
CONCLUSIONS
A MoCA cutoff score of 23, rather than the initially recommended score of 26, lowers the false positive rate and shows overall better diagnostic accuracy. We recommend the use of this cutoff score going forward. Copyright © 2017 John Wiley & Sons, Ltd.
Topics: Aging; Cognition; Cognitive Dysfunction; False Positive Reactions; Humans; Mass Screening; Mental Status and Dementia Tests; Reference Values; Sensitivity and Specificity
PubMed: 28731508
DOI: 10.1002/gps.4756 -
JAMA Network Open Nov 2021COVID-19 has disproportionately affected racial and ethnic minority groups, and race and ethnicity have been associated with disease severity. However, the association... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
COVID-19 has disproportionately affected racial and ethnic minority groups, and race and ethnicity have been associated with disease severity. However, the association of socioeconomic determinants with racial disparities in COVID-19 outcomes remains unclear.
OBJECTIVE
To evaluate the association of race and ethnicity with COVID-19 outcomes and to examine the association between race, ethnicity, COVID-19 outcomes, and socioeconomic determinants.
DATA SOURCES
A systematic search of PubMed, medRxiv, bioRxiv, Embase, and the World Health Organization COVID-19 databases was performed for studies published from January 1, 2020, to January 6, 2021.
STUDY SELECTION
Studies that reported data on associations between race and ethnicity and COVID-19 positivity, disease severity, and socioeconomic status were included and screened by 2 independent reviewers. Studies that did not have a satisfactory quality score were excluded. Overall, less than 1% (0.47%) of initially identified studies met selection criteria.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Associations were assessed using adjusted and unadjusted risk ratios (RRs) and odds ratios (ORs), combined prevalence, and metaregression. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
The main measures were RRs, ORs, and combined prevalence values.
RESULTS
A total of 4 318 929 patients from 68 studies were included in this meta-analysis. Overall, 370 933 patients (8.6%) were African American, 9082 (0.2%) were American Indian or Alaska Native, 101 793 (2.4%) were Asian American, 851 392 identified as Hispanic/Latino (19.7%), 7417 (0.2%) were Pacific Islander, 1 037 996 (24.0%) were White, and 269 040 (6.2%) identified as multiracial and another race or ethnicity. In age- and sex-adjusted analyses, African American individuals (RR, 3.54; 95% CI, 1.38-9.07; P = .008) and Hispanic individuals (RR, 4.68; 95% CI, 1.28-17.20; P = .02) were the most likely to test positive for COVID-19. Asian American individuals had the highest risk of intensive care unit admission (RR, 1.93; 95% CI, 1.60-2.34, P < .001). The area deprivation index was positively correlated with mortality rates in Asian American and Hispanic individuals (P < .001). Decreased access to clinical care was positively correlated with COVID-19 positivity in Hispanic individuals (P < .001) and African American individuals (P < .001).
CONCLUSIONS AND RELEVANCE
In this study, members of racial and ethnic minority groups had higher risks of COVID-19 positivity and disease severity. Furthermore, socioeconomic determinants were strongly associated with COVID-19 outcomes in racial and ethnic minority populations.
Topics: COVID-19; Humans; Outcome Assessment, Health Care; Prevalence; Racial Groups; Social Class; United States
PubMed: 34762110
DOI: 10.1001/jamanetworkopen.2021.34147 -
Allergy Feb 2023Food allergy (FA) is increasingly reported in Europe, however, the latest prevalence estimates were based on studies published a decade ago. The present work provides... (Meta-Analysis)
Meta-Analysis Review
Food allergy (FA) is increasingly reported in Europe, however, the latest prevalence estimates were based on studies published a decade ago. The present work provides the most updated estimates of the prevalence and trends of FA in Europe. Databases were searched for studies published between 2012 and 2021, added to studies published up to 2012. In total, 110 studies were included in this update. Most studies were graded as moderate risk of bias. Pooled lifetime and point prevalence of self-reported FA were 19.9% (95% CI 16.6-23.3) and 13.1% (95% CI 11.3-14.8), respectively. The point prevalence of sensitization based on specific IgE (slgE) was 16.6% (95% CI 12.3-20.8), skin prick test (SPT) 5.7% (95% CI 3.9-7.4), and positive food challenge 0.8% (95% CI 0.5-0.9). While lifetime prevalence of self-reported FA and food challenge positivity only slightly changed, the point prevalence of self-reported FA, sIgE and SPT positivity increased from previous estimates. This may reflect a real increase, increased awareness, increased number of foods assessed, or increased number of studies from countries with less data in the first review. Future studies require rigorous designs and implementation of standardized methodology in diagnosing FA, including use of double-blinded placebo-controlled food challenge to minimize potential biases.
Topics: Humans; Immunoglobulin E; Food Hypersensitivity; Food; Skin Tests; Allergens; Europe
PubMed: 36271775
DOI: 10.1111/all.15560 -
International Journal of Nursing Studies Sep 2021The contribution of work to positive mental health is increasingly apparent. Transition into the workplace causes a range of stressors for new graduate nurses who... (Review)
Review
BACKGROUND
The contribution of work to positive mental health is increasingly apparent. Transition into the workplace causes a range of stressors for new graduate nurses who experience both psychological wellbeing and illbeing in their first year of practice.
OBJECTIVE
To determine published prevalence, predictors, barriers and enablers of new graduate registered nurse wellbeing, work wellbeing and mental health.
DESIGN
Systematic review of quantitative research.
DATA SOURCES
Databases included Cumulative Index of Nursing and Allied Health Literature, Excerpta Medica database, Medical Literature Analysis and Retrieval System Online and Psychological Information. Quantitative and mixed-methods studies were considered for inclusion if published in English from 2009 to 2019 reporting primary data analysis including new graduate nurses' wellbeing, work wellbeing and mental health.
REVIEW METHODS
Quantitative studies were systematically identified then screened and appraised against pre-determined inclusion criteria. Analysis was conducted by grouping according to analytical methods and results reported as a narrative synthesis.
RESULTS
Thirty-four studies were included. The quality of the evidence was variable with just a quarter of the studies being assessed as meeting the quality criteria on all nine measures. For the new graduate nurses prevalence of wellbeing, levels of resilience, optimism, and hope were found to be high. For work wellbeing, most reported higher job satisfaction by 12-months. For work illbeing, levels of burnout were moderately high, predominantly in terms of emotional exhaustion, and stress was initially high, particularly in terms of workload, but decreased over time. For the predictors, job satisfaction was positively predicted by structural empowerment and career satisfaction, and negatively predicted by co-worker incivility, supervisor incivility and emotional exhaustion. For work illbeing, stress was a positive predictor for intent to leave. Stress reductions were associated with momentary levels of high task mastery, social acceptance and role clarity.
CONCLUSIONS
For new graduate nurses, levels of emotional exhaustion, workload and stress were moderately high to high initially, decreasing over time as the graduate nurses' job satisfaction increased. Most studies focused on the nurses' intent to resign or stay and both psychological capital and work engagement positively predicted intent to stay whereas work stress positively predicted intent to resign. Resilience and group cohesion moderated the negative effects of some variables, thus may be potential enablers of work wellbeing. The standards of research reporting or design were generally sub-optimal according to quality indicators. Systematic review registration number: (CRD42020148812).
Topics: Burnout, Professional; Education, Nursing, Graduate; Humans; Job Satisfaction; Mental Health; Workplace
PubMed: 34218048
DOI: 10.1016/j.ijnurstu.2021.103997 -
The Lancet. Oncology Apr 2023Human papillomavirus (HPV) DNA and p16 positivity have crucial roles in the pathogenesis of vulvar cancer and vulvar intraepithelial neoplasia. We aimed to examine the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human papillomavirus (HPV) DNA and p16 positivity have crucial roles in the pathogenesis of vulvar cancer and vulvar intraepithelial neoplasia. We aimed to examine the pooled prevalence of HPV DNA and p16 positivity in vulvar cancer and vulvar intraepithelial neoplasia worldwide.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library databases for studies published between Jan 1, 1986, and May 6, 2022, that reported the prevalence of HPV DNA, or p16 positivity, or both, in histologically verified vulvar cancer or vulvar intraepithelial neoplasia. Studies on a minimum of five cases were included. Study-level data were extracted from the published studies. Random effect models were used to examine the pooled prevalence of HPV DNA and p16 positivity in both vulvar cancer and vulvar intraepithelial neoplasia, which were further investigated using stratified analyses by histological subtype, geographical region, HPV DNA or p16 detection method, tissue sample type, HPV genotype, publication year, and age at diagnosis. Additionally, meta-regression was applied to explore sources of heterogeneity.
FINDINGS
We retrieved 6393 search results, of which 6233 were excluded for being duplicates or after application of our inclusion and exclusion criteria. We also identified two studies from manual searches of references lists. 162 studies were eligible for inclusion in the systematic review and meta-analysis. The prevalence of HPV in vulvar cancer (91 studies; n=8200) was 39·1% (95% CI 35·3-42·9) and in vulvar intraepithelial neoplasia (60 studies; n=3140) was 76·1% (70·7-81·1). The most predominant HPV genotype in vulvar cancer was HPV16 (78·1% [95% CI 73·5-82·3]), followed by HPV33 (7·5% [4·9-10·7]). Similarly, HPV16 (80·8% [95% CI 75·9-85·2]) and HPV33 (6·3% [3·9-9·2]) were also the most two predominant HPV genotypes in vulvar intraepithelial neoplasia. The distribution of type-specific HPV genotypes in vulvar cancer among geographical regions was different, with HPV16 varying between regions, showing a high prevalence in Oceania (89·0% [95% CI 67·6-99·5]) and a low prevalence in South America (54·3% [30·2-77·4]). The prevalence of p16 positivity in patients with vulvar cancer was 34·1% (95% CI 30·9-37·4; 52 studies; n=6352), and it was 65·7% (52·5-77·7; 23 studies; n=896) in patients with vulvar intraepithelial neoplasia. Furthermore, among patients with HPV-positive vulvar cancer, p16 positivity prevalence was 73·3% (95% CI 64·7-81·2), compared with 13·8% (10·0-18·1) in HPV-negative vulvar cancer. The prevalence of double positivity for HPV and p16 was 19·6% (95% CI 16·3-23·0) in vulvar cancer and 44·2% (26·3-62·8) in vulvar intraepithelial neoplasia. Most analyses had large heterogeneity (I>75%).
INTERPRETATION
The high prevalence of HPV16 and HPV33 in vulvar cancer and vulvar intraepithelial neoplasia emphasised the importance of nine-valent HPV vaccination in preventing vulvar neoplasm. Additionally, this study highlighted the potential clinical significance of double positivity for HPV DNA and p16 in vulvar neoplasm.
FUNDING
Taishan Scholar Youth Project of Shandong Province, China.
Topics: Female; Humans; Adolescent; Vulvar Neoplasms; Cyclin-Dependent Kinase Inhibitor p16; Human Papillomavirus Viruses; DNA, Viral; Prevalence; Papillomavirus Infections; Carcinoma in Situ; Carcinoma, Squamous Cell; Papillomaviridae; Human papillomavirus 16
PubMed: 36933562
DOI: 10.1016/S1470-2045(23)00066-9 -
European Urology Apr 2020Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment.... (Meta-Analysis)
Meta-Analysis
Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer-Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis.
CONTEXT
Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of Ga-PSMA PET in this setting.
OBJECTIVE
To perform a systematic review and meta-analysis to update reported predictors of positive Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles.
EVIDENCE ACQUISITION
We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.
EVIDENCE SYNTHESIS
A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥2ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed.
CONCLUSIONS
Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings.
PATIENT SUMMARY
Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Topics: Antigens, Surface; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Glutamate Carboxypeptidase II; Humans; Male; Neoplasm Staging; Oligopeptides; Positron-Emission Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 30773328
DOI: 10.1016/j.eururo.2019.01.049 -
American Journal of Epidemiology Jan 2021Health-care workers (HCWs) are at the frontline of response to coronavirus disease 2019 (COVID-19), being at a higher risk of acquiring the disease and, subsequently,... (Meta-Analysis)
Meta-Analysis
Health-care workers (HCWs) are at the frontline of response to coronavirus disease 2019 (COVID-19), being at a higher risk of acquiring the disease and, subsequently, exposing patients and others. Searches of 8 bibliographic databases were performed to systematically review the evidence on the prevalence, risk factors, clinical characteristics, and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs. A total of 97 studies (all published in 2020) met the inclusion criteria. The estimated prevalence of SARS-CoV-2 infection from HCWs' samples, using reverse transcription-polymerase chain reaction and the presence of antibodies, was 11% (95% confidence interval (CI): 7, 15) and 7% (95% CI: 4, 11), respectively. The most frequently affected personnel were nurses (48%, 95% CI: 41, 56), whereas most of the COVID-19-positive medical personnel were working in hospital nonemergency wards during screening (43%, 95% CI: 28, 59). Anosmia, fever, and myalgia were the only symptoms associated with HCW SARS-CoV-2 positivity. Among HCWs positive for COVID-19 by reverse transcription-polymerase chain reaction, 40% (95% CI: 17, 65) were asymptomatic at time of diagnosis. Finally, severe clinical complications developed in 5% (95% CI: 3, 8) of the COVID-19-positive HCWs, and 0.5% (95% CI: 0.02, 1.3) died. Health-care workers suffer a significant burden from COVID-19, with those working in hospital nonemergency wards and nurses being the most commonly infected personnel.
Topics: COVID-19; Global Health; Health Personnel; Humans; Prevalence; Risk Factors; SARS-CoV-2
PubMed: 32870978
DOI: 10.1093/aje/kwaa191 -
The Cochrane Database of Systematic... Aug 2018Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a million people were newly diagnosed with rifampicin-resistant TB in 2016. Xpert MTB/RIF (Xpert) is a World Health Organization (WHO)-recommended, rapid, automated, nucleic acid amplification assay that is used widely for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum specimens. This Cochrane Review assessed the accuracy of Xpert in extrapulmonary specimens.
OBJECTIVES
To determine the diagnostic accuracy of Xpert a) for extrapulmonary TB by site of disease in people presumed to have extrapulmonary TB; and b) for rifampicin resistance in people presumed to have extrapulmonary TB.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature (LILACS), Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number (ISRCTN) Registry, and ProQuest up to 7 August 2017 without language restriction.
SELECTION CRITERIA
We included diagnostic accuracy studies of Xpert in people presumed to have extrapulmonary TB. We included TB meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB. We used culture as the reference standard. For pleural TB, we also included a composite reference standard, which defined a positive result as the presence of granulomatous inflammation or a positive culture result. For rifampicin resistance, we used culture-based drug susceptibility testing or MTBDRplus as the reference standard.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed risk of bias and applicability using the QUADAS-2 tool. We determined pooled predicted sensitivity and specificity for TB, grouped by type of extrapulmonary specimen, and for rifampicin resistance. For TB detection, we used a bivariate random-effects model. Recognizing that use of culture may lead to misclassification of cases of extrapulmonary TB as 'not TB' owing to the paucibacillary nature of the disease, we adjusted accuracy estimates by applying a latent class meta-analysis model. For rifampicin resistance detection, we performed univariate meta-analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected. We used theoretical populations with an assumed prevalence to provide illustrative numbers of patients with false positive and false negative results.
MAIN RESULTS
We included 66 unique studies that evaluated 16,213 specimens for detection of extrapulmonary TB and rifampicin resistance. We identified only one study that evaluated the newest test version, Xpert MTB/RIF Ultra (Ultra), for TB meningitis. Fifty studies (76%) took place in low- or middle-income countries. Risk of bias was low for patient selection, index test, and flow and timing domains and was high or unclear for the reference standard domain (most of these studies decontaminated sterile specimens before culture inoculation). Regarding applicability, in the patient selection domain, we scored high or unclear concern for most studies because either patients were evaluated exclusively as inpatients at tertiary care centres, or we were not sure about the clinical settings.Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid); Xpert sensitivity was > 80% in urine and bone or joint fluid and tissue. Pooled Xpert specificity (defined by culture) varied less than sensitivity (82% in bone or joint tissue to 99% in pleural fluid and urine). Xpert specificity was ≥ 98% in cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid.Xpert testing in cerebrospinal fluidXpert pooled sensitivity and specificity (95% credible interval (CrI)) against culture were 71.1% (60.9% to 80.4%) and 98.0% (97.0% to 98.8%), respectively (29 studies, 3774 specimens; moderate-certainty evidence).For a population of 1000 people where 100 have TB meningitis on culture, 89 would be Xpert-positive: of these, 18 (20%) would not have TB (false-positives); and 911 would be Xpert-negative: of these, 29 (3%) would have TB (false-negatives).For TB meningitis, ultra sensitivity and specificity against culture (95% confidence interval (CI)) were 90% (55% to 100%) and 90% (83% to 95%), respectively (one study, 129 participants).Xpert testing in pleural fluidXpert pooled sensitivity and specificity (95% CrI) against culture were 50.9% (39.7% to 62.8%) and 99.2% (98.2% to 99.7%), respectively (27 studies, 4006 specimens; low-certainty evidence).For a population of 1000 people where 150 have pleural TB on culture, 83 would be Xpert-positive: of these, seven (8%) would not have TB (false-positives); and 917 would be Xpert-negative: of these, 74 (8%) would have TB (false-negatives).Xpert testing in urineXpert pooled sensitivity and specificity (95% CrI) against culture were 82.7% (69.6% to 91.1%) and 98.7% (94.8% to 99.7%), respectively (13 studies, 1199 specimens; moderate-certainty evidence).For a population of 1000 people where 70 have genitourinary TB on culture, 70 would be Xpert-positive: of these, 12 (17%) would not have TB (false-positives); and 930 would be Xpert-negative: of these, 12 (1%) would have TB (false-negatives).Xpert testing for rifampicin resistanceXpert pooled sensitivity (20 studies, 148 specimens) and specificity (39 studies, 1088 specimens) were 95.0% (89.7% to 97.9%) and 98.7% (97.8% to 99.4%), respectively (high-certainty evidence).For a population of 1000 people where 120 have rifampicin-resistant TB, 125 would be positive for rifampicin-resistant TB: of these, 11 (9%) would not have rifampicin resistance (false-positives); and 875 would be negative for rifampicin-resistant TB: of these, 6 (1%) would have rifampicin resistance (false-negatives).For lymph node TB, the accuracy of culture, the reference standard used, presented a greater concern for bias than in other forms of extrapulmonary TB.
AUTHORS' CONCLUSIONS
In people presumed to have extrapulmonary TB, Xpert may be helpful in confirming the diagnosis. Xpert sensitivity varies across different extrapulmonary specimens, while for most specimens, specificity is high, the test rarely yielding a positive result for people without TB (defined by culture). Xpert is accurate for detection of rifampicin resistance. For people with presumed TB meningitis, treatment should be based on clinical judgement, and not withheld solely on an Xpert result, as is common practice when culture results are negative.
Topics: Antibiotics, Antitubercular; Bacterial Proteins; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Humans; Mycobacterium tuberculosis; Reagent Kits, Diagnostic; Reference Standards; Rifampin; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Meningeal
PubMed: 30148542
DOI: 10.1002/14651858.CD012768.pub2