Childhood Intra-Thoracic Tuberculosis Clinical Presentation Determines Yield of Laboratory Diagnostic Assays
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SUBMITTER: Singh U
PROVIDER: S-EPMC8425475 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceLaboratory testing is an important target for high-value care initiatives, constituting the highest volume of medical procedures. Prior studies have found that up to half of all inpatient laboratory tests may be medically unnecessary, but a systematic method to identify these unnecessary tests in individual cases is lacking.ObjectiveTo systematically identify low-yield inpatient laboratory testing through personalized predictions.Design, setting, and participantsIn this retrospective diagnostic study with multivariable prediction models, 116 637 inpatients treated at Stanford University Hospital from January 1, 2008, to December 31, 2017, a total of 60 929 inpatients treated at University of Michigan from January 1, 2015, to December 31, 2018, and 13 940 inpatients treated at the University of California, San Francisco from January 1 to December 31, 2018, were assessed.Main outcomes and measuresDiagnostic accuracy measures, including sensitivity, specificity, negative predictive values (NPVs), positive predictive values (PPVs), and area under the receiver operating characteristic curve (AUROC), of machine learning models when predicting whether inpatient laboratory tests yield a normal result as defined by local laboratory reference ranges.ResultsIn the recent data sets (July 1, 2014, to June 30, 2017) from Stanford University Hospital (including 22 664 female inpatients with a mean [SD] age of 58.8 [19.0] years and 22 016 male inpatients with a mean [SD] age of 59.0 [18.1] years), among the top 20 highest-volume tests, 792 397 were repeats of orders within 24 hours, including tests that are physiologically unlikely to yield new information that quickly (eg, white blood cell differential, glycated hemoglobin, and serum albumin level). The best-performing machine learning models predicted normal results with an AUROC of 0.90 or greater for 12 stand-alone laboratory tests (eg, sodium AUROC, 0.92 [95% CI, 0.91-0.93]; sensitivity, 98%; specificity, 35%; PPV, 66%; NPV, 93%; lactate dehydrogenase AUROC, 0.93 [95% CI, 0.93-0.94]; sensitivity, 96%; specificity, 65%; PPV, 71%; NPV, 95%; and troponin I AUROC, 0.92 [95% CI, 0.91-0.93]; sensitivity, 88%; specificity, 79%; PPV, 67%; NPV, 93%) and 10 common laboratory test components (eg, hemoglobin AUROC, 0.94 [95% CI, 0.92-0.95]; sensitivity, 99%; specificity, 17%; PPV, 90%; NPV, 81%; creatinine AUROC, 0.96 [95% CI, 0.96-0.97]; sensitivity, 93%; specificity, 83%; PPV, 79%; NPV, 94%; and urea nitrogen AUROC, 0.95 [95% CI, 0.94, 0.96]; sensitivity, 87%; specificity, 89%; PPV, 77%; NPV 94%).Conclusions and relevanceThe findings suggest that low-yield diagnostic testing is common and can be systematically identified through data-driven methods and patient context-aware predictions. Implementing machine learning models appear to be able to quantify the level of uncertainty and expected information gained from diagnostic tests explicitly, with the potential to encourage useful testing and discourage low-value testing that incurs direct costs and indirect harms.
| S-EPMC6739729 | biostudies-literature
Project description:IntroductionAnalysis of fibrinolytic disorders is challenging and may potentially lead to underdiagnosis of patients with an increased bleeding tendency.AimTo compare clinical characteristics, laboratory measurements, and treatment modalities in a monocenter cohort of patients in whom fibrinolytic studies were performed.MethodsRetrospective study of patients in whom fibrinolytic studies were performed between January 2016 and February 2020 in the Hemophilia Treatment Center, Nijmegen-Eindhoven-Maastricht, the Netherlands. Plasminogen activator inhibitor type 1 (PAI-1) antigen and activity level, α2-antiplasmin activity, tissue plasminogen activator, and euglobulin clot lysis time (ECLT) before and after venous compression were determined in all patients. Data of bleeding assessment tool (BAT) score, clinical characteristics, results of primary and secondary hemostasis assays, and general treatment plans were collected.ResultsIn total, 160 patients were included: 97 (61%) without and 63 (39%) with a laboratory-based fibrinolytic disorder. Mean BAT score did not differ between the groups (9.3 vs 9.8, respectively). The presumptive fibrinolytic disorders were distributed as follows: 34 patients had an increased ECLT ratio or low baseline ECLT, 25 patients had low PAI-1 antigen and activity level, and four patients had both. The majority of these patients were treated with tranexamic acid monotherapy (60%) with only 40% additional treatment options, whereas 80% of patients without a presumptive fibrinolytic disorder had multiple treatment modalities.DiscussionAnalysis of fibrinolytic disorders in selected patients has a high diagnostic yield. General incorporation of fibrinolytic analysis in the diagnostic workup of patients with bleeding of unknown cause can improve diagnosis and management of their bleeding episodes.
| S-EPMC8922970 | biostudies-literature
Project description:Background and objectivesSpinal muscular atrophy (SMA) is mainly caused by homozygous SMN1 gene deletions on 5q13. Non-5q SMA patients' series are lacking, and the diagnostic yield of next-generation sequencing (NGS) is largely unknown. The aim of this study was to describe the clinical and genetic landscape of non-5q SMA and evaluate the performance of neuropathy gene panels in these disorders.MethodsDescription of patients with non-5q SMA followed in the different neuromuscular reference centers in France as well as in London, United Kingdom. Patients without a genetic diagnosis had undergone at least a neuropathy or large neuromuscular gene panel.ResultsSeventy-one patients from 65 different families were included, mostly sporadic cases (60.6%). At presentation, 21 patients (29.6%) showed exclusive proximal weakness (P-SMA), 35 (49.3%) showed associated distal weakness (PD-SMA), and 15 (21.1%) a scapuloperoneal phenotype (SP-SMA). Thirty-two patients (45.1%) had a genetic diagnosis: BICD2 (n = 9), DYNC1H1 (n = 7), TRPV4 (n = 4), VCP, HSBP1, AR (n = 2), VRK1, DNAJB2, MORC2, ASAH1, HEXB, and unexpectedly, COL6A3 (n = 1). The genetic diagnostic yield was lowest in P-SMA (6/21, 28.6%) compared with PD-SMA (16/35, 45.7%) and SP-SMA (10/15, 66.7%). An earlier disease onset and a family history of the disease or consanguinity were independent predictors of a positive genetic diagnosis. Neuropathy gene panels were performed in 59 patients with a 32.2% diagnostic yield (19/59). In 13 additional patients, a genetic diagnosis was achieved through individual gene sequencing or an alternative neuromuscular NGS.DiscussionNon-5q SMA is genetically heterogeneous, and neuropathy gene panels achieve a molecular diagnosis in one-third of the patients. The diagnostic yield can be increased by sequencing of other neuromuscular and neurometabolic genes. Nevertheless, there is an unmet need to cluster these patients to aid in the identification of new genes.
| S-EPMC10352921 | biostudies-literature
Project description:BackgroundBringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance.MethodsWe conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra.ResultsOf 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67-78%) and 80% (95% CI 75-84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27-47%) and 47% (95% CI 37-58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62-95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF.ConclusionWe found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays.
| S-EPMC8607906 | biostudies-literature
Project description:Foot-and-mouth disease (FMD) affects economically important livestock and is one of the most contagious viral diseases. The most commonly used FMD diagnostic assay is a sandwich ELISA. However, the main disadvantage of this ELISA is that it requires anti-FMD virus (FMDV) serotype-specific antibodies raised in small animals. This problem can be, in part, overcome by using anti-FMDV monoclonal antibodies (MAbs) as detecting reagents. However, the long-term use of MAbs may be problematic and they may need to be replaced. Here we have constructed chimeric antibodies (mouse/rabbit D9) and Fabs (fragment antigen-binding) (mouse/cattle D9) using the Fv (fragment variable) regions of a mouse MAb, D9 (MAb D9), which recognises type O FMDV. The mouse/rabbit D9 chimeric antibody retained the FMDV serotype-specificity of MAb D9 and performed well in a FMDV detection ELISA as well as in routine laboratory assays. Cryo-electron microscopy analysis confirmed engagement with antigenic site 1 and peptide competition studies identified the aspartic acid at residue VP1 147 as a novel component of the D9 epitope. This chimeric expression approach is a simple but effective way to preserve valuable FMDV antibodies, and has the potential for unlimited generation of antibodies and antibody fragments in recombinant systems with the concomitant positive impacts on the 3Rs (Replacement, Reduction and Refinement) principles.
| S-EPMC6095514 | biostudies-literature
Project description:A number of Helicobacter species may confound experimental data because of their association with disease progressing in various kinds of laboratory animals. Screening of Helicobacter species is particularly desirable, because they are prevalent in commercial and research animal facilities. The aim of the present study was to compare three diagnostic methods [e.g. Helicobacter stool antigen kit (HpSA), polymerase chain reaction (PCR) and rapid urease test (RUT)] for the identification of Helicobacter spp. in stools or gastric biopsy specimens collected from eight dogs suffering from gastritis. The gastroscopic biopsy specimens were tested using RUT and PCR, while stool specimens were evaluated using both HpSA and PCR. DNAs from the gastric biopsies and stool specimens were analyzed by both a consensus PCR that amplified the RNA polymerase beta-subunit-coding gene (rpoB) of Helicobacter spp. and a species-specific PCR to amplify the urease B gene of Helicobacter heilmannii, Helicobacter pylori, and Helicobacter felis. Helicobacter spp. were detected in 62.5% of the dogs, while H. heilmannii and H. felis were identified in 37.5 and 25% of the dogs, respectively. The HpSA did not efficiently detect Helicobacter spp. in the stool samples compared to the RUT and PCR assays, both of which successfully detected Helicobacter spp. in the two sample types. Finally, we recommend that consensus PCR with stool specimens could be used before the species-specific PCR for identifying Helicobacter species in laboratory dogs.
| S-EPMC4490150 | biostudies-literature
Project description:BACKGROUNDInadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden, and accurate point-of-care tests (POCTs) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM) POCT for TB diagnosis in HIV-negative outpatients and compared it with Alere Determine TB LAM Ag (AlereLAM) POCT and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM).METHODSIn this multicenter diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient health care centers in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM, and EclLAM, and the diagnostic accuracy was assessed against a microbiological reference standard (MRS) and a composite reference standard.RESULTSThree hundred seventy-two HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared with the MRS, the sensitivities of AlereLAM, FujiLAM, and EclLAM were 10.8% (95% confidence interval [CI] 6.3%-18.0%), 53.2% (95% CI 43.9%-62.1%), and 66.7% (95% CI 57.5%-74.7%), respectively. The specificities of AlereLAM, FujiLAM, and EclLAM were 92.3% (95% CI 88.5%-95.0%), 98.9% (95% CI 96.7%-99.6%), and 98.1% (95% CI 95.6%-99.2%), respectively. Positive likelihood ratios of AlereLAM, FujiLAM, and EclLAM were 1.4, 46.2, and 34.8, respectively, and positive predictive values were 37.5%, 95.2%, and 93.7%, respectively.CONCLUSIONCompared with AlereLAM, FujiLAM detected 5 times more patients with TB in HIV-negative participants, had a high positive predictive value, and has the potential to improve rapid diagnosis of TB at the point-of-care. EclLAM demonstrated that additional sensitivity gains are possible, which highlights LAM's potential as a biomarker. Additional research is required to assess FujiLAM's performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings.FUNDINGGlobal Health Innovative Technology Fund, the UK Department for International Development, the Dutch Ministry of Foreign Affairs, the Bill and Melinda Gates Foundation, the Australian Department of Foreign Affairs and Trade, the German Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, and the NIH and National Institute of Allergy and Infectious Diseases.
| S-EPMC7598043 | biostudies-literature
Project description:Evaluation of tests for the diagnosis of childhood pulmonary tuberculosis (CPTB) is complicated by the absence of an accurate reference test. We present a Bayesian latent class analysis in which we evaluated the accuracy of 5 diagnostic tests for CPTB. We used data from a study of 749 hospitalized South African children suspected to have CPTB from 2009 to 2014. The following tests were used: mycobacterial culture, smear microscopy, Xpert MTB/RIF (Cepheid Inc.), tuberculin skin test (TST), and chest radiography. We estimated the prevalence of CPTB to be 27% (95% credible interval (CrI): 21, 35). The sensitivities of culture, Xpert, and smear microscopy were estimated to be 60% (95% CrI: 46, 76), 49% (95% CrI: 38, 62), and 22% (95% CrI: 16, 30), respectively; specificities of these tests were estimated in accordance with prior information and were close to 100%. Chest radiography was estimated to have a sensitivity of 64% (95% CrI: 55, 73) and a specificity of 78% (95% CrI: 73, 83). Sensitivity of the TST was estimated to be 75% (95% CrI: 61, 84), and it decreased substantially among children who were malnourished and infected with human immunodeficiency virus (56%). The specificity of the TST was 69% (95% CrI: 63%, 76%). Furthermore, it was estimated that 46% (95% CrI: 42, 49) of CPTB-negative cases and 93% (95% CrI: 82; 98) of CPTB-positive cases received antituberculosis treatment, which indicates substantial overtreatment and limited undertreatment.
| S-EPMC5100832 | biostudies-other
Project description:BackgroundRapid and sensitive Tuberculosis (TB) diagnosis closer to patients is a key global TB control priority. Truenat assays (MTB, MTB Plus, and MTB-RIF Dx) are new TB molecular diagnostic tools for the detection of TB and Rifampicin (RIF)-resistance from sputum samples. The diagnostic accuracy of the assays is needed prior to implementation in clinical use in Ethiopia. This study aimed to determine the sensitivity and specificity of Truenat assays; and aimed to compare the assays to the Xpert MTB/RIF assay.MethodsA prospective evaluation study was conducted among 200 presumptive TB patients in microscopy centers in Addis Ababa, Ethiopia from May 2019 to December 2020. Culture (Solid and Liquid methods) and phenotypic (liquid method) drug susceptibility testing (DST) were used as a reference standard.ResultsOf 200 adult participants, culture confirmed TB cases were 25 (12.5%), and only one isolate was resistant to RIF by phenotypic DST. The sensitivity of Truenat MTB was 88.0% [95% CI 70.1, 95.8], while 91.7 [95% CI 74.2, 97.7] for Truenat MTB Plus at the microscopy centers. The specificity of Truenat MTB was 97.2% [95% CI 93.1, 98.9], while for Truenat MTB Plus was 97.2% [95% CI 93.0, 99.0]. The sensitivity of Truenat MTB was 90.5% while for MTB Plus, 100% compared to the Xpert MTB/RIF assay.ConclusionTruenat assays were found to have high diagnostic accuracy. The assays have the potential to be used as a point of care (POC) TB diagnostic tests.
| S-EPMC8714111 | biostudies-literature
Project description:Objectives: There is a lack of evidence-based consensus for the utility of gastrointestinal endoscopy (GIE) in an array of frequently occurring symptoms in children. We aimed to assess the diagnostic yield of endoscopy in an effort to aid clinical decision making. Methods: Retrospective analysis included patients ≤18 years who underwent GIE during one calendar year at Shaare Zedek Medical Center. We excluded children referred for predefined obvious indications for GIE, planned follow-up procedures, and therapeutic endoscopy. Clinician-assigned indication for endoscopy as well as endoscopic and histologic findings were recorded. Diagnostic yield of GIE was determined according to referral indication. Results: There were 794 endoscopies performed of which 329 were included in the analysis (mean age 9.3 ± 5.0 years, 51% female). No significant complications of GIE were recorded. Six major referral indications were identified among which abdominal pain was the most frequent 88/329 (26%) of whom 32/88 (36%) had a significant diagnostic finding. Among the other major indications, diagnostic findings were found in 36/85 (43%) children with primary indication of chronic diarrhea, 14/33 (42%) failure to thrive, 15/32 (46%) short stature, 30/56 (54%) iron deficiency, and 20/48 (42%) weight loss. Conclusions: Pediatric GIE is a safe procedure with diverse clinical indications. The diagnostic yield of endoscopy is variable, depending on the referral indication. These data can assist formulating judicious referral practices.
| S-EPMC8586696 | biostudies-literature