Add-on Test Research Articles

Bone Scintigraphy After a Negative Radiological Skeletal Survey Improves the Detection Rate of Inflicted Skeletal Injury in Children.

Background: Timely diagnosis of child physical abuse is of paramount importance. The added value of bone scintigraphy (BS) after a negative radiological skeletal survey (RSS) in children with suspected physical abuse has never been evaluated.Objective: The objective of this study was to assess the extent to which BS could improve the detection rate of skeletal injury in children with suspected physical abuse with an initial negative RSS.Methods: We used discharge codes to retrospectively identify children evaluated for suspected physical abuse in a university hospital (Nantes, France). We included all consecutive children younger than 3 years old who underwent both RSS and BS, with an interval of ≤96 h between tests, from 2013 to 2019. BS and RSS results were interpreted independently during the study period. We specifically analyzed BS results for children with a negative RSS to assess the value of BS as an add-on test.Results: Among the 268 children ≤3 years old with suspected physical abuse who underwent RSS, 140 (52%) also underwent BS within 96 h and were included in the analysis. The median age was 6 months old (interquartile range: 3–8). The detection rate of ≥1 skeletal injury with RSS alone was 49% (n = 69/140, 95% CI: 41–58%) vs. 58% (n = 81/140, 50–66%) with RSS followed by add-on BS, for an absolute increase in the detection rate of 9% points (95% CI: 4–14%). The number of children with a negative RSS who would need to undergo BS to detect one additional child with ≥1 skeletal injury was 6 (95% CI: 4–11).Conclusion: In young children with suspected physical abuse with a negative RSS, add-on BS would allow for a clinically significant improvement in the detection rate of skeletal injuries for a limited number of BS procedures required. Prospective multicenter studies are needed to confirm these findings.

Diagnostic Value of Perfusion MR Imaging as a Potential Ancillary Test for Brain Death.

Objective:The purpose of this study is to determine the potential role of dynamic susceptibility contrast (DSC) magnetic resonance (MR) perfusion imaging in diagnosing brain death.Materials and Methods:The study population was composed of 61 subjects (the Glasgow Coma Scale [GCS] score was 3 for all subjects), and 26 subjects were assigned to the control group (GCS scores between 4 and 6). At least four regions of interest (ROIs) from different anatomical regions were measured, the mean transit time (MTT), cerebral blood flow (CBF), and signal intensity time-to-course graphic were calculated. A second neurological examination (including an apnea test) was accepted as the gold standard method for the diagnosis of brain death.Results:DSC-MR perfusion imaging diagnosed brain death with a specificity of 100% (61/61) and a sensitivity of 86.8% (53/61). A cut-off value of maximum 3.5% decrease in the signal intensity time-to-course graphic was calculated by the Youden’s index and established for the to differentiate brain death from other conditions.Conclusion:DSC-MR perfusion imaging is a promising tool that may be used as a reliable add-on confirmatory diagnostic test for the brain death.

Sensitivity and specificity of different imaging modalities in diagnosing necrotising enterocolitis in a Polish population of preterm infants: a diagnostic test accuracy study protocol

IntroductionNecrotising enterocolitis (NEC) is one of the most serious conditions in newborn infants, affecting up to 10% of very low birth weight (VLBW) infants. Mortality rates can rise as high...

Ballistic performance of unidirectionally oriented carbon fiber reinforced composite armor with high-velocity impact

For the last few decades, composite materials have been more popular than other conventional metal materials in the aircraft industry. Having better mechanical properties (strength, fatigue life, impact strength, corrosion resistance, etc.) and being lighter than conventional engineering materials, composites have become very important in defense industry as well. In spite of the fact that some of the composite materials such as aramid-based composites have been effectively used in body protection, they have not been so successful in heavy armored vehicles which are generally equipped with different types of add-on armor blocks for protecting against threats. These add-on armors are mostly composed of armor steels and ceramics. This study specifically aims to investigate high-velocity impact behavior of unidirectionally oriented carbon fiber reinforced/epoxy layer sandwiched with armor steel plates that are exposed to kinetic energy projectile. Carbon fibers are normally very brittle to transverse loading direction, contrarily, to its axial tension or compression direction. This is the reason why it is claimed that this high compression strength property of carbon fibers could be used for manufacturing a layer in order to replace ceramics in add-on multilayer composite armor. In order to prove this hypothesis, an experimental analysis has been carried out by performing impact tests on these manufactured add-on armor test samples. Testing was carried out in accordance with the STANAG 4569 level-4 standard. The results indicated that the multilayer carbon fiber reinforced epoxy composite–armor steel hybrid panels can provide level-4 protection with a lower areal density compared to Rolled Homogenous Armor.

Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules.

Thyroid nodules are very common in general medical practice, but rarely turn out to be a medullary thyroid carcinoma (MTC). Calcitonin is a sensitive tumour marker for the detection of MTC (basal calcitonin). Sometimes a stimulation test is used to improve specificity (stimulated calcitonin). Although the European Thyroid Association's guideline advocates calcitonin determination in people with thyroid nodules, the role of routine calcitonin testing in individuals with thyroid nodules is still questionable. The objective of this review was to determine the diagnostic accuracy of basal and/or stimulated calcitonin as a triage or add-on test for detection of MTC in people with thyroid nodules. We searched CENTRAL, MEDLINE, Embase and Web of Science from inception to June 2018. We included all retrospective and prospective cohort studies in which all participants with thyroid nodules had undergone determination of basal calcitonin levels (and stimulated calcitonin, if performed). Two review authors independently scanned all retrieved records. We extracted data using a standard data extraction form. We assessed risk of bias and applicability using the QUADAS-2 tool. Using the hierarchical summary receiver operating characteristic (HSROC) model, we estimated summary curves across different thresholds and also obtained summary estimates of sensitivity and specificity at a common threshold when possible. In 16 studies, we identified 72,368 participants with nodular thyroid disease in whom routinely calcitonin testing was performed. All included studies performed the calcitonin test as a triage test. Median prevalence of MTC was 0.32%. Sensitivity in these studies ranged between 83% and 100% and specificity ranged between 94% and 100%. An important limitation in 15 of the 16 studies (94%) was the absence of adequate reference standards and follow-up in calcitonin-negative participants. This resulted in a high risk of bias with regard to flow and timing in the methodological quality assessment. At the median specificity of 96.6% from the included studies, the estimated sensitivity (95% confidence interval (CI)) from the summary curve was 99.7% ( 68.8% to 100%). For the median prevalence of MTC of 0.23%, the positive predictive value (PPV) for basal calcitonin testing at a threshold of 10 pg/mL was 7.7% (4.9% to 12.1%). Summary estimates of sensitivity and specificity for the threshold of 10 pg/mL of basal calcitonin testing was 100% (95% CI 99.7 to 100) and 97.2% (95% CI 95.9 to 98.6), respectively. For combined basal and stimulated calcitonin testing, sensitivity ranged between 82% and 100% with specificity between 99% and 100%. The median specificity was 99.8% with an estimated sensitivity of 98.8% (95% CI 65.8 to 100) . Both basal and combined basal and stimulated calcitonin testing have a high sensitivity and specificity. However, this may be an overestimation due to high risk of bias in the use and choice of reference standard The value of routine testing in patients with thyroid nodules remains questionable, due to the low prevalence, which results in a low PPV of basal calcitonin testing. Whether routine calcitonin testing improves prognosis in MTC patients remains unclear.

Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study

SummaryBackgroundBlood transcriptional signatures are candidates for non-sputum triage or confirmatory tests of tuberculosis. Prospective head-to-head comparisons of their diagnostic accuracy in real-world settings are necessary to assess their clinical use. We aimed to compare the diagnostic accuracy of candidate transcriptional signatures identified by systematic review, in a setting with a high burden of tuberculosis and HIV.MethodsWe did a prospective observational study nested within a diagnostic accuracy study of sputum Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) tests for pulmonary tuberculosis. We recruited consecutive symptomatic adults aged 18 years or older self-presenting to a tuberculosis clinic in Cape Town, South Africa. Participants provided blood for RNA sequencing, and sputum samples for liquid culture and molecular testing using Xpert and Ultra. We assessed the diagnostic accuracy of candidate blood transcriptional signatures for active tuberculosis (including those intended to distinguish active tuberculosis from other diseases) identified by systematic review, compared with culture or Xpert MTB/RIF positivity as the standard reference. In our primary analysis, patients with tuberculosis were defined as those with either a positive liquid culture or Xpert result. Patients with missing blood RNA or sputum results were excluded. Our primary objective was to benchmark the diagnostic accuracy of candidate transcriptional signatures against the WHO target product profile (TPP) for a tuberculosis triage test.FindingsBetween Feb 12, 2016, and July 18, 2017, we obtained paired sputum and RNA sequencing data from 181 participants, 54 (30%) of whom had confirmed pulmonary tuberculosis. Of 27 eligible signatures identified by systematic review, four achieved the highest diagnostic accuracy with similar area under the receiver operating characteristic curves (Sweeney3: 90·6% [95% CI 85·6–95·6]; Kaforou25: 86·9% [80·9–92·9]; Roe3: 86·9% [80·3–93·5]; and BATF2: 86·8% [80·6–93·1]), independent of age, sex, HIV status, previous tuberculosis, or sputum smear result. At test thresholds that gave 70% specificity (the minimum WHO TPP specificity for a triage test), these four signatures achieved sensitivities between 83·3% (95% CI 71·3–91·0) and 90·7% (80·1–96·0). No signature met the optimum criteria, of 95% sensitivity and 80% specificity proposed by WHO for a triage test, or the minimum criteria (of 65% sensitivity and 98% specificity) for a confirmatory test, but all four correctly identified Ultra-positive, culture-negative patients.InterpretationSelected blood transcriptional signatures met the minimum WHO benchmarks for a tuberculosis triage test but not for a confirmatory test. Further development of the signatures is warranted to investigate their possible effects on clinical and health economic outcomes as part of a triage strategy, or when used as add-on confirmatory test in conjunction with the highly sensitive Ultra test for Mycobacterium tuberculosis DNA.FundingRoyal Society Newton Advanced Fellowship, Wellcome Trust, National Institute of Health Research, and UK Medical Research Council.

Structural magnetic resonance imaging for the early diagnosis of dementia due to Alzheimer's disease in people with mild cognitive impairment.

Structural magnetic resonance imaging for the early diagnosis of dementia due to Alzheimer's disease in people with mild cognitive impairment.

Ultrasonographic morphological diagnosis of chronic liver disease: 2-dimensional shear wave elastography as an add-on test.

PurposeThis study investigated the impact of liver stiffness measurements (LSM) made using 2-dimensional (2D) shear wave elastography (SWE) on the diagnosis and grading of hepatic fibrosis and liver cirrhosis (LC) using grayscale ultrasonography (US).MethodsThis retrospective study included 46 patients who underwent liver biopsy for chronic liver disease and 33 non-biopsied subjects with no or mild fibrosis (an aspartate aminotransferase-to-platelet ratio index <0.50 and a Forns score <4.21). Two abdominal radiologists reviewed randomized grayscale hepatic sonogram sets with and without LSM, separated by a 4-week interval. They graded the features of echogenicity, echotexture, surface nodularity, and edge blunting and classified patients by fibrosis grade. Interobserver agreement and correlations with the fibrosis grades were compared before and after the reviewers were informed regarding LSM, and the impact of LSM on diagnostic performance was evaluated.ResultsThe standard diagnoses were no or mild fibrosis (F0-1, n=39), moderate to advanced fibrosis (F2-3, n=23), or LC (n=17). The correlations between US and the diagnostic reference standard increased significantly with LSM incorporation (0.499 and 0.312 to 0.782 and 0.804, P<0.01 for both reviewers), as did interobserver agreement (0.318 to 0.753, P<0.01). The areas under the receiver operating characteristic curve (AUCs) for the diagnosis of significant fibrosis increased when LSM was included (0.682 and 0.591 to 0.855 and 0.907, P<0.01 for both reviewers), while the AUCs for the diagnosis of LC did not change significantly (0.891 and 0.783 to 0.904 and 0.900, P=0.849 and P=0.166).ConclusionIncorporating LSM values obtained by 2D-SWE improved the diagnostic accuracy and interobserver agreement of grayscale US for hepatic fibrosis.

The impact of computed radiography and teleradiology on patients' diagnosis and treatment in Mweso, the Democratic Republic of Congo.

IntroductionHigh quality diagnostic imaging can provide increased diagnostic accuracy and help guide medical decision-making and management, however challenges for radiology in resource-limited settings are numerous. Diagnostic imaging and teleradiology have financial and logistical implications, so evidence of impact is crucial. We sought to test the hypothesis that the implementation of computed radiography with teleradiology consultation support will significantly change diagnoses and treatment plans in a resource limited setting.MethodPaired before-after study to determine the therapeutic impact of an add-on diagnostic test. ‘Preliminary Plan’ and ‘Final Plan’ forms allowed direct comparison of diagnosis and treatment plans at initial consultation and following radiography and teleradiology. Consecutive consenting patients were included until the sample size (600) was reached. Changes in both diagnosis and treatment plan were analysed in the whole cohort, with sub-analyses of children aged <5 years, and cases of chest radiography.ResultsFinal analysis included 536 cases. Diagnosis changed following radiography and teleradiology in 62% of cases, and treatment plans changed in 61%. In chest radiography cases, 70% of diagnoses and 62% of treatment plans changed, while in children <5 years 66% of diagnoses and 58% of treatment plans changed.Reduced final treatment plans were most common for exploratory surgery (72% decrease), surgical orthopaedic intervention (62% decrease), and TB treatment (52% decrease), allowing more conservative medical or surgical management in 61 cases. Increased final treatment plans were highest in the orthopaedic and interventional surgery and referral categories. Of 42 cases requiring interventional surgery in the final plan, 26 (62%) were identified only after radiography and teleradiology. 16 additional cases were indicated for orthopaedic surgery, 10 cases required patient transfer, and TB treatment was indicated in 45 cases. A change in the original prescription plan occurred in 41% of 536 cases, with one or more prescriptions stopped in 28% of all cases.ConclusionWe found that computed radiography with teleradiology had significant clinical value in this resource-limited setting, with the potential to affect both patient outcomes and treatment costs through providing improved diagnostics and avoiding unnecessary treatments and medications.

Computed tomography for diagnosis of acute appendicitis in adults.

Diagnosing acute appendicitis (appendicitis) based on clinical evaluation, blood testing, and urinalysis can be difficult. Therefore, in persons with suspected appendicitis, abdominopelvic computed tomography (CT) is often used as an add-on test following the initial evaluation to reduce remaining diagnostic uncertainty. The aim of using CT is to assist the clinician in discriminating between persons who need surgery with appendicectomy and persons who do not. Primary objective Our primary objective was to evaluate the accuracy of CT for diagnosing appendicitis in adults with suspected appendicitis. Secondary objectives Our secondary objectives were to compare the accuracy of contrast-enhanced versus non-contrast-enhanced CT, to compare the accuracy of low-dose versus standard-dose CT, and to explore the influence of CT-scanner generation, radiologist experience, degree of clinical suspicion of appendicitis, and aspects of methodological quality on diagnostic accuracy. We searched MEDLINE, Embase, and Science Citation Index until 16 June 2017. We also searched references lists. We did not exclude studies on the basis of language or publication status. We included prospective studies that compared results of CT versus outcomes of a reference standard in adults (> 14 years of age) with suspected appendicitis. We excluded studies recruiting only pregnant women; studies in persons with abdominal pain at any location and with no particular suspicion of appendicitis; studies in which all participants had undergone ultrasonography (US) before CT and the decision to perform CT depended on the US outcome; studies using a case-control design; studies with fewer than 10 participants; and studies that did not report the numbers of true-positives, false-positives, false-negatives, and true-negatives. Two review authors independently screened and selected studies for inclusion. Two review authors independently collected the data from each study and evaluated methodological quality according to the Quality Assessment of Studies of Diagnostic Accuracy - Revised (QUADAS-2) tool. We used the bivariate random-effects model to obtain summary estimates of sensitivity and specificity. We identified 64 studies including 71 separate study populations with a total of 10,280 participants (4583 with and 5697 without acute appendicitis). Estimates of sensitivity ranged from 0.72 to 1.0 and estimates of specificity ranged from 0.5 to 1.0 across the 71 study populations. Summary sensitivity was 0.95 (95% confidence interval (CI) 0.93 to 0.96), and summary specificity was 0.94 (95% CI 0.92 to 0.95). At the median prevalence of appendicitis (0.43), the probability of having appendicitis following a positive CT result was 0.92 (95% CI 0.90 to 0.94), and the probability of having appendicitis following a negative CT result was 0.04 (95% CI 0.03 to 0.05). In subgroup analyses according to contrast enhancement, summary sensitivity was higher for CT with intravenous contrast (0.96, 95% CI 0.92 to 0.98), CT with rectal contrast (0.97, 95% CI 0.93 to 0.99), and CT with intravenous and oral contrast enhancement (0.96, 95% CI 0.93 to 0.98) than for unenhanced CT (0.91, 95% CI 0.87 to 0.93). Summary sensitivity of CT with oral contrast enhancement (0.89, 95% CI 0.81 to 0.94) and unenhanced CT was similar. Results show practically no differences in summary specificity, which varied from 0.93 (95% CI 0.90 to 0.95) to 0.95 (95% CI 0.90 to 0.98) between subgroups. Summary sensitivity for low-dose CT (0.94, 95% 0.90 to 0.97) was similar to summary sensitivity for standard-dose or unspecified-dose CT (0.95, 95% 0.93 to 0.96); summary specificity did not differ between low-dose and standard-dose or unspecified-dose CT. No studies had high methodological quality as evaluated by the QUADAS-2 tool. Major methodological problems were poor reference standards and partial verification primarily due to inadequate and incomplete follow-up in persons who did not have surgery. The sensitivity and specificity of CT for diagnosing appendicitis in adults are high. Unenhanced standard-dose CT appears to have lower sensitivity than standard-dose CT with intravenous, rectal, or oral and intravenous contrast enhancement. Use of different types of contrast enhancement or no enhancement does not appear to affect specificity. Differences in sensitivity and specificity between low-dose and standard-dose CT appear to be negligible. The results of this review should be interpreted with caution for two reasons. First, these results are based on studies of low methodological quality. Second, the comparisons between types of contrast enhancement and radiation dose may be unreliable because they are based on indirect comparisons that may be confounded by other factors.

The Burden of Add-On Orders in a Laboratory With Manual Processing

Abstract In order to avoid additional blood draws for their patients, clinicians frequently order add-on tests on existing specimens in the laboratory. Manually processing these add-ons is problematic, utilizes tremendous resources, and raises concerns regarding specimen integrity. The objective of this study was to analyze add-on ordering patterns and assess the time and resources required to complete these orders. In this retrospective study conducted at a large, multisite, academic medical center, a report was generated from the laboratory information system (LIS) to identify all the add-on orders that were placed with details about the type of add-on test, which specimen it was added to, and location from where an add-on order was placed for a 2-month period (August 5 to October 4, 2018). The workflow was observed and financial cost was calculated. The laboratory received 5,658 add-on orders during the study period. By laboratory protocol, 859 tests were cancelled, leaving 4,799 tests to be processed. Add-on orders were most common for liver tests (7.48%), creatine kinase (6.35%), troponin (6.31%), vancomycin level (5.93%), thyroid-stimulating hormone (4.91%), magnesium (4.81%), and vitamin B12 (4.33%). The add-on orders were mainly generated for inpatient (74.07%) followed by emergency (17.79%) and outpatient departments (8.12%). The add-on request is placed by the clinical provider in the hospital information system (HIS) as a generic “Add-on Order” test, with free text to specify the test and specimen. A clerk in the laboratory uses the LIS-generated work list to electronically order the requested tests to the original specimen. Subsequently, a clerk must manually locate the original specimen and deliver it to the performing lab to run the add-on test. The median turnaround time from the provider placing the generic add-on order in the HIS to the lab placing the add-on in the LIS is 119 minutes. The median time for the provider to place an add-on after the initial order is 462 minutes. The average time needed to monitor the add-on work list, electronically place the add-on to the original order, and retrieve the sample for one test for a skilled senior statistical clerk is 7 minutes. The average number of add-on requests received daily is 71. Therefore, the daily time to process add-ons is 497 minutes (8.2 hours). Based on the hourly cost and fringe in the laboratory ($28.92/hour), these add-on tests cost $237/day in labor ($86,000/year). Our study demonstrates the significant cost and labor burden of add-on tests in a laboratory with manual processing. The laboratory is considering transitioning to direct provider ordering of add-ons to existing specimens using laboratory-defined rules in the HIS and moving to total laboratory automation with robotic specimen archival and retrieval to reduce the manual efforts, which would streamline the add-on workflow.

Accuracy of Tumour-Associated Circulating Endothelial Cells as a Screening Biomarker for Clinically Significant Prostate Cancer

Even though more than 350,000 men die from prostate cancer every year, broad-based screening for the disease remains a controversial topic. Guidelines demand that the only commonly accepted screening tool, prostate-specific antigen (PSA) testing, must be followed by prostate biopsy if results are elevated. Due to the procedure’s low positive predictive value (PPV), however, over 80% of biopsies are performed on healthy men or men with clinically insignificant cancer—prompting calls for new ways of vetting equivocal PSA readings prior to the procedure. Responding to the challenge, the present study investigated the diagnostic potential of tumour-associated circulating endothelial cells (tCECs), which have previously been described as a novel, blood-based biomarker for clinically significant cancers. Specifically, the objective was to determine the diagnostic accuracy of a tCEC-based blood test to detect clinically significant prostate cancer (defined as Gleason score ≥ 3 + 4) in high-risk patients. Performed in a blinded, prospective, single-centre set-up, it compared a novel tCEC index test with transrectal ultrasound-guided biopsy as a reference on a total of 170 patients and found that a tCEC add-on test will almost double the PPV of a standalone PSA test (32% vs. 17%; p = 0.0012), while retaining a negative predictive value above 90%.

MON-LB097 The Genomic Landscape of Preoperative FNAs Positive for the Afirma GSC Medullary Thyroid Cancer Classifier

Background The Afirma Genomic Sequencing Classifier (GSC) uses RNA sequencing to assess FNA specimens from cytologically indeterminate thyroid nodules, which are also tested for specific molecular aberrations associated with thyroid cancer via a suite of highly accurate malignancy classifiers. This suite can also be applied independently to Bethesda V/VI nodules. The Afirma Xpression Atlas (XA) is an optional add-on test to GSC and the malignancy classifiers that reports nucleotide variants and fusions across 511 cancer-associated genes. Medullary thyroid cancer (MTC) is a rare subtype of thyroid cancer that can appear in every Bethesda category. Herein, we report the prevalence and genomic landscape of MTC classifier positive (MTC+) FNA samples in a CLIA certified clinical laboratory. Methods All Afirma GSC and malignancy classifier tests run between July 2017 and November 2018 were deidentified and examined for MTC+ cases. Afirma XA was run on all MTC cases and all variants and fusions were tabulated. Results Examination of 22,130 FNAs revealed 77 MTC cases. Among consecutive GSC tests, 28 were Bethesda III (0.16% out of 17,245) and 27 were Bethesda IV (0.65% out of 4,182). Provider-ordered testing was done on an additional 14 and 8 MTC cases from Bethesda V and VI nodules, respectively. Examining all MTC+ samples revealed that 55.8% harbored a RET variant (+/- others), 9.1% contained a KRAS variant (+/- others), 6.5% had an HRAS variant, 2.6% possessed fusions, and 26.0% included no variant/fusion. Conclusions In indeterminate FNA samples, the Afirma GSC can help to clarify the risk of MTC. In our cohort, the Afirma XA identified a variant or fusion in 74.0% of MTC+ FNAs. Limitations of this study include the lack of knowledge regarding germline RET status (which should be checked in all patients with an identified RET variant or confirmed MTC) and final pathology on MTC+ samples. Future studies may investigate how the preoperative identification of a known MTC driver mutation in a biopsy sample can inform the pre-operative evaluation, the surgical plan, and the potential role of targeted therapy. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Assessment of Diagnostic Strategy for Early Recognition of Bullous and Nonbullous Variants of Pemphigoid

A substantial number of patients with bullous pemphigoid do not develop skin blisters and may not have received the correct diagnosis. Diagnostic criteria and an optimal diagnostic strategy are needed for early recognition and trials. To assess the minimal requirements for diagnosis of bullous and nonbullous forms of pemphigoid and to evaluate the optimal diagnostic strategy. This paired, multivariable, diagnostic accuracy study analyzed data from 1125 consecutive patients with suspected pemphigoid who were referred to the Groningen Center for Blistering Diseases from secondary and tertiary care hospitals throughout the Netherlands. Eligible participants were patients with paired data on at least (1) a skin biopsy specimen for the direct immunofluorescence (DIF) microscopy test; (2) indirect immunofluorescence on a human salt-split skin substrate (IIF SSS) test; and (3) 1 or more routine immunoserologic tests administered between January 1, 2002, and May 1, 2015. Samples were taken from patients at the time of first diagnosis, before introduction of immunosuppressive therapy, and within an inclusion window of a maximum of 4 weeks. Data analysis was conducted from October 1, 2015, to December 1, 2017. Pairwise DIF, IIF SSS, IIF on monkey esophagus, BP180 and BP230 enzyme-linked immunosorbent assays, and immunoblot for BP180 and BP230 tests were performed. The results were reported in accordance with 2015 version of the Standards for Reporting Diagnostic Accuracy. Of the 1125 patients analyzed, 653 (58.0%) were women and 472 (42.0%) were men, with a mean (SD) age of 63.2 (19.9) years. In total, 343 participants received a pemphigoid diagnosis, with 782 controls. Of the 343 patients, 74 (21.6%, or 1 in 5) presented with nonbullous pemphigoid. The DIF microscopy was the most sensitive diagnostic test (88.3% [n = 303]; 95% CI, 84.5%-91.3%), whereas IIF SSS was less sensitive (77.0% [n = 263]; 95% CI, 72.2%-81.1%) but was highly specific (99.9%; 95% CI, 99.3%-100%) and complemented most cases with negative DIF findings. Results of the BP180 NC16A enzyme-linked immunosorbent assay did not add diagnostic value for initial diagnosis in multivariable logistic regression analysis of combined tests. These findings lead to the proposed minimal criteria for diagnosing pemphigoid: (1) pruritus and/or predominant cutaneous blisters, (2) linear IgG and/or C3c deposits (in an n-serrated pattern) by DIF on a skin biopsy specimen, and (3) positive epidermal side staining of IgG by IIF SSS on a serum sample; this proposal extends bullous pemphigoid with the unrecognized nonbullous form. Both DIF and IIF SSS tests should be performed for diagnosis of the bullous and nonbullous variants of pemphigoid, and the BP180 NC16A enzyme-linked immunosorbent assay is recommended as an add-on test for disease activity monitoring.

Xpert negative means no TB: A mixed-methods study into early implementation of Xpert in Puducherry, India.

Introduction:Xpert MTB/RIF was implemented in 2016 as the initial diagnostic test for extrapulmonary, pediatric, and human immunodeficiency virus–associated tuberculosis (TB) and as an add-on test for sputum microscopy–negative patients under Revised National TB Control Programme, Puducherry, India. We intended to study the change in TB case notification rates (CNRs) after 2015 and explore the enablers and barriers for implementation of Xpert.Materials and Methods:Sequential mixed-methods study, quantitative phase followed by a descriptive qualitative phase (key informant interviews with healthcare providers in the program).Results:The TB (all forms) CNR increased in 2016 followed by a drop to 2015 levels in 2017. There was a reduction in patients notified as sputum-negative pulmonary TB and pediatric TB during 2016–2017. Healthcare providers used a negative Xpert result in ruling out TB among patients who would previously get diagnosed clinically. Perceived benefits of Xpert were efficiency, rapid results, and detecting resistance. Barriers included poor awareness among medical colleges and the private sector, difficulty in motivating sputum microscopy–negative patients for Xpert, and incompletely filled referral forms.Conclusion:Xpert-negative results should be interpreted cautiously after clinical assessment. Identified barriers should be addressed to ensure that all eligible undergo testing.

Diagnostic Performance of Shear Wave Elastography as Add-on Test in Thyroid Nodules: a Systematic Review and Meta-Analysis

Diagnostic Performance of Shear Wave Elastography as Add-on Test in Thyroid Nodules: a Systematic Review and Meta-Analysis

Effectiveness of real-time polymerase chain reaction assay for the detection of Mycobacterium tuberculosis in pathological samples: a systematic review and meta-analysis

BackgroundRapid and accurate diagnosis of tuberculosis (TB) is key to manage the disease and to control and prevent its transmission. Many established diagnostic methods suffer from low sensitivity or delay of timely results and are inadequate for rapid detection of Mycobacterium tuberculosis (MTB) in pulmonary and extra-pulmonary clinical samples. This study examined whether a real-time polymerase chain reaction (RT-PCR) assay, with a turn-a-round time of 2 h, would prove effective for routine detection of MTB by clinical microbiology laboratories.MethodsA systematic literature search was performed for publications in any language on the detection of MTB in pathological samples by RT-PCR assay. The following sources were used MEDLINE via PubMed, EMBASE, BIOSIS Citation Index, Web of Science, SCOPUS, ISI Web of Knowledge and Cochrane Infectious Diseases Group Specialised Register, grey literature, World Health Organization and Centres for Disease Control and Prevention websites. Forty-six studies met set inclusion criteria. Generated pooled summary estimates (95% CIs) were calculated for overall accuracy and bivariate meta-regression model was used for meta-analysis.ResultsSummary estimates for pulmonary TB (31 studies) were as follows: sensitivity 0.82 (95% CI 0.81–0.83), specificity 0.99 (95% CI 0.99–0.99), positive likelihood ratio 43.00 (28.23–64.81), negative likelihood ratio 0.16 (0.12–0.20), diagnostic odds ratio 324.26 (95% CI 189.08–556.09) and area under curve 0.99. Summary estimates for extra-pulmonary TB (25 studies) were as follows: sensitivity 0.70 (95% CI 0.67–0.72), specificity 0.99 (95% CI 0.99–0.99), positive likelihood ratio 29.82 (17.86–49.78), negative likelihood ratio 0.33 (0.26–0.42), diagnostic odds ratio 125.20 (95% CI 65.75–238.36) and area under curve 0.96.ConclusionsRT-PCR assay demonstrated a high degree of sensitivity for pulmonary TB and good sensitivity for extra-pulmonary TB. It indicated a high degree of specificity for ruling in TB infection from sampling regimes. This was acceptable, but may better as a rule out add-on diagnostic test. RT-PCR assays demonstrate both a high degree of sensitivity in pulmonary samples and rapidity of detection of TB which is an important factor in achieving effective global control and for patient management in terms of initiating early and appropriate anti-tubercular therapy.Systematic review registrationPROSPERO CRD42015027534.

Stability of plasma electrolytes in Barricor and PST II tubes under different storage conditions.

IntroductionSample stability can be influenced by many different factors; evaporation and leakage from residual cells are the most relevant factors for electrolytes. During the analytical phase, samples are usually kept uncapped at room temperature. Once samples are processed, they are usually stored sealed and refrigerated. Long turnaround time and the possibility of “add-on test” need consideration for electrolyte stability. The aim of our study is to examine short-term electrolyte stability in this two-common laboratory working conditions in two different lithium heparin plasma tubes (Barricor and PST II, Becton Dickinson).Materials and methodsIn 39 plasma samples from voluntary subjects we measured sodium (Na+), potassium (K+) and chloride (Cl–) at 6 time points since centrifugation (0h, 3h, 6h, 9h, 12h and 15h). Maximum allowable bias (clinically significant change) was based in SEQC (Sociedad Espańola de Química Clínica) recommendations; 1% for Cl–, 0.6% for Na+ and 4% for K+.ResultsIn open room temperature tubes, clinically significant changes appeared in Na+ and Cl– after 3 hours and in K+ after 9 hours in both types of tubes. In refrigerated sealed tubes, all the analytes were clinically stable up to 12 hours in both kinds of plasma tubes. We observed a statistically significant progressive increase in K+ levels, which was less pronounced in Barricor tubes.ConclusionStability of electrolytes is compromised after 3 hours in open tubes and after 12 hours in sealed tubes.

Diagnostic accuracy of different imaging modalities following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer.

Periampullary cancer includes cancer of the head and neck of the pancreas, cancer of the distal end of the bile duct, cancer of the ampulla of Vater, and cancer of the second part of the duodenum. Surgical resection is the only established potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Other imaging methods such as magnetic resonance imaging (MRI), positron emission tomography (PET), PET-CT, and endoscopic ultrasound (EUS) have been used to detect local invasion or distant metastases not visualised on CT scanning which could prevent unnecessary laparotomy. No systematic review or meta-analysis has examined the role of different imaging modalities in assessing the resectability with curative intent in patients with pancreatic and periampullary cancer. To determine the diagnostic accuracy of MRI, PET scan, and EUS performed as an add-on test or PET-CT as a replacement test to CT scanning in detecting curative resectability in pancreatic and periampullary cancer. We searched MEDLINE, Embase, Science Citation Index Expanded, and Health Technology Assessment (HTA) databases up to 5 November 2015. Two review authors independently screened the references and selected the studies for inclusion. We also searched for articles related to the included studies by performing the "related search" function in MEDLINE (OvidSP) and Embase (OvidSP) and a "citing reference" search (by searching the articles that cite the included articles). We included diagnostic accuracy studies of MRI, PET scan, PET-CT, and EUS in patients with potentially resectable pancreatic and periampullary cancer on CT scan. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies. Two review authors independently performed data extraction and quality assessment using the QUADAS-2 (quality assessment of diagnostic accuracy studies - 2) tool. Although we planned to use bivariate methods for analysis of sensitivities and specificities, we were able to fit only the univariate fixed-effect models for both sensitivity and specificity because of the paucity of data. We calculated the probability of unresectability in patients who had a positive index test (post-test probability of unresectability in people with a positive test result) and in those with negative index test (post-test probability of unresectability in people with a positive test result) using the mean probability of unresectability (pre-test probability) from the included studies and the positive and negative likelihood ratios derived from the model. The difference between the pre-test and post-test probabilities gave the overall added value of the index test compared to the standard practice of CT scan staging alone. Only two studies (34 participants) met the inclusion criteria of this systematic review. Both studies evaluated the diagnostic test accuracy of EUS in assessing the resectability with curative intent in pancreatic cancers. There was low concerns about applicability for most domains in both studies. The overall risk of bias was low in one study and unclear or high in the second study. The mean probability of unresectable disease after CT scan across studies was 60.5% (that is 61 out of 100 patients who had resectable cancer after CT scan had unresectable disease on laparotomy). The summary estimate of sensitivity of EUS for unresectability was 0.87 (95% confidence interval (CI) 0.54 to 0.97) and the summary estimate of specificity for unresectability was 0.80 (95% CI 0.40 to 0.96). The positive likelihood ratio and negative likelihood ratio were 4.3 (95% CI 1.0 to 18.6) and 0.2 (95% CI 0.0 to 0.8) respectively. At the mean pre-test probability of 60.5%, the post-test probability of unresectable disease for people with a positive EUS (EUS indicating unresectability) was 86.9% (95% CI 60.9% to 96.6%) and the post-test probability of unresectable disease for people with a negative EUS (EUS indicating resectability) was 20.0% (5.1% to 53.7%). This means that 13% of people (95% CI 3% to 39%) with positive EUS have potentially resectable cancer and 20% (5% to 53%) of people with negative EUS have unresectable cancer. Based on two small studies, there is significant uncertainty in the utility of EUS in people with pancreatic cancer found to have resectable disease on CT scan. No studies have assessed the utility of EUS in people with periampullary cancer.There is no evidence to suggest that it should be performed routinely in people with pancreatic cancer or periampullary cancer found to have resectable disease on CT scan.

Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer.

Surgical resection is the only potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Laparoscopy can detect metastases not visualised on CT scanning, enabling better assessment of the spread of cancer (staging of cancer). This is an update to a previous Cochrane Review published in 2013 evaluating the role of diagnostic laparoscopy in assessing the resectability with curative intent in people with pancreatic and periampullary cancer. To determine the diagnostic accuracy of diagnostic laparoscopy performed as an add-on test to CT scanning in the assessment of curative resectability in pancreatic and periampullary cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, EMBASE via OvidSP (from inception to 15 May 2016), and Science Citation Index Expanded (from 1980 to 15 May 2016). We included diagnostic accuracy studies of diagnostic laparoscopy in people with potentially resectable pancreatic and periampullary cancer on CT scan, where confirmation of liver or peritoneal involvement was by histopathological examination of suspicious (liver or peritoneal) lesions obtained at diagnostic laparoscopy or laparotomy. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies. Two review authors independently performed data extraction and quality assessment using the QUADAS-2 tool. The specificity of diagnostic laparoscopy in all studies was 1 because there were no false positives since laparoscopy and the reference standard are one and the same if histological examination after diagnostic laparoscopy is positive. The sensitivities were therefore meta-analysed using a univariate random-effects logistic regression model. The probability of unresectability in people who had a negative laparoscopy (post-test probability for people with a negative test result) was calculated using the median probability of unresectability (pre-test probability) from the included studies, and the negative likelihood ratio derived from the model (specificity of 1 assumed). The difference between the pre-test and post-test probabilities gave the overall added value of diagnostic laparoscopy compared to the standard practice of CT scan staging alone. We included 16 studies with a total of 1146 participants in the meta-analysis. Only one study including 52 participants had a low risk of bias and low applicability concern in the patient selection domain. The median pre-test probability of unresectable disease after CT scanning across studies was 41.4% (that is 41 out of 100 participants who had resectable cancer after CT scan were found to have unresectable disease on laparotomy). The summary sensitivity of diagnostic laparoscopy was 64.4% (95% confidence interval (CI) 50.1% to 76.6%). Assuming a pre-test probability of 41.4%, the post-test probability of unresectable disease for participants with a negative test result was 0.20 (95% CI 0.15 to 0.27). This indicates that if a person is said to have resectable disease after diagnostic laparoscopy and CT scan, there is a 20% probability that their cancer will be unresectable compared to a 41% probability for those receiving CT alone.A subgroup analysis of people with pancreatic cancer gave a summary sensitivity of 67.9% (95% CI 41.1% to 86.5%). The post-test probability of unresectable disease after being considered resectable on both CT and diagnostic laparoscopy was 18% compared to 40.0% for those receiving CT alone. Diagnostic laparoscopy may decrease the rate of unnecessary laparotomy in people with pancreatic and periampullary cancer found to have resectable disease on CT scan. On average, using diagnostic laparoscopy with biopsy and histopathological confirmation of suspicious lesions prior to laparotomy would avoid 21 unnecessary laparotomies in 100 people in whom resection of cancer with curative intent is planned.