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Diagnostic value of 18F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis.

PURPOSE: To retrospectively evaluate the diagnostic value of (18)F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis. METHODS: Thirty-three partial body (18)F-FDG PET/CT scans were performed in 33 patients with trauma suspected of having chronic osteomyelitis. In 10 and 23 patients, infection was suspected in the axial and appendicular skeleton, respectively. In 18 patients, PET/CT was performed in the presence of metallic implants. Histopathology or bacteriological culture was used as the standard of reference. For statistical analysis, sensitivity, specificity and accuracy were calculated in relation to findings of the reference standard. RESULTS: Of 33 PET/CT scans, 17 were true positive, 13 true negative, two false positive and one false negative. Eighteen patients had chronic osteomyelitis and 15 had no osseous infection according to the reference standard. Sensitivity, specificity and accuracy for (18)F-FDG PET/CT was 94%, 87% and 91% for the whole group, 88%, 100% and 90% for the axial skeleton and 100%, 85% and 91% for the appendicular skeleton, respectively. CONCLUSION: (18)F-FDG PET/CT is a highly sensitive and specific method for the evaluation of chronic infection in the axial and appendicular skeleton in patients with trauma. PET/CT allows precise anatomical localisation and characterisation of the infectious focus and demonstrates the extent of chronic osteomyelitis with a high degree of accuracy.

Adult↗

Peroneal tendon subluxation and dislocation: detection on volume-rendered images--initial experience.

Institutional review board approval was received and informed consent was not required for this Health Insurance Portability and Accountability Act-compliant study. The purpose of this study was to retrospectively assess the time efficiency of three-dimensional volume-rendered images obtained from multi-detector row computed tomographic data for the diagnosis of peroneal tendon subluxation or dislocation by using the consensus interpretation of multiplanar reformatted (MPR) images as the reference standard. The reference standard was provided by two musculoskeletal radiologists, and two less experienced readers evaluated 37 images in 32 patients (24 men, eight women; mean age, 41 years; age range, 18-75 years) with acute calcaneal fractures. An analysis of variance was used to compare interpretation time, and the Wilcoxon signed rank test was used to analyze diagnostic difficulty. The average time required for diagnosis was significantly shorter with volume-rendered images than with MPR images (reader 1: 42 vs 78 seconds, P<.001; reader 2: 50 vs 69 seconds, P<.01).

Adolescent↗

Three-dimensional, navigator-echo MR coronary angiography in detecting stenoses of the major epicardial vessels, with conventional coronary angiography as the standard of reference.

PURPOSE: To test three-dimensional (3D), navigator-echo magnetic resonance (MR) coronary angiography in detecting stenoses of the coronary arteries. MATERIALS AND METHODS: Forty-two patients (age range, 50-79 years) underwent MR coronary angiography (1.5 T). A navigator-echo sequence was used. Two or three 15% overlapped transverse slabs were acquired. Data were analyzed by readers blinded to conventional coronary angiographic results. On conventional coronary angiograms, coronary arterial stenoses of 50% or greater narrowing were considered significant. On MR coronary angiograms, the major coronary vessels were subdivided into proximal (within 5 cm) and distal (beyond 5 cm) segments, except for the left main vessel. Stenoses of 50% or greater were identified on reformatted multiplanar MR coronary angiograms. RESULTS: Three MR coronary angiographic examinations were aborted because of patient claustrophobia; 39 of 39 left main, 117 of 117 proximal, and 78 of 117 distal segments were visualized. MR coronary angiography showed a sensitivity of 82% (95% CI: 73%, 91%) and a specificity of 89% (95% CI: 85%, 94%) in overall stenoses identification, of 90% (95% CI: 81%, 99%) and 90% (95% CI: 83%, 96%) for proximal segments, and of 68% (95% CI: 50%, 86%) and 81% (95% CI: 71%, 92%) for distal segments, respectively. CONCLUSION: Navigator-echo, 3D MR coronary angiography is a promising sequence for assessing coronary arterial stenoses, but further improvements are required for distal segments.

Aged↗

Permanent turbidity standards.

Permanent turbidity reference standards suitable for measurement of microbial suspensions were prepared by suspending finely divided titanium dioxide in aryl sulfonamide-formaldehyde or methylstyrene resins. Turbidities of these standards, adjusted to a useful range for microbiological and immunological studies, were compared with other reference standards in use today. Tube holders for a Coleman Photonephelometer and a Nepho-Colorimeter were modified to eliminate the water well and to allow use of optically standardized 10-, 16-, or 18-mm test tubes. The standards and the tube holders have been used satisfactorily for more than 12 years.

Allergy and Immunology↗

A randomized crossover trial of PAPNET for primary cervical screening.

OBJECTIVE: To develop and demonstrate efficient methods to estimate the relative true positive and false positive rates of two cervical screening tests (conventional cytology and PAPNET). METHODS: We designed the study to meet stringent methodologic criteria for comparison of two tests while simultaneously minimizing the numbers requiring reference standard verification. We used a cytology reference standard and also assessed histology when available. For the primary analysis, slides with discordant results around the test threshold (CIN 1) were reviewed by a panel of two cytopathologists, blind to previous results, to establish the reference standard result (reference standard threshold for abnormality CIN2). Where histology was available, a secondary analysis was conducted with the reference standard based on the highest grade lesion (either cytology or histology). RESULTS: Among 21,747 Pap smears, 372 were discordant around the test threshold, requiring verification. In the primary analysis PAPNET detected four more true positives than conventional reading; difference in sensitivity 1.29% (95%CI -5.79 to 8.36%, P=.40). There were two extra false positives using PAPNET; difference in the false positive rate 0.0097% (95%CI -0.122 to 0.142%, P=.47). The results of the combined cytology and histology analysis were similar; difference in true positive rate 0.29% (95%CI -6.76 to 7.34%, P=.50) and difference in false positive rate 0.024% (95%CI -0.098 to 0.15%, P=.39). CONCLUSION: This is an efficient and valid study design where the objective is to examine the comparative accuracy of two tests. The design provides an efficient means of estimating the difference between true positive and false positive detection by the two tests, which often is sufficient information for policy decisions.

Adolescent↗

[Consideration of the newly standardized interventional reference point].

The interventional reference point is standardized by the International Electrotechnical Commission (IEC), and is adapted to adult cardiovascular studies. We examined the precision of the indicated incident dose at the interventional reference point. As a fundamental examination, we compared entrance phantom dose and incident dose at the interventional reference point. We also compared the entrance skin dose of patients with incident dose at the interventional reference point and evaluated the possibility of clinical application. Results showed that the incident dose at the interventional reference point indicated an underestimation of 0.77 times to an overestimation of 2.2 times when representing entrance surface dose. In clinical application, the incident dose at the interventional reference point calculated from the dose area product tended to overestimate by about 1.17 times the entrance skin dose measured by thermoluminescence dosimeter (TLD). Furthermore, the evaluation varied according to the angles of the C-arm of the x-ray system. A interventional reference point is a useful standard for simple, real-time dose measurement by the indirect method. It is important to understand the characteristics of the indicated incident dose at the interventional reference point in clinical use.

Coronary Angiography↗

Quality control limits for the standard anaerobic reference agar dilution susceptibility test procedure of the National Committee for Clinical Laboratory Standards.

Multilaboratory studies were performed to develop MIC quality control limits for the National Committee for Clinical Laboratory Standards reference agar dilution method for anaerobic susceptibility tests. Acceptable MICs were defined as those which include greater than 95% of all 100 MICs generated by the study. Most MIC control limits included either 2- or 3-dilution intervals rather than the more traditional 3-dilution intervals that are described as the mode +/- 1 doubling dilution.

Amoxicillin↗

Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.

BACKGROUND: In 2023, an estimated 1.3 million children (aged 0-14 years) became ill with tuberculosis, and 166,000 children (aged 0-15 years) died from the disease. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that detects Mycobacterium tuberculosis complex and rifampicin resistance. This is an update of a Cochrane review first published in 2020 and last updated in 2022. Parts of the current update informed the 2024 WHO updated guidance for the diagnosis of tuberculosis. OBJECTIVES: To assess the diagnostic accuracy of Xpert Ultra for detecting pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance in children (aged 0-9 years) with presumed tuberculosis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 6 October 2023. SELECTION CRITERIA: For study design, we included cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children aged birth to nine years. Regarding specimen type, we included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis); cerebrospinal fluid (tuberculous meningitis); and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). Reference standards for detection of tuberculosis were microbiological reference standard (MRS; including culture) or composite reference standard (CRS); for stool, we considered Xpert Ultra in sputum or gastric aspirates in addition to culture. Reference standards for detection of rifampicin resistance in sputum were phenotypic drug susceptibility testing or targeted or whole genome sequencing. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed methodological quality using the tailored QUADAS-2 tool, judging risk of bias separately for each target condition and sample type. We conducted separate meta-analyses for detection of pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance. We used a bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We assessed certainty of evidence using the GRADE approach. MAIN RESULTS: This update included 23 studies (including 9 new studies since the previous review) that evaluated detection of pulmonary tuberculosis (21 studies, 9223 children), tuberculous meningitis (3 studies, 215 children), lymph node tuberculosis (2 studies, 58 children), and rifampicin resistance (3 studies, 130 children). Seventeen studies (74%) took place in countries with a high tuberculosis burden. Overall, risk of bias and applicability concerns were low. Detection of pulmonary tuberculosis (microbiological reference standard) Sputum (11 studies) Xpert Ultra summary sensitivity was 75.3% (95% CI 68.9% to 80.8%; 345 children; moderate-certainty evidence), and specificity was 95.9% (95% CI 92.3% to 97.9%; 2645 children; high-certainty evidence). Gastric aspirate (12 studies) Xpert Ultra summary sensitivity was 69.6% (95% CI 60.3% to 77.6%; 167 children; moderate-certainty evidence), and specificity was 91.0% (95% CI 82.5% to 95.6%; 1792 children; moderate-certainty evidence). Stool (10 studies) Xpert Ultra summary sensitivity was 68.0% (95% CI 50.3% to 81.7%; 255 children; moderate-certainty evidence), and specificity was 98.2% (95% CI 96.3% to 99.1%; 2630 children; high-certainty evidence). Nasopharyngeal aspirate (6 studies) Xpert Ultra summary sensitivity was 46.2% (95% CI 34.9% to 57.9%; 94 children; moderate-certainty evidence), and specificity was 97.5% (95% CI 95.1% to 98.7%; 1259 children; high-certainty evidence). Xpert Ultra sensitivity was lower against CRS than against MRS for all specimen types, while the specificities were similar. Extrapulmonary tuberculosis Meta-analysis was not possible for lymph node tuberculosis and tuberculous meningitis due to low study numbers. Interpretation of results For a population of 1000 children, where 100 have pulmonary tuberculosis: In sputum: &#x2022; 112 would be Xpert Ultra positive, of whom 75 would have pulmonary tuberculosis (true positives) and 37 would not (false positives). &#x2022; 888 would be Xpert Ultra negative, of whom 863 would not have pulmonary tuberculosis (true negatives) and 25 would have pulmonary tuberculosis (false negatives). In gastric aspirate: &#x2022; 151 would be Xpert Ultra positive, of whom 70 would have pulmonary tuberculosis (true positives) and 81 would not (false positives). &#x2022; 849 would be Xpert Ultra negative, of whom 819 would not have pulmonary tuberculosis (true negatives) and 30 would have pulmonary tuberculosis (false negatives). In stool: &#x2022; 85 would be Xpert Ultra positive, of whom 68 would have pulmonary tuberculosis (true positives) and 17 would not (false positives). &#x2022; 915 would be Xpert Ultra negative, of whom 883 would not have pulmonary tuberculosis (true negatives) and 32 would have pulmonary tuberculosis (false negatives). In nasopharyngeal aspirate: &#x2022; 68 would be Xpert Ultra positive, of whom 46 would have pulmonary tuberculosis (true positives) and 22 would not (false positives). &#x2022; 932 would be Xpert Ultra negative, of whom 878 would not have pulmonary tuberculosis (true negatives), and 54 would have pulmonary tuberculosis (false negatives). Detection of rifampicin resistance Three studies with 76 children evaluated detection of rifampicin resistance (sputum only); two of these studies reported no cases and one reported rifampicin resistance in two children. AUTHORS' CONCLUSIONS: Xpert Ultra sensitivity was moderate in sputum, gastric aspirate, and stool specimens. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both MRS and CRS. We were unable to determine the accuracy of Xpert Ultra for detecting tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance due to a paucity of data. FUNDING: This update was funded through WHO. REGISTRATION: The protocol for this review was originally published through Cochrane in 2019. The protocol for this update was a generic protocol that consolidated previously published Cochrane protocols of Xpert Ultra for tuberculosis detection and can be accessed at https://osf.io/26wg7/. Protocol (2019) DOI: 10.1002/14651858.CD013359 Original review (2020) DOI: 10.1002/14651858.CD013359.pub2 Review update (2022) DOI: 10.1002/14651858.CD013359.pub3.

Adolescent↗

Qualitative assessment of liver for fatty infiltration on contrast-enhanced CT: is muscle a better standard of reference than spleen?

PURPOSE: Our goal was to determine whether spleen or muscle can be used as a qualitative standard of reference for diagnosing fatty infiltration of liver on contrast-enhanced CT. METHOD: Qualitative visual comparisons and quantitative region-of-interest measurements of liver, spleen, and muscle were made on scans of 96 patients who underwent dynamic CT before and after injection of intravenous contrast material. As the standard of reference, the portion of liver assessed was considered fatty if its attenuation measured less than spleen on noncontrast CT. RESULTS: In 16 (17%) scans, the portion of liver assessed was fatty on noncontrast CT. After contrast material administration, the attenuation of that portion of liver measured less than splenic attenuation in 93 (97%) of 96 cases (including all 16 fatty livers). Only four (25%) fatty livers, and no nonfatty livers, were visually judged to be less attenuating than muscle after contrast material; these four were the most fatty shown on noncontrast CT. Comparing hepatic and splenic attenuation on postcontrast CT resulted in a specificity of 30% and a positive predictive value of 20%; comparing hepatic and muscle attenuation on postcontrast CT yielded corresponding values of 100 and 100% but a sensitivity of 25%. CONCLUSION: For the visual assessment of fatty liver, spleen is not an accurate reference standard on contrast-enhanced CT. However, fatty liver can be diagnosed on contrast-enhanced CT if liver appears less attenuating than muscle-a situation that occurs only if fatty infiltration is pronounced.

Contrast Media↗

Determination of anti GAD65 autoantibodies with an ELISA before and after standardization with the new international reference serum.

The serum of a stiff-man syndrome patient was declared international GAD reference standard at the "1st GAD Antibody Workshop" held at the "12th International Immunology and Diabetes Workshop" in Orlando, Florida, USA 1993. A comparative study was performed with 123 diabetic and non-diabetic patients to evaluate whether standardization of this reference serum had changed the properties of a commercially available ELISA assay. All samples classified positive with the old test were confirmed with the new assay. Four additional samples with high "normal" values became positive with the new test. One of them was a control person having a family history of diabetes and genetic loci DR4/DR11. These findings might implicate a higher risk for the development of IDDM. The new standardization and adaptation of the ELISA seems to have influenced the sensitivity of the test positively.

Autoantibodies↗

Accurate nucleic acid concentrations by nuclear magnetic resonance.

Determination of the concentration of biochemical samples often yields values with uncertainties of 10-20% or more. This paper details a protocol for use with 500- to 600-MHz NMR spectrometers to measure approximately 1mM concentrations within +/-1-3% accuracy. With suitable precautions, all compounds have equal NMR "absorption coefficients" for protons. About 2mg of sample are needed for proteins and nucleic acids with MW=5000, although less accurate determinations could be made with smaller amounts. The technique utilizes standardized internal reference reagent compounds, cacodylic acid or 3-(trimethylsilyl)propionic-2,2,3,3-d(4) acid sodium salt. Spectra were signal-averaged using long interpulse delays so that integrals of nonexchangeable protons could be quantified relative to the reference standard. Accurate determinations require careful optimization of the homogeneity of the magnetic field and meticulous attention to sample preparation and spectral processing. The main source of error is usually the accuracy of micropipets. If sample preparation errors could be eliminated, the lower limit of accuracy with the current generation of NMR spectrometers is probably near 0.4%. However, this would require >99.5% sample purity. Methods are described to establish the concentration of the standards, and applications are illustrated with DNA mono- and oligonucleotides. Similar procedures should apply to proteins, polysaccharides, and other biomolecules, with about the same accuracy and precision.

Cacodylic Acid↗

An alternative to the hand searching gold standard: validating methodological search filters using relative recall.

BACKGROUND: Search filters or hedges play an important role in evidence-based medicine but their development depends on the availability of a "gold standard"--a reference standard against which to establish the performance of the filter. We demonstrate the feasibility of using relative recall of included studies from multiple systematic reviews to validate methodological search filters as an alternative to validation against a gold standard formed through hand searching. METHODS: We identified 105 Cochrane reviews that used the Highly Sensitive Search Strategy (HSSS), included randomized or quasi-randomized controlled trials, and reported their included studies. We measured the ability of two published and one novel variant of the HSSS to retrieve the MEDLINE-index studies included in these reviews. RESULTS: The systematic reviews were comprehensive in their searches. 72% of included primary studies were indexed in MEDLINE. Relative recall of the three strategies ranged from .98 to .91 across all reviews and more comprehensive strategies showed higher recall. CONCLUSION: An approach using relative recall instead of a hand searching gold standard proved feasible and produced recall figures that were congruent with previously published figures for the HSSS. This technique would permit validation of a methodological filter using a collection of approximately 100 studies of the chosen design drawn from the included studies of multiple systematic reviews that used comprehensive search strategies.

Abstracting and Indexing↗

Development of a wet-chemical method for the speciation of iron in atmospheric aerosols.

The ability to quantify the chemical and physical forms of transition metals in atmospheric particulate matter (PM) is essential in determining potential human health and ecological effects. A method for the speciation of iron in atmospheric PM has been adapted which involves extraction in a well-defined solution followed by oxidation state specific detection. The method was applied to a suite of environmental aerosols. Ambient atmospheric aerosols in an urban area of St. Louis (the St. Louis-Midwest Supersite) were collected on Teflon substrates and were leached in one of four different solutions: (1) >18.0 Momega water; (2) 140 microM NaCl solution; (3) pH = 7.4 NaHCO3 solution; and (4) pH = 4.3 acetate buffering system. Fe(ll) was determined directly using the Ferrozine method as adapted to liquid waveguide spectrophotometry using a 1 m path-length cell. Fe(lll) was determined similarly after reduction to Fe(ll). It was found that, at low ionic strength, pH exerted a major influence on Fe(ll) solubility with the greatest Fe(ll) concentration consistently found in the pH = 4.3 acetate buffer. Soluble Fe(lll) (as defined by a 0.2 microm filter) varied little with extractant, which implies that most of the Fe(lll) detected was colloidal. To characterize well-defined materials for future reference, NIST standard reference materials were also analyzed for soluble Fe(ll) and Fe(lll). For all SRMs tested, a maximum of 2.4% of the total iron (Urban Dust 1649a) was soluble in pH = 4.3 acetate buffer. For calibration curves covering the ranges of 0.5-20 microg/L Fe(ll), excellent linearity was observed in all leaching solutions with R2 values of > 0.999. Co-located filters were used to test the effect of storage time on iron oxidation state in the ambient particles as a function of time. On two samples, an average Fe(ll) decay rate of 0.89 and 0.57 ng Fe(ll) g(-1) PM day(-1) was determined from the slope of the regression, however this decrease was determined not to be significant over 3 months (95% confidence). As an application of this method to mobile source emissions, size-resolved PM10 samples were collected at the inlet and outlet of the Caldecott Motor Vehicle Tunnel in northern California. These samples indicate that the coarse fraction (PM10-PM2.5) contains almost 50% of the total soluble Fe(ll) in the aerosol.

Aerosols↗

Quantification in enzyme-linked immunosorbent assay of a C3 neoepitope expressed on activated human complement factor C3.

A sensitive double antibody enzyme-linked immunosorbent assay (ELISA) for quantification of C3 activation products in human plasma, synovial fluid, and cerebrospinal fluid is described. The monoclonal antibody MoAb bH6, which is specific for a C3 neoepitope expressed on C3b, iC3b, and C3c, was used as capture antibody. Detection antibody was a polyclonal rabbit anti-human C3c followed by development with a peroxidase-conjugated anti-rabbit Ig antiserum. The activity in normal human EDTA plasma was 1.5% of that in zymosan-activated serum (ZAS). The interassay and intra-assay coefficients of variation were 15% and 3%, respectively. The lower detection limit was 0.0005% of the ZAS standard. Reference range (1.1-2.1% of ZAS) was obtained by measuring EDTA plasma from 40 healthy blood donors. A positive correlation rs = +0.92; P less than 0.0002) was found between the present assay and an already established C3'g' activation ELISA, when samples from 16 patients were examined in both assays simultaneously. The present assay and an assay detecting the terminal complement complex showed virtually identical activation patterns in consecutively drawn samples from a patient undergoing extracorporal circulation.

Blood Preservation↗