UNASSIGNED: The accurate measurement of α-fetoprotein (AFP) is critical for clinical diagnosis. However, different AFP immunoassays may yield different results. Appropriate AFP reference materials (RMs) were selected and assigned accurate values for applications with external quality assessment (EQA) programs to standardize AFP measurements.
UNASSIGNED: Forty individual clinical samples and six different concentrations of candidate RMs (Can-RMs, L1-L6) were prepared by the Beijing Center for Clinical Laboratories. The Can-RMs were assigned target values by performing five immunoassays, using WHO International Standard 72/225 as a calibrator, and sent to 45 clinical laboratories in Beijing for AFP measurements. The commutability of all RMs was assessed based on CLSI and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approaches. Analytical performance was assessed for compliance based on accuracy (total error, TE), trueness (bias), and precision (CV).
UNASSIGNED: The Can-RMs were commutable for all immunoassays using the CLSI approach and for 6 of 10 assay combinations using the IFCC approach. RMs diluted in WHO RM 72/225 were commutable among all assays with the CLSI approach, except for serum matrix (Autolumo vs. Roche analyzer) and diluted water matrix (Abbott vs. Roche/Mindray analyzer), whereas some inconclusive and non-commutable results were found using the IFCC approach. The average pass rates based on the TE, bias, and CV were 91%, 81%, and 95%, respectively.
UNASSIGNED: The commutability of the RMs differed between both evaluation approaches. The Can-RMs exhibited good commutability with the CLSI approach, suggesting their suitability for use with that approach as commutable EQA materials with assigned values and for monitoring the performance of AFP measurements.

The growing use of botulinum neurotoxins (BoNTs) for medical and aesthetic purposes has led to the development and marketing of an increasing number of BoNT products. Given that BoNTs are biological medications, their characteristics are heavily influenced by their manufacturing methods, leading to unique products with distinct clinical characteristics. The manufacturing and formulation processes for each BoNT are proprietary, including the potency determination of reference standards and other features of the assays used to measure unit potency. As a result of these differences, units of BoNT products are not interchangeable or convertible using dose ratios. The intrinsic, product-level differences among BoNTs are compounded by differences in the injected tissues, which are innervated by different nerve fiber types (e.g., motor, sensory, and/or autonomic nerves) and require unique dosing and injection sites that are particularly evident when treating complex therapeutic and aesthetic conditions. It is also difficult to compare across studies due to inherent differences in patient populations and trial methods, necessitating attention to study details underlying each outcome reported. Ultimately, each BoNT possesses a unique clinical profile for which unit doses and injection paradigms must be determined individually for each indication. This practice will help minimize unexpected adverse events and maximize efficacy, duration, and patient satisfaction. With this approach, BoNT is poised to continue as a unique tool for achieving individual goals for an increasing number of medical and aesthetic indications.

Accurate assessments of symptoms and diagnoses are essential for health research and clinical practice but face many challenges. The absence of a single error-free measure is currently addressed by assessment methods involving experts reviewing several sources of information to achieve a more accurate or best-estimate assessment. Three bodies of work spanning medicine, psychiatry, and psychology propose similar assessment methods: The Expert Panel, the Best-Estimate Diagnosis, and the Longitudinal Expert All Data (LEAD). However, the quality of such best-estimate assessments is typically very difficult to evaluate due to poor reporting of the assessment methods and when it is reported, the reporting quality varies substantially. Here we tackle this gap by developing reporting guidelines for such studies, using a four-stage approach: 1) drafting reporting standards accompanied by rationales and empirical evidence, which were further developed with a patient organization for depression, 2) incorporating expert feedback through a two-round Delphi procedure, 3) refining the guideline based on an expert consensus meeting, and 4) testing the guideline by i) having two researchers test it and ii) using it to examine the extent previously published articles report the standards. The last step also demonstrates the need for the guideline: 18 to 58% (Mean = 33%) of the standards were not reported across fifteen randomly selected studies. The LEADING guideline comprises 20 reporting standards related to four groups: The Longitudinal design; the Appropriate data; the Evaluation - experts, materials, and procedures; and the Validity group. We hope that the LEADING guideline will be useful in assisting researchers in planning, reporting, and evaluating research aiming to achieve best-estimate assessments.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignant tumor involving adenomas that develop into malignant lesions. Carcinoembryonic antigen (CEA) is a non-specific serum biomarker upregulated in CRC. The concentration of CEA is modulated by tumor stage and grade, tumor site in the colon, ploidy status, and patient smoking status. This study aimed to evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.
OBJECTIVE: To evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.
METHODS: A systematic search was performed using four databases: MEDLINE, Cochrane Trials, EMBASE, and the Web of Science. The inclusion criteria were as follows: Adult patients aged ≥ 18 years who had completed CRC curative treatment and were followed up postoperatively; reporting the number of CRC recurrences as an outcome; and randomized, clinical, cohort, and case-control study designs. Studies that were not published in English and animal studies were excluded. The following data were extracted by three independent reviewers: Study design, index tests, follow-up, patient characteristics, and primary outcomes. All statistical analyses were performed using the RevMan 5.4.1.
RESULTS: A total of 3232 studies were identified, with 73 remaining following the elimination of duplicates. After screening on predetermined criteria, 12 studies were included in the final analysis. At a reference standard of 5 mg/L, CEA detected only approximately half of recurrent CRCs, with a pooled sensitivity of 59% (range, 33%-83%) and sensitivity of 89% (range, 58%-97%).
CONCLUSIONS: CEA is a significant marker for CRC diagnosis. However, it has insufficient sensitivity and specificity to be used as a single biomarker of early CRC recurrence, with an essential proportion of false negatives.

BACKGROUND: Current guidelines of the radioiodine uptake (RAIU) test allow the use of different equipment, isotopes, activity and region-of-interest (ROI). We evaluated presence and extent of these differences in clinical practice and evaluated the effect of some of these variations on RAIU outcomes. Also, gamma camera-specific reference standards were calculated and retrospectively compared with measurements obtained during clinical RAIU tests.
METHODS: First, questionnaires were sent to Dutch nuclear medicine departments requesting information about equipment usage, isotope, isotope formulation, activity and measurement techniques. Secondly, a neck phantom containing a range of activities in capsule or water-dissolved formulation was scanned. Counts were measured using automatic ROI, square box ROI or all counts in the image. Thirdly, clinical RAIU data were collected during 2015-2018 using three different gamma cameras. Reference standards for each scanner were calculated using regression analysis between reference activity and measured counts. Uptake measurements using this gamma camera-specific reference standard were compared with original measurements.
RESULTS: The survey demonstrated significant differences in isotope, isotope formulation, activity, use of neck phantoms, frequency and duration of reference measurements, distance to collimator, use of background measurements and ROI delineation. The phantom study demonstrated higher counts for the water-dissolved formulation than capsules using both automatic and square box ROI. Also, higher counts were found using a square box ROI than an automatic ROI. The retrospective study showed feasibility of RAIU calculations using camera-specific reference standards and good correlation with the original RAIU measurements.
CONCLUSIONS: This study demonstrated considerable technical variation in RAIU measurement in clinical practice. The phantom study demonstrated that these differences could result in differences in count measurements, potentially resulting in different dose calculations for radioactive iodine therapy. Retrospective data suggest that camera-specific reference standards may be used instead of individual reference measurements using separate activity sources, which may thus eliminate some sources of variation.

Most diagnostic studies exclude missing values and inconclusive results from the analysis or apply simple methods resulting in biased accuracy estimates. This may be due to the lack of availability or awareness of appropriate methods. This scoping review aimed to provide an overview of strategies to handle missing values and inconclusive results in the reference standard or index test in diagnostic accuracy studies. Conducting a systematic literature search in MEDLINE, Cochrane Library, and Web of Science, we could identify many articles proposing methods for addressing missing values in the reference standard. There are also several articles describing methods regarding missing values or inconclusive results in the index test. The latter encompass imputation, frequentist and Bayesian likelihood, model-based, and latent class methods. While methods for missing values in the reference standard are regularly applied in practice, this is not true for methods addressing missing values and inconclusive results in the index test. Our comprehensive overview and description of available methods may raise further awareness of these methods and will enhance their application. Future research is needed to compare the performance of these methods under different conditions to give valid and robust recommendations for their usage in various diagnostic accuracy research scenarios.

(1) Background: although digital infrared thermographic imaging (DITI) is used for diverse medical conditions of the upper limbs, no reference standards have been established. This study aims to establish reference standards by analyzing DITI results of the upper limbs. (2) Methods: we recruited 905 healthy Korean adults and conducted thermography on six regions (dorsal arm, ventral arm, lateral arm, medial arm, dorsal hand, and ventral hand region). We analyzed the data based on the proximity of regions of interest (ROIs), sex, and age. (3) Results: the average temperature (°C) and temperature discrepancy between the right and the left sides (ΔT) of each ROI varied significantly (p < 0.001), ranging from 28.45 ± 5.71 to 29.74 ± 5.14 and from 0.01 ± 0.49 to 0.15 ± 0.62, respectively. The temperature decreased towards the distal ROIs compared to proximal ROIs. The average temperatures of the same ROIs were significantly higher for men than women in all regions (p < 0.001). Across all regions, except the dorsal hand region, average temperatures tended to increase with age, particularly in individuals in their 30s and older (p < 0.001). (4) Conclusions: these data could be used as DITI reference standards to identify skin temperature abnormalities of the upper limbs. However, it is important to consider various confounding factors, and further research is required to validate the accuracy of our results under pathological conditions.

UNASSIGNED: The accuracy of diagnostic tests available in primary care to identify the disc, sacroiliac joint, and facet joint as the source of low back pain is uncertain.
UNASSIGNED: Systematic review of diagnostic tests available in primary care. MEDLINE, CINAHL, and EMBASE were searched between March 2006 and 25th January 2023. Pairs of reviewers independently screened all studies, extracted data, and assessed risk of bias using QUADAS-2. Pooling was performed for homogenous studies. Positive likelihood ratios (+LR) ≥2 and negative likelihood ratios (-LR) ≤0.5 were considered informative. This review is registered with PROSPERO (CRD42020169828).
UNASSIGNED: We included 62 studies: 35 investigated the disc, 14 the facet joint, 11 the sacroiliac joint, and 2 investigated all three structures in patients with persistent low back pain. For risk of bias, the domain \'reference standard\' scored worst, however approximately half the studies were of low risk of bias for every other domain. For the disc, pooling demonstrated MRI findings of disc degeneration and annular fissure resulted in informative +LRs: 2.53 (95% CI: 1.57-4.07) and 2.88 (95% CI: 2.02-4.10) and -LRs: 0.15 (95% CI: 0.09-0.24) and 0.24 (95% CI: 0.10-0.55) respectively. Pooled results for Modic type 1, Modic type 2, and HIZ on MRI, and centralisation phenomenon yielded informative +LRs: 10.00 (95% CI: 4.20-23.82), 8.03 (95% CI: 3.23-19.97), 3.10 (95% CI: 2.27-4.25), and 3.06 (95% CI: 1.44-6.50) respectively, but uninformative -LRs: 0.84 (95% CI: 0.74-0.96), 0.88 (95% CI: 0.80-0.96), 0.61 (95% CI: 0.48-0.77), and 0.66 (95% CI: 0.52-0.84) respectively. For the facet joint, pooling demonstrated facet joint uptake on SPECT resulted in informative +LRs: 2.80 (95% CI: 1.82-4.31) and -LRs: 0.44 (95% CI: 0.25-0.77). For the sacroiliac joint, a combination of pain provocation tests and absence of midline low back pain resulted in informative +LRs of 2.41 (95% CI: 1.89-3.07) and 2.44 (95% CI: 1.50-3.98) and -LRs of 0.35 (95% CI: 0.12-1.01) and 0.31 (95% CI: 0.21-0.47) respectively. Radionuclide imaging yielded an informative +LR 7.33 (95% CI: 1.42-37.80) but an uninformative -LR 0.74 (95% CI: 0.41-1.34).
UNASSIGNED: There are informative diagnostic tests for the disc, sacroiliac joint, and facet joint (only one test). The evidence suggests a diagnosis may be possible for some patients with low back pain, potentially guiding targeted and specific treatment approaches.
UNASSIGNED: There was no funding for this study.

BACKGROUND: Measuring the level of nicotine addiction among smokers is an integral part of enhancing smoking cessation as nicotine dependence is one of the barriers to smoking cessation. In this study, we compared the level of agreement between FTND and HSI in detecting high nicotine dependence among daily smokers.
METHODS: We collected data from participants of a public smoking cessation clinic in Selangor. A trained pharmacist conducted face-to-face interviews with 152 daily smokers using a structured validated questionnaire. Respondents were classified as having high nicotine dependence using both the HSI (score ≥4) and the FTND (score ≥6), and concordance between the two measures, kappa statistics and sensitivity, specificity of the HSI were then determined with the FTND classification as the reference standard.
RESULTS: The HSI had a substantial agreement with the FTND (Cohen\'s kappa=0.72) in measuring high levels of nicotine addiction, with good sensitivity (83.3%) and specificity (89.4%).
CONCLUSIONS: The findings suggest that the HSI can be used instead of the FTND in clinical-based investigations to screen for high nicotine dependence among daily smokers in the clinical setting.

UNASSIGNED: A reliable pediatric triage tool is essential for nurses working in pediatric emergency departments to quickly identify children requiring priority care (high-level emergencies) and those who can wait (low-level emergencies). In the absence of a gold standard in France, the objective of our study was to validate our 5-level pediatric triage tool -pediaTRI- against the reference tool: the Pediatric Early Warning Score (PEWS) System.
UNASSIGNED: We prospectively included 100,506 children who visited the Pediatric Emergency Department at Lenval Children\'s Hospital (Nice, France) in 2016 and 2017. The performance of pediaTRI to identify high-level emergencies (severity levels 1 and 2) was evaluated in comparison with a PEWS ≥ 4/9. Data from 2018-19 was used as an independent validation cohort.
UNASSIGNED: pediaTRI agreed with the PEWS score for 84,896 of the patients (84.5%): 15.0% (14.8-15.2) of the patients were over-triaged and 0.5% (0.5-0.6) under-triaged compared with the PEWS score. pediaTRI had a sensitivity of 76.4% (74.6-78.2), a specificity of 84.7% (84.4-84.9), and positive and negative likelihood ratios of 5.0 (4.8-5.1) and 0.3 (0.3-0.3), respectively, for the identification of high-level emergencies. However, the positive likelihood ratios were lower for patients presenting with a medical complaint [4.1 (4.0-4.2) v 10.4 (7.9-13.7 for trauma), and for younger children [1.2 (1.1-1.2) from 0 to 28 days, and 1.9 (1.8-2.0) from 28 days to 3 months].
UNASSIGNED: pediaTRI has a moderate to good validity to triage children in a Pediatric Emergency Department with a tendency to over-triage compared with the PEWS system. Its validity is lower for younger children and for children consulting for a medical complaint.