Journal of Applied Laboratory Medicine最新文献

Background: To evaluate diagnostic tests for low prevalence conditions, classification accuracy metrics such as sensitivity, specificity, and positive likelihood ratio (PLR) and negative likelihood ratio (NLR) are advantageous because they are prevalence-independent and thus estimable in studies enriched for the condition. However, classification accuracy goals are often chosen without a clear understanding of whether they are clinically meaningful. Pennello (2021) proposed a risk stratification framework for determining classification accuracy goals. A software application is needed to determine the goals and provide data analysis.

Methods: We introduce DxGoals, a freely available, R-Shiny software application for determining, visualizing, and analyzing classification accuracy goals for diagnostic tests. Given prevalence p for the target condition and specification that a test's positive and negative predictive values PPVand NPV=1-cNPV should satisfy PPV>PPV* and cNPV

Results: We illustrate DxGoals on tests for penicillin allergy, ovarian cancer, and cervical cancer. The inputs cNPV*,p, and PPV* were informed by clinical management guidelines.

Conclusions: DxGoals facilitates determination, visualization, and analysis of clinically meaningful standalone and comparative classification accuracy goals. It is a potentially useful tool for diagnostic test evaluation.

Background: People experiencing homelessness (PEH) are underrepresented in public health and clinical research. Study methods that can improve participation by this group are needed.

Methods: In late 2022, the Centers for Disease Control and Prevention conducted an mpox serological survey using venipuncture among PEH in San Francisco, California. Blood collection by a minimally invasive device was offered if venipuncture was not possible or preferred. Participants who had a successful blood draw using the device were asked about device acceptability.

Results: Of the 209 successful blood collections, 137 (66%) were among participants who underwent venipuncture and 72 (34%) were among participants who used the device. Use of the device increased overall blood collection participation by 53%. Participants reported high acceptability and preference for the device over venipuncture.

Conclusions: Minimally invasive blood collection devices may increase participation and representation of PEH in serosurveys.

Background: Cardiac troponin T (cTnT) is key in diagnosing myocardial infarction (MI) but is also elevated in end-stage renal disease (ESRD) patients. Specific larger cTnT proteoforms were identified for the acute phase of MI, while in serum of ESRD patients solely small cTnT fragments were found. However, others allocated this to a pre-analytic effect due to abundant thrombin generation in serum. Therefore, we investigated the effect of various anticoagulation methods on cTnT composition and concentration and compared the cTnT composition of MI and ESRD patients.

Methods: The agreement of cTnT concentrations between simultaneously collected serum, lithium-heparin (LH) plasma, and ethylenediaminetetraacetic acid (EDTA) plasma was studied using the high-sensitivity (hs-)cTnT immunoassay. cTnT proteoform composition was investigated in a standardized time-dependent manner through spike experiments and in simultaneously collected blood matrixes of MI and ESRD patients.

Results: Excellent hs-cTnT concentration agreements were observed across all blood matrixes (slopes > 0.98; 95% CI, 0.96-1.04). Time-dependent degradation (40 kDa intact:29 kDa fragment:15 to 18 kDa fragments) was found in LH plasma and EDTA plasma, and serum in ratios (%) of 90:10:0, 0:5:95, and 0:0:100, respectively (48 h after blood collection). Moreover, gel filtration chromatography (GFC) profiles illustrated mainly larger cTnT proteoforms in MI patients, while in ESRD patients mainly 15 to 18 kDa fragments were found for all matrices.

Conclusions: The extent of cTnT degradation in vitro is dependent on the (anti)coagulation method, without impacting hs-cTnT concentrations. Furthermore, mainly larger cTnT proteoforms were present in MI patients, while in ESRD patients mainly small 15 to 18 kDa cTnT fragments were found. These insights are essential when developing a novel hs-cTnT assay targeting larger cTnT proteoforms.