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Record W4403072084 · doi:10.1093/clinchem/hvae106.645

B-288 Turning False Positive Screening into True Positive Results

2024· article· en· W4403072084 on OpenAlexaff
Michael J. Bennett, M Biscope, David W. Kinniburgh

Bibliographic record

VenueClinical Chemistry · 2024
Typearticle
Languageen
FieldMathematics
TopicStatistical Methods in Clinical Trials
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsMedicine

Abstract

fetched live from OpenAlex

Abstract Background After conducting a retrospective analysis of our laboratory data, we identified a notable disparity between immunoassay screen and mass spectrometry confirmation results for benzodiazepines. This prompted an investigation into whether the prevalence of false negative benzodiazepine results stemmed from the inadequacy of the immunoassay or the absence of new psychoactive substances (NPS) in our mass spectrometry confirmation assay. To determine the latter, we added four NPS benzodiazepines and their metabolites to our confirmation panel. Monitoring drug seizure records as well as reports detailing emerging substances were helpful in guiding which NPS to add. The objective of this study was to determine whether the addition of NPS benzodiazepines to our confirmation panel would increase the agreement between screen and confirmation benzodiazepine results in an opioid dependent population. Methods Urine samples that screened positive for benzodiazepines with immunoassay and confirmed negative by mass spectrometry over a 6-month timeframe were selected for analysis. Four NPS were added to our confirmation panel which included bromazolam, flubromazepam, flubromazolam, flualprazolam as well as their metabolites alpha-OH bromazolam, 3-OH flubromazepam, alpha-OH flubromazolam and alpha-OH flualprazolam. Immunoassay data was obtained using an Olympus AU480 instrument, while mass spectrometry results were acquired through an internally developed dynamic multiple reaction monitoring method on an Agilent 6470 triple quadrupole instrument. Results In the analysis of 476 urine samples using a cut-off value of 50 ng/mL, 55.3% of the samples tested positive for bromazolam, 83.0% for alpha-OH bromazolam, 0% for flubromazepam, 41.8% for 3-OH flubromazepam, 0% for flubromazolam, 0.2% for alpha-OH flubromazolam, 1.3% for flualprazolam and 6.7% for alpha-OH flualprazolam. Using a cut-off value of 10 ng/mL which represents the limit of quantitation, 75.4% tested positive for bromazolam, 89.9% for alpha-OH bromazolam, 2.1% for flubromazepam, 60.5% for 3-OH flubromazepam, 0% for flubromazolam, 0.2% for alpha-OH flubromazolam, 3.4% for flualprazolam and 9.7% for alpha-OH flualprazolam. In total, among the 476 samples that initially screened positive but confirmed negative, 95.8% confirmed positive for benzodiazepines with the inclusion of the four NPS benzodiazepines and their metabolites into our confirmation panel. Of the samples that tested positive for NPS benzodiazepines, 77.1% were also positive for fentanyl, and 95.2% were positive for norfentanyl. Conclusions The incorporation of NPS benzodiazepines into our confirmation panel significantly enhanced the concordance between immunoassay screen and mass spectrometry confirmation results. The discrepancies we observed with benzodiazepines were not predominantly linked to immunoassay challenges. Rather, they were due to the presence of NPS benzodiazepines commonly found in benzo-dope preparations, not accounted for in our mass spectrometry confirmation panel. The inclusion of NPS benzodiazepines into our confirmation panel has improved the reporting of useful diagnostic information which can be used to support harm reduction efforts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.008
metaresearch head score (Gemma)0.278
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.853
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0080.278
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.452
GPT teacher head0.595
Teacher spread0.143 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designTheoretical or conceptual
Domainnot available
GenreMethods

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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