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Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia

2022· preprint· en· W4304698211 on OpenAlexaff
Vilas Navapurkar, Josefin Bartholdson Scott, Mailis Maes, Thomas P Hellyer, Ellen E. Higginson, Joana Pereira-Dias, Surendra Parmar, Emma Heasman-Hunt, Petra Polgarova, Joanne Brown, Lissamma Titti, William Smith, Jonathan Scott, Anthony Rostron, Matthew Routledge, David Sapsford, M. Estée Török, Ronan McMullan, David Enoch, Vanessa Wong, Martin D. Curran, Nicholas M. Brown, A. John Simpson, Jürgen Herre, Gordon Dougan, Andrew Conway Morris

Bibliographic record

VenueWellcome Open Research · 2022
Typepreprint
Languageen
FieldMedicine
TopicPneumonia and Respiratory Infections
Canadian institutionsInstitute of Infection and Immunity
FundersNIHR Cambridge Biomedical Research CentreAcademy of Medical SciencesMedical Research CouncilNational Institute for Health and Care ResearchWellcome Trust
KeywordsPneumoniaMedicineCohortInternal medicine

Abstract

fetched live from OpenAlex

<ns4:p> <ns4:bold>Background:</ns4:bold> The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was <ns4:bold/> to <ns4:bold/> establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. </ns4:p> <ns4:p/> <ns4:p> <ns4:bold>Methods:</ns4:bold> The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. </ns4:p> <ns4:p>Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group.</ns4:p> <ns4:p> <ns4:bold>Results:</ns4:bold> 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). </ns4:p> <ns4:p> <ns4:bold>Conclusions:</ns4:bold> Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing. </ns4:p>

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)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.478
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.003
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.132
GPT teacher head0.439
Teacher spread0.308 · 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 designObservational
Domainnot available
GenreEmpirical

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

Citations7
Published2022
Admission routes1
Has abstractyes

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