Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis

Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis. Dhana, A., Gupta, R. K, Hamada, Y., Kengne, A. P, Kerkhoff, A. D, Yoon, C., Cattamanchi, A., Reeve, B. W P, Theron, G., Ndlangalavu, G., Wood, R., Drain, P. K, Calderwood, C. J, Noursadeghi, M., Boyles, T., Meintjes, G. A, Maartens, G., & Barr, D. A European Respiratory Review, 32(168):230021, European Respiratory Society, jun, 2023.

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Background: The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg˙L−1 cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs). Methods: Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal–external cross-validation to evaluate performance. Results: We pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg˙L−1 cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91% of tuberculosis cases and require confirmatory testing for 78% of participants. CRP (5 mg˙L−1 cut-off), the extended CPM (4.2% threshold) and the CRP-only CPM (3.6% threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36%, respectively. Conclusions: CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg˙L−1 cut-off or in a CPM depends on available resources. C-reactive protein at a 5 mg cut-off and two newly developed clinical prediction models from this study show clinical utility for TB screening among outpatient PLHIV, while the WHO-recommended four-symptom screen showed suboptimal clinical utility \textlesshttps://bit.ly/3yShJ3m\textgreater

@article{Dhana2023,
abstract = {Background: The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg{\textperiodcentered}L−1 cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs). Methods: Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal–external cross-validation to evaluate performance. Results: We pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg{\textperiodcentered}L−1 cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91{\%} of tuberculosis cases and require confirmatory testing for 78{\%} of participants. CRP (5 mg{\textperiodcentered}L−1 cut-off), the extended CPM (4.2{\%} threshold) and the CRP-only CPM (3.6{\%} threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36{\%}, respectively. Conclusions: CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg{\textperiodcentered}L−1 cut-off or in a CPM depends on available resources. C-reactive protein at a 5 mg cut-off and two newly developed clinical prediction models from this study show clinical utility for TB screening among outpatient PLHIV, while the WHO-recommended four-symptom screen showed suboptimal clinical utility {\textless}https://bit.ly/3yShJ3m{\textgreater}},
author = {Dhana, Ashar and Gupta, Rishi K and Hamada, Yohhei and Kengne, Andre P and Kerkhoff, Andrew D and Yoon, Christina and Cattamanchi, Adithya and Reeve, Byron W P and Theron, Grant and Ndlangalavu, Gcobisa and Wood, Robin and Drain, Paul K and Calderwood, Claire J and Noursadeghi, Mahdad and Boyles, Tom and Meintjes, Graeme A and Maartens, Gary and Barr, David A},
doi = {10.1183/16000617.0021-2023},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Dhana et al. - 2023 - Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction mo.pdf:pdf},
issn = {0905-9180},
journal = {European Respiratory Review},
keywords = {OA,OA{\_}PMC,fund{\_}ack,review},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,review},
month = {jun},
number = {168},
pages = {230021},
pmid = {37286216},
publisher = {European Respiratory Society},
title = {{Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis}},
url = {https://err.ersjournals.com/content/32/168/230021 https://err.ersjournals.com/content/32/168/230021.abstract},
volume = {32},
year = {2023}
}

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We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs). Methods: Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal–external cross-validation to evaluate performance. Results: We pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg˙L−1 cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91% of tuberculosis cases and require confirmatory testing for 78% of participants. CRP (5 mg˙L−1 cut-off), the extended CPM (4.2% threshold) and the CRP-only CPM (3.6% threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36%, respectively. Conclusions: CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg˙L−1 cut-off or in a CPM depends on available resources. 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