Prognostic models for 9-month mortality in tuberculous meningitis

Le Thi Phuong Thao, A. Dorothee Heemskerk, Ronald B. Geskus, Nguyen Thi Hoang Mai, Dang Thi Minh Ha, Tran Thi Hong Chau, Nguyen Hoan Phu, Nguyen Van Vinh Chau, Maxine Caws, Nguyen Huu Lan, Do Dang Anh Thu, Nguyen Thuy Thuong Thuong, Jeremy Day, Jeremy J. Farrar, M. Estee Torok, Nguyen Duc Bang, Guy E. Thwaites, Marcel Wolbers

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Abstract

Background. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. Methods. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Webbased app (https://thaole.shinyapps.io/tbmapp/). Results. 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIVinfected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. Conclusions. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.

Original languageEnglish
Pages (from-to)523-532
Number of pages10
JournalClinical Infectious Diseases
Volume66
Issue number4
DOIs
Publication statusPublished - 15 Feb 2018
Externally publishedYes

Keywords

  • HIV
  • Mortality
  • Prognostic models
  • Tuberculous meningitis

Cite this

Thao, L. T. P., Heemskerk, A. D., Geskus, R. B., Mai, N. T. H., Ha, D. T. M., Chau, T. T. H., ... Wolbers, M. (2018). Prognostic models for 9-month mortality in tuberculous meningitis. Clinical Infectious Diseases, 66(4), 523-532. https://doi.org/10.1093/cid/cix849
Thao, Le Thi Phuong ; Heemskerk, A. Dorothee ; Geskus, Ronald B. ; Mai, Nguyen Thi Hoang ; Ha, Dang Thi Minh ; Chau, Tran Thi Hong ; Phu, Nguyen Hoan ; Chau, Nguyen Van Vinh ; Caws, Maxine ; Lan, Nguyen Huu ; Thu, Do Dang Anh ; Thuong, Nguyen Thuy Thuong ; Day, Jeremy ; Farrar, Jeremy J. ; Torok, M. Estee ; Bang, Nguyen Duc ; Thwaites, Guy E. ; Wolbers, Marcel. / Prognostic models for 9-month mortality in tuberculous meningitis. In: Clinical Infectious Diseases. 2018 ; Vol. 66, No. 4. pp. 523-532.
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abstract = "Background. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. Methods. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Webbased app (https://thaole.shinyapps.io/tbmapp/). Results. 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0{\%}) and 384 of 748 (51.3{\%}) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIVinfected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. Conclusions. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.",
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Thao, LTP, Heemskerk, AD, Geskus, RB, Mai, NTH, Ha, DTM, Chau, TTH, Phu, NH, Chau, NVV, Caws, M, Lan, NH, Thu, DDA, Thuong, NTT, Day, J, Farrar, JJ, Torok, ME, Bang, ND, Thwaites, GE & Wolbers, M 2018, 'Prognostic models for 9-month mortality in tuberculous meningitis', Clinical Infectious Diseases, vol. 66, no. 4, pp. 523-532. https://doi.org/10.1093/cid/cix849

Prognostic models for 9-month mortality in tuberculous meningitis. / Thao, Le Thi Phuong; Heemskerk, A. Dorothee; Geskus, Ronald B.; Mai, Nguyen Thi Hoang; Ha, Dang Thi Minh; Chau, Tran Thi Hong; Phu, Nguyen Hoan; Chau, Nguyen Van Vinh; Caws, Maxine; Lan, Nguyen Huu; Thu, Do Dang Anh; Thuong, Nguyen Thuy Thuong; Day, Jeremy; Farrar, Jeremy J.; Torok, M. Estee; Bang, Nguyen Duc; Thwaites, Guy E.; Wolbers, Marcel.

In: Clinical Infectious Diseases, Vol. 66, No. 4, 15.02.2018, p. 523-532.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Prognostic models for 9-month mortality in tuberculous meningitis

AU - Thao, Le Thi Phuong

AU - Heemskerk, A. Dorothee

AU - Geskus, Ronald B.

AU - Mai, Nguyen Thi Hoang

AU - Ha, Dang Thi Minh

AU - Chau, Tran Thi Hong

AU - Phu, Nguyen Hoan

AU - Chau, Nguyen Van Vinh

AU - Caws, Maxine

AU - Lan, Nguyen Huu

AU - Thu, Do Dang Anh

AU - Thuong, Nguyen Thuy Thuong

AU - Day, Jeremy

AU - Farrar, Jeremy J.

AU - Torok, M. Estee

AU - Bang, Nguyen Duc

AU - Thwaites, Guy E.

AU - Wolbers, Marcel

PY - 2018/2/15

Y1 - 2018/2/15

N2 - Background. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. Methods. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Webbased app (https://thaole.shinyapps.io/tbmapp/). Results. 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIVinfected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. Conclusions. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.

AB - Background. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. Methods. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Webbased app (https://thaole.shinyapps.io/tbmapp/). Results. 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIVinfected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. Conclusions. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.

KW - HIV

KW - Mortality

KW - Prognostic models

KW - Tuberculous meningitis

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U2 - 10.1093/cid/cix849

DO - 10.1093/cid/cix849

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JO - Clinical Infectious Diseases

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SN - 1058-4838

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Thao LTP, Heemskerk AD, Geskus RB, Mai NTH, Ha DTM, Chau TTH et al. Prognostic models for 9-month mortality in tuberculous meningitis. Clinical Infectious Diseases. 2018 Feb 15;66(4):523-532. https://doi.org/10.1093/cid/cix849