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 language | English |
|---|---|
| Pages (from-to) | 523-532 |
| Number of pages | 10 |
| Journal | Clinical Infectious Diseases |
| Volume | 66 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 15 Feb 2018 |
| Externally published | Yes |
Keywords
- HIV
- Mortality
- Prognostic models
- Tuberculous meningitis
Cite this
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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 journal › Article › Research › peer-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
UR - http://www.scopus.com/inward/record.url?scp=85042044435&partnerID=8YFLogxK
U2 - 10.1093/cid/cix849
DO - 10.1093/cid/cix849
M3 - Article
VL - 66
SP - 523
EP - 532
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 4
ER -