Prediction models for mortality in tuberculous meningitis

Tuberculous meningitis (TBM) is the most severe manifestation of tuberculosis, killing or disabling nearly half of all sufferers despite proper antituberculosis treatment. The British Medical Research Council (MRC) grade, which was first introduced in 1948, is the most widely used grading system for TBM severity. Despite its age and its lack of statistical derivation, improved and robust prediction models for poor outcomes in TBM based on large cohort studies and rigorous statistical methodology are still lacking. In addition, no studies have exploited repeated measurements to update the risk prediction. The purpose of my DPhil thesis is to develop prognostic models for mortality in adult TBM patients and to address statistical issues that may arise during the modelling process. Firstly, I present prognostic models for 9-month mortality based on patient characteristics at diagnosis. Separate models were constructed for patients with and without HIV coinfection. The models were developed and validated based on a large pooled database of 748 HIV-infected and 951 HIV-uninfected subjects. This is the largest database of prospectively characterized TBM patients to date. The final models showed good performance ... (continues)