Longitudinal-Survival Models for Case-Based Tuberculosis Progression

Abstract

Introduction: Tuberculosis (TB) disease continues to be responsible for a high global burden with an estimated 10 million people falling ill each year and an estimated 1.45 million deaths. Widely carried out analyses to utilize routine data coming from this disease, and well-established in literature, have paid attention to time-to-event with sputum smear results being considered only at baseline or even ignored. Also, logistic regression models have been used to demonstrate importance of sputum smear results in patient outcomes. A feature presented by this disease, however, is that each individual patient is usually followed over a period of time with sputum smear results being documented at different points of the treatment curve. This provides both repeated measures and survival times, which may require a joint modeling approach. This study aimed to investigate the association between sputum smear results and the risk of experiencing unfavorable outcome among TB patients and dynamically predict survival probabilities.Method: A joint model for longitudinal and time-to-event data was used to analyze longitudinally measured smear test results with time to experiencing unfavorable outcome for TB patients. A generalized linear mixed-effects model was specified for the longitudinal submodel and cox proportional hazards model for the time-to-event submodel with baseline hazard approximated using penalized B-splines. The two submodels were then assumed to be related via the current value association structure. Bayesian approach was used to approximate parameter estimates using Markov Chain Monte Carlo (MCMC) algorithm. The obtained joint model was used to predict the subject's future risk of survival based on sputum smear results trajectories. Data were sourced from routinely collected TB data stored at National TB Program database.Results: The average baseline age was 35 (SD: 15). Female TB patients constituted 36.42%. Patients with previous history of TB treatment constituted 6.38% (event: 15.25%; no event: 5.29%). TB/HIV co-infection was at 31.23% (event: 47.87%; no event: 29.20%). The association parameter 1.03 (CI[1.03,1.04]) was found to be positive and significantly different from zero, interpreted as follows: The estimate of the association parameter α = 1.033 denoted the log hazard ratio for a unit increase in the log odds of having smear positive results. HIV status (negative) 0.47 (CI [0.46,49]) and history of TB treatment (previously treated) (2.52 CI [2.41,2.63]), sex (female) (0.82 CI [0.78,0.84]), and body mass index (BMI) categories (severe malnutrition being reference) were shown to be statistically significant.Conclusion: Sputum smear result is important in estimating the risk to unfavorable outcome among TB patients. Men, previously treated, TB/HIV co-infected and severely malnourished TB patients are at higher risk of unfavorable outcomes.

Gendered gaps to tuberculosis prevention and care in Kenya: a political economy analysis study

“…Men account for roughly twice the TB burden compared to females while displaying low health-seeking behaviors with the highest TB treatment interruptions 32–34. Further, men with a TB infection face unfavorable outcomes of TB deaths and treatment failure, possibly due to non-adherence to treatment 32 34.…”

“… 46 47 Food has a long-term impact on health since it can lead to malnutrition and mental health. 46 47 TB patients with severe malnutrition have higher risks of failure rates or deaths 34 and it is a vital driver of the TB epidemic in Kenya. 48 Therefore, a substantial contributor to TB treatment access in Kenya is food insecurity.…”

“…Gender concerns related to TB care Gender disparity in TB care Men account for roughly twice the TB burden compared to females while displaying low health-seeking behaviors with the highest TB treatment interruptions. [32][33][34] Further, men with a TB infection face unfavorable outcomes of TB deaths and treatment failure, possibly due to non-adherence to treatment. 32 34 The qualitative inquiry reported on the concerns around limited, targeted interventions towards men, which in turn do not meet the needs of men, thereby influencing their overall access to TB services.…”

Gendered Gaps to Tb Prevention and Care in Kenya: A Political Economy Analysis Study

“…Men account for roughly twice the TB burden while displaying extremely low health-seeking behaviors with the highest TB treatment interruptions [26][27][28]. Further, men with a TB infection face unfavorable outcomes of TB deaths and treatment failure possibly due to nonadherence to treatment [26,28].…”

“…Men account for roughly twice the TB burden while displaying extremely low health-seeking behaviors with the highest TB treatment interruptions [26][27][28]. Further, men with a TB infection face unfavorable outcomes of TB deaths and treatment failure possibly due to nonadherence to treatment [26,28]. The qualitative inquiry reported on the concerns around limited targeted interventions towards men which in turn do not meet the needs of men, thereby influencing their overall access to TB services.…”