TY - JOUR
T1 - Therapy duration and long-term outcomes in extra-pulmonary tuberculosis
AU - Pusch, Tobias
AU - Pasipanodya, Jotam G.
AU - Hall, Ronald G.
AU - Gumbo, Tawanda
N1 - Funding Information:
TP, JGP, RGH-no conflict of interest. TG has received research grants from Merck for work on antifungal agents; TG also founded and owns Jacaranda Biomed, Inc.
Funding Information:
This study was funded by National Institutes of Health (NIH) Grant R01AI079497 and NIH New Innovator Award DP2 OD001886-01. The sponsors were not involved in the design and conduct of the study, data collection, management, analysis, and interpretation of data as well as preparation, or review, or approval of the manuscript.
PY - 2014/3/1
Y1 - 2014/3/1
N2 - Background: Tuberculosis is classified as either pulmonary or extra-pulmonary (EPTB). While much focus has been paid to pulmonary tuberculosis, EPTB has received scant attention. Moreover, EPTB is viewed as one wastebasket diagnosis, as " the other" which is not pulmonary.Methods: This is a retrospective cohort study of all patients treated for EPTB in the state of Texas between January 2000 and December 2005, who had no pulmonary disease. Clinical and epidemiological factors were abstracted from electronic records of the Report of Verified Case of Tuberculosis. The long-term outcome, which is death by December 2011, was established using the Social Security Administration Death Master File database. Survival in EPTB patients was compared to those with latent tuberculosis, as well as between different types of EPTB, using Cox proportional hazard models. A hybrid of the machine learning method of classification and regression tree analyses and standard regression models was used to identify high-order interactions and clinical factors predictive of long-term all-cause mortality.Results: Four hundred and thirty eight patients met study criteria; the median study follow-up period for the cohort was 7.8 (inter-quartile range 6.0-10.1) years. The overall all-cause mortality rate was 0.025 (95% confidence interval [CI]: 0.021-0.030) per 100 person-year of follow-up. The significant predictors of poor long-term outcome were age (hazard ratio [HR] for each year of age-at-diagnosis was 1.05 [CI: 1.04-1.06], treatment duration, type of EPTB and HIV-infection (HR = 2.16; CI: 1.22, 3.83). Mortality in genitourinary tuberculosis was no different from latent tuberculosis, while meningitis had the poorest long-term outcome of 46.2%. Compared to meningitis the HR for death was 0.50 (CI: 0.27-0.91) for lymphatic disease, 0.42 (CI: 0.21-0.81) for bone/joint disease, and 0.59 (CI: 0.27-1.31) for peritonitis. The relationship between mortality and therapy duration for each type of EPTB was a unique " V" shaped curve, with the lowest mortality observed at different therapy durations for each, beyond which mortality increased.Conclusions: EPTB is comprised of several different diseases with different outcomes and durations of therapy. The " V" shaped relationship between therapy duration and outcome leads to the hypothesis that longer duration of therapy may lead to higher patient mortality.
AB - Background: Tuberculosis is classified as either pulmonary or extra-pulmonary (EPTB). While much focus has been paid to pulmonary tuberculosis, EPTB has received scant attention. Moreover, EPTB is viewed as one wastebasket diagnosis, as " the other" which is not pulmonary.Methods: This is a retrospective cohort study of all patients treated for EPTB in the state of Texas between January 2000 and December 2005, who had no pulmonary disease. Clinical and epidemiological factors were abstracted from electronic records of the Report of Verified Case of Tuberculosis. The long-term outcome, which is death by December 2011, was established using the Social Security Administration Death Master File database. Survival in EPTB patients was compared to those with latent tuberculosis, as well as between different types of EPTB, using Cox proportional hazard models. A hybrid of the machine learning method of classification and regression tree analyses and standard regression models was used to identify high-order interactions and clinical factors predictive of long-term all-cause mortality.Results: Four hundred and thirty eight patients met study criteria; the median study follow-up period for the cohort was 7.8 (inter-quartile range 6.0-10.1) years. The overall all-cause mortality rate was 0.025 (95% confidence interval [CI]: 0.021-0.030) per 100 person-year of follow-up. The significant predictors of poor long-term outcome were age (hazard ratio [HR] for each year of age-at-diagnosis was 1.05 [CI: 1.04-1.06], treatment duration, type of EPTB and HIV-infection (HR = 2.16; CI: 1.22, 3.83). Mortality in genitourinary tuberculosis was no different from latent tuberculosis, while meningitis had the poorest long-term outcome of 46.2%. Compared to meningitis the HR for death was 0.50 (CI: 0.27-0.91) for lymphatic disease, 0.42 (CI: 0.21-0.81) for bone/joint disease, and 0.59 (CI: 0.27-1.31) for peritonitis. The relationship between mortality and therapy duration for each type of EPTB was a unique " V" shaped curve, with the lowest mortality observed at different therapy durations for each, beyond which mortality increased.Conclusions: EPTB is comprised of several different diseases with different outcomes and durations of therapy. The " V" shaped relationship between therapy duration and outcome leads to the hypothesis that longer duration of therapy may lead to higher patient mortality.
KW - Extra-pulmonary tuberculosis
KW - Meningitis
KW - Peritoneal
KW - Survival
KW - Therapy duration
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U2 - 10.1186/1471-2334-14-115
DO - 10.1186/1471-2334-14-115
M3 - Article
C2 - 24580808
AN - SCOPUS:84895423216
SN - 1471-2334
VL - 14
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
IS - 1
M1 - 115
ER -