Application of Cox Proportional Hazards Model in Case of Tuberculosis Patients in Selected Addis Ababa Health Centres, Ethiopia

Tolosie, Kabtamu; Sharma, Mahendra

doi:10.1155/2014/536976

Cited by 24 publications

(32 citation statements)

References 12 publications

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“…Early mortality reflects advanced disease and could be attributed to delayed treatment and late diagnosis [ 26 ]. In our study, 67.9% of the deaths occurred during the two month (intensive phase) TB treatment period.…”

Section: Discussionmentioning

confidence: 99%

Total Delay Is Associated with Unfavorable Treatment Outcome among Pulmonary Tuberculosis Patients in West Gojjam Zone, Northwest Ethiopia: A Prospective Cohort Study

2016

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Backgrounddelay in diagnosis and treatment of tuberculosis (TB) may worsen the disease, increase mortality and enhance transmission in the community. This study aimed at assessing the association between total delay and unfavorable treatment outcome among newly diagnosed pulmonary TB (PTB) patients.MethodsA prospective cohort study was conducted in West Gojjam Zone, Amhara Region of Ethiopia from October 2013 to May 2015. Newly diagnosed PTB patients who were ≥15 years of age were consecutively enrolled in the study from 30 randomly selected public health facilities. Total delay (the time period from onset of TB symptoms to first start of anti-TB treatment) was measured. Median total delay was calculated. Mixed effect logistics regression was used to analyze factors associated with unfavorable treatment outcome.ResultsSeven hundred six patients were enrolled in the study. The median total delay was 60 days. Patients with total delay of > 60 days were more likely to have unfavorable TB treatment outcome than patients with total delay of ≤ 60 days (adjusted odds ratio [AOR], 2.33; 95% confidence interval [CI], 1.04–5.26). Human immunodeficiency virus (HIV) positive TB patients were 8.46 times more likely to experience unfavorable treatment outcome than HIV negative TB patients (AOR, 8.46; 95% CI, 3.14–22.79).ConclusionsLong total delay and TB/HIV coinfection were associated with unfavorable treatment outcome. Targeted interventions that can reduce delay in diagnosis and treatment of TB, and early comprehensive management of TB/HIV coinfection are needed to reduce increased risk of unfavorable treatment outcome.

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Section: Discussionmentioning

confidence: 99%

Total Delay Is Associated with Unfavorable Treatment Outcome among Pulmonary Tuberculosis Patients in West Gojjam Zone, Northwest Ethiopia: A Prospective Cohort Study

2016

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“…This model also considers the effect of each factor in delaying the onset of disease rather than just modelling through a binary ‘protected’ or ‘diseased’ outcome. Similar regression modelling has been described to predict outcomes for tuberculosis patients after treatment, effect of hospital-acquired Clostridium difficile on hospital stay and survival of Staphylococcus aureus in milk (73-75). The model assumes that eventually all mice will succumb to disease and due to the constraints in our data, it cannot determine threshold levels of cytokines that will predict disease outcomes.…”

Section: Discussionmentioning

confidence: 97%

Vaccine-specific immune responses againstMycobacterium ulceransinfection in a low-dose murine challenge model

Mangas

Buultjens

Porter

et al. 2019

Preprint

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25The neglected tropical disease Buruli ulcer (BU) is an infection of subcutaneous tissue with 26 Mycobacterium ulcerans. There is no effective BU vaccine. Here, we assessed an experimental 27 prime-boost vaccine in a low-dose murine tail infection model. We used the enoyl-reductase (ER) 28 domain of the M. ulcerans mycolactone polyketide synthases electrostatically coupled with a 29 previously described TLR-2 agonist-based lipopeptide adjuvant, R4Pam2Cys. Mice were vaccinated 30 and then challenged via tail inoculation with 14-20 colony forming units (CFU) of an engineered 31 bioluminescent strain of M. ulcerans. Mice receiving either the experimental ER vaccine or 32Mycobacterium bovis Bacille Calmette-Guérin (BCG) were equally well protected, with both groups 33 faring significantly better than non-vaccinated animals (p<0.05). A suite of 29 immune parameters 34 were assessed in the mice at the end of the experimental period. Multivariate statistical approaches 35were then used to interrogate the immune response data to develop disease-prognostic models. 36High levels of IL-2 and low IFN-! produced in the spleen best predicted control of infection across 37 all vaccine groups. Univariate logistic regression then revealed vaccine-specific profiles of 38 protection. High titres of ER-specific IgG serum antibodies together with IL-2 and IL-4 in the draining 39 lymph node (DLN) were associated with protection induced by the experimental ER vaccine. In 40 contrast, high titres of IL-6, TNF-", IFN-! and IL-10 in the DLN and low IFN! titres in the spleen were 41 associated with protection following BCG vaccination. This study suggests an effective BU vaccine 42 must induce localized, tissue-specific immune profiles with controlled inflammatory responses at 43 the site of infection. 44 45 46 47 Results: 121 Formulation of the ER-R4Pam2Cys subunit vaccine candidate 122Mycolactone is the key virulence factor produced by M. ulcerans and an attractive vaccine target, 123 but the molecule is poorly immunogenic (55). However, the PKS enzymes used by the bacterium to 124 synthesize mycolactones -are highly conserved and immunogenic (49,(56)(57)(58). Therefore, we 125 hypothesized that targeting the conserved enzymatic domains of the mycolactone PKS could be an 126 effective vaccine strategy. One domain in particular, the enoyl reductase (ER) protein domain, elicits 127 serum antibodies in BU patients and healthy controls in BU endemic regions (57). The ER protein 128 expressed as an antigen in a DNA-protein prime-boost vaccine has also been shown to reduce 129 bacterial burden in a mouse footpad M. ulcerans challenge model (49). Here, we utilised the ER 130 protein to create a novel BU vaccine candidate by electrostatically associating it with the TLR-2 131 agonist-based lipopeptide R4Pam2Cys. To formulate this vaccine, recombinant 6xHis-tagged ER 132 protein (37 kDa) was first produced and confirmed by SDS-PAGE ( Fig. 1A) and western blotting (Fig. 133 1B). This protein antigen was formulated with R4Pam2Cys at various rat...

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“…PH assumption and homogeneity of censoring mechanism need to check before selecting suitable methods. There are three different methods to evaluate PH assumption: 1) graphical assessment (KM curves and ln (-ln(S(t))) vs ln(t) Curves); 2) add a time interaction, x*log(t), into COX regression and test its signi cance; 3) check global good of tness by plotting and testing association between ranked survival time and Schoenfeld residuals [12,13]. violations of the PH assumption suggests existence of interactions between one or more covariates and time.…”

Section: Flowchart For Statistical Methodsmentioning

confidence: 99%

A univariable and multivariable analysis of right censored time-to-event data based on restricted mean survival time: A combination with traditional survival methods.

Lyv

Deng

et al. 2020

Preprint

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Background: Many traditional survival analyses and restricted mean survival time (RMST) based analyses have been proposed for dealing with right censored time-to-event data. It is necessary to sort out the conditions and relationship among these methods for instruction. Comparison between hazard ratio (HR) and RMST in a study may promote appropriate understanding and application of the two effect measures.Method : Traditional survival analyses and RMST-based analyses were integrated into a flowchart and applied for univariable and multivariable analyses, RMST-based analyses included group comparison for difference in RMST, pseudo-value (PV) regressions, inverse probability of censoring probability (IPCW) regressions with group-specific weights and individual weights with homogeneity of censoring mechanism assumption. 4405 osteosarcomas were captured from Surveillance, Epidemiology and End Results Program Database. HR and difference in RMST (survival time lost or gain, STL or STG) were considered as effect measures and the effect of all included covariates on overall survival were reported for comparison. The relationship between difference in RMST and HR were explored when proportional hazard (PH) assumption was and was not met, respectively. Results: In group comparison and univariable regressions, using difference in RMST calculated by Kaplan-Meier methods as reference, PV regressions (R2=0.99) and IPCW regressions with group-specific weights (R2=1.00) provided more consistent estimation on difference in RMST than IPCW with individual weights (R2=0.09). In multivariable analysis, age (HR:1.03, STL: 3.86 months), diagnosis in 1970~1980s (HR:1.39 STL:27.49 months), metastasis (HR:4.47, STL: 202 months), surgery (HR:0.58, SLG:35.55 months) and radiation (HR:1.46, SLT:44.65 months) met PH assumption and were main independent factors for overall survival. In both univariable and multivariable variables, a robust negative logarithmic linear relationship between HRs estimated by Cox regression and differences in RMST by pseudo-value regressions was only observed when PH assumption was hold. Conclusion: The flowchart may be intuitive and helpful to instruct appropriate use of RMST based and traditional methods. PH assumption and homogeneity of censoring mechanism assumption will determine the appropriate selection of these method. HR and difference in RMST can be reported comprehensively.

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Application of Cox Proportional Hazards Model in Case of Tuberculosis Patients in Selected Addis Ababa Health Centres, Ethiopia

Cited by 24 publications

References 12 publications

Total Delay Is Associated with Unfavorable Treatment Outcome among Pulmonary Tuberculosis Patients in West Gojjam Zone, Northwest Ethiopia: A Prospective Cohort Study

Total Delay Is Associated with Unfavorable Treatment Outcome among Pulmonary Tuberculosis Patients in West Gojjam Zone, Northwest Ethiopia: A Prospective Cohort Study

Vaccine-specific immune responses againstMycobacterium ulceransinfection in a low-dose murine challenge model

A univariable and multivariable analysis of right censored time-to-event data based on restricted mean survival time: A combination with traditional survival methods.

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