Comparison of the validity of smear and culture conversion as a prognostic marker of treatment outcome in patients with multidrug-resistant tuberculosis

Background The World Health Organization (WHO) has conditionally recommended the use of sputum smear microscopy and culture examination for the monitoring of multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to assess and compare the validity of smear and culture conversion at different time points during treatment for MDR-TB, as a prognostic marker for end-of-treatment outcomes. Methods We undertook a retrospective observational cohort study using data obtained from Hunan Chest Hospital, China and Gondar University Hospital, Ethiopia. The sensitivity and specificity of culture and sputum smear conversion for predicting treatment outcomes were analysed using a random-effects generalized linear mixed model. Results A total of 429 bacteriologically confirmed MDR-TB patients with a culture and smear positive result were included. Overall, 345 (80%) patients had a successful treatment outcome, and 84 (20%) patients had poor treatment outcomes. The sensitivity of smear and culture conversion to predict a successful treatment outcome were: 77.9% and 68.9% at 2 months after starting treatment (difference between tests, p = 0.007); 95.9% and 92.7% at 4 months (p = 0.06); 97.4% and 96.2% at 6 months (p = 0.386); and 99.4% and 98.9% at 12 months (p = 0.412), respectively. The specificity of smear and culture non-conversion to predict a poor treatment outcome were: 41.6% and 60.7% at 2 months (p = 0.012); 23.8% and 48.8% at 4 months (p<0.001); and 20.2% and 42.8% at 6 months (p<0.001); and 15.4% and 32.1% (p<0.001) at 12 months, respectively. The sensitivity of culture and smear conversion increased as the month of conversion increased but at the cost of decreased specificity. The optimum time points after conversion to provide the best prognostic marker of a successful treatment outcome were between two and four months after treatment commencement for smear, and between four and six months for culture. The common optimum time point for smear and culture conversion was four months. At this time point, culture conversion (AUROC curve = 0.71) was significantly better than smear conversion (AUROC curve = 0.6) in predicting successful treatment outcomes (p < 0.001). However, the validity of smear conversion (AUROC curve = 0.7) was equivalent to culture conversion (AUROC curve = 0.71) in predicting treatment outcomes when demographic and clinical factors were included in the model. The positive and negative predictive values for smear conversion were: 57.3% and 65.7% at two months, 55.7% and 85.4% at four months, and 55.0% and 88.6% at six months; and for culture conversions it was: 63.7% and 66.2% at two months, 64.4% and 87.1% at four months, and 62.7% and 91.9% at six months, respectively. Conclusions The validity of smear conversion is significantly lower than culture conversion in predicting MDR-TB treatment outcomes. We support the WHO recommendation of using both smear and culture examination rather than smear alone for the monitoring of MDR-TB patients for a better prediction of successful treatment outcomes. The optimum time points to predict a future successful treatment outcome were between two and four months after treatment commencement for sputum smear conversion and between four and six months for culture conversion. The common optimum times for culture and smear conversion together was four months

Comparison of the validity of smear and culture conversion as a prognostic marker of treatment outcome in patients with multidrug-resistant tuberculosis

Background The World Health Organization (WHO) has conditionally recommended the use of sputum smear microscopy and culture examination for the monitoring of multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to assess and compare the validity of smear and culture conversion at different time points during treatment for MDR-TB, as a prognostic marker for end-of-treatment outcomes. Methods We undertook a retrospective observational cohort study using data obtained from Hunan Chest Hospital, China and Gondar University Hospital, Ethiopia. The sensitivity and specificity of culture and sputum smear conversion for predicting treatment outcomes were analysed using a random-effects generalized linear mixed model. Results A total of 429 bacteriologically confirmed MDR-TB patients with a culture and smear positive result were included. Overall, 345 (80%) patients had a successful treatment outcome, and 84 (20%) patients had poor treatment outcomes. The sensitivity of smear and culture conversion to predict a successful treatment outcome were: 77.9% and 68.9% at 2 months after starting treatment (difference between tests, p = 0.007); 95.9% and 92.7% at 4 months (p = 0.06); 97.4% and 96.2% at 6 months (p = 0.386); and 99.4% and 98.9% at 12 months (p = 0.412), respectively. The specificity of smear and culture non-conversion to predict a poor treatment outcome were: 41.6% and 60.7% at 2 months (p = 0.012); 23.8% and 48.8% at 4 months (p<0.001); and 20.2% and 42.8% at 6 months (p<0.001); and 15.4% and 32.1% (p<0.001) at 12 months, respectively. The sensitivity of culture and smear conversion increased as the month of conversion increased but at the cost of decreased specificity. The optimum time points after conversion to provide the best prognostic marker of a successful treatment outcome were between two and four months after treatment commencement for smear, and between four and six months for culture. The common optimum time point for smear and culture conversion was four months. At this time point, culture conversion (AUROC curve = 0.71) was significantly better than smear conversion (AUROC curve = 0.6) in predicting successful treatment outcomes (p < 0.001). However, the validity of smear conversion (AUROC curve = 0.7) was equivalent to culture conversion (AUROC curve = 0.71) in predicting treatment outcomes when demographic and clinical factors were included in the model. The positive and negative predictive values for smear conversion were: 57.3% and 65.7% at two months, 55.7% and 85.4% at four months, and 55.0% and 88.6% at six months; and for culture conversions it was: 63.7% and 66.2% at two months, 64.4% and 87.1% at four months, and 62.7% and 91.9% at six months, respectively. Conclusions The validity of smear conversion is significantly lower than culture conversion in predicting MDR-TB treatment outcomes. We support the WHO recommendation of using both smear and culture examination rather than smear alone for the monitoring of MDR-TB patients for a better prediction of successful treatment outcomes. The optimum time points to predict a future successful treatment outcome were between two and four months after treatment commencement for sputum smear conversion and between four and six months for culture conversion. The common optimum times for culture and smear conversion together was four months

Treatment outcomes of patients with multidrug-resistant and extensively drug resistant tuberculosis in Hunan Province, China

Background The worldwide emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has posed additional challenges for global tuberculosis (TB) control efforts, as limited treatment options are available and treatment outcomes are often sub-optimal. This study determined treatment outcomes among a cohort of MDR-TB and XDR-TB patients in Hunan Province, China, and identified factors associated with poor treatment outcomes. Methods We conducted a retrospective study using data obtained from medical records of TB patients in Hunan Chest Hospital, and from the internet-based TB management information system managed by the Tuberculosis Control Institute of Hunan Province, for the period 2011 to 2014. Treatment outcomes were assessed for patients diagnosed with MDR-TB (TB resistant to at least isoniazid and rifampicin) and XDR-TB (MDR-TB plus resistance to any fluoroquinolone and at least 1 second-line injectable drug). Cumulative incidence functions were used to estimate time to events (i.e. poor treatment outcomes, loss to follow-up, and unfavourable treatment outcomes); and a competing-risks survival regression model was used to identify predictors of treatment outcomes. Result Of 481 bacteriologically-confirmed patients, with a mean age of 40 years (standard deviation SD ± 13 years), 10 (2%) had XDR-TB and the remainder (471; 98%) had MDR-TB. For the entire cohort, treatment success was 57% (n = 275); 58% (n = 272) for MDR-TB and 30% (n = 3) for XDR-TB. Overall, 27% were lost to follow-up (n = 130), 27% (n = 126) for MDR-TB and 40% (n = 4) for XDR-TB; and 16% had a poor treatment outcome (n = 76), 15% for MDR-TB and 30% (n = 3) for XDR-TB. Of the 10 XDR-TB patients, 3 (30%) completed treatment, 3 (30%) died and 4 (40%) were lost to follow-up. Of the 471 MDR-TB patients, 258 (57%) were cured, 16 (3%) completed treatment, 13 (3%) died, 60 (13%) experienced treatment failure, and 126 (27%) were lost to follow-up. Resistance to ofloxacin was an independent predictor of poor (AHR = 3.1; 95%CI = 1.5, 6.3), and unfavourable (AHR = 1.7; 95%CI = 1.07, 2.9) treatment outcomes. Patients who started treatment during 2011–2012 (AHR = 2.8; 95% CI = 1.5, 5.3) and 2013 (AHR = 2.1; 95% CI = 1.2, 3.9) had poorer treatment outcomes compared to patients who started treatment during 2014. Conclusion Patients with MDR-TB and XDR-TB had low rates of treatment success in Hunan Province, especially among patients who started treatment during 2011 to 2013, with evidence of improved treatment outcomes in 2014. Resistance to ofloxacin was an independent predictor of poor treatment outcomes

Dead-time Influence on Control Quality

Cilj završnog rada jest prikazati utjecaj transportnog kašnjenja (tzv. mrtvog vremena) procesa u sustavima upravljanja, ući u problematiku upravljanja tih sustava, te pronaći rješenje kvalitetnog upravljanja sustava s transportnim kašnjenjem. U radu su korištena dva realna industrijska procesa s transportnim kašnjenjem. Izvršena je analiza tih procesa, primjenjena je jedna od klasičnih metoda upravljanja (PID regulacija), te interpretacija rezultata kroz odzive sustava na skokovitu funkciju i kroz neposredne parametre kakvoće upravljanja. Iskazane su negativnosti klasičnih metoda regulacije nad procesima s transportnim kašnjenjem, te prikazano je rješenje kvalitetnijeg upravljanja sustavom idejom Smithovog prediktora. Realiziran je prediktivni PI regulator (tzv. PPI) na konceptu upravljanja Smithovim prediktorom, također projektirana je njegova varijacija FPPI dodavanjem filtra prvog reda u vanjsku povratnu vezu. Dodavanje filtra PPI regulatoru povećava robusnost sustava. Prikazano je ponašanje različitih vrsta regulatora u slučaju promjenjivog mrtvog vremena procesa. Kao rezultat završni rad kroz detaljnu analizu prikazuje i definira rješenje problematike upravljanja sustavima s transportnim kašnjenjem nad stvarnim industrijskim procesima.The goals of this dissertation are to show the influence of a transport delay (often referred to as dead time) in control systems, define the issues of controlling such systems and find a quality solution of controlling systems with long dead time. Two actual industrial processes with dead time were used in this research. One of the classic control system methods (PID control) was used for the purpose of analyzing the systems and the results were interpreted through a step response and direct parameters of the quality of regulation. The disadvantages of classic control methods over dead time processes were defined and a better solution of the quality regulation, the idea of the Smith prediction, was shown. The predictive PI controller (so called PPI) based on the concept of the Smith predictor was designed. Additionally, its variation FPPI was designed by adding a first order filter into the outer loop. Adding a filter to the PPI controller improves the system robustness. The behavior of different types of controllers in the case of the variable process dead time was shown. Conducting a detailed analysis, a solution to the problematic actual industrial dead time process system control was shown and defined

Polymorphisms in PI3K/AKT genes and gene‑smoking interaction are associated with susceptibility to tuberculosis

AbstractBackground Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) are involved in the clearance of Mycobacterium tuberculosis (MTB) by macrophages.Aim This study aimed to investigate the effects of polymorphisms in the PI3K/AKT genes and the gene-smoking interaction on susceptibility to TB.Methods This case-control study used stratified sampling to randomly select 503 TB patients and 494 control subjects. Logistic regression analysis was used to determine the association between the polymorphisms and TB. Simultaneously, the marginal structure linear dominance model was used to estimate the gene-smoking interaction.Results Genotypes GA (OR 1.562), AA (OR 2.282), and GA + AA (OR 1.650) at rs3730089 of the PI3KR1 gene were significantly associated with the risk to develop TB. Genotypes AG (OR 1.460), GG (OR 2.785), and AG + GG (OR 1.622) at rs1130233 of the AKT1 gene were significantly associated with the risk to develop TB. In addition, the relative excess risk of interaction (RERI) between rs3730089 and smoking was 0.9608 (95% CI: 0.5959, 1.3256, p < 0.05), which suggests a positive interaction.Conclusion We conclude that rs3730089 and rs1130233 are associated with susceptibility to TB, and there was positive interaction between rs3730089 and smoking on susceptibility to TB

Time to initial sputum smear and culture conversion in patients with multidrug resistant tuberculosis by treatment outcomes from Hunan Chest and Gondar University Hospitals, 2010–2014.

<p>Time to initial sputum smear and culture conversion in patients with multidrug resistant tuberculosis by treatment outcomes from Hunan Chest and Gondar University Hospitals, 2010–2014.</p

The performance of smear and culture conversion at different months after commencement of treatment for multi-drug resistant tuberculosis to predict treatment outcome (successful vs poor treatment outcomes), for patients from Hunan Chest and Gondar University Hospitals, 2010 to 2014.

<p>The performance of smear and culture conversion at different months after commencement of treatment for multi-drug resistant tuberculosis to predict treatment outcome (successful vs poor treatment outcomes), for patients from Hunan Chest and Gondar University Hospitals, 2010 to 2014.</p

Number of patients with sputum smear and culture conversion after 2, 4, 6, and 12 months of treatment for multidrug resistant tuberculosis, among patients from Hunan Chest and Gondar University Hospitals, 2010 to 2014, stratified by successful and poor treatment outcomes.

<p>Number of patients with sputum smear and culture conversion after 2, 4, 6, and 12 months of treatment for multidrug resistant tuberculosis, among patients from Hunan Chest and Gondar University Hospitals, 2010 to 2014, stratified by successful and poor treatment outcomes.</p

Association of initial sputum smear and culture conversion at different months with treatment success in patients with multidrug resistant tuberculosis from Gondar University and Hunan Chest Hospital, 2010–2014, and adjusted odds ration with 95% confidence interval.

<p>Association of initial sputum smear and culture conversion at different months with treatment success in patients with multidrug resistant tuberculosis from Gondar University and Hunan Chest Hospital, 2010–2014, and adjusted odds ration with 95% confidence interval.</p

Discriminatory performance of risk scores for differentiating poor treatment outcomes from successful treatment outcomes among patients with multi drug resistant tuberculosis, using smear and culture conversion at two months only, as well as other demographic and clinical factors, from Hunan Chest and Gondar University Hospitals, 2010–2014.

<p>Discriminatory performance of risk scores for differentiating poor treatment outcomes from successful treatment outcomes among patients with multi drug resistant tuberculosis, using smear and culture conversion at two months only, as well as other demographic and clinical factors, from Hunan Chest and Gondar University Hospitals, 2010–2014.</p