***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Early-phase and pre clinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated , smear-positive pulmonary tuberculosis . METHODS We conducted a r and omized , double-blind , placebo-controlled , phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen . One group of patients received isoniazid , rifampin , pyrazinamide , and ethambutol for 8 weeks , followed by 18 weeks of isoniazid and rifampin ( control group ) . In the second group , we replaced ethambutol with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( isoniazid group ) , and in the third group , we replaced isoniazid with moxifloxacin for 17 weeks , followed by 9 weeks of placebo ( ethambutol group ) . The primary end point was treatment failure or relapse within 18 months after r and omization . RESULTS Of the 1931 patients who underwent r and omization , in the per- protocol analysis , a favorable outcome was reported in fewer patients in the isoniazid group ( 85 % ) and the ethambutol group ( 80 % ) than in the control group ( 92 % ) , for a difference favoring the control group of 6.1 percentage points ( 97.5 % confidence interval [ CI ] , 1.7 to 10.5 ) versus the isoniazid group and 11.4 percentage points ( 97.5 % CI , 6.7 to 16.1 ) versus the ethambutol group . Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses . The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups , as compared with the control group , ranged from 1.17 to 1.25 , indicating a shorter duration , with the lower bounds of the 95 % confidence intervals exceeding 1.00 in all cases . There was no significant difference in the incidence of grade 3 or 4 adverse events , with events reported in 127 patients ( 19 % ) in the isoniazid group , 111 ( 17 % ) in the ethambutol group , and 123 ( 19 % ) in the control group . CONCLUSIONS The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load , as compared with the control group . However , noninferiority for these regimens was not shown , which indicates that shortening treatment to 4 months was not effective in this setting . ( Funded by the Global Alliance for TB Drug Development and others ; REMoxTB Clinical Trials.gov number , NCT00864383 . ) RATIONALE Cavitary disease and delayed culture conversion have been associated with relapse . Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients . OBJECTIVES To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months . METHODS This study was a r and omized , open-label equivalence trial . HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid , rifampin , pyrazinamide , and ethambutol for 2 months , followed by 2 months of isoniazid and rifampin . After 4 months , patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were r and omly assigned to continue treatment for 2 more months or to stop treatment . Patients were followed for relapse for 30 months after beginning treatment . MEASUREMENTS AND MAIN RESULTS Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm . A total of 370 patients were eligible for per protocol analysis . Thirteen patients in the 4-month arm relapsed , compared with three subjects in the 6-month arm ( 7.0 vs. 1.6 % ; risk difference , 0.054 ; 95 % confidence interval with Hauck- And erson correction , 0.01 - 0.10 ) . CONCLUSION Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs result ed in a greater relapse rate . The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse BACKGROUND Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control . This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis . METHODS We conducted a noninferiority , r and omized , open-label , controlled trial involving patients 18 to 65 years of age with smear-positive , rifampin-sensitive , newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries . A st and ard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin ( 400 mg per day ) was substituted for ethambutol during the intensive phase and was continued , along with rifampin and isoniazid , during the continuation phase . The primary efficacy end point was an unfavorable outcome ( treatment failure , recurrence , or death or study dropout during treatment ) measured 24 months after the end of treatment , with a noninferiority margin of 6 percentage points , adjusted for country . RESULTS A total of 1836 patients were assigned to the 4-month regimen ( experimental group ) or the st and ard regimen  ( control group ) . Baseline characteristics were well balanced between the groups . At 24 months after the end of treatment , the adjusted difference in the risk of an unfavorable outcome ( experimental group [ 21.0 % ] minus control group [ 17.2 % ] ) in the modified intention-to-treat population ( 1356 patients ) was 3.5 percentage points ( 95 % confidence interval , -0.7 to 7.7 ) . There was heterogeneity across countries ( P=0.02 for interaction , with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal ) and in baseline cavitary status ( P=0.04 for interaction ) and body-mass index ( P=0.10 for interaction ) . The st and ard regimen , as compared with the 4-month regimen , was associated with a higher dropout rate during treatment ( 5.0 % vs. 2.7 % ) and more treatment failures ( 2.4 % vs. 1.7 % ) but fewer recurrences ( 7.1 % vs. 14.6 % ) . There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen . CONCLUSIONS Noninferiority of the 4-month regimen to the st and ard regimen with respect to the primary efficacy end point was not shown . ( Funded by the Special Program for Research and Training in Tropical Diseases and others ; Clinical Trials.gov number , NCT00216385 . ) BACKGROUND WHO guidelines recommend early initiation of antiretroviral therapy ( ART ) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV , but evidence supporting this approach is poor quality . We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per μL or more . METHODS We did this r and omised , placebo-controlled trial between Jan 1 , 2008 , and April 31 , 2013 at 26 treatment centres in South Africa , Tanzania , Ug and a , and Zambia . We enrolled HIV-positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis short course chemotherapy . Participants were r and omly allocated ( 1:1 ) to early ART ( starting after 2 weeks of tuberculosis treatment ) or delayed ART ( placebo , then starting ART at the end of 6 months of tuberculosis treatment ) . R and omisation was computer generated , with permuted blocks of size eight , and stratified by CD4 count ( 220 - 349 cells per μL vs ≥350 cells per μL ) . Patients and investigators were masked to treatment allocation until completion of 6-months ' tuberculosis treatment , after which the study was open label . The primary endpoint was a composite of failure of tuberculosis treatment , tuberculosis recurrence , and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population . Secondary endpoints included mortality . The study is registered with controlled-trials.com ( IS RCT N77861053 ) . FINDINGS We screened 13,588 patients and enrolled 1675 : 834 assigned  early ART , 841 delayed ART . The primary endpoint was reached by 65 ( 8·5 % ) of 767 patients in the early ART group versus 71 ( 9·2 % ) of 771 in the delayed ART group ( relative risk [ RR ] 0·91 , 95 % CI 0·64 - 1·30 ; p=0·9 ) . Of patients with a CD4 cell count of 220 - 349 cells per μL , 26 ( 7·9 % ) of 331 patients versus 33 ( 9·6 % ) of 342 reached the primary endpoint ( RR 0·80 , 95 % CI 0·46 - 1·39 ; p=0·6 ) . For those with 350 cells per μL or more , 39 ( 8·9 % ) of 436 versus 38 ( 8·9 % ) of 429 reached the primary endpoint ( RR 1·01 , 95 % CI 0·63 - 1·62 ; p=0·4 ) . Mortality did not differ significantly between treatment groups ( RR 1·4 , 95 % CI 0·8 - 2·3 ; p=0·23 ) . Grade 3 and 4 adverse events occurred in 149 ( 18 % ) of 834 patients assigned early ART versus 174 ( 21 % ) of 841 assigned delayed ART ( p=0·37 ) . 87 ( 10 % ) of 834 versus 84 ( 10 % ) of 841 had immune reconstitution inflammatory syndrome ( p=0·56 ) . INTERPRETATION ART can be delayed until after completion of 6 months of tuberculosis treatment for HIV-positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per μL. WHO guidelines should be up date d accordingly . FUNDING USAID , Zambia Ministry of Health , Tanzania Commission for Science and Technology , WHO-TDR The impact of smoking on tuberculosis outcome was evaluated in a territory-wide treatment programme . 16 345 consecutive patients undergoing chemotherapy for active tuberculosis in government chest clinics in Hong Kong from 2001 to 2003 were followed up prospect ively for 2 years for treatment outcome and subsequently tracked through the territory-wide tuberculosis notification registry for relapse until the end of 2012 . Smoking was associated with more extensive lung disease , lung cavitation and positive sputum smear and culture at the baseline . In both current smokers and ex-smokers  , sputum smears and cultures were significantly more likely to remain positive after 2 months of treatment . Both categories of smokers were significantly less likely to achieve cure or treatment completion within 2 years . Overall , 16.7 % of unsuccessful treatment outcomes were attributable to smoking , with the key contributor being default in current smokers and death in ex-smokers . Among successful treatment completers , there was a clear gradient ( hazard ratios of 1.00 , 1.33 and 1.63 ) of relapse risk from never-smokers to ex-smokers and current smokers , with an overall population attributable risk of 19.4 % ( current smokers : 12.2 % ; ex-smokers : 7.2 % ) . Smoking adversely affects baseline disease severity , bacteriological response , treatment outcome and relapse in tuberculosis . Smoking cessation likely reduces relapse and secondary transmission . Smoking adversely affects treatment response in TB . Smoking cessation reduces relapse and secondary transmission . BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed . METHODS We r and omly assigned patients with newly diagnosed , smear-positive , drug-sensitive tuberculosis to one of three regimens : a control regimen that included 2 months of ethambutol , isoniazid , rifampicin , and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin ; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months ; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 
    Output:
    
Conclusion Despite its poor predictive value , our results indicate that the combined presence of cavitary disease and 2-month positive smear status may be the best currently available marker for identifying individuals at an increased risk of relapse , particularly in re source -limited setting .