***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 The occurrence of acquired rifamycin resistance despite use of directly observed therapy for tuberculosis is associated with advanced human immunodeficiency virus ( HIV ) disease and highly intermittent administration of antituberculosis drugs . Beyond these associations , the pathogenesis of acquired rifamycin resistance is unknown . METHODS We performed a pharmacokinetic sub study of patients in a trial of treatment with twice-weekly rifabutin and isoniazid .  RESULTS A total of 102 ( 60 % ) of 169 patients in the treatment trial participated in the pharmacokinetic sub study , including 7 of 8 patients in whom tuberculosis treatment failure or relapse occurred in association with acquired rifamycin-resistant mycobacteria ( hereafter , " ARR failure or relapse " ) . The median rifabutin area under the concentration-time curve ( AUC(0 - 24 ) ) was lower for patients with than for patients without ARR failure or relapse ( 3.3 vs. 5.2 microg*h/mL ; P = .06 , by the Mann-Whitney exact test ) . In a multivariate analysis adjusted for CD4 + T cell count , the mean rifabutin AUC(0 - 24 ) was significantly lower for patients with ARR failure or relapse than for other patients ( 3.0 microg*h/mL [ 95 % confidence interval { CI } , 1.9 - 4.5 ] vs. 5.2 microg*h/mL [ 95 % CI , 4.6 - 5.8 ] ; P = .02 , by analysis of covariance ) . The median isoniazid AUC(0 - 12 ) was not significantly associated with ARR failure or relapse ( 20.6 vs. 28.0 microg*h/mL ; P = .24 , by the Mann-Whitney exact test ) . However , in a multivariate logistic regression model that adjusted for the rifabutin AUC(0 - 24 ) , a lower isoniazid AUC(0 - 12 ) was associated with ARR failure or relapse ( OR , 10.5 ; 95 % CI , 1.1 - 100 ; P = .04 ) . CONCLUSIONS Lower plasma concentrations of rifabutin and , perhaps , isoniazid were associated with ARR failure or relapse in patients with tuberculosis and HIV infection treated with twice-weekly therapy This report from the Tuberculosis Chemotherapy Centre , Madras , summarizes the progress over a 5-year period of 193 patients with newly diagnosed , sputum-positive pulmonary tuberculosis who were admitted to a concurrent comparison of home and sanatorium treatment for one year with isoniazid plus PAS .  Previous reports have shown that , despite the traditional advantages of sanatorium treatment-rest , adequate diet , nursing and supervised drug-administration-the home patients responded nearly as well as the sanatorium patients in the first year ; further , the relapse rates over a 2-year period of follow-up were similar . The findings in the present report are based on a 4-year period of follow-up and extend these conclusions , the relapse rates over the period being 7 % for the home patients and 10 % for the sanatorium patients . Patients who failed to respond to treatment in the first year and those who had a bacteriological relapse in the second or subsequent years were usually re-treated with reserve regimens , first with streptomycin plus pyrazinamide and , if this was ineffective , with cycloserine plus ethionamide . Considering the findings over the entire 5-year period , five home patients and three sanatorium patients died from non-tuberculous causes . Of the remainder , 5 % of the home patients and 6 % of the sanatorium patients died of tuberculosis , 4 % in each series had bacteriologically active disease at five years and 90 % and 89 % , respectively , had bacteriologically quiescent disease at that time . These findings are very encouraging , particularly for developing countries such as India , where tuberculosis is a major problem and sanatorium beds are very few This report is the last of a series of nine publications from the Tuberculosis Chemotherapy Centre , Madras , concerning various aspects of an investigation of the role of ambulatory chemotherapy for pulmonary tuberculosis . It presents the attack rates of tuberculosis over a 5-year period of follow-up of close family contacts of patients , all of whom were treated for one year with isoniazid plus PAS , half ( selected at r and om ) in sanatorium and half at home .  The incidence of active tuberculosis and of tuberculous infections was no greater in the contacts of patients treated at home than in the contacts of patients treated in sanatorium , either in the first year or over the subsequent four years . The major risk to the contacts result ed from exposure to the patient before diagnosis . These findings reaffirm that close family contacts of patients treated at home were at no additional risk of developing tuberculosis , provided the patients received effective chemotherapy . Finally , this study has shown that it is possible in South India to obtain extremely good co-operation from a group of families over a period of several years While directly observed treatment ( DOT ) has been recommended as the st and ard approach to tuberculosis control , empirical data on its feasibility and efficiency are still scarce . We conducted a controlled trial of DOT at 15 health care facilities at various levels of the government health care system in Thail and . A total of 836 patients diagnosed between August 1996 and October 1997 were r and omly assigned to be treated either under DOT or self-supervised using monthly drug supplies ( SS ) .  Options for treatment supervisors were health staff , community members or members of the patients ' families . Treatment outcomes were compared on the basis of cure , treatment-completion , default and death rates . In both study arms , treatment outcomes were improved compared to pre- study conditions . Cure and treatment-completion rates were significantly higher in the DOT cohort ( 76 % and 84 % ) than in the SS group ( 67 % and 76 % ) . The benefits of DOT were more pronounced at district and provincial hospitals ( DOT cure rate 81 % vs. 69 % in the SS group ) , while differences for patients treated at referral centres were non-significant ( DOT cure rate 72 % vs. 66 % in the SS group ) . No significant differences in outcomes could be observed between patient groups receiving DOT under the various options for treatment supervisors . DOT appears especially suited for treatment at de central ized facilities . While a general focus on programme performance can improve outcomes , DOT provides significant additional benefits . If basic conditions are met , a DOT strategy can be tailored to country-specific conditions by exploring multiple observation options , without decreasing its effectiveness The bacteriological relapse rates up to 30 months after the start of chemotherapy have been compared for 4 daily short-course regimens for pulmonary tuberculosis . All 4 had the same initial 2-month intensive phase of streptomycin , isoniazid , rifampicin and pyrazinamide ( SHRZ ) followed by isoniazid plus rifampicin for 4 months ( 4HR ) , or isoniazid plus pyrazinamide for 4 months ( 4HZ ) , or isoniazid alone for 4 months ( 4H ) , or isoniazid alone for 6 months ( 6H ) . In patients with fully sensitive strains pretreatment , the 6-month regimen with rifampicin throughout ( 4HR ) was highly effective , only 2 % of 166 patients relapsing bacteriologically in 24 months of follow-up after stopping chemotherapy . This regimen was significantly better than the 4H regimen which had a relapse rate of 10 % in 156 patients ( P less than 0.02 ) and the 4HZ regimen which had a relapse rate of 8 % in 164 patients ( P = 0.05 ) . The 6H regimen was also highly effective , only 3 % of the 123 patients relapsing , compared with 10 % of the 156 on the 4H regimen ( P = 0.06 ) . The relapse rate of the regimen with pyrazinamide throughout ( 4HZ ) , was not significantly different from that of either of the regimens with isoniazid alone in the continuation phase . All except 3 ( 1 4HR , 1 4HZ , 1 4H ) of the 36 relapses were with fully drug-sensitive strains . In patients with strains resistant to isoniazid alone pretreatment none of the 23 on the 4HR or 4HZ regimens had an unfavourable bacteriological status at the end of chemotherapy compared with 8 of the 17 patients ( P less than 0.005 ) on 4H or 6H regimens . Of the patients assessed , 3 of 20 receiving rifampicin or pyrazinamide throughout relapsed compared with 2 of 8 who did not To underst and why once-weekly isoniazid/rifapentine therapy for tuberculosis was less effective than twice-weekly isoniazid/rifampin , we studied human immunodeficiency virus-seronegative patients with either failure ( n = 4 ) , relapse ( n = 35 ) , or cure ( n = 94 ) , recruited from a comparative treatment trial . In multivariate analyses that were adjusted for severity of disease , low plasma concentrations of isoniazid  were associated with failure/relapse with once-weekly isoniazid/rifapentine ( median isoniazid area under the concentration-time curve for 12 hours after the dose [ AUC(0 - 12 ) ] was 36 microg x hour/ml in failure/relapse versus 56 microg x hour/ml in control cases p = 0.005 ) , but not with twice-weekly isoniazid/rifampin . Furthermore , two patients who relapsed with Mycobacterium tuberculosis monoresistant to rifamycin had very low concentrations of isoniazid . Finally , isoniazid acetylator status determined by N-acetyltransferase type 2 genotype was associated with outcome with once-weekly isoniazid/rifapentine ( p = 0.03 ) but not twice-weekly isoniazid/rifampin . No rifamycin  pharmacokinetic parameter was consistently and significantly associated with outcome ( p > 0.10 ) . Because low isoniazid concentrations were associated with failure/relapse , a drug with consistently greater area under the concentration-time curve than isoniazid may be needed to achieve highly active once-weekly therapy with rifapentine One daily and 3 thrice weekly retreatment regimens given for 12 months under programme conditions were compared . The daily regimen was rifampicin and ethambutol ( RE7 ) . The three intermittent regimens also contained rifampicin and ethambutol : one of them , rifampicin and ethambutol throughout ( RE3 ) ; the next one supplemented with pyrazinamide for the first 3 months ( REZ3 ) ; the last one supplemented with prothionamide for the first 3 months ( REPt3 ) . The pyrazinamide containing regimen was subdivided into ordinary and high dose groups . The subjects for retreatment were those who have had , at least , more than 6 months of initial triple chemotherapy of isoniazid , PAS and streptomycin at the health centres , and failed to convert to bacteriologically negative status . Among 419 patients who were available for sensitivity tests before commencing retreatment , 393 ( 94.3 % ) were resistant to isoniazid . Six hundred and seventy-four patients ( 674 ) were allocated r and omly to the regimens : 64 patients were excluded due to various pretreatment reasons and 109 did not complete 12 months of chemotherapy . There remain 501 patients who completed their retreatment . As assessed at 12 months , a bacteriologically favourable response was achieved in 68 % of 135 RE7 patients , 62 % of 129 RE3 patients , 74 % of 132 REZ3 patients , and in 79 % of 108 REPt3 patients . Adverse reactions were uncommon : 4 % in RE7 , 5 % in RE3 and 9 % in REZ3 , but 32 % in REPt3 . Relapse rates during 2 years after termination of chemotherapy were 15 % in RE7 , 14 % in RE3 and REZ3 , and 26 % in REPt3 , as calculated by life table analysis BACKGROUND Tuberculosis is a major public-health problem in South Africa , made worse by poor adherence to and frequent interruption of treatment . Direct observation ( DO ) of tuberculosis patients taking their drugs is supposed to improve treatment completion and outcome . We compared DO with self-supervision , in which patients on the same drug regimen are not observed taking their pills , to assess the effect of each on the success of tuberculosis treatment . METHODS We undertook an unblinded r and omised controlled trial in two communities with large tuberculosis caseloads . The trial included 216 adults who started pulmonary tuberculosis treatment for the first time , or who had a second course of treatment ( retreatment patients ) . No changes to existing treatment delivery were made other than r and omisation . Analysis was by intention to treat . Individual patient data from the two communities were combined . FINDINGS Treatment for tuberculosis was more successful among self-supervised patients ( 60 % of patients ) than among those on DO ( 54 % of patients , difference between groups 6 % [ 90 % CI -5.1 to 17.0 ] ) . Retreatment patients had significantly more successful treatment outcomes if self-supervised ( 74 % of patients ) than on DO ( 42 % of patients , difference between groups 32 % [ 11%-52 % ] ) . INTERPRETATION At high rates of treatment interruption , self 
    Output:
    
Findings suggest high levels of evidence for using daily dosing schedules , especially during the initial phase in the presence of cavitation , isoniazid resistance and advanced HIV co-infection , to reduce the risk of treatment failure , recurrence and acquired drug resistance including acquired rifamycin resistance .