***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: OBJECTIVE : To describe the rates of cure , treatment failure , and treatment ab and onment obtained with the basic regimen recommended by the Brazilian National Ministry of Health-rifampin , isoniazid , pyrazinamide , and ethambutol for two months , followed by isoniazid and rifampin for four months-involving the use of fixed-dose combination tablets ( self-administered treatment ) , as well as to describe adverse events and their potential impact on treatment outcomes . METHODS : This was a descriptive study based on prospect i ve data obtained from the medical records of tuberculosis patients ( ≥ 18 years of age ) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia , Brazil . RESULTS : The study sample comprised 40 tuberculosis patients . The rate of cure was 67.5 % , the rate of treatment ab and onment was 17.5 % , and there were no cases of treatment failure . Of the 40 patients in the sample , 19 ( 47 % ) reported adverse reactions , which were mild and moderate , respectively , in 87 % and 13 % of the cases . It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated . CONCLUSIONS : The rate of cure obtained with the self-administered , fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous basic regimen . The rate of treatment ab and onment in our sample was much higher than that considered appropriate ( up to 5 % ) BACKGROUND Novel treatment options are urgently needed for multidrug-resistant ( MDR ) and extensively drug-resistant ( XDR ) tuberculosis , which are associated with immune dysfunction and poor treatment outcomes . Mesenchymal stromal cells ( MSCs ) are immunomodulatory and adjunct autologous treatment with bone marrow-derived MSCs might improve clinical outcome by transforming chronic inflammation into productive immune responses . Our aim was to assess the safety of infusion of autologous MSCs as an adjunct treatment in patients with tuberculosis . METHODS 30 patients with microbiologically confirmed MDR or XDR tuberculosis were treated with single-dose autologous bone marrow-derived MSCs ( aim ed for 1 × 10(6 ) cells per kg ) , within 4 weeks of the start of antituberculosis-drug treatment in a specialist centre in Minsk , Belarus . Inclusion patients were those with pulmonary tuberculosis confirmed by sputum smear microscopy , culture , or both ; MDR or XDR tuberculosis confirmed by drug-susceptibility testing to first-line and second-line drugs ; age older than 21 years to 65 years or younger ; and absence of lesion compatible with a malignant process or ongoing tuberculosis in organs other than the lungs and pleura . In addition to the inclusion criteria , patients were excluded if they were pregnant , coinfected with HIV , or infected with hepatitis B , C , or both . The primary endpoint was safety measured by MSC-infusion related events ; any tuberculosis-related event within the 6 month observation period that related to a worsening of the underlying infectious disease , measured by conversion of Mycobacterium tuberculosis culture or microscopic examination ; or any adverse event defined clinical ly or by changes in blood haematology and biochemistry variables , measured monthly for 6 months after MSC infusion per protocol . This study is registered with the German Clinical Trials Registry , number DRKS00000763 . FINDINGS The most common ( grade 1 or 2 ) adverse events were high cholesterol levels ( 14 of 30 patients ) , nausea ( 11 of 30 patients ) , and lymphopenia or diarrhoea ( ten of 30 patients ) . There were no serious adverse events reported . We recorded two grade 3 events that were transitory-ie , increased plasma potassium ion concentrations in one patient and a transitory grade 3 γ-glutamyltransferase elevation in another patient . INTERPRETATION MSCs as an adjunct therapy are safe and can now be explored further for the treatment of patients with MDR or XDR tuberculosis in combination with st and ard drug regimens . Adjunct treatment with MSCs needs to be evaluated in controlled phase 2 trials to assess effects on immune responses and clinical and microbiological outcomes There is a growing appreciation that our current approach to clinical research leaves important gaps in evidence from the perspective of patients , clinicians , and payers wishing to make evidence -based clinical and health policy decisions . This has been a major driver in the rapid increase in interest in comparative effectiveness research ( CER ) , which aims to compare the benefits , risks , and sometimes costs of alternative health-care interventions in ‘ the real world ’ . While a broad range of experimental and nonexperimental methods will be used in conducting CER studies , many important questions are likely to require experimental approaches – that is , r and omized controlled trials ( RCTs ) . Concerns about the generalizability , feasibility , and cost of RCTs have been frequently articulated in CER method discussion s. Pragmatic RCTs ( or ‘ p RCTs ’ ) are intended to maintain the internal validity of RCTs while being design ed and implemented in ways that would better address the dem and for evidence about real-world risks and benefits for informing clinical and health policy decisions . While the level of interest and activity in conducting p RCTs is increasing , many challenges remain for their routine use . This article discusses those challenges and offers some potential ways forward SETTING Health centres in the South Sulawesi Province , Republic of Indonesia . OBJECTIVES To compare complaints , side-effects and treatment outcome in new smear-positive patients treated with a single-drug short-course ( National TB Programme ( NTP ) ) regimen with those treated with a four-drug fixed-dose combination ( 4FDC ) regimen .  DESIGN A prospect i ve study in which patients are r and omly allocated to the NTP or the 4FDC regimen . RESULTS Preliminary results of the first 360 patients ( 162 treated with the NTP regimen and 198 with the 4FDC regimen ) show that two patients , treated with the NTP regimen , developed jaundice . During the intensive phase of treatment , gastro-intestinal and muscle-joint complaints of any duration and gastro-intestinal complaints lasting for 2 consecutive weeks or more were more frequent in patients treated with the NTP regimen . Sputum conversion was 89 % in patients treated with the NTP regimen and 94 % in those treated with the 4FDC regimen . Nine-five per cent of patients , both regimens , were cured . CONCLUSION The results so far show that complaints during the intensive phase of treatment are less frequent among patients treated with the 4FDC regimen . The lower dose of pyrazinamide might be the reason . Treatment results are excellent for both regimens SETTING Veterans General Hospital-Taipei , Taiwan . OBJECTIVE To assess the efficacy and safety of a fixed-dose combination ( FDC ) of Rifater (RFT)/Rifinah ( RFN ) in the treatment of newly diagnosed smear-positive pulmonary tuberculosis . DESIGN Patients were r and omly assigned to two 6-month short-course chemotherapy regimens . One group of patients was treated with FDCs and another was given the four component drugs ( INH , RMP , EMB and PZA ) as separate formulations . RESULTS The 105 patients enrolled in the study were divided into two treatment groups . Fifty-one patients who had completed treatment without interruption , 26 in the FDC group and 25 in the separate regimen , were eligible for analysis at the end of 2 years . Among the patients with a drug susceptibility test result available , four in the FDC group had bacilli resistant to pyrazinamide . In the separate regimen group , two patients had bacilli resistant to ethambutol and six had bacilli resistant to pyrazinamide . The two regimens were of similar effectiveness with regard to sputum conversion , compliance and radiological improvement . No patient with FDC treatment developed gastointestinal symptoms , visual disturbance or peripheral neuropathy ( P < 0.05 ) . However , FDC treatment result ed in drug-induced fever in one patient . One patient ( 3.8 % ) in the FDC group relapsed 5 months after completing treatment . CONCLUSION This study suggests that the two regimens had similar effectiveness in the treatment of smear-positive pulmonary tuberculosis . However , the fewer adverse drug events among those patients treated with the FDC regimen suggests that it has a better safety profile OBJECTIVE To compare the efficacy , safety and acceptability of two short-course regimens of isoniazid , rifampicin , pyrazinamide and ethambutol ( HRZE ) given either as fixed-dose combination ( 4-FDC ) tablets or as single tablets ( ST ) in patients with newly diagnosed pulmonary tuberculosis ( PTB ) . DESIGN This r and omised , open , multicentre , multinational study was conducted in 26 centres and included 1159 patients with smear-positive PTB .  4-FDC daily for 2 months then H+R for 4 months , or single preparations of H , R , Z and E for 2 months followed by H and R for 4 months were administered daily . Sputum smear conversion rates at 2 , 4 and 6 months ( end of treatment [ EOT ] , primary endpoint ) and at 9 and 12 months ( follow-up ) were measured , together with adverse events and the acceptability of the formulations . RESULTS Smear conversion rates for 4-FDC and ST at EOT were 80.4 % ( 468/582 patients ) vs. 82.7 % ( 477/577 ) in the intent-to-treat ( ITT ) population , and 98.1 % ( 404/412 ) vs. 98.6 % ( 416/422 ) in the per- protocol ( PP ) subgroup . Non-inferiority of 4-FDC was demonstrated at month 2 , EOT and follow-up in both the ITT and the PP population s. Overall numbers of adverse events were not significantly different between the groups . CONCLUSION The efficacy of the 4-FDC regimen was non-inferior to that of the ST regimens , but patient acceptability significantly improved with 4-FDC To evaluate the clinical and therapeutic value of 4 and 3 drug fixed dose combinations verses single drug formulations to treat pulmonary tuberculosis patients . The occurrence of adverse effects was also monitored . A total of 293 patients having sputum positive pulmonary tuberculosis were enrolled ( Male : 187 and Female : 106 ) . Patients with renal , hepatic , diabetic , cardiac problem and pregnancy were excluded from study . Patients were r and omly selected into three groups ( A , B , C ) . Group A and B were given FDCs and group C was given single drug formulations . All patients received 4 drugs in the intensive phase and 3 drugs in the continuation phase . Group A showed the highest percentage of patients who achieved sputum conversion ( 98.9 % ) . The numbers of days taken to achieve sputum conversion on average were the least for Group B ( 32 days ) . When comparing the adverse effects , the patients of Group C suffered the most , with 22 patients who vomited repeatedly , 3 complaining of itching , 2 with Jaundice and 1 dead . There was no significant difference in the efficacy among the three treatment regimens . However the side effects observed in all three groups strongly indicate that FDCs are safer for treating TB patients . There were no side effects in the continuation phase CONTEXT Fixed-dose combinations ( FDCs ) of drugs for treatment of tuberculosis have been advocated to prevent the emergence of drug resistance . OBJECTIVE To assess the efficacy and safety of a 4-drug FDC for the treatment of tuberculosis . DESIGN , SETTING , AND PATIENTS The Study C trial , a parallel-group , open-label , noninferiority , r and omized controlled trial conducted in 11 sites in Africa , Asia , and Latin America between 2003 and 2008 . Patients were 1585 adults with newly diagnosed smear-positive pulmonary tuberculosis . INTERVENTIONS Patients were r and omized to receive daily treatment with 4 drugs ( rifampicin , isoniazid , pyrazinamide , ethambutol ) given as an FDC ( n = 798 patients ) or separately ( n = 787 ) in the 8-week intensive phase of treatment . MAIN OUTCOME MEASURE Favorable treatment outcome , defined as negative culture result at 18 months post r and omization and not having already been classified as unfavorable . Noninferiority was dependent on consistent results from a per- protocol and modified intention-to-treat analysis , using 2 different models for the latter , classifying all changes of treatment or refusal to continue treatment ( eg , bacteriological failure/relapse , adverse event , default , drug resistance ) as unfavorable ( model 1 ) and classifying changes of treatment for reasons other than therapeutic outcomes according to their 18-month bacteriological outcome if available ( post hoc model 2 ) . The prespecified noninferiority margin was 4 % . RESULTS In the per- protocol analysis , 555 of 591 patients ( 93.9 % ) had a favorable outcome in the FDC group vs 548 of 579 ( 94.6 % ) in the separate-drugs group ( risk difference , -0.7 % [ 90 % confidence interval { CI } , -3.0 % to 1.5 % ] ) . In the model 1 analysis , 570 of 684 patients ( 83.3 % ) had a favorable outcome in the FDC group vs 56 
    Output:
    
There were no significant differences between the groups in overall incidence of adverse effects .
Conclusions The review ed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects , as well as simplifying pharmaceutical management at all levels