***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 Tuberculosis ( TB ) is a major cause of morbidity and mortality among children infected with HIV . Strategies to prevent TB in children include isoniazid preventive therapy ( IPT ) and antiretroviral therapy ( ART ) . IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children . Objective To investigate the combined effect of IPT and ART on TB risk in children infected with HIV . Methods A cohort analysis was done within a prospect i ve , double-blinded , placebo-controlled trial of isoniazid ( INH ) compared with placebo in children infected with HIV in Cape Town , South Africa , a high TB incidence setting . In May 2004 the placebo arm was terminated and all children were switched to INH . ART was not widely available at the start of the study , but children were started on ART following the establishment of the national ART program in 2004 . Data were analysed using Cox proportional hazard regression . Results After adjusting for age , nutritional status and immunodeficiency at enrolment , INH alone , ART alone and INH combined with ART reduced the risk of TB disease by 0.22 ( 95 % CI 0.09 to 0.53 ) , 0.32 ( 95 % CI 0.07 to 1.55 ) and 0.11 ( 95 % CI 0.04 to 0.32 ) respectively . INH reduced the risk of TB disease in children on ART by 0.23 ( 95 % CI 0.05 to 1.00 ) . Conclusions The finding that IPT may offer additional protection in children on ART has significant public health implication s because this offers a possible strategy for reducing TB in children infected with HIV . Widespread use of this strategy will however require screening of children for active TB disease . Trial registration Trial registration — Clinical Trials NCT00330304 The data from 2 U. S. Public Health Service trials of isoniazid preventive therapy  were review ed in an effort to evaluate the risk of death from cancer among persons who received such therapy . Each of these prospect i ve trials used r and om assignment to either isoniazid or placebo .  More than 25,000 persons participated in each of the trials . The length of follow-up ranged from 10 to 14 years in one trial and from 9 to 11 years in the other . No significant difference in the incidence of death from cancer was noted between groups treated with placebo or with isoniazid in either of the studies . This was true even when deaths due to specific types of cancer and age-specific cancer death rates were compared . These data do not support a carcinogenic effect of isoniazid in humans BACKGROUND The dual epidemic of human immunodeficiency virus ( HIV ) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa . We conducted a double-blind , r and omized , placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period . METHODS We r and omly assigned 548 HIV-infected and 804 HIV-uninfected infants ( 91 to 120 days of age ) to isoniazid ( 10 to 20 mg per kilogram of body weight per day ) or matching placebo for 96 weeks . All patients received bacille Calmette-Guérin ( BCG ) vaccination against tuberculosis within 30 days after birth . HIV-infected children had access to antiretroviral therapy . The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection , tuberculosis disease , and death in HIV-uninfected children within 96 to 108 weeks after r and omization . RESULTS Antiretroviral therapy was initiated in 98.9 % of HIV-infected children during the study . Among HIV-infected children , protocol -defined tuberculosis or death occurred in 52 children ( 19.0 % ) in the isoniazid group and 53 ( 19.3 % ) in the placebo group ( P=0.93 ) . Among HIV-uninfected children , there was no significant difference in the combined incidence of tuberculosis infection , tuberculosis disease , or death between the isoniazid group ( 39 children , 10 % ) and the placebo group ( 45 children , 11 % ; P=0.44 ) . The rate of tuberculosis was 121 cases per 1000 child-years ( 95 % confidence interval [ CI ] , 95 to 153 ) among HIV-infected children as compared with 41 per 1000 child-years ( 95 % CI , 31 to 52 ) among HIV-uninfected children . There were no significant differences in clinical or severe laboratory toxic effects between treatment groups . CONCLUSIONS Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine . Despite access to antiretroviral therapy , the burden of tuberculosis remained high among HIV-infected children . ( Funded by the National Institutes of Health and Secure the Future ; Clinical Trials.gov number , NCT00080119 . ) OBJECTIVE To compare the adverse effects and treatment adherence between 2 months of rifampin plus pyrazinamide ( 2RZ ) and 6 months of isoniazid ( 6H ) . BACKGROUND Patients with silicosis in Hong Kong are at high risk of acquiring tuberculosis . A previous study showed that treatment with 6H reduced the risk of silico-tuberculosis by one half . METHOD Patients with silicosis and a Mantoux skin test reaction > or = 10 mm were r and omized to receive either 2RZ or 6H daily .  Liver function testing was done monthly during the initial 2 months . The adverse effects and treatment adherence were compared between the two regimens . RESULTS Forty patients ( mean age , 61.6 + /- 9.1 years ) and 36 patients ( mean age , 57.6 + /- 9.7 years ) were r and omized to the 2RZ and 6H arms , respectively ( p > 0.05 ) [ + /- SD ] . Baseline characteristics were comparable . Nineteen patients in the 2RZ arm had peak alanine transaminase ( ALT ) levels > 1.5 times the upper limit of normal ( ULN ) in comparison with only five study subjects of the 6H arm ( 47.5 % vs 13.9 % , p < 0.01 ) . Fourteen patients ( 35 % ) in the 2RZ arm and 1 patient ( 2.8 % ) in the 6H arm had peak ALT levels more than five times the ULN ( p < 0.001 ) . Only seven patients had symptoms suggestive of hepatitis ; none of the patients had jaundice . All recovered after withholding treatment . In the 2RZ study arm , none of the baseline characteristics predicted hepatotoxicity . Other adverse effects were generally mild and comparable between both study arms . Treatment was stopped prematurely in 45 % and 36.1 % of patients in the 2RZ and 6H arms , respectively ( p = 0.43 ) . The main reasons were hepatotoxicity for the 2RZ arm and voluntary withdrawal after experiencing other minor adverse effects for the 6H arm . CONCLUSION A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong This article reports the findings from a clinical study that examined the impact of health education and counseling on the decision of a patient infected with tuberculosis ( TB ) to complete a regimen of isoniazid ( INH ) chemoprophylaxis for 6 months to prevent TB . Forty patients were divided into two groups ; both groups were administered a question naire to collect demographic data and medical history . One group received additional health education and counseling independent of clinic staff , and the other group only received health education and counseling from clinic staff . The proportion of patients in the first group who completed INH for 6 months ( 63.6 % ) was significantly greater than the proportion of patients in the second group ( 11.1 % ) . These findings suggest that health education and counseling did make an impact on the decision of a patient infected with TB to conform with a rational choice when provided with information and a supportive relationship about the consequences of TB infection SETTING An 8-month isoniazid ( INH , H ) and ethambutol ( EMB , E ) based regimen recommended by the World Health Organization ( WHO ) had never been evaluated in a r and omised controlled multicentre trial . OBJECTIVE To compare , in a non-inferiority study design , two 8-month INH+EMB-based regimens with a st and ard INH and rifampicin ( RMP , R ) based regimen . DESIGN A total of 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were r and omly allocated to receive 1 ) daily EMB , INH , RMP and pyrazinamide ( PZA , Z ) for 2 months , followed by EMB+INH for 6 months ( 2EHRZ/6HE ) ; 2 ) the same drugs in the intensive phase but given three times weekly , followed by the same continuation phase of daily EMB+INH ( 2(EHRZ)(3)/6HE ) ; or 3 ) a control regimen with the same intensive phase as in regimen 1 , followed by 4 months of daily RMP+INH ( 2EHRZ/4HR ) . All patients were to be seen and sputum examinations for microscopy and culture carried out at regular intervals up to 30 months after r and omisation . RESULTS At 30 months , failure/relapse rates were 11.7 % of 281 2EHRZ/6HE , 15.3 % of 301 2(EHRZ)(3)/6HE and 6.0 % of 282 2EHRZ/4HR patients ( χ(2 ) , 2 degrees of freedom = 12.8 , P = 0.002 ) . CONCLUSION These results confirm earlier findings demonstrating the inferiority of the INH+EMB-based regimens to the st and ard 6-month regimen . The WHO has withdrawn its recommendation of these regimens Rationale Treatment for latent tuberculosis infection with isoniazid for 9 months ( 9INH ) has poor completion and serious adverse events , while treatment for 4 months with daily rifampin ( 4RIF ) has significantly higher completion and fewer adverse events . Objectives To compare the health system costs of 4RIF and 9INH . Methods In a r and omised trial conducted in five Canadian centres , one Brazilian and one Saudi Arabian centre , consenting subjects were r and omised to receive 4RIF or 9INH .  Health system costs were estimated from healthcare utilisation including scheduled and unscheduled visits , investigations and drugs . All activities for all subjects were evaluated using financial information from 2007 from the Montreal Chest Institute . Costs were expressed in Canadian dollars . Results Total health system cost per patient allocated to 4RIF was $ 854 compared with $ 970 for 9INH ( p<0.0001 ) . The average cost per patient for the 328 of 420 ( 78 % ) who completed 4RIF therapy was $ 1094 compared with $ 1625 for the 254 of 427 ( 60 % ) completing 9INH ( p<0.0001 ) . Costs were modestly increased in patients with minor intolerance and substantially increased if the treating physician stopped treatment because of possible adverse events . Total costs related to management of adverse events with 9INH were $ 48 142 compared with $ 25 684 for 4RIF ( p=0.008 ) . Using these data , incremental cost-effectiveness analyses showed that 4RIF would be cost saving and prevent more cases within 2 years if efficacy exceeded 74 % , and cost saving if efficacy exceeded 65 % . Conclusions The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events . RCT registration number NCT00170209 BACKGROUND Cases of severe and fatal liver injury were reported after a 2-month course of rifampin-pyrazinamide therapy was recommended in 2000 as an alternative to isoniazid for treatment of latent tuberculosis infection . We estimated rates of rifampin-pyrazinamide-associated liver injury and compared these with historical rates for isoniazid . METHODS We conducted a survey of state and city tuberculosis programs and other health care setting s in the United States where  rifampin-pyrazinamide was prescribed . The number of rifampin-pyrazinamide therapy initiations was collected , as well as the number of occurrences of ( 1 ) asymptomatic aspartate aminotransferase serum concentration > 5 times the upper limit of normal , ( 2 ) symptomatic hepatitis ( in which the patient was not hospitalized ) , ( 3 ) hospitalization for liver injury , ( 4 ) death with liver injury , and ( 5 ) treatment completion . We also search ed a national pharmacy cl aims data base ( Verispan ) . Rates of these events were calculated . RESULTS Among 139 programs , 110 ( 79 % 
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The directly-observed , shorter regimen had higher treatment completion ( 82 % vs 69 % , RR 1.19 , 95 % CI 1.16 to 1.22 , moderate quality evidence ) , and less hepatotoxicity ( 0.4 % versus 2.4 % ; RR 0.16 , 95 % CI 0.10 to 0.27 ; high quality evidence ) , though treatment-limiting adverse events were more frequent ( 4.9 % versus 3.7 % ; RR 1.32 , 95 % CI 1.07 to 1.64 moderate quality evidence ) AUTHORS ' CONCLUSIONS Trials to date of shortened prophylactic regimens using rifampicin alone have not demonstrated higher rates of active TB when compared to longer regimens with INH .
Treatment completion is probably higher and adverse events may be fewer with shorter rifampicin regimens .
Shortened regimens of rifampicin with INH may offer no advantage over longer INH regimens .
Rifampicin combined with pyrazinamide is associated with more adverse events .
A weekly regimen of rifapentine plus INH has higher completion rates , and less liver toxicity , though treatment discontinuation due to adverse events is probably more likely than with INH