***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 Evidence of protection from childhood Bacillus Calmette-Guerin ( BCG ) against tuberculosis ( TB ) in adulthood , when most transmission occurs , is important for TB control and re source allocation . Methods We conducted a population -based case-control study of protection by BCG given to children aged 12 - 13 years against tuberculosis occurring 10 - 29 years later . We recruited UK-born White subjects with tuberculosis and r and omly sample d White community controls .  Hazard ratios and 95 % confidence intervals ( CIs ) were estimated using case-cohort Cox regression , adjusting for potential confounding factors , including socio-economic status , smoking , drug use , prison and homelessness . Vaccine effectiveness ( VE = 1 - hazard ratio ) was assessed at successive intervals more than 10 years following vaccination . Results We obtained 677 cases and 1170 controls after a 65 % response rate in both groups . Confounding by deprivation , education and lifestyle factors was slight 10 - 20 years after vaccination , and more evident after 20 years . VE 10 - 15 years after vaccination was 51 % ( 95 % CI 21 , 69 % ) and 57 % ( CI 33 , 72 % ) at 15 - 20 years . Subsequently , BCG protection appeared to wane ; 20 - 25 years VE = 25 % ( CI -14 % , 51 % ) and 25 - 29 years VE = 1 % ( CI -84 % , 47 % ) . Based on multiple imputation of missing data ( in 17 % subjects ) , VE estimated in the same intervals after vaccination were similar [ 56 % ( CI 33 , 72 % ) , 57 % ( CI 36 , 71 % ) , 25 % ( -10 , 48 % ) , 21 % ( -39 , 55 % ) ] . Conclusions School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years , which is longer than previously thought . This has implication s for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions The authors developed and tested a framework for identifying evidence gaps and prioritizing comparative effectiveness research by using a combination of clinical practice guidelines and systematic review s. In phase 1 of the project , reported elsewhere , 45 clinical questions on the management of primary open-angle glaucoma were derived from practice guidelines and prioritized by using a 2-round Delphi survey of clinicians . On the basis of the clinicians ' responses , 9 questions were classified as high-priority . In phase 2 , reported here , systematic review s that addressed the 45 clinical questions were identified . The review s were classified as at low , high , or unclear risk of bias , and evidence gaps ( in which no systematic review was at low risk of bias ) were identified . The following comparative effectiveness research agenda is proposed : Two of the 9 high-priority questions require new primary research ( such as a r and omized , controlled trial ) and 4 require a new systematic review . The utility and limitations of the framework and future adaptations are discussed Background Help and treatment seeking behavior of men and women suffering from tuberculosis is largely determined by how he/she and those around them perceive the causes , regard the diagnosis , accept the treatment , and adhere to the treatment . Objectives To critically appraise and synthesize the best available evidence on gender‐based determinants of help and treatment seeking behavior of tuberculosis patients . Inclusion criteria Male and female tuberculosis patients ( > = 15 years ) living in developed and developing countries were included . Quantitative studies examining gender differences in help and treatment seeking among tuberculosis patients with cross‐sectional , retrospective and prospect i ve cohort were included . Types of primary outcomes Outcomes related to determinants of help seeking : pattern of distress , perceived cause of tuberculosis and stigma related to tuberculosis patients and determinants of treatment seeking : delay in diagnosis , health service utilization , and consequence of treatment seeking ; treatment outcomes . Search strategy The review considered both published and unpublished studies in the English language published between January 1990 and December 2010 . Data bases of the Joanna Briggs Institute , PubMed , Popline , Cochrane Library , CINAHL and MedNar were search ed . The search focused on key elements of objectives ( participants , comparator , and outcome ) and a thorough search was undertaken utilizing a st and ardized three step approach . Method ological quality Considered papers were critically appraised by two independent review ers using st and ardized Joanna Briggs Institute tools . Data was extracted using the Joanna Briggs Institute Meta Analysis of Statistical Assessment and Review Instrument data extraction tool . Data was analyzed using Revman 5.1 software from the Cochrane collaboration . Results Nine cross‐sectional , two retrospective and one prospect i ve cohort studies were included in the review . Males were 49 % less likely to have psychological distress than females ( OR=0.51 , 95 % CI=0.32‐0.83 ) . Males were 46 % less likely to perceive health , illness and injuries as a cause of tuberculosis infection than females ( OR=0.54 , 95 % CI=0.31‐0.96 ) . Males were 78 % less likely to use a traditional healer as health service utilization than females ( OR=0.22 , 95 % CI=0.07‐0.66 ) . Males were almost twice more likely to be diagnosed within 30 days in a health institution than females ( OR=1.76 , 95 % CI=1.09‐2.84 ) however , they were 23 % less likely to successfully complete tuberculosis treatment ( OR=0.77 , 95 % CI=0.68‐0.87 ) . Conclusions Gender differences were observed on determinants of help seeking such as distress , perceived causes of tuberculosis infection and stigma components . Determinants of treatment seeking that showed significant gender differences were utilization of health services for diagnosis and treatment , patient delay in seeking health service and treatment outcome of tuberculosis . Implication s for Practice Gender specific strategies for behavioral change should be implemented by health professionals on causes of tuberculosis , early treatment seeking , signs/symptoms , related stigma and adherence of treatment to raise awareness in the community . Practitioners should suspect tuberculosis among women at early stages of their visits to health facilities and screen for tuberculosis . Special efforts should be made by practitioners for male tuberculosis patients to complete the treatment . Implication s for Research Further research with gender perspective should be conducted using behavioral change models on screening of patients and sensitizing communities to uptake of tuberculosis facilities for tuberculosis control BACKGROUND A vaccine to interrupt the transmission of tuberculosis is needed . METHODS We conducted a r and omized , double‐blind , placebo‐controlled , phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya , South Africa , and Zambia . Human immunodeficiency virus (HIV)–negative adults 18 to 50 years of age with latent M. tuberculosis infection ( by interferon‐γ release assay ) were r and omly assigned ( in a 1:1 ratio ) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart . Most participants had previously received the bacille Calmette – Guérin vaccine .  We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease . Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase‐chain‐reaction test , mycobacterial culture , or both . RESULTS We report the primary analysis ( conducted after a mean of 2.3 years of follow‐up ) of the ongoing trial . A total of 1786 participants received M72/AS01E and 1787 received placebo  , and 1623 and 1660 participants in the respective groups were included in the according‐to‐ protocol efficacy cohort . A total of 10 participants in the M72/AS01E group met the primary case definition ( bacteriologically confirmed active pulmonary tuberculosis , with confirmation before treatment ) , as compared with 22 participants in the placebo group ( incidence , 0.3 cases vs. 0.6 cases per 100 person‐years ) . The vaccine efficacy was 54.0 % ( 90 % confidence interval [ CI ] , 13.9 to 75.4 ; 95 % CI , 2.9 to 78.2 ; P=0.04 ) . Results for the total vaccinated efficacy cohort were similar ( vaccine efficacy , 57.0 % ; 90 % CI , 19.9 to 76.9 ; 95 % CI , 9.7 to 79.5 ; P=0.03 ) . There were more unsolicited reports of adverse events in the M72/AS01E group ( 67.4 % ) than in the placebo group ( 45.4 % ) within 30 days after injection , with the difference attributed mainly to injection‐site reactions and influenza‐like symptoms . Serious adverse events , potential immune‐mediated diseases , and deaths occurred with similar frequencies in the two groups . CONCLUSIONS M72/AS01E provided 54.0 % protection for M. tuberculosis – infected adults against active pulmonary tuberculosis disease , without evident safety concerns . ( Funded by GlaxoSmithKline Biologicals and Aeras ; Clinical Trials.gov number , NCT01755598 . 
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We summarised the strength of review level evidence for interventions as " sufficient " , " tentative " , " insufficient " or " no " using a framework based on the consistency of evidence within and between review s. RESULTS We found sufficient review level evidence for direct effects on TB incidence/case prevention of vaccination and treatment of latent TB infection .
We also found sufficient evidence of beneficial indirect effects attributable to drug susceptibility testing and adverse indirect effects ( measured as sub-optimal treatment outcomes ) in relation to use of st and ardised first-line drug regimens for isoniazid-resistant TB and intermittent dosing regimens .
We found insufficient review level evidence for direct or indirect effects of interventions in other areas , including screening , adherence , multidrug-resistant TB , and healthcare-associated infection .