***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 adequacy of exposure of purine analogs as measured by 6-thioguanine nucleotides concentrations in the setting of combination therapy remains poorly understood . The aim of this study was to investigate the relationship between the mean corpuscular volume ( MCV ) value ( as a surrogate marker of 6-thioguanine nucleotides concentration ) and Crohn 's disease outcomes in the setting of combination therapy with infliximab . Methods : The SONIC trial was a r and omized controlled trial comparing infliximab to azathioprine and to infliximab plus azathioprine in 508 Crohn 's disease patients . An increase of at least 7 femtoliter ( fL ) of the MCV ( & Dgr;MCV ) was used for statistical analysis . Results : At week 26 , the mean increase of MCV was similar among patients treated with azathioprine alone ( mean of 7.9 fL ) or in combination with infliximab ( mean of 8.5 fL ) . In the azathioprine group , 63.6 % of patients with & Dgr;MCV > 7 were in steroid-free clinical remission at week 26 as compared with 33.3 % of patients without & Dgr;MCV > 7 ( P = 0.0046 ) . In the combination therapy group , & Dgr;MCV above 7 was associated with mucosal healing ( 75.0 % for & Dgr;MCV > 7 versus 47.1 % for & Dgr;MCV < 7 , P = 0.0172 ) but not with steroid-free clinical remission . Patients with a & Dgr;MCV above 7 were more likely to have  infliximab trough level above 3 & mgr;g/mL at week 30 ( 68.4 % versus 38.8 % for & Dgr;MCV < 7 , P = 0.0032 ) . Conclusions : These results suggest that & Dgr;MCV above 7 ( which is a surrogate for a higher 6-thioguanine nucleotides concentration ) leads to improved Crohn 's disease outcomes , even when combined with infliximab . It also suggests the possibility that a lower azathioprine exposure might be less effective in combination therapy UNLABELLED RATIONALE , AIMS & OBJECTIVE : Tools for the assessment of the quality of research studies tend to be specific to a particular research design ( e.g. r and omized controlled trials , or qualitative interviews ) . This makes it difficult to assess the quality of a body of research that addresses the same or a similar research question but using different approaches . The aim of this paper is to describe the development and preliminary evaluation of a  quality assessment tool that can be applied to a method ologically diverse set of research articles . METHODS The  16-item quality assessment tool ( QATSDD )  was assessed to determine its reliability and validity when used by health services research ers in the disciplines of psychology , sociology and nursing . Qualitative feedback was also gathered from mixed- methods health research ers regarding the comprehension , content , perceived value and usability of the tool . RESULTS Reference to existing widely used quality assessment tools and experts in systematic review confirmed that the components of the tool represented the construct of ' good research technique ' being assessed . Face validity was subsequently established through feedback from a sample of nine health research ers .  Inter-rater reliability was established through substantial agreement between three review ers when applying the tool to a set of three research papers ( κ = 71.5 % ) , and good to substantial agreement between their scores at time 1 and after a 6-week interval at time 2 confirmed test-retest reliability . CONCLUSIONS The QATSDD shows good reliability and validity for use in the quality assessment of a diversity of studies , and may be an extremely useful tool for review ers to st and ardize and increase the rigour of their assessment s in review s of the published papers which include qualitative and quantitative work BACKGROUND & AIMS Genetic polymorphism in thiopurine methyltransferase ( TPMT ) activity may influence clinical responsiveness to azathioprine ( AZA ) therapy . Our aim was to determine if the measurement of erythrocyte TPMT enzyme activity could be used to optimize clinical responsiveness to AZA therapy in patients with inflammatory bowel disease ( IBD ) . METHODS A total of 142 consecutive patients were studied . Forty-one patients ( 32 with Crohn 's disease [ CD ] and 9 with ulcerative colitis [ UC ] ) were enrolled in a 4-month prospect i ve nonr and omized study  with AZA  , and 101 ( 65 with CD and 36 with UC ) were on either maintenance AZA or 6-mercaptopurine ( 6-MP ) .  Erythrocyte TPMT activity and AZA metabolite levels were measured blinded to the clinical response . RESULTS The response rate after 4 months of continuous AZA therapy was 69 % ( 9/13 ) in those patients with below-average ( < /=12 U/mL blood ) TPMT activity , and 29 % ( 8/27 ) in patients with enzyme activity levels > 12 U/mL blood ( P < 0.001 ) . Patients with TPMT activity < /=12 achieved a mean ( SEM ) erythrocyte 6-thioguanine ribonucleotide ( 6-TGn ) level of 394 + /- 29 pmol/8 x 10(8 ) red blood cells ( RBCs ) ; higher than in patients with TPMT activity > 12 ( 218 + /- 28 ) , despite similar mean ( 1.6 mg/kg/day ) dosages of AZA ( P < 0.001 ) . By multivariate logistic regression analysis , patients with a TPMT level < 15.3 U/mL blood were 6.2 times more likely to respond to AZA therapy . A 6-TGn level of > 292 pmol/8 x 10(8 ) RBCs was associated with a positive predictive value of clinical response of 85.7 % . CONCLUSIONS Patients with higher than average TPMT activity ( > 12 ) may remain refractory to conventional dosages of AZA , and may require high ( > 292 ) 6-TGn levels . Prospect i ve , r and omized , controlled trials are needed to determine whether prior TPMT phenotype testing can be used to adjust the dose of AZA effectively to improve clinical response time and rate Background : Metabolite monitoring and response predictors to azathioprine ( AZA ) in pediatric inflammatory bowel disease ( IBD ) are debatable . In an attempt to optimize thiopurine therapy and underst and the mechanism of action of thiopurines , we correlated metabolites and other factors with AZA efficacy in children with IBD . Methods : Data from 86 children with IBD with 440 metabolite measurements were retrospectively analyzed using multilevel logistic regression analyses . A therapeutic response was defined as a pediatric Crohn 's disease activity index ⩽10 for Crohn 's disease or a pediatric ulcerative colitis activity index ⩽10 for ulcerative colitis without any treatment with steroids , antitumor necrosis factor , other immunomodulators , or exclusive enteral nutrition . Results : The 6-thioguanine nucleotide levels > 250 pmol per 8 × 108 red blood cells correlated with a higher response ( odds ratio , 4.14 ; 95 % confidence interval , 1.49–11.46 , P = 0.007 ) , whereas 6-methyl-mercaptopurine and 6-methyl-mercaptopurine:6-thioguanine nucleotide ratio showed no correlation . Other novel response predictors in children with IBD were relative leukopenia ( odds ratio , 14.01 ; 95 % confidence interval , 3.77–52.10 ; P < 0.001 ) and the absence of lymphopenia ( odds ratio , 3.71 ; 95 % confidence interval , 1.26–10.89 ; P = 0.017 ) . Lower thiopurine methyltransferase activity ( P = 0.015 ) , lower platelet count ( P = 0.020 ) , and higher aspartate aminotransferase level ( P = 0.009 ) also predicted therapeutic response . Age , gender , patient adherence , the duration of AZA therapy , IBD type , erythrocyte count , and erythrocyte sedimentation rate did not predict efficacy . The high interindividual variability accounting for 57.7 % of variance in therapeutic response was observed . Conclusions : The significant 6-thioguanine nucleotide level – response relationship may support metabolite monitoring to improve thiopurine efficacy in pediatric IBD . The reported response predictors may be helpful for treatment optimization in AZA-treated children with IBD , but should be proved in prospect i ve studies Abstract Objective : It remains controversial whether 6-thioguanine nucleotide (6-TGN)-based dose adjusting can be beneficial in azathioprine ( AZA ) therapy . This study is design ed to assess the role of 6-TGN concentrations in maintaining clinical remission in Chinese patients with Crohn ’s disease ( CD ) . Material and method : We performed a prospect i ve observational study and collected data of CD patients in the First Affiliated Hospital of Anhui Medical University from June 2013 to April 2014 .  Demographic material , CD activity index , 6-TGN concentration , and laboratory tests were recorded at baseline and at each visit . In addition , 6-TGN was measured when drug adverse effects occurred . All patients achieved maintenance stage were administered a stable AZA dose at least 3 months before enrollment and were followed up at least 12 months . Thiopurine S-methyltransferase ( TPMT ) genotype was measured before AZA treatment . Results : Sixty-nine patients receiving maintenance therapy were analyzed . A positive correlation was found between 6-TGN levels and AZA dose ( r = 0.258 , p = 0.032 ) . The mean 6-TGN concentration was 302.06 ± 115.84 in the remission group vs. 264.94 ± 164.53 pmol/8 × 108 RBC in those with active disease ( t = 0.847 , p = 0.40 ) , and 197.74 ± 66.54 pmol/8 × 108 RBC in patients who relapsed vs. 310.26 ± 122.38 pmol/8 × 108 RBC for those in sustained remission ( t= −2.541 , p = 0.013 ) . In the leukopenia group , the 6-TGN concentration was 469.11 ± 115.53 pmol/8 × 108 RBC vs. 257.31 ± 83.74 pmol/8 × 108 RBC in the non-leukopenia group ( t = 7.622 , p < 0.001 ) . There was a significant negative correlation between leukocyte count and 6-TGN concentration ( r= −0.326 , p = 0.006 ) . Conclusions : 6-TGN measurement is a helpful method of preventing disease relapse and avoiding leukopenia in individual azathioprine maintenance therapy Objectives : There is some uncertainty regarding how to best dose and therapeutically monitor 6-mercaptopurine or azathioprine in patients with inflammatory bowel disease . The purpose of this study was to assess the relation between clinical response , 6-mercaptopurine metabolite levels , relative leukopenia , and drug dose . Methods : 60 patients with inflammatory bowel disease who were on stable doses of 6-mercaptopurine or azathioprine for ≥ 3 months and who had measurements of 6-mercaptopurine metabolite levels were evaluated . Patients were classified as complete responders ( N = 24 ) , partial responders ( N = 7 ) , or non-responders ( N = 29 ) . Results : Drug dose was associated with clinical response when we analyzed adjusted doses based on molecular drug weight ( P = 0.002 ) . 6-Thioguanine levels also were associated with clinical response ( P = 0.003 ) and the maximal difference between responders and non-responders was seen at 6-thioguanine levels greater than 260 pmol/8 × 108 RBC . Relative leukopenia , defined as white blood cell count less than either 5.0 or 4.0 K/ u L , was not associated with clinical response ( P = 0.13 and 0.77 respectively ) . Conclusions :1 . Drug dose and 6-thioguanine levels are related to clinical response in patients with inflammatory bowel disease on 6-mercaptopurine or azathioprine  . 2 . For 6-thioguanine levels , there is a fair amount of overlap , but maximal differentiation between responders and non-responders is seen at levels > 260 pmol/8 × 108 RBC . 3 . Relative leukopenia does not correlate well with clinical response BACKGROUND AND AIM There have been no reports on 6-thioguanine nucleotide ( 6-TGN ) concentrations in Japanese patients with inflammatory bowel disease ( IBD ) undergoing azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) therapy .  The aim of this study was to assess 6 
    Output:
    
Conclusions This study reinforces the link between 6-thioguanine nucleotide levels and clinical remission in inflammatory bowel diseases , also exploring the validity of specific 6-thioguanine nucleotide thresholds to predict clinical outcomes