***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 Chronic immune thrombocytopenia ( ITP ) in children can negatively impact their health‐related quality of life ( HRQoL ) and impose a burden on their parents . This study sought to examine the effect of romiplostim on HRQoL and parental burden in children with primary ITP . Procedure This was a phase 3 , r and omized , double‐blind , placebo‐controlled study . Children aged < 18 years with ITP ≥6 months were r and omly assigned to receive romiplostim or placebo for 24 weeks . The Kids ’ ITP Tool ( KIT ) was used to measure HRQoL and was administered to patients and /or their parents at baseline and weeks 8 , 16 , and 25 . Mean KIT scores at each assessment and mean changes in KIT scores from baseline were calculated overall by treatment group and platelet response status . Psychometric properties of the KIT were evaluated and the minimally important difference ( MID ) was estimated for different KIT versions . Results Sixty‐two patients ( 42 romiplostim and 20 placebo ) were enrolled .  Changes in KIT scores by treatment group showed numerically greater and more often statistically significant improvements from baseline to each assessment for children receiving romiplostim versus placebo . Mixed‐effects analysis demonstrated statistically significantly greater reduction in parental burden from baseline in the romiplostim group versus placebo . Ranges for the MID were estimated as 9–13 points for the Child Self‐Report version and 11–13 points for the Parent Impact version . Conclusions The treatment with romiplostim may be associated with improved HRQoL in children with primary ITP and reduced burden to their parents Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce . To assess a possible influence of eltrombopag we compared platelet function of  eltrombopag-treated immune thrombocytopenia ( ITP ) patients ( group 1 ; n=10 ) after treatment response to that from control ITP patients ( group 2 ; n=12 ) . We further analysed platelet function at baseline and after one , three , and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise . The formation of platelet-monocyte aggregates ( PMA ) , P-selectin expression [ MFI ] , and platelet adhesion under high shear conditions ( surface coverage , SC ) in vivo and after in vitro addition of agonists ( ADP , TRAP-6 , Collagen ) were similar between both groups after response to eltrombopag treatment . Only TRAP-6 induced a lower SC in the eltrombopag group ( p=0.03 ) . All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag .  PMA , naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts . P-selectin expression decreased , when measured without and upon addition of ADP , increased in the presence of TRAP-6 , and remained unchanged after addition of Collagen . SC increased during the eltrombopag-induced platelet rise . All significant changes of platelet function correlated to changes in platelet counts . Two patients developed venous thromboses during eltrombopag treatment , but no association with any distinct single platelet function parameter or combinations thereof was identifiable . Thus , eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND The oral thrombopoietin receptor agonist eltrombopag is approved for treatment of adults with chronic immune thrombocytopenia . In the PETIT trial , we aim ed to investigate the efficacy and safety of eltrombopag in children with persistent or chronic immune thrombocytopenia . METHODS PETIT was a three-part , r and omised , multicentre , placebo-controlled study done at 22 centres in the USA , UK , Canada , Spain , France , and the Netherl and s. Patients aged 1 - 17 years with immune thrombocytopenia lasting for 6 months or longer and platelets less than 30 × 10(9 ) per L who had received at least one previous treatment were enrolled . We enrolled patients into three cohorts consisting of patients aged 12 - 17 , 6 - 11 , and 1 - 5 years . We established patients ' starting doses with an open-label , dose-finding phase with five patients in each cohort . During the dose-finding phase , patients aged 6 - 17 years started eltrombopag at 25 mg once per day ( 12·5 mg for those weighing < 27 kg ) and patients aged 1 - 5 years received 0·7 mg/kg per day to a maximum of 2 mg/kg unless otherwise approved . We permitted dose adjustments on the basis of platelet response up to a maximum dosage of 75 mg per day . Additional patients were then recruited and r and omly assigned ( 2:1 ) to receive either eltrombopag or placebo tablets ( or oral suspension formulation if aged 1 - 5 years ) once per day for 7 weeks at the previously established doses . Starting doses for the double-blind phase were 37·5 mg/day for patients aged 12 - 17 years ; 50 mg/day for patients weighing 27 kg or more ( 25 mg for east Asian patients ) and 25 mg/day for patients weighing less than 27 kg ( 12·5 mg once per day for east Asian patients ) for patients aged 6 - 11 years ; and 1·5 mg/kg once per day ( 0·8 mg/kg once per day for east Asian patients ) for patients aged 1 - 5 years . R and omisation was done by the GlaxoSmithKline Registration /Medication Ordering System and both patients and study personnel were masked to treatment assignments . Patients who completed treatment were then enrolled into an open-label phase and all patients could receive up to 24 weeks of eltrombopag . The primary outcome was the proportion of patients achieving a platelet count of 50 × 10(9 ) per L or more at least once from weeks 1 - 6 ( days 8 to 43 ) of the r and omised phase of the study in the absence of rescue therapy . We assessed efficacy in the intent-to-treat population , which consisted of all patients assigned to treatment , and we assessed safety in all patients who received at least one dose of study treatment . This trial is registered with Clinical Trials.gov , number NCT00908037 . FINDINGS Between Oct 2 , 2009 , and June 22 , 2011 , we recruited 15 patients , with five patients in each age cohort , into the open-label dose-finding phase who did not progress into the double-blind phase . From March 17 , 2010 , to Jan 15 , 2013 , we r and omly assigned 67 patients to treatment , with 45 patients assigned to receive eltrombopag ( 16 children aged 12 - 17 years , 19 aged 6 - 11 years , and ten aged 1 - 5 years ) and 22 to receive placebo ( eight children aged 12 - 17 years , nine aged 6 - 11 years , and five aged 1 - 5 years ) . However , two patients assigned to receive eltrombopag did not receive the study drug and one was lost to follow-up , and one patient assigned to receive placebo was given eltrombopag . From weeks 1 to 6 , 28 ( 62 % ) patients who received eltrombopag , compared with seven ( 32 % ) who received placebo , achieved the primary endpoint of platelet count 50 × 10(9 ) per L or more at least once without rescue ( odds ratio 4·31 , 95 % CI 1·39 - 13·34 , p=0·011 ) . The most common adverse events with eltrombopag were headache ( 13 [ 30 % ] patients receiving eltrombopag vs nine [ 43 % ] patients receiving placebo ) , upper respiratory tract infection ( 11 [ 25 % ] patients vs two [ 10 % ] patients ) , and diarrhoea ( seven [ 16 % ] patients vs one [ 5 % ] patient ) . Grade 3 or 4 adverse events occurred in five ( 11 % ) patients receiving eltrombopag and four ( 19 % ) patients receiving placebo , and serious adverse events ( four [ 9 % ] patients receiving eltrombopag and two ( 10 % ) patients receiving placebo ) were similarly infrequent in both groups . No thrombotic events or malignancies occurred . Increased alanine aminotransferase concentrations caused two ( 3 % ) of 65 patients to discontinue eltrombopag in the open-label phase . INTERPRETATION Our results showed that eltrombopag could be used to increase platelet counts and reduce clinical ly significant bleeding  in children with persistent or chronic immune thrombocytopenia . Prevalence of increased liver laboratory values was similar to that seen in adults . FUNDING GlaxoSmithKline Abstract Objectives : The objective of this study was to obtain utilities , or preference-based quality -of-life values , from the Canadian general public , for potential health states experienced by immune thrombocytopenia ( ITP ) patients receiving either romiplostim ( a new thrombopoietin mimetic agent ) or ‘ watch and rescue ’ therapy .  Utilities are needed to conduct a cost-utility analysis of romiplostim for formulary and reimbursement decisions . Methods : An electronic Time Trade-off ( TTO ) survey was developed and administered to a sample of the general public in Canada , with 12 distinct health states derived from two r and omized clinical trials of romiplostim vs watch and rescue treatment . Two pilot tests assessed interpretability and respondent burden . In the final survey , each subject was administered the TTO for four r and omly-selected health states . Descriptive statistics were computed for utility scores , and differences between health states were evaluated with an analysis of variance model . Results : Eight hundred and twenty-one adults completed the TTO survey . Mean age was 36.4 ( SD = 15 ) years ; 63 % were female .  Mean ( SD ) utility scores ranged from 0.476 ( 0.271 ) for the most severe health state ( significant bleeding ) to 0.633 ( 0.282 ) for the least severe health state depicting successful treatment with romiplostim . Statistical significance was found on the mean difference between the most severe health state and five other health states ( p < 0.05 ) . After adjusting utilities for matching Canadian demographic parameters , no substantial difference was found between original utility scores and adjusted scores . Conclusions : This study provides evidence of the Canadian general public ’s preference for 12 ITP health states pertaining to romiplostim treatment or watch and rescue . This study had a number of limitations , the main ones being the lack of perfect match in demographics between this sample and the Canadian population , as well as the fact that the scenario descriptions were based on both published literature and expert opinion . Despite those limitations , the obtained utility scores may be used in cost-utility models of romiplostim as a treatment for ITP patients in Canada This study aim ed to compare the efficacy and safety of rituximab ( RTX ) plus recombinant human thrombopoietin ( rhTPO ) with RTX alone in patients with immune thrombocytopenia ( ITP ) who had failed to respond to corticosteroids or relapsed . Recruited patients were r and omized at a ratio of 2:1 into 2 groups : the combination group ( RTX + rhTPO , n = 77 ) and the monotherapy group ( RTX , n = 38 ) . Overall response was achieved in 79.2 % of patients in the combination group vs 71.1 % in the monotherapy group ( P = .36 ) , and the complete response ( CR ) rate was 45.4 % in the combination group compared with 23.7 % in the monotherapy group ( P = .026 ) . The combination group had significantly shorter time to response ( TTR ; median and range , 7 and 4 - 28 days ) compared with the monotherapy group ( 28 and 4 - 90 days ) ( P < .01 ) . There was no difference between these 2 groups in terms of the long-term response ( P = .12 ) . Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response . This study is registered at www . clinical trials.gov as # NCT01525836 Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia ( ITP ) .  Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow . This report describes bone marrow findings from  romiplostim-treated rats , a retrospective analysis of reticulin observed in romiplostim ITP clinical trials , and a prospect i ve clinical study of the effects of romiplostim on bone marrow morphology . In rats , romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal . Of 271 ITP patients in romiplostim clinical trials , 10 were reported to have  reticulin deposition ; reticulin grade was increased in 4 of 5 patients with 
    Output:
    
These findings demonstrate that TPO-RAs are an effective and safe second-line treatment option for primary ITP patients