***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: The aim of this study was to characterise the pharmacokinetics of the  anticancer agent topotecan  , and explore the influence of patient covariates and interoccasion variability on drug disposition .  Data were obtained from 190 patients who received the drug as a 30-min infusion ( N=72 ) or orally ( N=118 ) . The population model was built with the use of NONMEM to identify c and i date covariates , and obtain models for clearance ( CL ) and volume of distribution . The final models were based on first-order absorption with lag-time ( oral data ) , and a two-compartment model with linear elimination from the central compartment . The Cockcroft – Gault creatinine clearance ( CrCl ) and WHO performance status ( PS ) were the only significant covariates : CL=(12.8 + 2.1 × CrCl ) × ( 1−0.12 × PS ) . For the volume of distribution , a correlation was found between body weight and the central volume (V1)=0.58 × body weight . Based on the structural models , a limited-sampling strategy was developed with minor bias and good precision that can be applied a posteriori using timed sample s obtained at 1.5 , and 6 h after the administration of topotecan . In conclusion , a population pharmacokinetic model for topotecan has been developed that incorporates measures of renal function and PS to predict CL . In combination with drug monitoring , the limited sampling strategy allows individualised treatment for patients receiving oral topotecan Imatinib mesylate ( imatinib ) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia ( CML ) . Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong , patient adherence is critical . The ADAGIO ( Adherence Assessment with Glivec : Indicators and Outcomes ) study aim ed to assess prospect ively over a 90-day period the prevalence of  imatinib nonadherence in patients with CML ; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence ; and to examine whether treatment response is associated with adherence levels . A total of 202 patients were recruited from 34 centers in Belgium , of whom 169 were evaluable . One-third of patients were considered to be nonadherent . Only 14.2 % of patients were perfectly adherent with 100 % of prescribed imatinib taken . On average , patients with suboptimal response had significantly higher mean percentages of imatinib not taken ( 23.2 % , st and ard deviation [ SD ] = 23.8 ) than did those with optimal response ( 7.3 % , SD = 19.3 , P = .005 ; percentages calculated as proportions x 100 ) . Nonadherence is more prevalent than patients , physicians , and family members believe it is , and therefore should be assessed routinely . It is associated with poorer response to imatinib .  Several determinants may serve as alert signals , many of which are clinical ly modifiable Purpose In this prospect i ve multi-centre observational cohort study , we investigated the effect of an intensified multidisciplinary pharmaceutical care programme on the adherence of cancer patients treated with capecitabine , a prodrug of fluorouracil . Patients and methods Twenty-four colorectal and 24 breast cancer patients participated in this study . Patients of the control group ( n = 24 ) received st and ard care , patients of the intervention group ( n = 24 ) received intensified pharmaceutical care consisting of written and spoken information .  Adherence to capecitabine chemotherapy was measured using an  electronic medication event monitoring system ( MEMS ™ ) . Results Patients in the intervention group exhibited an enhanced but not significantly different mean overall adherence compared to the control group ( 97.9 % vs 90.5 % , p = 0.069 ) . Mean daily adherence was significantly higher in the intervention group ( 96.8 % vs 87.2 % , p = 0.029 ) . Variability of both adherence parameters was considerably reduced when pharmaceutical care was provided . At the end of the observation period of 126 days , the probability of still being treated  with capecitabine was found to be 48 % in the control group and 83 % in the intervention group ( p = 0.019 , log-rank test ) . The relative risk for a deviating drug intake interval , i.e. < 10 or > 14 instead of 12 h , in the intervention group was found to be 0.51 ( 95 % CI , 0.46–0.56 ) compared with the control group ( p < 0.05 , Chi-square test ) . Conclusions The provision of intensified pharmaceutical care  can enhance adherence to and prolong treatment with capecitabine . The results underline the importance of multidisciplinary care to assure the effectiveness of oral chemotherapy BACKGROUND The cause of chronic myeloid leukemia ( CML ) is a constitutively active BCR-ABL tyrosine kinase . Imatinib inhibits this kinase , and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase . For 5 years , we followed patients with CML who received imatinib as initial therapy . METHODS We r and omly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine  and then evaluated them for overall and event-free survival ; progression to accelerated-phase CML or blast crisis ; hematologic , cytogenetic , and molecular responses ; and adverse events . RESULTS The median follow-up was 60 months . Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69 % by 12 months and 87 % by 60 months . An estimated 7 % of patients progressed to accelerated-phase CML or blast crisis , and the estimated overall survival of patients who received imatinib as initial therapy was 89 % at 60 months . Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response ( P<0.001 ) . Grade 3 or 4 adverse events diminished over time , and there was no clinical ly significant change in the profile of adverse events . CONCLUSIONS After 5 years of follow-up , continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients . ( Clinical Trials.gov number , NCT00006343 [ Clinical Trials.gov ] . Abstract . Background : The aim of this study was to explore the characteristics and efficacy of psychoeducational family intervention for persons with schizophrenia in rural China . Methods : A cluster r and omised controlled trial of psychoeducational family intervention for families experiencing schizophrenia ( three groups , 326 cases ) was conducted in Xinjin County , Chengdu . Treatment groups consisted of family intervention and medication , medication alone , and a control . Results : The results showed a gain in knowledge , a change in the relatives ' caring attitudes towards the patients , and an increase in treatment compliance in the psychoeducational family intervention group ( p < 0.05 , 0.001 ) . Most importantly , the relapse rate over 9 months in this group ( 16.3 % ) was half that of the drug-only group ( 37.8 % ) , and just over one-quarter of that of the control group ( 61.5 % ) ( p < 0.05 ) . Antipsychotic drug treatment and families ' attitudes towards patients after the 9-month follow-up were significantly associated with clinical outcome ( p < 0.05 ) . Conclusions : In rural China , family intervention should focus on improving the relatives ' recognition of illness , the caring attitude towards the patients , treatment compliance , relapse prevention , and the training of the patients ' social functioning . This trial , one of the largest in the literature , has shown that psychoeducational family intervention is effective and suitable for psychiatric rehabilitation in Chinese rural communities 
    Output:
    
Studies that used both tailored and educational interventions showed significant relationship between adherence and clinical outcomes ; however , the study that used dosage simplification did not .
Interventions to improve adherence with oral chemotherapies in hematological malignancies remain limited .
Though they were heterogeneous in nature , interventions tested in the retained studies suggested a positive impact on the adherence outcome ; some established a significant relationship between adherence and clinical outcomes .