Rare tumors: a blue ocean of investigation / 医学前沿

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

Effectiveness analysis of the clinical research coordinators management carried out by drug clinical trial institutions / 中华医学科研管理杂志

Objective:To analyze the problems existing in the management mode of clinical research coordinator (CRC) in the new context, propose improvement measures and analyze the effectiveness of improvement.Methods:Four types of stakeholders related to CRC, including investigators, clinical research associates(CRA), institutional managers and human subjects were investigated in regular monthly questionnaire survey on the basis of CRC management comparasionat home and abroad. The new CRC management countermeasures implemented by our institution in July 2020 were taken as the time node, and the data from January to June 2020 were taken as the pre-implementation group, and the data from July to December 2020 were taken as the post-implementation group. Compare the monthly scores of CRCs′ work effect for 30 projects in the institution before and after the implementation of such countermeasures.Results:The scores of CRCs′ working effectiveness were improved after the implementation of CRC management countermeasures, whcih including standardizing the entry of CRC, updating of the training and assessment mechanisms, conducting regular communication meetings and developing reward and punishment measures. The scores from investigators increased by 20.17%, scores from CRAs increased by 11.54%, scores from institutional managers increased by 14.26%, scores from subjects increased by 10.64%, and the total scores increased by 14.13%( P<0.01). Conclusions:Countermeasures to optimize CRC management taken by drug clinical trial institutions can significantly improve CRCs′ working effectiveness in multiple dimensions.

Establishment and effectiveness evaluation of clinical pharmacist diabetes chronic disease management model / 药学实践杂志

Objective To evaluate the role of clinical pharmacists on the pharmacological monitoring and management of diabetic patients. Methods 406 adult outpatients with diabetes in outpatient were selected as research object. The patients were given the questionnaire and intervened with diabetes education and management by the clinical pharmacist regularly. The patient’s knowledge of the diabetes medication before and after intervention, blood glucose and glycosylated hemoglobin values, treatment compliance, non-reserved outpatient visit, emergency, hospitalization, etc. were compared and statistically analyzed. Results After pharmacy intervention, the patients' knowledge of diabetes and drug-related information, treatment compliance, blood glucose and glycosylated hemoglobin were better than before intervention, P<0.01. Non-reserved outpatient visits and emergency cases were better than before intervention, P<0.05. There are significant differences. Conclusion Clinical pharmacists carry out diabetes chronic disease management and build a clinical pharmacist-led chronic disease management model, which helps to promote standardized treatment, improve patient compliance, promote rationalized medication, achieve the goal of controlling blood sugar and reduce complications.

Evaluation of the practicability of limited sampling strategies for the estimation of mycophenolic acid exposure in Chinese adult renal recipients.

The immunosuppressive potential of mycophenolic acid (MPA) correlates well with MPA exposure [area under the concentration-time curve (AUC)]. Monitoring MPA AUC is important and helpful for maintaining the efficacy of mycophenolate mofetil while minimizing its side effects, but full MPA AUC monitoring is laborious, cost prohibitive, and impractical. Limited sampling strategies have been proposed as an alternative method for estimating MPA exposure. The objective of this study was to evaluate the practicability of different limited sampling strategies for the estimation of MPA exposure. A total of 56 pharmacokinetic profiles from 53 adult renal recipients were used to evaluate the practicability of 10 published models. Standard correlation and linear regression analysis were used to compare the estimated MPA AUCs and corresponding full MPA AUCs, and the percentage of profiles for which prediction error fell within +/-20% was also used to assess the practicability of these models. Agreement between the estimated MPA AUCs and full MPA AUCs was further tested by Bland and Altman analysis. The model, based on four sampling time points, used the formula AUC = 12.61 + 0.37 x C0.5 + 0.49 x C1 + 3.22 x C4 + 8.17 x C10, was superior to all other evaluated models, with the highest coefficient of determination (r = 0.88), a low percentage prediction error (2.79%), and good agreement according to Bland and Altman analysis. Prediction errors of 87.5% (49/56) of profiles were within 20%, which was the highest of all the models. This algorithm can be reliably used for estimating MPA exposure in adult renal transplant patients treated with cyclosporine as concomitant immunosuppressant. Another model based on the formula AUC = 8.22 + 3.16 x C0 + 0.99 x C1 + 1.33 x C2 + 4.18 x C4 also has acceptable predictive performance, and it may also be practical, especially in outpatient settings, in view of its distribution of time points.

Limited sampling strategy for the estimation of mycophenolic acid area under the plasma concentration-time curve in adult patients undergoing liver transplant.

Mycophenolate mofetil (MMF), the oral prodrug of mycophenolic acid (MPA), is increasingly used in liver transplantation and plays a central role in the immunosuppressive regimen in liver transplantation. To study pharmacokinetic-pharmacodynamic relationships and therapeutic drug monitoring of MPA in the clinical setting, limited sampling strategies have been investigated for the estimation of MPA areas under the curves (AUCs). Thirty-eight adult patients undergoing liver transplant (31 males, seven females) receiving 1.0 g MMF twice daily and concomitant tacrolimus provided a total of 72 pharmacokinetic profiles. Multiple stepwise regression analysis was used to determine the algorithms for limited sampling strategies. Twenty-eight one-, two-, three-, and four-sampling estimation models were fitted (r = 0.288-0.964) to all the profiles using linear regression and were used to estimate MPA AUC0-12h comparing those estimates with the corresponding AUC0-12h values calculated with the linear trapezoidal rule, including all 10 timed MPA concentrations. The four-point estimates at C1h, C2h, C6h, and C8h resulted in the best correlation between estimated AUC and true AUC when using the formula AUC = 6.03 + 0.89C1h + 1.94C2h + 2.24C6h + 4.64 C8h (r = 0.911). Bland and Altman analysis revealed good agreement between estimated AUC and AUC from the full profile. This limited sampling strategy provides an effective approach for estimation of full MPA AUC0-12h in patients undergoing liver transplant receiving concomitant tacrolimus therapy.

Investigation on pharmacokinetics of mycophenolic acid in Chinese adult renal transplant patients.

AIMS: To characterize the pharmacokinetics of mycophenolic acid (MPA) in Chinese renal transplant patients. METHODS: Thirty-one renal transplant patients (17 male, 14 female) receiving mycophenolate mofetil (MMF) 1.0 g twice daily were included in this study. A pharmacokinetic study was performed during an interval in dosing after steady state had been reached within 2 months after transplantation. The plasma MPA concentration were measured by high-performance liquid chromatography (HPLC) at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software. SAS software was used for statistical analysis. Multiple linear regression analysis was used to determine limited sampling approaches. RESULTS: The mean peak plasma concentration (C(max)) and area under the concentration-time curve (AUC(0-12)) were 19.67 +/- 8.21 microg ml(-1) and 52.16 +/- 12.50 microg h ml(-1), but there was large variability in these pharmacokinetic parameters. Regression analysis between each plasma concentration and AUC for the limited sampling strategy of MMF therapeutic drug monitoring demonstrated that each of the concentrations at 0.5, 1, 4 and 10 h was positively correlated with AUC (r = 0.60, P = 0.0004; r = 0.60, P = 0.0003; r = 0.61, P = 0.0003; r = 0.64, P = 0.0001, respectively). The combined use of these four samples explained over 90% of the variance in the total (nine-point) AUC(0-12). A formula was obtained for the assessment of MPA AUC based on four samples: MPA AUC = 12.61 + 0.37 x C(0.5) + 0.49 x C(1) + 3.22 x C(4) + 8.17 x C(10). CONCLUSIONS: Chinese renal transplant patients had higher median AUCs than caucasians and African-Americans. As in other studies, there was large interindividual variability. A limited four-point AUC was in good agreement with the 12-h AUC and provided the basis of a predictive formula.

Content Determination of Itraconazole and Its Metabolit Hydroxy-itraconazole in Rabbit Plasma by HPLC-Fluorometric Methods / 中国药房

OBJECTIVE: To establish a high-performance liquid chromatographic(HPLC)-fluorometric method for the concentration determination of itraconazole (ITZ) and its metabolite hydroxy-itraconazole(HITZ) in rabbit plasma simultaneously.METHODS: Separation was achieved with Agilent Eclipse C18,the mobile phase consisted of acetonitrile(adjusted to pH=2.5 with 85% phosphoric acid)-water(63∶37),and the flow rate was 1.0 mL?min-1.The excitation and emission wavelengths were 260 nm and 365 nm.The analysis was performed at room temperature..RESULTS: The linear concentration range of ITZ and HITZ were 7.4～296 0 ng?mL-1(r=0.999 1)and 5.4～216 0 ng?mL-1(r=0.999 3), respectively.The limit of detection was 0.518 and 0.318 ng?mL-1,respectively.The extraction and method recovery rate of ITZ and HITZ were more than 80%.The intra-day and inter-day RSD of ITZ and HITZ were less than 4.47%. CONCLUSIONS: The method is simple,sensitive,accurate and reliable for monitoring ITZ and HITZ in rabbit plasma and pharmacokinetic studies.