To develop a rapid, robust and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of methylnaltrexone in human plasma.

The plasma samples were pretreated by filtering using solid-phase extraction (SPE) with a weak cation-exchange cartridge. The filtrate samples were separated on an Ultra PFP Propyl column (100 mm×2.1 mm, 5.0 μm) using 20 mmol·L^-1 ammonium acetate (containing 1% formic acid) in water-acetonitrile (15∶85, v/v) as mobile phase and methylnaltrexone-d3 as the internal standard (IS). The flow rate was set at 0.4 mL·min^-1. Methylnaltrexone and IS were ionized with an ESI source and MRM mode was applied and operated in positive ion mode. The detected ions were m/z 356.3→284.2 and m/z 359.3→287.1, respectively.

The linear range of the developed method was 0.1~120 ng·mL^-1, with the lower limit of quantification being 0.1 ng·mL^-1. The intra-day and inter-day precisions of the method were less than 7.2% across three validation runs, and the accuracy ranged 94.5%~100.7%. The extraction method using SPE reached a mean recovery of 81.4% for methylnaltrexone, and the mean normalized matrix effect was 99.1%. This method was successfully applied for the pharmacokinetic study of subcutaneous injection of methylnaltrexone bromide in 12 healthy volunteers.

This LC-MS/MS method is proven sensitive, rapid and reproducible, and meets the regulatory requirements of biological analysis.

To evaluate the analgesic and adverse effects of pregabalin after laparoscopic surgery.

Pubmed, Embase, Cochrane library, China Knowledge Network, Wanfang database and VIP database were searched for randomized controlled trials (RCT) that investigated pregabalin analgesa in adult patients undergoing laparoscopic surgery from inception to October 2019. RevMan 5.3 was used to perform analysis.

Eighteen RCTs with a total of 1169 subjects were included. Pregabalin was associated with a significant reduction in pain scores and opioid consumption at 24 h compared with placebo (MD=-8.34 mm, 95%CI: -11.68~-4.99, P<0.001 and MD=-5.88 mg, 95%CI: -7.66~-4.11, P<0.001). Patients receiving pregabalin had less postoperative nausea and vomiting compared with placebo (RR=0.75, 95%CI: 0.62~0.92, P=0.006). Visual disturbance was more common in pregabalin group compared with placebo group (RR=2.86, 95%CI: 1.33~6.18, P=0.007). There was no significant difference in the incidence of dizziness and sedation between the two groups (RR=1.08, 95%CI: 0.82~1.42, P=0.59; RR=2.41, 95%CI: 0.44~13.17, P=0.31).

Perioperative administration of pregabalin may decrease pain scores, opioid consumption, nausea and vomiting when used in different types of laparoscopic surgery. Single preoperative dose is recommended to reduce the occurrence of visual disturbance.

To quantitatively evaluate the efficacy, safety, and economic characteristics of tofacitinib for the treatment of rheumatoid arthritis (RA) patients by using the method of health technology assessment (HTA) and to provide evidence for medication selection and decision making based on the actual application of tofacitinib in clinical practice.

The HTA reports, systematic reviews/Meta analyses, and pharmacoeconomic researches published before May 31, 2019 were systematically searched. The databases and websites we searched included HTA official websites, English databases (PubMed and the Cochrane Library), and Chinese databases such as China Knowledge Network (CNKI), Wanfang and Weipu.

No HTA reports, but 21 Meta-analyses and 3 economic studies were included in this study. The results show that tofacitinib alone or combined with methotrexate treatment can clearly improve the efficacy of ACR, HAQ scores and other indicators of patients with RA, while the incidence of adverse events such as severe infections did not significantly increase. It can bring higher quality of life to patients with lower cost.

Tofacitinib and biologics are similar in efficacy and safety, and can improve patient medication compliance with a lower cost.

To compare the economics of prefilled syringe vs. injection of propofol medium and long chain fat emulsion, and to evaluate the satisfaction of dispensers.

Adopting simulated field test method, five dispensers used prefilled syringe or injection to prepare propofol medium and long chain fat emulsion in the Pharmacy Intravenous Admixture Services. The time saving was compared, and cost minimization analysis was conducted to evaluate the economics. The satisfaction of dispensers was investigated with a questionnaire survey, and the scores from 1 to 5 stand for being very dissatisfied to very satisfied.

Prefilled syringes shortened the time for preparing a single propofol by at least (40.20±5.15) s, P=0.000 1, and reduced the preparation cost in a single operation by at least (12.18±0.74) RMB, P<0.000 1. The score was (1.8±1.64) points higher in using prefilled syringes for the overall satisfaction (P=0.071), (2.0±1.58) points higher for improving the safety of dispensers (P=0.047), (2.2±1.64) points higher for facilitating the preparations (P=0.040), and (1.4±1.52) points higher for avoiding preparation errors (P=0.11).

It significantly reduced costs and shortened the preparation time to prepare propofol medium and long chain fat emulsion prefilled syringes. Dispensers were more satisfied with prefilled syringes.

This study aims to analyze the cost-utility of the add-on of Dengzhan Shengmai (DZSM) capsule with standard medical therapy and standard medical therapy alone in secondary stroke prevention.

A Markov model was constructed based on the societal perspective and the costs and health unities were simulated for a time horizon of 5 years. The model included 4 health states, included healthy, recurrent stroke-independent (mRS0-2), recurrent stroke-dependent (mRS3-5) and death. Clinical data and utilities for the modelling analysis were obtained from published literatures. Direct costs included medication costs obtained from public database, and costs for hospitalization, post-discharge rehabilitation service, and secondary prevention were sourced from published literatures. 2019 inflation-adjusted costs were calculated using Consumer Price Index (CPI) for medical care. Indirect costs included loss of salary for patients and their families caused by the disease which were derived from China statistical yearbook.

Base-case analysis results showed that the incremental costs of DZSM group (29 284 RMB) over 5 years were higher than the control group (21 551 RMB). The incremental health utilities of DZSM group (3.91 QALYs) over 5 years were also greater than the control group (3.81 QALYs). The incremental costs of the two group were 7 734 RMB, while the incremental utilities were 0.1 QALYs. The incremental cost-utility ratio was 74 479 RMB/QALY, which equals to approximately 1.05 times of GDP per capita and less than 3 times of GDP per capita, indicating that the add-on of DZSM capsule with standard medical therapy were more cost-effective. Sensitivity analyses revealed robust results.

Compared to standard medical therapy alone, the add-on of DZSM capsule has economic advantages in secondary stroke prevention.

This study summarizes the practical experience of remote monitoring in clinical trials, preliminarily discusses the advantages and consideration factors, and provides reference for monitoring and management of clinical trials.

In view of the problem that on-site monitor cannot be conducted on time during the COVID-19, our hospital launched the online remote monitoring system in time relying on the DPAP technology for the use of sponsor and CRO. The application of remote monitoring by September 15, 2020 were counted through the system backstage. The effect of application was objectively evaluated by comparing the defect detection rate per subject found by remote monitoring and on-site monitoring with chi-square. The user experience, advantages and disadvantages of remote monitoring system were investigated through homemade questionnaire and in-depth interview. The method of health economics evaluation was used to estimate the cost of simple on-site monitoring mode, remote monitoring and on-site monitoring combined mode.

The hospital officially launched the remote monitoring system on February 10, 2020. Until September 15, 2020, 176 CRAs from 76 sponsors/CRO have used the remote monitoring system for totally 10 470 times to conduct remote monitoring, involving 228 projects, 1 318 subjects, 16 departments in our hospital. A total of 3 820 findings have been found during the remote monitoring of 228 trials. Compared with the on-site monitoring of the same project in 2019, the remote monitoring achieved the on-site monitoring effect in terms of checking protocol deviation, case report form (CRF), combined drug use and biological samples; however, it is not as good as the on-site monitoring in terms of original records, informed consent, adverse events and experimental drugs, which involves more paper materials. 72.61% of CRAs believed that remote monitoring system effectively supported the completion of monitoring work, and 62.50% of CRAs thought that it reduced the time of on-site monitoring. The in-depth interviews with 16 CRAs showed that remote monitoring had advantages and was highly praised. The cost of the combination of routine on-site monitoring visit, remote monitoring and on-site monitoring was calculated, resulting that on-site monitoring visit frequency was reduced by 16 times, saving 73 600 RMB of travel expenses and 624 hours of travel time. But remote monitoring should be considered and standardized in system verification, subject informed consent monitoring and privacy protection, data security, implementation and other aspects.

The remote monitoring mode made the monitoring free from location and time constraints, timely found the problems in the trials, greatly improved the efficiency of the monitoring, and reduced the risk and cost of clinical trials. In the future, it can be applied and explored in more aspects, but still needs to be further supplemented with data sources and standardized in the aspects of system verification.