Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

AIMS: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. METHODS: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesize available evidence. A multicentre cross-sectional study was conducted using questionnaires to evaluate patients' perception and willingness concerning individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. RESULTS: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to administration (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), and management of toxicities. Of these, 12 are strong recommendations. CONCLUSIONS: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX administration to health care providers.

Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. METHODS: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. RESULTS: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. CONCLUSIONS: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.

Design, synthesis, and antitumor activity of desmosdumotin C analogues.

Desmosdumotin C (Des C), a natural product isolated from the roots of Desmos dumosus, has shown good antitumor activity. A three dimensional quantitative structure-activity relationship (QSAR) study using the comparative molecular field analysis (CoMFA) method was performed on 32 Des C analogues. Based on the QSAR, 18 new Des C analogues were designed and synthesized. An efficient three-step synthetic strategy toward Des C and its analogues was developed from commercial available 2, 4, 6-trihydroxyacetophenone. All synthesized compounds were evaluated against a panel of human cancer cell lines and showed ED50 values ranging from 1.1 to 25.1 µΜ.

Patient Access to Orphan Drugs Covered by Medical Insurance in China: Real-World Evidence From Patient Survey.

BACKGROUND: After the inclusion of more high-cost orphan drugs in China's National Reimbursement Drugs List, this study investigated issues relating to patient access to the 7 medicines for 4 rare diseases after listing. METHODS: This study collected data from a national survey conducted in China. Three aspects associated with the accessibility of medicines, namely, approachability, availability, and affordability, were analyzed using descriptive statistics. In addition, multilevel logistic regression models were used to investigate the associations between patient characteristics and the accessibility of surveyed orphan drugs. RESULTS: Of the 999 completed responses included in the study, 15% of the patients (n = 150) did not use the medicines because of non-medicine-related issues. Among the 849 patients using the surveyed medications, 64.4% (n = 547) encountered the problem of unavailability, whereas 51.2% (n = 435) reported affordability as an issue, and 49.6% (n = 320) had health expenditure beyond the catastrophic threshold. The data also indicated that Commercial Medical Insurance helped patients to relieve the cost burden on orphan drugs, but the payout of Commercial Medical Insurance failed to influence patients' decisions to continue the treatments. CONCLUSION: Accessibility of orphan drugs has improved in China after their inclusion in the National Reimbursement Drugs List. Nevertheless, the availability and affordability of medicines remained the barriers for patients to access the desired treatments. It is recommended that further policy refinement in conjunction with the collaboration among healthcare stakeholders is required to deliver better care for patients with rare disease.

Willingness to pay per quality-adjusted life year: is one threshold enough for decision-making?: results from a study in patients with chronic prostatitis.

OBJECTIVE: To estimate the willingness to pay (WTP) per quality-adjusted life year (QALY) ratio with the stated preference data and compare the results obtained between chronic prostatitis (CP) patients and general population (GP). METHODS: WTP per QALY was calculated with the subjects' own health-related utility and the WTP value. Two widely used preference-based health-related quality of life instruments, EuroQol (EQ-5D) and Short Form 6D (SF-6D), were used to elicit utility for participants' own health. The monthly WTP values for moving from participants' current health to a perfect health were elicited using closed-ended iterative bidding contingent valuation method. RESULTS: A total of 268 CP patients and 364 participants from GP completed the questionnaire. We obtained 4 WTP/QALY ratios ranging from $4700 to $7400, which is close to the lower bound of local gross domestic product per capita, a threshold proposed by World Health Organization. Nevertheless, these values were lower than other proposed thresholds and published empirical researches on diseases with mortality risk. Furthermore, the WTP/QALY ratios from the GP were significantly lower than those from the CP patients, and different determinants were associated with the within group variation identified by multiple linear regression. CONCLUSIONS: Preference elicitation methods are acceptable and feasible in the socio-cultural context of an Asian environment and the calculation of WTP/QALY ratio produced meaningful answers. The necessity of considering the QALY type or disease-specific QALY in estimating WTP/QALY ratio was highlighted and 1 to 3 times of gross domestic product/capita recommended by World Health Organization could potentially serve as a benchmark for threshold in this Asian context.

Current Development and Practice of Pharmacoeconomic Evaluation Guidelines for Universal Health Coverage in China.

BACKGROUND: China has achieved near-universal health coverage (UHC) for 95 percent of its population (>1.3 billion lives) as a result of healthcare reforms that began in 2009. However, one of many remaining issues in the Chinese healthcare system is the need to better optimize the allocation and use of healthcare resources in order to meet growing healthcare demands. OBJECTIVES: The goals are to highlight the components of the China Guidelines for Pharmacoeconomic Evaluations (CGPE) 2020 Edition and discuss its future development for UHC in China. METHODS: We review the development process of the CGPE 2020 edition, discuss the contemporary practice of the CGPE for UHC in China, describe new opportunities and challenges to the CGPE, and provide suggestions on the future development of the CGPE based on the current state of the healthcare system in China. RESULTS: Pharmacoeconomics provides tools to evaluate the health returns and economic costs of pharmaceutical products in a scientific way for the optimal allocation of healthcare resources. Considering the great potential of pharmacoeconomics in China, demonstrated by its rapid development and recognition as a research field in the past decade, the standardization of pharmacoeconomic evaluations has become particularly important to improve the accuracy of evaluation results used for drug selection, price negotiations and adjustments. CONCLUSION: Suggestions are made for the integration of CGPE into current framework of UHC in China, including standardizing the pharmacoeconomic evaluation process and updating CGPE on topics such as ethics and real-world research. The CGPE 2020 edition offers a standard to improve the quality of pharmacoeconomic evaluation research and enhance the value and efficiency of UHC in China.

Validation and comparison of EuroQol and short form 6D in chronic prostatitis patients.

OBJECTIVE: Generic, preference-based health-related quality of life (HRQoL) instruments is increasingly used in health-care decision-making process. However, to our knowledge, no such HRQoL instrument has been validated or used in chronic prostatitis. We therefore aimed to assess and compare the psychometric properties of EuroQol (EQ-5D) and Short Form 6D (SF-6D) among chronic prostatitis patients in China. METHODS: Consenting patients were interviewed using EQ-5D and SF-6D. Convergent and discriminative construct validities were examined with five and two a priori hypotheses, respectively. Sensitivity was compared using receiver operating characteristic (ROC) curves and relative efficiency (RE) statistics. Agreement between instruments was assessed with intra-class correlation coefficients and Bland-Altman plot, while factors affecting utility difference were explored with multiple liner regression models. RESULTS: In 268 subjects, mean (SD) EQ-5D and SF-6D utility scores were comparable at 0.73 (0.15) and 0.75 (0.10), respectively. Five of the seven hypotheses for construct validity were fulfilled in both instruments. The areas under ROC of them all exceeded 0.5 (P < 0.001). SF-6D had 9.7-19.9% higher efficiency than EQ-5D at detecting the difference in chronic prostatitis symptom severity. Despite no significant difference in utility scores between two instruments, lack of agreement was observed with low intraclass correlation coefficient (0.218-0.630) and Bland-Altman plot analysis. Chronic prostatitis symptom severity significantly (P < 0.05) influenced differences in utility scores between EQ-5D and SF-6D. CONCLUSIONS: Both EQ-5D and SF-6D are demonstrated to be valid and sensitive HRQoL measures in Chinese chronic prostatitis patients, with SF-6D showing better HRQoL dimension coverage, greater sensitivity, lower ceiling effect, and more rational distribution. Further research is needed to determine longitudinal response and reliability.

Health-related quality of life in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE: To examine the health-related quality of life (HRQoL) and factors associated with HRQoL in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using two generic preference-based HRQoL instruments, EQ-5D (plus EQ-VAS) and SF-6D, with the results compared with general population. METHOD: CP/CPPS patients were recruited from two tertiary referral hospitals, and the general populations were randomly approached. After informed consent, subjects were interviewed using EQ-5D, EQ-VAS and SF-6D, and their socio-demographic and medical information was solicited. RESULTS: Compared to the general population (n = 364), CP/CPPS patients (n = 268) reported significantly worse HRQoL with median score of the EQ-5D utility index (0.73 vs. 0.85), SF-6D utility index (0.76 vs. 0.81), and EQ-VAS (70.0 vs. 85.0). Multiple linear regression analyses showed pain symptom had the strongest predictive power for HRQoL, compared to symptom duration and urinary symptom. Socio-demographic factors and comorbidities did not significantly contribute to poorer HRQoL. CONCLUSION: CP/CPPS patients experienced deteriorated HRQoL with lower health-related utility scores compared to general population, and pain severity was the main physical symptom predicting decreased health-related utility. Further studies are needed to provide the reference utility index for the comparison and better characterizing the influence of geographic and cultural factors on variation of health-related utility of CP/CPPS patients.

The Burden of Hypoglycemia in Patients With Insulin-Treated Diabetes Mellitus in China: Analysis of Electronic Medical Records From 4 Tertiary Hospitals.

BACKGROUND: Hypoglycemia is a common acute complication in patients with diabetes and markedly impacts on medical resource use. OBJECTIVES: To make an initial assessment of the incidence of hypoglycemia and the associated utilization of medical resources and medical costs in insulin-treated patients with diabetes using medical records from 4 tertiary hospitals in China. METHODS: A retrospective cohort study was conducted using electronic medical records from 4 tertiary hospitals in Beijing, Henan, and Guangzhou from 2012 to 2015. The targeted patients were those diagnosed with either type 1 or type 2 diabetes and treated with insulin. Diabetes was identified with International Classification of Diseases, Tenth Revision diagnosis codes. Hypoglycemia was identified based on glycemic value and the description of diagnosis. The incidence of hypoglycemia, medical resource utilization, and medical costs were analyzed. One-to-one propensity score matching was used to match age, sex, type of diabetes, and complications to patients with and without hypoglycemia and patients with severe and non-severe hypoglycemia, to compare their medical resource utilization and medical costs. RESULTS: A total of 14 044 patients (95.3% had type 2 diabetes and 93.7% with complications) were treated with insulin. There were 1930 patients who had outpatient visits and 310 patients who had inpatient visits owing to hypoglycemia. Incidences of hypoglycemia were 111.3 events per 100 patient-years for outpatient visits and 5.9 events per 100 patient-years for inpatient visits. Patients with hypoglycemia had more outpatient visits (8.09 vs 6.22 times/year, P < .05) and higher annual medical costs ($2147.4 vs $1426.8/person, P < .05) compared with patients without hypoglycemia. Among patients with hypoglycemia, those with severe hypoglycemia had more inpatient visits (2.06 vs 1.13 times/year, P < .05) and higher annual inpatient medical costs ($6204.0 vs $2017.9/person, P < .05) compared with patients with non-severe hypoglycemia. CONCLUSION: The burden of hypoglycemia, especially severe hypoglycemia, is substantial and associated with increased use of medical resources and expenditures among the target population, which serves as a vital first glance at patients with insulin-treated diabetes in China overall.

[Study for drug-resistance of epithelial ovarian cancer by serum protein profiling].

OBJECTIVE: To develop the rationales for ovarian cancer-specific protein profiles in serum and to analyze the protein profiles of multidrug resistance P-glucoprotein (MDR1) and multidrug resistance-associated protein (MRP) positive and negative expression sets for a rapid and sensitive serum protein pattern. METHOD: Serum protein profiles from 36 epithelial ovarian cancer cases were compared with 30 healthy controls using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (DELDI-TOF-MS). Blinded test was conducted subsequently for identification of the protein pattern. Expression of MDR and MRP were detected in set of training cases by immunohistochemistry. The spectra were analyzed statistically between positive and negative groups. RESULTS: Twenty-nine peaks were significantly different between ovarian cancer and healthy controls (P < 0.01, 15 peaks up-regulated and 14 down-regulated). A set of three peaks, at 5 486, 6 463 and 8 575 m/z respectively, were selected from 29 sense peaks as an ovarian cancer biomarker. The sensitivity was 100% and specificity 93.33%. Identification by blinded validation indicated a positive predictive value of 90%. MDR1 expression in ovarian cancer was 69.4 %. Twenty peaks were significantly different between positive and negative sets (P < 0.01). MRP expression in ovarian cancer was 63.8%. But one peak was detected (P < 0.01). CONCLUSION: It was an ideal pattern for employing the SELDI mass spectrum approach to diagnose ovarian cancer and select the multidrug resistance cases. Serum biomarkers for detecting drug resistance in ovarian cancer can be established on the basis of MDR1 immunohistochemistry.

Anti-nociceptive activity of aqueous fraction from the MeOH extracts of Paederia scandens in mice.

AIM OF THE STUDY: We examined the effects of the aqueous fraction (AF) on nociception models mice induced by the chemical and the thermal stimuli so as to elucidate the analgesic activity and provide scientific basis for the clinical use of Paederia scandens. MATERIALS AND METHODS: The AF of MeOH extract from P. scandens was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception. RESULTS: Given orally, the aqueous fraction at doses of 200, 400 and 800 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin injections and on thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at dose of 800 mg/kg of this fraction. In the pentobarbital sodium -induced sleeping time test and the open-field test, the aqueous fraction neither significantly enhanced the pentobarbital sodium -induced sleeping time nor impaired the motor performance, indicating that the observed anti-nociception was unlikely due to sedation or motor abnormality. CONCLUSIONS: These results suggested that the aqueous fraction produced anti-nociception possibly related to the iridoid glycosides and polysaccharides in this fraction.

Recent Pricing Negotiations on Innovative Medicines Pilot in China: Experiences, Implications, and Suggestions.

The China National Formulary (CNF) for reimbursable drug use, also known as the National Reimbursement Drug List (NRDL), was formally established in 2000, revised in 2004 and 2009, and covers 52% of China's population under the government urban health insurance programs. A third major and long-awaited update to the formulary was completed in February 2017 based on intensive reviews by a group of experts in medicine, pharmacology, health economics, and health policy. Shortly after this major update, a pilot project at the central government level was implemented for negotiations mainly on innovative but expensive medicines that were still outside the National Formulary. The pilot, conducted between March and July 2017, eventually reached an overall agreement rate of 81.8% regarding approved indications and drug prices between China's government and the pharmaceutical companies. This pilot showcased numerous leading edge features including a working definition of innovative medicines and opportunities to submit dossiers on drug clinical and economic information. This pilot covered 44 medications for negotiations in a breakthrough attempt to increase the appropriate access to innovative but expensive medicines. The implications to the future of the CNF go beyond the drugs included in the pilot. This paper describes the background of the CNF and the negotiation pilot. In addition, authors of this paper make six recommendations critical to CNF future developments, including enhancing criteria and process for evaluations, standardizing the dossier format, specifying data requirements, refining pricing calculation, and cultivating evaluation professional development.

Cost-effectiveness of de-escalation from micafungin versus escalation from fluconazole for invasive candidiasis in China.

AIMS: Guidelines on treating invasive candidiasis recommend initial treatment with a broad-spectrum echinocandin (e.g. micafungin), then switching to fluconazole if isolates prove sensitive (de-escalation strategy). This study aimed to evaluate the cost-effectiveness of de-escalation from micafungin vs escalation from fluconazole from a Chinese public payers perspective. MATERIALS AND METHODS: Cost-effectiveness was estimated using a decision analytic model, in which patients begin treatment with fluconazole 400 mg/day (escalation) or micafungin 100 mg/day (de-escalation). From Day 3, when susceptibility results are available, patients are treated with either fluconazole (if isolates are fluconazole-sensitive/dose-dependent) or micafungin (if isolates are resistant). The total duration of (appropriate) treatment is 14 days. Model inputs are early (Day 3) and end-of-treatment mortality rates, treatment success rates, and health resource utilization. Model outputs are costs of health resource utilization over 42 days, incremental cost per life-year, and incremental cost per quality-adjusted life-year (QALY) over a lifetime horizon. RESULTS: In the base-case analysis, the de-escalation strategy was associated with longer survival and higher treatment success rates compared with escalation, at a lower overall cost (-¥1,154; -175 United States Dollars). Life-years and QALYs were also better with de-escalation. Thus, this strategy dominated the escalation strategy for all outcomes. In a probabilistic sensitivity analysis, 99% of 10,000 simulations were below the very cost-effective threshold (1 × gross domestic product). LIMITATIONS: The main limitation of the study was the lack of real-world input data for clinical outcomes on treatment with micafungin in China; data from other countries were included in the model. CONCLUSION: A de-escalation strategy is cost-saving from the Chinese public health payer perspective compared with escalation. It improves outcomes and reduces costs to the health system by reducing hospitalization, due to an increase in the proportion of patients receiving appropriate treatment.

Antitumor agents 259. Design, syntheses, and structure-activity relationship study of desmosdumotin C analogs.

Desmosdumotin C (1) and its analogs previously showed potent, selective in vitro anticancer activity. To explore structure-activity relationships of 1 and further increase potency and selectivity, 15 novel analogs (7-15 and 21-26) were synthesized and evaluated for cytotoxity against several human tumor cell lines, as well as inhibition of human endothelial (HUVEC) replication. 4-Bromo-3',3',5'-tripropyl analog 26 showed significant cytotoxity against A549, A431, 1A9, and HCT-8 with ED50 values of 1.0, 1.2, 0.9, and 1.3 mug/mL, respectively. Compound 26 also strongly inhibited the growth of matched tumor cells, KB-VIN and its parent cell KB. Furthermore, analogs 13 and 21 were over 5-fold more potent against KB-VIN than KB. Bromination of ring-B and tripropyl functionalization of ring-A enhanced activity, while alkylation of ring-B promoted KB-VIN/KB selectivity. 2-Furyl analog 16 showed selective activity against HUVEC, suggesting that it may have potential as a new prototype for angiogenesis inhibition.

[Progress in study of flavonoids from Annonaceae and biological activities of these compounds].

More than 50 new flavonoids derived from Annonaceae are reported in the last two decades. Many genuses in Annonaceae contain flavonoids having structural novelty and broad pharmacological activities. Due to the pharmacological interest of some of these compounds, chemical investigations on this topic have grown considerably in the decades. Here the biological activities of some of these flavonoids are also briefly discussed.

Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis.

BACKGROUND: Influenza is a common viral respiratory infection that causes epidemics and pandemics in the human population. Oseltamivir is a neuraminidase inhibitor-a new class of antiviral therapy for influenza. Although its efficacy and safety have been established, there is uncertainty regarding whether influenza-like illness (ILI) in children is best managed by oseltamivir at the onset of illness, and its cost-effectiveness in children has not been studied in China. OBJECTIVE: To evaluate the cost-effectiveness of post rapid influenza diagnostic test (RIDT) treatment with oseltamivir and empiric treatment with oseltamivir comparing with no antiviral therapy against influenza for children with ILI. METHODS: We developed a decision-analytic model based on previously published evidence to simulate and evaluate 1-year potential clinical and economic outcomes associated with three managing strategies for children presenting with symptoms of influenza. Model inputs were derived from literature and expert opinion of clinical practice and research in China. Outcome measures included costs and quality-adjusted life year (QALY). All the interventions were compared with incremental cost-effectiveness ratios (ICER). RESULTS: In base case analysis, empiric treatment with oseltamivir consistently produced the greatest gains in QALY. When compared with no antiviral therapy, the empiric treatment with oseltamivir strategy is very cost effective with an ICER of RMB 4,438. When compared with the post RIDT treatment with oseltamivir, the empiric treatment with oseltamivir strategy is dominant. Probabilistic sensitivity analysis projected that there is a 100% probability that empiric oseltamivir treatment would be considered as a very cost-effective strategy compared to the no antiviral therapy, according to the WHO recommendations for cost-effectiveness thresholds. The same was concluded with 99% probability for empiric oseltamivir treatment being a very cost-effective strategy compared to the post RIDT treatment with oseltamivir. CONCLUSION: In the Chinese setting of current health system, our modelling based simulation analysis suggests that empiric treatment with oseltamivir to be a cost-saving and very cost-effective strategy in managing children with ILI.

Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564 analogues based on betulinic acid.

The betulinic acid derivative IC9564 inhibits human immunodeficiency virus (HIV)-1 entry. Among a series of IC9564 derivatives, 5 and 20 were the most promising compounds against HIV infection with EC(50) values of 0.33 and 0.46 microM, respectively. Both compounds inhibited syncytium formation with EC(50) values of 0.40 and 0.33 microM, respectively. The comparable EC(50) values in the two assays suggested that these compounds are fusion inhibitors. The structure-activity relationship data also indicated that a double bond in IC9564 can be eliminated and the statine moiety can be replaced with L-leucine while retaining anti-HIV activity.

[Studies on the chemical constituents from marine brown alga Ishige okamurai (3)].

OBJECTIVE: To study the chemical constituents of Ishige okamurai. METHOD: Compounds were isolated by Pyricularia oryzae bioassay-guided fractionation method in combination with extraction and partitionation as well as multi-chromatography. Their structures were determined by spectral analysis and chemical evidence. RESULT: Seven compounds were obtained and identified as (2S)-1-O-palmitoyl-2-O-(11Z-octadecenoyl)-3-O-beta-D-galacto-pyranosyl glycerol (I), (2S)-1-O-palmitoyl-2-O-myristoyl-3-O-(6-sulfo-alpha-D- quinovopyranosyl) glycerol (II), (2S)-1-O-palmitoyl-2-O-palmitoyl-3-O-(6'-sulfo-alpha-D- quinovopyranosyl) glycerol (III) and (2S)-1-O-palmitoyl-2-O-(11Z-octadecenoyl)-3-O-(6'-sulfo-alpha-D- quinovopyranosyl) glycerol (IV), stearic acid (V), methyl myristate(VI) and palmitic acid (VII). CONCLUSION: Compounds I-VI were isolated from the alga for the first time while I, II and IV are new natural products. I-IV showed activity causing morphological abnormality of P. oryzae mycelia.

Pharmaceutical pricing: an empirical study of market competition in Chinese hospitals.

BACKGROUND: High pharmaceutical prices and over-prescribing of high-priced pharmaceuticals in Chinese hospitals has long been criticized. Although policy makers have tried to address these issues, they have not yet found an effective balance between government regulation and market forces. OBJECTIVE: Our objective was to explore the impact of market competition on pharmaceutical pricing under Chinese government regulation. METHODS: Data from 11 public tertiary hospitals in three cities in China from 2002 to 2005 were used to explore the effect of generic and therapeutic competition on prices of antibiotics and cardiovascular products. A quasi-hedonic regression model was employed to estimate the impact of competition. The inputs to our model were specific attributes of the products and manufacturers, with the exception of competition variables. RESULTS: Our results suggest that pharmaceutical prices are inversely related to the number of generic and therapeutic competitors, but positively related to the number of therapeutic classes. In addition, the product prices of leading local manufacturers are not only significantly lower than those of global manufacturers, but are also lower than their non-leading counterparts when other product attributes are controlled for. CONCLUSION: Under the highly price-regulated market in China, competition from generic and therapeutic competitors did decrease pharmaceutical prices. Further research is needed to explore whether this competition increases consumer welfare in China's healthcare setting.