Trends in anti-HER2 drugs consumption and influencing factors.

Background: Human epidermal growth factor receptor 2 (HER2) inhibitors have been approved to treat various cancers with HER2 amplification. The Chinese government has made great efforts to improve the availability and affordability of these drugs. This study aimed to analyze the trends in anti-HER2 drug consumptions in Nanjing from 2012 to 2021, and explore influencing factors. Methods: Data about use of anti-HER2 drugs in 2012-2021 were extracted from Jiangsu Medicine Information Institute. Six types of anti-HER2 drugs were included. Drug consumption was expressed as defined daily doses (DDDs) and expenditure. Time series analysis was adopted to find trends in consumption, while interrupted time series was used in analyzing the impact of policy on consumption. The correlation between DDDs and defined daily cost (DDC) was analyzed by Pearson's correlation test. Results: The DDC, DDDs, and expenditure of anti-HER2 drugs changed little from 2012 to 2016. The DDC decreased intermittently, while the DDDs and expenditure of these drugs grew continuously from 2017 to 2021. The anti-HER2 monoclonal antibodies contributed to the majority of total consumption in 2012-2019. The DDDs of anti-HER2 tyrosine kinase inhibitors surpassed the DDDs of monoclonal antibodies in 2020-2021. Trastuzumab was the predominantly prescribed drug in 2012-2019, but the DDDs of pyrotinib surpassed the DDDs of trastuzumab in 2020-2021. The ln value of DDC or self-paid DDC of trastuzumab was negatively correlated with the ln value of its DDDs. The national health insurance coverage (NHIC) and national drug price negotiation policy about anti-HER2 drugs were initiated in 2017. Low-price generics and biosimilar of trastuzumab came into the market in 2020 and 2021, separately. Interrupted time series analysis showed that the DDDs increased significantly after the implementation of NHIC, price negotiation or generic drug replacement. Conclusion: The consumption of anti-HER2 drugs has significantly increased and their DDC has decreased after the implementation of NHIC, price negotiation, or low-price generic drug replacement since 2017. Further efforts are needed to translate the high consumption into clinical benefits.

Consumption and cost trends of EGFR TKIs: influences of reimbursement and national price negotiation.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used in the treatment of EGFR mutation non-small-cell lung cancer. The Chinese government has made great efforts to improve the availability and affordability of these drugs. The aim of this study was to investigate the trends in the consumption and cost of EGFR TKIs in Nanjing, a developed city in China, and evaluate the influence of health insurance coverage and national price negotiation on drug consumption. METHODS: Data about EGFR TKIs applications in 2010-2019 were extracted from Jiangsu Medicine Information Institute. Five types of EGFR TKIs were included. Consumption was expressed in defined daily doses (DDDs) and expenditure. The correlation between defined daily cost (DDC) and DDDs was analyzed by Pearson's correlation test. RESULTS: The DDC, number of DDDs and expenditure of EGFR TKIs changed little from 2010 to 2015. National price negotiation was initiated as a policy and low-price generic gefitinib came into the market in 2016. Three types of EGFR TKIs moved into the coverage of the national health insurance since 2017. Hence, the DDC decreased, and the number of DDDs increased significantly year by year since 2016. The first generation TKIs always made up of comprised the majority of the total consumption. The predominantly prescribed TKIs were gefitinib and icotinib. DDC was negatively correlated with the number of DDDs. The number of DDDs increased significantly after health insurance enrollment, price negotiation and generic drug replacement. CONCLUSION: The consumption of EGFT TKIs has increased and the DDC of EGFR TKIs has decreased since 2016. These trends may be attributed to drug reimbursement, price negotiation and generic drug replacement. Further efforts are needed to translate the high consumption of EGFR TKIs into clinical benefits.

The impact of policy on availability and price of low-price medicines in public healthcare institutions: A retrospective survey in Nanjing, China.

In an effort to promote rational drug pricing and relieve the pressure of drug shortages, the Chinese government implemented a low-price medicine (LPM) policy in July 2014, and abolished price regulations for most medications in June 2015. This study examines trends in the availability and pricing of LPMs since policy implementation. Data on price and availability of 752 LPMs during 2013-2017 were obtained from the Jiangsu Institute of Medicine Information. Availability was defined as the proportion of facilities in which a medicine was in inventory during each survey period. A price index was constructed based on purchasing prices in 40 public healthcare facilities, using a standard method developed by the International Labour Organization. Mean availability fluctuated slightly but held at low levels (<15%). Levels were conspicuously lower in primary hospitals than in secondary and tertiary hospitals. Our logistic regression model showed that the essential medicine designation was the main factor facilitating availability. The overall price index remained static before implementation of the policy, while there was a marked upward trend after implementation of the policy. Further efforts are needed to improve the pharmaceutical supply system, and simultaneously curb unreasonable inflation in medicine costs.

Evolution of PtCu tripod nanocrystals to dendritic triangular nanocrystals and study of the electrochemical performance to alcohol electrooxidation.

In the field of catalysis, the design and construction of nanomaterials is an efficient way to optimize the catalytic activity of catalysts. This study presents the synthesis of PtCu tripod nanocrystals with branching structures and high purity prepared using a simple hydrothermal method. The dendritic PtCu triangular nanocrystals were successfully synthesized by regulating the amount of I- ions to achieve different degrees of branching on PtCu nanocrystals, and the process was systematically studied and analyzed. Meanwhile, dumbbell nanocrystals of PtCu were successfully synthesized through slight adjustments to synthesis conditions. In electrochemical tests, the obtained dendritic PtCu triangular nanocrystals exhibited prominent electrocatalytic activity and long-term stability for ethylene glycol, methanol, and ethanol oxidation reactions due to the unique nanostructures as well as alloyed virtue, and were much better than commercial Pt/C. In addition, this study provides a general strategy for designing novel branched Pt-based nanomaterials with high electrocatalytic performance.

Impact of the National Health Insurance Coverage Policy on the Utilisation and Accessibility of Innovative Anti-cancer Medicines in China: An Interrupted Time-Series Study.

Objective: The study aimed to evaluate the impact of the National Health Insurance Coverage (NHIC) policy on the utilisation and accessibility of innovative anti-cancer medicines in Nanjing, China. Methods: We used the adjusted World Health Organisation and Health Action International methodology to calculate the price and availability of 15 innovative anti-cancer medicines included in the National Health Insurance drug list in 20 tertiary hospitals and six secondary hospitals in Nanjing before and after NHIC policy implementation. Interrupted time-series regression was used to analyse the changes in the utilisation of the study medicines. Results: The price reduction rates of innovative anti-cancer medicines ranged between 34 and 65%. The mean availability rate was 27.44% before policy implementation and increased to 47.33% after policy implementation. The utilisation of anti-cancer medicines suddenly increased with a slope of 33.19-2,628.39 when the policy was implemented. Moreover, the usage rate of bevacizumab, bortezomib, and apatinib significantly increased (p < 0.001, p = 0.009, and p < 0.001, respectively) after policy implementation. With regard to price reduction and medical insurance reimbursement, the medicines became more affordable after policy implementation (0.06-1.90 times the per capita annual disposable income for urban patients and 0.13-4.46 times the per capita annual disposable income for rural patients). Conclusion: The NHIC policy, which was released by the central government, effectively improved the utilisation and affordability of innovative anti-cancer medicines. However, the availability of innovative anti-cancer medicines in hospitals remained low and the utilisation of innovative anti-cancer medicines was affected by some factors, including the incidence of cancer, limitation of indications within the insurance program, and the rational use of innovative anti-cancer medicines. It is necessary to improve relevant supporting policies to promote the affordability of patients. The government should speed up the process of price negotiation to include more innovative anti-cancer medicines in the medical insurance coverage, consider including both medical examinations and adjuvant chemotherapy in the medical insurance, and increase investment in health care.

Availability, affordability and price components of insulin products in different-level hospital pharmacies: Evidence from two cross-sectional surveys in Nanjing, China.

The essential medicine--insulin cannot be easily accessed and afforded in many countries. To help address this issue, we evaluated the availability, affordability and price of insulin products in Nanjing, eastern China. Two cross-sectional studies were conducted in 2016 and 2018. A total of 56 hospital pharmacies were sampled, using a simplified and adapted World Health Organization/Health Action International (WHO/HAI) methodology. Prices were expressed as Median Price Ratios (MPRs) to Australian Pharmaceutical Benefit Scheme (PBS) prices. In addition, we investigated the price components of seven selected insulin products as a case study before and after the Online Centralized Procurement Policy for Hospital Drugs in May, 2018. Affordability was presented as the number of daily wages of the lowest paid unskilled government worker (LPGW) required to purchase 1000IU of insulin based on the average courses of treatment, approximately 30 days' treatment. The availability of insulin products was very high in secondary hospitals and tertiary hospitals both in 2016 and 2018, but in community hospitals was very low. In 2018, the availability of prandial insulin products showed fluctuation compared to 2016. The availability of pre-mixed human insulin products was over 95% overall, and also very high (80%) in community hospitals in 2018. The prices of insulin products were much lower than PBS prices of Australian in this study, with the MPRs less than 1 (0.32 to 0.71 in 2016 vs. 0.30 to 0.68 in 2018) for all insulin types. But insulin products in Nanjing in 2016 and 2018 were considered unaffordable, because the number of daily wages of the LPGW needed to purchase for the 30 days treatment of insulin products ranged from 2.26 to 8.49 in 2016 and 1.88 to 7.09 in 2018. The manufacturers' selling price contributed the main part (74.15% to 77.70% before and 74.86% to 91.51% after the implementation of the bidding policy) of the price components of target insulin brands. The availability of insulin products was high in secondary hospitals and tertiary hospitals, but lower in community hospitals. However, the affordability in community hospitals was better than other hospitals, but the insulin products were still unaffordable for patients on low incomes. Further improvements of the availability accessibility and affordability of medicines in advancing health insurance policies and lowering drug prices should be put forward.

Availability, cost and affordability of selected antibiotics and antiviral medicines against infectious diseases from 2013 to 2019 in Nanjing, China.

OBJECTIVES: As economic globalisation develops in-depth, infectious diseases that occur in a country or region no longer remains a regional issue. Antibiotics and antiviral medicines are essential medicines for the therapy of infectious diseases. This study aims to evaluate their availability, cost and affordability of AaAMs against infectious diseases in 41 public hospitals from 2013 to 2019 in Nanjing, China. METHODS: Data on the availability and price of 17 antibiotics and 6 antiviral medicines in 41 public hospitals were obtained from the Jiangsu Institute of Medicine Information. We adopted the WHO/Health Action International method to measure the availability, cost and affordability of these medicines. RESULTS: The availability of selected medicines against infectious diseases was relatively low; the median availability of originator brands was near-zero and that of lowest-priced generics during the survey period less than 50%. The total availability of medicines was poor in primary hospitals as compared to secondary and tertiary hospitals. The median daily-defined dose cost of originator brands was expensive (range from 66.11 RMB to 107.83 RMB), whereas that of lowest price generics was fairly acceptable at < 8 RMB. The affordability of most surveyed medicines was reasonable, which showed significant improvement over time, but the daily cost of a few medicines for originator brands exceeded the average daily wage. CONCLUSIONS: In general, the affordability of medicines surveyed was acceptable, while the availability was too low. There should be a great concern for improving the reserve system of anti-infective medicines in healthcare institutions. Policy should focus on improving the availability of generic drugs in hospitals and encouraging preferentially prescribed.

Effects of puerarin on the pharmacokinetics of astragaloside IV in rats and its potential mechanism.

Context: Puerarin and astragaloside IV (AS-IV) are sometimes used together for the treatment of disease in Chinese clinics, however, the drug-drug interaction between puerarin and AS-IV is still unknown.Objective: This study investigates the effects of puerarin on the pharmacokinetics of astragaloside IV in rats and clarifies its main mechanism.Materials and methods: The pharmacokinetic profiles of oral administration of astragaloside IV (20 mg/kg) in Sprague-Dawley rats, with or without pre-treatment of puerarin (100 mg/kg/day for 7 days) were investigated. The effects of puerarin on the transport and metabolic stability of AS-IV were also investigated using Caco-2 cell transwell model and rat liver microsomes.Results: The results showed that puerarin could significantly increase the peak plasma concentration (from 48.58 ± 7.26 to 72.71 ± 0.62 ng/mL), and decrease the oral clearance (from 47.5 ± 8.91 to 27.15 ± 9.27 L/h/kg) of AS-IV. The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of astragaloside IV from 1.89 to 1.26, and the intrinsic clearance rate of astragaloside IV was decreased by the pre-treatment with puerarin (34.8 ± 2.9 vs. 41.5 ± 3.8 µL/min/mg protein).Discussion and conclusions: These results indicated that puerarin could significantly change the pharmacokinetic profiles of astragaloside IV, via increasing the absorption of astragaloside IV or inhibiting the metabolism of astragaloside IV in rats.

Clinical significance of serum levels of microRNA-27a and its correlation with interleukin-10 in patients with multiple organ dysfunction syndrome caused by acute paraquat poisoning.

The aims of the present study were to examine the clinical significance of serum microRNA-27a (miR-27a) levels in patients with multiple organ dysfunction syndrome (MODS) caused by acute paraquat poisoning and to investigate the correlation between miR-27a and interleukin (IL)-10. A total of 82 patients with MODS induced by acute paraquat poisoning and 88 healthy controls were recruited in the present study. Reverse transcription-quantitative PCR was used to measure serum miR-27a expression levels in patients with MODS and the control group. IL-10 serum levels were determined using ELISA. Decreased serum miR-27a level and increased IL-10 expression levels were detected in patients with paraquat poisoning compared with healthy controls (P<0.001). A moderately negative correlation was identified between the serum expression levels of miR-27a and IL-10 (r=-0.5225; P<0.001). miR-27a expression level was found to be associated with blood urea nitrogen, partial pressure of carbon dioxide, arterial blood lactic acid, and the acute physiology and chronic health evaluation II score (APACHE II; P<0.05). The area under the curve for miR-27a was 0.946, with a sensitivity of 86.6% and specificity of 87.5% at a cutoff value of 2.10. The non-survival patient group had lower miR-27a expression levels compared with the survival group (P<0.01). Multivariate Cox regression analyses suggested miR-27a expression level and APACHE II score were independent prognostic factors for 30-day mortality (P<0.01). The present results suggested that serum miR-27a level may be a potential novel diagnostic and prognostic factor for MODS caused by paraquat poisoning. Collectively, miR-27a may be involved in the process of MODS induced by paraquat poisoning by regulating the inflammatory response.

Influence of glycyrrhetinic acid on the pharmacokinetics of warfarin in rats.

1. Combination of different drugs has been widely applied in clinics in China. Both glycyrrhetinic acid (GA) and warfarin possess various pharmacological activities, the co-administration of them is becoming popular. However, the herb-drug interaction between GA and warfarin is still unknown.2. The herb-drug interaction between GA and warfarin in vivo and in vitro was studied, to clarify the effect of GA on the pharmacokinetics of warfarin and its main mechanism.3. The pharmacokinetics of intragastric administered warfarin (0.5 mg/kg) with or without GA pretreatment (100 mg/kg/day, 7 days) were investigated. The rat liver microsomes incubation systems were used to study the effect of GA on the metabolic stability of warfarin and support the in vivo pharmacokinetic data.4. The pharmacokinetic results indicated that co-administration of GA could increase the systemic exposure of warfarin, including area under the curve (48.87 ± 2.89 µg·h·mL-1 without GA versus 58.63 ± 1.90 µg·h·mL-1 with GA), maximum plasma concentration and t1/2. The metabolic stability of warfarin increased from 23.8 ± 5.9 to 41.4 ± 7.1 min with the pretreatment of GA.5. These results indicated that GA could change the pharmacokinetic profile of warfarin. The metabolism of warfarin was slowed down in rat liver and the systemic exposure increased by GA, via inhibiting the activity of CYP3A4.

Consumption trends and prescription patterns of opioids from 2011 to 2016: a survey in a Chinese city.

OBJECTIVE: Opioid consumption in China has been very less and has varied widely since 1995. The representatively high level of consumption in Mainland China has never been reported. Our aim was to describe the consumption trends and prescription patterns of opioids in Nanjing, a highly developed city of Mainland China, and compare the results with selected worldwide regions. METHODS: Application data of opioids in 2011-2016 were extracted from the Jiangsu Medicine Information Institute. Six opioids were included. Consumption was expressed in terms of defined daily doses (DDDs), morphine equivalents (MEs) and expenditure. The correlation between consumption of opioids and gross domestic product (GDP), Human Development Index (HDI) and cancer incidence was analysed by Pearson's correlation test. RESULTS: DDDs, expenditure and MEs of opioids were, respectively, 256.04, $599.24 and 13.07 g in 2011, and increased to 361.27, $1041.79 and 18.09 g in 2016. DDDs in Nanjing were 2.80-fold that in Mainland China, 1.42-fold that in East and South-East Asia, but only equivalent to 8.89% of the worldwide average level. From 2011 to 2016, the consumption had a linear correlation with GDP, HDI and cancer incidence (p<0.05). However, DDDs varied greatly in countries with similar GDP or HDI. Within 45 Asian countries, the GDP only contributed to 10.47% of change in DDDs, while the HDI contributed to 20.32%. Consumption of non-intravenous opioids or strong opioids always comprised majority of the total consumption. The opioids prescribed predominantly were fentanyl, oxycodone and morphine. Fentanyl and oxycodone account for most of the increase in consumption. CONCLUSION: Opioid consumption has increased >40% from 2011 to 2016, with consumption of fentanyl and oxycodone accounting for most of that increase. The consumption in Nanjing was higher than the average Chinese level, but lower than the global average. An increase in pain control services might be needed, but this need should be highly regulated.

SPC25 upregulation increases cancer stem cell properties in non-small cell lung adenocarcinoma cells and independently predicts poor survival.

In this study, we investigated the functional role and prognostic value of spindle pole body component 25 (SPC25) in non-small cell lung cancer (NSCLC). SPC25 expression profile in lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and normal lung tissues was examined by using data from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA). LUAD A549 cells and LUSC H520 cells were used to investigate the influence of SPC25 on cancer stem cell (CSC) properties in terms of the proportion of CD133+ cells, tumorsphere formation and CSC markers, including CD133, ALDH1 and Sox2. Data mining was also performed in the Kaplan-Meier plotter and TCGA-NSCLC to assess the independent prognostic value of SPC25. Results showed SPC25 was significantly upregulated in LUAD and LUSC tissues compared with normal lung tissues. SPC25 overexpression significantly increased the CSC properties and invasion of A549 cells, but not H520 cells. In comparison, SPC25 knockdown impaired the CSC properties and invasion of A549 cells, but not H520 cells. Univariate and multivariate analysis confirmed that high SPC25 expression was an independent prognostic factor for poor overall survival (OS) (HR: 1.622, 95%CI: 1.207-2.178, p = .001) and recurrence-free survival (RFS) (HR: 1.726, 95%CI: 1.242-2.399, p = .001) in LUAD patients. However, no independent prognostic value of SPC25 was observed in LUSC patients even under the best cut-off model. Based on these findings, we infer that SPC25 upregulation can increase CSC properties in LUAD and independently predict poor survival in this histological subtype.