Treatment of non-small cell lung cancer with Yiqi Buxue prescriptions combined with adjuvant chemotherapy on the cancer therapy-related cardiovascular toxicity: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The treatment and prognosis of patients with non-small cell lung cancer (NSCLC) was affected by the occurrence of cancer therapy-related cardiovascular toxicity (CTR-CVT). Yiqi Buxue prescriptions were a class of traditional single or compounded formulations that have become a consensus for NSCLC. There was no clear information and or summary available for Yiqi Buxue prescriptions combined with adjuvant chemotherapy for NSCLC in reducing CTR-CVT. AIM OF THE STUDY: To systematically evaluate the Yiqi Buxue prescriptions combined with adjuvant chemotherapy in reducing CTR-CVT for patients with NSCLC. MATERIALS AND METHODS: Search strategies were developed to identify relevant randomized controlled trials (RCTs) in PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure (CNKI), SinoMed and WanFang Data from database inception date to October 2022. The methodological quality of evidence was assessed using the Cochrane risk of bias (ROBs) assessment tool, and the meta-analysis was analyzed using RevMan 5.3. RESULTS: A total of 9 studies were included. Compared with the adjuvant chemotherapy group, Yiqi Buxue prescriptions combined with adjuvant chemotherapy group showed no statistically significant in reducing CTR-CVT (RR 0.67, 95%CI 0.11 to 3.93, P = 0.65) and in CD4+/CD8+(MR 0.32, 95%CI -0.13 to 0.77, P = 0.16). However, it significantly improved the objective response rate (ORR) (RR 1.57, 95%CI 1.32 to 1.87, P < 0.00001), disease control rate (DCR) (RR 1.25, 95%CI 1.15 to 1.35, P < 0.00001), Karnofsky performance status (KPS) improvement rate (RR 1.34, 95%CI 1.16 to 1.55, P < 0.0001), CD3+ (MR 4.17, 95%CI 3.68 to 4.66, P < 0.00001), CD4+ (MR 4.87, 95%CI 4.28 to 5.46, P < 0.00001), and CD8+ (MR 3.12, 95%CI 2.57 to 3.67, P < 0.00001). CONCLUSIONS: The current RCTs are hampered by small sample sizes and poor methodological quality. More rigorously designed and large sample RCTs with primary outcome of CTR-CVT are needed to investigate the effectiveness of Yiqi Buxue prescriptions combined with adjuvant chemotherapy in reducing CTR-CVT for patients with NSCLC.

Corrigendum: Therapy by physician-pharmacist combination and economic returns for cancer pain management in China: a cost-effectiveness analysis.

[This corrects the article DOI: 10.3389/fphar.2023.1073939.].

Therapy by physician-pharmacist combination and economic returns for cancer pain management in China: a cost-effectiveness analysis.

Objective: To examine whether joint management of cancer pain by physicians and pharmacists in clinics provides economic advantages from the perspective of the Chinese healthcare system. Methods: From February 2018 to March 2020, 100 patients who visited the joint cancer pain clinic at the Xiangya Hospital of Central South University were included. These patients were randomly assigned to either the control or intervention groups. The control group received regular outpatient services from a physician, while the intervention group received regular outpatient services from a physician and medication education provided by a pharmacist. The study considered various direct costs, including drug expenses, physician-pharmacist outpatient services, adverse event management, consultations, examinations, and readmissions. The outcome indicators considered were the cancer pain control rate and the reduction in pain scores. Decision tree modeling, single-factor sensitivity analysis, and probabilistic sensitivity analysis were performed to evaluate the cost-effectiveness of joint physician-pharmacist outpatient services compared to physician-alone outpatient services. Results: The intervention group showed a significantly higher cancer pain control rate than the control group (0.69 vs. 0.39, p = 0.03). In the decision tree model, the intervention group had a significantly lower pain score than the control group (0.23 vs. 0.14). The cost per person in the intervention group was $165.39, while it was $191.1 per person in the control group. The univariate sensitivity analysis showed that the cost of self-management for patients in the control group was identified as the primary sensitivity factor. Probabilistic sensitivity analysis indicated that the joint clinic group had a favorable incremental cost-effectiveness compared to the physician clinic group. In addition, the probabilistic sensitivity analysis demonstrated an absolute advantage in the incremental cost-effectiveness of the joint clinic group over the outpatient physician group. Conclusion: The participation of pharmacists in joint cancer pain clinic services led to improved pain management for patients, demonstrating a clear advantage in terms of cost-effectiveness.

Signal mining and analysis for central nervous system adverse events due to taking oxycodone based on FAERS database. / 基于FAERSæ•°æ®åº“çš„ç¾Ÿè€ƒé ®ä¸­æž¢ç¥žç»ç³»ç»Ÿä¸è‰¯äº‹ä»¶ä¿¡å·æŒ–æŽ˜åŠåˆ†æž.

OBJECTIVES: Central nervous system adverse events (AEs) occur when oxycodone is used in combination with benzodiazepines, antidepressants and anticonvulsants. There have been no reports of central nervous system AEs with oxycodone alone or in combination with oxycodone. Based on USA Food and Drug Administration Adverse Event Reporting System (FAERS) data, this study aims to explore the risk signals of central nervous system AEs with oxycodone alone or in combination with benzodiazepines, antidepressants and anticonvulsants, and to provide a reference for the safe and rational use of this drug. METHODS: Extracted AEs data from the FAERS for oxycodone alone and in combination with benzodiazepines, antidepressants, and anticonvulsants from Q1 2004 to Q2 2021. The risk signal mining analysis of AEs was performed using the proportional imbalance method and Bayesian method. Number of reports ≥3 and lower 95% CI limit of reporting odds ratio (ROR)>1; number of reports ≥3, proportional reporting ratio (PRR)≥2 and χ2≥4; lower information components (IC) lower 95% CI limit (IC025)>0; empirical Bayes geometric mean (EBGM) lower 95% CI limit (EBGM05)>2, and N>0 were defined as positive signals. RESULTS: A total of 5 793 reports of central nervous system AEs with oxycodone alone were tapped, and 366, 622, and 740 reports of combined benzodiazepines, antidepressants, and anticonvulsants, respectively. Consumers and physicians were the main reporting population. The age distribution of oxycodone alone was mainly from 61 to 80 years old. The age distribution of oxycodone in combination with related drugs was mainly from 46 to 60 years old. The risk of AEs was greater in women than in men, and the United States was the predominant reporting country. Oxycodone alone was strongly associated with myoclonus [ROR=2.92, 95% CI 2.28 to 3.76); PRR=2.92, χ2(77.49); IC=1.52, IC025(0.65); EBGM=2.89, EBGM05(2.33)], delirium [ROR=4.69, 95% CI 4.24 to 5.21; PRR=4.66, χ2(1 052.64); IC=2.17, IC025(1.81); EBGM=4.50, EBGM05 (4.13)], mental disorder [ROR=2.95, 95% CI 2.53 to 3.44; PRR=2.94, χ2(206.93); IC=1.56, IC025(0.96); EBGM=2.95, EBGM05(2.58)], and acute central respiratory depression [ROR=2.87, 95% CI 2.68 to 3.08); PRR=2.82, χ2(971.62); IC=1.52, IC025(1.33), EBGM=2.87, EBGM05 (2.76)]. Combination of benzodiazepines was most strongly associated with mental disorder [ROR=10.08, 95% CI 9.38 to 10.78; PRR=9.90, χ2(64.06); IC=3.33, IC025 (1.65); EBGM=10.08, EBGM05(5.61)], and tremor [ROR=3.09, 95% CI 2.76 to 3.42); PRR=3.08, χ2(48.93); IC=1.63, IC025 (1.17); EBGM=3.09, EBGM05(2.34)]. Combination of antidepressants was most strongly associated with delirium [ROR=13.23, 95% CI 12.23 to 14.23; PRR=12.87, χ2(43.86); IC=3.69, IC025(1.36); EBGM=12.23, EBGM05 (5.32)] and somnolence [ROR=6.74, 95% CI 6.15 to 7.33); PRR=6.73, χ2(53.42); IC=2.75, IC025(1.52); EBGM=6.73, EBGM05(4.10)]. Combination of anticonvulsants was most strongly associated with myoclonus [ROR=17.89, 95% CI 17.46 to 18.32; PRR=17.72, χ2(971.39); IC=4.16, IC025(2.70); EBGM=17.89, EBGM05(12.46)] and delirium [ROR=4.86, 95% CI 4.45 to 5.27); PRR=4.82, χ2(69.49); IC=2.28, IC025 (1.51); EBGM=4.86, EBGM05(3.44)]. CONCLUSIONS: Based on pharmacovigilance studies of the FAERS database, clinical medication monitoring of oxycodone alone and in combination with benzodiazepines, antidepressants, and anticonvulsants should be strengthened to be alert to the occurrence of central nervous system-related AEs.

Evaluation of anticholinergic burden in elderly outpatients and the risk factors. / è€å¹´é—¨è¯Šæ‚£è€ æŠ—èƒ†ç¢±èƒ½å¤„æ–¹è´Ÿæ‹ è¯„ä»·åŠå ¶å±é™©å› ç´ .

OBJECTIVES: The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs. METHODS: A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia. RESULTS: A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine). CONCLUSIONS: There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

Scutellarin Mediates Cytochrome P450 3A4 and 2C19 Expression via Pregnane X Receptor and Constitutive Androstane Receptor.

BACKGROUND: Breviscapine is a flavonoid extracted from Erigeron breviscapus (Vant.) Hand.-Mazz., and mainly contains scutellarin. Nuclear receptors play important roles in regulating transporter and drug metabolic enzymes. OBJECTIVE: To investigate the regulatory effects of scutellarin on CYP3A4 and 2C19 in HepG2 and Caco-2 cells based on nuclear receptors PXR and CAR. METHODS: The proteins and mRNA levels of CYP3A4 and CYP2C19 treated with scutellarin were detected by Western Blot and RT-qPCR. Using assays of the dual-luciferase reporter, promoter sequences containing hPXR and hCAR protein recognition and binding regulatory elements CYP3A4 and CYP2C19 were inserted upstream of the reporter gene, and the expression vector and the reporter vector were cotransfected into HepG2 and Caco-2 cells. RESULTS: Scutellarin inhibited mRNA of CYP3A4 and PXR, and promoted mRNA expression of CYP2C19 and CAR in RT-qPCR results. Western-blot results showed scutellarin inhibited the expression of CYP3A4 and promoted the expression of CYP2C19. The dual-luciferase reporter genes showed that scutellarin enhanced the expression level of CYP2C19, and when its concentration was 40 and 80µmol/L, CYP3A4 was significantly increased. CONCLUSION: Scutellarin down-regulates CYP3A4 through PXR, and its mechanism may work by up-regulating CAR, binding to PXR to inhibit PXR-mediated expression of CYP3A4. Scutellarin up-regulates CYP2C19 through CAR.

Development of the Practice of Pharmaceutical Care for Cancer Pain Management in Outpatient Clinics Using the Delphi Method.

Background: There exists no broad agreement of experts on the practice of pharmaceutical care for cancer pain management in outpatient clinics. Objectives: This study aimed to use the Delphi consensus process to provide expert recommendations on the practice of cancer pain management in outpatient clinics from the point of view of pharmaceutical care in clinical practice and future clinical trials. Methods: A comprehensive literature review was conducted to draft the initial practice. In this process, 30-40 senior experts from various provinces in China were invited to rank the items of practice during the two Delphi consultations. The definitions of consensus included a combination with an average score of ≥4, the percentage of experts rating the scores at >4 points, and the coefficient of variation of the scores. Results: The expert panel comprised 18 pharmacists, 3 anesthesiologists, 6 oncologists, and 9 nurses. As a result of a comprehensive review, 33 items were initially formed. Among them, the consensus was reached for 27 items after the first Delphi round. The other six items and a total of five items for supplementation entered the second round, among which consensus was reached for eight items and three items were excluded. Expert consensus was achieved on 35 items after two rounds of consultation, which involved the collection of patient basic information, comprehensive pain assessment, breakthrough or neuropathic pain assessment, analgesic treatment evaluation, out-of-hospital follow-up, medical records, and evidence-based documents for reference. Conclusion: The final list of 35 items could be used to develop the practice of pharmaceutical care for cancer pain management in outpatient clinics in China. The practice may aid in the standardization of pharmaceutical care for pain, relieve pain to the greatest extent possible, and enhance the level of pain management in China.

Based on the Beers Criteria 2019 Edition Over-the-Counter Drugs Risk Confirmation of Elderly Chinese.

OBJECTIVE: To explore OTC (over-the-counter drugs) in Chinese community pharmacies often causes ADE (adverse drug event) in elderly patients. METHODS: Use the drugs in the Beers Criteria 2019 potentially inappropriate medication use (PIM) list as search terms. Search for drugs registered on the National Medical Products Administration of China website before December 2019 to determine the drugs containing PIM active ingredients and, then, search the Chinese OTC selection and conversion catalog database to determine it as OTC. Two databases are considered to be the same drug if they have the same drug composition. RESULTS: The incidence of PIM in elderly patients in our community is relatively high, and the management of OTC may be related to risk factors. Statistics found that 71 OTC contained the Beers Criteria ingredients, including 65 chemicals and six Chinese patent medicines. Varieties of compound preparations accounted for 78.9% and cold medicines accounted for 47.9%. CONCLUSIONS: The high detection rate of the Beers Criteria in Chinese OTC suggests that medical practitioners in China, especially community pharmacists, should pay attention to the rational use of OTC in the elderly.

Correction: Effect of Physician-Pharmacist Participation in the Management of Ambulatory Cancer Pain Through a Digital Health Platform: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/24555.].

Effect of Physician-Pharmacist Participation in the Management of Ambulatory Cancer Pain Through a Digital Health Platform: Randomized Controlled Trial.

BACKGROUND: Self-management of ambulatory cancer pain is full of challenges. Motivated by the need for better pain management, we developed a WeChat-supported platform, Medication Housekeeper (MediHK), to enhance communication, optimize outcomes, and promote self-management in the home setting. OBJECTIVE: We conducted a randomized controlled trial to assess whether the joint physician-pharmacist team through MediHK would provide better self-management of ambulatory patients with cancer pain. METHODS: Patients were randomly assigned to either an intervention group or control group. During the 4-week study period, the pharmacist would send 24-hour pain diaries daily, adverse drug reaction (ADR) forms every 3 days, and the Brief Pain Inventory form every 15 days to patients in the intervention group via MediHK. If a patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician, who was then responsible for prescribing or adjusting pain medications. If no adjustments were needed, the pharmacist provided appropriate targeted education based on knowledge deficits. Patients in the control group received conventional care and did not receive reminders to fill out the forms. However, if the control group patients filled out a form via MediHK, the pain management team would review and respond in the same way as for the intervention group. The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included patient-reported outcome measures, medication adherence, ADRs, and rehospitalization rates. RESULTS: A total of 100 patients were included, with 51 (51%) in the intervention group and 49 (49%) in the control group. The worst pain scores, least pain scores, and average pain scores in the intervention group and the control group were statistically different, with median values of 4 (IQR 3-7) vs 7 (IQR 6-8; P=.001), 1 (IQR 0-2) vs 2 (IQR 1-3; P=.02), and 2 (IQR 2-4) vs 4 (IQR 3-5; P=.001), respectively, at the end of the study. The pain interference on patients' general activity, mood, relationships with others, and interests was reduced, but the difference was not statistically significant compared with the control group (Ps=.10-.76). The medication adherence rate increased from 43% to 63% in the intervention group, compared with an increase of 33% to 51% in the control group (P<.001). The overall number of ADRs increased at 4 weeks, and more ADRs were monitored in the intervention group (P=.003). Rehospitalization rates were similar between the 2 groups. CONCLUSIONS: The joint physician-pharmacist team operating through MediHK improved pain management. This study supports the feasibility of integrating the internet into the self-management of cancer pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900023075; https://www.chictr.org.cn/showproj.aspx?proj=36901.

Relationship between xanthine oxidase gene polymorphisms and anti-tuberculosis drug-induced liver injury in a Chinese population.

This study was designed to investigate the association of the xanthine oxidase (XO) polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury (ATDILI) in Chinese population. A total of 183 tuberculosis patients were enrolled. Patients with ATDILI were classified as cases and those without ATDILI were classified as controls. Genotyping for XO polymorphisms was determined by polymerase chain reaction and direct sequencing. The allele frequencies and genotype distribution was analyzed using the Chi square test to analyze the association between the gene polymorphisms and ATDILI. Binary logistic regression analysis was performed to assess the risk factors of ATDILI. A total of 21 patients were developed liver injury during anti-tuberculosis treatment in this study, with an incidence of 11.48%. In genotype analysis, no significant difference was observed in the alleles and genotypes frequencies of the six SNPs between two groups (P > 0.05). In haplotype analysis, carriers with GGGATA (rs1884725- rs2295475 -rs45523133- rs206812- rs206813- rs7575607) haplotype had a significantly higher risk of ATDILI compared with other haplotypes (OR = 2.445, 95%CI: 1.058-5.652, P < 0.05). This study suggested that the haplotype GGGATA constructed with rs206812 and rs7575607 mutant alleles might contribute to ATDILI susceptibility in a Chinese population.

Effects of a physician- and pharmacist-managed clinic on pain management in cancer patients in China.

In China, pharmacists have started to manage cancer pain at outpatient clinics. This retrospective study performed at a tertiary teaching hospital was aimed to evaluate the effects of a physician-pharmacist joint clinic for cancer pain management. The study was performed between December 2016 and August 2019 and included 113 outpatients with moderate to severe cancer-related pain. Patients were divided into two groups according to the clinic each patient visited: the physician-pharmacist joint clinic (joint group, n = 59) or physician-only clinic (usual group, n = 54). Brief Pain Inventory (BPI) and Morisky Medication Adherence Measure (MMAM) were used to collect data on pain intensity, interference and medication adherence. Pain Management Index (PMI) was also calculated. BPI, MMAM and PMI were assessed at baseline (patients' first visit, week 0) and week 4 follow-up. The Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was used to assess patients' health-related quality of life (HRQoL) at week 4. The primary outcomes were the improvement in pain intensity, adequacy of pain management and medication adherence. The secondary outcome was the improvement in HRQoL. At week 4, compared to the usual group, the BPI pain intensity categories except the pain right now were significantly lower in the joint group: worst pain, 4 (3-7) vs 6 (4-8), P = .020; least pain, 1 (0-2) vs 2 (1-3), P = .010; average pain, 3 (2-4) vs 4 (2-5), P = .023; pain right now, 2 (1-3) vs 2 (0-4), P = .796. For the seven pain interference categories, there were no significant improvements in the joint group (P > .05). Significantly more patients achieved adequate pain control in the joint group than the usual group ((P = .002). There was also a significant difference in medication adherence between the two groups (P = .001). There were no significant differences in HRQoL between the two groups. The study suggests that pharmacist participation in outpatient cancer pain management is associated with improvement of patients' pain control and medication adherence.

Influencing factors of end-of-dose failure in patients with cancer pain after oral oxycodone sustained-release tablets: a retrospective, case-control study.

OBJECTIVE: Comparing the characteristics of end-of-dose failure patients and non-end-of-dose failure patients in the Chinese population and exploring the factors that may affect the occurrence of end-of-dose failure in cancer pain patients. METHODS: The outpatient with cancer pain from 2016 to 2019 were collected through hospital information system, and patients were included who met the following criteria: patients with the average numerical rating scale  ≥4 points within 3 days after taking the oxycodone sustained-release preparation, titrated to an effective therapeutic dose suitable for patients, had at least two clinical visits information of the patient with a minimum of ≥3 days between visits, the average numerical rating scale of the next visit after the treatment of occasional pain is ≥4, and were divided into end-of-dose failure group and non-end-of-dose failure group. RESULTS: Age (P < 0.05, odds ratio 0.933), diagnosis of nasopharyngeal carcinoma (P < 0.05, odds ratio 0.009), pain site is the head and neck (P < 0.05, odds ratio 0.005) and the abdomen (P < 0.01, odds ratio 0.021), and the metastatic site is the liver (P < 0.05, odds ratio 0.001) are related to the occurrence of end-of-dose failure. CONCLUSIONS: Younger patients are more likely to develop end-of-dose failure. Patients diagnosed with nasopharyngeal cancer, with pain in the head and neck and abdomen, and with liver metastases have a lower incidence of end-of-dose failure.

Effect of CYP2C9 genetic polymorphism and breviscapine on losartan pharmacokinetics in healthy subjects.

1. Breviscapine was an active ingredient of flavonoid glycosides. Our present study was conducted to evaluate the impact of breviscapine on the pharmacokinetics of losartan and its active metabolite E-3174, and that relationship with the gene polymorphism of CYP2C9 in healthy Chinese volunteers, to provide a basis for clinical rational drug use.2. The genotypes of 217 healthy Chinese subjects were determined using PCR-RFLP. Twelve healthy subjects were selected and were known CYP2C9 genotypes (six CYP2C9*1/*3 and six CYP2C9*1/*1) in a two-phase randomised crossover design study. These subjects were given daily doses of 120 mg (40 mg, three times a day) of breviscapine or a placebo for 14 days, followed by 50 mg losartan on day 15.3. Compared with individuals carrying the CYP2C9*1/*1 genotype, the CYP2C9*1/*3 genotype showed an increase in the AUC(0-36) (833.6 ± 379.8 ng h ml-1 vs. 526.1 ± 140.1 ng h ml-1, p < 0.05) and a decrease in the MR (the metabolic ratio of losartan, AUCE-3174/AUClosartan) (2.67 ± 1.40 vs. 4.56 ± 0.83, p < 0.05) of losartan during the placebo treatment phase. Individuals with genotype CYP2C9*1/*3 showed a significant increase in AUC(0-36) (2335 ± 851.8 ng h ml-1 vs. 1927 ± 949.5 ng h ml-1, p < 0.05) and AUC(0-∞) (2363 ± 875.6 ng h ml-1 vs. 1966 ± 966.1 ng h ml-1, p < 0.05) of E-3174 after breviscapine treatment compared to the placebo group.4. In healthy subjects, breviscapine had no significant effect on the pharmacokinetics of losartan. The activity of CYP2C9 enzyme to losartan metabolism was more significant in subjects with CYP2C9*1/*3 than those with CYP2C9*1/*1 genotype.