Adherence to Analgesic Drugs and its Associated Factors among Patients with Cancer Pain: A Crosssectional Study in China.

Objectives: Pain is one of the most common and distressing symptoms co-occurring with cancer progression and treatment, and medication adherence plays an important role in achieving good pain control. However, research on medication adherence and influential factors among individuals with cancer pain (CP) is limited in China. The present study aimed to investigate the adherence to analgesics in patients with CP in China and to identify factors that may influence adherence. Methods: A cross-sectional study was conducted from June 2020 to February 2021. Study instruments consisted of a set of validated questionnaires, 5 measurement instruments including the numerical rating scale (NRS), ID-Pain, Morisky Medication Adherence Scale-Chinese validated version (MMAS-C), Beliefs about Medicines Questionnaire (BMQ) - Specific, and the Hospital Anxiety and Depression Scale (HADS). Results: A total of 141 participants with CP including 71 males (50.4%), aged 54.5±15.5 years were surveyed in this study. Overall, 83 patients (58.9%) showed adherence, but 58 patients (41.1%) showed non-adherence to analgesics. The univariate analysis showed that analgesic adherence was associated with pain duration of>3 months, outbreaks of pain in the last 24 hours, presence of side effects, getting analgesics in time, presence of neuropathic pain, stopping analgesics or adjusting dosage by themselves, presence of anxiety and depression, and beliefs about medicines. Moreover, the multivariate logistic regression showed that getting analgesic drugs in time (odds ratio [OR]=5.218, 95% confidence interval [CI] 1.691-16.100) and high BMQ-Necessity (OR=1.907, 95% CI 1.418-2.565) were associated with high adherence, stopping analgesics or adjusting dosage by themselves (OR=7.958, 95% CI 2.443-25.926) and high BMQ-Concern (OR=0.760, 95% CI 0.600-0.964) were more likely to be associated with non-adherence. Conclusion: In view of our findings, it may be critical for individuals to have a better understanding and strong beliefs about their prescribed analgesic drugs. Pain education, counseling and follow-up of patients and their caregivers, and removal of barriers to accessing analgesic drugs could be considered in further intervention strategies.

Impacts of Pharmacists-Managed Oncology Outpatient Clinic on Resolving Drug-Related Problems in Ambulatory Neoplasm Patients: A Prospective Study in China.

Pharmacists are health care professionals who are actively involved in identifying and solving drug-related problems (DRPs) in neoplasm patients. However, the effectiveness of pharmaceutical services at outpatient clinic for neoplasm patients have not been reported in China. This study aims to describe and investigate the impacts of pharmacists-managed oncology outpatient clinic on ambulatory neoplasm patients. We performed a descriptive, prospective study from June 6, 2018 to June 6, 2020. Firstly, we established a pharmacists-managed oncology outpatient clinic and a Pharmacists Work System of Medication Therapy Management (MTM) software with the cooperation of oncologists, pharmacists and software engineers in 2018. Subjects were neoplasm patients who visited the pharmacists-managed outpatient clinic. The pharmacists performed a comprehensive assessment of the patient's medication and made planned interventions based on the DRPs identified. A total of 215 eligible patients with 707 visits were enrolled and recorded in the MTM software. A total of 316 DRPs (1.47 per patient) were identified. Adverse reactions, non-adherence, untreated indication, and drug interactions were the leading DRPs. 261 (82.6%) of the identified DRPs had been confirmed as resolved and 104 (78.2%) of adverse reactions were improved following pharmacist interventions and 2 to 3 course follow-up. Of the 382 planned interventions, 345 (90.3%) were accepted by patients or physicians. This is the first pharmacists-managed oncology outpatient clinic to describe the type of DRPs in neoplasm patients and evaluate the effectiveness of pharmacist interventions in China. Pharmacist interventions were efficacious in resolving DRPs and improving adverse reactions. We confirmed that pharmacists have an important role in ambulatory neoplasm patients care.

The effectiveness of an independent anti-neoplastic medication therapy management system in ambulatory cancer patients.

BACKGROUND: Cancer has always been a serious health threat for human. Patients with cancer are at high risk of drug-related problems (DRPs) due to multi-morbidity associated polypharmacy. However, data is lacking in identifying and addressing potential DRPs in cancer patients in China. This study aims to investigate the prevalence of DRPs and evaluate the effectiveness of an independent anti-neoplastic medication therapy management (MTM) system in ambulatory cancer patients. METHODS: This is a retrospective study. An independent anti-neoplastic MTM system in Shanghai Jiao Tong University affiliated sixth People's Hospital was established in 2018 with the collaboration of oncologists, clinical pharmacists and software engineers. The system contains an independent clinic of pharmacy and MTM software. The software consisted of six modules to help clinical pharmacists serve the tumor patients. The six modules include medication therapy review, intervention plan, personal medication record, medication-related action plan, intervention and/or referral, and documentation and follow-up. RESULTS: A total of 173 eligible tumor patients visited the anti-neoplastic pharmaceutical clinic and were recorded in the independent anti-neoplastic MTM system from Jun 2018 to May 2019. The average clinic visits were 2.4 times of the study participants. Two thirds patients (117/173) had one or more identified DRPs in medication therapy review. Adverse drug reaction, potential drug interaction and non-adherence were the leading DRPs. 85.8% of DRPs could be resolved (cured or improved) in four weeks. Tumor patients showed medication adherence reached 84-100% after three or four times of follow-up and intervention. CONCLUSIONS: The participation of clinical pharmacists in managing polypharmacy tumor patients, with the independent anti-neoplastic MTM system, facilitated the identifying and solving DRPs, especially improving medication adherence of patients, and thus enhancing the effectiveness, safety and rational use of medication.

Tropisetron attenuates lipopolysaccharide induced neuroinflammation by inhibiting NF-κB and SP/NK1R signaling pathway.

Tropisetron, an antagonist of serotonin type 3 receptors (5-HT3Rs), has been investigated in colonic inflammatory process. Since substance P/neurokinin 1 receptor (SP/NK1R) signaling pathway plays a key role in several sensory neuronal inflammatory. We evaluated the anti-inflammatory activity of tropisetron in mice cerebral cortex, and discovered that it was a potential inhibitor in LPS-mediated neuron inflammation through SP/NK1R signaling pathway. We found that tropisetron significantly reduced the increased number of iba-1 positive microglia, down-regulated the gene transcription and protein expression of IL-1ß,IL-6 and TNF-α in LPS stimulated cerebral cortex. To characterize the inhibitory mechanism of tropisetron at the SP response in inflammation, we further examined the effect of tropisetron on NF-κB and SP/NK1R signaling pathway in the process of mice cerebral cortex inflammation. We found that tropisetron inhibited the gene transcription and protein expression of NF-κB, SP, NK1R via inhibiting 5-HT3R activity. These findings might provide new insights into the anti-inflammatory activities of 5-HT3R inhibitor tropisetron, which would be the interaction of serotonin receptor signaling and SP/NK1R pathway. These might highlight their potential to design novel therapeutic strategies to manage inflammatory diseases.

Combination of sorafenib and Valproic acid synergistically induces cell apoptosis and inhibits hepatocellular carcinoma growth via down-regulating Notch3 and pAkt.

Sorafenib is currently the only approved first-line targeted drug against advanced hepatocellular carcinoma (HCC). However, unsatisfactory efficacy and resistance of sorafenib raises the urgent need to develop more effective therapeutic strategies for HCC. Here, we evaluated the effects of combination of histone deacetylase inhibitor Valproic acid (VPA) and sorafenib in HCC both in vitro and in vivo. Co-treatment of sorafenib and VPA synergistically inhibited HCC cell viability, induced cell apoptosis, along with the up-regulation of p21, Bax, cleaved caspase9, cleaved caspase3, cleaved PARP and down-regulation of Bcl-xL, suggesting this combination activated intrinsic apoptotic pathway. Our further experiment results showed that sorafenib plus VPA decreased tumor burden more effectively than sorafenib or VPA mono-therapy in nude mice subcutaneous xenograft model. Histological and serological analysis demonstrated well tolerance of this combination in vivo. On a molecular level, our results presented a possible crosstalk between Notch3 and Akt signaling. Sorafenib increased the expression of Notch3 in a dosage dependent manner, along with the phosphorylation of Akt in HCC cells. In comparison, this induction of Notch3 and pAkt could be decreased by VPA, implying that Notch3 and pAkt are of significance in the treatment of HCC, which may account for the synergism of sorafenib and VPA. In conclusion, the combination of sorafenib and VPA offers a potential targeting therapeutic regimen for HCC in the future.