Efficacy and safety of traditional Chinese medicine for cancer-related fatigue: a systematic literature review of randomized controlled trials.

BACKGROUND: Cancer-related fatigue (CRF) is an extremely common and long-term condition that affects the physical and mental health of oncology patients. While the treatment for CRF with western medicine and non-pharmacological therapy remains uncertain and challenging, traditional Chinese medicine (TCM) has become a trending option for the patients. Based on the findings from randomized controlled trials (RCTs), this study aims to identify and evaluate the evidence about the efficacy and safety of TCM for CRF. METHODS: A systematic literature search was conducted according to the PRISMA literature research guidelines. Seven electronic databases including PubMed, the Cochrane Library, Embase, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI) and Wanfang database were searched to identify RCTs which investigated TCM in the treatment of CRF published since inception to December 2022. RCTs comparing TCM with no treatment, placebo, or pharmacological interventions were considered eligible for this review. The Consolidated Standards of Reporting Trials Statement extensions for Chinese herbal medicine Formulas (CONSORT-CHM) and the Cochrane Collaboration's Risk of Bias tool were used in this review to evaluate the quality and the risk of bias of all included trials. RESULTS: A total of 82 RCTs were included in this review, regardless of whether they were published in English or Chinese. After data extraction and results evaluation, 78 trials demonstrated overall efficacy in using TCM for CRF patients compared with the control group, in which 33 trials showed that the efficacy rate was statistically significant (p < 0.05 or p < 0.01). TCM was also shown to be beneficial in improving the scores of relevant scales (e.g., PFS, QoL, TCM syndrome score, other fatigue scales etc.) or physical tests indicators (e.g., cytokines, blood test etc.). The most common herbs found in Chinese medicine were Astragali Radix, Ginseng Radix and Codonopsis Radix. Some TCM products, such as Kangai Injection, Buzhong Yiqi Decoction and Shenqi Fuzheng Injection could provide a reference for medication in this review. A range of non-serious, reversible adverse effects associated with the use of TCM was also reported. However, the result of evaluation showed that none of the trials fully met all the CONSORT-CHM criteria, the quality of included trials was generally poor and the risk of bias was mostly uncertain. CONCLUSION: There is some evidence supporting the efficacy and safety of TCM in managing CRF in this systematic review. However, no clear conclusion can be made due to the inadequate reporting of efficacy and adverse reactions. In view of some concerns about the existing evidence after the evaluation, it is essential to standardize the comprehensive identification and efficacy measurement standards, improve the quality of RCTs and conduct more multicomponent therapies to provide an updated reference for CRF patients medication in the future. The protocol of this systematic review has been registered on PROSPERO (CRD42023413625). [ https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023413625 ].

Comparative analysis of disease modelling for health economic evaluations of systemic therapies in advanced hepatocellular carcinoma.

BACKGROUND: The objective of this study was to systematically analyse methodological and structural assumptions utilised in model-based health economic evaluations of systemic advanced hepatocellular carcinoma (HCC) therapies, discuss the existing challenges, and develop methodological recommendations for future models in advanced HCC. METHODS: We performed literature searches using five databases (Embase, PubMed, Web of Science, Econlit, and CNKI) up to December 4, 2022. Technology appraisals from Canada, England, Australia, and the United States were also considered. Model-based full economic evaluations of systemic advanced HCC therapies in English or Chinese met the eligibility criteria. The reporting quality was assessed by using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. RESULTS: Of 12,863 records retrieved, 55 were eligible for inclusion. Markov model (n = 29, 53%) and partitioned survival model (n = 27, 49%) were the most commonly used modelling techniques. Most studies were based on health-state-driven structure (n = 51, 93%), followed by treatment-line-driven structure (n = 2, 4%) and combination structure (n = 1, 2%). Only three studies (5%) adopted external real-world data to extrapolate the overall survival or calibrate the extrapolation. Few studies reported the assumptions of transition probabilities. Utility modelling approaches were state-based (n = 51, 93%) and time-to-death (n = 1, 2%). Only 13 studies (24%) reported five types of model validation. Economic evaluation results of specific treatment strategies varied among studies. CONCLUSIONS: Disease modelling for health economic evaluations of systemic therapies in advanced HCC has adopted various modelling approaches and assumptions, leading to marked uncertainties in results. By proposing methodological recommendations, we suggest that future model-based studies for health economic evaluation of HCC therapies should follow good modelling practice guidelines and improve modelling methods to generate reliable health and economic evidence.

Modelling 30-day hospital readmission after discharge for COPD patients based on electronic health records.

Chronic Obstructive Pulmonary Disease (COPD) is the third most common chronic disease in China with frequent exacerbations, resulting in increased hospitalization and readmission rate. COPD readmission within 30 days after discharge is an important indicator of care transitions, patient's quality of life and disease management. Identifying risk factors and improving 30-day readmission prediction help inform appropriate interventions, reducing readmissions and financial burden. This study aimed to develop a 30-day readmission prediction model using decision tree by learning from the data extracted from the electronic health record of COPD patients in Macao. Health records data of COPD inpatients from Kiang Wu Hospital, Macao, from January 1, 2018, to December 31, 2019 were reviewed and analyzed. A total of 782 hospitalizations for AECOPD were enrolled, where the 30-day readmission rate was 26.5% (207). A balanced dataset was randomly generated, where male accounted for 69.1% and mean age was 80.73 years old. Age, length of stay, history of tobacco smoking, hemoglobin, systemic steroids use, antibiotics use and number of hospital admission due to COPD in last 12 months were found to be significant risk factors for 30-day readmission of CODP patients (P < 0.01). A data-driven decision tree-based modelling approach with Bayesian hyperparameter optimization was developed. The mean precision-recall and AUC value for the classifier were 73.85, 73.7 and 0.7506, showing a satisfying prediction performance. The number of hospital admission due to AECOPD in last 12 months, smoke status and patients' age were the top factors for 30-day readmission in Macao population.

Real-world clinical effectiveness of once-weekly semaglutide in patients with type 2 diabetes: a systematic literature review.

INTRODUCTION: The efficacy of once-weekly (O.W.) semaglutide for the treatment of type 2 diabetes mellitus (T2DM) has been demonstrated in clinical trials. The aim of this systematic literature review was to summarize real-world evidence for O.W. semaglutide. METHODS: A comprehensive search of PubMed, Web of Science, Embase, and Scilit databases was performed from January 2017 to June 2022 to identify eligible real-world studies examining O.W. semaglutide in T2DM. RESULTS: Thirty-one records (18 full-text and 13 abstracts) were identified. The general characteristics of studies and included patients were summarized. Changes in glycated hemoglobin (HbA1c) and body weight were analyzed across studies and according to patient characteristics: baseline HbA1c/weight level, GLP-1 RA-naïve/ GLP-1RA-experienced. The effectiveness of O.W. semaglutide compared with dulaglutide, and the dose of O.W. semaglutide in the real world were also summarized. CONCLUSIONS: This systematic literature review provided complementary evidence to findings from the clinical trials and provided a more comprehensive picture of the use of O.W. semaglutide in routine clinical practice. Results of the review suggested that O.W. semaglutide therapy was associated with improving glycemic control and weight loss in both T2DM patients naïve to GLP-1RA and those previously treated with other GLP-1RA in routine clinical practice. PROSPERO REGISTRATION: CRD42022306164.

Effectiveness of Hospital Pharmacist Interventions for COPD Patients: A Systematic Literature Review and Logic Model.

Purpose: This review aimed to summarize empirical evidence about pharmacist-led interventions for chronic obstructive pulmonary disease (COPD) patients in hospital settings and to identify the components of a logic model (including input, interventions, output, outcome and contextual factors) to inform the development of hospital pharmacist's role in COPD management. Methods: A systematic review of literature retrieved from four English databases (PubMed, Web of Science, Scopus, ScienceDirect) and one Chinese database (CNKI) were conducted to identify eligible studies published from inception to March 2022. Studies concerning pharmacist and COPD were identified to screen for randomized controlled studies that focused on pharmacist interventions for COPD at the hospital setting. Results: Twenty-nine studies were included in this review. The components of interventions identified were categorized according to the six service domains in the International Pharmaceutical Federation's Basel Statements, and mainly concerned prescribing, preparation, administration and monitoring but not procurement and training. Extended interventions were also identified including life guidance, psychological counseling, and respiratory function exercise. The most common outputs reported were improvement in medication adherence, rational drug use, level of knowledge, and inhalation technique. The clinical outcomes (symptomatic control, lung function, rates of hospital readmission, length of hospital stay, and adverse drug adverse reactions), humanistic outcomes (quality of life and patient satisfaction), and economic outcomes (drug costs, hospitalization costs, antibiotic costs, and direct costs) were reported only in some studies. The contextual factors mainly included geographical factors, education level of patients, socio-economic factors, and no-smoking policy. Conclusion: The evidence for hospital pharmacists' interventions in improving COPD patients' outcome is growing. However, considering the challenges of COPD management, hospital pharmacists should further leverage the advantages of cross-sector and multi-disciplinary collaboration in order to provide more comprehensive support to better address the needs of their patients.

Efficacy and safety of monotherapy and combination therapy of immune checkpoint inhibitors as first-line treatment for unresectable hepatocellular carcinoma: a systematic review, meta-analysis and network meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the cancers with the highest morbidity and mortality. Sorafenib used to be the main treatment for unresectable HCC patients. However, regimens based on immune checkpoint inhibitors (ICIs) have attracted attention in recent years because of their reported benefits. This study aimed to evaluate the efficacy and safety of monotherapy and combination therapy of ICIs as first-line treatment for unresectable HCC patients by conducting a systematic review, meta-analysis, and network meta-analysis. METHODS: Studies published up to 11st August 2022 were searched from 4 commonly used databases, including PubMed, Web of Science, Embase, and Clinical trials.gov. All eligible clinical trials were included. Data about reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were extracted. RESULTS: Of the 8579 studies retrieved, 24 met the inclusion criteria. In patients with unresectable HCC taking ICIs-based therapy as first-line treatment, the pooled result of median PFS and median OS was 5.76 months (95% CI 4.82-6.69) and 16.35 months (95% CI 15.19-17.51) The ORR and DCR were 25.1% (95% CI 20.8-29.5%) and 75.2% (95% CI 70.3-80.2%) measured by RECIST v1.1 or 40.2% (95% CI 31.7-48.6%) with 75.2% (95% CI 68.3-82.1%) measured by mRECIST v1.1. Compared to sorafenib, ICIs-based therapy significantly prolonged OS. The combination treatment of sintilimab plus IBI305 had the highest ORR, while atezolizumab plus bevacizumab had the highest DCR. The pooled incidence of any grade TRAEs was 82.3% (95% CI 73.9-90.7%), with highest incidence appeared in dysphonia. CONCLUSIONS: This study demonstrated that first-line ICIs-based therapies could provide survival benefits for patients with unresectable HCC, with manageable TRAEs. The potential of combination treatment to become the new treatment trend in clinical practice is promising.

Viral etiology among children hospitalized for acute respiratory tract infections and its association with meteorological factors and air pollutants: a time-series study (2014-2017) in Macao.

BACKGROUND: The associations between viral etiology of acute respiratory infections (ARI) with meteorological factors and air pollutants among children is not fully understood. This study aimed to explore the viral etiology among children hospitalized for ARI and the association of meteorological factors and air pollutants with children hospitalization due to viral ARI. METHODS: Electronic health record data about children (aged between 1 month and 14 years) admitted for ARI at Kiang Wu Hospital in Macao between 2014 and 2017 was analyzed retrospectively. xMAP multiplex assays were used to detect viruses in the nasopharyngeal swab and distributed-lag nonlinear model (DLNM) was used to evaluate associations. RESULTS: Among the 4880 cases of children hospitalization due to ARI, 3767 (77.2%) were tested positive for at least one virus and 676 (18%) exhibited multiple infections. Enterovirus (EV)/rhinovirus (HRV), adenovirus (ADV), respiratory syncytial virus (RSV) and influenza virus (IFV) were the most common viral pathogens associated with ARI and human bocavirus (hBOV) exhibited the highest multiple infection rates. Meteorological factors and air pollutants (PM10, PM2.5 and NO2) were associated with the risk of viral ARI hospitalization. The relative risk of viral infection increased with daily mean temperature but plateaued when temperature exceeded 23 °C, and increased when the relative humidity was < 70% and peaked at 50%. The effect of solar radiation was insignificant. Air pollutants (including PM10, PM2.5, NO2 and O3) showed strong and immediate effect on the incidence of viral infection. CONCLUSIONS: The effects of mean temperature, relative humidity and air pollutants should be taken into account when considering management of ARI among children.

Economic Burden and Quality of Life of Hepatocellular Carcinoma in Greater China: A Systematic Review.

Background: Hepatocellular carcinoma (HCC) accounts for more than 85%-90% of primary liver cancer globally, and approximately 45% of deaths from HCC occur in greater China. This disease poses a significant economic burden for patients, payers and society and significantly affects patients' quality of life (QoL). However, such impact of HCC in greater China has not been well characterized. This review was conducted to analyze the current evidence about the economic and humanistic impact of HCC in greater China for informing national disease management and identifying clinical gaps yet to be resolved. Methods: A systematic search literature using seven databases (Web of Science, PubMed, Medline, Cochrane Central, China National Knowledge Infrastructure, Wanfang, and Weipu) was performed to identify interventional and observational studies that reported the impact of HCC on cost or QoL and published before April 6, 2021. The focus population included adult patients with HCC in greater China. This review excluded any studies that focused on any specific treatment. Study quality was assessed using the Effective Public Health Practice Project tool. Results: Of 39,930 studies retrieved, 27 were deemed eligible for inclusion. The methodologies, perspectives and data sources used in studies were heterogeneous. In greater China, while few studies reported the health expenditures of HCC patients and investigations about economic burden at national level was lacking, the significant economic impact of HCC on patients and their families had been reported. Health-related costs increased as the disease deteriorated. Additionally, HCC also has a negative impact on the QoL of patients, mostly in terms of physical, cognitive, social functioning and severe symptoms. Conclusions: HCC has brought significant economic and QoL burden to patients in greater China. Both physical and psychological factors predicted QoL in patients with HCC in greater China. Future studies should explore the disease-related economic effects on Chinese patients and their families, the effects of physical and psychological factors on QoL and the relationships of physical and psychological factors in the region.Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?RecordID=278421, PROSPERO: CRD42021278421.

Epidemiology and disease burden of non-alcoholic steatohepatitis in greater China: a systematic review.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a progression of non-alcoholic fatty liver disease. The increasing burden of NASH has become a major concern of public health in greater China. This study aimed to characterize the epidemiology, disease burden, and treatment of NASH in greater China to better inform national disease management and delivery of health services. METHODS: We conducted a systematic review searching four English databases (Web of Science, PubMed, Medline, and Cochrane Central) and three Chinese databases (CNKI, Wanfang, and VIP). We identified articles published from database inception to October 10, 2020 which reported NASH epidemiology, disease burden, and/or intervention in Chinese adults. RESULTS: Of 44,115 articles retrieved, 33 were eligible for inclusion. Overall prevalence of NASH ranged from 2.4 to 6.1% in greater China, with a more substantial burden among males, the aged, and those in Hong Kong and Taiwan. Most NASH patients suffered from several comorbidities, including obesity, diabetes, and cardiovascular conditions. PNPLA3 rs738409 G allele and haptoglobin 2-2 genotype drove the fibrosis progression in NASH. Increasingly prevalent cases of cirrhosis and hepatocellular carcinoma caused a higher NASH-related mortality. Compared with normal population, NASH patients experienced markedly poorer quality of life and heavier costs. CONCLUSION: This is the first comprehensive overview of NASH among Chinese population that revealed an overwhelming impact of social and healthcare burden associated with the condition. Further high-quality studies are needed to improve the understanding and management of NASH in greater China.

Health technology assessment-informed pricing negotiation in China: higher negotiated price for more effective targeted anticancer medicines?

BACKGROUND: In China, health technology assessment (HTA) has recently been adopted in pricing negotiation for medicine listing in the National Reimbursement Drug List. At present, how HTA is applied to inform the decision-making process remains underreported. In order to explore how the adoption of HTA was translated into listing and price negotiation results in light of the confidential nature of the negotiating process, this study aimed to compare the negotiated price and the clinical benefit of selected targeted anticancer medicines (TAMs) involved in the 2019 negotiation. MAIN TEXT: Among 16 TAMs successfully negotiated, only four TAMs representing four indication groups had appropriate reference medicines for comparison and were, therefore, included in the analysis. The price and clinical benefit of the four TAMs were compared against one or two reference medicines with the same initial indications. The sales prices for nine TAMs before and after the negotiation were extracted from the centralized medication procurement system. Clinical benefits were evaluated based on evidence from published articles and clinical guidelines. The results suggested that, despite the application of HTA, both rational and irrational decisions had been made about the reimbursement of TAMs in the 2019 negotiation, warranting further investigation. CONCLUSION: While the development and adoption of HTA has seen significant progress in China, actions are needed to ensure that the adoption of HTA is effectively applied in decisions on the reimbursement of medicines.

Trends of Negotiated Targeted Anticancer Medicines Use in China: An Interrupted Time Series Analysis.

BACKGROUND: In order to relieve the financial burden of the patients in China, the Ministry of Health (MoH) conducted the first national price negotiation and successfully negotiated three expensive medicines including 2 targeted anticancer medicines (TAMs), icotinib and gefitinib. However, little evidence was available to demonstrate the impact of the national negotiation on TAMs use. The purpose of the study is to evaluate the implementation of the national price negotiation policy in China on TAMs use. METHODS: We used interrupted time series (ITS) design to examine the changes in the daily cost, the monthly hospital purchasing volume and spending of icotinib and gefitinib with pharmaceutical procurement data from 594 tertiary hospitals in 29 provinces of mainland China between January 2015 and July 2017. The period between May and July 2016 was applied to assess the impact of policy. RESULTS: The daily cost of icotinib and gefitinib decreased by 50.08% (P<.001) and 53.89% (P<.001) 12 months after the national negotiation, respectively. In terms of volume, the negotiation was associated with increases in the trend of the monthly hospital purchasing volume of icotinib and gefitinib by 4.87 thousand defined daily doses (DDDs) (P<.001) and 6.89 thousand DDDs (P<.001). However, the monthly hospital purchasing spending of icotinib and gefitinib decreased rapidly by US$0.51 million (P<.010) and US$0.82 million (P<.050) following policy implementation, respectively. CONCLUSION: The first national negotiation had successfully cut off the price of two negotiated TAMs and promoted TAMs use in China. In the future, government should conduct further price negotiations and include more medicines with clinical benefits into reimbursement schemes to alleviate patients' financial burden and promote their access to essential treatment.

Efficacy and Safety of First-Line Targeted Treatment and Immunotherapy for Patients with Biliary Tract Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Biliary tract cancer is one of the most aggressive and fatal tumours. Gemcitabine with cisplatin chemotherapy has long been the first-line treatment, but the prognosis is poor. In recent years, targeted treatment and immunotherapy have produced encouraging outcomes requiring a thorough review and meta-analysis. METHOD: For this systematic review and meta-analysis, we searched four databases, starting from the inception dates of databases to 11 January 2022. This study comprised randomised clinical trials and cohort studies that used immunotherapy or targeted treatment as the first line of treatment for patients with biliary tract cancer. RESULTS: From the 888 studies extracted, 33 trials were examined and found to meet the criteria. These included 3087 patients, 16 single-arm trials, 13 RCTs, one nRCT, a prospective single-arm pilot study, and a clinical setting in the real world. From 2010 to 2020, 33 studies were conducted using targeted treatment or immunologic therapies as first-line treatments for BTC patients, and 18 of those studies had positive outcomes. CONCLUSION: This study demonstrates that immunotherapy combined with chemotherapy as first-line treatment can provide survival benefits by improving the objective response rate for patients with unresectable biliary tract cancer. The potential for combination therapy to become a new trend in clinical treatment is promising but needs further clinical evaluation.

Clinical Outcomes Associated with Monotherapy and Combination Therapy of Immune Checkpoint Inhibitors as First-Line Treatment for Advanced Hepatocellular Carcinoma in Real-World Practice: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs)-based therapy has recently been demonstrated to greatly ameliorate survival outcomes in advanced hepatocellular carcinoma (HCC). We aimed to evaluate clinical outcomes of ICIs-based monotherapy and combination therapy as first-line treatment of adults with advanced HCC in real-world practice by conducting a systematic literature review and meta-analysis. METHODS: PubMed, Web of Science, and Embase were searched up to 25 April 2022. Retrospective or prospective real-world studies evaluating progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) of patients with advanced HCC receiving first-line ICIs-based therapy were included. RESULTS: Of 7805 studies retrieved, 38 were deemed eligible for inclusion. For patients receiving first-line ICIs-based therapy in real-world practice, the pooled median PFS and OS were 7.03 (95% CI: 5.55-8.51) and 14.39 (95% CI: 10.91-17.86) months. The ORR and DCR were 0.432 (95% CI: 0.327-0.538) and 0.756 (95% CI: 0.677-0.836), according to mRECIST 1.1, 0.317 (95% CI: 0.218-0.416) and 0.740 (95% CI: 0.644-0.835), judged by RECIST 1.1. The best outcomes of survival and response rate were observed in ICIs-based combination therapy of ICIs, TKIs, plus LRTs. Furthermore, ORR, DCR judged by mRECIST 1.1, and PFS could be potential prognostic factors for OS. CONCLUSIONS: This research revealed diversified first-line ICIs-based therapies for advanced HCC in real-world practice. Future studies are needed to adopt prospective, multicentric and comparative designs to test the ICIs-based combination therapies, especially triple therapies of ICIs, TKIs, plus LRTs.

Treatment patterns and outcomes in children with infantile hemangiomas: A retrospective observational analysis.

OBJECTIVE: This study aimed to make use of real-world medical records to explore the clinical characteristics, treatments, and outcomes of infantile hemangiomas in southeastern China. METHODS: This study applied a retrospective observational method using real-world data derived from the electronic medical records of the Foshan Women and Children Hospital, southeastern China dated between June 2014 and June 2019. RESULTS: A total of 2427 patients with infantile hemangiomas were recruited in this study, including 942 (38.8%) males and 1485 (61.2%) females. Among the participants, 620 (25.5%) were high-risk infantile hemangioma, 449 (18.5%) were medium risk, and 1358 (56.0%) were low risk. A total of 14 treatment patterns in clinical practice were identified. The top 3 treatment patterns in each group of risk levels were the same: laser therapy, a combination of laser therapy and topical timolol maleate, and topical timolol maleate. The outcomes of the top 3 treatment patterns were significantly (P < 0.05) different in each risk group. CONCLUSION: Among the top 3 treatment patterns, laser therapy or a combination of laser therapy and topical timolol maleate were more likely to have an "Excellent" outcome.

Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae.

PcActx peptide, identified from the transcriptome of zoantharian Palythoa caribaeorum, was clustered into the phylogeny of analgesic polypeptides from sea anemone Heteractis crispa (known as APHC peptides). APHC peptides were considered as inhibitors of transient receptor potential cation channel subfamily V member 1 (TRPV1). TRPV1 is a calcium-permeable channel expressed in epileptic brain areas, serving as a potential target for preventing epileptic seizures. Through in silico and in vitro analysis, PcActx peptide was shown to be a potential TRPV1 channel blocker. In vivo studies showed that the linear and oxidized PcActx peptides caused concentration-dependent increases in mortality of zebrafish larvae. However, monotreatment with PcActx peptides below the maximum tolerated doses (MTD) did not affect locomotor behavior. Moreover, PcActx peptides (both linear and oxidized forms) could effectively reverse pentylenetetrazol (PTZ)-induced seizure-related behavior in zebrafish larvae and prevent overexpression of c-fos and npas4a at the mRNA level. The excessive production of ROS induced by PTZ was markedly attenuated by both linear and oxidized PcActx peptides. It was also verified that the oxidized PcActx peptide was more effective than the linear one. In particular, oxidized PcActx peptide notably modulated the mRNA expression of genes involved in calcium signaling and γ-aminobutyric acid (GABA)ergic-glutamatergic signaling, including calb1, calb2, gabra1, grm1, gria1b, grin2b, gat1, slc1a2b, gad1b, and glsa. Taken together, PcActx peptide, as a novel neuroactive peptide, exhibits prominent anti-epileptic activity, probably through modulating calcium signaling and GABAergic-glutamatergic signaling, and is a promising candidate for epilepsy management.

Drug Utilization for Pain Management during Perioperative Period of Total Knee Arthroplasty in China: A Retrospective Research Using Real-World Data.

Background and Objective: Total knee arthroplasty (TKA) is one of the most painful procedures and perioperative pain usually requires the use of many analgesics to relieve it. The appropriate use of analgesics to relieve patient pain is an important issue of TKA. To characterize the drug utilization for pain management during perioperative period of TKA in China using real-world data of electronic medical records. Materials and Methods: This research used the data of all inpatients who received TKA at 145 hospitals covered 31 provinces in China from 1 January 2016 to 31 December 2018. The exclusion criteria included pregnancy and cancer diagnosis. In the analysis of drug utilization mode (DUM), medicines were classified into 5 groups: non-steroidal anti-inflammatory drugs (NSAIDs), opioids, non-opioid central analgesics, acetaminophen and others. Results: Among the 2017 patients included in this study, there were 1537 (76.20%) female and 480 (23.80%) male, aged 65.77 ± 7.73 years. Regarding the surgery characteristics, 1658 (82.20%) were unilateral; 1220 (60.49%) was graded Level 4; 1312 (65.05%) used local anesthesia as the main anesthesia method, and 1450 (71.89%) lasted for more than 2 h. The most common DUM was "NSAIDs + opioids" (55.92%), followed by "NSAIDs only" (17.85%), and "NSAIDs + Opioids + Non-opioid central analgesics" (17.15%). The results of the Chi-square test showed that differences in DUM were associated with surgery types, surgery levels, surgery duration, and types of anesthesia used. Up to 81.14% of the total drug expenses for pain management was spent on NSAIDs. Due to the limitation of database, this study could not subdivide operation stages, anesthesia methods, dosage forms of drugs. Conclusion: In China, the use of analgesics in perioperative period of TKA was diversified and influenced by a number of surgery characteristics. The rational use of analgesics should be considered in combination with surgery type, surgery level, surgery duration and anesthesia method.

Factors Influencing the Length of Hospital Stay Among Patients with Chronic Obstructive Pulmonary Disease (COPD) in Macao Population: A Retrospective Study of Inpatient Health Record.

Purpose: This study aims to identify the effects of patient and clinical therapy factors on the length of hospital stay (LOS) for admission due to chronic obstructive pulmonary disease (COPD) in Macao. Patients and Methods: Health record of patients with COPD admitted to Kiang Wu Hospital from January 2017 to December 2019 was retrospectively analyzed. Demographic information, blood test results, clinical therapies, and LOS were described and analyzed by multivariable regression. Results: A total of 1116 admissions were included with the average LOS being 12.28 (±9.23) days. Among them, 735 (66.6%) were male with mean age 79.42 (±10.35) years old, 697 were current or previous smokers (62.5%), and 360 (32.2%) had 3 or more comorbidities. During hospitalization, the most common treatments received were oxygen therapy (n=991,88.8%), antibiotics (n=828,74.2%), and systemic steroids (n=596,53.4%); only 120 (10.8%) had pulmonary rehabilitation (PR) and 128 (11.5%) received noninvasive ventilation (NIV). Inhaled medications were used during nearly 95% of hospitalization cases, while 2 and 3 types of inhaled medications were used during 230 (20.6%) and 582 (52.2%) hospitalization cases, respectively. Patient factors including age (B=0.178, 95% CI:0.535-1.072), being female (B=-1.147, 95% CI:-0.138-0.056), being current (B=-0.086, 95% CI:-0.124-0.018) or previous smoker (B=0.072, 95% CI:0.004-0.087), having 1, 2, 3 and over 3 comorbidities (B=0.126, 95% CI:0.034-0.147; B=0.125, 95% CI:0.031-0.144; B=0.116, 95% CI:0.028-0.146, B=0.090, 95% CI:0.021-0.166) and having low hemoglobin level (B=-0.118, 95% CI:-0.629- -0.214) exhibited significant associations with LOS. The use of NIV (B=0.080, 95% CI:0.022-0.138), pulmonary rehabilitation (B=0.269, 95% CI:0.212-0.327), two and three types of inhaled medications (B=0.109, 95% CI:0.003-0.166, B=0.255, 95% CI:0.083-0.237) were significantly associated with longer LOS (P<0.05). Conclusion: NIV, PR and combined inhaled medications, which are often used for AECOPD, are the main clinical therapies associated with longer LOS in Macao. Smoking cessation, early treatments of comorbidities may be crucial to avoiding AECOPD and reducing LOS and disease burden.

Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017.

BACKGROUND: Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. METHODS: A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. RESULTS: Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. CONCLUSIONS: This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

Oxyphylla A ameliorates cognitive deficits and alleviates neuropathology via the Akt-GSK3ß and Nrf2-Keap1-HO-1 pathways in vitro and in vivo murine models of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive brain disorder, and one of the most common causes of dementia and amnesia. Due to the complex pathogenesis of AD, the underlying mechanisms remain unclear. Although scientists have made increasing efforts to develop drugs for AD, no effective therapeutic agents have been found. Objectives: Natural products and their constituents have shown promise for treating neurodegenerative diseases, including AD. Thus, in-depth study of medical plants, and the main active ingredients thereof against AD, is necessary to devise therapeutic agents. Methods: In this study, N2a/APP cells and SAMP8 mice were employed as in vitro and in vivo models of AD. Multiple molecular biological methods were used to investigate the potential therapeutic actions of oxyphylla A, and the underlying mechanisms. Results: Results showed that oxyphylla A, a novel compound extracted from Alpinia oxyphylla, could reduce the expression levels of amyloid precursor protein (APP) and amyloid beta (Aß) proteins, and attenuate cognitive decline in SAMP8 mice. Further investigation of the underlying mechanisms showed that oxyphylla A exerted an antioxidative effect through the Akt-GSK3ß and Nrf2-Keap1-HO-1 pathways.Conclusions.Taken together, our results suggest a new horizon for the discovery of therapeutic agents for AD.

Promoting Community Pharmacy Practice for Chronic Obstructive Pulmonary Disease (COPD) Management: A Systematic Review and Logic Model.

Purpose: This study aimed 1) to identify and analyse the professional services provided by community pharmacists for chronic obstructive pulmonary disease (COPD) management; and 2) to develop a logic model for community pharmacy practice for COPD management. Methods: A systematic review with a logic model was applied. English-language databases (PubMed, Web of Science, Embase, and Scopus) and a Chinese database (CNKI) were searched for articles published between January 2009 and June 2019. Studies concerning pharmacists and COPD were identified to screen for studies that focused on professional services provided at a community pharmacy level. Evidence on economic, clinical, and humanistic outcomes of interventions was summarized. Results: Twenty-five articles were included in this study. Four categories of COPD-related interventions by community pharmacists were identified: 1) primary prevention; 2) early detection; 3) therapy management; and 4) long-term health management. The most common outputs examined were improvement in inhaler technique, medication adherence, and rate of smoking cessation. The clinical (improved quality of life, reduced frequency and severity of symptoms and exacerbation), humanistic (patient satisfaction), and economic (overall healthcare costs) outcomes were tested for some interventions through clinical studies. Contextual factors concerning pharmacists, healthcare providers, patients, facilities, clinic context, and socio-economic aspects were also identified. Conclusion: Studies in the literature have proposed and examined different components of professional services provided by community pharmacists for COPD management. However, relationships among outcomes, comprehensive professional services of community pharmacists, and contextual factors have not been systematically tested. More well-designed, rigorous studies with more sensitive and specific outcomes measures need to be conducted to assess the effect of community pharmacy practice for COPD management.