Factors influencing concentrations of risperidone and 9-hydroxyrisperidone in psychiatric outpatients taking immediate-release formulations of risperidone.

OBJECTIVES: To analyze the factors affecting the concentrations of the active moiety of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in psychiatric outpatients taking immediate-release formulations. METHODS: This is a retrospective study on the therapeutic drug monitoring (TDM) data regarding RIS and 9-OH-RIS in adult psychiatric outpatients. TDM data with simultaneous RIS and 9-OH-RIS monitoring from March 2018 to February 2020 and relevant medical records (including dosage, dosage form, sex, age, diagnosis, combined medication, and comorbid disease) from 399 adult psychiatric outpatients (223 males and 176 females) were included in this study. RESULTS: The daily dose of RIS was 5.56 ± 2.05 mg, the concentration of total active moiety was 42.35 ± 25.46 ng/mL, and the dose-adjusted plasma concentration (C/D) of active moiety was 7.83 ± 3.87 (ng/ml)/(mg/day). Dose, sex, and age were identified as important factors influencing concentrations of RIS and 9-OH-RIS in adult psychiatric outpatients. CONCLUSIONS: Individualized medication adjustments should be made according to the specific conditions of psychiatric outpatients. The findings strongly support the use of TDM to guide dosing decisions in psychiatric outpatients taking RIS.

Population pharmacokinetics and dosing optimization of olanzapine in Chinese paediatric patients: Based on the impact of sex and concomitant valproate on clearance.

WHAT IS KNOWN AND OBJECTIVE: Olanzapine is an atypical antipsychotic drug used for mental disorders. There are limited studies providing sufficient pharmacokinetic data, thus the variability of concentrations of olanzapine used in Chinese paediatric patients aged 10 to 17 years remains to be evaluated. METHODS: Therapeutic drug monitoring data were collected from 151 paediatric patients aged 10 to 17 years who received olanzapine. The model was developed with a NONMEM software program. The final model validation and evaluation were assessed by bootstrap, diagnostic scatter plots, and normalized prediction distribution error (NPDE). Regimens of different dosages were simulated to reach the target concentration levels of 20 ng/ml, by using the final model with typical parameters. RESULTS: The one-compartment model was considered the best fit for the data. Typical estimates of the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) in the final model were 0.142 h-1 , 15.4 L/h, and 322 L, respectively. Sex and concomitant valproate (VPA) were included as significant predictors of olanzapine clearance, which was described by the following equation: CL/F = 15.4 × (1 + 0.546 × SEX) × (1 + 0.264 × VPA). Results of Monte-Carlo simulation suggested that male paediatric patients with concomitant VPA were advised to take no less than 15 mg per day of olanzapine orally, and in female paediatric patients with concomitant VPA, a dosing regimen of 10 mg may be sufficient to achieve the therapeutic range of olanzapine. WHAT IS NEW AND CONCLUSION: Our results identified concomitant valproate and sex as significant covariates in olanzapine population pharmacokinetics. Our model may be a useful tool for recommending dosage adjustments for physicians. The pharmacokinetics of olanzapine in patients aged 10 to 17 years was generally similar to that of adults and the elderly.

A Retrospective Analysis of Steady-State Olanzapine Concentrations in Chinese Patients Using Therapeutic Drug Monitoring: Effects of Valproate and Other Factors.

BACKGROUND: The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years. METHODS: Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring database of the Affiliated Brain Hospital of Guangzhou Medical University. The effects of covariates on serum olanzapine concentration, dose-normalized concentration (C/D ratio), and normalized concentration (C/D/weight) were investigated. RESULTS: Generally, male patients had lower olanzapine concentration, C/D ratio, and C/D/weight than female patients (P < 0.001). Smoking and drinking reduced olanzapine concentration, C/D ratio, and C/D/weight (P < 0.001). Coadministration with valproate decreased olanzapine concentration, C/D ratio, and C/D/weight by about 16%, 30%, and 40%, respectively (P < 0.001). Patients younger than 60 years had higher olanzapine concentrations (P < 0.05) but lower C/D ratios and C/D/weight (P < 0.001) than patients older than 60 years. Age was correlated with olanzapine concentration (r = -0.082, P < 0.05), C/D ratio (r = 0.196, P < 0.001), and C/D/weight (r = 0.169, P < 0.001). Sample timing after dose and diagnostic factors also contributed to the olanzapine concentrations. Multiple linear regression analysis revealed significant influences of dosage, age, sex, valproate comedication, smoking, postdose interval, and schizophrenia (vs bipolar affective disorders) on serum olanzapine concentrations. CONCLUSIONS: The metabolism of olanzapine may be altered by several factors. Patients characterized with a combination of factors may benefit from therapeutic drug monitoring for the adjustment of olanzapine dose to minimize adverse reactions.

Preliminary comparative analysis of kynurenine pathway metabolites in chronic ketamine users, schizophrenic patients, and healthy controls.

OBJECTIVE: The serum kynurenine pathway metabolites kynurenic acid (KYNA), kynurenine (KYN), and tryptophan (TRP) were examined in chronic ketamine users and in schizophrenic patients. The correlations of the metabolites with sociodemographic data, clinical characteristics, and drug use status were analyzed. METHODS: Seventy-nine healthy controls, 78 ketamine users, and 80 schizophrenic patients were recruited. Serum TRP, KYN, and KYNA levels were measured by high-performance liquid chromatography following tandem mass spectrometry (MS/MS). Psychotic symptoms were evaluated using the positive and negative syndrome scale (PANSS), the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI). RESULTS: Serum levels of TRP, KYNA, and KYN (in ketamine users only) were lower in ketamine users and schizophrenic patients than in controls (p < .05). TRP and KYN were lower in ketamine users than in schizophrenic patients (p < .01). KYNA levels were positively correlated with the current frequency of ketamine use in ketamine users (p = .031), and serum KYNA levels were negatively correlated with the duration of schizophrenia (p = .015). CONCLUSION: TRP, KYNA, and KYN were lower in chronic ketamine users than in controls, and the alterations were in the same direction as those observed in schizophrenic patients.

Effects of Alcohol on the Pharmacokinetics of Blonanserin and N-Deethylated Blonanserin in Healthy Chinese Subjects.

PURPOSE/BACKGROUND: Blonanserin is a novel antipsychotic drug approved for the treatment of schizophrenia in East Asia. The main objective of the present study was to investigate the effect of alcohol on the pharmacokinetic properties of blonanserin and its metabolite N-deethyl blonanserin in healthy Chinese male subjects under fasting conditions. METHODS/PROCEDURES: The study was designed as a randomized, open-label, crossover clinical investigation in 10 male volunteers, each of whom received 2 treatments under fasted conditions: treatment A, blonanserin (8 mg) with water, and treatment B, blonanserin (8 mg) with alcohol (1 mL/kg). FINDINGS/RESULTS: The average values of areas under the curve (AUCs) and mean peak plasma concentrations (Cmax) were noticeably increased by alcohol consumption. In treatment A, average values of AUC0-24h, AUC0-∞, and Cmax were 3178 ng/h/L, 3879 ng/h/L, and 492 ng/L for blonanserin, and 1932 ng/h/L, 4208 ng/h/L, and 137 ng/L for N-deethylated blonanserin, respectively. In treatment B, AUC0-∞ and Cmax were both increased 2.4-fold for blonanserin and 1.4-fold and 1.7-fold, respectively, for N-deethylated blonanserin (P < 0.05). Compared with treatment A, clearance (Clz/F) of blonanserin and N-deethylated blonanserin decreased significantly (2.4-fold and 1.7-fold, respectively) in treatment B (P < 0.05). Alcohol delayed the absorption and reduced the clearance of blonanserin, leading to a 1.8-fold increase in the time to reach Cmax (Tmax) and half life time (t1/2) (P < 0.05). IMPLICATIONS/CONCLUSIONS: Alcohol increased the bioavailability of blonanserin and N-deethyl blonanserin in healthy subjects and the marked effect of alcohol on blonanserin bioavailability should be taken into consideration in deciding dosing schedules in clinical therapy.

Effects of food and grapefruit juice on single-dose pharmacokinetics of blonanserin in healthy Chinese subjects.

PURPOSE: The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. METHODS: This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. RESULTS: All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUCt) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. CONCLUSIONS: These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about the ingestion of grapefruit juice.

Pharmacokinetics of guaifenesin, pseudoephedrine and hydrocodone in a combination oral liquid formulation, administered as single and multiple doses in healthy Chinese volunteers, and comparison with data for individual compounds formulated as Antuss®.

1. A new oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone is effective in improving the symptoms of common cold. The pharmacokinetic properties of the individual components were evaluated in a randomized, open-label, four-period study in 12 healthy Chinese volunteers following single and multiple doses. The data were compared with data for the individual ingredients in Antuss®. 2. In the single-dose period, exposure levels (AUC and Cmax) for guaifenesin, pseudoephedrine and hydrocodone increased directly as the dose of the oral liquid formulation increased from 5 to 15 mL. Only minor amounts of guaifenesin and hydrocodone were excreted in urine (∼0.10% and 4.66%, respectively). Pseudoephedrine was mainly excreted unchanged, with 44.95% of the dose excreted in urine within 24 h. After multiple dosing, there was no obvious accumulation of any drug, as assessed by AUC. When considering Cmax, there was a trend toward accumulation of hydrocodone and pseudoephedrine. The pharmacokinetic profiles of guaifenesin and pseudoephedrine in the oral liquid formulation were similar to those in the branded preparation, Antuss®. 3. The newly developed oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone was safe and well tolerated and might provide a reliable alternative to the branded formulation for patients with common colds.

Effect of grapefruit juice and food on the pharmacokinetics of pirfenidone in healthy Chinese volunteers: a diet-drug interaction study.

1. Ingestion of grapefruit juice and food could be factors affecting the pharmacokinetics of pirfenidone, a promising drug for treatment of idiopathic pulmonary fibrosis. 2. A randomized, open-label, three-period crossover study was carried out in 12 healthy Chinese male volunteers who were randomized to one of the three treatments: pirfenidone tablets (0.4 g) were orally administered to fasted or fed subjects, or with grapefruit juice. The washout period was 7 d. 3. Significantly reduced maximum plasma concentration (Cmax, 5.0 5 ± 1.39 versus 10.9 0 ± 2.94 mg·L(- 1)), modestly affected area-under-the-plasma concentration-time curve (AUC) from time zero to 12 h post dosing (AUC0-12 h, 21.8 9 ± 6.47 versus 26.1 6 ± 7.32 mg·h·L(- 1)) and delayed time to reach Cmax (Tmax) were observed in fed group compared with fasted group. Similar effects on Cmax (5.8 2 ± 1.23 versus 10.9 0 ± 2.94 mg·L(- 1)) and AUC0-12 h (modest but not statistically significant, 24.4 4 ± 7.40 versus 26.1 6 ± 7.32 mg·h·L(- 1)) were observed for grapefruit juice compared to fasted subjects. 4. Co-administration of pirfenidone with grapefruit juice resulted in modestly reduced overall oral absorption and significantly reduced peak concentrations compared to fasting, which was similar to effect of food ingestion. No adverse events were observed in the study, but relatively dramatic reduction of peak concentrations should raise concerns for clinical efficacy and safety.

The effect of food on the pharmacokinetic properties and bioequivalence of two formulations of pitavastatin calcium in healthy Chinese male subjects.

1. Pitavastatin is an effective treatment for primary hyperlipidemia and mixed dyslipidemia. The aim of the present study was to investigate the effect of food on the pharmacokinetic properties and bioequivalence of the original, branded, formulation of pitavastatin calcium and a new generic formulation in healthy Chinese male subjects under fasting and fed conditions. 2. Under fasting and fed conditions, 90% CIs of the geometric mean of generic/branded AUC0-48 h ratios were 92.2-102.4%, 93.1-104.5%, the ratios of ln(AUC0-∞) were 92.6-103.7%, 93.2-103.5%, and ln(Cmax) ratios were 90.7-110.3%, 84.7-100.8%, respectively. The generic and branded formulations were bioequivalent in terms of rate and extent of absorption under both the conditions. The average values of AUC0-48 h, AUC0-∞ and Cmax decreased noticeably following a high-fat breakfast. Values for AUC0-48 h were 87.69% and 83.7%, values for AUC0-∞ were 87.5% and 84.6%, and values for Cmax were 45.0% and 50.4% in subjects given the generic and branded preparations, respectively. The absorption of pitavastatin calcium tablets was delayed following a high-fat meal, with Tmax increasing by up to 2.43-fold. 3. Both formulations were generally well tolerated, with no serious adverse reactions reported. The newly developed generic formulation may provide a reliable alternative to the branded tablets for patients with primary hyperlipidemia or mixed dyslipidemia.

Development and psychometric validation of the Chinese version of Skindex-29 and Skindex-16.

BACKGROUND: Dermatological disease significantly affects patient's health-related quality of life (HrQoL). Skindex is one of the most frequently used dermatology-specific HrQoL measures. Currently no Chinese version of Skindex is available. The aim of this study was to translate and culturally adapt Skindex-29 and Skindex-16 into Chinese, and to evaluate their reliability and validity. METHODS: Translation and cultural adaption were performed following guidelines for cross-cultural adaption of health-related quality of life measures. Subsequently, a cross-sectional study was conducted in which patients with dermatological disease (n = 225) were enrolled. The Chinese version of Skindex-29 and Skindex-16 and Dermatology Life Quality Index (DLQI) were completed. Reliability was evaluated with internal consistency using Cronbach's alpha. Validity was evaluated using known-groups validity, convergent validity and factor structure validity. RESULTS: There were both seven items of Skindex-29 and Skindex-16 requiring a second forward- and backward- translation to achieve the final satisfactory Chinese version. The internal consistency reliability was high (range of Cronbach's alpha for the scales of Skindex-29 0.85-0.97, Skindex-16 0.86-0.96). Known-group validity was demonstrated by higher scores from patients with inflammatory dermatosis than from patients with isolated skin lesions (P < 0.05). Evidence of factor structure validity of the Skindex-29 and Skindex-16 was demonstrated by both exploratory factor analysis that accounted for 68.66% and 77.78% of the total variance, respectively, and confirmatory factor analysis with acceptable fitness into the expected three-factor structure. CONCLUSION: This study has developed semantically equivalent translations of Skindex-29 and Skindex-16 into Chinese. The evaluation of the instruments' psychometric properties shows they have substantial evidence of reliability and validity for use as HrQoL instruments in Chinese patients with dermatological disease.

Chinese herbal medicine and acupuncture for insomnia in stroke patients: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Insomnia is highly prevalent in stroke patients; however, there is no ideal intervention. This systematic review examined the effect and safety of Chinese herbal medicine (CHM) and acupuncture on sleep in adults with stroke. METHODS: Six databases were searched from inception to June 2023 to identify randomised controlled trials (RCTs). The primary outcome was Pittsburgh Sleep Quality Index (PSQI) scores. Risk of bias and evidence quality was assessed. A pairwise random-effect meta-analysis was performed. RESULTS: A total of 54 RCTs published in 55 articles were finally included in the systematic review, including 35 of CHM and 19 of acupuncture therapies. Compared with placebo/sham procedure, CHM and acupuncture were more effective in improving PSQI scores. The evidence of moderate quality suggested that CHM outperformed benzodiazepine drugs (BZDs) while it presented an effect similar to that of non-BZDs in improving sleep quality. CHM and acupuncture also provided additional benefits to the patients treated with pharmacological agents alone. However, the evidence specific to individual CHM prescriptions lay in various factors and methodological quality, and the evidence on the comparative effectiveness between acupuncture and other therapies was conflicting or limited. CONCLUSIONS: Overall, CHM and acupuncture used alone or in combination with pharmacotherapy can safely improve sleep in stroke patients with insomnia. In the future, RCTs on outstanding CHM prescriptions and the comparative effectiveness research between acupuncture and other therapies are needed. REGISTRATION: PROSPERO No. CRD42020194029 and No. CRD42020194030.

Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake.

OBJECTIVE: The aim of the study was to better understand blonanserin population pharmacokinetic (PK) characteristics in Chinese healthy subjects. METHODS: Data from two studies with 50 subjects were analyzed to investigate the population PK characteristics of blonanserin at single dose (4, 8, and 12 mg) under fasting, multidose (4 mg bid or 8 mg qd for 7 days) and under food intake condition (single dose, 8 mg). Blonanserin plasma concentrations were detected using the high performance liquid chromatography tandem mass spectrometry (LC/MS/MS). A nonlinear mixed-effects model was developed to describe the blonanserin concentration-time profiles. RESULTS: A two compartment model with first-order absorption was built to describe the time-course of blonanserin. The population-predicted system apparent clearance (CL/F), volume of apparent distribution in center (V(1)/F), and the first-order absorption rate constant (Ka) of blonanserin under fasting was 1230 L/h, 9500 L, and 3.02 h(-1), respectively. Food intake decreased Ka of blonanserin to 0.78 h(-1). The relative bioavailability between fasting and food intake estimated by the final model was 55%. No clinically significant safety issues were identified. CONCLUSION: This is the first study assessing the PK profile of blonanserin with population PKs method. The results can be used for simulation in further clinical trial and optimize individual dosage regimens using a Bayesian methodology in patients.

Medium- and long-term efficacy of ligustrazine plus conventional medication on ischemic stroke: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the medium- to long-term efficacy of ligustrazine plus conventional medicine treating ischemic stroke. METHODS: Randomized controlled trials (RCTs) testing ligustrazine in the treatment of acute ischemic stroke were retrieved from Cochrane Library, PubMed, Excerpta Medica Database, Chinese Medical Journal Database, Chinese Biomedical Database, China National Knowledge Infrastructure Database, and Chinese Clinical Trial Register, and then identified by the inclusive and exclusive criteria. The quality of trials was assessed with the Cochrane Handbook 5.1, a risk of bias assessment tool. RevMan 5.1 was used for meta-analysis. RESULTS: Three RCTs involving 643 patients were included. Compared to conventional medicine treatment alone, ligustrazine plus conventional medicine treatment showed significant difference in reduction of stroke recurrence either at the end of 1-year follow-up [RR = 0.42, 95% CI (0.18, 0.94), P < 0.05] or 3-years observation [RR = 0.48, 95% CI (0.27, 0.83), P < 0.05]. The ligustrazine group also showed higher survival rate [RR =1.67, 95% II (1.02, 0.2.71), P <0.05] and significantly better effective rate [R R= 1.28, 95% II (1.10, 1.50), P <0.05] than that of the control group at the end of 1 year visit. Only one trial conducted safety assessment and no adverse events were reported. The methodological quality of all the trials included was generally poor. CONCLUSION: The findings provided evidence that the combination of ligustrazine and conventional medication was medium- and long-term beneficial to the patients suffering ischemic stroke. But more RCTs of high quality are needed to further prove the efficacy and safety of using ligustrazine for ischemic stroke.

The preliminary evidence on the association of the gut microbiota with stroke risk stratification in South Chinese population.

Aims: This study aimed to investigate the association between the gut microbiota and the risk of stroke. Methods: Faecal samples from 60 participants in South China, including 45 individuals with risk factors for stroke and 15 healthy controls, were collected and subjected to 16S rRNA sequencing. A bioinformatics analysis was performed to characterise the gut microbial diversity and taxonomic compositions at different risk levels (low, moderate, and high) of stroke. Functional prediction and correlation analyses between the microbiota and laboratory markers were performed to explore the potential mechanisms. Results: A significant difference in beta diversity was observed between the participants from the stroke risk and healthy control groups. Linear discriminant effect size analysis revealed a large number of vascular beneficial bacteria enriched in the participants from the healthy control and low-risk groups, but a few vascular harmful bacteria were more abundant in the participants from the high-risk group than in those from the other groups. In addition, Anaerostipes, Clostridium_XlVb, and Flavonifractor, all of which belonged to the Firmicutes phylum, were enriched in the participants from the low-risk group, and their relative abundances gradually decreased as the stroke risk increased. Spearman's analysis revealed that these outstanding microbiota correlated with the levels of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, white blood cells, neutrophils, and carotid intima-media thickness. Conclusion: The preliminary evidence suggests that gut microbiota is associated with stroke risk. It potentially ameliorates atherosclerosis by targeting lipid metabolism and inflammation. This provides novel insights into the early screening of stroke risk and primary prevention.

Efficacy of acupuncture for cardiopulmonary cerebral resuscitation: A systematic review and meta-analysis.

Background: Cerebral resuscitation is one of the main therapeutic aims in the treatment of cardiac arrest (CA) patients who experience a return of spontaneous circulation (ROSC). However, the therapeutic effects of current treatments are not ideal. The purpose of this study was to evaluate the efficacy of neurological function of acupuncture combined with conventional cardiopulmonary cerebral resuscitationthe (CPCR) for patients after ROSC. Methods: Seven electronic databases and other related websites were searched to identify studies on acupuncture combined with conventional CPCR for patients after ROSC. R software was used to conduct a meta-analysis, and the outcomes that could not be pooled were analyzed using a descriptive analysis. Results: Seven RCTs involving 411 participants who had experienced ROSC were eligible for inclusion. The main acupoints were Neiguan (PC6), Shuigou (DU26), Baihui (DU20), Yongquan (KI1), and Sanyinjiao (SP6). Compared to conventional CPCR, acupuncture combined with conventional CPCR led to significantly higher Glasgow Coma Scale (GCS) scores on day 3 (mean difference (MD)=0.89, 95% CI: 0.43, 1.35, I2 = 0%), day 5 (MD = 1.21, 95% CI: 0.27, 2.15; I2 = 0%), and day 7 (MD = 1.92, 95% CI: 1.35, 2.50; I2 = 0%). Conclusion: Acupuncture-assisted conventional CPCR may have a potential role in improving neurological function in CA patients after ROSC, but the certainty of evidence is very low and more high-quality studies are required. Protocol registration: This review was registered at the International Prospective Registry of Systematic Reviews (PROSPERO): CRD42021262262.

Knowledge atlas of the involvement of glutamate and GABA in alcohol use disorder: A bibliometric and scientometric analysis.

Introduction: Abnormal neurotransmission of glutamate and γ-aminobutyric acid (GABA) is a key characteristic of alcohol-related disorders. To track research output, we conducted a bibliometric analysis to explore the current status and trends in this field over the past decades. Methods: Studies related to neurotransmitters and alcohol use disorder published in English from 2005-2021 were retrieved from the Web of Science Core Collection and Scopus databases. The R-bibliometrix package was used for a descriptive analysis of the publications. Citespace, WOSviewer, and R-bibliometrix were used to construct networks of countries/institutions/authors based on co-authorship, co-citation analysis of cited references and co-occurrence as well as burst detection of keywords. Results: A total of 4,250 unique articles and reviews were included in the final analysis. The annual growth rate of publications was 5.4%. The USA was the most productive country in this field, contributing nearly half of the total documents. The top ten most productive institutions were all located in the USA. The most frequent worldwide collaboration was between the USA and Italy. The most productive and influential institution was the University of California. The author contributing the most productions to this field was Marisa Roberto from the Scripps Research Institute. The top co-cited reference was a review titled "Neurocircuitry of addiction." The top journal in terms of the number of records and citations was Alcoholism: Clinical and Experimental Research. Comprehensive analyses have been conducted over past decades based on co-cited reference analysis, including modulators, transporters, receptor subtypes, and animal models. In recent years, the research frontiers have been shifting to the identification of risk factors/biomarkers, drug development for alcohol use disorder, and mechanisms related to alcoholic and non-alcoholic fatty liver. Conclusion: Our bibliometric analysis shows that glutamate and GABA continue to be of interest in alcohol use disorder. The focus has evolved from mechanisms and medications related to glutamate and GABA in alcohol use disorder, to novel drug development, risk factor/biomarker identification targeting neurotransmitters, and the mechanisms of related diseases.

Traditional Chinese Medicine for Post-stroke Sleep Disorders: The Evidence Mapping of Clinical Studies.

Background and Purpose: Recently, there are a number of clinical studies on traditional Chinese medicine (TCM) for post-stroke sleep disorders (PSSDs). This study aimed to map the current clinical studies and identify gaps to inform future study agendas. Methods: PubMed, Embase, Cochrane Library, and Chinese databases, including SinoMed, CNKI, and Wanfang, were searched for clinical studies on PSSDs treated with TCM from their inception to September 2021. Evidence sources, number of studies, types of PSSDs, intervention categories, effectiveness, and quality assessment were graphically displayed. Results: The evidence map involved 810 clinical studies, of which the earliest report was dated back to 1993, and an advanced growth of the whole evidence was observed in 2012. Randomized controlled trials (RCTs) were the most common type of study design (78.15%), and post-stroke insomnia was the most common type of sleep disorders (65.80%). The benefits of Chinese herbal medicine (CHM) and acupuncture therapies for post-stroke insomnia have been widely reported in RCTs (81.60% and 75.38%, respectively). However, the benefits of CHM interventions were assessed using a global approach rather than being based on a specific formula, and the highest level of evidence supporting the effectiveness of acupuncture therapies was of low methodological quality. In addition, evidence from primary studies was insufficient in the areas of TCM for post-stroke sleep-related breathing disorders (SBDs) and Chinese mind-body exercises for post-stroke insomnia. Conclusions: PSSDs treated with TCM have been widely assessed in clinical studies. For better evidence translation, clinical trials on specific CHM interventions and high-quality systematic reviews on acupuncture for post-stroke insomnia should be conducted. For a better solution to clinical questions, TCM on SBDs after stroke and the benefits of Chinese mind-body exercises for post-stroke insomnia should be explored in future clinical studies.

Risk of Stroke Among Different Metabolic Obesity Phenotypes: A Systematic Review and Meta-Analysis.

Background and Purpose: Overweight/obesity is a modified risk factor for stroke. This systematic review and meta-analysis aimed to assess the impact of different obesity phenotypes on stroke risk in adults. Methods: The PubMed, Embase, and Cochrane Library databases were searched from their inception to 7 March 2021 to identify the prospective cohort studies investigating stroke risk among different metabolic overweight/obesity phenotypes. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results: A total of eleven prospective cohorts (n = 5,609,945 participants) were included in the systematic review, nine of which were included in the meta-analysis. All metabolically unhealthy phenotypes had a higher risk of stroke than the metabolically healthy normal-weight phenotypes, including metabolically unhealthy normal weight (HR = 1.63, 95% CI: 1.41-1.89, I2 = 89.74%, n = 7 cohort studies, 1,042,542 participants), metabolically unhealthy overweight (HR = 1.94, 95% CI: 1.58-2.40, I2 = 91.17%, n = 4 cohort studies, 676,166 participants), and metabolically unhealthy obese (HR = 1.99, 95% CI: 1.66-2.40, I2 = 93.49%, n = 6 cohort studies, 1,035,420 participants) phenotypes. However, no risk of stroke was observed in the populations with metabolically healthy overweight (MHOW) (HR = 1.07, 95% CI: 1.00-1.14, I2 = 69.50%, n = 5 studies, 4,171,943 participants) and metabolically healthy obese (MHO) (HR = 1.07, 95% CI: 0.99-1.16, I2 = 54.82%, n = 8 studies, 5,333,485 participants) phenotypes. The subgroup analyses for the MHO studies suggested that the risk of stroke increased only when the MHO participants were mainly females, from North America, and when the World Health Organization standard was applied to define obesity. In the subgroup analysis of the risk of stroke in MHOW, a longer follow-up duration was also associated with a higher risk of stroke. Conclusion: The risk of stroke increase for all metabolically unhealthy phenotypes irrespective of the body mass index (BMI). The associated risk of stroke with metabolic health but high BMI shows substantial heterogeneity, which requires future research considering the impact of sex and transition of the metabolic status on the risk of stroke. Systematic Review Registration: The study protocol was prospectively registered in PROSPERO (No. CRD42021251021).

The role of acupuncture and moxibustion in the treatment, prevention, and rehabilitation of patients with COVID-19: A scoping review.

Introduction: This study aims to summarize the available evidence and guideline/consensus recommendations for acupuncture and moxibustion in the treatment, prevention and rehabilitation of patients with coronavirus disease 2019 (COVID-19). Methods: A scoping review was performed. Eight electronic databases and other related websites were searched. All studies related to acupuncture and moxibustion for COVID-19 were considered. Descriptive analysis was applied to analyze the all included studies and guideline recommendations. Results: We ultimately included 131 eligible studies. The main topics of the included studies were the treatment (82.4%) and prevention (38.9%) of COVID-19. The most included studies were literature reviews (65, 49.6%), protocols of systematic reviews (20, 15.3%), and guidelines and consensuses (18, 13.7%). The 18 (13.7%) COVID-19 guidelines and consensuses included 47 recommendations on acupuncture and moxibustion, which focused on the treatment (21/47, 44.7%), rehabilitation (17/47, 36.2%) and prevention (6, 12.8%) of COVID-19 patients. Zusanli (ST36), Feishu (BL13), Guanyuan (RN4) were recommended mostly for the treatment, rehabilitation and prevention respectively. Conclusion: Acupuncture and moxibustion are effective in the treatment of COVID-19 patients to some extent. However, more high-quality of clinical trials still needed to determine the feasibility of acupuncture and moxibustion in COVID-19 patients to better guide clinical practice. Study registration: Open Science Framework Registries (Registration DOI: 10.17605/OSF.IO/Z35WN; https://osf.io/z35wn).

Clinical Evidence on the Use of Chinese Herbal Medicine for Acute Infectious Diseases: An Overview of Systematic Reviews.

Background: Acute infectious diseases constitute the most prevalent public health emergency (PHE) in China. Chinese herbal medicine (CHM) has long been used in the treatment of acute infections, but the overall evidence of its benefit and harm has not been comprehensively and systematically evaluated. Methods: We searched CBM, CNKI, Wanfang, PubMed, Cochrane Library, embase and preprint platforms to retrieve systematic reviews (SRs) on CHM for acute infectious. Participants with COVID-19, SARS, H1N1, tuberculosis, bacillary dysentery, mumps, herpangina, hand-foot-and-mouth disease (HFMD), and other acute infectious diseases were included. Interventional group consisting of patients treated with CHM combined with Western medicine or CHM alone. The AMSTAR 2 tool was used to assess the methodological quality of the retrieved studies. Information on interventions, control measures and outcomes of the included studies was extracted, and meta-analyses were qualitatively synthesized. Results: A total of 51 SRs and meta-analyses were eligible for this overview, including 19 for COVID-19, 11 for hand-foot-and-mouth disease, 8 for severe acute respiratory syndrome (SARS), 4 for tuberculosis, 3 for mumps, 2 for bacillary dysentery, 2 for H1N1 influenza and 2 for herpangina. Six systematic reviews were of high quality, all of which were on the use of CHM for COVID-19; 24 were of moderate quality; 10 were of low quality; and 11 were of very low quality. CHM appeared to have potential benefits in improving clinical symptoms and signs for most infections with an acceptable safety profile, and the clinical evidence of the benefits of CHM for acute respiratory infections such as COVID-19, SARS and H1N1 seems more sufficient than that for other acute infections. Conclusion: Overall, CHM, both decoction and Chinese patent medicine, used alone or in combination with conventional medicine may offer potential benefits to relieving symptoms of people with acute respiratory infections. Full reporting of disease typing, staging, and severity, and intervention details is further required for a better evidence translation to the responses for PHE. Future CHM research should focus mainly on the specific aspects of respiratory infections such as its single use for mild infections, and the adjunct administration for sever infections, and individual CHM prescriptions for well-selected outcomes should be prioritized.