Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier.

Elicitation of VRC01-class broadly neutralizing antibodies (bnAbs) is an appealing approach for a preventative HIV-1 vaccine. Despite extensive investigations, strategies to induce VRC01-class bnAbs and overcome the barrier posed by the envelope N276 glycan have not been successful. Here, we inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation. Env immunogens designed on reverted VRC01-class bnAbs bound to VRC01 UCA with affinity sufficient to activate naive B cells. Early mutations defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B cell maturation toward the development of neutralization breadth. Finally, VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan.

Protective human antibodies against a conserved epitope in pre- and postfusion influenza hemagglutinin.

Phylogenetically and antigenically distinct influenza A and B viruses (IAV and IBV) circulate in human populations, causing widespread morbidity. Antibodies (Abs) that bind epitopes conserved in both IAV and IBV hemagglutinins (HAs) could protect against disease by diverse virus subtypes. Only one reported HA Ab, isolated from a combinatorial display library, protects against both IAV and IBV. Thus, there has been so far no information on the likelihood of finding naturally occurring human Abs that bind HAs of diverse IAV subtypes and IBV lineages. We have now recovered from several unrelated human donors five clonal Abs that bind a conserved epitope preferentially exposed in the postfusion conformation of IAV and IVB HA2. These Abs lack neutralizing activity in vitro but in mice provide strong, IgG subtype-dependent protection against lethal IAV and IBV infections. Strategies to elicit similar Abs routinely might contribute to more effective influenza vaccines.

Photosynthetic-Membrane-Like Ion Translocation in Visible-Light-Harvesting Nanofluidic Channels.

The selective uphill and downhill movement of protons in and out of photosynthetic membrane enabled by ion pumps and ion channels is key to photosynthesis. Reproducing the functions of photosynthetic membranes in artificial systems has been a persistent goal. Here, a visible-light-harvesting nanofluidic channels is reported which experimentally demonstrates the ion translocation functions of photosynthetic membranes. A molecular junction consisting of photosensitive ruthenium complexes linked to TiO2 electron acceptors forms the reaction centers in the nanofluidic channels. The visible-light-triggered vectorial electron injection into TiO2 establishes a difference in transmembrane potential across the channels, which enables uphill transport of ions against a 5-fold concentration gradient. In addition, the asymmetric charge distribution across the channels enables the unidirectional downhill movement of ions, demonstrating an ion rectification effect with a ratio of 18:1. This work, for the first time, mimics both the uphill and downhill ion translocation functions of photosynthetic membranes, which lays a foundation for nanofluidic energy conversion.

[Guidelines for economic evaluation of post-marketing Chinese patent medicine].

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.

Dietary dibutyryl cAMP supplementation regulates the fat deposition in adipose tissues of finishing pigs via cAMP/PKA pathway.

This study investigated potential mechanism of dibutyryl-cAMP (db-cAMP) on porcine fat deposition. (1) Exp.1, 72 finishing pigs were allotted to 3 treatments (0, 10 or 20 mg/kg dbcAMP) with 6 replicates. dbcAMP increased the hormone sensitive lipase (HSL) activity and expression of ß-adrenergic receptor (ß-AR) and growth hormone receptor (GHR), but decreased expression of peroxisome proliferator-activated receptor gamma 2 (PPAR-γ2) and adipocyte fatty acid binding protein (A-FABP) in back fat. dbcAMP upregulated expression of ß-AR, GHR, PPAR-γ2 and A-FABP, but decreased insulin receptor (INSR) expression in abdominal fat. Dietary dbcAMP increased HSL activity and expression of G protein-coupled receptor (GPCR), cAMP-response element-binding protein (CREB) and insulin-like growth factor-1 (IGF-1), but decreased fatty acid synthase (FAS) and lipoprotein lipase (LPL) activities, and expression of INSR, cAMP-response element-binding protein (C/EBP-α) and A-FABP in perirenal fat. (2) Exp. 2, dbcAMP suppressed the proliferation and differentiation of porcine preadipocytes in a time- and dose-dependent manner, which might be associated with increased activities of cAMP and protein kinase A (PKA), and expression of GPCR, ß-AR, GHR and CREB via inhibiting C/EBP-α and PPAR-γ2 expression. Collectively, dbcAMP treatment may reduce fat deposition by regulating gene expression related to adipocyte differentiation and fat metabolism partially via cAMP-PKA pathway.

Cation-Selective Oxide Semiconductor Mesoporous Membranes for Biomimetic Ion Rectification and Light-Powered Ion Pumping.

Artificial membranes precisely imitating the biological functions of ion channels and ion pumps have attracted significant attention to explore nanofluidic energy conversion. Herein, inspired by the cyclic ion transport for the photosynthesis in purple bacteria, a bilayer inorganic membrane (TiO2 /AAO) composed of oxide semiconductor (TiO2 ) mesopores on anodic alumina (AAO) macropores is we developed. This inorganic membrane achieves the functions of ion channels and ion pumps, including the ion rectification and light-powered ion pumping. The asymmetric charge distribution across the bilayer membrane contributes to the cationic selectivity and ion rectification characteristics. The electrons induced by ultraviolet irradiation introduce a built-in electric field across TiO2 /AAO membrane, which pumps the active ion transport from a low to a high concentration. This work integrates the functions of biological ion channels and ion pumps within an artificial membrane for the first time, which paves the way to explore multifunctional membranes analogous to its biological counterpart.

Light-Powered Ion Pumping in a Cation-Selective Conducting Polymer Membrane.

The simulation of the ion pumping against a proton gradient energized by light in photosynthesis is of significant importance for the energy conversion in a non-biological environment. Herein, we report light-powered ion pumping in a polystyrene sulfonate anion (PSS) doped polypyrrole (PPy) conducting polymer membrane (PSS-PPy) with a symmetric geometry. This PSS-PPy conducting polymer membrane exhibits a cationic selectivity and a light-responsive surface-charge-governed ion transport attributed to the negatively charged PSS groups. An asymmetric visible irradiation on one side of the PSS-PPy membrane induces a built-in electric field across the membrane due to the intrinsic photoelectronic property of PPy, which drives the cationic transport against the concentration gradient, demonstrating an ion-pumping effect. This work is a prototype that uses a geometry-symmetric conducting polymer membrane as a light-powered artificial ion pump for active ion transport, which exhibits potential applications in nanofluidic energy conversion.

Potentially inappropriate medications among elderly patients in community healthcare institutions in Beijing, China.

PURPOSE: To evaluate potentially inappropriate medications (PIMs) prevalence and predictors in community healthcare institutions (CHIs) for the elderly. METHODS: We conducted a retrospective observational study, deriving data of patients aged ≥60 from 66 CHIs in Beijing, 2014-2018. The system of Criteria of PIM for Older Adults in China was applied to identify PIMs. The primary outcome was the prevalence of visits with at least one PIM; secondary outcomes were the frequency and rate per thousand visits of specific PIMs. We used descriptive analysis and generalized linear models to analyzed PIMs and the predictors, and marginal effects methods were applied to estimate the mean adjusted PIMs prevalence. RESULTS: Overall, 4 528 884 elderly patient visits from 2014 to 2018 were eligible for inclusion. A total of 719 757 PIMs were detected, with 14.1% of the visits contained at least one PIM. PIM prevalence was significantly correlated with age, number of prescribed medications and number of diagnoses. Overall, 6.0 per thousand elderly patients in CHIs were exposed to at least one high-risk PIM, while 117.5 per thousand were exposed to at least one low-risk PIM. In 2018, 20% of GPs were responsible for more than half of overall PIM visits. CONCLUSION: Prescribing of PIMs for older adults is common in CHIs in China, especially for patients who are aged, having multiple medications and diagnostic diseases. Strategies should be developed to enhance prescribing quality for geriatric patients, with special targeting of doctors responsible for a high number of PIMs.

Microbiome and metabolome analyses reveal significant alterations of gut microbiota and bile acid metabolism in ETEC-challenged weaned piglets by dietary berberine supplementation.

This study mainly investigated the effects of berberine (BBR) on the bile acid metabolism in gut-liver axis and the microbial community in large intestine of weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC) by microbiome and metabolome analyses. Sixty-four piglets were randomly assigned to four groups including Control group, BBR group, ETEC group, and BBR + ETEC group. Dietary BBR supplementation upregulated the colonic mRNA expression of Occludin, Claudin-5, trefoil factor 3 (TFF3), and interleukin (IL)-10, and downregulated colonic IL-1ß and IL-8 mRNA expression in piglets challenged with ETEC K88 (p < 0.05). The hepatic non-targeted metabolome results showed that dietary BBR supplementation enriched the metabolic pathways of primary bile acid biosynthesis, tricarboxylic acid cycle, and taurine metabolism. The hepatic targeted metabolome analyses showed that BBR treatment increased the hepatic concentrations of taurocholic acid (TCA) and taurochenodeoxycholic acid (TDCA), but decreased the hepatic cholic acid (CA) concentration (p < 0.05). Further intestinal targeted metabolome analyses indicated that the deoxycholic acid (DCA), hyocholic acid (HCA), 7-ketodeoxycholic acid (7-KDCA), and the unconjugated bile acid concentrations in ileal mucosa was decreased by dietary BBR treatment (p < 0.05). Additionally, BBR treatment significantly upregulated the hepatic holesterol 7 α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) mRNA expression, and upregulated the ileal mRNA expression of farnesoid X receptor (FXR) and apical sodium-dependent bile acid transporter (ASBT) as well as the colonic mRNA expression of FXR, fibroblast growth factor19 (FGF19), takeda G protein-coupled receptor 5 (TGR5) and organic solute transporters beta (OST-ß) in piglets (p < 0.05). Moreover, the microbiome analysis showed that BBR significantly altered the composition and diversity of colonic and cecal microbiota community, with the abundances of Firmicutes (phylum), and Lactobacillus and Megasphaera (genus) significantly increased in the large intestine of piglets (p < 0.05). Spearman correlation analysis showed that the relative abundances of Megasphaera (genus) were positively correlated with Claudin-5, Occludin, TFF3, and hepatic TCDCA concentration, but negatively correlated with hepatic CA and glycocholic acid (GCA) concentration (p < 0.05). Moreover, the relative abundances of Firmicute (phylum) and Lactobacillus (genus) were positively correlated with hepatic TCDCA concentration (p < 0.05). Collectively, dietary BBR supplementation could regulate the gut microbiota and bile acid metabolism through modulation of gut-liver axis, and attenuate the decreased intestinal tight junction expression caused by ETEC, which might help maintain intestinal homeostasis in weaned piglets.

Influencing Factors of Generic Prescribing Behavior of Physicians: A Structural Equation Model Based on the Theory of Planned Behavior.

Background: Although affordable generics could probably contribute to the solution of rapidly increasing pharmaceutical expenditure, those drugs are prescribed at a lower rate in China. Physicians' perception and knowledge of generics have a great influence on their prescribing behavior. Objective: This study aimed to identify factors that affect physicians' generic prescribing behavior based on the theory of planned behaviors (TPB). Methods: Data were collected by both electronic and paper-based surveys from 1297 Chinese physicians, and 1047 surveys were retained. The structural equation model (SEM) was employed to investigate the relationship between four behavioral constructs, namely, attitudes, subjective norms, perceived control of behaviors, and intentions. Results: About 50% of Chinese physicians had a positive attitude towards generic drugs that had passed the "Consistency Evaluation of Quality and Efficacy of Generic Drugs" (high-quality generic drugs), but their knowledge of generic drugs was relatively inadequate. The path coefficients for the effect of attitudes, subjective norms, and perceived behavioral control on behavioral intention were 0.285, 0.366, and 0.322 respectively. The path coefficients for the effect of behavioral intention and perceived behavioral control on prescribing behavior were 0.009 and 0.410 respectively. Conclusion: Physicians' attitudes, subjective norms, and perceived behavioral control were significant positive correlation predictors of behavioral intention. Subjective norms and perceived behavior control had a greater impact than attitude on physicians' prescribing intention. However, the generic prescribing behavior is not under the volitional control of Chinese physicians. Physicians' prescribing practice is likely affected by perceived strong control over prescribing generic drugs.

Pharmacogenomic Polygenic Model of Clopidogrel Predicts Recurrent Ischemic Events in Chinese Patients With Coronary Artery Disease.

PURPOSE: Patients with coronary artery disease (CAD) need to take antiplatelet drugs regularly in order to prevent thrombosis; however, there is existing inter-individual variability in drug response. Pharmacogenomic studies indicate that drug response may also be influenced by genetic variants, and multiple genetic variants may work together. We assumed that patients carrying more risk alleles might have a worse clopidogrel drug response and that a polygenic model integrated different single variants might have the potential to explain clopidogrel drug response variability better. We aimed to investigate whether the polygenic model could be used to predict clopidogrel drug response. METHODS: A total of 935 CAD patients were enrolled in the study. We investigated the association between 19 clopidogrel-related single-nucleotide polymorphisms (SNPs) and the incidence of recurrent ischemic events. Additionally, a polygenic model was constructed to assess the risk of ischemic events. FINDINGS: There were only 2 SNPs of CYP2C8 gene (rs1934980 and rs17110453) that were nominally associated with incidence of recurrent ischemic events. We constructed a polygenic model integrated with 6 clopidogrel-related SNPs. When compared with patients carrying 6 or fewer risk alleles, patients with 7 or more risk alleles had a higher risk of ischemic events (hazard ratio = 1.87; P = 0.04). IMPLICATIONS: The polygenetic model may be useful for clopidogrel drug response prediction in patients with CAD.

Macrophage-derived FGFR1 drives atherosclerosis through PLCγ-mediated activation of NF-κB inflammatory signaling pathway.

BACKGROUND: Atherosclerosis is a leading cause of cardiovascular morbidity and mortality. Atherosclerotic lesions show increased levels of proteins associated with the fibroblast growth factor receptor (FGFR) pathway. However, the functional significance and mechanisms governed by FGFR signaling in atherosclerosis are not known. In the present study, we investigated FGFR1 signaling in atherosclerosis development and progression. METHODS AND RESULTS: Examination of human atherosclerotic lesions and aortas of Apoe-/- mice fed a high-fat diet (HFD) showed increased levels of FGFR1 in macrophages. We deleted myeloid-expressed Fgfr1 in Apoe-/- mice and showed that Fgfr1 deficiency reduces atherosclerotic lesions and lipid accumulations in both male and female mice upon HFD feeding. These protective effects of myeloid Fgfr1 deficiency were also observed when mice with intact FGFR1 were treated with FGFR inhibitor AZD4547. To understand the mechanistic basis of this protection, we harvested macrophages from mice and show that FGFR1 is required for macrophage inflammatory responses and uptake of oxidized LDL. RNA sequencing showed that FGFR1 activity is mediated through phospholipase-C-gamma (PLCγ) and the activation of nuclear factor-κB (NF-κB) but is independent of FGFR substrate 2. CONCLUSION: Our study provides evidence of a new FGFR1-PLCγ- NF-κB axis in macrophages in inflammatory atherosclerosis, supporting FGFR1 as a potentially therapeutic target for atherosclerosis-related diseases.

Roles and regulation of Aquaporin-3 in maintaining the gut health: an updated review.

Aquaporin-3 (AQP3) is a predominant water channel protein expressed in the intestine, and plays important roles in the gut physiology and pathophysiology due to its permeability to water, glycerol and hydrogen peroxide. In this review, we systematically summarized the current understanding of the expression of AQP3 in the intestine of different species, and focused on the potential roles of AQP3 in water transport, different types of diarrhea and constipation, intestinal inflammation, intestinal barrier function, oxidative stress, and autophagy. These updated findings have supported that AQP3 may function as an important target in maintaining gut health of human and animals.

Research Note: Dietary resveratrol supplementation improves the hepatic antioxidant capacity and attenuates lipopolysaccharide-induced inflammation in yellow-feathered broilers.

This experiment investigated the protective effect of resveratrol (RES) on the hepatic antioxidant status and systemic inflammation in yellow-feathered broilers challenged with lipopolysaccharide (LPS). A total of 240 healthy 1-day-old yellow-feathered broilers were randomly divided into 4 groups (control, LPS, RES, and RES+LPS), with 5 replicates of 12 chickens per replicate. The experiment lasted 21 d. The broilers were fed with either the basal diet or the basal diet supplemented with 400 mg/kg RES followed by intraperitoneal challenge with LPS (1 mg/kg body weight) or the same amount of saline at d 16, 18, and 20. The results showed that dietary RES supplementation could improve the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in the liver of yellow-feathered broilers challenged with LPS (P < 0.05). Furthermore, LPS challenge increased the plasma interleukin-17 (IL-17) concentration, the hepatic interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) concentrations, as well as the concentrations of tumor necrosis factor (TNF-α), IL-6, and IL-1ß in the spleen (P < 0.05), and decreased the transforming growth factor-ß (TGF-ß) concentrations in the plasma, liver, and spleen (P < 0.05). However, dietary RES supplementation could reduce the increased TNF-α levels in the plasma, liver, and spleen induced by LPS, and increased TGF-ß level in the liver and spleen (P < 0.05). Collectively, these results suggest that dietary RES supplementation could effectively improve the hepatic antioxidant capacity and attenuate LPS-induced inflammation in yellow-feathered broilers during the starter stage.

Efficacy, safety, and cost-effectiveness of therapeutic drug monitoring (TDM) for TNF inhibitor therapy in rheumatic disease: A systematic review and meta-analysis.

OBJECTIVE: The benefits of TDM-guided TNFi therapy in patients with rheumatic disease was still controversial. This systematic review and meta-analysis was conducted to explore if the TDM-guided TNFi therapy is superior to empirical-guided therapy. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and EMBASE databases for articles published between database inception and October 05, 2023. Studies reporting endpoints in TDM-guided TNFi therapy and empirical therapy were included. Results would be presented in risk ratio (RR) and mean difference, with 95 % confidence interval (CI) reported. This study is registered with PROSPERO (CRD42022353956). RESULTS: A total of 14 studies (eight RCTs and six cohort studies) involving 2427 patients were included in this meta-analysis. In the scenario of response prediction, compared with empirical-guided therapy, TDM-guided TNFi therapy had association with higher treat-to-target rates (RR 1.30, 95 % CI 1.02-1.65, P=0.03, I2=79 %), more specifically, higher low disease activity rates (RR 2.11, 95 % CI 1.22-3.66, P=0.007, I2=61 %), but no difference in clinical remission rates (RR 0.98,95 % CI 0.87-1.11, P=0.75, I2=0 %). In the scenario of dose reduction prediction, lower relapse rates (RR 0.73, 95 % CI 0.65-0.82, P <0.00001, I2=0 %) were observed compared with empirical-guided dose reduction strategy, but no difference (RR 1.24, 95 % CI 0.85-1.80, P=0.27, I2=57 %) between TDM-guided dose reduction and standard-dosing therapy. No significant difference was observed in change of disease activity score, mean disease activity score, radiographic progression, and safety. And TDM-guided therapy was associated with reduced cost per patient per year calculated as the total accumulated sum of therapy cost. CONCLUSION: TDM-guided TNFi therapy was associated with increased rates of low disease activity and decreased risks of relapse, and may save cost compared with empirical-guided therapy in patients with rheumatic disease. But this does not mean that the use of TDM-guided TNFi therapy can be advocated, because there is no difference in clinical remission rates and many other outcomes. More researches, especially randomized clinical trials are needed to verify this conclusion in the future.

Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials.

Background: Chimeric antigen receptor T cells treatment targeting B cell maturation antigen (BCMA) is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) and has demonstrated outstanding outcomes in clinical studies. Objective: The aim of this comprehensive review and meta-analysis was to summarize the effectiveness and safety of anti-BCMA CAR-T treatment for patients with relapsed/refractory multiple myeloma (RRMM). Our research identifies variables influencing outcome measures to provide additional evidence for CAR-T product updates, clinical trial design, and clinical treatment guidance. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard was followed for conducting this comprehensive review and meta-analysis, which was submitted to PROSPERO (CRD42023390037). From the inception of the study until 10 September 2022, PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and WanFang databases were searched for eligible studies. Stata software (version 16.0) was used to assess effectiveness and safety outcomes. Results: Out of 875 papers, we found 21 relevant trials with 761 patients diagnosed as RRMM and were given anti-BCMA CAR-T treatment. The overall response rate (ORR) for the entire sample was 87% (95% CI: 80-93%) complete response rate (CRR) was 44% (95% CI: 34-54%). The minimal residual disease (MRD) negativity rate within responders was 78% (95% CI: 65-89%). The combined incidence of cytokine release syndrome was 82% (95% CI: 72-91%) and neurotoxicity was 10% (95% CI: 5%-17%). The median progression-free survival (PFS) was 8.77 months (95% CI: 7.48-10.06), the median overall survival (OS) was 18.87 months (95% CI: 17.20-20.54) and the median duration of response (DOR) was 10.32 months (95% CI: 9.34-11.31). Conclusion: According to this meta-analysis, RRMM patients who received anti-BCMA CAR-T treatment have demonstrated both effectiveness and safety. Subgroup analysis confirmed the anticipated inter-study heterogeneity and pinpointed potential factors contributing to safety and efficacy, which may help with the development of CAR-T cell studies and lead to optimized BCMA CAR-T-cell products. Systematic Review Registration: Clinicaltrials.gov, PROSPERO, CRD42023390037.

The Impact of Prescribing Monitoring Policy on Drug Use and Expenditures in China: A Multi-center Interrupted Time Series Study.

BACKGROUND: A prescribing monitoring policy (PMP) was implemented in November 2015 in Anhui province, China, the first province to pilot this policy to manage the use and costs of select drugs based on their large prescription volumes and/ or costs in hospitals. This study evaluated the impact of PMP on the use and expenditures of different drugs in three tertiary hospitals in Anhui. METHODS: We obtained monthly drug use and expenditures data from three tertiary hospitals in Anhui (November 2014 through September 2017). An interrupted time series (ITS) design was used to estimate changes in defined daily doses (DDDs per month) and drug expenditures (dollars per month) of policy-targeted and non-targeted drugs after PMP implementation. Drugs were grouped based on whether they were recommended (recommended drugs) by any clinical guidelines or not (non-recommended drugs), or if they were potentially over-used (proton pump inhibitors, PPIs). RESULTS: After PMP, DDDs and costs of the targeted PPIs (omeprazole) declined while use of non-targeted PPIs increased correspondingly with overall sustained declines in total PPIs. The policy impact on recommended drugs varied based on whether the targeted drugs have appropriate alternatives. The DDDs and costs of recommended drugs that have readily accessible appropriate alternatives (atorvastatin) declined, which offset increases in its alternative non-target drugs (rosuvastatin), while there was no significant change in those recommended drugs that did not have appropriate alternative drugs (clopidogrel and ticagrelor). Finally, the DDDs and costs of non-recommended drugs decreased significantly. CONCLUSION: PMP policy impact was not the same across different drug groups. PMP did help contain the use and costs of potentially over-used drugs and non-recommended drugs. PMP did not seem to reduce the use of first-line therapeutic drugs recommended by clinical treatment guidelines, especially those lacking alternatives; such drugs are unlikely appropriate candidates for PMP.

Traditional Chinese medicine for frozen shoulder: An evidence-based guideline.

BACKGROUND: Frozen shoulder is a common disorder that can lead to long-lasting impairment in shoulder-related daily activities. Traditional Chinese medicine (TCM) has played an important role in the effort to manage frozen shoulder. PURPOSE: We aimed to develop an evidence-based guideline for treating frozen shoulder with traditional Chinese medicine. STUDY DESIGN: Evidence-based guideline. METHODS: We developed this guideline based on internationally recognized and accepted guideline standards. The guideline development group used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate the certainty of evidence and the strength of recommendations. The benefits and harms, resources, accessibility, and other factors were fully taken into account, and the GRADE grid method was used to reach consensus on all recommendations. RESULTS: We established a multidisciplinary guideline development panel. Based on a systematic literature search and a face-to-face meeting, nine clinical questions were identified. Finally, twelve recommendations were reached by consensus, comprehensively considering the balance of benefits and harms, certainty of evidence, costs, clinical feasibility, accessibility, and clinical acceptability. CONCLUSION: This guideline panel made twelve recommendations, which covered the use of manual therapy, acupuncture, needle knife, Cheezheng Xiaotong plaster, Gutong plaster, exercise therapy and integrated TCM and Western medicine, such as combined modalities and corticosteroid injections. Most of them were weakly recommended or consensus based. The users of this guideline are most likely to be clinicians and health administrators.

Trends in the utilization of psychotropic medications in China from 2018 to 2021.

Background: Monitoring psychotropic medicine consumption trends can provide information on the extent of pharmacological interventions for mental disorders and availability of psychotropic medicines. Objectives: This study aimed to illustrate the trends in psychotropic drug utilization in China's hospitals. Methods: We retrospectively analyzed the aggregated monthly psychotropic procurement records of 1009 hospitals from 31 provinces in China from January 2018 to September 2021. Total psychotropic medicine consumption included the sales of antipsychotics, antidepressants, anxiolytics, mood stabilizers, and sedatives or hypnotics. Information, including generic name, procurement amount, dosage form, strength, purchase time, and geographical data, was collected. Population-weighted psychotropic utilization was expressed in defined daily dose per 1000 inhabitants per day (DDD/1000/day). Results: Psychotropic medicine sales increased from 4.5 DDD/1000/day in Q1 2018 to 6.4 DDD/1000/day in Q3 2021; total utilization in China's hospitals increased by 42.2%. The use of each class of psychotropics showed a gradually increasing trend. Antidepressants were the most consumed psychotropics, accounting for 48.4% of the total psychotropic utilization (3.1/6.4 DDD/1000/day), followed by sedatives or hypnotics (31.3%; 2.0/6.4 DDD/1000/day) and antipsychotics (15.6%; 1.0/6.7 DDD/1000/day). Among all sub-classes of psychotropics, a most significant growth in DDD per 1000 inhabitants per day was seen for selective serotonin reuptake inhibitors (1.2-1.9 DDD/1000/day), whereas the consumption of typical antipsychotics (from 0.1 to 0.09 DDD/1000/day) and tricyclic antidepressants (from 0.05 to 0.03 DDD/1000/day) decreased during the study period. Psychotropic utilization substantially increased between Q1 2018 and Q3 2021 in regions with different economic levels. In Q3 2021, total psychotropic utilization in secondary and tertiary hospitals was 9.4 DDD/1000/day and 6.0 DDD/1000/day, respectively. Sedatives or hypnotics in secondary hospitals accounted for the largest proportion of utilized psychotropics (43.6%; 4.1/9.4 DDD/1000/day), whereas antidepressants were the most commonly used psychotropic in tertiary hospitals (50.0%, 3.0/6.0 DDD/1000/day). Conclusion: This study showed that despite increases in psychotropic medication use, the consumption of medicines is still much lower than in other countries and regions internationally. With reference to the estimated prevalence of corresponding mental disorders, our study illustrates that a large treatment gap for mental health problems exists in China. In addition, the wide use of psychotropics with weak clinical evidence raises serious concerns regarding rational use. Greater efforts are needed to increase the availability of psychotropic medicines and to facilitate proper psychotropic use.