ABSTRACT
Psoriasis is a global health concern, and biological therapies have proven to be highly effective in treating psoriatic patients in many countries. We performed a bibliometric analysis of current research on biological agents for the treatments of psoriasis, investigating research patterns and public interest in this area. We conducted a thorough review of articles on biological agents for psoriasis in the Web of Science Core Collection spanning from 2000 to 2022. Our study involved examining the distribution of these articles based on publication year, affiliations, countries, authors, and journals. To visualize this data effectively, we employed bibliometric tools like CiteSpace and the R package bibliometrix. Our analysis encompassed 8,047 publications. The number of papers published sharply increased from 2009, either reaching its peak in 2022 or not yet reaching it. The United States (n = 2,292), Kristian Reich (n = 166), and British Journal of Dermatology (n = 368) emerged as the top countries, author, and journal, respectively, in terms of publication productivity. The burst references predominantly focused on evaluating the safety and efficacy of biological treatments. The keyword citation network identified 11 clusters, with research themes revolving around "double blind", "efficacy", "therapy", "safety", and "psoriatic arthritis" were the research focuses. Additionally, potential future research areas such as "multicenter," "drug survival," and "severity" were emphasized. This study sheds light on the evolving research landscape and public interest in biological agents for psoriasis. The results suggest rapid expansion in this field, with the United States at the forefront. Enhanced international collaboration is recommended, and forthcoming research endeavors may concentrate on predicting treatment outcomes and adverse effects. Researching new biological agents, broadening the indications for biological agent treatment, and creating personalized treatment plans may pave the way for further research.
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BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.
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ETHNOPHARMACOLOGICAL RELEVANCE: As reported in the Ancient Chinese Medicinal Books, Ginkgo biloba L. fruit has been used as a traditional Chinese medicine for the treatment asthma and cough or as a disinfectant. Our previous study demonstrated that G. biloba exocarp extract (GBEE), an extract of a traditional Chinese herb, inhibits the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. However, GBEE is a crude extract that contains many components, and the underlying mechanisms of purified GBEE fractions extracted with solvents of different polarities are unknown. AIM OF THE STUDY: This study aimed to investigate the different components in GBEE fractions extracted with solvents of different polarities and their antibacterial effects and mechanisms against MRSA and Staphylococcus haemolyticus biofilms both in vitro and in vivo. METHODS: The components in different fractions were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). Microbroth dilution assays and time growth curves were used to determine the antibacterial effects of the fractions on 15 clinical bacterial isolates. Crystal violet staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to identify the fractions that affected bacterial biofilm formation. The potential MRSA targets of the GBEE fraction obtained with petroleum ether (PE), denoted GBEE-PE, were screened by transcriptome sequencing, and the gene expression profile was verified by quantitative polymerase chain reaction (qPCR). RESULTS: HPLC-HRMS analysis revealed that the four GBEE fractions (extracted with petroleum ether, ethyl acetate, n-butanol, and water) contained different ginkgo components, and the antibacterial effects decreased as the polarity of the extraction solvent increased. The antibacterial activity of GBEE-PE was greater than that of the GBEE fraction extracted with ethyl acetate (EA). GBEE-PE improved H. illucens survival and reduced MRSA colonization in model mouse organs. Crystal violet staining and SEM and TEM analyses revealed that GBEE-PE inhibited MRSA and S. haemolyticus biofilm formation. Transcriptional analysis revealed that GBEE-PE inhibits MRSA biofilms by altering ion transport, cell wall metabolism and virulence-related gene expression. In addition, the LO2 cell viability and H. illucens toxicity assay data showed that GBEE-PE at 20 mg/kg was nontoxic. CONCLUSION: The GBEE fractions contained different components, and their antibacterial effects decreased with increases in the polarity of the extraction solvent. GBEE-PE limited MRSA growth and biofilm formation by affecting ion transport, cell wall synthesis, and virulence-related pathways. This research provides a more detailed overview of the mechanism by which GBEE-PE inhibits MRSA both in vitro and in vivo and suggests that GBEE-PE is a new prospective antimicrobial with the potential to be used in MRSA therapeutics in the future.
Subject(s)
Acetates , Alkanes , Methicillin-Resistant Staphylococcus aureus , Animals , Mice , Ginkgo biloba/chemistry , Virulence , Gentian Violet/pharmacology , Prospective Studies , Plant Extracts/pharmacology , Solvents/chemistry , Anti-Bacterial Agents/pharmacology , Biofilms , Microbial Sensitivity TestsABSTRACT
A facile method was developed for the selective thioetherification of uracils using sulfonyl hydrazide as the thioetherification reagent. This method offers advantages such as avoiding the use of additives and expensive metal catalysts, and providing good to excellent yields of various uracil thioethers. Experimental studies have demonstrated that the reaction follows a free radical pathway. Notably, the reaction can be carried out without solvent.
ABSTRACT
Scientific irrigation is of great significance to plant seed production. With two excellent native plant species in desert steppe, Agropyron mongolicum and Lespedeza potaninii, as the objects, and full irrigation as the control, we explored the effects of deficit irrigation in different growth stages on the seed production and water use efficiency (WUE) of those two species. The results showed that, compared with the control, soil water content of both species decreased under deficit irrigation. The decrease of soil water content of A. mongolicum mainly occurred in the 0-60 cm soil layer, while there was no obvious stratification for the reduction of soil water content of L. potaninii. There were significant differences in the yield components of A. mongolica under deficit irrigation. The seed yield of deficit irrigation at the flowering stage was the highest. There were significant differences in the numbers of fertile tillers, florets and pods of L. potaninii among treatments, but no significant difference in seed yield. There were positive correlations between seed yield of A. mongolicum and the numbers of fertile tillers (r=0.776) and spikelets (r=0.717). The racemes of L. potaninii was significantly negatively correlated with the number of fertile tillers (r=-0.685), and positively correlated with the number of florets (r=0.412). Compared with full irrigation, water consumption of seed production of the two native plant species was reduced under deficit irrigation, but water use efficiency was improved, with the strongest improvement at the flowering stage of A. mongolicum (32.9%) and at the branching stage of L. potaninii (27.4%). Therefore, proper deficit irrigation could improve water use efficiency of both plant species. From the perspective of water use efficiency and seed yield, deficit irrigation could be used for artificial breeding of A. mongolicum and L. potaninii seeds in arid area, with the suitable growth stage for deficit being the flowering and the branching stages, respectively.
Subject(s)
Agricultural Irrigation , Water , Agricultural Irrigation/methods , Biomass , Plant Breeding , Seeds , SoilABSTRACT
AIMS: Schizophrenia is a major mental disorder with a wide range of psychiatric symptoms. This study explored the structure of psychiatric symptoms of schizophrenia using network analysis in a large representative Asian sample based on a survey of clinical features and treatment used in schizophrenia patients across 15 countries/territories in Asia. METHODS: Data on the demographic characteristics and psychiatric symptoms in schizophrenia patients were extracted from the dataset of the fourth Research on Asia Psychotropic Prescription for Antipsychotics (REAP-AP) project. The presence of the following psychiatric symptoms including delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms, social/occupational dysfunction, verbal aggression, physical aggression, and affective symptoms were analyzed. RESULTS: A total of 3681 patients were included. The network analysis revealed that verbal aggression, hallucinations, and social/occupational dysfunction were the most central symptoms, while the connections between social/occupational dysfunction and verbal aggression, and between hallucinations and disorganized speech were the two strongest edges. There were significant gender differences in the network structure based on the network structure invariance test (M=0.74, P = 0.03) and invariant edge strength test. The positive correlation between verbal aggression and hallucinations was significantly stronger in the female network than that in the male network (P = 0.03), while a negative correlation between affective symptoms and negative symptoms was found in the female, but not the male network (P < 0.01). CONCLUSION: Central symptoms including verbal aggression, hallucinations, and socio-occupational dysfunction should be addressed in developing targeted treatment strategy for schizophrenia patients.
Subject(s)
Antipsychotic Agents , Schizophrenia , Antipsychotic Agents/therapeutic use , Female , Hallucinations/drug therapy , Humans , Male , Prescriptions , Psychotropic Drugs/therapeutic use , Schizophrenia/drug therapyABSTRACT
Coated zinc oxide nanoparticles (ZnO-NPs) are more commonly applied in commercial products but current risk assessments mostly focus on bare ZnO-NPs. To investigate the impacts of surface coatings, this study examined acute and chronic toxicities of six chemicals, including bare ZnO-NPs, ZnO-NPs with three silane coatings of different hydrophobicity, zinc oxide bulk particles (ZnO-BKs), and zinc ions (Zn-IONs), toward a marine copepod, Tigriopus japonicus. In acute tests, bare ZnO-NPs and hydrophobic ZnO-NPs were less toxic than hydrophilic ZnO-NPs. Analyses of the copepod's antioxidant gene expression suggested that such differences were governed by hydrodynamic size and ion dissolution of the particles, which affected zinc bioaccumulation in copepods. Conversely, all test particles, except the least toxic hydrophobic ZnO-NPs, shared similar chronic toxicity as Zn-IONs because they mostly dissolved into zinc ions at low test concentrations. The metadata analysis, together with our test results, further suggested that the toxicity of coated metal-associated nanoparticles could be predicted by the hydrophobicity and density of their surface coatings. This study evidenced the influence of surface coatings on the physicochemical properties, toxicity, and toxic mechanisms of ZnO-NPs and provided insights into the toxicity prediction of coated nanoparticles from their coating properties to improve their future risk assessment and management.
Subject(s)
Copepoda , Metal Nanoparticles , Nanoparticles , Zinc Oxide , Animals , Hydrophobic and Hydrophilic Interactions , Nanoparticles/toxicity , Zinc/toxicity , Zinc Oxide/toxicityABSTRACT
OBJECTIVE: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses). METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates. RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses. CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.
Subject(s)
Antimanic Agents/administration & dosage , Antipsychotic Agents/administration & dosage , Practice Patterns, Physicians'/statistics & numerical data , Schizophrenia/drug therapy , Adult , Asia , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Schizophrenia/physiopathology , Severity of Illness Index , Young AdultABSTRACT
BACKGROUND: Omalizumab has been proposed as a possible effective treatment of chronic spontaneous urticaria (CSU). STUDY QUESTION: We aimed to access the efficacy and safety of omalizumab in the treatment of CSU based on qualified, randomized controlled trials (RCTs). DATA SOURCES: PubMed, the Cochrane library, and Embase databases. STUDY DESIGN: Computerized search by index words was performed to identify qualified RCTs, and relevant literature sources were also searched. RESULT: Nine RCTs were included in the meta-analysis with 1612 patients in the omalizumab group and 1251 patients in the placebo group. Compared with the placebo group, omalizumab significantly decreased the weekly itch score after therapy [Weighted Mean Difference (WMD), -3.94; 95% confidence interval (CI), -4.64 to -3.24], the weekly hive score (WMD, -5.27; 95% CI, -6.17 to -4.38), the dermatology life quality index (DLQI; WMD, -3.58; 95% CI, -4.66 to -2.50), and the urticaria activity score over 7 days (UAS7; WMD, -9.51; 95% CI, -10.94 to -8.08). There was no significant difference in the incidence of adverse events (AE) [relative risk (RR), 1.01; 95% CI, 0.91-1.12], serious AE (RR, 0.85; 95% CI, 0.57-1.27), and severe AE (RR, 0.83; 95% CI, 0.60-1.14) between the 2 groups. Compared with the placebo, omalizumab significantly decreased the weekly itch score and weekly hive score after therapy in patients receiving 75, 150, and 300 mg omalizumab, respectively. DLQI was significantly reduced in patients receiving 150 and 300 mg of omalizumab, respectively. In all the subgroup of UAS7, omalizumab significantly decreased the score compared with the placebo. Only patients receiving 600-mg omalizumab had a significantly higher AE incidence versus placebo. There was no significant difference in serious and severe AE between the 2 groups. CONCLUSION: Omalizumab caused a significantly greater reduction in weekly itch score, weekly hive score, DLQI, and UAS7 in CSU patients than the placebo. However, high-quality, multicenter RCTs with a larger sample size are needed to confirm the safety of omalizumab, and whether AEs are caused by omalizumab or other factors.
Subject(s)
Anti-Allergic Agents/administration & dosage , Chronic Urticaria/drug therapy , Omalizumab/administration & dosage , Pruritus/drug therapy , Anti-Allergic Agents/adverse effects , Chronic Urticaria/complications , Chronic Urticaria/diagnosis , Chronic Urticaria/immunology , Humans , Omalizumab/adverse effects , Pruritus/diagnosis , Pruritus/immunology , Quality of Life , Randomized Controlled Trials as Topic , Severity of Illness Index , Treatment OutcomeABSTRACT
INTRODUCTION: Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established. METHODS: Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region. RESULTS: Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications. DISCUSSION: These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.
Subject(s)
Antipsychotic Agents/therapeutic use , Drug Prescriptions/statistics & numerical data , Hospitalization/statistics & numerical data , Schizophrenia/drug therapy , Schizophrenia/physiopathology , Adult , Antipsychotic Agents/administration & dosage , Asia, Southeastern , Asia, Western , Delayed-Action Preparations , Female , Humans , Injections , Male , Middle Aged , Sex FactorsABSTRACT
Pyoderma gangrenosum is an uncommon ulcerative cutaneous lesion manifesting as rapidly progressing single or multiple skin ulcers. Permanent stoma in inflammatory bowel disease patients remains an independent risk of pyoderma gangrenosum. In the current report, we describe a case of pyoderma gangrenosum in a post-colostomy ulcerative colitis patient with chronic hepatitis B. Pyoderma gangrenosum began seemingly as peristomal dermatitis that rapidly developed into painful ulcerations with subsequent appearance of sterile pustules and ulcerations in the left lower leg. The patient significantly improved after active management with prednisolone, antiviral therapy with entecavir, and wound dressings. Our case suggests that physicians and surgeons should have a high index of suspicion of pyoderma gangrenosum in post-colostomy ulcerative colitis patients who develop peristomal dermatitis.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Colitis, Ulcerative/surgery , Colostomy/adverse effects , Cutaneous Fistula/complications , Hepatitis B, Chronic/complications , Pyoderma Gangrenosum/drug therapy , Pyoderma Gangrenosum/etiology , Adult , Cutaneous Fistula/microbiology , Humans , Male , Treatment OutcomeABSTRACT
Clozapine is an effective antipsychotic medication for treatment resistant schizophrenia and is widely used in Asian countries. This study investigated clozapine prescription patterns and their associated factors in Asian countries and territories based on the database of the Research on Asian Psychotropic prescription study (REAP) conducted in 2016. Demographic and clinical information of 3744 schizophrenia patients in 15 Asian countries and territories was collected with a standardized data collection form. In total, 18.4% of the sample received clozapine, ranging from 2.6% in Japan to 32.3% in Hong Kong. Binary logistic regression analysis revealed that higher antipsychotic dose (OR = 1.002, P < 0.001), less frequent first admission in the sample (OR = 0.6, P < 0.001), more severe negative symptoms (OR = 1.4, Pâ¯=â¯0.001) and less first generation antipsychotics (FGAs) (OR = 0.2, P < 0.001) were independently and significantly associated with clozapine prescription. Clozapine is frequently and increasingly prescribed for schizophrenia in Asia, with large variation across countries and territories. Given the diverse prescription patterns of clozapine found in Asian countries/territories, the clinical rationale of clozapine prescription needs careful consideration in Asia with more local input.
Subject(s)
Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Prescriptions/statistics & numerical data , Schizophrenia/drug therapy , Schizophrenia/ethnology , Adult , Asian People , Female , Hong Kong , Hospitalization , Humans , Japan , Male , Middle Aged , Psychotropic Drugs/therapeutic use , Surveys and QuestionnairesABSTRACT
Background: We conducted this meta-analysis to compare the efficacy and safety of imiquimod with other treatments in patients with basal cell carcinoma (BCC).Methods: A comprehensive literature search was performed in the database of PubMed, Embase, and Web of Science, focusing on studies that evaluated the efficacy and safety profile of BCC patients who were treated with imiquimod. The main outcome measures included histological/composite clearance rate, success rate, complete response rate, tumor free survival, and adverse events. Results were expressed as risk ratio (RR) with 95% confidence intervals (CIs). Pooled estimates were calculated using a fixed-effects or random-effects model according to the heterogeneity among studies.Results: A total of 13 studies involving 4256 patients were included in this meta-analysis. Imiquimod was associated with significantly higher histological clearance rate and composite clearance rate. Moreover, imiquimod also significantly increased complete response rate but had no effect in the success rate and probability of tumor free survival, as compared with other treatments. There were more patients with imiquimod developed adverse events than those with other treatments.Conclusion: The present meta-analysis indicated the effects of imiquimod in improving the histological/composite clearance rates as compared with other treatments.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Basal Cell/drug therapy , Imiquimod/administration & dosage , Skin Neoplasms/drug therapy , Administration, Topical , Antineoplastic Agents/adverse effects , Disease-Free Survival , Humans , Imiquimod/adverse effects , Randomized Controlled Trials as Topic , Skin CreamABSTRACT
OBJECTIVE: Regular surveys are important to monitor the use of psychotropic medications in clinical practice. This study examined the psychotropic prescription patterns in adult Asian schizophrenia patients based on the data of the Research on Asian Psychotropic Prescription (REAP) 2016 survey. METHODS: This cross-sectional survey across 15 Asian countries/territories collected socio-demographic and clinical data with standardized procedures between March and May 2016. The socio-demographic and clinical characteristics of the patients were recorded with a standardized questionnaire. RESULTS: Altogether 3,537 adult patients with schizophrenia were consecutively screened and enrolled in the survey. The mean age was 38.66⯱â¯11.55 years and 59.7% of the sample were male. The mean dose of antipsychotics in chlorpromazine equivalents (CPZeq) was 424⯱â¯376â¯mg/day; 31.3% and 80.8% received first- and second- generation antipsychotics, respectively and 42.6% had antipsychotic polypharmacy, 11.7% had antidepressants, 13.7% had mood stabilizers, 27.8% had benzodiazepines, and 45.6% had anticholinergics. CONCLUSIONS: Psychotropic prescription patterns in Asian adult patients with schizophrenia varied across countries. Regular surveys on psychotropic medications for schizophrenia are important to monitor pharmacotherapy practice in Asia.
Subject(s)
Antipsychotic Agents/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Schizophrenia/drug therapy , Adult , Antidepressive Agents/therapeutic use , Asia , Benzodiazepines/therapeutic use , Cholinergic Antagonists/therapeutic use , Cross-Sectional Studies , Drug Prescriptions/statistics & numerical data , Female , Health Surveys , Humans , MaleABSTRACT
BACKGROUND AND OBJECTIVE: Antipsychotic polypharmacy (APP) is a controversial topic in the treatment of older adults with schizophrenia. The objective of this study was to examine the use of APP in older adult Asian patients with schizophrenia and its associated demographic and clinical factors. METHODS: This study was based on the fourth survey of the consortium known as the Research on Asian Psychotropic Prescription Pattern for Antipsychotics. Fifteen Asian countries/territories participated in this survey, including Bangladesh, Mainland China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, Thailand, and Vietnam. Basic demographic and clinical characteristics were collected using a standardized data collection form. RESULTS: Among the 879 older adults with schizophrenia included in the survey, the rate of APP was 40.5%. Multiple logistic regression analysis revealed that higher antipsychotic doses (P < .001, odds ratio [OR] = 1.003, 95% confidence interval [CI]: 1.002-1.003), longer duration of illness (P = .02, OR = 1.845, 95% CI: 1.087-3.132), and the prescription of anticholinergics (P < .001, OR = 1.871, 95% CI: 1.329-2.635), second-generation antipsychotics (P = .001, OR = 2.264, 95% CI: 1.453-3.529), and first-generation antipsychotics (P < .001, OR = 3.344, 95% CI: 2.307-4.847) were significantly associated with APP. CONCLUSION: Antipsychotic polypharmacy was common in older adult Asian patients with schizophrenia. Compared to the results of previous surveys, the use of APP showed a declining trend over time. Considering the general poor health status of older patients with schizophrenia and their increased risk of drug-induced adverse events, the use of APP in this population needs careful consideration.
Subject(s)
Antipsychotic Agents/therapeutic use , Polypharmacy , Schizophrenia/drug therapy , Aged , Aged, 80 and over , Aging , Antipsychotic Agents/pharmacology , Asian People , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: There is an unmet need for a safer and more effective treatment for obesity. This study assessed the effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with type 2 diabetes mellitus (T2DM) and/or obesity. METHODS: Patients with obesity (BMI, 35-50 kg/m2 ) were enrolled into a 12-week study (N = 88; licogliflozin 150 mg q.d.). Patients with T2DM were enrolled into a second, two-part study, comprising a single-dose cross-over study (N = 12; 2.5 - 300 mg) and a 14-day dosing study (N = 30; 15 mg q.d). Primary endpoints included effects on body weight, effects on glucose, safety and tolerability. Secondary endpoints included urinary glucose excretion (UGE24 ) and pharmacokinetics, while exploratory endpoints assessed the effects on incretin hormones (total GLP-1, PYY3-36 , and GIP), insulin and glucagon. RESULTS: Treatment with licogliflozin 150 mg q.d. for 12 weeks in patients with obesity significantly reduced body weight by 5.7% vs placebo (P < 0.001) and improved metabolic parameters such as significantly reduced postprandial glucose excursion (21%; P < 0.001), reduced insulin levels (80%; P < 0.001) and increased glucagon (59%; P < 0.001). In patients with T2DM, a single dose of licogliflozin 300 mg in the morning prior to an oral glucose tolerance test (OGTT) remarkably reduced glucose excursion by 93% (P < 0.001; incremental AUC0-4h ) and suppressed insulin by 90% (P < 0.01; incremental AUC0-4h ). Treatment with licogliflozin 15 mg q.d. for 14 days reduced 24-hour average glucose levels by 26% (41 mg/dL; P < 0.001) and increased UGE24 to 100 g (P < 0.001) in patients with T2DM. In addition, this treatment regimen significantly increased total GLP-1 by 54% (P < 0.001) and PYY3-36 by 67% (P < 0.05) post OGTT vs placebo, while significantly reducing GIP levels by 53% (P < 0.001). Treatment with licogliflozin was generally safe and well tolerated. Diarrhea (increased numbers of loose stool) was the most common adverse event in all studies (90% with licogliflozin vs 25% with placebo in the 12-week study), while a lower incidence of flatulence, abdominal pain and abdominal distension (25%-43% with licogliflozin vs 9%-11% with placebo in the 12-week study) were among the other gastrointestinal events reported. CONCLUSION: Licogliflozin treatment (1-84 days) leads to significant weight loss and favourable changes in a variety of metabolic parameters and incretin hormones. Dual inhibition of SGLT1/2 with licogliflozin in the gut and kidneys is an attractive strategy for treating obesity and diabetes.
Subject(s)
Anhydrides/pharmacology , Body Weight/drug effects , Diabetes Mellitus, Type 2/complications , Obesity/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sorbitol/analogs & derivatives , Adult , Anhydrides/administration & dosage , Anhydrides/adverse effects , Blood Glucose/metabolism , Cross-Over Studies , Diabetes Mellitus, Type 2/blood , Female , Humans , Male , Middle Aged , Obesity/blood , Obesity/complications , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sorbitol/administration & dosage , Sorbitol/adverse effects , Sorbitol/pharmacology , Young AdultABSTRACT
Historical geological and climatic events are the most important drivers of population expansions/contractions, range shifts, and interspecific divergence in plants. However, the species divergence and spatiotemporal population dynamics of alpine cold-tolerant herbal plants in the high-altitude Qinghai-Tibetan Plateau (QTP) and adjacent areas remain poorly understood. In this study, we investigated population evolutionary history of four endangered Notopterygium herb species in the QTP and adjacent regions. We sequenced 10 nuclear loci, 2 mitochondrial DNA regions, and 4 chloroplast DNA regions in a total of 72 natural populations from the 4 species, and tested the hypothesis that the population history of these alpine herbs was markedly affected by the Miocene-Pliocene QTP uplifts and Quaternary climatic oscillations. We found that the four Notopterygium species had generally low levels of nucleotide variability within populations. Molecular dating and isolation-with-migration analyses suggested that Notopterygium species diverged ~1.74-7.82 million years ago and their differentiation was significantly associated with recent uplifts of the eastern margin of the QTP. In addition, ecological niche modeling and population history analysis showed that N. incisum and N. franchetii underwent considerable demographic expansions during the last glacial period of the Pleistocene, whereas a demographic contraction and a expansion occurred for N. forrestii and N. oviforme during the antepenultimate interglacial period and penultimate glacial period, respectively. These findings highlight the importance of geological and climatic changes during the Miocene-Pliocene and Pleistocene as causes of species divergence and changes in population structure within cold-tolerant herbs in the QTP biodiversity hotspot.
Subject(s)
Plants, Medicinal/genetics , Plants/genetics , Biodiversity , Biological Evolution , DNA, Chloroplast/genetics , DNA, Mitochondrial/genetics , DNA, Plant/genetics , Ecosystem , Genetic Variation/genetics , Species Specificity , TibetABSTRACT
Species identification and discrimination is the basis of biodiversity research. In general, it is considered that numerous nucleotide variations (e.g., whole chloroplast genomes) can identify species with higher resolution than a few loci, e.g., partial chloroplast or nuclear gene fragments. In this study, we tested this hypothesis by sampling population genetics samples of the endangered herb genus Notopterygium. We sequenced the complete plastomes, five nuclear gene regions, three chloroplast DNA fragments, and a nuclear internal transcribed spacer (nrITS) region for 18 populations sampled throughout most of the geographic ranges of all six Notopterygium species. Species identification analysis showed that four DNA barcodes (matK, rbcL, trnS-trnG, and nrITS) and/or combinations of these markers achieved Notopterygium species discrimination at higher resolution than the general plastomes and nuclear gene sequences. In particular, nrITS had the highest discriminatory power among all of the individual markers. Molecular data sets and morphological evidence indicated that all six Notopterygium species could be reclassified unambiguously to four putative species clades. N. oviforme and N. franchetii had the closest relationship. Molecular dating showed that the origin and divergence of Notopterygium species was significantly associated with geological and climatic fluctuations during the middle of the Pliocene. In conclusion, our results suggest that a few nucleotide variations can achieve species discrimination with higher resolution than numerous plastomes and general nuclear gene fragments when discerning related Notopterygium species.
Subject(s)
Apiaceae/genetics , Endangered Species , Genetic Loci , Genetic Variation , DNA, Chloroplast/genetics , DNA, Plant/genetics , Genetic Markers , Genome, Chloroplast , Phylogeny , Species Specificity , Time FactorsABSTRACT
A new self-rating functional scale (SRFS) was developed to assess the functionality of patients with schizophrenia, referred to the structure of Personal and Social Performance Scale (PSP). The main aim of this study was to evaluate the reliability and validity of the SRFS. A total of 210 patients with schizophrenia were recruited from outpatient clinics in six sites in China. Demographic information, SRFS, PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale were assessed. Spearman's correlation coefficient and path analysis were used to assess the reliability and validity of the SRFS. Cronbach's α coefficient was used to assess the internal consistency reliability. Cronbach's α was 0.83, and ranged from 0.80 to 0.82 stably, indicating that the scale was reliable in internal consistency. Spearman's correlation coefficient between split two parts was 0.68 (P<0.01), suggesting a moderate to strong split-half reliability. The standardized regression coefficients ranged from 0.48 to 0.79, indicating moderate construct validity. Spearman's correlation coefficients between SRFS and PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale are 0.59, 0.65, and 0.47 (all P<0.01), respectively, indicating moderate criteria validities. The SRFS is a reliable and valid instrument for assessing personal and social functionality in patients with schizophrenia.
Subject(s)
Psychiatric Status Rating Scales/standards , Schizophrenia/physiopathology , Adolescent , Adult , Age Factors , Aged , Aggression/psychology , China , Female , Humans , Interpersonal Relations , Male , Middle Aged , Psychometrics , Reproducibility of Results , Self Care , Self Report , Severity of Illness Index , Sex Factors , Socioeconomic Factors , World Health Organization , Young AdultABSTRACT
PURPOSE: Little is known regarding the trend of polypharmacy in Asia. We used data from 5 Asian countries to examine the patterns of antidepressant (AD) prescription and trends of psychotropic polypharmacy over time. METHODS: We used the cross-sectional, pharmacoepidemiological data from 2004 and 2013 REAP-AD (Research on Asian Psychotropic Prescription Patterns for Antidepressants) to examine the patterns of AD prescriptions in clinical settings in China, Japan, Korea, Singapore, and Taiwan. We compared the trend in polypharmacy (ie, concomitant use of ≥2 classes of psychotropic) among individuals receiving AD prescriptions in 2004 and 2013 using multivariable logistic regression models in different diagnostic categories. RESULTS: The proportion of patients with psychotropic polypharmacy decreased from 2004 to 2013 in all 3 diagnostic categories, including mood disorders (adjusted odds ratio [aOR], 0.44 [0.35-0.56]; P < 0.001), anxiety disorders (aOR, 0.58 [0.36-0.94]; P = 0.028), and psychotic disorders (aOR, 0.18 [0.05-0.60]; P = 0.006). Among individuals with AD prescriptions, concomitant use of anxiolytics (including sedative-hypnotics) decreased in patients with mood disorders (aOR, 0.34 [0.27-0.42]; P < 0.001) and anxiety disorders (aOR, 0.43 [0.27-0.67]; P < 0.001). In contrast, concomitant use of antipsychotics in patients with mood disorders increased (aOR, 1.43 [1.15-1.77]; P = 0.001), and concomitant use of mood stabilizers in patients with psychotic disorders also increased (aOR, 3.49 [1.50-8.14]; P = 0.004). CONCLUSIONS: This is the first study examining trends in psychotropic polypharmacy in East Asia. We found a generally decreasing trend of psychotropic polypharmacy in contrast to the increasing trend reported from Western countries. These findings could offer significant implications for health system reform or policy making.