Medicine Group Research Articles

Post-Marketing Safety of Ustekinumab Based on 14-Year Follow-Up in Danish National Patient Data.

Psoriasis (PsO), a chronic inflammatory skin disorder affecting a substantial proportion of populations globally, often necessitates systemic treatment including biologics. This 14-year cohort study, based on Danish national register data, aimed to investigate the enduring safety profile of ustekinumab compared to other systemic psoriasis treatments. Using comprehensive Danish national register data, this study scrutinized patients diagnosed with psoriasis or psoriatic arthritis (PsA) who received ustekinumab. The treatment group comparators were non-biological systemic treatment (non-biologic), tumor necrosis factor α inhibitor medicine groups (TNF-α), interleukin (IL)-17 inhibitors (IL-17), and IL-23 inhibitors (IL-23). The study periods for comparisons were 2009-2022 for non-biologic and TNF-α, 2015-2022 for IL-17, and 2018-2022 for IL-23. Outcomes were malignancies, cardiovascular events, serious infections, and serious hypersensitivity reactions. Cox proportional hazards regression models were employed to analyze two estimands: a standard intention-to-treat (ITT) estimand and a continuous-index-treatment (CIT) estimand, which considered switch and re-initiation of treatments within individuals. Users of ustekinumab were found to be younger on average, with an average age of 45.1 years compared to 51.6, 47.2, 49.0, and 48.4 years in the non-biologic, TNF-α, IL-17, and IL-23 groups, respectively. Also, 57.3% of the ustekinumab users were male, compared to 46.7%, 48.9%, 50.9%, and 58.3% for the non-biologic, TNF-α, IL-17, and IL-23 groups, respectively. Although the hazard ratio estimates varied across comparators, ustekinumab was found to be safe: regardless of PsA status, no discernible safety signals in terms of malignancy, MACE, severe infections, or severe hypersensitivity reactions were observed for ustekinumab when compared to the treatment comparators. The present study corroborated the enduring safety of ustekinumab in the context of PsO treatment.

Traditional Chinese medicine application and evidence analysis of 1426 cases of long COVID: A retrospective study

BackgroundIn recent years, with the increase in COVID-19 infection cases, the focus of treatment and rehabilitation has shifted to symptoms and complications that arise during the recovery period. Traditional Chinese medicine (TCM) has certain advantages in treatment and rehabilitation, but there is currently a lack of systematic clinical research. ObjectiveTo preliminarily evaluate the clinical efficacy of integrated Chinese and Western medical treatment plans and to describe the characteristics of "long COVID'' syndromes. MethodsEligible "long COVID'' patients diagnosed between December 2022 and June 2023 at the Third Affiliated Hospital of Zhejiang Chinese Medical University were identified through electronic medical records. Baseline demographic information was collected, and patients were divided into a TCM group and a Western medicine group based on their treatment methods. The primary outcome for efficacy evaluation was TCM syndrome scores and symptom improvement time, with secondary outcomes including symptom improvement rates. Survival curve analysis was used to assess symptom improvement time, and a Cox regression model was employed to identify potential risk factors affecting symptom prognosis. Chi-square tests were used to compare binary data between or among groups. The Jaccard method was applied for systematic clustering of TCM syndromes, and clinical characteristics at the start and end of treatment were reported. ResultsAnalysis showed that younger patients, those with underweight, and those receiving TCM treatment had shorter recovery times (P < 0.0001). Systematic clustering of the main symptom elements (33 elements with a frequency ≥ 5 %) identified six core combinations. The main symptoms of long COVID included cough, excessive sputum, nasal congestion, chest tightness, sore throat, and fatigue. Notably, symptoms such as fatigue, shortness of breath, and loss of appetite, classified as deficiency syndromes in TCM, had longer recovery times. ConclusionElderly, obesity, underlying diseases, and exclusive Western medicine treatment were associated with poorer prognosis. The early recovery period is characterized by a mix of deficiency and excess syndromes, whereas the later period is dominated by deficiency syndromes. TCM treatment can effectively improve clinical symptoms and shorten symptom duration, but further research is needed.

Dietary supplementation use for outpatient treatment in children: A cross-sectional study

Dietary supplements (DSs) are commonly used supplements among children to support disease treatment, however, overuse and inappropriate prescription of outpatient DS can negatively affect health and treatment costs. This study aimed to evaluate DS use in outpatient treatment in children. The present study used a cross-sectional descriptive retrospective method based on data from 188,579 outpatient prescriptions of children for 1 year. DSs were commonly prescribed in pediatric patients ≤5 years old (63.48%) with diagnosing respiratory, infectious, and gastrointestinal diseases (>50%). DS costs account for a high proportion (24.86%) of total outpatient prescription costs. In addition, pediatric prescriptions containing one DS product (88.16%) showed a higher rate than prescriptions containing two DS products (11.84%) with the main ingredients being vitamin D3 (80.55%), vitamin B6 (63.01%), vitamin B1 (60.22%), and vitamin B2 (59.04%), and calcium (51.0%). The majority of DS products contained multivitamins (69.52%) with DS containing ≥5 vitamins of 59.04% and DS containing 2-4 vitamins of 10.48%. Besides, non-compliance with DS prescribing guidelines for age (21.38%), dose (14.13%), and both age and dose (5.54%) was found primarily in highly prescribed DSs (vitamin-amino acid-mineral ingredients), pediatric patients <2 years old, prescriptions containing one DS product or multivitamins, and respiratory disease group (J and R04-09 ICD). The univariate and multivariate regression analyses showed that vitamin-mineral products and groups <2 years old were significantly associated with guideline-adherent DS prescribing for age and/or dose. Meanwhile, foreign DSs and vitamin-mineral ingredients of prescription showed significant associations with guideline-adherent DS prescribing for age or dose. Instructions for DS use regarding recommended age and maximum dosage may not be carefully considered by doctors due to belonging to an over-the-counter medicine group. Therefore, there is a strong need for a national public policy to prevent and control overprescribing and inappropriate prescribing of DS.

Assessing the Reliability and Validity of a Questionnaire Evaluating Medical Students’ Attitudes, Knowledge, and Perceptions of Antibiotic Education and Antimicrobial Resistance in University Training

The misuse and overuse of antibiotics represent a critical global issue and one of the most pressing public health challenges of the 21st century. Training future healthcare professionals effectively is essential for ensuring responsible antibiotic use. This study aimed to validate a questionnaire designed to evaluate the knowledge, attitudes, and perceptions of medical students regarding the education they receive on infectious diseases, antimicrobial resistance, and antibiotic stewardship during their university studies. Methods: A self-administered questionnaire was developed and distributed to medical students at the University of Santiago de Compostela. Comprising 44 items, the questionnaire assessed eight key dimensions: “infection diagnosis”, “criteria for not prescribing antibiotics”, “initial antibiotic therapy”, “re-evaluation of therapy”, “quality of care”, “communication skills”, “antibiotic resistance”, and “teaching methodology”. Validation was carried out in two stages: Phase 1 involved content and face validity, while Phase 2 focused on reliability analysis. Results: A total of 295 students completed the questionnaire, with a mean age of 23.15 ± 1.78 years. The sample included 86 male (29.2%) and 209 female (70.8%) respondents. Content and face validity were established by a nominal group of five experts and a focus group of medicine and pharmacy students to ensure consensus on item understanding in the Spanish language. The questionnaire demonstrated high internal consistency with a Cronbach’s alpha of 0.92 and satisfactory item discrimination. Construct validity was confirmed through principal component analysis, which supported the presence of the eight predefined dimensions. Conclusions: The validated questionnaire exhibited strong reliability and validity, making it a valuable tool for assessing medical students’ training in antibiotic-related topics. Its application will enable the identification of areas for improvement in university curricula, ultimately contributing to the promotion of appropriate antibiotic use and the reduction of antimicrobial resistance.

Clinical and non-clinical aspects of reimbursement policy for orphan drugs in selected European countries.

The aim of the study was to assess the reimbursement policy for orphan drugs (ODs) in selected European countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedures and reimbursement decision-making. A list of authorized ODs was extracted from a web-based registry of the European Medicines Agency, including information on active substance, Anatomical Therapeutic Chemical (ATC) classification code, and therapeutic area. A country-based questionnaire survey was conducted between September 2022 and September 2023 among selected experts from 12 European countries. A descriptive and statistical analysis was performed to identify correlations between country characteristic, HTA procedures, drug indication and positive recommendations or reimbursement decisions for ODs. Safety assessment for ODs was mandatory in 10 countries, while it was optional in one country (Italy) and not required in one country (Iceland). Efficacy assessment for ODs was mandatory in 11 countries and not required in one country (Iceland). The impact of safety and efficacy assessment on reimbursement decisions was rated as high in 10 countries and as low in one country (Germany). Dedicated OD legislation and policies were reported in seven countries. In two countries (Belgium, Iceland), the HTA was not mandatory, and in one country (Germany), it only had an informative function. A positive recommendation (from an HTA agency or advisory body) guaranteed reimbursement in four countries, while a negative recommendation excluded reimbursement only in one country (Iceland). The proportion of reimbursed ODs ranged from 23.5% in Iceland to 86% in Germany (p < 0.001). ODs with ATC code L represented the largest group of medicines (n = 49). They were also very frequently reimbursed ODs in the countries studied, with a mean of 61.8% (p < 0.001). European countries differ in terms of the impact of clinical issues and additional clinical aspects on the reimbursement policy for ODs. Reimbursement decisions were affected by OD-specific legislation, policies, and EMA authorization status. HTA dossiers and procedures significantly influenced reimbursement decisions, although some ODs were reimbursed regardless of the positive or negative recommendations. ATC codes were significantly correlated with reimbursement status and positive recommendation.

Non-dispensed prescriptions – A nationwide descriptive study

BackgroundMedication non-adherence is associated with suboptimal health outcomes, higher mortality, and increased healthcare costs. ObjectiveThe aim of this study was to estimate the number and share of non-dispensed prescriptions at a national level and in specific patient and medicine subgroups. MethodsThe study was a nationwide retrospective register-based study. The data consisted of prescriptions prescribed in Finland in 2020 and dispensed between 2020 and 2022. A prescription was considered non-dispensed if it had not been dispensed within the two-year validity period. For each prescription, information on the patient's birth date, sex, and income as well as details of the prescribed medicine and physician's employment sector (public/private) were collected. Distributions and odds ratios (ORs) with corresponding 95 % confidence intervals (CI) were used in the analyses. ResultsOf the 26 million prescriptions, 13.3 % were never filled. Over 1.7 million people (43.3 % of all people with prescriptions issued in 2020) had at least one non-dispensed prescription. The share of non-dispensed prescriptions was lower in men than women (12.9 % vs. 13.5 %; OR:0.95; CI:0.95–0.95). Compared to the youngest age group, the share of non-dispensed prescriptions was lower in the older age groups. The lowest share of non-dispensed medicines was in antineoplastic and immunomodulating agents (7.8 %) and in cardiovascular system medicines (8.1 %), whereas the highest was in dermatologicals (20.2 %). The proportion of non-dispensed prescriptions varied between medicine groups, from 5 % for thyroid therapy to 38 % for other nervous system drugs. The most frequently non-dispensed medications were paracetamol, ibuprofen, and salbutamol. ConclusionThe share and number of non-dispensed prescriptions varied across therapeutic areas, medicine groups, active pharmaceutical ingredients, and patient groups. Healthcare professionals should avoid unnecessary prescribing and improve medication adherence to ensure safer and more effective care.

Evidence synthesis of medical cannabis research: current challenges and opportunities.

As a wide group of medicines, the effectiveness and safety of 'medical cannabis' products is likely to vary in relation to product-specific dimensions such as potency, dosage, route of administration, and cannabinoid composition. Systematic reviews can perform a crucial role in analysing and synthesising the outcomes of medical cannabis interventions found in empirical research. We analysed 23 contemporary systematic reviews on the effectiveness and safety of medical cannabis to discern the extent to which this body of work aimed to capture, and ultimately captured, the differing outcomes of medical cannabis products by product-specific dimensions of treatment. We further highlighted the methodological reasons given by authors for an inability to describe this granular level of information. We found that a minority of systematic reviews explicitly aimed to perform a subgroup analysis to determine differences in treatment outcomes by product-specific dimensions of medical cannabis, with even fewer subsequently doing so. Authors' stated reasons for this concerned either overly large or overly small levels of variation in the characteristics, compositions, and administrations of medical cannabis products used, rendering subgroup analyses methodologically inappropriate or inapplicable. Furthering systematic reviews' abilities to capture granular information on medical cannabis treatment outcomes in relation to product-specific dimensions of treatments will require further standardisation of treatments in empirical studies.

Fuzheng-Buyi formula for treating castration-resistant prostate cancer: A systematic review and meta-analysis.

The study was designed to systematically evaluate the efficacy and safety of Fuzheng-Buyi formula in treating castration-resistant prostate cancer (CRPC). A computer-based search were conducted in the databases, including CNKI, WanFang Data, VIP, CBM, PubMed, EMbase, and the Cochrane database to identify all randomized controlled trials. The studies investigating the efficacy and safety of Fuzheng-Buyi formula combined with Western medicine for the treatment of CRPC were included from January 1st, 2010 to December 31st, 2023. The quality of the included studies was evaluated according to the Cochrane Handbook manual, and meta-analysis was performed using Review Manager 5.3 and R Studio 4.2.3 software. In this study, a total of 18 trials were included, encompassing a population of 1093 patients diagnosed with CRPC. The results of the meta-analysis showed that the combination of Fuzheng-Buyi formula and Western drugs was more effective in increasing the overall efficacy rate (risk ratio = 1.31, 95% confidence interval [CI] [1.17, 1.46], P < .00001), decreasing Traditional Chinese Medicine syndrome score (mean difference [MD] = -4.40, 95% CI [-6.10, -2.70], P < .00001), and quality of life scale (physiological condition MD = -2.31, 95% CI [-3.13, -1.48], P < .00001; social well-being MD = 1.26, 95% CI [0. 59, 1.94], P = .0002; emotional well-being MD = -2.04, 95% CI [-2.96, -1.12], P < .00001; functional well-being MD = -3.18, 95% CI [2.11, 4.26], P < .00001; others should be paid to MD = -3.15, 95% CI [-4.93, -1.37], P = .0005) compared with the Western medicine alone. And the incidence of adverse events was significantly lower in the combination treatment group compared with Western medicine group (risk ratio = 0.58, 95% CI [0.46, 0.73], P < .00001). The combination of Fuzheng-Buyi formula and Western medicine was more effective in improving the clinical efficacy and quality of life of CRPC patients, with lower incidence of adverse events compared with Western medicine alone.

Efficacy of integrated traditional Chinese and western medicine in managing mild-moderate acute pancreatitis: a real-world clinical perspective analysis.

Given the prevalent utilization of integrated traditional Chinese and western medicine (ITCWM) in the management of acute pancreatitis, the majority of studies have concentrated on severe cases, lacking robust evidence-based medical research. Real-world investigations can provide an objective assessment of the clinical effectiveness of combining traditional Chinese medicine with western medicine. Consequently, relying on real-world research, we intend to evaluate the clinical efficacy and safety of the combined approach in treating mild to moderate acute pancreatitis. A total of 563 AP patients from Henan Provincial Hospital of Traditional Chinese Medicine were collected from January 2019 to October 2023. A propensity score matching (PSM) analysis was conducted to evaluate the clinical efficacy of traditional Chinese medicine (TCM) in treating mild to moderate acute pancreatitis. Patients were divided into a control group (61 cases) and an integrated traditional Chinese and Western medicine (ITCWM) group (120 cases). To further assess the clinical efficacy of TCM enema in the treatment of mild to moderate acute pancreatitis, PSM analysis was conducted across three groups. The patients were categorized into a control group (n = 49), an oral TCM treatment group (OCM group, n = 274), and an oral TCM plus enema treatment group (OCM+E group, n = 131). Logistic regression was used to analyze factors after treatment in each group, and the Kaplan-Meier method compared symptom duration in each group. Compared with the control group, the ITCWM group significantly decreased C-reactive protein (CRP, mg/L) (17.8 [1.2-59.5] vs. 8.0 [3.3-33.5], P = 0.022), shortened the duration of abdominal distension, abdominal pain, nausea and bitter taste symptoms (P < 0.05), and shortened the length of hospital stay (median 19.0 and 11.5 days, respectively, P = 0.001); Compared with the other two groups, the neutrophil percentage (NEUT%) was lower (74.1 vs. 61.9 vs. 59.5, P < 0.05) and serum prealbumin (PA, mg/L) was higher (116.0 vs. 184.4 vs. 220.0, P < 0.05), the length of hospitalization (days) was shortened (19.0 vs.12.0 vs.10.0, P < 0.05) in the OCM+E group. The combination of traditional Chinese medicine and modern medicine has been shown to effectively decrease inflammatory indicators in patients with mild to moderate acute pancreatitis, leading to a reduction in symptom duration and hospitalization period, as well as promoting disease recovery. Notably, the use of traditional Chinese medicine in conjunction with enema therapy yields more pronounced benefits.

Clinical features and outcomes of patients diagnosed with diabetic ketoacidosis (DKA) who were hospitalized for conditions outside of internal medicine

AimsTo assess the clinical features and outcomes of patients diagnosed with DKA who were hospitalized for conditions outside of internal medicine. MethodsRetrospective analysis of admissions for DKA in adult patients between 2005 and 2022 at a tertiary hospital in Israel. Patients with DKA were stratified into medical vs non-medical groups, the primary outcome was in-hospital mortality. Results429 patients were included in the study, 385 patients (89.7 %) were treated by an internal medicine team, while 44 patients (10.3 %) were hospitalized with surgical or obstetrical conditions. Patients in the non-internal medicine group were older (52 ± 18.9 vs 43.6 ± 20.4, p < 0.005) and had higher rates of diabetes complications such as chronic ischemic heart disease (20.5 % vs. 4.2 %, p < 0.0001) and chronic kidney disease (50 % vs. 3.4 %, p < 0.001). Glucose level on presentation was lower for non-internal medicine patients (398 ± 221 mg/dL vs 551 ± 180 mg/dL) and outcomes of mechanical ventilation and length of hospitalization were more severe (29.5 % vs. 6 %, p < 0.001 and 8.0 vs. 3.0, p < 0.001). Multivariate analysis demonstrated that composite outcome of in-hospital mortality, ICU admission and longer hospitalization was more likely in the non-internal medicine group (OR 3.99, CI 1.89–8.4, p < 0.001). ConclusionDKA is a universal pathology that concerns various medical fields. It is essential for every clinician to be familiar with this condition. Patients diagnosed with DKA who were hospitalized for conditions outside of internal medicine may be at high risk and may present with lower glycemic levels. Future research is needed to characterize the unique features of subgroups of patients with DKA.

Effect of radiofrequency ablation on improving cardiac structure and function in patients with atrial fibrillation and functional mitral regurgitation

Objective: Exploring the effect of radiofrequency ablation treatment to restore sinus rhythm on the improvement of functional mitral regurgitation (FMR) and cardiac structure in patients with atrial fibrillation combined with moderate or severe FMR, compared with drug therapy alone. Methods: This retrospective cohort study consecutively enrolled patients diagnosed with persistent atrial fibrillation and moderate or severe FMR who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2021. Forty-eight patients who were treated with radiofrequency ablation and maintained sinus rhythm were enrolled in the ablation group, and 63 patients who were treated with medication alone during the same period were in the medicine group. Patients in the ablation group and medicine group were matched in a 1∶1 ratio using a propensity score, and 41 patients were finally included in each of the 2 groups. All patients reexamined echocardiography after 3-month of treatment. The proportion of patients with FMR improvement and the differences in changes of cardiac structural and functional parameters were compared between groups. Results: After propensity score matching, the ablation group was aged (69.3±7.1) years with 21 males (51.2%) and the medicine group was aged (71.3±9.4) years with 21 males (51.2%). The echocardiography after 3-month of treatment showed the rate of FMR improvement was significantly higher in the ablation group than in the medicine group (19 (46.3%) vs. 33 (80.5%), P<0.001), and patients in the ablation group showed a significant decrease in FMR extent (Δmitral regurgitation area: (-1.30±2.64) cm2 vs. (-3.55±2.50) cm2, P<0.001), left atrial size (Δleft atrial diameter: (-0.17±3.78) mm vs. (-2.46±4.01) mm, P=0.009) and E/e' (ΔE/e':-2.54±7.34 vs.-6.34±7.08, P=0.021) compared with the medicine group. There was also a significant decrease in left ventricular size (Δleft ventricular end diastolic diameter: (-3.12±6.62) mm vs. (-0.73±3.62) mm, P=0.046) and significant increase in left ventricular ejection fraction (Δleft ventricular ejection fraction: (2.73±9.69) % vs. (-0.93±5.41) %, P=0.038) in ablation group. Conclusion: Performing radiofrequency ablation to restore sinus rhythm can effectively reduce the severity of mitral regurgitation and improve left atrial and left ventricular remodeling and cardiac function in patients with atrial fibrillation and FMR.

Target Fisher: A Consensus Structure-Based Target Prediction Tool, and its Application in the Discovery of Selective MAO-B Inhibitors.

In this work we introduce Target Fisher, a consensus structure-based target prediction tool that integrates molecular docking and machine learning with the aim to aid in the identification of potential biological targets and the optimization of the use of bioassays. Target Fisher uses per-residue energy decomposition profiles extracted from docking poses as fingerprints to train target-specific machine learning models. It provides predictions for a curated set of 37 protein targets, covering a diverse range of biological entities, and offers a user-friendly interface accessible via a web server (https://gqc.quimica.unlp.edu.ar/targetfisher/). In this sense, Target Fisher is a valuable tool to aid organic and medicinal chemistry groups in target identification, drug discovery and drug repurposing. As a case study, we demonstrate the efficacy of Target Fisher by screening a small library of assorted natural products for targets relevant to neurodegenerative diseases, which resulted in the identification and experimental validation of selective inhibitors of monoamine oxidase B (MAO-B).

Prescribing by level of deprivation in Wales: an investigation of selected medicine groups

BackgroundPrescribing is the most common intervention made by healthcare professionals. Our study aimed to compare prescribing between general practitioner (GP) practices with the highest and lowest levels of deprivation.MethodsThe deprivation...

Treatment of microvascular angina pectoris by activating blood circulation to remove blood stasis: A systematic review and meta-analysis.

To systematically evaluate the clinical efficacy of using the method of activating blood circulation and removing blood stasis in the treatment of microvascular angina (MVA) based on the meta-analysis method. A comprehensive search of randomized controlled trials on the treatment of MVA using the method of activating blood circulation and removing blood stasis in Chinese and English databases such as China National Knowledge Infrastructure Database, Wanfang Data Knowledge Service Platform, Vipshop Journal Resource Integration Service Platform, PubMed, Cochrane Library, Embase, Web of Science, and CBM was conducted, and the search time limit was from the establishment of each database to February 2023. All retrieved literature was screened, and data extracted according to the specified inclusion and exclusion criteria, and data analysis was completed using Revman 5.4 software. Fifteen studies with a total of 1031 patients were finally included, and the results of the meta-analysis showed that the treatment with the method of activating blood circulation and removing blood stasis was more advantageous compared with the group of Western medicine alone. Among them, clinical effect of activating blood circulation and removing blood stasis (relative risk = 1.20, 95% confidence intervals [CI] [1.11, 1.31], P < .0001) and electrocardiographic efficacy (relative risk = 1.32, 95% CI [1.15, 1.51], P < .0001) were more effective, concentration levels of endothelin-1 (standardized mean difference = -2.14, 95% CI [-2.97, -1.31], P < .00001) and high sensitivity C-reactive protein (mean difference = -0.84, 95% CI [-0.93, -0.75], P < .00001) were lower, concentration levels of nitric oxide (standardized mean difference = 0.61, 95% CI [0.33, 0.89], P < .0001) was higher, and ST-segment depression range (mean difference = -0.07, 95% CI [-0.09, -0. 04], P < .00001) was smaller. Compared with the treatment with Western medicine alone, the treatment of MVA is more effective by choosing the method of activating blood circulation and removing blood stasis.

Esophageal transit of solid oral dosage forms – impact of different surface materials characterized in vitro and in vivo by MRI in healthy volunteers

Acceptable swallowability and complete esophageal transit are decisive for the safe and effective administration of solid oral dosage forms. This applies in particular to the main user group of medicines, older adults, who often suffer from swallowing difficulties. It is well known that surface properties play an important role in this respect. In the past, this has led to the development of numerous coating formulations for tablets with improved swallowability. However, in vitro and especially in vivo data investigating a positive effect of different coating materials is limited. Therefore, we investigated coating materials being based on polyvinyl alcohol, hydroxypropyl methylcellulose, and a copolymer of methacrylate in respect to their influence on swallowability and esophageal transit of a tablet formulation. They were compared to uncoated tablets as well as to hard gelatin capsules. Three in vitro assays suitable for routine use in pharmaceutical development were performed: i.) Wettability test in artificial saliva; ii.) Swelling measurement in artificial saliva; iii.) Measurement of the adhesion between surface materials and a simulated mucosa surface. All three assays resulted in a differentiation of the surface materials. The coated tablets showed favorable behavior compared to uncoated tablets and hard gelatin capsules. To test the effect of the different materials in vivo, an intervention study was conducted. 36 adults were included and the likeliness of prolonged esophageal transit of (un-)coated tablets as well as a hard gelatin capsule of the same weight was objectively evaluated by means of magnetic resonance imaging. While hard gelatin capsules showed highest rates for prolonged esophageal transit, the tendency for adhesion was reduced for uncoated tablets, and least for coated tablets, i.e., prolonged esophageal transit in 22.2 %, 11.1 %, and ≤5.6 % of the cases, respectively. Further differentiation of the coating materials was not possible. Subjective evaluations of each participant with respect to subjective swallowability and esophageal transit did not correlate well with the objective measurements by means of magnetic resonance imaging. The use of coatings in general has a positive influence on esophageal transit. However, the selection of coating type seems to be of greater importance in respect to patients' oral perception of the dosage forms compared to their influence on the probability for prolonged esophageal transit.

Differentiation of wild accessions within the Panax bipinnatifidus complex using newly developed polymorphic microsatellite markers

Abstract Panax L., renowned as ginseng genus, is a famous medicinal group of family Araliaceae. Within this genus, the taxa of Panax bipinnatifidus complex are mainly distributed in Himalayas and Hengduan Mountain areas. Due to the complex evolutionary history and short-term rapid radiation, the relationships among species within the complex have not been clearly resolved, and the taxa identification is difficult due to the intermediate morphological traits. This study aimed to use the available restriction-site associated DNA sequence data from 29 individuals of P. bipinnatifidus complex to mine high-polymorphic simple sequence repeat (SSR) markers, with the goal of evaluating their utility in taxa identification. Eleven polymorphic SSR loci were ultimately selected and validated through polymerase chain reactions amplifying across 63 individuals of P. bipinnatifidus complex and 13 individuals of three outgroup species. The subsequent genetic diversity analysis uncovered 76 alleles in total, ranging from 5 to 15 per locus. Observed heterozygosity spanned 0.241–0.512, while expected heterozygosity ranged between 0.345 and 0.644. The genetic kinship analysis revealed a sister relationship between Panax zingiberensis and Panax vietnamensis. The analysis result also supported the classification of samples from Hunan and Hubei provinces into a single genetic unit within the P. bipinnatifidus complex. These newly developed SSR markers will facilitate the identification of wild ginseng plants.

Effect of Acupuncture on Cognitive Function in Patients With Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

To investigate the impact of acupuncture on post-stroke cognitive impairment (PSCI). PSCI is a major barrier to stroke patients' rehabilitation, and acupuncture is one of the treatments. However, the benefit of acupuncture on PSCI is unclear. A meta-analysis and systematic review of randomized controlled trials (RCTs). Up to February 1, 2024, databases in PubMed, MEDLINE, Scopus, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang Data were searched. The risk of bias was investigated using the Cochrane Handbook for systematic reviews of treatments. Random-effect and fix-effect models were used to report the effects. There were 29 randomized clinical trials with 2477 participants included. The findings demonstrated that the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scores were higher in the acupuncture group than medicine group (mean difference [MD]=1.74, 95% confidence interval (CI) CI [1.26, 2.23], I2=59%, p<0.01). Compared to medicine group, the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score exhibited a significant decrease and demonstrated improvement in the acupuncture group. Statistically significant outcomes were observed in the Barthel Index scores and P300 event-related potential (ERP). According to subgroup analysis, acupuncture was superior to conventional therapy for improving cognitive function in PSCI patients at 4 weeks after treatment. Acupuncture therapy has shown promise in ameliorating cognitive deficits and enhancing daily functional abilities in individuals diagnosed with PSCI. But future research should focus on the duration and implement large sample, high-quality RCTs. Clinical workers in practical clinical work can select appropriate acupoints according to the actual conditions of patients, as well as confirm the treatment course of PSCI patients, while paying attention to observing and evaluating the therapeutic efficacy of acupuncture, to improve the health outcomes of patients in a patient-centered way.

DFT, Structure Activity Relationship, Fukui, Wave Function, NBO, NLO, Spectral and Hole-Electron Analyses of Dexmethylphenidate

Dexmethylphenidate (DMP) is used to treat attention deficit hyperactivity disorder (ADHD) and belongs to the central nervous system (CNS) stimulant group of medicines. The physical properties of DMP were analyzed under the DFT/B3LYP/6-311++G(d,p) basis set. The ESP study reveals the electrophilic attack is possible, while FMO analysis shows that the molecule is hard, stable and an electron donor. The non-covalent interaction (NCI) study explains that van der Waals and steric repulsion forces are observed. The HEI studies indicated that this molecule has CT excitation in the S0→S5 state. The shaded surface map analysis reveals the presence of electron depletion regions in this molecule. The UV-Vis spectral analysis was carried out in various solvents. The Fukui function analysis conveys that 7C is the best domain for electrophilic attack. Theoretical IR determinations and NLO properties were also performed. The structure-activity relationship findings were performed in order to improve the docking score.

Efficacy of Danlou tablets in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a multicenter prospective cohort study.

Danlou tablets (DLTs) have been widely used to treat coronary heart disease in China. However, the benefits associated with DLT for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in routine practice require further investigation. To investigate the effectiveness of DLT in patients with ACS undergoing PCI. This multicenter prospective cohort study for patients with ACS undergoing PCI was conducted in 40 centers in mainland China from February 2012 to December 2018. This trial is registered under ChiCTR-OOC-14005552. Patients were assigned to either the DLT group or the conventional medicine (CM) group based on whether they used DLT prior to enrollment. The duration of DLT use (1.5 g, three times a day) was 12 months. The primary endpoint comprised of cardiac death, non-fatal myocardial infarction, and urgent revascularization. Secondary endpoint included rehospitalization owing to ACS, heart failure, stroke, and other thrombotic events. The Seattle Angina Questionnaire (SAQ) was used to assess quality of life (QOL). Primary and secondary endpoints were followed up for 36 months, and the SAQ was followed up for 12 months. The Cox proportional hazards regression model was used to analyze the independent effect of DLT on primary and secondary endpoints. Propensity score matching (PSM) analyses were performed to mitigate bias. Survival estimation was performed using Kaplan-Meier survival curves and log-rank tests in the PSM cohort, and landmark analyses were used for further evaluation of primary and secondary endpoints. Subgroup analyses and interactions confirmed the robustness of the findings. Linear mixed effects models were used to assess the QOL. Overall, 936 patients were enrolled in this cohort study, of whom 875 completed follow-up. The primary and secondary endpoints had no significantly difference between the DLT and CM groups after Cox proportional hazards models. Kaplan-Meier survival curves and log-rank tests performed in the PSM cohort also found no significant differences between the two groups on primary and secondary endpoints. However, landmark analysis showed significant benefit in the primary endpoint for the DLT group after 200 days (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.22-0.93, P = 0.03). Landmark analysis also showed a significant benefit in the secondary endpoint in the DLT group within 200 days (HR 0.33, 95% CI 0.15-0.73, P = 0.006). Moreover, DLT improves the SAQ summary score, and scores in the physical limitation, treatment satisfaction, and disease perception domains for patients with ACS undergoing PCI. DLT combined with conventional treatment reduced the risk of the primary endpoint after 200 days and the secondary endpoint within 200 days during the 3-year follow-up. Additionally, DLT can improve the QOL without adverse effects.

Intervention of traditional Chinese patent medicine based on syndrome differentiation in female patients after percutaneous coronary intervention due to acute coronary syndrome: a nationwide multicenter prospective cohort study

Objective: To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Methods: The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis. Results: A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95%CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95%CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint (HR=0.62,95%CI 0.40-0.97,P=0.033) and second endpoint (HR=0.56, 95%CI 0.37-0.87,P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion: On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.