• Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE): genetics, mechanisms and precision therapy.
    2 weeks ago
    Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a recently defined malformation of cortical development that is an important cause of childhood-onset drug-resistant epilepsy. Clinically, the epilepsies associated with MOGHE are heterogeneous, with infantile epileptic spasms syndrome (IESS) being the most common manifestation. Histopathologically, MOGHE demonstrates subtle cortical dyslamination, heterotopic neurons in the white matter, hypomyelination, and a distinctive increase in the density and clustering of oligodendroglial cells, features that distinguish it from other malformations of cortical development such as focal cortical dysplasia (FCD). Recent genetic analyses of epileptogenic tissue resected from individuals with MOGHE have identified somatic mosaic loss-of-function variants in SLC35A2. This gene encodes the Golgi transmembrane UDP-galactose transporter, suggesting disrupted N-glycosylation as a distinct pathogenic mechanism underlying epilepsy in this disorder. In this review, we present the current clinical, histopathological, and molecular understanding of MOGHE, with a particular focus on recent insights gained from experimental rodent and human cellular models of SLC35A2 deficiency. We contextualise these findings against established models of mTORopathies including FCD type 2, placing MOGHE within the broader malformation of cortical development spectrum. Synthesising this evidence, we observe that neuronal activity in models of both MOGHE and mTORopathies such as FCD type 2 converge on reduced action potential firing, despite their distinct genetic aetiologies. Finally, we discuss how these findings inform our understanding of epileptogenesis, especially the emergence of infantile epileptic spasms, and the development of future precision therapeutic strategies across malformations of cortical development.
    Mental Health
    Care/Management
  • Effect of medial opening wedge high tibial osteotomy versus unicompartmental knee arthroplasty on mental health: a comparative study with propensity score-matched analysis.
    2 weeks ago
    Medial opening wedge high tibial osteotomy (MOWHTO) and unicompartmental knee arthroplasty (UKA) are established treatments for knee osteoarthritis (KOA). This study compared their effects on mental health outcomes.

    A retrospective cohort study was conducted on patients who underwent MOWHTO or UKA between 2019 and 2023 at a single tertiary institution. The primary outcome measure, the Short Form-36 mental component score (SF-36 MCS), was recorded at baseline, six months and two years post-procedure. Secondary outcomes included the SF-36 physical component score (PCS) and the Oxford knee score (OKS). A total of 105 MOWHTO and 89 UKA procedures were performed. Propensity score matching accounted for preoperative scores, age, gender and body mass index, yielding 51 patients per group. Multivariable regression was used to examine associations between preoperative MCS and postoperative outcomes. Baseline predictors of postoperative MCS were analysed. The level of significance was set at P < 0.05.

    At six months postoperatively, the UKA group demonstrated better PCS (MOWHTO 42.0 vs UKA 49.6, P < 0.001) and OKS (MOWHTO 23.0 vs UKA 18.8, P = 0.002). At two years, both groups achieved similar improvements in SF-36 MCS, SF-36 PCS and OKS. Preoperative MCS showed a moderate association with postoperative MCS and weak associations with postoperative PCS and OKS. Preoperative MCS was the only baseline factor independently associated with postoperative MCS.

    In patients with KOA, MOWHTO and UKA achieved similar improvements in mental health scores at two years. Preoperative mental health is an important determinant of postoperative mental health, highlighting its importance in preoperative assessment and counselling.
    Mental Health
    Care/Management
  • Second victim: a concept analysis based on Rodgers' evolutionary model.
    2 weeks ago
    Healthcare-related incidents affect both patients and professionals involved. The impact on these professionals, known as "second victims," is one of the major hidden burdens of harm.

    To analyze the concept of the "second victim" from Rodgers' evolutionary perspective.

    This study conducted a concept analysis based on Rodgers' evolutionary perspective, using a scoping review to identify attributes, antecedents, consequences, surrogate terms, and related concepts associated with the "second victim" concept.

    The attributes of the "second victim" concept involve persistent physical, emotional, and psychological consequences. Antecedents include a punitive culture and a lack of institutional and peer support. Consequences include sleep disorders, anger, fear, sadness, shame, intrusive memories, anxiety, depression, isolation, absenteeism, and leaving the profession. Related terms include patient safety and mental health, while surrogate terms include the "second victim phenomenon" and "second victim syndrome".

    Punitive environments exacerbate negative impacts, undermine patient safety, promote error concealment, and increase underreporting, thereby hindering organizational learning and the correction of failures.

    The "second victim" concept refers to healthcare workers, scholars, and administrative or support staff who are directly or indirectly involved in patient care and who, when involved in an unintentional healthcare-related incident, manifest physical, emotional, and psychological reactions with repercussions across biopsychosocial, ethical, and legal dimensions. Without adequate and timely support, these reactions can become chronic and, eventually, pathological.
    Mental Health
    Care/Management
  • Effectiveness of Assertive Therapy for Parents in Managing Adolescent Emotions.
    2 weeks ago
    Adolescents experienced significant psychosocial stressors during the COVID-19 pandemic due to movement restrictions, social isolation, and disruptions in routine, which adversely affected emotional regulation. As primary caregivers, parents play a critical role in supporting adolescents' emotional well-being, particularly during prolonged home confinement. Assertiveness training may enhance parents' ability to manage adolescents' emotional responses by improving communication, emotional control, and problem-solving skills.

    To determine the effectiveness of assertiveness training for parents in improving their ability to manage adolescents' emotional regulation.

    This study employed a quantitative quasi-experimental design with a control group. A total of 92 parents were recruited and allocated to either the intervention group (n = 46) or the control group (n = 46) using simple random sampling. The intervention consisted of assertiveness training delivered over six structured sessions, focusing on enhancing parents' assertive communication and emotional management strategies in addressing adolescent problems. Outcome measures assessed parents' ability to manage adolescent emotions before and after the intervention.

    Participants ranged in age from 22 to 65 years, with the largest proportion aged 43-45 years. Most respondents were married (82.6%), had adolescent daughters (43.4%), and had attained a low educational level (80.4%). Post-intervention analysis demonstrated a statistically significant improvement in parents' ability to manage adolescent emotions in the intervention group compared with the control group (p <0.05). An associated increase in adolescents' emotional understanding, as perceived by parents, was also observed following the intervention.

    Assertiveness training is effective in enhancing parents' capacity to manage adolescents' emotional regulation. Collaboration between the Department of Health and psychiatric nursing specialists is recommended to integrate assertiveness training into community-based mental health programs. Incorporating this intervention as a core competency for psychiatric nursing specialists in community health settings may strengthen family-centered mental health services, particularly during public health emergencies.
    Mental Health
    Policy
  • Potential preventive role of low-dose methotrexate against incident recorded psychosis: a retrospective cohort study based on electronic health records.
    2 weeks ago
    Recent evidence suggests that low-dose methotrexate might have antipsychotic properties. However, it remains unknown whether low-dose methotrexate is associated with a reduced risk of incident recorded psychosis in real-world data, whether these associations extend to other putatively immune-related common psychiatric conditions, or whether similar associations are observed with other disease-modifying anti-rheumatic drugs (DMARDs).

    In this retrospective cohort study using electronic health records (TriNetX US Collaborative Network), we identified adults with rheumatoid arthritis (age ≤45 years at treatment initiation; data extracted from 1 January 2000 to 21 December 2025). The 5-year risk of an incident recorded psychosis (primary outcome) and bipolar, depression, or anxiety disorders (secondary outcomes) were compared between low-dose methotrexate and each of 14 comparator drugs used in rheumatoid arthritis - three primary comparators (non-steroidal anti-inflammatory drugs; NSAIDs, naproxen, diclofenac and celecoxib) and 11 secondary and exploratory DMARDs comparators. Cumulative incidences and ratios of restricted mean time lost (rRMTL) are reported. Results were Bonferroni-corrected for multiple comparison.

    Comparator cohort sizes ranged from 1161 to 21,445 (mean ages 33.7-37.4 years). For the primary outcome of psychosis, initiation of low-dose methotrexate was associated with lower 5-year incidence of newly recorded psychosis than initiation of naproxen (rRMTL 0.69, 95% CI 0.55-0.87) or diclofenac (rRMTL 0.71, 0.56-0.89); no significant difference was observed versus celecoxib or biologic DMARDs. For the secondary outcomes, low-dose methotrexate was similarly associated with lower 5-year incidence of newly recorded bipolar disorder, depression, and anxiety compared with non-selective NSAIDs naproxen and diclofenac, with the mood and anxiety associations extending to the selective cyclo-oxygenase-2 inhibitor celecoxib.

    In a real-world rheumatoid arthritis cohort, initiation of low-dose methotrexate was associated with lower 5-year incidence of newly recorded psychosis, bipolar disorder, depression, and anxiety than initiation of non-selective NSAIDs. Given that extensive trials of broad anti-inflammatories have yielded limited psychiatric benefit, the differential profile of low-dose methotrexate is consistent with a mechanism beyond simple inflammation suppression. We hypothesise potentiation of regulatory T cell-mediated control of systemic inflammation and neuro-glial regulation. The active-comparator observational design cannot establish causation; these findings are hypothesis-generating and confirmatory inference will require interventional studies.

    UK Research and Innovation (UKRI) Medical Research Council [grant number UKRI4403] Mental Health Platform. The National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research.
    Mental Health
    Policy
  • Bayesian Workflow for Minimal PBPK Models: Case Study of Dapagliflozin.
    2 weeks ago
    Numerous clinical trials (CTs) and population pharmacokinetic (PK) models have been published on dapagliflozin, an approved SGLT2 inhibitor used to treat type 2 diabetes, heart failure, and chronic kidney disease. This study proposes a Bayesian workflow for the development of minimal physiologically-based PK models (mPBPK) that integrates all available PK information, to support uncertainty quantification and informed drug development. First, a systematic collection of published dapagliflozin PK data and models was performed. A mPBPK model was then developed, and posterior parameter distributions were obtained based on data from parallel-design CTs. Three Bayesian modeling packages: NIMBLE (v1.1.0), MCSim (v6.2.0), and Torsten (v0.89.0), and three alternative prior specifications were evaluated. Model validation was performed using PK data from crossover CTs and urinary recovery data, followed by sensitivity analysis. 18 studies reporting PK data and 10 reporting PK models were identified. Posterior distributions were comparable across programs: 95% credible intervals overlapped. Torsten showed superior sampling efficiency, as compared to NIMBLE and MCSim (5.7 and 10.0 times higher in tails and central posterior regions, respectively); however, the average effective sample size per hour was comparable for Torsten and MCSim. The predicted urinary recovery was 2.2%-4.4% (mean 3.2%), while the observed values were in the 0.8%-4.0% range (mean 2.0%). Glomerular filtration rate and fraction unbound were the main contributors to inter-trial variability in urinary recovery, while volume of distribution and clearance had the highest influence on maximum concentration and area-under-the-concentration curve, respectively. The proposed Bayesian workflow is flexible and transferable to other mechanistic model types.
    Diabetes
    Diabetes type 2
    Access
    Care/Management
    Advocacy
  • [Distribution patterns and clinical characteristics of traditional Chinese medicine syndromes in diabetic peripheral neuropathy].
    2 weeks ago
    Using multiple statistical methods, this study investigated the core diagnostic information from the four diagnostic methods, the distribution patterns of syndrome elements, and their relationship with laboratory biochemical indicators in diabetic peripheral neuropathy(DPN). The aim is to deepen the understanding of the disease-symptom-syndrome relationship in DPN. A retrospective study was conducted on 1 420 inpatients diagnosed with DPN patients at the Department of Endocrinology, the First Affiliated Hospital of Anhui University of Chinese Medicine, from June 2014 and June 2023. Data mining techniques, including frequency statistics, association rule analysis, factor analysis, cluster analysis, and Bayesian network analysis, were applied to examine general patient information, TCM diagnostic data from the four diagnostic methods, and laboratory biochemical indicators. The core clinical manifestations in DPN patients were dry mouth, limb numbness, blurred vision, fatigue, thirst, and a thready pulse. Association rule analysis indicated Yin deficiency leading to blood stasis is the core pathogenesis. Factor analysis indicated that the disease location primarily involved the spleen, kidney, and liver, while main disease nature elements were Yin deficiency, Qi deficiency, and blood stasis, often complicated by concomitant phlegm turbidity, Yang deficiency, and essence depletion. Cluster analysis identified five syndrome patterns: Yin deficiency with blood stasis syndrome, Qi deficiency with blood stasis syndrome, Yang deficiency with cold aggregation syndrome, phlegm stasis obstructing collateral syndrome, and liver-kidney deficiency syndrome. Among these, Yin deficiency with blood stasis syndrome and Qi deficiency with blood stasis syndrome were the most prevalent. Bayesian network analysis revealed associations between abnormal fasting blood glucose(FBG) and symptoms such as chest tightness, palpitations, dizziness, insomnia, and constipation. Abnormal glycosylated hemoglobin(HbA1c) was associated with frequent urination, polyphagia, polydipsia, thirst and dry mouth. Abnormal total cholesterol(TC) was linked to emaciation, fear of cold and cold limbs, and a weak pulse. Abnormal serum creatinine(SCr) was associated with slow reaction, a wiry pulse, and limb pain. The distribution of TCM syndromes in DPN primarily involves Yin deficiency with blood stasis syndrome and Qi deficiency with blood stasis syndrome. The core pathogenesis is Yin deficiency leading to blood stasis, with the disease location in the spleen, kidney, and liver. The identified associations between FBG, HbA1c, TC, SCr and specific TCM syndromes provide an objective basis for the microscopic syndrome differentiation of DPN and its integrated diagnosis and treatment combining Chinese and western medicine.
    Diabetes
    Access
    Care/Management
    Advocacy
  • [Roles of vascular smooth muscle cells phenotype transformation in mediating progression of diabetic macroangiopathy and current status of traditional Chinese medicine treatment].
    2 weeks ago
    Diabetic macroangiopathy, a major chronic complication of diabetes, is characterized by atherosclerosis. Its pathological core involves the phenotype transformation of vascular smooth muscle cells(VSMCs) towards synthesis, aging, calcification, macrophage-like and fibroblast-like phenotypes. These phenotypic transformations jointly drive atherosclerotic plaque formation, vascular remodeling and calcification, leading to high-risk events such as myocardial infarction and stroke, which are important causes of disability and mortality in diabetic patients. Current conventional treatment provides insufficient long-term protection against macroangiopathy. In contrast, traditional Chinese medicine(TCM), through its holistic regulation via multi-component and multi-target mechanisms, has shown unique advantages in regulating VSMCs phenotype transformation. The progression of diabetic macroangiopathy mediated by VSMCs phenotypic transformation is characterized by deficiency in origin and excess in superficiality in TCM theory. Conceptualizing this phenotypic switching as &quot;phlegm turbidity and blood stasis obstructing the collaterals&quot;, therapeutic strategies should focus on resolving phlegm and turbidity, transforming stasis and unblocking collaterals, while simultaneously reinforcing healthy Qi and tonifying deficiencies. A growing body of research indicates that monomers such as matrine, baicalein, and tanshinone Ⅱ_A, as well as sour Chinese herbal medicines and compound formulas such as Huoluo Xiaoling Dan, can inhibit pathological VSMCs phenotype transformations, including abnormal proliferation, migration, aging, and calcification. These interventions align with the pathogenesis and therapeutic principles, thereby delaying the progression of vascular lesions. This review briefly outlined the pathological progression of diabetic macroangiopathy, elaborated on how VSMCs phenotype transformation mediated diabetic macroangiopathy, and summarized key studies on the intervention of TCM active compounds, monomers and formulas in diabetic macroangiopathy by regulating VSMCs phenotype transformation. It aims to provide new strategies for the prevention and treatment of diabetic macroangiopathy and ultimately enhance clinical diagnosis and treatment.
    Diabetes
    Cardiovascular diseases
    Care/Management
    Policy
  • [Prescription patterns of Carthami Flos-containing compound formulas in intervention of diabetic peripheral neuropathy based on data mining].
    2 weeks ago
    Based on a data science perspective, this study systematically elucidated the prescription patterns and core compatibility mechanisms of Carthami Flos-containing formulas in the treatment of diabetic peripheral neuropathy(DPN), aiming to provide scientific evidence for optimizing evidence-based TCM therapeutic strategies. A comprehensive literature search was conducted across CNKI, Wanfang, VIP, and PubMed databases, covering publications from database inception to September 18, 2025. Following rigorous screening, 297 clinical studies were included, all focusing on DPN as the primary condition, employing orally administered Chinese herbal medicines, and reporting effective clinical outcomes, encompassing a total of 12 783 cases. Frequency analysis was performed using R software, combined with association rule mining, network topology analysis, prescription similarity assessment, and cluster analysis, to clarify the structural composition and dosage distribution patterns of Carthami Flos-containing formulas. Data analysis showed that decoctions were the predominant dosage form in the clinical treatment of DPN. The core syndrome patterns were highly concentrated in Qi deficiency with blood stasis and combined Qi-Yin deficiency. Major outcome measures included nerve conduction velocity, blood glucose levels, and hemorheological parameters. Within the high-frequency herbal spectrum, Carthami Flos, Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, and Paeoniae Radix Rubra occupied dominant positions. The core prescription network exhibited a compatibility structure centered on Astragali Radix, Chuanxiong Rhizoma, and Angelicae Sinensis Radix, with the &quot;Astragali Radix-Angelicae Sinensis Radix&quot; combination demonstrating the highest support in association rule analysis. The core network-derived combination of &quot;Carthami Flos-Chuanxiong Rhizoma-Paeoniae Radix Rubra-Pheretima-Angelicae Sinensis Radix-Persicae Semen&quot; closely corresponded to the classical formula Buyang Huanwu Decoction. Dosage analysis further revealed that the most common compatibility ratio of Astragali Radix to Carthami Flos was 3∶1, and that the dosages of Astragali Radix(mean 36 g) and Angelicae Sinensis Radix(mean 12 g) frequently exceeded standard pharmacopeial recommendations, reflecting a therapeutic strategy characterized by high-dose Qi supplementation to promote blood circulation. The findings suggest that, despite the complex and mixed deficiency-excess pathogenesis of DPN, blood stasis persists throughout the disease course. Carthami Flos-containing formulas primarily act through tonifying Qi, activating blood circulation, resolving stasis, and unblocking the collaterals, embodying a modern clinical strategy of simultaneous regulation of Qi and blood. This study not only quantitatively validates the guiding significance of classical TCM theories in modern DPN management and elucidates the dose-effect relationships of core prescriptions, but also provides a reproducible methodological framework for mining prescription patterns in complex diseases, offering substantial academic value for the modernization and internationalization of TCM.
    Diabetes
    Care/Management
    Policy
  • Effect of a pharmacist-led mHealth app on adherence, quality of life, and glycaemic control in diabetes: A multicentre RCT.
    2 weeks ago
    To evaluate whether CareAide®, a pharmacist-driven mHealth application, improves medication adherence, health-related quality of life (HRQoL), and glycaemic control in diabetes mellitus using structural equation modelling.

    Pre-specified secondary analysis of the type 2 diabetes mellitus cohort from a 6-month multicentre open-label randomised controlled trial (N = 663) across three Malaysian hospitals. Adherence was assessed by MMAS-8 (subjective) and Proportion of Days Covered (PDC; pharmacy-verified). HRQoL was measured by AQoL-6D and EQ-5D-5 L. Structural equation modelling (SEM), Necessary Condition Analysis, and Importance-Performance Map Analysis (cIPMA) were applied.

    CareAide® produced large adherence gains (MMAS-8: 7.31 vs 5.55, d = 1.64; PDC ≥ 80%: 81.6% vs 33.0%; both p < 0.001). Early 3-month adherence was the strongest predictor of sustained 6-month adherence in both models (β std = 0.567 and 0.688; p < 0.001). AQoL-6D utility improved significantly (0.669 vs 0.618; d = 0.353, p < 0.001), driven by coping (d = 0.447) and relationships (d = 0.254) domains. HRQoL did not mediate adherence; gains were a direct independent benefit. The intervention effect on HbA1c was not statistically significant in the PDC-based SEM model (β =  - 0.333, p = 0.065); a group difference was, however, supported by baseline-adjusted ANCOVA (β =  - 0.41%, p = 0.002), and the complete-case comparison was non-significant (p = 0.153), so glycaemic findings warrant cautious interpretation. cIPMA identified the intervention as the primary optimisation target.

    CareAide® significantly improves medication adherence and psychosocial quality of life. Evidence for glycaemic benefit came from baseline-adjusted analysis (ANCOVA), though findings should be interpreted with caution given incomplete HbA1c data at one site. The first three months are the most critical period for pharmacist support. In this dataset, PDC appeared more sensitive than MMAS-8 to the HbA1c signal within 6 months, but this finding requires confirmation in longer studies with more complete HbA1c data.

    ClinicalTrials.gov NCT06068309.
    Diabetes
    Diabetes type 2
    Care/Management