As third-year medical students transition into high-stakes, high-stress clinical environments like the emergency department (ED), they may experience significant personal trauma. However, little is known about how this trauma is experienced early in their training - specifically during the transition from preclinical to clinical learning environments. This study addresses that gap by exploring third-year medical students' experiences of trauma during the emergency medicine (EM) clerkship through the lens of Trauma-Informed Care (TIC) and identifies workplace factors and intersectional demographics influencing these experiences. This qualitative study used the critical incident technique to explore emotionally-significant events encountered by third-year medical students immediately after completing the EM clerkship as their first core clerkship at a single academic institution. We conducted a thematic analysis using the Substance Abuse and Mental Health Services Administration's six TIC principles. Data were triangulated with quantitative demographic data, and data saturation was confirmed through constant comparison and reflexive team discussions. Seventeen students participated, describing 19 critical incidents of trauma. The most common trauma types involved lack of peer support and lack of empowerment or voice. Intersectional factors such as race, gender, and age shaped both the type and nature of trauma. Clinical uncertainty, power differentials, and unprofessional behavior emerged as frequent triggers. Applying a trauma-informed framework to medical education reveals how structural and interpersonal factors contribute to student trauma when they transition to the clinical learning environment. These findings highlight opportunities for trauma-informed clerkship design and structured support to create safer, more inclusive learning spaces. Not applicable.
Intimate partner violence is a major public health issue, affecting around 10% of women each year in France. Its consequences extend beyond the psychological sphere, directly influencing the control of chronic diseases and the occurrence of psychosomatic disorders frequently encountered in internal medicine. Prolonged exposure to stress and partner coercion perpetuates a vicious cycle between chronic illnesses, diffuse pain, unexplained fatigue, and somatic decompensations. Internists, given the comprehensive nature of their practice and the regular follow-up of vulnerable patients, are often confronted with the challenge of identifying such situations. Screening relies on attentive history-taking, observation of suggestive signs (social isolation, anxiety, medical nomadism), and the use of validated tools such as the WAST or the Violentomètre. Management should be multidisciplinary, integrating psychological, social, and legal support, through referral to specialized structures such as Maisons des Femmes, and through the training of healthcare professionals to improve detection and help break the cycle of violence.
Recurrent aphthous stomatitis is a common inflammatory condition of the oral mucosa characterized by painful ulcers that heal spontaneously but recur unpredictably. Although lesions resolve clinically, the biological processes occurring during remission remain poorly understood. This exploratory study investigated whether salivary molecular profiles persist after clinical healing and may be associated with the recurrent nature of the disease. In this hypothesis-generating case-control study, saliva samples were collected from patients with recurrent aphthous stomatitis during ulcerative and remission stages and from healthy controls. The salivary pellet was analyzed using discovery-based mass spectrometry proteomics. Complement components and dipeptidyl peptidase-4 (DPP4) were evaluated using immunological assays. Microbial identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitative polymerase chain reaction. The functional interaction between bacteria and oral keratinocytes was explored in vitro using a high-dose infection model to probe epithelial responsiveness. Proteomic analysis identified stage-dependent molecular differences across the clinical course of recurrent aphthous stomatitis. Complement-related proteins and Mammaglobin-B (SCGB2A1) were found to be enriched during remission compared with healthy controls, suggesting persistent molecular signatures of epithelial and immune activity after clinical healing. Microbial profiling revealed enrichment of Streptococcus pneumoniae and Clostridium species in disease stages. In a controlled experimental setting, exposure of oral keratinocytes to Streptococcus pneumoniae was associated with increased DPP4 expression and activation of pathways linked to epithelial stress and immune signaling. Collectively, these exploratory findings suggest that remission is characterized by molecular features distinct from the healthy state. This exploratory proteomic study suggests that persistent molecular features associated with inflammation and epithelial stress can be detected in saliva after clinical healing in recurrent aphthous stomatitis. Complement-related protein enrichment, epithelial stress markers, and microbial associations were observed during remission, pointing to incomplete molecular recovery of the oral mucosa. While causality cannot be inferred, these hypothesis-generating findings offer a basis for future mechanistic studies and suggest that salivary molecular features warrant investigation as potential candidates for monitoring disease activity.
Although artificial intelligence (AI) models have demonstrated high accuracy in diagnosing Parkinson's disease (PD) from speech signals, their "black-box" nature prevents mechanistic understanding of vocal impairment, limiting clinical trust and utility. A paradigm shift from correlation-based explanation to causal reasoning is needed to unlock the potential of AI in computational medicine. We propose the Voice Causal Generative Model (VCGM), a novel computational framework designed to infer physiologically plausible causal pathways from observational speech data. The core technical innovation of VCGM is the integration of biophysical knowledge as hard constraints within a linear non-Gaussian acyclic model. We formalize this in Theorem 1, which proves that these domain-specific hierarchical constraints guarantee the unique identifiability of the underlying causal structure, a condition unachievable by unconstrained methods. We implemented VCGM using a constrained DirectLiNGAM algorithm and conducted rigorous validation, including bootstrap analysis for stability, an ablation study, and comparison with traditional causal discovery algorithms. The VCGM uncovered a stable, medically plausible causal pathway for PD dysphonia. The model revealed a hierarchical cascade from disease status to physiological instability (e.g., the robust Shimmer→HNR pathway) and finally to acoustic distortion (e.g., HNR→MFCC2). VCGM reduced physiologically implausible edges by 100% compared to unconstrained LiNGAM (5 implausible edges) and GES (5 implausible edges). while a conventional SHAP-based associative model failed to provide any directional mechanistic insights. The VCGM provides a validated, "white-box" framework for deconstructing pathophysiology from complex biosignals. Its primary technical contribution is a provably identifiable modeling approach that makes causal discovery feasible and reliable in hierarchically structured domains. It marks a critical step from the associative "what" to the causal "why" in computational biomedicine, offering a blueprint for more transparent, trustworthy, and clinically insightful AI systems. To facilitate clinical translation and reproducibility, all code and data are publicly available under an open-source license.
While scholarly activities are considered essential for medical advancement and improved patient outcomes, the educational value and potential impact on postgraduate medical trainees' well-being has not been well studied. We examined whether clinical research experience and scholarly activity requirements during early postgraduate medical training affect trainees' competency and well-being. We conducted a cross-sectional study of Japanese early postgraduate medical trainees (postgraduate year [PGY]1-2) recruited from hospitals participating in the General Medicine In-Training Examination (GM-ITE) in January 2024 and from teaching hospitals with scholarly activity requirements that did not participate in GM-ITE. Participants were classified into three groups based on scholarly activity experience: no scholarly activity, scholarly activity without clinical research, and scholarly activity with clinical research. The primary outcome was evidence-based medicine (EBM) competency assessed using the Japanese version of the Assessing Competency in EBM (ACE) tool. Secondary outcomes included GM-ITE scores, future scholarly activity intentions, depression symptoms, and well-being measures. Associations between scholarly activity experience and outcomes were examined using multiple regression analysis for continuous outcomes and logistic regression analysis for binary outcomes, adjusting for potential confounders; missing data were addressed using multiple imputation. Among 1,152 participants (1,150 from GM-ITE-participating hospitals and 2 from non-participating hospitals), 656 (57.0%) reported engaging in scholarly activities during early postgraduate medical training, with 60 (9.1%) conducting clinical research. After adjusting for potential confounders, compared to trainees without scholarly activity, the difference in ACE tool scores was 0.22 points (95% confidence interval [CI]: 0.02 to 0.41) for those who engaged in scholarly activities without clinical research and 0.40 points (95% CI: -0.02 to 0.83) for those who conducted clinical research. Stratification by program requirements revealed differences of 0.34 points (95% CI: 0.09 to 0.58) for voluntary scholarly activities and 0.09 points (95% CI: -0.19 to 0.37) for required activities. Trainees who conducted clinical research or engaged in required scholarly activities showed higher odds of future academic interest (adjusted odds ratio [OR]: 2.68 [95% CI: 1.33-5.37] and 1.52 [1.02-2.25], respectively), while those who engaged in scholarly activities without clinical research or without requirements showed similar odds to the reference group (adjusted OR: 1.27 [0.97-1.68] and 1.24 [0.88-1.74], respectively) Well-being measures showed minimal differences across groups. Scholarly activities during early postgraduate medical training, whether required by programs or not, had little impact on trainees' competency and well-being. However, trainees who engaged in clinical research showed increased interest in future academic activities, suggesting the importance of establishing supportive environments for interested trainees.
Integration of Artificial Intelligence (AI), particularly deep learning, into medical imaging represents a profound shift in diagnostic medicine, moving from purely descriptive analysis to advanced predictive and prescriptive analytics. This Collection explores the rapid advancement of AI-driven tools in their specific fields such as oncology, cardiology, ophthalmology and so on, highlighting their potential to improve diagnostic accuracy, workflow efficiency, and personalized treatment planning. However, significant challenges remain, including the heterogeneity of medical image data, the "black box" nature of some intelligent models, and the critical hurdles of clinical integration and validation. The research presented here addresses these frontiers, showcasing innovations in algorithm development, explainable AI, and translational application. This Editorial synthesizes the contributions and outlines the essential collaborative pathway-uniting computer scientists, clinicians, and regulatory bodies-required to translate algorithmic promise into robust, trustworthy, and equitable clinical tools that genuinely improve patient care.
Inflammaging refers to the chronic, low-grade, sterile inflammatory state that emerges as a hallmark of biological aging and is increasingly recognized as a contributor to functional decline, frailty, and the progression of multiple age-associated diseases. While acute inflammation supports host defense and tissue repair, persistent and unresolved inflammatory signaling promotes tissue damage, metabolic dysregulation, and impaired immune homeostasis. Inflammaging reflects a dysregulated physiological state associated with elevated damage-associated molecular patterns (DAMPs), pro-inflammatory cytokines, altered immune cell composition, metabolic imbalance, and the accumulation of senescent cells exhibiting a senescence-associated secretory phenotype (SASP). Together, these processes impair immune surveillance, increase oxidative stress, and tissue vulnerability, potentially accelerating functional decline and amplifying disease trajectories that may originate earlier in life. Despite ongoing challenges in precisely defining and measuring inflammaging, evidence suggests that its development is shaped not only by chronological aging but also by behavioral, environmental, psychosocial, and genetic factors, highlighting its dynamic and potentially modifiable nature. In this review, we distinguish inflammaging from general chronic inflammation, synthesize current understanding of its biological origins and mechanistic drivers, and examine its role in clinical outcomes including sarcopenia, neurodegeneration, and cardiovascular disease. We propose a conceptual translational framework linking biological mechanisms of inflammaging to multilayer biomarker signatures, AI-based risk stratification, and precision interventions. Additionally, we discuss the opportunities and limitations of these approaches for identifying individuals at risk for chronic disease and informing multi-dimensional strategies to promote resilience and extend health-span.
Nitric oxide (NO) delivery from diazeniumdiolate donors is widely explored in biomaterial design for wound healing and regenerative medicine. However, accurate quantification of NO release remains challenging due to its gaseous nature, short half-life, and high reactivity. The hemoglobin assay provides a direct, stoichiometric method for NO detection but is typically limited in throughput and temporal resolution. Here, we adapt this assay to a microscale, multiwell spectrophotometric format to monitor NO release from electrospun methacrylated alginate hydrogels, with and without mesoporous silica nanoparticles. The miniaturized assay enabled continuous, parallel monitoring of NO release over 24 h while reducing reagent consumption. Four diazeniumdiolate donors (commercial and in-house synthesized) were evaluated at 0.05 and 0.1 mg/ml, yielding cumulative NO concentrations of approximately 2-7 μM. Nonlinear exponential modeling (C(t) = A·(1 - e^(-kt)) revealed donor-specific release kinetics consistent with known diazeniumdiolate decomposition behavior. Unprotected donors exhibited rapid initial release (k ≈ 0.2-0.5 1/h), whereas sterically protected analogs showed slower, more sustained release (k < 0.1 1/h). Incorporation of mesoporous silica nanoparticles modulated release behavior in a donor-dependent manner. Statistical analysis identified donor chemistry as the primary determinant of release kinetics, while concentration acted mainly as a scaling factor. This microscale hemoglobin assay provides a resource-efficient platform for parallel, time-resolved quantification of NO release from biomaterials. It enables comparison of donor chemistry and matrix effects under standardized conditions, facilitating the evaluation of NO-releasing systems for biomedical applications.
Diagnostic integration technology represents a significant advancement in cancer diagnosis and treatment. The combination of fluorescence probe-based imaging methods with photodynamic therapy (PDT) offers distinct advantages due to its high sensitivity and minimally invasive nature. However, the effective detection depth and spatial resolution of fluorescence imaging are limited by light scattering effects in biological tissues. Additionally, high concentrations of GSH in the tumor microenvironment (TME) neutralize reactive oxygen species (ROS) generated by PDT, directly inhibiting therapeutic efficacy. Therefore, developing a highly sensitive, high-resolution fluorescent probe to achieve integrated tumor diagnosis and treatment is of great significance. This study developed an activatable diagnostic-therapeutic probe, MB-2O-MB. In MB-2O-MB, methylene blue (MB) served as both the photosensitizer and signal reporting moiety, while a thiols-sensitive disulfide bond was introduced as the linker and response unit. When the probe reacted with GSH in tumor regions, the disulfide bond broke, causing structural dissociation and releasing free MB molecules. Experiments demonstrated that the probe exhibited strong interference resistance, and high sensitivity (LOD = 57.99 nM) for this reaction. Furthermore, the photoacoustic (PA) signal generated upon probe activation compensated for the limited tissue penetration depth of fluorescence imaging, enabling more precise spatial localization of tumor regions. Therapeutically, upon irradiation with 660 nm near-infrared (NIR) laser light, the released MB efficiently generated singlet oxygen, effectively inducing 4T1 tumor cell death. In vivo data further validated the significant tumor suppression effect of MB-2O-MB via PDT. In summary, MB-2O-MB achieves precise tumor localization and complete eradication through the synergistic combination of NIR fluorescence/PA dual-modality imaging and PDT. This strategy simultaneously overcomes the drug resistance bottleneck and imaging limitations of conventional photodynamic therapy, paving a new pathway for constructing highly selective and potent smart diagnostic and therapeutic systems, and significantly advancing precision medicine.
Elevated serum vitamin B12 levels have emerged as a paradoxical prognostic marker associated with increased mortality across various clinical settings, yet their significance in hospitalized dementia patients remains unexplored. Given the high vulnerability of this population, we aimed to investigate the association between elevated serum vitamin B12 levels and all-cause mortality. This retrospective cohort study evaluated 90-day outcomes in hospitalized adults with dementia who had serum vitamin B12 levels measured within 7 days of admission (2010-2024). Patients were categorized into exposure (vitamin B12 ≥ 900 pg/mL) and control (300-900 pg/mL) groups. Propensity score matching balanced baseline characteristics, including demographics, comorbidities, and laboratory parameters. The primary endpoint was all-cause mortality within 90 days. Secondary endpoints comprised sepsis, pneumonia, urinary tract infection, and admission to the intensive care unit (ICU). Sensitivity analyses restricted the cohort to patients with unspecified dementia and to patients with a dementia diagnosis established at least 1 year before the index admission. After propensity score matching, 16,513 patients were included in each cohort. Elevated vitamin B12 was significantly associated with increased 90-day mortality (10.9% vs 8.3%; odds ratio [OR] 1.36, 95% confidence interval [CI] 1.26-1.46, P < .001), sepsis (4.2% vs 3.0%; OR 1.43, 95% CI 1.27-1.61, P < .001), pneumonia (8.3% vs 6.6%; OR 1.28, 95% CI 1.18-1.39, P < .001), and ICU admission (3.9% vs 3.0%; OR 1.31, 95% CI 1.16-1.47, P < .001). No association was observed with urinary tract infection (OR 0.97, 95% CI 0.90-1.04, P = .377). The findings remained robust across sensitivity and subgroup analyses. Elevated vitamin B12 levels are associated with increased short-term mortality, infectious complications, and ICU admission in hospitalized patients with dementia. This readily available biomarker may serve as a potential indicator for risk stratification in this vulnerable population. However, given the observational nature of this study, future prospective studies are warranted to confirm these findings and elucidate the underlying mechanisms.
Acute gout attacks cause severe pain, and short-video platforms have become patients' primary source of information. However, the quality and reliability of this information are increasingly concerning. This study will systematically evaluate the information quality of gouty arthritis-related content on Bilibili and TikTok video-sharing platforms, along with factors influencing video quality. This study systematically evaluated the quality and reliability of 100 popular gout-related videos each from Bilibili and TikTok. Video quality and reliability were assessed using the global quality score, Modified DISCERN (mDISCERN), JAMA Benchmark Standard, and Hexagonal Radar Schema (HRS) tools. Correlations between video quality and metrics such as likes, comments, saves, and shares were also analyzed. Results showed median scores across 4 metrics on Bilibili: global quality score 3.0 (2.00, 4.00), mDISCERN3..0 (3.00, 4.00), JAMA 3.0 (2.00, 3.00), HRS 5.0 (4.00, 6.00); TikTok's corresponding scores were 3.0 (IQR 3.00-4.00), 3.0 (IQR 3.00-4.00), 3.0 (IQR 3.00-3.75), and 3.0 (IQR 2.00-4.50). Although Bilibili's HRS scores were higher than TikTok's, video quality was generally poor across both platforms. Furthermore, the study found a positive correlation between video length and quality. Increased likes and shares may not always reflect improved video quality, as these metrics can be influenced by the entertainment nature of online videos and may not fully indicate quality. Our research indicates that the health information short videos related to gouty arthritis on Bilibili and TikTok have poor quality, but the videos uploaded by medical professionals are considered reliable in terms of comprehensiveness and content quality. Health information seekers must carefully evaluate the scientific accuracy and reliability of short videos providing medical information on Bilibili and TikTok before making healthcare decisions.
In the context of gamete donation, cytomegalovirus (CMV) serological screening was originally implemented to mitigate concerns about viral transmission, particularly following the HIV epidemic. Although emerging evidence questions the reliability of serological markers in accurately reflecting the presence of the virus in genital secretions, current North American practices still heavily rely on CMV serological testing to identify sperm donors at risk of transmitting CMV during fertility treatments. This review explores the complexities of CMV transmission in assisted reproductive technologies (ART), underscoring the unpredictable nature of viral shedding in semen and the inherent limitations of relying solely on serostatus for risk assessment. Additionally, the available data suggest that the risk of congenital CMV (cCMV) following ART appears low, although significant gaps in the literature highlight the need for more comprehensive studies to better evaluate transmission risks. Finally, this review advocates for the revision of CMV screening societies' guidelines, emphasizing the need for broader, evidence-based preventive strategies. Preventing CMV risk in fertility treatments may include more significant action such as patient education on simple hygiene measures to prevent infection during pregnancy-instead of current, potentially unnecessary measures such as CMV serostatus matching.
Background Type 2 diabetes mellitus (T2DM) is a chronic, non-communicable condition that causes insulin resistance and β-cell malfunction over time. The traditional food scene in India has changed dramatically as a result of rising urbanization and increased consumption of processed, Westernized diets heavy in refined carbs, saturated fats, and added sugars. These dietary changes have greatly contributed to the increased prevalence of type 2 diabetes. Medical nutrition therapy (MNT) is a systematic approach to nutrition management that aims to improve metabolic regulation and treatment results. MNT is often provided by a registered dietitian in collaboration with a diabetologist, and it focuses on personalized, evidence-based dietary guidelines. In this regard, NutroActive Industries Pvt. Ltd., India, has created a diabetic low glycemic load (GL) food product. The product kit contains Diabexy flour, Diabexy sugar substitute drops, Diabexy almond cookies, and Diabexy coconut burfi. These products are intended to provide a structured, low-GL meal plan that may support glycemic management. Although their formulation is nutritionally appropriate, clinical data for its effectiveness and safety are sparse. This randomized pilot trial sought to explore the potential effects of these products in improving glycemic parameters, such as fasting plasma glucose (FPG), postprandial glucose (PPG), and glycated hemoglobin (HbA1c), as well as their tolerance and safety. Method A total of 30 individuals with type 2 diabetes were randomly assigned to control and intervention groups. Baseline characteristics, including age, vital signs, and anthropometric parameters, were comparable between groups (p > 0.03), indicating adequate randomization. Ten participants demonstrated significantly lower postprandial glucose responses to Diabexy atta compared with glucose (iAUC: 52 vs. 241 mmol·min/L), corresponding to a low glycemic index (GI) of 22%. In the intervention group, the low-GL kit was associated with stable HbA1c, changes in fasting insulin that were interpreted alongside HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) to assess insulin dynamics, and improved quality-of-life scores. Safety assessments showed no adverse effects on liver, kidney, or lipid parameters. Indigestion was reported in one participant during the study period; however, it was transient and not considered related to the low-GL intervention kit. Overall, these findings suggest a potential metabolic benefit of Diabexy atta as part of a low-GL dietary approach, within the limitations of this pilot study. Conclusion In this randomized, open-label pilot study, the low-GL dietary intervention was associated with reductions in postprandial glucose levels, stabilization of HbA1c, and improvements in insulin resistance compared with standard care. No clinically significant safety concerns were observed over the study period based on clinical and laboratory assessments. While these findings suggest a potential metabolic benefit of the low-GL approach in individuals with T2DM, they should be interpreted cautiously given the small sample size, short duration, and exploratory nature of the study. Larger, well-controlled trials are warranted to confirm these preliminary observations.
Prior research suggests that low-carbohydrate diets may reduce the frequency of headache attacks in individuals with migraine. However, the association between dietary carbohydrate intake and migraine in adults remains unclear. Given migraine's significant public health burden and the modifiable nature of diet, understanding this relationship is vital for prevention. This study therefore investigated whether carbohydrate intake is associated with severe headache or migraine in a nationally representative sample of US adults. Using National Health and Nutrition Examination Survey (NHANES) data (1999-2004), this study examined the association between dietary carbohydrate intake and severe headache or migraine in adults aged over 20. Multivariable logistic regression was used, adjusting for demographics, socioeconomic status, lifestyle factors, and comorbidities. The study surveyed 10,413 participants, with 2062 reporting severe headache or migraine. Analysis of carbohydrate energy percentage revealed: compared to Q1 (≤42.7%), odds ratios (ORs) for severe headache or migraine were 1.04 for Q2 (42.7% to ≤50.5%, P = 0.642), 1.13 for Q3 (50.5% to ≤58.0%, P = 0.176), and 1.32 for Q4 (>58.0%, P = 0.008). A non-linear association was found between dietary carbohydrate intake and severe headache or migraine among U.S. adults (P for non-linearity = 0.002). The group with carbohydrate intake ≥51.1% of total energy had an OR of 1.22 (95% CI: 1.09-1.38, P = 0.002) compared to those below this level. The data suggest a significant association, with an important inflection point occurring at approximately 51.1%. This research uncovered a non-linear link between carbohydrate intake from diet and the chance of suffering from severe headache or migraine among American adults.
Preventive tumor vaccines exhibit substantial potential in averting tumorigenesis; nevertheless, their clinical efficacy remains constrained by challenges in eliciting potent and long-lasting immune activation, which ultimately leads to subpar overall therapeutic performance. In this study, we designed a biofilm-based hydrogel as a highly efficient single-dose prophylactic tumor vaccine. A hybrid biofilm (TMBM), which combines bacterial membrane (BM) and tumor cell membrane (TM), was modified with methacrylated hyaluronic acid-gelatin methacrylate (HAMA-GelMA) to form a gel formulation (HG-TMBM hydrogel). This hydrogel can encapsulate ginsenoside Rg3 (Rg3) within its micropores and rapidly gelate in situ following subcutaneous injection. Upon single administration of the HG-TMBM hydrogel/Rg3 vaccine, both TMBM and Rg3 are sustainably released owing to the degradable nature of the HAMA-GelMA matrix. TMBM actively targets dendritic cells (DCs) and efficiently induces their maturation. Concurrently, Rg3 modulates the immune microenvironment and enhances antigen presentation efficiency, providing robust support for subsequent antigen cross-presentation. Ultimately, the vaccine successfully elicits potent and long-lasting T lymphocyte-mediated immune responses and exhibits significant preventive efficacy against colon tumors. The present work constructs a sustained-action system for tumor prophylaxis, offering an innovative approach for the creative development of single-administration preventive tumor vaccines.
The use of injectable end-of-life symptom control medications is complex and a risk-prone healthcare activity in the community. Attention is often directed towards the immediate causes of medication-related incidents; however, valuable learning can be gained by examining 'origin incidents', the first adverse event occurring in incident chains that resulted in patient harm or the potential for harm. Understanding these origin incidents can underpin improvements in system resilience to ensure the provision of timely, effective and safe symptom management. System resilience arises from capacities at individual, team and structural levels that enable a complex system to adapt practices and maintain essential functions under varying conditions. To understand the nature of reported origin incidents involving injectable end-of-life symptom control medication in the community and to identify how system resilience can be improved. Retrospective observational study and mixed-methods analysis of nationally reported community injectable medication patient safety incidents, sourced via the National Reporting and Learning System database. Community-based care in England and Wales. A stratified random sample of 2150 incidents was screened for eligibility: 317 incident reports were included. Incident reports involving injectable end-of-life symptom control medications were included. These related to adult patients (aged 18+) receiving end-of-life care in the community, between 2017 and 2022. Eligible incidents involved reported chains of incidents (events) influenced by an origin incident. Incident narratives were coded to classify incident types, contributory factors, patient impact and harm severity. Data analysis utilised a mixed methods approach. An initial quantitative descriptive analysis informed subsequent qualitative thematic analysis lines of inquiry. Ineffective and unsafe symptom control care is influenced by injectable medication origin incidents occurring across the full range of medication management processes. 67.5% (214/317) of reports described actual harm to patients. System resilience was impeded by ineffective transfers of care, difficulties sourcing timely symptom management input from clinical teams, and medication stock and supplies issues. Chains of negative incidents were often exacerbated by discontinuity of care, inadequate communication between in-hours and out-of-hours care providers, mistakes and omissions, failure to follow protocols and insufficient staffing capacity. Examining upstream origin incidents generated valuable system-wide insights, as these initial events influence subsequent actions and system resilience. Enhancing system resilience to support timely and safe symptom management requires improved coordination during transfers of care, reliable access to equipment and valid permission to administer charts, and adequate staffing to provide responsive, cross-organisational care.
Fatigue is a common and disabling non-motor symptom in Parkinson's disease (PD), significantly affecting patients' quality of life. However, it is often underdiagnosed due to its subjective nature and the lack of a clear definition, hindering the development of effective treatments. This study aims to investigate the prevalence of fatigue and its associations with sociodemographic factors, disease severity, levodopa equivalent daily dosage (LEDD) and motor, non-motor, and cognitive symptoms in an Italian cohort of patients with PD. An observational cross-sectional study was carried out in three Italian centers from January to May 2024. One hundred PD patients (H&Y ≤ 4) were assessed using validated tools: Parkinson Fatigue Scale (PFS), Fatigue Severity Scale, and Modified Fatigue Impact Scale. Motor and non-motor signs and symptoms, cognitive status, and LEDD were analyzed using non-parametric tests and Spearman's correlations. Fatigue prevalence was determined based on PFS score ≥ 3.09. Fatigue was present in 36% of patients, more prevalent in women and more severe in those with H&Y > 2. Fatigue correlated strongly with non-motor symptoms (MDS-UPDRS Part I; ρ > 0.6, p < 0.001) and moderately with motor complications (0.4 < ρ < 0.5, p < 0.001), but weakly with disease duration, LEDD and age (ρ < 0.3, 0.002 < p < 0.05). Significant intercorrelations among fatigue scales supported their ability to consistently measure the fatigue construct. Fatigue in PD is a multidimensional phenomenon influenced mainly by non-motor symptoms. Gender-specific differences and the association with disease progression underscore the need of comprehensive and integrated management strategies to address this challenging symptom.
Therapeutic plasma exchange (TPE) is being increasingly utilized in the clinical management of severe rheumatic immune diseases, providing an effective means for rapidly removing pathogenic autoantibodies and inflammatory mediators. However, the non-selective nature of this technique can also lead to the unintended clearance of concomitantly administered antirheumatic drugs, potentially compromising therapeutic efficacy and disease control. Therefore, effective management of potential drug removal process during TPE and the implementation of individualized risk assessment are crucial for optimizing treatment outcomes in patients undergoing TPE. The variability in the extent of drug removal during TPE is primarily determined by their distinct pharmacokinetic characteristics, necessitating the establishment of a systematic, evidence-based strategy for adjusting drug administration regimens in patients receiving TPE treatment. This review synthesizes current evidence from 65 studies on the removal of antirheumatic drugs during TPE, identifying key determinants influencing clearance rates, including volume of distribution, protein binding, molecular size, and elimination half-life. Our analysis reveals that the risk of drug removal exists as a continuous spectrum: large monoclonal antibodies (e.g., rituximab, natalizumab), characterized by a large molecule size, low volume of distribution, with which mostly confined to the vascular space, are cleared with high efficiency. This finding supports the clinical recommendation of administering such drugs after TPE. For drugs with limited direct evidence, we propose a predictive model based on fundamental pharmacokinetic parameters to estimate their removal risk and guide clinical decision-making. Based on this evidence, we have constructed a stratified clinical management framework. It aims to maintain effective therapeutic drug exposure levels during chronic TPE therapy and to provide a rationale for the judicious application of TPE in overdose scenarios. Implementing this pharmacokinetic-informed, risk-adapted individualized strategy is important for ensuring treatment continuity, enhancing patient safety, and advancing empiricism-based therapy towards precision medicine.
Osteoarthritis (OA) poses a significant challenge because of its complex pathology, involving factors such as hypoxia, inflammation, angiogenesis, oxidative stress within cell, and fibroblast-driven instability of fibrocartilage. Traditional scaffold-based treatments often fail to provide the mechanical properties and bioactivity required for effective cartilage repair. To overcome these challenges, this work introduces an injectable hydrogel system composed of alginate-tyramine-curcumin (ALG-TYR-CUR), reinforced using near-infrared (NIR) irradiation. The approach utilizes NIR-induced reactive oxygen species (ROS) generation to enhance the mechanical strength of hydrogel, eradicate potential angiogenesis, and establish a hypoxic nature favorable for chondrogenesis. The outcomes showed remarkable improvements in the ALG-TYR-CUR hydrogel's mechanical characteristics. In vitro studies revealed selective regulation and management of oxidative stress, promoting the activity of chondrocytes while suppressing aberrant proliferation of fibroblasts. In a rat model of OA created by anterior cruciate ligament transection, the ALG-TYR-CUR gel system demonstrated notably reduced inflammation, cartilage regeneration, normalization of angiogenesis, and restoration of joint functionality. This NIR-ALG-TYR-CUR system provides a non-invasive, multimodal approach to managing OA by targeting critical pathological mechanisms. These results underscore its promise as a versatile platform for cartilage repair and as a promising solution for the management of inflammation illnesses and regenerative medication.
Professional identity formation in healthcare professions education (HPE) is a complex and often fraught process. Physicians and trainees experience identity struggles as they navigate their personal and professional development, along with the conflicting expectations, cultural norms and systemic pressures within the healthcare environment. Despite growing attention to these challenges, conceptual clarity around identity struggle remains limited. To advance theoretical understanding of identity struggle, we conducted a critical narrative review of identity theories from developmental psychology, social psychology and sociology. We selected three major theoretical traditions-Neo-Eriksonian, symbolic interactionist and social identity theories-and analysed their conceptualizations of identity, identity development and identity struggle. We examined these diverse perspectives to inform research and educational practice on professional identity formation in HPE. Each theoretical tradition offers distinct insights into identity struggle. Neo-Eriksonian theories emphasize exploration and commitment as central processes, framing struggle as developmental and potentially productive. Symbolic Interactionist theories highlight the role of socialization and identity dissonance, viewing struggle as emerging from tensions between personal agency and societal norms. Social Identity theories focus on group belonging and intergroup dynamics, conceptualizing struggle at both individual and socio-contextual levels. We provide common critiques and limitations of each theoretical tradition. These perspectives illuminate varied mechanisms through which identity struggle manifests and evolves. This review underscores the multifaceted nature of identity struggle and the value of theoretical pluralism in understanding professional identity formation. Struggle is not inherently negative; rather, it can be a catalyst for growth when appropriately framed and supported. We propose how educators and researchers might use these theoretical lenses to design interventions that foster productive identity development and address systemic contributors to identity struggles. We invite scholars drawing on critical perspectives of power and structure to challenge and deepen the conversation on identity struggle in HPE.