Misconceptions in pharmacology can undermine learning and compromise both clinical and scientific reasoning, yet few validated tools exist to identify them. Consequently, we developed and validated the Pharmacology Concept Inventory (PCI), which can be used to identify misconceptions, assess learning gains, and evaluate teaching effectiveness. This PCI was designed based on the IUPHAR-Education Section (IUPHAR-Ed) Core Concepts of Pharmacology Project, addressing eight core concepts: drug efficacy, drug-target interaction, steady-state concentration, structure-activity relationship, drug tolerance, drug bioavailability, volume of distribution, and drug clearance. A triangulated design strategy integrated theoretical frameworks, expert review, and student perspectives. Experts examined quality, content validity, and cognitive alignment. The pilot PCI was then administered to a student cohort to evaluate its psychometric properties, providing preliminary evidence for further refinement. Item-level content validity indices ranged from 0.67 to 1.00, with a scale-level average of 0.93. Seventy students completed the pilot survey, leading to the exclusion of items with low discrimination and reliability. Items on drug-target interaction were removed due to consistently poor performance. The final PCI included 26 items covering seven concepts, with strong discrimination indices (0.36-0.75) and difficulty indices (0.26-0.71). Internal consistency was high (Cronbach's alpha = 0.91), and concept-level reliability ranged from 0.64 to 0.85. The PCI provides strong evidence for identifying misconceptions and assessing learning outcomes through a pre-post-test approach. Although the PCI currently addresses only a subset of concepts, continued refinements informed by surveys and interviews will enhance its utility and expand its scope for concept-based learning and curriculum evaluation.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Traumatic spinal cord injury (SCI) is a debilitating condition with serious neurological and quality of life impact. Despite advances in surgical, medical and rehabilitative care, no approved therapies currently promote neural repair or regeneration. Repulsive Guidance Molecule a (RGMa) is a potent inhibitor of neurite growth that also regulates neuronal survival and differentiation during development. In the adult central nervous system (CNS), RGMa is expressed at low levels and rapidly upregulated in multiple cell types following SCI. RGMa-neogenin signaling induces growth cone collapse, inhibits axonal regeneration, and contributes to neuronal death and neuroinflammation, limiting recovery. Human monoclonal antibodies targeting RGMa, including elezanumab, have shown neuroprotective and neuroregenerative effects in preclinical models, supporting clinical investigation. This review outlines SCI pathophysiology, RGMa upregulation after injury, key CNS signaling mechanisms, and the early development of anti-RGMa monoclonal antibodies. Two concurrent, independent clinical trials of anti-RGMa antibodies offer a unique opportunity for cross-validation and comparison across patient populations. However, these trials were recently completed, and results are not yet reported. The translation of SCI therapeutics to clinical practice is historically challenging and the controlled conditions of preclinical studies may not fully capture the complexity and variability of human SCI.
The Medication Adherence Risk Score (MARS) is an objective adherence-based score, derived from transactional dispensary data. This study provides expert consensus to validate the use of the MARS as a predictor of mortality risk. A systematic review and assessment of South African health legislation and professional guidelines informed the development of consensus statements regarding the relevance, validity, predictive power, and implementation feasibility of the MARS. A two-round modified Delphi approach using a 5-point Likert scale was employed. Consensus was reached if at least 80% of respondents selected "agree" or "strongly agree." Nonconsensus statements were revised based on qualitative feedback and subsequently reevaluated in a second round. Thirteen clinical, actuarial, and academic experts were successfully recruited. Consensus was achieved for 20 of the 28 statements in Round 1. Five of 18 (27.8%; risk score components), 1 of 3 (33.3%, validity/predictive power), and 2 of 7 statements (26.5%, real-world implementation) did not initially reach consensus. Nonconsensus statements were revised to provide clarity, after which consensus was achieved for all statements by the end of Round 2. Expert consensus supports the inclusion, exclusion, and weighting of MARS risk factors. The panel agreed that the score offers predictive value for mortality outcomes, and that real-world application for enhancing risk stratification and reducing healthcare costs is feasible. Future statistical analysis is necessary to demonstrate its relationship with mortality risk. Developing practical implementation strategies will facilitate incorporation into clinical practice and public health interventions.
Chronic noninfectious diarrhea remains a clinically important but often underrecognized complication in patients receiving long-term antiretroviral therapy (ART). Although modern human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatment has transformed survival, gastrointestinal adverse effects can impair adherence, quality of life, nutrition, social functioning, and treatment satisfaction. Crofelemer is an oral, plant-derived botanical drug developed as a non-systemic antisecretory therapy for noninfectious diarrhea in adults with HIV/AIDS receiving ART. This review evaluates crofelemer as a plant-derived pharmacotherapy for chronic noninfectious diarrhea. It discusses the clinical need, limitations of current antidiarrheal approaches, botanical origin, chloride-channel mechanism, pharmacology, clinical efficacy evidence, safety and tolerability, practical prescribing considerations, real-world positioning, and investigational expansion into cancer therapy-related diarrhea and rare intestinal-failure disorders. Crofelemer offers a mechanistically distinct option for selected patients with chronic watery, noninfectious diarrhea whose symptoms remain burdensome despite appropriate clinical evaluation and supportive care. However, its use should be guided by realistic expectations, careful patient selection, and recognition that response is not universal. Future clinical value will depend on phenotype-based prescribing, real-world effectiveness data, comparative studies, affordability, and patient-reported outcomes.
Hypertrophic cardiomyopathy (HCM) is a heritable cardiac disorder characterized by increased left ventricular (LV) wall thickness, often leading to heart failure (HF). The role of cardiovascular magnetic resonance (CMR) imaging in predicting new onset of HF symptoms in patients with HCM remains unknown. This study aimed to identify CMR predictors of new-onset HF symptoms in individuals with HCM. This study was a single-centre retrospective cohort study of HCM patients treated at a tertiary referral centre in the USA who underwent CMR examination between 1998 and 2018, had no HF symptoms at baseline CMR, and at least 1 year of follow-up. Clinical data were collected by review of electronic medical records, and CMR images were analyzed by a blinded expert cardiac radiologis. The primary outcome was new onset of HF symptoms, defined as New York Heart Association (NYHA) class ≥ II at follow-up. Kaplan-Meier analyses and Cox proportional hazard analyses were performed. Of 1462 patients diagnosed with HCM who had at least 1 CMR, 276 HCM patients without HF symptoms (average age 52.7 years, 33.3% female),median maximum left ventricular (LV) wall thickness was 19 mm ([IQR] 17-22) with a and median LV ejection fraction of 71% (IQR 66-77). Late gadolinium enhancement was detected in 56.2%) patients (60.7% had mild; 30.7% moderate; 8.6% severe). During a median follow-up period of 6.3 years, 93 patients developed HF symptoms (NYHA class II in 56 (60.2%); class III in 31 (33.3%); and class IV in 6 (6.5%). Multivariable analysis adjusted for age showed that LA enlargement (HR 1.626; 95% CI 1.01-2.62; P = .045) and LV mass index (HR 1.014; 95% CI 1.007-1.022; P≤ .001) and sex (HR 1.7; 95% CI 1.074-2.691; P = .023) were independent predictors of new onset of HF symptoms in patients with HCM. Nearly half of the patients with HCM developed HF symptoms within 6.3 years. Left atrial enlargement, LV mass index, and sex were independent predictors of new onset of HF symptoms in HCM patients. These findings emphasize the value of CMR in HF risk stratification.
Liver cirrhosis profoundly alters pharmacokinetics and is frequently associated with medication-related problems. Stage-specific dosing guidance remains inconsistent, and prescribing information often lacks clarity. As a result, treatment decisions rely on individual clinical judgement and may differ between professional groups. This study assessed drug-selection and dose-adjustment practices among hepatologists, clinical pharmacologists, and clinical pharmacists, quantified consensus across Child-Pugh stages, and evaluated alignment with prescribing information as a basis for harmonised dosing guidance. Twelve experts from hepatology, clinical pharmacology, and clinical pharmacy evaluated prioritised drugs for patients with liver cirrhosis across Child-Pugh stages A-C in a structured survey. For each drug, experts indicated whether they would apply no dose adjustment, modify the dose, or avoid administration. Consensus was defined as at least 75% agreement, and interrater agreement was assessed by pairwise percentage agreement. Consensus recommendations were compared with the dosing information provided in each drug's Summary of Product Characteristics. Consensus or strong consensus was achieved for only 20% of 177 recommendations, mainly for no dose adjustment or avoidance. Agreement decreased with disease severity (Child-Pugh A 83%; B 47%; C 41%). Of 36 consensus recommendations, 18 matched the summary of product characteristics, while six diverged from it. Pharmacists and clinical pharmacologists more often recommended dose adjustments, especially in Child-Pugh B and C, whereas hepatologists preferred standard dosing or avoidance. Expert recommendations for dosing in cirrhosis showed marked variability and limited concordance with prescribing information, underscoring the need for harmonised interdisciplinary guidance integrating pharmacokinetic evidence and clinical feasibility.
What is this summary about?This summary describes key findings from an analysis that looked at the relationship between levels of aripiprazole in the blood and the chance of experiencing a new mood episode in people diagnosed with bipolar I disorder treated with a once-monthly injection of aripiprazole monohydrate.What are the key takeaways?Higher levels of aripiprazole in the blood were linked to a lower chance of experiencing a new mood episode. The best way to describe this relationship was continuous, meaning that the chance of staying well increased gradually as the level of aripiprazole in the blood increased. People with an aripiprazole level of 95 ng/mL or higher after starting the once-monthly injection of aripiprazole monohydrate had a 36% lower chance of having a new mood episode, compared with people whose levels were below this point.What are the main conclusions reported by the researchers?The level of aripiprazole in the blood is an important factor in predicting whether people diagnosed with bipolar I disorder treated with a once-monthly injection of aripiprazole monohydrate will stay well or experience another mood episode. Those with higher levels of aripiprazole in their blood have a lower chance of having a new mood episode. These findings highlight the importance of receiving once-monthly injections of aripiprazole monohydrate on time, to keep aripiprazole levels in the blood high enough to reduce the chance of having a new mood episode.
Prostate cancer is well known to be androgen-dependent, with growth directly relying on the androgen receptor signaling pathway. In fact, androgen deprivation therapy, with or without Docetaxel and/or newer hormonal drugs such as Abiraterone acetate, Enzalutamide, Apalutamide, and Darolutamide, remains the most effective systemic treatment for metastatic disease. Beyond PSA detection, there is a lack of standardized biohumoral markers to understand the biology of metastatic castrate-sensitive prostate cancer (mCSPC), predict response to newer therapies such as immunotherapy, and identify a true oligometastatic state. A comprehensive, non-systematic literature review across Scopus, Google Scholar, Medline, EMBASE, and the Cochrane Library was conducted. New evidence was identified, gathered, and screened for relevance, limited to English-language publications. Information and recommendations on the emerging mCSPC biomarkers, their possible integration, and application for care decisions were evaluated. Our work aimed to summarize the current understanding of molecular characterization of mCSPC and the evidence on the role of emerging molecular biomarkers in guiding personalized treatment for mCSPC. The integration of data extracted from imaging with the molecular and genetic profiles of a specific tissue, using artificial intelligence, will help assess the genetic and biochemical makeup of living tissue.
Drug repurposing is the strategy of identifying novel therapeutic uses for existing, unapproved, or failed drugs distinct from their original indications. Given the unique nature of repurposing, clinical trials for repurposed agents warrant specific design considerations. This article covers specific factors to consider when designing clinical trials for repurposed agents. The specific factors identified are the drug's characteristics, its clinical context, the design and methodology of the repurposing trial, the quality and management of supporting data, and other ethical and organizational concerns specific to repurposing. Drug repurposing is a natural approach to reduce costs and increase the efficiency of drug development, and such trials may offer ethical advantages in terms of participant risk and social value. In the modern landscape of clinical trials, numerous barriers to initiating repurposing efforts exist. Notably, these include challenges related to intellectual property, data availability, and the unexpected and widespread consequences of off-label use and drug access. Other barriers to safe and effective repurposing will continue to challenge trialists and stakeholders, especially regarding the reuse of data, communication, documentation, and other potential confounding factors not experienced in standard trials. Thus, careful ethical assessment of trial characteristics is necessary.
Despite the availability of drugs which prevent vomiting, treatment gaps in controlling nausea and vomiting remain. New approaches are needed. We identify unmet clinical needs by examining clinical reviews (last 5-years), adding our experience in drug discovery/emesis research. Mechanisms of nausea and vomiting are given. We identify emerging research and new approaches before discussing the challenges of quantifying nausea and vomiting in future trials. As single agents, drugs which prevent vomiting have efficacy in some but not all groups of patients, with NK1 receptor antagonists possessing the widest spectrum of action. Drug combinations have improved efficacy in specific clinical settings. However, treatment gaps remain (e.g. gastroparesis, cyclic vomiting syndrome) and efficacy is lower against nausea compared with vomiting. The latter requires greater attention in trial design and regulatory assessments. The issue of nausea is difficult because in humans it is inadequately quantified (with high temporal resolution), there is a lack of clinical research into nausea, and animal models only measure 'nausea-like behaviours,' with challenges in translating to humans. In drug discovery, more systematic and critical analysis of the pharmacology of the diverse agents which induce or reduce nausea and vomiting may help identify new therapeutic mechanisms.
Warfarin dosing varies widely due to genetic, demographic, and clinical factors, but it is unknown whether the importance, equilibrium, and prediction uncertainty of established pharmacogenetic predictors (VKORC1 and CYP2C9) differ between arterial (AF/stroke) and venous (DVT/PE) thromboembolic indications. This exploratory study (early clinical evaluation) synthesizes findings from the International Warfarin Pharmacogenetics Consortium dataset. We evaluated five machine learning (ML) models, and SHapley Additive exPlanations (SHAP) and Bayesian Additive Regression Trees (BART) analyses were carried out. Random Forest demonstrated slightly better predictive performance than other ML models. SHAP analysis quantified feature contributions, revealing that VKORC1 G/G genotype as the most influential in AF/Stroke, while VKORC1 A/A genotype followed by age in the DVT/PE group. BART provided probabilistic predictions and identified indication-specific uncertainty drivers. Age possibly has an interaction effect in the requirements of reduced warfarin doses with AF/Stroke. Our findings reveal that while core genetic and anthropometric predictors of warfarin dose transcend thromboembolic indication, the equilibrium among these factors and sources of prediction uncertainty possibly differ between arterial and venous disease. Integration of ML with SHAP offers a roadmap for personalized warfarin dosing, though prospective validation is needed before clinical implementation.
Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is a key therapy in managing type 2 diabetes (T2D), offering significant improvements in glycemic control, weight loss, and cardiovascular protection. Beyond these clinical benefits, multi-omics research is clarifying the molecular mechanisms underlying its systemic metabolic effects. This review synthesizes findings from major clinical trials and recent proteomic and metabolomic studies to explain how semaglutide affects inflammatory, lipid, and extracellular matrix (ECM) pathways in multiple organs. Key molecular mediators, including adiponectin, fibroblast growth factor 21 (FGF21), apolipoprotein C-III (ApoC-III), ceramides, and ECM-remodeling proteins (MMPs, CTGF, α-SMA), are linked to improved insulin sensitivity, reduced adipose inflammation, and restored metabolic flexibility. The review also discusses the use of artificial intelligence (AI) and machine learning (ML) to connect omics biomarkers with clinical outcomes. Semaglutide exemplifies a precision medicine approach for T2D by linking clinical efficacy to molecular adaptation. Longitudinal validation of omics biomarkers and their integration into AI-driven diagnostic platforms could enable personalized, mechanism-based therapy that goes beyond glucose control to deliver comprehensive cardiometabolic protection.
Type 2 diabetes mellitus (T2DM) pharmacotherapy guidelines recommend the assessment of individual cardiovascular (CV) risk. However, obesity still seems of lesser importance in the context of CV risk. Importantly, obesity-targeting pharmacotherapy use is limited. A PubMed database search, up to August 2025, was performed. This review explores the rationale for prioritizing weight reduction as a key treatment strategy for overweight/obese T2DM patients and provides evidence supporting a weight-centric approach. Furthermore, it addresses the challenges associated with implementing weight management strategies in clinical practice. Higher doses of medications approved for obesity treatment may be indicated compared with those recommended for T2DM therapy. Additionally, the high cost and the lack of reimbursement policies for these drugs create a significant financial burden. Drug side effects may also minimize their use. The effectiveness of available pharmacotherapy in treating obesity in T2DM patients is discussed. There is still an urgent need to raise awareness regarding the importance of weight-centric management in overweight/obese T2DM patients. There is a need for a multidisciplinary approach, including health-care providers, the health system and policy makers, taking into consideration the multiple challenges, health inequity concerns and disparities in medication accessibility.
Alopecia areata (AA) is a chronic autoimmune disease characterized by non-scarring hair loss driven by cytotoxic attack against anagen hair follicles. Janus kinase (JAK) inhibitors disrupt the pathogenic signaling and have revolutionized treatment landscape for severe AA. Nevertheless, clinical unmet needs remain for the primary non-responders, relapse during treatment, and lack of reliable biomarkers to guide treatment discontinuation. This review summarizes evidence from pivotal clinical trials and real-world studies of JAK inhibitors in AA.  Post-hoc analyses addressing relapse after withdrawal, and dose reduction are also discussed. Furthermore, we overview real-world data highlighting clinical factors associated with treatment responses. A literature search was conducted primarily in PubMed for articles published up to November 2025, with additional website searches for company announcements and clinical trial related updates when relevant. JAK inhibitors have redefined the therapeutic framework for severe AA and serve as the functional probes that clarify disease biology underlying AA. Emerging evidence suggests that early intervention and standardized monitoring based on clinical information should guide treatment design. Future challenges include systematizing strategies for continuation, dose reduction, temporary interruption, and reinitiation based on patient background, as well as developing more effective combination therapies.
Obesity is a chronic, relapsing disease associated with substantial cardiometabolic morbidity and reduced quality of life. Although pharmacotherapy has advanced rapidly, current treatment options remain limited by tolerability concerns, access barriers, discontinuation, and reluctance toward injectable agents. Orforglipron, a once-daily oral glucagon-like peptide-1 receptor agonist, represents a potentially important step in expanding effective anti-obesity therapy. This review evaluates the emerging role of orforglipron in obesity pharmacotherapy, with emphasis on its mechanistic basis, clinical pharmacology, efficacy, safety, and likely place in therapy. Particular attention is given to its therapeutic rationale as an oral incretin-based agent, evidence supporting clinically meaningful weight reduction, common adverse effects and prescribing considerations, and its potential positioning relative to established oral anti-obesity drugs and injectable incretin therapies. The review also considers treatment sequencing and the practical implications of integrating oral GLP-1 therapy into routine obesity care. Orforglipron may benefit patients requiring effective weight-management pharmacotherapy who prefer oral treatment. However, its role should be interpreted cautiously: comparative efficacy may not exceed leading injectable incretin therapies, and long-term durability, persistence, affordability, and real-world safety remain uncertain. Its value will depend on route preference, tolerability, access, and individualized treatment goals.
Acute promyelocytic leukemia (APL) is a highly curable subtype of AML, largely due to the introduction of differentiating therapy with all-trans retinoic acid and arsenic trioxide. While intravenous arsenic trioxide (ATO) is considered the standard-of-care in the United States, its prolonged administration and monitoring requirements pose logistical challenges that require high healthcare resource utilization and negatively impact quality of life. This review summarizes the development and clinical evaluation of intravenous and oral arsenic formulations in APL. We discuss the pharmacokinetics, safety, and efficacy of oral arsenic compared with intravenous ATO across populations, including children and patients with obesity or renal impairment. A PubMed search using the terms 'oral arsenic,' 'arsenic trioxide,' 'arsenic formulations,' 'acute promyelocytic leukemia,' and 'pharmacokinetics' was used to compile data. It draws on current pharmacokinetic and clinical evidence, including data from retrospective publications, phase 3 trials, meta-analyses, and long-term follow-up studies. Oral arsenic formulations achieve comparable molecular remission, long-term survival, and toxicity profiles to intravenous ATO. These oral formulations may offer meaningful advantages in quality of life, cost, and overall availability of optimal treatment. Continued clinical trials are expected to further define oral arsenic's role in frontline therapy in the United States.
Ultrasound is among the most widely used imaging modalities in clinical trials, and yet its dependence on operator skill and equipment settings has historically limited the reproducibility of ultrasound-based endpoints in multi-center studies. Artificial intelligence (AI) now addresses this limitation across two complementary dimensions: automated measurement algorithms that quantify cardiac function, organ volume, and vascular parameters with reproducibility approaching or, in select settings, exceeding that of trained human readers and real-time acquisition guidance systems that enable clinicians with no formal sonography training to perform diagnostic-level examinations, making remote and decentralized assessment increasingly feasible. This narrative review synthesizes current evidence and regulatory developments across three interconnected domains. First, use of automated ultrasound to ascertain endpoints has advanced from single-institution validation to prospective and randomized evidence, with deep learning measurement of the left ventricular ejection fraction demonstrating formal equivalence to expert readers across multiple echocardiographic parameters and AI-first workflows shortening the time to diagnosis in a blinded non-inferiority trial. Second, AI-guided ultrasound acquisition by nurses and other non-expert operators has achieved a high rate of diagnostic acceptability in cardiac and pulmonary ultrasound, laying the groundwork for use of ultrasound-based endpoints in decentralized clinical trial designs, as reflected in Food and Drug Administration (FDA) guidance on decentralized trial elements. Third, the regulatory frameworks governing AI-enabled medical devices - including the U.S. FDA's Predetermined Change Control Plan guidance, the EU Artificial Intelligence Act, and internationally harmonized good machine learning practice relevant to Japan and other jurisdictions - increasingly emphasize overlapping principles such as specification of prospective performance, post-marketing oversight, and transparent reporting. Addressing remaining challenges in domain generalization across vendors, subgroup fairness, and algorithm change management during ongoing trials will be essential for AI-assisted ultrasound to fulfill its potential as a robust, scalable endpoint in clinical research worldwide.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystemic disorder mostly triggered by viral infections, with core symptoms including post-exertional malaise (PEM), fatigue, pain, and cognitive dysfunction. Its prevalence has increased significantly in the context of the coronavirus disease 2019 (COVID-19) pandemic. Despite its severity and impact on patients' quality of life, ME/CFS remains poorly understood. On May 12 and 13, 2025, the 3rd International Conference hosted by the Charité Fatigue Center brought together nearly 200 researchers from various disciplines on-site, and around 3,700 participants online to discuss recent advances in ME/CFS research, diagnostics, clinical care, and therapeutic trials. The program featured 33 lectures by international experts on key topics such as post-COVID syndrome (PCS), care structures, and pathophysiological mechanisms including cardiovascular dysregulation, immune dysregulation, autoimmune mechanisms, and metabolic dysfunction. In addition, results from clinical trials addressing disease mechanisms, including those specifically targeting autoantibodies, were presented. While public awareness and funding opportunities have increased in the wake of the pandemic and the emergence of PCS, ME/CFS remains severely underresearched. Sustained and adequately funded research efforts are urgently required to advance understanding, identify diagnostic markers, and develop targeted therapeutic interventions.
Acute severe ulcerative colitis is a potentially life-threatening manifestation of ulcerative colitis requiring hospitalization and prompt intervention. Despite corticosteroids being the cornerstone of initial therapy, 30-40% of patients exhibit steroid-refractory disease and require rescue treatment with infliximab or cyclosporine, with colectomy rates remaining substantial. The introduction of Janus kinase inhibitors, including tofacitinib, upadacitinib, and filgotinib, has expanded the therapeutic options for ulcerative colitis, offering a rapid onset of action and oral administration. This review summarizes the current evidence on the use of Janus kinase inhibitors in acute severe ulcerative colitis, with a primary focus on tofacitinib and upadacitinib with multiple retrospective studies and one randomized controlled trial suggesting efficacy in inducing clinical response and reducing colectomy rates. A comprehensive search of PubMed, Embase, and Scopus identified observational retrospective and prospective studies and randomized trials on JAK inhibitors in ulcerative colitis. While safety concerns persist, available evidence suggests an acceptable safety profile. Janus kinase inhibitors may represent a viable alternative in acute severe ulcerative colitis.