Search Results (412)

Background/Objectives: Propranolol (PROP) is a non-selective β-blocker widely prescribed for cardiovascular and neurological disorders. Its pharmacokinetics (PK) are highly variable, and co-administration with omeprazole (OME), a CYP2C19 substrate and inhibitor, may alter systemic exposure. Herein, this study aimed to investigate factors influencing PROP PK variability and evaluate the effect of OME coadministration using physiologically based pharmacokinetic (PBPK) modeling and population PK (popPK) analysis. Methods: PBPK models for PROP and OME were developed and validated against published data. DDI simulations were conducted across clinically relevant dosing regimens. A two-period fixed-sequence virtual trial of 125 subjects was simulated with PROP alone and PROP combined with OME. Population PK (popPK) analysis was performed on simulated plasma concentration data to identify covariates affecting PROP disposition and quantify DDI magnitude. Results: PBPK models were successfully developed and validated. PROP disposition was best described by a two-compartment model with linear elimination. Health status was found to influence clearance, and body surface area (BSA) affected the central volume of distribution. Co-administration with OME increased PROP exposure, with larger effects in patients with renal impairment. Simulated plasma concentrations remained below established toxicity thresholds. Conclusions: Virtual clinical trials integrating PBPK and popPK modeling provide a robust approach to identifying key determinants of PK variability and DDI risk. Although these findings were not directly translated to clinical observations, this helps identify sources of PK variability in PROP treatment settings and factors that may intensify its interaction with OME, thereby supporting model-informed precision dosing to enhance safety and efficacy. Full article

Background: Transcatheter mitral valve implantation (TMVI) represents an evolving therapeutic strategy for patients with severe mitral valve disease who are at high or prohibitive risk for conventional surgery. Since the first human implantation in 2012, multiple dedicated and adapted devices have entered clinical investigation, yet only one dedicated system—the Tendyne prosthesis (Abbott Structural)—holds regulatory approval. This systematic review evaluates the current landscape of available and emerging TMVI devices, examines the clinical outcome data, discusses key indications and limitations, analyses the role of computed tomography (CT) in predicting left ventricular outflow tract (LVOT) obstruction caused by the unopposed anterior mitral leaflet, and compares TMVI outcomes with conventional surgical mitral valve replacement (SMVR) in the specific context of severe mitral annular calcification (MAC). Methods: A systematic search of PubMed, EMBASE, Cochrane Central, and Web of Science was performed for studies published from January 2010 to March 2025 reporting outcomes of TMVI in native valve disease, valve-in-valve (ViV), valve-in-ring (ViR), or valve-in-MAC (ViMAC) procedures. Studies reporting CT-based LVOT planning, neo-LVOT quantification, and LVOT obstruction outcomes were specifically sought. Meta-analyses comparing TMVI with redo surgical mitral valve replacement were included. A total of 63 studies (n > 12,000 patients across all subgroups) were included in the qualitative synthesis; 28 studies were included in the quantitative synthesis. Results: Nine dedicated TMVI devices are currently under clinical investigation, with only Tendyne holding CE Mark and FDA approval. In ViV/ViR cohorts, TMVI was associated with significantly lower in-hospital mortality (OR 0.72, 95% CI 0.57–0.92; p = 0.008) and 30-day mortality (OR 0.49; p = 0.04) compared with redo SMVR, with no significant difference at one year (OR 1.03; p = 0.91). In ViMAC cohorts, 30-day mortality ranged from 14 to 24%, which was substantially higher than in the ViV outcomes. CT-based virtual simulation of the neo-LVOT area—the residual outflow tract created by anterior mitral leaflet displacement—is the most validated predictor of LVOT obstruction, with a threshold of ≤1.7 cm² yielding 96% sensitivity and 92% specificity. The LAMPOON technique (laceration of the anterior mitral leaflet to prevent outflow obstruction) has expanded the eligibility for patients who were previously excluded due to LVOT risk. Surgical MVR in severe MAC carries a median 30-day mortality of 6.3% (range 0–27.3%), while ViMAC TMVI with dedicated devices yields 6.8% 30-day mortality, without a definitive randomised comparison. Conclusions: TMVI offers a viable alternative to redo surgery in high-risk patients with failed bioprostheses or rings. In severe MAC, both surgical and transcatheter approaches carry significant risk; patient selection, CT-guided LVOT planning, and use of dedicated devices are critical to optimising outcomes. The ongoing SUMMIT randomised controlled trial will provide the first high-quality comparative data. Future developments in transseptal delivery and LVOT-safe device architectures are expected to broaden the eligible population. Full article

Background: Haptic simulation technologies are increasingly integrated into preclinical dental education to support procedural skill development. However, the extent to which haptic simulators improve performance compared to traditional phantom-head-based training remains unclear. Our goal is to systematically evaluate the effectiveness of haptic simulators in operative dentistry training, compared with conventional approaches. Methods: A systematic literature search was conducted in PubMed, Scopus, and Cochrane (2015–2025), complemented by manual searching, to identify studies evaluating virtual reality haptic simulators in preclinical operative dentistry education. The search strategy, structured according to the PICO framework, included preclinical undergraduate dental students, interventions with virtual reality haptic simulators, comparisons with conventional methods, and objective assessment of technical performance. Relevant data were extracted in a standardized manner, and the methodological quality of randomized controlled trials was assessed using RoB 2.0, while non-randomized studies were evaluated using ROBINS-I v2. Results: Of the 66 identified articles, 5 studies were included. The use of virtual reality simulators with haptic feedback in preclinical dental students was associated with increased efficiency in cavity preparation, reflected by reduced execution time and improved learning curves, as well as specific technical gains such as depth control. Overall cavity preparation quality was comparable to that achieved with conventional methods, with virtual reality being well accepted as an effective complementary tool in preclinical operative dentistry education. Conclusions: Haptic simulators appear effective for early preclinical skill development in operative dentistry and may complement traditional instruction. Evidence remains insufficient to confirm superiority over conventional methods or long-term clinical benefit. Higher-quality multicenter randomized trials with standardized performance measures are needed to strengthen the evidence base. Full article

Bringing a new drug to market is a complex, costly, and lengthy process, averaging $2.6 billion and about ten years of research and development. It involves multiple stages, from target discovery to post-approval monitoring, and relies heavily on innovation driven by collaboration among pharmaceutical sciences, biology, biochemistry, engineering, and artificial intelligence. Drug discovery can be divided into four main stages: target selection and validation; compound screening and optimization; preclinical studies; and clinical trials. First, researchers identify and validate a biological target associated with a disease using genomic, proteomic, and bioinformatic approaches. Next, potential compounds (“hits”) are identified through methods such as high-throughput and virtual screening, followed by iterative chemical optimization and functional testing. Promising candidates undergo preclinical in vivo studies to assess pharmacokinetics, pharmacodynamics, and toxicity. Clinical development proceeds in three phases: Phase I evaluates safety in healthy volunteers; Phase II assesses efficacy in patients; and Phase III confirms efficacy and safety in larger populations. After successful trials, regulatory agencies review the data for approval. While small molecules have long dominated due to their stability and oral bioavailability, biologics—such as monoclonal antibodies and mRNA-based therapies—have grown rapidly, highlighted by COVID-19 vaccine development and increasing FDA approvals. Full article

Background/Objectives: The placement of central venous access devices, including peripherally inserted central catheters (PICCs) and PICC-PORTs, is a routine procedure in oncology care. Usually associated with limited physical pain, these procedures may nevertheless generate significant anxiety and negatively influence the overall procedural experience. Virtual reality (VR) has emerged as a non-pharmacological intervention capable of modulating attentional and emotional responses during medical procedures; however, evidence in adult oncology patients undergoing vascular access placement remains scarce. The aim of this study is to evaluate the effect of VR on an oncological patient’s overall procedural experience. Methods: This manuscript outlines the design and methodology of a prospective, single-centre randomised controlled trial. Adult oncology patients scheduled for PICC/PICC-PORT placement are randomised to receive standard care alone or standard care combined with an immersive VR intervention delivered via a head-mounted display during the procedure under pragmatic, real-world clinical conditions. The primary outcome is a composite patient-reported procedural experience endpoint, assessed through a non-aggregated framework encompassing procedural anxiety, comfort, satisfaction and procedural tolerability. Procedural anxiety constitutes the main quantitative driver; the remaining domains are analysed as individual component dimensions and interpreted jointly to contextualise the overall experience. Secondary outcomes include procedural pain, physiological parameters and procedural characteristics. A mixed-methods approach integrates quantitative assessment with qualitative phenomenological analysis. Results: The study is expected to provide methodological and clinical insight into the role of immersive VR in improving procedural experience and support future multicentre trials. Conclusions: This trial will contribute to the expanding field of digital and immersive health technologies by evaluating VR as a patient-centred adjunct intervention in oncological procedural care using a predefined patient-reported experience-based primary endpoint. The protocol has been submitted to ClinicalTrials.gov with the registration number NCT07384741. Full article

Binge-eating disorder (BED), defined as recurrent episodes of consuming large amounts of food in a short period of time while experiencing a loss of control, remains difficult to manage. Although several pharmacological options are available, they often provide limited long-term benefit and may cause adverse effects. Emerging evidence suggests that gut microbiota dysbiosis contributes to BED pathophysiology. Cytokine infiltration of the gut barrier ultimately causes neuroinflammation, highlighting the gut–brain axis as a potential therapeutic target. This systematic review and meta-analysis evaluated the effectiveness and safety of central nervous system-targeting pharmacotherapies and psychobiotics for BED. Cochrane Library, PubMed, and the Virtual Health Library were searched for randomized controlled trials published from January 2000 to January 2026. Eligible studies evaluated monotherapy with a central nervous system-acting drug or psychobiotics in clinically diagnosed BED populations. Twenty pharmacological trials (n = 2154) and five psychobiotic trials (n = 304) met the inclusion criteria. Risk of bias was assessed using the Cochrane RoB 2 tool, and pooled estimates were calculated using random-effects models. Pharmacological interventions showed a significant pooled effect versus placebo (Standard Mean Difference (SMD) = 0.307, 95% Confidence Interval (CI): 0.103–0.511, p = 0.003), although heterogeneity warrants cautious interpretation. Psychobiotics showed a moderate and significant effect (SMD = 0.680, 95% CI: 0.448–0.913; I² (heterogeneity index) = 0%) and no reported adverse events. Overall, our study implies that psychobiotics may be a safe and potentially effective adjunctive approach for BED, but larger, well-designed trials are needed. Full article

Purpose: Virtual reality (VR) and augmented reality (AR) are increasingly being explored as tools with potential applications in radiation oncology, with applications in education, patient care, and workflow optimization. This review evaluates the current landscape and future potential of immersive technologies in clinical practice. Methods: A comprehensive literature review was conducted via PubMed and Scopus (search date: January 2026) using a Boolean search strategy combining terms for virtual/augmented/mixed reality, radiotherapy, and education/anxiety/training; articles published between 2010 and 2026 were screened independently by two reviewers. An online survey assessed experience with and perceptions of VR among Canadian radiation oncologists. Semi-structured interviews with physicians, residents, therapists, physicists, and a staff psychologist at a large academic tertiary-care center in Canada explored qualitative insights into current use and attitudes toward immersive technologies. Results: VR and AR show utility across multiple domains. In education, platforms such as the Virtual Environment for Radiotherapy Training (VERT) enable therapists to practice in simulated treatment environments, while VR-based contouring tools reduce segmentation time by 41–58% and improve spatial understanding. For patient care, immersive VR interventions reduce pre-treatment anxiety by 26–56%, enhance understanding of procedures, and may decrease sedation in pediatric populations. AR-guided positioning systems demonstrate feasibility with acceptable accuracy, offering radiation-free setup verification. Survey findings revealed limited adoption (>80% reported no use), though 40% believed VR could enhance patient education and 39% desired expanded integration over the next decade. Barriers included cost, limited institutional awareness, and lack of training infrastructure. Conclusions: VR and AR show early potential for improving education, reducing patient anxiety, and enhancing positioning accuracy in radiation oncology. Despite implementation barriers, ongoing trials and technological advances are gradually building the evidence needed to clarify the role of immersive technologies in clinical practice. Full article

Background: Low-cost virtual reality exergames may help maintain and improve postural control in children with spastic hemiplegia cerebral palsy (CP). This study aimed to evaluate the comparative effectiveness of the same six-week, low-cost exergame programme delivered via telerehabilitation (TR) and face-to-face (FF) in CP children. Methods: In this randomised controlled trial, 15 CP patients completed 18 sessions over 6 weeks. The TR group received remotely delivered sessions, whereas the FF control group completed in-person sessions with a physiotherapist. Outcomes were assessed at baseline; weeks 2, 4, and 6; and follow-ups at weeks 8 and 10. Postural control (centre-of-pressure sway area; CoP_sway) was measured during eyes open (EO), eyes closed (EC), voluntary mediolateral sway to a 30 bpm auditory cue (EO/EC), and during exergames targeting mediolateral (ML-WS) and anteroposterior (AP-WS) weight-shifting. Timed Up and Go (TUG) and Modified Modified Ashworth Scale (MMAS) were also assessed. Results: At week 6, both TR and FF significantly reduced CoP_sway (TR: p = 0.001, EC; FF: p = 0.01, EO). TR also improved dynamic postural control (p < 0.05) and TUG scores (p = 0.03), with functional gains sustained until week 10. Between-group comparisons revealed that TR achieved significantly greater reductions in AP weight-shifting (SD_ML, p = 0.001; V_ML, p = 0.004) and TUG (p = 0.009) than FF, with these advantages persisting throughout follow-up as revealed by post hoc analysis. Conversely, only FF significantly reduced ankle muscle tone (MMAS, p = 0.05). TR demonstrated broader improvements in secondary CoP metrics and superior long-term retention of functional mobility gains. Conclusions: Both six-week exergame interventions led to improvements in postural control. This trial demonstrated that telerehabilitation is a viable, comparable alternative to face-to-face delivery. Long-term retention suggests both modalities are complementary, offering flexible solutions to enhance routine physiotherapy service pathways. These findings provide a basis for validating these models across larger clinical cohorts. Full article

Background: Poor mental health is prevalent among veterans who suffer from post-traumatic stress disorder (PTSD) and other psychiatric conditions. Canine-assisted interventions may improve psychological and social health in veterans. The parent study, a randomized controlled trial, revealed improvements in PTSD following both a service dog training program and an active control condition consisting of virtual dog training lessons. Thus, in the present post hoc secondary analysis, we analyzed both groups together (pooled arms) to examine gender-based differences in the effects of the altruistic service dog training programs on psychosocial outcomes. Methods: Veterans (N = 59) participated either in hands-on (with a dog and trainer) or virtual (no dog present) dog training programs over eight weeks and completed self-reported psychosocial measures before and after the program. Mixed-effect linear models were used to assess the interaction between time and gender on a series of psychosocial outcomes in the pooled sample. Results: The findings supported greater psychosocial improvements for female participants compared to male participants, including significant improvements in PTSD, perceived stress, and perceived physical health, and feeling greater closeness and lower avoidance in close relationships (ps < 0.05). The results revealed moderate to large effect sizes among female participants, suggesting meaningful clinical effects of the interventions (ds = 0.47–0.70). Conclusions: While the secondary analysis and small sample size limit causal inferences, the exploratory evidence suggests greater improvements in psychosocial health in female veterans after participating in the service dog training programs. Future research should tailor interventions to optimize the therapeutic effects for male and female veterans and identify other individual characteristics involved, such as combat exposure or post-traumatic stress symptom severity. Full article

Psychosis presents significant treatment challenges, and standard Cognitive Behavioral Therapy for psychosis often faces limitations due to patient engagement issues and reliance on subjective self-reporting. The integration of Virtual Reality (VR), physiological biosensors, and artificial intelligence offers a transformative opportunity to address these challenges. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. A thorough literature search was performed across seven databases. Twelve randomized controlled trials involving 1504 participants were included to assess VR-assisted CBT, VR treatment, and AVATAR therapy. Meta-analyses showed that VR interventions significantly decreased auditory verbal hallucinations (pooled SMD = −0.24, p = 0.0011) and paranoid thoughts (SMD = −0.26, p < 0.0001) compared to control conditions. This review supports integrating multi-modal biosensors to collect real-time, objective physiological data. Such integration enables the development of AI-driven, closed-loop systems that dynamically adjust the virtual environment based on the patient’s physiological state. VR-assisted therapies effectively reduce positive symptoms of psychosis. Incorporating biosensors is a crucial step toward a data-driven approach for personalized, closed-loop psychiatric care. Future efforts should focus on large-scale clinical trials, biomarker validation, and robust ethical frameworks to ensure safe and effective implementation. Full article

Artificial intelligence has evolved to generative AI (GenAI), a paradigm shift that has shifted the emphasis away from the evaluation of existing patterns to the generation of novel biological and medical material. This study examines GenAI achievements in biosciences and medical fields the last five years in these fields using databases such as PubMed and Scopus. The paper highlights the recent evolution in biomedical research from virtual screening to de novo design. It illustrates how models like RFdiffusion and ProteinMPNN leverage “inverse folding” to assemble novel of proteins and drugs. Ultimately, these generative methods yield candidate with enhanced binding affinity and structural stability. For example, exploratory studies suggest GenAI has the potential to address inefficiencies via automatic documentation in the therapeutic sector, and it may enhance research capabilities by using Generative Adversarial Networks (GANs) and Variational Autoencoders (VAEs) to generate synthetic clinical trial data that preserves confidentiality. In addition, the review argues that though GenAI democratizes medical education through scalable simulations, it raises questions about long-term knowledge retention. Finally, GenAI also offers a transformative “write” capability for biology, but its responsible application will require addressing model “hallucinations” and building Explainable AI (XAI) and robust ethical frameworks. Full article

Dry eye disease, a multifactorial and symptomatic disease characterized by tear film instability and ocular surface dysfunction, has emerged as an increasingly pressing global health concern—particularly against the backdrop of increasing digital device usage and the widespread application of virtual learning. Traditional pharmacotherapies, such as artificial tears, yield only transient symptomatic relief. Compared with pharmacological agents, surgical treatments are further restricted in clinical application, primarily because of their invasiveness, technical complexity, postoperative complications, and high costs. Consequently, the development of novel therapeutic strategies has emerged as imperative. This review summarizes advances in pharmacotherapy, including nanomedicine and biological agents, as well as emerging physiotherapies, such as photobiomodulation, thermal pulsation, and neurostimulation. These innovative therapeutic approaches address the partial limitations of conventional treatments through three main molecular mechanisms: improved drug delivery, multitargeted pharmacology, and enhanced biocompatibility. Nevertheless, the clinical translation of many innovative therapies requires large-scale clinical trials to validate clinical efficacy, optimize dosage regimens, and assess long-term safety profiles. In the future, integrating lifestyle modifications, effective clinician–patient communication, and patient-centric diagnostic approaches will facilitate the establishment of therapeutic alliances and support the success of precision medicine. Full article

Background: Chronic nonspecific low back pain (CNLBP) with lumbar hyperlordosis leads to pain, dysfunction, and poor quality of life. Virtual reality (VR)-based training may enhance exercise engagement and outcomes. This study compared VR-based pelvic rocking training with conventional pelvic rocking training exercises. Methods: A triple-blind randomized controlled trial enrolled 100 participants with CNLBP and hyperlordosis, who were randomly allocated into two groups: the group, which performed pelvic rocking exercises using the TBed VR system (TbG), and the conventional group (CG), which performed the same exercises without VR. Both groups completed three sessions per week for eight weeks. Primary outcomes included pain (Numerical Pain Rating Scale, NPRS), lumbar lordotic angle (LLA), lumbar range of motion (ROM), and functional disability (Oswestry Disability Index, ODI). Secondary outcomes were patient satisfaction and commitment to exercise sessions. Assessments were conducted at baseline, immediately post-intervention, and after a one-month follow-up. Results: Both groups showed significant improvements in all outcome measures post-treatment (p < 0.016). Furthermore, some outcomes—specifically pain, LLA, and extension ROM—continued to improve during the follow-up period. The TbG demonstrated significantly greater reductions in pain, greater ROM improvements, greater functional gains, and higher levels of satisfaction and commitment than the CG (p < 0.05). These between-group differences persisted at the one-month follow-up, particularly for pain and ROM, which remained statistically significantly better in the TbG. Moreover, all between-group differences demonstrated medium to high clinical effects (d ≥ 0.3). Conclusions: Pelvic rocking exercises using the TBed VR system were superior to conventional exercises in terms of pain, ROM, and function at the immediate and intermediate time points. Using TBed led to better patient satisfaction and higher exercise commitment. Full article

Firefighters are regularly exposed to occupational stress and potentially traumatic events. However, few evidence-based, fire service-specific interventions exist. Brief, mindfulness-based interventions may help address these challenges by improving regulation skills and reducing psychological distress. This pilot randomized controlled trial primarily evaluated the feasibility and acceptability of a one-session, group-based, virtual mindful attention training workshop developed specifically for firefighters, with secondary evaluation of preliminary efficacy. Firefighters (N = 82) were recruited from multiple fire departments across a large U.S. Southwestern metropolitan area and randomized to the mindful attention workshop (n = 45) or a waitlist control condition (n = 37). Feasibility outcomes were mixed, with strong enrollment among eligible participants (74.5%) but relatively low workshop attendance among those randomized to the intervention (53.3%). A total of 24 firefighters completed the workshop and found it to be helpful, informative, and relevant to the challenges faced in the fire service, with group processes characterized by high comfort, understanding, and low conflict. However, no significant between-group differences were observed in reductions in symptom severity or increases in mindfulness-based outcomes. Post hoc descriptive analyses revealed that most firefighters expressed strong interest in digitally delivered mental health content and the vast majority perceived online or app-based firefighter-specific mental health resources as helpful. Findings indicate mixed feasibility, strong acceptability among attendees, and a lack of preliminary efficacy, and highlight directions for refining intervention delivery of this pilot workshop and evaluating clinical impact in future trials. Full article

Streptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide, with current polysaccharide-based vaccines offering limited serotype coverage, high production costs, and reduced efficacy in vulnerable populations. These limitations have prompted the search for conserved pneumococcal proteins as universal vaccine candidates. Among them, pneumococcal surface protein A (PspA) stands out as a major virulence factor, present in virtually all clinically relevant strains, and capable of interfering with complement activation, opsonophagocytosis, and host defense mechanisms. Over three decades of research have demonstrated PspA’s strong immunogenicity, protective efficacy in multiple animal models, and safety in early-phase clinical trials. Here, we critically review advances in PspA-based vaccine development, including recombinant protein fragments, fusion constructs, nanoparticle formulations, and live-vector platforms. We highlight the structural and immunological determinants underlying its protective potential, while discussing major challenges such as antigenic variability and cross-reactivity across pneumococcal strains expressing distinct PspA clades. By integrating recent experimental and translational findings, this review outlines the opportunities and obstacles for the implementation of serotype-independent PspA-based vaccines. Full article