Longstanding distinctions between "verbal" and "mathematical" minds continue to shape educational assessment, curriculum design, and how learners are categorized by perceived cognitive strengths. Yet plenty of evidence from psychology and cognitive neuroscience points to a more unified model of intelligence that refutes the false dichotomy. In this article, I propose dual-domain cognitive fluency (DDCF) as a way to describe how the human mind can move fluidly between words and numbers and derive meaning from both. Building on research in symbolic cognition, executive function, and cognitive flexibility, this article identifies three dimensions: symbolic translation between modalities, cognitive flexibility across task demands, and layered reasoning, which integrates propositional logic with linguistic abstraction. DDCF captures the symbolic agility now required in knowledge-based environments where the integration of representational systems matters more than isolated domain expertise. Examples range from data storytelling in journalism to algebraic modeling in the social sciences-contexts in which verbal and quantitative reasoning operate in tandem. These insights matter for pedagogy, curriculum design, and the evolving demands of data-intensive workplaces. Far from a niche ability, dual-domain fluency reflects a generalizable cognitive capacity that existing models of intelligence have struggled to measure, reward, or systematically support.
Cyberbullying has emerged as a prominent form of online aggression, yet evidence on the role of online media remains fragmented because media-related variables are often treated as broad and undifferentiated constructs. This meta-analysis synthesized associations between six characteristics of online media use and cyberbullying perpetration. A systematic search of international databases identified 97 eligible studies published between 2004 and 2025, comprising 248,316 participants. Random-effects models were used to estimate pooled correlations, and moderator analyses examined cultural background and temporal patterns of content exposure. Five of the six focal variables were significantly associated with cyberbullying perpetration. Exposure to online violent content, exposure to online sexually explicit content, duration of online media use, and perceived online anonymity were positively associated with cyberbullying, whereas media literacy was negatively associated with it. Among these variables, perceived online anonymity showed the strongest association. By contrast, exposure to online prosocial content was not significantly associated with cyberbullying. Moderator analyses indicated that temporal pattern significantly moderated the association between exposure to online violent content and cyberbullying, with stronger coefficients for short-term than for long-term exposure. Most other subgroup differences were not significant. Sensitivity analyses showed that, despite substantial heterogeneity in most models, the overall pattern of findings remained stable. These findings suggest that online media should not be treated as a unitary correlate of cyberbullying. Distinguishing specific media characteristics may help refine theory and inform more targeted prevention efforts in online contexts.
Antidepressant medications are an effective treatment for major depressive disorder, yet antidepressant discontinuation early in the course of treatment remains common. Almost three-quarters of patients who are treated for depression receive their treatment exclusively from primary care providers who have relatively short visits with their depressed patients and little capacity to monitor their treatment adherence. There is a critical need to develop effective, low barrier strategies to support and promote antidepressant adherence for patients seen in primary care. We are conducting a 3-arm randomised controlled trial to compare the effectiveness of two adherence support strategies with usual care among adult primary care patients with depression who have been newly prescribed antidepressant medications. We are examining whether daily text messages with and without financial incentives improve depression symptoms and antidepressant adherence as compared with treatment as usual, assessed via wireless pill bottle and survey administration at 6 and 12 weeks. The primary outcome is symptom response at 12 weeks, defined as a ≥50% reduction from baseline depression symptom severity as measured by the Patient Health Questionnaire 9. Secondary outcomes include symptom response at 6 weeks and daily antidepressant adherence at 6 and 12 weeks. This study is registered on clinicaltrials.gov and has been approved by the University of Pennsylvania Institutional Review Board (#856160). All subjects provide informed consent to participate in research procedures prior to enrolment. Trial results will be published in peer-reviewed journals and presented at scientific meetings. NCT06496646.
Vestibular rehabilitation training (VRT) has become an indispensable part of treatment for dizziness disorders. VRT is an exercise method that can alleviate dizziness and improve gaze stability and postural control, mainly used for the treatment of patients with vestibular dysfunction. To analyse the current status, hot spots and trends in research on vestibular rehabilitation, data were collected from the Web of Science Core Collection and Scopus databases, and selected publications related to dizziness vestibular rehabilitation from 2014 to 2024. Visual analysis tools were utilized to build knowledge maps of the research field, analyzing the distribution of publications, authors, institutions, journals, collaboration networks, co-occurrence, clustering, and burst detection of keywords. A total of 907 publications were included in this study, with an upward trend in the number of annual publications. The United States led in publication quantity, with the University of Pittsburgh ranking first among institutions. Professor Susan L. Whitney (University of Pittsburgh) was the most productive researcher. Recent research hotspots concentrated on unilateral vestibular hypofunction, vestibular neuronitis, and postural balance, providing clinical evidence for targeted VRT intervention. Research on VRT for dizziness is expanding progressively, with vestibular compensation and postural balance as core hotspots. The findings consolidate VRT's clinical application value in guiding personalized intervention for different vestibular disorders. Future research trends will focus on expanding VRT's application scope, formulating individualized protocols, and developing AI-aided targeted VRT, which will optimize clinical efficacy and promote the standardized development of this field.
Academic engagement in plastic and reconstructive surgery (PRS) has grown substantially, marked by an increasing number of professional societies, annual meetings, and peer-reviewed journals. While this growth has facilitated innovation, collaboration, and knowledge sharing, it has also introduced financial burdens. These costs may limit access to academic involvement, especially for early-career surgeons and those without institutional funding. Despite the implications these financial barriers pose for equity, academic engagement, and innovation within the field, the cumulative cost of academic involvement in PRS remains poorly quantified. A cross-sectional review was conducted to assess the financial costs of academic engagement in PRS in the United States. Between January and April 2025, data were collected from official websites of national and subspecialty PRS societies, journals, continuing medical education (CME) platforms, and board-certifying bodies. Annual dues, meeting fees, CME costs, journal subscription, publishing fees, and board-related expenses were compiled. A comparative analysis with five other surgical subspecialties was conducted. Thirty-two major PRS societies were identified. Membership dues ranged from $150 to $1,299. Meeting registration was $250 to $1,495. Journal subscription costs ranged from $44.90 to $1,518, and open-access (OA) article processing charges (APCs) from $700 to $5,334. PRS-board certification costs averaged $9,045. CME cost-per-credit reached up to $600. Among the six surgical specialties in the United States that were included in the comparative analysis, PRS ranked second in baseline academic engagement (BAE) costs after Neurosurgery, averaging $10,109. Academic engagement in PRS carries significant financial burdens that may limit access. Addressing these barriers is essential to maintaining equity and innovation.
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To analyze the adherence of Checklist for Artificial Intelligence (AI) in Medical Imaging (CLAIM) in top medical imaging journals. A search for AI research in top medical imaging journals was performed from Web of Science Core Collection. The adherence was assessed by the reporting score and compliance rate of CLAIM. Potential influencing factors were also analyzed. A total of 501 articles were included. After quality assessment, the median CLAIM score was 19 points (25th-75th: 17-21 points), and the median overall compliance rate was 51.4% (25th-75th: 46.2%-57.9%). Among the 42 items, 14 items had compliance rates of ≥80%, 11 items had compliance rates of 40%-79%, while 17 items had compliance rates of <40%. Low compliance rates were predominantly concentrated on items such as quality control of annotations, sample size determination, model robustness evaluation, failure analysis, and code/data availability. In terms of temporal trends, both the overall score (ρ = 0.119, p = 0.008) and compliance rate (ρ = 0.139, p = 0.002) showed weak positive correlations with the publication year. Furthermore, compliance for items 2 (structured abstract) (ρ = 0.129, p = 0.004), 33 (participant flow diagram) (ρ = 0.131, p = 0.003), 34 (demographic/clinical characteristics by partition) (ρ = 0.122, p = 0.006), 41 (study protocol/data/code availability) (ρ = 0.094, p = 0.036), and 42 (funding sources) (ρ = 0.128, p = 0.004) demonstrated significant upward trends over time. Logistic regression analysis identified the following negative predictors of reporting quality: research objectives focused on image reconstruction (OR = 0.416, 95% CI: 0.203-0.842, p = 0.015), artifact reduction (OR = 0.072, 95% CI: 0.009-0.365, p = 0.004), multimodal imaging (OR = 0.301, 95% CI: 0.090-0.899, p = 0.038), use of public (OR = 0.508, 95% CI: 0.289-0.883, p = 0.017) and public-private hybrid (OR = 0.339, 95% CI: 0.146-0.759, p = 0.010) development datasets. Conversely, positive predictors were: publication year (OR = 1.246, 95% CI: 1.067-1.458, p = 0.006); being published in a CLAIM adopting journal (OR = 1.737, 95% CI: 1.070-2.481, p = 0.026); code availability (OR = 1.929, 95% CI: 1.181-3.186, p = 0.009); and development datasets sizes of 100-199 cases (OR = 2.187, 95% CI: 1.121-4.320, p = 0.023), 500-999 cases (OR = 3.409, 95% CI: 1.508-7.902, p = 0.004), and ≥1000 cases (OR = 2.798, 95% CI: 1.335-5.979, p = 0.007). The adherence of CLAIM among AI research in top medical imaging journals is still inadequate. It is needed to join efforts of researchers, editors, and reviewers to strengthen the application of CLAIM to improve the research quality and reproducibility.
Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in clinically node-negative breast cancer. Traditionally, SLNB is performed using technetium-labelled (99mTc) nanocolloid, with or without blue dye. However, both tracers have important limitations. Blue dye poses safety risks, while 99mTc-nanocolloid introduces additional hospital visits, radiation exposure, logistical complexity and high costs. Indocyanine green (ICG) fluorescence is a non-radioactive alternative, offering real-time visualisation while addressing many limitations of traditional tracers. Yet, adoption of ICG-guided SLNB remains limited. This trial aims to guide the implementation of ICG-guided SLNB via axillary incision, evaluate its real-world effectiveness and inform conditions for nationwide scale-up. The INFINITE trial is a multicentre, hybrid effectiveness-implementation study employing a stepped-wedge cluster design across seven Dutch hospitals. Clusters sequentially transition from SLNB using 99mTc-nanocolloid alone (Phase I) to ICG as the primary tracer and 99mTc-nanocolloid as a within-patient control (Phase II), and finally to ICG alone (Phase III). The hybrid design enables evaluation of implementation outcomes (penetration, adoption, fidelity, appropriateness, feasibility, acceptability), intervention outcomes (effectiveness, safety, costs) and patient-reported experience (patient satisfaction). The primary outcome is penetration, the proportion of Phase III SLNB procedures performed with ICG alone. An integrated implementation approach combines the Grol and Wensing model (process model), the Consolidated Framework for Implementation Research (determinant framework) and Proctor's outcomes framework (evaluation framework). Outcomes are assessed quantitatively, supplemented by an embedded mixed-methods component to explain variation in implementation across centres. Ethical approval was obtained from the Medical Research Ethics Committees United (6 November 2024; NL87551.100.24). Results will be submitted to open-access, peer-reviewed journals and presented at conferences focused on oncological or image-guided surgery. Implementation tools, including a clinical protocol, implementation guide, educational materials and patient information, will be developed to support national adoption. NCT07146295.
Chimeric antigen receptor T-cell (CAR-T) therapy shows limited efficacy against solid tumors due to the immunosuppressive tumor microenvironment (TME). Macrophages possess superior infiltration capabilities, yet their therapeutic potential remains under-realized. We engineered a synNotch-iNOS CAR-macrophage (CAR iNOS-M) that releases nitric oxide (NO) upon CD19 recognition. Its efficacy was evaluated in syngeneic, immunocompetent murine models of metastatic melanoma. CAR iNOS-M therapy effectively reprogrammed the pulmonary tumor immune microenvironment (TIME), inducing potent antitumor responses independent of CD8+ T cells but strictly dependent on CD4+ T cells. Mechanistically, CAR iNOS-M treatment led to a significant reduction in pro-tumorigenic lung interstitial macrophages (IMs), subsequently decreasing platelet factor 4 (PF4) levels. This disruption of the PF4 signaling axis inhibited the polarization of immunosuppressive Th1-Tregs, alleviating T-cell exhaustion. This study delineates a novel indirect mechanism for CAR-M, shifting the focus from direct phagocytosis to strategic TIME remodeling, providing a foundation for treating solid tumors.
Acute kidney injury requiring dialysis (AKI-D) is a major contributor to morbidity and mortality worldwide, with the highest burden observed in low- and lower-middle-income countries (LLMICs). In Latin America (LATAM), a region composed largely of LLMICs, the lack of region-specific data leads to variable clinical practices and inconsistent health policies for AKI, which remain major barriers to optimal kidney care. The LATAM-AKID registry aims to fill this gap and systematically characterise the epidemiology, processes of care and outcomes of patients with AKI-D across representative countries of LATAM. LATAM-AKID is an international, multicentre, retrospective cohort study that will enrol consecutive critically ill adults with Kidney Disease: Improving Global Outcomes stage 3 AKI requiring dialysis. Different hospitals across 10 Latin American countries will contribute data through a standardised REDCap platform hosted at the University of Alabama at Birmingham. Deidentified data will be collected at baseline, intensive care unit (ICU) admission and renal replacement therapy (RRT) initiation, with follow-up for up to 7 days to capture ICU- and RRT-related clinical data. Study outcomes will be assessed at ICU and hospital discharge and at 90-day follow-up. The primary outcome is in-hospital mortality. Secondary outcomes include ICU mortality, 90-day mortality, ICU and hospital lengths of stay, status of renal recovery and RRT dependence at hospital discharge and at 90-day follow-up, and RRT processes and complications related to anticoagulation, catheter dysfunction, infection and circuit interruptions. Data will be analysed using multivariable logistic and Cox regression models, with planned subgroup analyses by RRT modality (continuous vs intermittent), patient-level illness severity, hospital characteristics and country gross national income categories. This study has been approved by the institutional review board of the University of Alabama at Birmingham (IRB-300013633). Local ethics committee approvals will also be obtained at all participating sites. Results from this work will be disseminated by publications in peer-reviewed journals and presentations at national and international scientific meetings. This study has been registered with clinicaltrials.gov (NCT07262320).
Post-publication peer review faces a emerging systemic vulnerability from 'letter-bombing'-the proliferation of high-volume, potentially machine-generated critiques that exploit citable correspondence units, creating a plausible risk of academic metric inflation. Driven by the democratization of Large Language Models (LLMs), these automated submissions frequently exploit formatting loopholes to manipulate public indicators like the h-index. The problem is particularly observable in data-intensive specialties like surgical oncology, where abstract-level statistical critiques targeting complex clinical trials risk muddying translational research communication. Drawing on documented bibliometric anomalies and confirmed editorial actions, this piece discusses operational definitions of abnormal correspondence volumes and proposes a multi-layered framework. To protect the scientific record, we propose an enforceable framework for editorial boards: implementing strict metadata labeling to close indexing loopholes, verifying author history, and mandating the "Right of Simultaneous Reply" as a universal baseline publishing standard.
Apoptotic cell clearance is essential for maintaining tissue homeostasis and preventing inflammation. While the involvement of certain lysosomal proteins in apoptotic cell clearance has been established, the roles of other lysosome-associated proteins remain unclear. Using genome-wide RNAi screening of lysosomal genes in Caenorhabditis elegans and tissue-specific analysis, we identified 14 lysosome-associated proteins crucial for apoptotic cell clearance, with the SaPosin-like protein SPP-10 being a key factor. The present study demonstrated that spp-10 defects significantly prolonged apoptotic cell persistence. Further investigations revealed that loss of spp-10 causes excessive accumulation of LAAT-1 and NUC-1 on phagolysosomes and sustained phagosomal acidification, which in turn impairs phagosomal degradation. The mammalian homolog of PSAP, whose knockdown reduces efferocytosis in mammalian cells, demonstrates that its function is evolutionarily conserved. Our findings reveal the essential role of spp-10 in apoptotic cell clearance and suggest that targeting lysosomal pathways may be a potential therapeutic strategy for diseases characterized by defective efferocytosis.
Healthcare continues to celebrate individual clinical excellence while overlooking the practical and ethical power of truly interdependent care. Drawing on theories of professional "flow" and virtue ethics, this essay argues that the physician-pharmacist relationship represents an underutilized model for safer, more effective primary care in Canada. It contrasts hierarchical, siloed structures with collaborative, duobased models that better reflect the complexity of modern patients and medication management. Evidence from Canadian primary care settings demonstrates improvements in safety, patient understanding and system performance when pharmacists and physicians work as equals. The paper concludes with pragmatic, low-cost recommendations to operationalize this virtuous partnership.
The Growth Hormone - Insulin-like Growh Factor - axis promotes linear growth in children and adolescents and accounts for approximately 1/3 of adult height. In Primary IGF-I deficiency (PIGFD) insensitivity to the actions of GH results in short stature. The most severe phenotype in children with genetic defects in the GH receptor gene is known as Laron Syndrome with height SDS of -6 to -12 in childhood and an adult height of 120-130 cm. Treatment with recombinant human (rh) IGF-1 is approved to promote linear growth in children with severe PIGFD and the EMA approval required that data on children on therapy and up to 5 years post-treatment is collected in the Global Increlex Growth Forum Database (IGFD) registry. In this review, the findings in five publications on rhIGF-1 therapy in children with SPIGFD based on data from the Global IGFD registry are discussed and compared with previous publications on cohorts of patients with severe PIGFD including children with Laron Syndrome. The registry started inclusion of patients in 2008 from 10 European countries (EU IGFD Registry) and have continued collecting data from eight European countries and the US since 2021 (Global IGFD registry). At data cut-off (03 April 2025), there were 346 patients in the registry database including patients with a large variation of phenotypes from Laron Syndrome to a less severe phenotype. The findings include real-world data on effectiveness assessing short- and long-term height gain as well as near adult height, pubertal development and growth dynamics and safety assessing hypoglycemic events, which is the most frequent targeted adverse event. Real-world data from the Global IGFD registry confirms previous data on rhIGF-1 therapy and demonstrates that short and long-term height improves in a majority of children with SPIGFD with similar height improvements compared to children with Laron Syndrome. The registry data points to baseline characteristics including age at treatment initiation that predicts response to therapy. Hypoglycemia is the most common adverse event and hypoglycemia prior to start of therapy or a diagnosis of Laron Syndrome increases the risk. However, very few events over a course of therapy are reported on an individual basis.
Klebsiella pneumoniae (K. pneumoniae) is a major pathogen involved in nosocomial and community-acquired infections, whose multidrug resistance (MDR) constitutes a public health emergency. Data reporting of antibiotic-resistant K. pneumoniae in healthcare settings in Burkina Faso is often insufficient and poorly documented. This study aimed to estimate, through a meta-analysis, the prevalence of phenotypic and molecular resistance to antibiotics of K. pneumoniae in Burkina Faso. A systematic review and meta-analysis were conducted using studies published between 2015 and 2025, identified through PubMed, African Journals Online, Scopus, and Google Scholar, using specific keywords, following the PRISMA guidelines. Data on resistance to different classes of antibiotics and genetic determinants were extracted. A meta-analysis of proportions using a random effects model was used to estimate the pooled resistance rates. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with registration ID: CRD420261290027. The pooled prevalence of resistance in K. pneumoniae was 44% (95% CI: 0.36-0.53). The highest resistance rates were observed to penicillin (85%) and third-generation cephalosporins (50%), while carbapenems remained the most effective class (11%). The molecular analysis revealed that aminoglycoside resistance genes were the most prevalent (53%), driven by aac(3)-IIc (78%) and aac(6')-Ib (62%) genes. Extended Spectrum Betalactamas (ESBL) genes (34%) were dominated by the blaCTX-M-15 variant (up to 100%). Finally, the emergence of carbapenemases was confirmed by the presence of blaNDM (10%) and blaIMP (25%). Our results indicate a burden of multidrug resistance in K. pneumoniae within Burkina Faso, characterized by the co-occurrence of various genotypic resistance markers. These findings call for a review of empirical treatment protocols and urgent reinforcement of molecular surveillance and hospital hygiene to preserve the last remaining treatment options. Not applicable.
A wealth of new literature is published annually in the growing field of perioperative medicine. The most noteworthy publications are often hard to find as they are spread over a variety of journals. We have undertaken a multi-database literature search from January to December of 2025 to identify the most impactful perioperative articles from the past year. We included original research articles, systematic reviews, meta-analyses, and guidelines. We excluded abstracts, case reports, letters, or literature pertaining to cardiovascular surgery, pediatrics, and obstetrics. Two authors reviewed each reference using the Distiller SR systematic review software (Evidence Partners Inc., Ottawa, Ontario, Canada). A modified Delphi technique was used to narrow down to seven of the most impactful publications and another eight tabular summaries. The purpose of this review is to highlight new literature to improve perioperative outcomes for patients.
Diaphragm dysfunction is associated with failure to wean from mechanical ventilation. Inspiratory muscle training (IMT) may help improve outcomes for difficult-to-wean patients, yet the optimal approach remains unknown. High load IMT causes a training effect on the extra-diaphragmatic inspiratory muscles, but does not improve weaning success, questioning the utility of frequently cited high intensity IMT loads. Additionally, patients may find IMT unpleasant and distressing due to dyspnoea experienced during IMT. The aim of this study is to define a diaphragm-focused IMT load which is acceptable to patients. This study is designed as a prospective, mixed methods study. Forty difficult to wean, tracheostomised patients on mechanical ventilation will perform IMT at 15, 30, 45 and 60% of their maximal inspiratory pressure (PImax) in a randomised order using a tapered flow resistive loading device (POWERBreathe KH2, POWERBreathe, UK). Electrical activity of the diaphragm will be measured using an oesophageal multipair catheter (NAVA, Getinge, Sweden); extra-diaphragmatic (parasternal, scalene and sternocleidomastoid) muscle activity will be measured using surface electromyography. Patient experience of each load will be explored by measuring perceived breathing difficulty and unpleasantness using 0-10 numeric rating scales, verbal or written communication techniques in line with the participants' communication ability, and/or bespoke communication boards co-designed with the study patient and public involvement (PPI) group. Quantitative and qualitative data will be integrated to inform a diaphragm-focused, patient-acceptable IMT load. Ethical approval was obtained from Wales Research Ethics Committee 4 (Reference 25/WA/0242) on 30 October 2025. Results from this study will be presented at scientific meetings and published in peer-reviewed journals. NCT07256821.
This article examines collaborative workshops as a method for researching violence against persons with intellectual disability. Participants included professionals from healthcare, social services and the police, and experts by experience who took part in three workshops focused on violence against persons with intellectual disability. Eleven participants and three researchers contributed, with researchers facilitating, documenting, and journaling the workshops. Data from documentation and journals were analyzed using reflexive thematic analysis. Participants' experiences were grouped into four themes: Expectations and mutual decisions, A learning experience, The workshop climate, and Being part of something important. Researchers' experiences were grouped into four themes: A mosaic, Atmosphere and commitment, The examined intervention, Expectations and ideas. The findings suggest that collaborative workshops can generate practice-relevant knowledge and integrate diverse perspectives. They also provide valuable learning opportunities for all involved. Successful workshops require careful planning, openness to participant input, and a supportive, inclusive atmosphere.
To synthesize literature on residual laxity following arthroscopic treatments of CAI. Literature search for articles published since 2015, reporting (i) on arthroscopic surgical treatment for CAI; (ii) pre- and post-operative talar tilt angle (TTA); and (iii) minimum follow-up of 2 years. 12 eligible studies representing 688 ankles were included, comprising 14 datasets (1 modified Broström with suture tape augmentation, 2 arthroscopic Broströms, 5 arthroscopic reconstructions, and 6 arthroscopic modified Broström-Gould). Subgroup analysis for TTA and anterior talar translation (ATT) showed no significant difference between techniques. Post-operative pooled proportions of TTA and ATT were not calculated due to high heterogeneity (TTA, I2 =99.1%, p < 0.001; ATT, I2 =98.4%, p < 0.001). No significant differences were found across surgical groups in post-operative laxity, whether assessed by TTA or ATT. All arthroscopic techniques demonstrated comparable outcomes, suggesting that residual laxity may depend on biological and patient factors rather than the choice of procedure. Level IV.
Conventional systolic blood pressure (SBP) indices, such as mean SBP or variability indices, fail to capture control consistency. SBP time in target range (TTR) improves risk prediction by measuring SBP control duration. However, it neglects the magnitude of SBP elevation, treating minor and severe elevations equally. We developed and validated the SBP burden, a novel metric integrating both the duration and magnitude of SBP elevation, to enhance cardiovascular risk prediction. This post hoc analysis of the SPRINT included 9,017 high-risk, nondiabetic participants (age, 67.0 [61.0-76.0] years; 64.7% men). SBP burden was calculated as the proportion of the over-target time multiplied by the over-target part proportion of SBP area under the curve [AUC] during that time, using SBP records in months 0-6 (target: 130 mm Hg). Its prediction performance was compared with mean SBP, SBP standard deviation (SD), SBP average real variability (ARV), SBP TTR, and SBP AUC. The primary outcome was the first occurrence of major adverse cardiovascular events (MACEs), including cardiovascular death (CVD death), myocardial infarction, stroke, and heart failure (HF) hospitalization. Over a median follow-up of 3.89 years, 568 MACEs occurred. After adjusting for traditional risk co-variables, the SBP burden showed an independent linear association with MACEs (hazard ratio [HR], 95% confidence interval [CI]: 1.17, 1.09-1.26; p < 0.01) and this association remained even after further adjustment for SBP SD and ARV. Mean SBP (HR, 95% CI: 1.13, 1.03-1.23; p < 0.01), SBP SD (HR, 95% CI: 1.10, 1.01-1.19; p = 0.03), SBP ARV (HR, 95% CI: 1.10, 1.01-1.18; p = 0.02), SBP AUC (HR, 95% CI: 1.15, 1.05-1.26; p < 0.01), and SBP TTR (HR, 95% CI: 0.88, 0.80-0.97; p = 0.01) were also independent risk predictors. Further, we confirmed SBP burden acheived the greatest improvement in discrimination and reclassification (Net reclassification improvement as 0.12 [0.03-0.22]; integrated discrimination improvement as 0.0032 [0.0006-0.0076]), and feature importance (relative informativeness and LASSO ranking as top 1) among tested SBP indices. In high-risk, nondiabetic patients, SBP burden is an independent predictor of cardiovascular outcomes. It overcomes the limitations of SBP TTR, outperforming other SBP indices in predictive performance and feature importance for cardiovascular outcomes. High systolic blood pressure (SBP) is a major risk factor for heart attacks, strokes, and heart failure (HF). While current measures assess average blood pressure levels, variability, or time spent within a safe range, each reflects only one dimension of blood pressure control. We developed “systolic blood pressure burden” (SBP burden), a metric that accounts for both the duration and magnitude of blood pressure elevation above a set threshold. We tested this measure in over 9,000 adults at high cardiovascular risk who were followed for approximately 4 years. Patients with a higher SBP burden faced significantly greater risks of heart attacks, strokes, HF, and CVD death, independent of other known risk factors and blood pressure fluctuations. Among all measures tested, blood pressure burden proved to be the strongest predictor of future heart-related events and offered the most significant improvement in identifying at-risk patients. These findings suggest that evaluating both the duration and severity of blood pressure elevation may better capture cardiovascular risk than conventional measures. Consequently, blood pressure burden could help doctors identify high-risk patients earlier and guide more timely treatment decisions.