Physical Limitations Research Articles

Factors Associated With Outdoor Frequency Among U.S. Community-Dwelling Medicare Beneficiaries: A Cross-Sectional Study.

Despite the benefits of outdoor activity in older adults, a paucity of research explores factors associated with the frequency of older adults going outdoors. The aim of the current study was to investigate if factors of cognitive status, physical performance, and neighborhood characteristics were associated with outdoor frequency among older adults. This cross-sectional study used National Health and Aging Trends Study data to characterize outdoor frequency among Medicare beneficiaries by participant demographics, health, and neighborhood characteristics, and estimated relationships between participant factors and outdoor frequency. The sample included 3,368 participants. The majority (51.6%) were aged 75 to 84 years and female (57.2%). Most (60.4%) participants went outside daily. Probable dementia, physical limitations, and presence of street disorder and sidewalk continuity were associated with decreased outdoor frequency. Research is needed to develop interventions addressing neighborhood conditions and promoting outdoor activity among older adults living with dementia and physical limitations. [Research in Gerontological Nursing, 18(1), 40-52.].

Mastering the canvas of life: Identifying the antecedents of sense of control using a lagged exposure-wide approach.

Accumulating studies have documented strong associations between a higher sense of control and improved health and well-being outcomes. However, less is known about the determinants of increased sense of control. Our analysis used data from 13,771 older adults in the Health and Retirement Study (HRS)-a diverse, longitudinal, and national study of adults aged >50 in the United States. Using generalized linear regression models, with a lagged exposure-wide approach, we evaluated how changes in 59 predictors (i.e., physical health, health behavior, and psychosocial factors) over a 4-year period (between t0;2006/2008 and t1;2010/2012) might lead to changes in sense of control another 4-years later (t2;2014/2016). After adjusting for a rich set of baseline covariates, changes in some health behaviors (e.g., sleep problems), physical health conditions (e.g., physical functioning limitations, eyesight), and psychosocial factors (e.g., positive affect, purpose in life) were associated with changes in sense of control four years later. However, there was little evidence that other factors were associated with a subsequent sense of control. A key challenge in advancing intervention development is the identification of antecedents that predict a sense of control. Our results identified several novel targets for interventions and policies aimed at increasing a sense of control.

Exploring ageism and elderly care in dentistry: A comprehensive scoping review.

This scoping review aims to investigate the perceptions of dental professionals regarding aging and geriatric dentistry, as well as to identify studies focused on ageism in dental care. The review followed guidelines from the Joanna Briggs Institute and PRISMA-ScR. A systematic search was conducted in the databases, covering the period from 2019 to 2024. PubMed, Scopus, and Web of Science were searched. Articles focusing on ageism or oral health in the elderly were included, while those with methodological flaws, duplicates, or unrelated content were excluded. A total of 28 articles were included in the final analysis. The results reveal significant cultural differences in how ageism impacts dental care, with many dental professionals unprepared to treat elderly patients with physical and cognitive limitations. Geriatric dentistry remains underrepresented in dental curricula in some countries, leading to a shortage of specialized professionals. This review underscores the need for further research on the perspectives of practicing dentists and elderly patients to improve care and address the barriers caused by ageism. The review emphasizes the critical need to address ageism in dental care to enhance the quality of treatment for elderly patients. Effective strategies to counteract age-related biases can lead to improved clinical outcomes and more equitable care for all age groups.

Development of a Caregiver-Teacher Supported Physical Activity Program for Elementary School Students

Childhood obesity has been a significant concern worldwide. According to World Health Organization data the pandemic, pose a danger to the world between March 2020 and May 2023, has deepened this concern given the restriction measures such as closures taken to avoid the spread. Following the pandemic, a gap in the literature has arisen concerning the assessment of the long-term impact and potential side effects of physical activity restrictions on children. This study aims to address this gap by developing a comprehensive, needs-based physical activity school program and a web application for home settings, specifically designed for elementary schoolers in Türkiye. To gather essential information on the needs and current status of children in terms of physical and emotional well-being, as well as motor skills and physical activity habits from the perspectives of their caregivers, a thorough needs analysis study was conducted. This study used surveys. 27 volunteer parents participated in the study. The data were analyzed using content analysis. With these findings, an individual activity program consisting of different components was developed, taking into account the development levels and physical fitness levels of elementary school students. Individualized physical activity programs developed within this framework were created taking into account the individual needs and abilities of students and in order to support these needs, and were planned in two separate structures to be implemented with teachers at school and with parents at home.

Everyday activity strategies perceived by people with advanced cancer: a qualitative explorative study

BackgroundDespite growing research on the daily life of people with advanced cancer, more specific knowledge is needed about the specific strategies these people use to manage everyday activities.PurposeThis study explores how people with advanced cancer manage their everyday activities and describe their specific strategies.MethodsThe qualitative study was designed with an explorative approach. Data from 28 people with advanced cancer was drawn from a trial including qualitative interviews to elicit participants’ perceptions about managing their everyday activities. Interviews were conducted in participants’ homes and analysed using an inductive thematic analysis.ResultsWithin an overarching theme of keeping ‘Daily life as usual’, the findings unfold participants’ specific strategies identified within two sub-themes ‘, Upholding routines’ and ‘Activity adaptations’. Upholding routines related to 1) Personal care and household and 2) Leisure-, social- and work-life. Activity adaptation about 1) Working with and around physical limitations; 2) Sharing, delegating, and letting go; and 3) Enlisting ‘outside’ support.ConclusionThis study specified participants’ specific and distinct self-developed strategies within routines and activity adaptations. The strategies reflect participants’ needs for maintaining functioning while relieving pain and mourning, which holds essential potential for informing person-centred intervention development integrating rehabilitation in palliative care.

Effectively Guiding Cell Elongation and Alignment by Constructing Micro/Nano Hierarchical Patterned Titania on Titanium Substrate.

Based on the innate sensitivity of cell to substrate topographical cues, modulating cell-directed growth behavior is crucial for promoting tissue repair and reconstruction. Although photolithography technology has been extensively employed to fabricate a variety of anisotropic patterned structures to guide cell growth, it remains a great challenge to design high-resolution micro/nano hierarchical structures directly onto medical titanium (Ti)-based implants. Herein, we present a rapid, reliable and reproducible approach combining photolithography and hydrothermal technology to construct a micro/nano hierarchical structure including anisotropic micro-strips and a porous structure composed of TiO2 nanotubes features. In vitro biological and physicochemical analyses revealed that the micro/nano hierarchical structures not only efficiently facilitate the localization and adsorption of BSA molecules, but also enhances the control of cell growth behavior. The synergistic effect between the physical limitation for organizing cellular cytoskeleton at micropattern and the control of focal adhesion sits at the nanoscale can effectively guide cells to maintain stable elongation and alignment, even at large micro-stripe width of 100 μm. This study presents a promising strategy to precisely construct micro/nano multi-level patterned structure on Ti substrate using biomaterials with excellent biocompatibility. These functional micro/nano hybrid micropatterns offer a powerful platform for regulating bioreagent localization and cell behaviors in various applications including tissue engineering, regenerative medicine, drug screening, and biosensors.

The relationship between fatigue levels and psychosocial adjustment in elderly individuals with chronic obstructive pulmonary disease: A descriptive study.

Chronic Obstructive Pulmonary Disease (COPD) is associated with physical limitations and significant social, psychological, and behavioral challenges. This study investigates the relationship between fatigue levels and psychosocial adjustment in COPD patients, considering their sociodemographic characteristics. A descriptive study was conducted with 160 COPD patients hospitalized in the Pulmonology Department of a university hospital. Data were collected via face-to-face interviews using a patient information form, the COPD and Asthma Fatigue Scale (CAFS), and the Psychosocial Adjustment to Illness Scale-Self-Report (PAIS-SR). Statistical analyses included Independent Sample t-test, One-Way ANOVA, Mann-Whitney U test, Kruskal-Wallis test, and Spearman correlation analysis, with significance set at p < 0.05. The mean age of participants was 68.70 ± 9.41years; 71.9% were male, and 67.9% had COPD for over six years. Most participants (74.4%) reported limitations in daily living activities due to the disease, and 91.9% reported having social support. Mean scores were 58.03 ± 15.80 on the CAFS and 64.19 ± 6.41 on the PAIS-SR. Significant differences were observed in fatigue and psychosocial adjustment scores based on gender, social support, and disease impact on daily activities (p < 0.05). A weak positive correlation was found between fatigue levels and psychosocial adjustment (p < 0.05). COPD patients experience moderate-to-high fatigue levels and challenges in psychosocial adjustment, with fatigue negatively influencing adjustment. Interventions should focus on enhancing coping strategies, addressing psychosocial needs, and leveraging social support systems to improve patient outcomes.

Risk Factors and Predictors for Persistent Dyspnea Post-COVID-19: A Systematic Review.

The most frequently reported post-coronavirus disease of 2019 (COVID-19) symptoms include shortness of breath, fatigue, and cognitive disturbances, with reports of persistent dyspnea ranging between 26% and 41%. There is an urgent need to understand the risk factors and predictors for persistent COVID-19 dyspnea in individuals at all levels of COVID-19 illness severity, to enable the implementation of targeted interventions for those likely to be most affected with persistent dyspnea. Thus, the purpose of this systematic review is to explore the risk factors and predictors that are associated with persistent dyspnea in the post-COVID-19 population. This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines and registered prospectively in PROSPERO as CRD42023466713. A search strategy was conducted across PubMed, CINAHL, Web of Science, and EMBASE databases, that included studies conducted from 2020 to March 2024. The Covidence platform was used for screening studies, scoring methodologic quality, and performing data extraction using a two-step independent review process. This review included 33 studies, addressing 83,920 participants across 20 countries. The strongest predictive risk factors for persistent dyspnea included the following: female sex, elevated body mass index, pulmonary comorbidities, pre-existing anxiety and depression, pre-COVID-19 physical limitations, the severity of the COVID-19 illness, and socioeconomic differences. Potential risk factors included increased age, smoking history, and COVID-19 variant type. The presence of biomarkers for persistent dyspnea in the post-COVID-19 population can be used by clinicians to prospectively identify those individuals who should be flagged. Early identification may then be leveraged for timely referral for prophylactic and rehabilitative interventions for dyspnea. A personalized plan to target those risk factors that are modifiable should follow.

ВИЗНАЧЕННЯ ВПЛИВУ ЕРГОНОМІЧНИХ ФАКТОРІВ НА ПРОЦЕС ФІЗКУЛЬТУРНО-СПОРТИВНОЇ РЕАБІЛІТАЦІЇ

Relevance of the research topic. To date, the scientific and methodological literature presents a large number of studies related to physical education and sports rehabilitation. At the same time, the studies do not fully cover the issue of the influence of ergonomic factors on the process of physical education and sports rehabilitation of war veterans with disabilities or limitations of daily functioning. The purpose of the article is to determine the impact of ergonomic factors on the process of conducting physical education and sports rehabilitation classes with war veterans with disabilities or limitations in daily functioning. Research methods. Analysis and synthesis of data from educational, scientific and methodological literature, the method of expert evaluation and methods of mathematical statistics. Results and conclusions. 1. The need to improve the effectiveness of the process of physical education and sports rehabilitation of war veterans with disabilities and limitations in daily functioning is unquestionable, it is possible to achieve this through the use of ergonomics, but this issue is practically not covered in the scientific literature. 2. Expertise was conducted using the ranking method regarding the influence of different groups of factors on the effectiveness of physical education and sports rehabilitation classes with war veterans with disabilities, or limitations in daily functioning, the opinions of experts are in agreement, as evidenced by the value of the concordance coefficient W=0.78 at the level of significance p &lt;0.01. 3. The use of ergonomics tools in the process of conducting physical education and sports rehabilitation classes with war veterans with disabilities or limitations in daily functioning is appropriate and can significantly increase the effectiveness of physical culture and sports rehabilitation. In particular, in the location of equipment, lighting and ventilation, compliance with building regulations for persons with disabilities in the premises where classes are held, the use of specialized simulators that allow taking into account physical limitations when performing physical exercises, the use of modern virtual reality technologies or movement monitoring and analysis systems.

Principles and Applications of Two-Dimensional Semiconductor Material Devices for Reconfigurable Electronics

With the advances in edge computing and artificial intelligence, the demands of multifunctional electronics with large area efficiency are increased. As the scaling down of the conventional transistor is restricted by physical limits, reconfigurable electronics are developed to promote the functional integration of integrated circuits. Reconfigurable electronics refer to electronics with switchable functionalities, including reconfigurable logic operation functionalities and reconfigurable responses to electrical or optical signals. Reconfigurable electronics integrate data-processing capabilities with reduced size. Two-dimensional (2D) semiconductor materials exhibit excellent modulation capabilities through electrical and optical signals, and structural designs of 2D material devices achieve versatile and switchable functionalities. 2D semiconductors have great potential to develop advanced reconfigurable electronics. Recent years witnessed the rapid development of 2D material devices for reconfigurable electronics. This work focuses on the working principles of 2D material devices used for reconfigurable electronics, discusses applications of 2D-material-based reconfigurable electronics in logic operation and artificial intelligence, and further provides a future outlook for the development of reconfigurable electronics based on 2D material devices.

Constraints to the drag-based reverse modeling

One of the most widely used space weather forecast models to simulate the propagation of coronal mass ejections (CMEs) is the analytical drag-based model (DBM). It predicts the CME arrival time and speed at Earth or at a specific target (planets, spacecraft) in the Solar System. The corresponding drag-based ensemble model (DBEM) additionally takes into account the uncertainty of the input parameters by making n ensembles and provides the most probable arrival time and speed as well as their uncertainty intervals. An important input parameter for DBM and DBEM is the drag parameter γ, which depends on the CME cross-section and mass, as well as the solar-wind density. The reverse-modeling technique applied to the DBM allows us to derive γ values that minimize transit time (TT) and arrival-speed (v_tar) errors. The present study highlights the limitations and constraints of such a procedure. We searched for optimal γ values that would yield the perfect TT within one hour of the actual observed CME transit time as well as perfect v_tar within ±75 km,s^-1. This optimal window for v_tar was found by increasing v_tar from ±10 to ±100 km,s^-1, where the ±75 km,s^-1 window gave the perfect TT and v_tar in the case of 87% of CMEs compared to the ±10 km,s^-1 window, which was used in some previous reverse-modeling studies and gave optimal results for only 45% of the events from our CME list. For our analysis, a 31 CME-ICME pair sample is used from the period spanning 1997 to 2018. The reverse-modeling method is applied using the DBEMv3 tool for different γ ranges from 0.01 to 10 times km^-1. We tested whether and how the obtained optimal γ depends on the chosen γ range. By increasing the γ range, we find that the optimal γ converges to a certain value for two thirds of the analyzed events. The highly constrained γ ranges resulted in shifted and skewed γ distributions. By using the largest γ range (0.01--10 times 10^ km^-1), the medians of the optimal γ distributions are obtained for two thirds of the events in the common operational DBEMv3 range of 0.01--0.5 times 10^ km^-1. We also found that the important quantity in determining the range of γ distribution and ability to find an optimal γ is the difference between the CME launch speed and the solar-wind speed (v_0-w), which together with γ define the drag acceleration in the DBM. For small v_0-w differences (e.g., &lt; 200 km,s^-1), the reverse modeling may not be the appropriate method to find the optimal γ due to large divergence of γ values found, which may additionally be caused by larger input uncertainties and physical model limitations in turn leading to inappropriate γ values.

Making semaglutide accessible in Pakistan: A crucial step for heart failure treatment

Madam, In 2019, the FDA approved a new Semaglutide pill to help adults with type 2 diabetes control their blood sugar.1 This medication works because it mimics a natural hormone called glucagon-like peptide-1 (GLP-1).1,2 Originally, it was considered an add-on treatment for people who already take other medications.1 But in January 2023, the FDA updated the approval so that Semaglutide can be used as the first medication for some adults with type 2 diabetes, along with healthy lifestyle changes.1 Recently,a SELECT trial was conducted, which shows its renoprotective function.4 Beyond these uses, research exposes the potential of semaglutide to dramatically improve heart health, even slashing the risk of death and heart failure.1,2,4 Although this holds an importance for heart failure patients, the greater importance of it comes from the fact that it has shown beneficial results in heart failure with preserved ejection fraction patients too, which is a type of heart failure that’s predominant among diabetic and obese individuals.3 This makes it a drug of interest in cardiology as we have only a limited number of drugs to treat the hopeful population. This letter examines the expanded role of Semaglutide, encompassing its existing uses and emerging application in hfpEF treatment. A new study by Michael et al., published in The New England Journal of Medicine in April 2024, investigated the use of Semaglutide for obese patients with heart failure with preserved ejection fraction (HfpEF) and type 2 diabetes (DM2). This double-blind, randomized, multinational trial enrolled 616 participants from 16 countries and compared Semaglutide treatment (STEP-HfpEF DM trial) to a placebo control group.The study included adults aged 18 and over with a body mass index (BMI) of 30 or greater who had been diagnosed with both HfpEF and DM2. Half the participants received once-weekly Semaglutide injections for a year, while the others received a placebo. Compared to the placebo group, those taking Semaglutide for the next 52 weeks showed significant improvements in heart failure symptoms and physical limitations (13.7 point increase vs. 6.4 point increase). Additionally, the Semaglutide group experienced a substantial weight loss (9.8% reduction) and a greater improvement in their six-minute walk test distance (12.7 meters on average).2 However,17.7% of participants reported side effects such as gastrointestinal disorders and infections.However, the overall findings suggest this drug may significantly improve heart failure symptoms, physical function, and weight loss in obese patients with HfpEF and DM2, with acceptable side effects.2,5 ---Continue

Optical Based Methods for Water Monitoring in Biological Tissue.

Skin homeostasis is strongly dependent on its hydration levels, making skin water content measurement vital across various fields, including medicine, cosmetology, and sports science. Noninvasive diagnostic techniques are particularly relevant for clinical applications due to their minimal risk of side effects. A range of optical methods have been developed for this purpose, each with unique physical principles, advantages, and limitations. This review provides an in-depth examination of optical techniques such as diffuse reflectance spectroscopy, optoacoustic spectroscopy, optoacoustic tomography, hyperspectral imaging, and Raman spectroscopy. We explore their efficacy in noninvasive monitoring of skin hydration and edema, which is characterized by an increase in interstitial fluid. By comparing the parameters, sensitivity, and clinical applications of these techniques, this review offers a comprehensive understanding of their potential to enhance diagnostic precision and improve patient care.

‘We can only grow grass here’: Unsettling the traditionality of grassland narrative

Abstract Ruminant livestock farming is predominant in England’s grassland regions, including the south-west of England (SWE). The common farming view that such regions are only good for growing grass amounts to a simplistic ‘traditionality of grasslands’ (TOG) narrative, which may discount the potential of these regions to align food production with diverse, sustainable consumption. We interrogate the assumptions underlying the TOG narrative through the analysis of contemporary and historical agricultural data sources and recent interviews with SWE food producers to reveal an SWE traditionality of mixed farming and diverse food production. By unsettling the TOG narrative, we draw attention to multiple elements intertwining physical limitations of land with powerful but mutable human-made limitations of the wider food system as drivers of land use in the SWE, underscoring the role and responsibility of policymakers to ensure wider dynamics of the food system enable the transition to diverse, sustainable food production in England’s grassland regions.

Safe self-adjusting trajectory tracking control method for air cushion vehicle

ABSTRACT The safety of autonomous driving systems is a critical factor in the operation of high-speed air cushion vehicle (ACV). This paper presents a safety-guaranteed trajectory tracking controller for ACV. A safe self-adjusting speed guidance law is developed based on the finite-time auxiliary system. It can autonomously regulate tracking errors in accordance with the vehicle’s motion states and control inputs. Building on this framework, a trajectory tracking controller is developed utilising Lyapunov stability theory and finite-time control techniques to ensure safe operation. The stability of the proposed controller is rigorously proven. Simulation results demonstrate that the controller effectively mitigates tracking errors, ensuring that key motion parameters – such as speed, turn rate and drift angle – remain within predefined safety limits. Moreover, the control signals generated by the controller are shown to be compatible with the physical limitations of the vehicle’s actuators during trajectory tracking.

Impact of paralympic sports on the resilience of people with disabilities: evaluation and key analysis

Objective: The aim of this study was to compare the degree of resilience in people with motor disabilities, both those who do and do not practice para-sports. Methodology: This cross-sectional, quantitative study was conducted with 351 para-athletes (PDAP - X̄ = 30.9 ± 11.7 years) and 90 non-practicing individuals with motor disabilities (PDNP - X̄ = 31.6 ± 9.3 years). Data collection was performed using a Google Forms questionnaire that included assessments of socioeconomic profile and resilience profile using the Wagnild and Young Resilience Scale. The data were analyzed using Chi-Square non-parametric tests, with significance set at p &lt; 0.05. Results: Both groups displayed homogeneous characteristics. Notably, 79.5% of para-athletes were male, while 40.0% of non-athletes were white. Most had incomplete high school, with a higher percentage among para-athletes (40.1%). The most common labor activity was "Works and takes care of family" (38.8%). PDAP scored higher in self-sufficiency (∆% = 22.0%, p = 0.037) and serenity (∆% = 51.2%, p = 0.025). In total, 81.6% showed high resilience, with PDAP significantly more likely to be in the high resilience category (∆% = 44.3%, p = 0.008). Given that the calculated power of this experiment indicates an 88% possibility of extrapolation to other sample groups (with a β error = 12%), these findings are robust and highly generalizable. Conclusion: Despite their physical disabilities, para-athletes demonstrated higher resilience than non-athletes, suggesting that para-sports may help them overcome physical limitations.

Plasmonic Single-Molecule Affinity Detection at 10-20 Molar.

DNA can be readily amplified through replication, enabling the detection of a single-target copy. A comparable performance for proteins in immunoassays has yet to be fully assessed. Surface-plasmon-resonance (SPR) serves as a probe capable of performing assays at concentrations typically around 10⁻⁹ molar. In this study, plasmonic single-molecule assays for both proteins and DNA are demonstrated, achieving limits-of-detections (LODs) as low as 10⁻2⁰ molar (1±1 molecule in 0.1mL), even in human serum, in 1 h. This represents an improvement in typical SPR LODs by eleven orders-of-magnitude. The single-molecule SPR assay is achieved with a millimeter-wide surface functionalized with a physisorbed biolayer comprising trillions of recognition-elements (antibodies or protein-probe complexes) which undergo an acidic or alkaline pH-conditioning. Potentiometric and surface-probing imaging experiments reveal the phenomenon underlying this extraordinary performance enhancement. The data suggest an unexplored amplification process within the biomaterial, where pH-conditioning, driving the biolayer in a metastable state, induces a self-propagating aggregation of partially misfolded proteins, following single-affinity binding. This process triggers an electrostatic rearrangement, resulting in the displacement of a charge equivalent to 1.5e per 102 recognition elements. Such findings open new opportunities for reliable SPR-based biosensing at the physical detection limits, with promising applications in point-of-care plasmonic systems.

Random resistive memory-based deep extreme point learning machine for unified visual processing

Visual sensors, including 3D light detection and ranging, neuromorphic dynamic vision sensor, and conventional frame cameras, are increasingly integrated into edge-side intelligent machines. However, their data are heterogeneous, causing complexity in system development. Moreover, conventional digital hardware is constrained by von Neumann bottleneck and the physical limit of transistor scaling. The computational demands of training ever-growing models further exacerbate these challenges. We propose a hardware-software co-designed random resistive memory-based deep extreme point learning machine. Data-wise, the multi-sensory data are unified as point set and processed universally. Software-wise, most weights are exempted from training. Hardware-wise, nanoscale resistive memory enables collocation of memory and processing, and leverages the inherent programming stochasticity for generating random weights. The co-design system is validated on 3D segmentation (ShapeNet), event recognition (DVS128 Gesture), and image classification (Fashion-MNIST) tasks, achieving accuracy comparable to conventional systems while delivering 6.78 × /21.04 × /15.79 × energy efficiency improvements and 70.12%/89.46%/85.61% training cost reductions.

Analisis Komunikasi Interpersonal Orang Tua dan Remaja Tunarungu Korban Bullying dalam Film Dear Frankie

Cases of bullying or what is known as bullying are a problem that never ends in society, especially among children and teenagers. This bullying behavior is carried out by stronger individuals against weaker individuals with the aim of hurting and intimidating. So children with special needs who have physical and mental limitations are often the victims of bullying. Problems that often occur in society require strong support from within or from the family to face external problems or the victim's environment. Therefore, interpersonal communication between parents is very important for children with special needs who are victims of bullying. This is presented in the film Dear Frankie, where there is interpersonal communication between Frankie's parents and Frankie, the child who is deaf. Where Frankie can act mature, independent and confident in facing his friend who is a bully.

Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA1c levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA1c. STEP-HFpEF DM, a double-blind, randomised, placebo-controlled trial conducted at 108 clinical research sites across 16 countries in Asia, Europe, and North and South America, included individuals aged 18 years or older with documented HFpEF (left ventricular ejection fraction ≥45%), type 2 diabetes, and obesity (BMI ≥30 kg/m2). Participants were randomly assigned (1:1), with a block size of four within each stratum using an interactive web response system, stratified by baseline BMI (<35 kg/m2vs ≥35 kg/m2), to receive either semaglutide 2·4 mg or placebo subcutaneously. The effects of semaglutide versus placebo on the efficacy endpoints were evaluated by HbA1c categories at baseline: low (<6·5%; <48 mmol/mol), medium (6·5% to <7·5%; 48 mmol/mol to <58 mmol/mol), and high (≥7·5%; ≥58 mmol/mol). The dual primary endpoints were change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and bodyweight percentage from baseline to 52 weeks and were assessed in all randomly assigned participants by intention to treat. Hypoglycaemia events were also analysed to assess safety in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04916470. Between June 27, 2021 and Sept 2, 2022, 616 participants were enrolled and randomly assigned (mean age 68·4 years [SD 8·9]; 273 [44%] were female, 343 [56%] were male, and 519 [84%] were White). The low baseline HbA1c group included 227 participants (112 assigned to semaglutide and 115 to placebo), the medium baseline HbA1c group included 226 participants (124 assigned to semaglutide and 102 to placebo), and the high baseline HbA1c group included 163 participants (74 assigned to semaglutide and 89 to placebo). The median duration of follow-up in the overall trial was 401 days (IQR 400-405). The change in KCCQ-CSS from baseline to 52 weeks was 12·4 points (95% CI 8·8 to 16·0) with semaglutide versus 5·7 points (2·1 to 9·2) with placebo (mean difference 6·7 points [1·6 to 11·8]) in the low baseline HbA1c group, 14·5 points (11·0 to 17·9) versus 8·5 points (4·8 to 12·2; 6·0 points [0·9 to 11·1]) in the medium baseline HbA1c group, and 14·5 points (10·0 to 19·0) versus 4·8 points (0·7 to 8·9; 9·6 points [3·5 to 15·7]) in the high baseline HbA1c group (pinteraction=0·64; ptrend=0·46). The change in bodyweight percentage from baseline to 52 weeks was -10·8 (95% CI -12·1 to -9·5) with semaglutide versus -3·3% (-4·6 to -2·0) with placebo (mean difference -7·5% [-9·4 to -5·6]) in the low baseline HbA1c group, -9·6% (-10·8 to -8·3) versus -3·3% (-4·7 to -1·9; -6·3 [-8·2 to -4·4]) in the medium baseline HbA1c group, and -8·6% (-10·2 to -7·0) versus -3·6% (-5·2 to -2·1; -5·0 [-7·2 to -2·7]) in the high baseline HbA1c group (pinteraction=0·22; ptrend=0·083). Hypoglycaemia events occurred in 30 (10%) of 310 participants (70 events; 22·9 events per 100 person-years) in the semaglutide group compared with 21 (7%) of 306 participants in the placebo group (90 events; 29·5 events per 100 person-years). Semaglutide 2·4 mg improved heart failure-related symptoms and physical limitations, and reduced bodyweight in patients with obesity-related HFpEF and type 2 diabetes, all independently of baseline HbA1c, and resulted in lower rates of hypoglycaemia than placebo, despite a well controlled baseline HbA1c and broad use of concomitant glucose-lowering medications. Novo Nordisk.