Measures Of Function Research Articles

Content comparison of multidimensional functional outcome measures in rehabilitation and the ICF clinical functioning information tool: A scoping literature review

Background: The ICF-based Clinical Functioning Information Tool (ClinFIT) was developed as a standardized tool to facilitate the assessment of functioning in clinical and, research settings. Objective: This review describes the contents of commonly used multidimensional outcome measures that describe functioning in rehabilitation settings and maps these measures to ICF categories covered by the ClinFIT to identify commonalities and discrepancies in the content. Methods: A scoping review included a systematic search of PubMed, Embase, Cochrane Library, and other resources. Twelve outcome measures were selected, and their meaningful concepts were linked to the ClinFIT by 2 authors using established ICF linking rules. Content density, bandwidth, and content diversity indices were calculated for each measure. Results: A total of 369 meaningful concepts from the 292 items from 12 measures were selected. Of these, 293 (79.4%) concepts were linked to the ClinFIT categories, with a majority (80.5%) linked to “activities and participation”; however, 76 (20.6%) meaningful concepts could not be linked to any ClinFIT categories. The extent of content coverage varied significantly between measures, reflecting the differences in the scope of each measure. The “activity and participation” categories had the highest bandwidth for all measures (range: 28.6%–71.4%), while the “body function” category was less represented (range: 0%–33.3%). Conclusions: ClinFIT can be the useful outcome measure for functional assessment in rehabilitation settings, as it covers wider concepts, considered important in rehabilitation settings, compared with other common functional outcome measures. It can establish comparability of a minimal data set on functional outcomes across various medical conditions and settings.

Natural assets, changes, and variations of the socioeconomic-environmental systems along the Asian drylands belt

Abstract The amount of and changes in a country's natural assets are crucial for developing national strategic plans and policies due to their foundational role in determining the resilience of social-environmental systems (SES), especially under a changing climate. Many integrated metrics on natural assets have been proposed based on individual measures to provide insights into the state of national natural resources. This is particularly true for countries experiencing extreme environmental stresses. Drawing on longitudinal data spanning from 1980 to 2020, the objective of this study is to analyze nuanced distinctions across 23 political entities (PEs) in the dryland regions of mid-latitudinal Asia, investigating their interannual variabilities over the four-decade study period and discerning potential driving forces. We examined three key integrated measures of the SES: ecosystem water use efficiency (WUE), human appropriation of net primary production (HANPP), and human appropriation of water resources (HAWR). We found increased variability as well as spikes in extreme values in each of these three measures of SES function among the 23 PEs over the study period. Water stress played an increasing and more important role than temperature in influencing the magnitude and variations of the three measures. Our results also indicate that human interventions may help increase the efficiency of water use in this dryland region of the world.

Fermatean fuzzy score function and distance measure based group decision making framework for household waste recycling plant location selection.

The household waste (HW) disposal and recycling have become a significant challenge due to increasing quantities of generated household wastes and increased levels of urbanization. Selecting locations/sites for building new HW recycling plant comprises numerous sustainability dimensions, thus, this work aims to develop new decision-making model for evaluating and prioritizing the HW recycling plant locations. This paper is categorized into three phases. First, we propose new improved score function to compare the Fermatean fuzzy numbers. Moreover, an example is presented to validate the effectiveness of proposed score function over the extant ones. Second, we introduce new distance measure to estimate the discrimination degree between Fermatean fuzzy sets (FFSs) and further discuss its advantages over the prior developed Fermatean fuzzy distance measures. Third, we introduce an integrated methodology by combining the method with the removal effects of criteria (MEREC), the stepwise weight assessment ratio analysis (SWARA) and the measurement alternatives and the ranking according to compromise solution (MARCOS) approaches with Fermatean fuzzy (FF) information, and named as the "FF-MEREC-SWARA-MARCOS" framework. In this method, the FF-distance measure is used to find the weights of involved decision-making experts. Moreover, an integrated criteria weighting method is presented with the combination of MEREC and SWARA models under the context of FFSs, while the combined FF-MEREC-SWARA-MARCOS model is applied to evaluate and prioritize the locations for HW recycling plant development, which illustrates its feasibility of the developed framework. Comparative study and sensitivity assessment are conducted to validate the obtained outcomes. This work provides a hybrid decision analysis approach, which marks a significant impact to the HW recycling plant location selection process with uncertain information.

Creative music therapy in preterm infants effects cerebrovascular oxygenation and perfusion.

Creative music therapy (CMT) has been shown to promote the development of brain function and structure in preterm infants. We aimed to investigate the effect of CMT on cerebral oxygenation and perfusion to examine how the brain reacts to CMT. Absolute levels of cerebrovascular oxygen saturation (StO2) were measured in clinically stable preterm-born neonates (n = 20, gestational age: ≥30 weeks and < 37 weeks) using two near-infrared spectroscopy (NIRS)-based tissue oximeters over the right prefrontal cortex and left auditory cortex. We applied the systemic physiology augmented functional NIRS approach. Each CMT session lasted 55min and involved 9 intervals, including two 10-minute intervals during which the music therapist hummed and held the neonate. We found that CMT-induced changes in cerebrovascular StO2, perfusion and systemic physiology (i) could be classified into two groups (group 1: increase in StO2 during the first singing interval, group 2: decrease in StO2), (ii) differed in female neonates compared to male neonates, and (iii) correlated with individual blood haematocrit levels. Our exploratory study (i) demonstrates the impact of CMT on the neonate's physiology and (ii) highlights the need to analyze functional NIRS measurements in neonates separately according to their response pattern to avoid erroneous conclusions, e.g. when only the group average of the signal change is determined.

Patient-Reported Outcomes in RLBP1 Retinal Dystrophy: Longitudinal Assessment in a Prospective Natural History Study.

To evaluate the performance of two non-disease-specific patient-reported outcome (PRO) instruments, the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and the Low Luminance Questionnaire (LLQ), in patients with retinaldehyde-binding protein 1 retinal dystrophy (RLBP1 RD). PROs were assessed using the VFQ-25 and LLQ. Rasch analysis was conducted to estimate person and item measures of the VFQ-25 and LLQ questionnaires to determine the association between the two PROs. In addition, the association between these two instruments and their correlations to weighted measures of visual function and disease progression were analyzed in this three-year PRO-focused sub-study of a five-year prospective natural history study. Forty-two patients participated, with most of them having completed at least two PRO follow-up visits at least one year apart. The mean VFQ-25 scores were lowest for distance activities (39.2-49.0) and peripheral vision (37.5-52.4), with mean LLQ subscale scores generally low (<41), except for the emotional distress subscale. Using Rasch analysis, calibrated item and person measures along with their standard errors were estimated for both ePROs. This indicated that the distribution of the VFQ-25 and LLQ item measures well covered the distribution of person function in this group. This suggests that the item difficulties well cover the person-level performance in this population. As well, the two PROs showed a strong and significant correlation at all assessed time points as assessed with Pearson correlation coefficient (0.81, 0.91, 0.81 and 0.87 at baseline, 1/1.5, 2/2.5 (P < 0.001) and 3/3.5 years (P = 0.002)). The composite scores of both PRO questionnaires strongly correlated with clinical measures of visual function. At 2 to 2.5 years of follow-up, meaningful statistically significant declines in peripheral vision (both VFQ-25 and LLQ), distance vision (VFQ-25), and extreme lighting in dark and bright light (LLQ) subscales were noted. This study demonstrated a strong association between VFQ-25 and LLQ scores and their association with clinical measures of visual function. PRO instruments can provide insights into the specific disabilities of this unique patient population and help to guide appropriate outcome measures for future clinical trials.

BIFROST: A method for registering diverse imaging datasets of the Drosophila brain

Imaging methods that span both functional measures in living tissue and anatomical measures in fixed tissue have played critical roles in advancing our understanding of the brain. However, making direct comparisons between different imaging modalities, particularly spanning living and fixed tissue, has remained challenging. For example, comparing brain-wide neural dynamics across experiments and aligning such data to anatomical resources, such as gene expression patterns or connectomes, requires precise alignment to a common set of anatomical coordinates. However, reaching this goal is difficult because registering in vivo functional imaging data to ex vivo reference atlases requires accommodating differences in imaging modality, microscope specification, and sample preparation. We overcome these challenges in Drosophila by building an in vivo reference atlas from multiphoton-imaged brains, called the Functional Drosophila Atlas. We then develop a registration pipeline, BrIdge For Registering Over Statistical Templates (BIFROST), for transforming neural imaging data into this common space and for importing ex vivo resources such as connectomes. Using genetically labeled cell types as ground truth, we demonstrate registration with a precision of less than 10 microns. Overall, BIFROST provides a pipeline for registering functional imaging datasets in the fly, both within and across experiments.

Exploring whether home-based neuromodulation can boost the analgesic effects of exercise in people with knee osteoarthritis: protocol for a double-blinded, pilot randomised controlled trial

IntroductionKnee osteoarthritis (OA) represents a leading cause of disability globally. Exercise has been demonstrated to improve pain and function in people with knee OA. However, when in pain, commencement of...

Evaluation of a six-minute walk test in the DE50-MD canine model of Duchenne muscular dystrophy and its effect on blood-borne biomarkers

Background Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by mutations in the dystrophin gene resulting in cycles of muscle degeneration, inflammation and regeneration. The 6-minute walk test (6MWT) is a key functional outcome measure for DMD patient clinical trials and has been adapted for use in animal models of the disease. The DE50-MD dog model of DMD closely reflects the DMD patient phenotype prior to loss of ambulation. For pre-clinical trials using this model, functional outcome measures must be established. Methods This longitudinal study compared distance walked in a 6MWT by DE50-MD and WT control dogs and assessed the utility of the 6MWT as a functional biomarker. Dogs underwent two 6MWTs conducted approximately 48-hours apart, at 3, 6, 9, 12, 15 and 18 months of age. In addition, we evaluated the stability of selected blood-borne biomarkers in 12-month old DE50-MD and WT dogs 0, 3, 6, 24 and 48 hours following a 6MWT. Results DE50-MD dogs exhibited significantly shorter 6-minute walk distance (6MWD) than WT dogs at all timepoints (P&lt;0.05), with no difference in 6MWD between the first and second 6MWT. C-C motif chemokine ligand 2 (CCL2), myomesin-3 (MYOM3) and myostatin (MSTN) were biomarkers of the DE50-MD phenotype that remained unchanged in DE50-MD dogs following the 6MWT, while creatine kinase (CK) activity significantly increased 3-hours following the test in DE50-MD dogs but remained unchanged in WT dogs. Conclusions The 6MWT effectively discriminates DE50-MD from WT dogs aged 3-18 months and a single 6MWT is sufficient for future studies. Serum MYOM3, CCL2 and MSTN are good biomarkers of the DE50-MD phenotype that are unaffected by this relatively low level exertion.

Characteristics of cerebellar cognitive affective syndrome in patients with acute cerebellar stroke and its impact on outcome

Purpose To evaluate the cerebellar cognitive affective syndrome scale (CCAS-S) in patients with acute cerebellar stroke (ACS) and examine its relationship with the discharge destination. Methods Patients with first-time ACS admitted to our hospital between April 2021 and April 2023 were included. The CCAS-S, Mini-Mental State Examination (MMSE), and Scale for the Assessment and Rating of Ataxia (SARA) were evaluated 1 week after stroke onset, and Functional Independence Measure (FIM)/Barthel Index (BI) at discharge, duration of hospitalization, and discharge destination were evaluated. The Mann–Whitney U test was used to compare CCAS-S and variables. Results Thirteen consecutive patients with ACS and age-matched comparison groups were included. The MMSE was within the normal range in all patients; however, patients with stroke had a lower total CCAS-S score (median 72, IQR 66–80) and a higher number of failed tests (median 4, IQR 3–5) than comparison. Significant deficits were observed in semantic fluency (p = 0.008), category switching (p = 0001), and similarity (p = 009). Definite CCAS were diagnosed 10 patients, respectively. Patients discharged home showed better SARA and FIM/BI but similar CCAS-S compared to those discharged to rehabilitation hospitals. Conclusion In patients with ACS, it is the impairment of motor function, not CCAS, that affects discharge destination.

Retinal Patterns and the Role of Autofluorescence in Choroideremia

Background: Choroideremia is a monogenic inherited retinal dystrophy that manifests in males with night blindness, progressive loss of peripheral vision, and ultimately profound sight loss, commonly by middle age. It is caused by genetic defects of the CHM gene, which result in a deficiency in Rab-escort protein-1, a key element for intracellular trafficking of vesicles, including those carrying melanin. As choroideremia primarily affects the retinal pigment epithelium, fundus autofluorescence, which focuses on the fluorescent properties of pigments within the retina, is an established imaging modality used for the assessment and monitoring of affected patients. Methods and Results: In this manuscript, we demonstrate the use of both short-wavelength blue and near-infrared autofluorescence and how these imaging modalities reveal distinct disease patterns in choroideremia. In addition, we show how these structural measurements relate to retinal functional measures, namely microperimetry, and discuss the potential role of these retinal imaging modalities in clinical practice and research studies. Moreover, we discuss the mechanisms underlying retinal autofluorescence patterns by imaging with a particular focus on melanin pigment. Conclusions: This could be of particular significance given the current progress in therapeutic options, including gene replacement therapy.

4DCT image artifact detection using deep learning.

Four-dimensional computed tomography (4DCT) is an es sential tool in radiation therapy. However, the 4D acquisition process may cause motion artifacts which can obscure anatomy and distort functional measurements from CTscans. We describe a deep learning algorithm to identify the location of artifacts within 4DCT images. Our method is flexible enough to handle different types of artifacts, including duplication, misalignment, truncation, andinterpolation. We trained and validated a U-net convolutional neural network artifact detection model on more than 23000 coronal slices extracted from 98 4DCT scans. The receiver operating characteristic (ROC) curve and precision-recall curve were used to evaluate the model's performance at identifying artifacts compared to a manually identified ground truth. The model was adjusted so that the sensitivity in identifying artifacts was equivalent to that of a human observer, as measured by computing the average ratio of artifact volume to lung volume in a givenscan. The model achieved a sensitivity, specificity, and precision of 0.78, 0.99, and 0.58, respectively. The ROC area-under-the-curve (AUC) was 0.99 and the precision-recall AUC was 0.73. Our model sensitivity is 8% higher than previously reported state-of-the-art artifact detectionmethods. The model developed in this study is versatile, designed to handle duplication, misalignment, truncation, and interpolation artifacts within a single image, unlike earlier models that were designed for a single artifact type.

The effect of topical medications on olfactory function: Barrier therapy

Introduction. Sensory organs help humans exist in the surrounding world, but the evaluation of olfaction remained “in the shadows” practically until the COVID-19 pandemic, although many questions are still insufficiently studied, such as the effect of intranasal medications on olfactory function.Aim. To assess the olfactory function in healthy volunteers before and after a course of using an ectoine nasal solution.Materials and methods. Under our observation were healthy volunteers (medical university students and healthcare workers aged 16 to 35 years) who, in addition to routine ENT examinations, underwent an assessment of their olfactory status using a professional set of odorants for olfactometry and subjectively using a self-assessment scale for olfaction before and after a course of ectoine nasal solution, as well as a self-assessment of its preventive effect. The collected data were recorded in Excel spreadsheets (Microsoft Office 365) for further statistical analysis.Results and discussion. The results showed an average increase of 1 point in the self-assessment of olfaction in the observation group, as well as an increase in the number of “correct” responses when using the set of odorants. However, discrepancies were noted between self-assessment and the objective evaluation of olfaction. The extent of the preventive effect (based on the self-assessment by participants using a 10-point visual analog scale) was rated at 5 points.Conclusions. 1. A one-month course of barrier therapy (ectoine nasal solution) does not cause any impairment in olfactory function, as evidenced by olfactometric testing (an average increase of 10% in correct responses across the group, with 80% of participants showing improvement) and olfaction self-assessment (an average increase of 1 point across the group, with 55% of participants showing improvement). 2. Self-assessment of olfaction cannot be considered a reliable measure of the actual olfactory function. 3. The use of barrier therapy (ectoine nasal solution) has a moderate preventive effect (5 points).

Worry about online fraud and older adults: Avoidant and protective responses

Given that cyber-enabled fraud makes up the vast majority of digital crime suffered by older adults, the impact of victimisation on this demographic group is of academic and practical relevance. This article examines the relationship between cyber fraud victimisation, worry about cyber fraud, and online avoidant behaviours and protective responses in older adults. The data come from the 2019 Special Eurobarometer 499, and the sample is made up of 6,257 Internet users aged 60 years and above. In addition to suffering cyber-enabled fraud, we also analyse various factors, such as the respondent's sex and knowledge of risks, which have been found to be associated with fear or worry about crime in other contexts. Our findings show that the respondent's sex and having experienced prior victimisation of oneself or family and friends is related to greater worry about online fraud. Moreover, we find that fraud victimisation of friends and family, knowledge of risks, and perceived self-efficacy are associated with dysfunctional avoidant behaviours and the adoption of functional security measures. We discuss the results in relation to gendered fear of crime socialisation and in terms of interventions with older adults that aim to respond to victimisation and to combat the digital divide.

Equine assisted services - an intervention in the motor disorders of a child with cytomegalovirus sequelae

Cytomegalovirus infection (CMV) represents the most prevalent infection correlated with congenital neurological impairment. After infection occurs several factors contribute for the child to have motor development deficits and possibly present several neurological manifestations. Equine assisted services- therapeutic and educational method that uses the horse within an interdisciplinary approach has shown positive results in the intervention of neurological dysfunctions. The objective to analyze the effect of equine assisted services on the gross motor function of a participant with sequelae caused by CMV infection. A quantitative and descriptive case study. It consisted of assessments pre- and post-equine assisted services interventions using the Gross Motor Function Measure (GMFM). The child participating in the study is classified as level III according to the Gross Motor Function Classification System (GMFCS). The results indicate a percentage increase in the total average between the pre- and post-intervention assessments, with results of 31.9 and 50.3%, respectively, and evolution in three of the five dimensions assessed through the GMFM, which are: lying and rolling, sitting, crawling and kneeling. It is concluded that equine assisted services are an effective tool for improving gross motor function of a participant with sequelae caused by cytomegalovirus infection.

Abstract 4126628: Worse Cardiac Structure and Function is Associated with Decline in Multiple Domains of Cognitive Function: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Cognitive impairment is cross-sectionally associated with worse cardiac structure/function. However, limited data exist regarding cardiac structure/function and longitudinal changes in cognitive function. Objective: Determine the association of cardiac structure and function with longitudinal changes in cognitive performance in late life. Methods: Among HF- and dementia-free participants in the community-based ARIC study who attended the 5th study visit (V5; 2011-2013), underwent protocol echocardiography, and completed a neurocognitive test battery at both V5 and study Visit 6 (V6; 2015-17), we assessed associations of cardiac structure and function measures with changes in both domain-specific and global cognitive scores between V5 and V6 using multivariable linear regression. Models were initially adjusted for demographics and education level, with additional models further adjusting for cardiovascular risk factors and disease at both V5 and V6. The neuropsychological test battery consisted of 10 neuropsychological tests that covered 3 domains of cognitive function: memory, executive functioning, and language. Factor scores were constructed for each cognitive domain, and their average represented a global composite score. Results: Among 2,988 included participants, mean age was 74±5 years, 60% were female, 20% reported Black race, and mean LVEF was 66±6%. Over a mean of 4.9±0.6 years (the V5 to V6 interval), raw scores declined for all neuropsychological tests. In fully adjusted models, worse diastolic function (larger LAVi) and LV remodeling (greater LV mass index) were associated with decline in executive function. Lower LVEF was associated with decline in language function, while worse LV longitudinal strain – a more sensitive measure of systolic dysfunction – was associated with decline in executive function, language function, and global cognition performance (all p&lt;0.05; Table). Conclusion: Subclinical LV remodeling and dysfunction is associated with greater declines in cognitive function over 5 years in late life. Differential associations were observed by cognitive domains, with executive function decline most uniformly associated with impairments in cardiac structure/function.

Abstract 4132909: Hemodynamic Indices of Right Ventricular Function Differentially Predict Adverse Clinical Outcomes in Heart Failure with Preserved vs Reduced Ejection Fraction

Background: While the critical role of right ventricular dysfunction (RVD) in heart failure (HF) is increasingly recognized, the prevalence and prognostic impact of RVD across HF subtypes is poorly understood. Research Questions/Aims: We aimed to characterize differences in hemodynamic indices of RV function among patients with HF with preserved vs reduced ejection fraction (HFpEF, EF≥50% vs HFrEF, EF&lt;50%) and to examine associations of RVD with longitudinal clinical outcomes by HF subtype. Methods: We identified patients with prevalent HF undergoing clinically indicated right heart catheterization at Massachusetts General Hospital (2005-2016). We examined three RV hemodynamic indices: right atrial to wedge pressure ratio (RA/PCWP), RV stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPi). We used multivariable linear regression to assess differences in RV indices in HFpEF vs HFrEF. We then used Cox models to examine the association of each index with HF hospitalizations (HFH), major adverse cardiac events (MACE), and death, stratified by HF subtype. Models were adjusted for age, sex, BMI, hypertension, diabetes, lung disease, sleep apnea, and prior MI. Results: Of 2,062 patients (age 66 years, 33% women), 1,242 (60%) had HFrEF and 820 (40%) had HFpEF. RVD (RVSWI &lt;450 mm Hg*ml/m 2 ) was present in 27% of HFrEF vs 21% of HFpEF patients. Those with HFpEF had higher RA/PCWP (β 0.12, SE 0.05, p=0.012) and RVSWI (β 0.22, SE 0.05, p&lt;0.001) relative to HFrEF. Over 4.1 median years follow-up, 915 HFH, 1,066 MACE, and 1,116 death events occurred. Among those with HFrEF, lower PAPi was associated with greater risk of HFH (HR 0.84 (0.77, 0.92); p&lt;0.001) and MACE (HR 0.88 (0.81, 0.96); p=0.003), and higher RVSWI was associated with greater risk of death (HR 1.17, (1.07, 1.27); p&lt;0.001, Figure ). In contrast, in those with HFpEF, only higher RA/PCWP was associated with greater risk of death (HR 1.11 (1.00, 1.23); p=0.042). Conclusion: RVD occurs frequently in both HFrEF and HFpEF, and hemodynamic measures of RV function are associated with greater risk of MACE, death, and HFH. Importantly, the prognostic value of RV indices varied by HF subtype, highlighting key differences in the role of RVD in HFrEF vs HFpEF.

Abstract 4134460: Application of Principal Component Analysis to Heterogenous Fontan Registry Data to Identify Independent Contributing Factors to Decline

Introduction: Single ventricle heart disease is a severe and life-threatening illness, and improvements in clinical outcomes of those with Fontan circulation have not yet yielded acceptable survival over the past two decades. Patients are at risk of developing a diverse variety of Fontan-associated comorbidities that may ultimately require heart transplant. Goal: Our study goal was to determine if principal component analysis (PCA), which determines unique directions of data variance, applied to data collected from a pediatric Fontan cohort can predict functional decline (N=140). Methods: Heterogeneous data broadly consisting of measures of cardiac and vascular function, exercise (VO 2max ), lymphatic biomarkers, and blood biomarkers were collected over 9 years at a single site as part of a prospectively applied clinical care pathway; in that time, 16 events occurred that are considered here in a composite adverse outcome measure. After standardization and PCA, principal components (PCs) representing &gt;5% of total variance were thematically labeled based on their constituents and tested for association with the composite outcome. Results: Our main findings suggest that the 6 th PC (PC6), representing 7.1% percent of the total variance in the set, is greatly influenced by albumin, alkaline phosphatase, total protein, BUN and BNP max and is a superior measure of proportional hazard compared to EF; it displayed the greatest accuracy for classifying Fontan patients as determined by AUC. In bivariate hazard analysis, we found that models combining systolic function (EF or PC5) and blood biomarkers (PC6) were most predictive, with the former having the greatest AIC, and the latter having the highest c-statistic. Conclusion: Our findings support the hypothesis that a broad, prospectively collected, multiorgan system model analyzed by way of unsupervised machine learning methods will improve prognosis of adverse outcomes in a Fontan cohort.

Abstract 4113164: Central Arterial Stiffness in Young Adults with Perinatal HIV Exposure

Intro: Young adults with perinatally acquired HIV (YPHIV) have higher morbidity and mortality than uninfected persons. Antiretroviral therapy (ART) has extended life expectancy making adult CV disease a concern. Perinatal exposure to HIV increases inflammation which is associated with increased arterial stiffness which predicts CV disease. Aims: We compared arterial stiffness between YPHIV and young adults perinatally HIV exposed but uninfected (YPHEU), and evaluated the association of type and duration of ART regimens, HIV disease severity, and cardiac structure and function with arterial stiffness. Methods: In a substudy of the Pediatric HIV/AIDS Cohort Study, 150 participants (95 YPHIV, 55 YPHEU, mean 23.4 yrs, 60% female, 72% Black, 24% Hispanic) had echocardiography and pulse wave velocity (PWV) measured. We compared PWV between YPHIV and YPHEU, adjusting for covariates. Among YPHIV, we fit linear regression models to evaluate the association of current (within 1 year of PWV) and historical measures of HIV disease severity with PWV. We computed correlations between PWV and measures of left ventricular (LV) structure and function, overall and by HIV status. Results: Mean PWV and hemodynamic parameters did not differ between YPHIV and YPHEU (YPHIV 5.63 vs YPHEU 5.39 m/s; p=0.5). HIV control was good (82% with viral load &lt;400 copies/ml), 91% used combination ART: integrase strand inhibitors (INSTIs; median duration 4.6 years), protease inhibitors (PIs 15.1 years), or non-nucleoside reverse transcriptase inhibitors (NNRTIs 5.2 years). Most participants had normal PWV compared to healthy controls but all values above 11.8 m/sec ( Figure , level associated with CV events in adults) were only in YPHIV. Only weak correlations were observed between PWV and echocardiographic measures (&lt;0.20) in both YPHEU and YPHIV. Among YPHIV, HIV severity measures were not associated with PWV using either current or historical measures. Mean PWV was 1.68 (-0.36, 3.72) m/s higher among YPHIV with current PI use than those on INSTIs, and 1.58 (-0.94, 4.11) m/s higher than those on NNRTIs, although these differences were not significant. Conclusions: PWV was within normal ranges in most YPHIV and YPHEU although 5% YPHIV had elevated PWV. PWV may be higher with PI use due to cardiometabolic side effects. Successful HIV treatment and control of traditional CV risk factors may prevent premature vascular aging and subsequent cardiac compromise in YPHIV.

Abstract 4118178: Echocardiographic Measure of Right Ventricular-Pulmonary Arterial Coupling Predicts Survival in Lung Cancer

Background: Echocardiographic indicators of pulmonary hypertension have been reported to predict decreased survival in lung cancer. We sought to test the hypothesis that this may be associated with impaired right ventricular (RV)-systolic pulmonary arterial pressure (sPAP) coupling, further enhancing the prognostic strength of echocardiography in lung cancer. Methods: This prospective observational study included 220 patients with non-small cell lung cancer (NSCLC) examined by Doppler, strain and 3D echocardiography before starting therapy. Prediction of overall survival was assessed by univariable analysis followed by multivariate Cox regression, receiver operating characteristic (ROC) curves and Kaplan-Meier analyses. Results: Echocardiographic examination was on average within normal limits, even though 30% of the patients had sPAP ≥35 mm Hg. In univariable analysis, overall survival was associated with measures of RV systolic function and probability of pulmonary hypertension. In multivariate Cox regression, only RV global longitudinal strain (GLS)/sPAP (HR: 5.766 [95% CI: 1.025–32.443]) and Eastern Cooperative Oncology Group performance status &lt;2 (HR: 0.332 [95% CI: 0.171–0.644]) independently predicted survival. The optimal ROC curve-derived RV GLS/sPAP cut-off to predict survival was −0.54%/mm Hg. Among patients in Union for International Cancer Control (UICC) stage 4, those with impaired RV-arterial coupling (RV GLS/sPAP &gt;−0.54%/mm Hg) had worse survival than those with maintained RV-arterial coupling (HR: 2.8 [95% CI: 1.5–5.3]); the latter subgroup had similar survival compared with patients in UICC stage 3 (HR: 0.57 [95% CI: 0.28–1.14]). Conclusion: RV GLS/sPAP as an echocardiographic measure of RV-arterial coupling adds to prognostication by the UICC status in NSCLC.

Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis refractory to biologic therapy: 2-year clinical and radiographic results from the open-label extension of the SELECT-AXIS 2 study.

The efficacy and safety of upadacitinib in patients with ankylosing spondylitis (AS) and inadequate response/intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR) were evaluated through 1 year in the SELECT-AXIS 2 study. Here, we assess 2-year efficacy, safety, and imaging outcomes in SELECT-AXIS 2. Patients who received continuous upadacitinib, and those who switched from placebo to upadacitinib at week 14, could enter the open-label extension (OLE). Efficacy endpoints included Assessment of SpondyloArthritis international Society (ASAS) and Axial Spondyloarthritis Disease Activity Score (ASDAS) responses, and changes from baseline in measures of disease activity, back pain, function, and quality of life. Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). As observed (AO) and AO with non-responder imputation (AO-NRI) analyses were used for binary endpoints; AO with mixed-effects model for repeated measures (AO-MMRM) for continuous endpoints; and AO-analysis of covariance for mSASSS. Treatment-emergent adverse events (TEAEs) in patients receiving ≥ 1 upadacitinib dose through week 104 are presented as events (E)/100 patient-years (PY). Subgroup analyses were performed by prior tumor necrosis factor/interleukin-17 inhibitor exposure and bDMARD lack of efficacy/intolerance. Of 420 patients who entered the bDMARD-IR AS study, 409 entered the OLE, and 331 (continuous upadacitinib, n = 163; placebo to upadacitinib, n = 168) completed week 104. Improvements in efficacy measures were sustained through the OLE, with similar response rates between the continuous upadacitinib and placebo to upadacitinib groups at week 104. At week 104, 64.9% and 61.7% of patients, respectively, had achieved ASAS 40% response (AO-NRI). Mean changes from baseline were similar between the two groups at week 104 across measures (ASDAS: -2.1 and -2.0; total back pain: -4.9 and -4.6, respectively; AO-MMRM). Over 93.0% of patients showed no radiographic progression (mSASSS mean change from baseline < 2) at week 104. The overall TEAE rate was 165.2 E/100 PY, with low rates of major adverse cardiovascular and venous thromboembolic events (0.3 E/100 PY each). Upadacitinib efficacy, including very low rates of radiographic progression, was demonstrated through 104 weeks in treatment-refractory patients with active AS. Treatment was well tolerated, with no newly identified safety signals. NCT04169373.