Total Assessment Score Research Articles

Teamwork matters: The association between nontechnical skills and cardiac arrest in trauma patients presenting with hypotension

BackgroundThe impact of trauma team dynamics on outcomes in injured patients is not completely understood. We sought to evaluate the association between trauma team function, as measured by a modified Trauma Non-Technical Skills assessment, and cardiac arrest in hypotensive trauma patients. We hypothesized that better team function is associated with a decreased probability of developing cardiac arrest. MethodsTrauma video review was used to collect data from resuscitations of adult hypotensive trauma patients at 19 centers. Hypotension at emergency department presentation was defined as an initial systolic blood pressure <90 mm Hg or an initial systolic blood pressure ≥90 mm Hg followed by a systolic blood pressure <90 mm Hg within the first 5 minutes. Team dynamics were scored using a modified Trauma Non-Technical Skills assessment composed of 5 domains with combined scores ranging from 5 (best) to 15 (worst). Scores were compared between cardiac arrest/noncardiac arrest cases in the trauma bay. Logistic regression was used to evaluate the independent association between the Trauma Non-Technical Skills assessment and cardiac arrest. ResultsA total of 430 patients were included (median age 43 years [interquartile range: 29–61]; 71.8% male; 36% penetrating mechanism; median Injury Severity Score 20 [10–33]; 11% experienced cardiac arrest in trauma bay). The median total Trauma Non-Technical Skills assessment score was 7 (6–9), higher in patients who experienced cardiac arrest in the trauma bay (9 [6–10] vs 7 [6–9]; P = .016). This association persisted after controlling for age, sex, mechanism, injury severity, initial systolic blood pressure, and initial Glasgow Coma Scale score (adjusted odds ratio: 1.28; 95% confidence interval:1.11–1.48; P < .001), indicating a ∼3% higher predicted probability of cardiac arrest per Trauma Non-Technical Skills point. ConclusionBetter team function is independently associated with a decreased probability of cardiac arrest in trauma patients presenting with hypotension. This suggests that trauma team training may improve outcomes in peri-arrest patients.

The relationship between social phobia and cognitive impairment in idiopathic generalized epilepsy patients: a cross-sectional study

Objectives: Epilepsy, a neurological disorder affecting approximately 65 million people worldwide, frequently presents with various comorbidities, including cognitive impairment. The factors contributing to cognitive impairment are complex and multifaceted. This study aimed to investigate the influence of social phobia on cognitive function in patients with idiopathic generalized tonic-clonic epilepsy. Methods: This prospective study recruited 87 adult idiopathic generalized tonic-clonic epilepsy patients diagnosed according to the International League Against Epilepsy 2017 classification. Differential diagnosis involved electroencephalography, magnetic resonance imaging, and neurological examinations. All participants were assessed for cognitive impairment, social phobia, depression, and anxiety using the Montreal Cognitive Assessment, Liebowitz Social Anxiety Scale, Beck Depression Inventory, and Beck Anxiety Inventory, respectively. Results: A significant majority (73.6%) of participants reported social phobia. Compared to those without social phobia, the Montreal Cognitive Assessment total score was significantly lower in the social phobia group (P=0.002). Additionally, epilepsy duration was significantly longer in the social phobia group (P=0.03). Montreal Cognitive Assessment scores showed a negative correlation with Liebowitz Social Anxiety Scale-avoidance, Liebowitz Social Anxiety Scale-total, and age (P=0.003, P=0.005, and P&amp;lt;0.001, respectively). Conclusions: This study suggests that individuals with idiopathic generalized tonic-clonic epilepsy experiencing social phobia may exhibit lower cognitive function compared to those without. This indicates that comorbid social phobia might negatively impact cognitive abilities in idiopathic generalized tonic-clonic epilepsy patients.

Implementation of peer-to-peer oral care objective structured clinical examination-based learning for nursing students.

Nurses' skills and confidence in providing oral care to patients play important roles in healthcare. Studies have proved that peer-to-peer learning and assessment can help improve nurses' skills and confidence. However, no study has investigated it using an objective assessment checklist. This study investigated an oral hygiene practice training program for nursing students. It focused on their oral healthcare skills, confidence, and perspectives regarding implementing an objective structured clinical examination (OSCE). A pre- and post-survey of 97 nursing students from a nursing school in Japan was conducted as a peer-to-peer oral health education training program that included an assessment and performance checklist. Confidence in performing and assessing oral care significantly improved after attending the program. Furthermore, the changes were significantly greater in the developed program than in the training program without the checklist. The mean total assessment scores (0-25) of the first, second, third, and fourth participants in the four-student groups were 22.1, 23.4, 23.9, and 24.1, respectively. The mean scores of the second, third, and fourth participant groups were significantly higher than that of the first participant group (p < .01). Fifty-two positive and 58 negative comments were received regarding the implementation of the program with professional assessments and the checklist. The most common positive comment mentioned that the evaluation by professionals improved oral care learning and skills. This study developed a program to improve nursing students' confidence and oral care delivery skill building in an OSCE-style delivery.

Automatic rehabilitation assessment method of upper limb motor function based on posture and distribution force.

The clinical rehabilitation assessment methods for hemiplegic upper limb motor function are often subjective, time-consuming, and non-uniform. This study proposes an automatic rehabilitation assessment method for upper limb motor function based on posture and distributed force measurements. Azure Kinect combined with MediaPipe was used to detect upper limb and hand movements, and the array distributed flexible thin film pressure sensor was employed to measure the distributed force of hand. This allowed for the automated measurement of 30 items within the Fugl-Meyer scale. Feature information was extracted separately from the affected and healthy sides, the feature ratios or deviation were then fed into a single/multiple fuzzy logic assessment model to determine the assessment score of each item. Finally, the total score of the hemiplegic upper limb motor function assessment was derived. Experiments were performed to evaluate the motor function of the subjects' upper extremities. Bland-Altman plots of physician and system scores showed good agreement. The results of the automated assessment system were highly correlated with the clinical Fugl-Meyer total score (r = 0.99, p < 0.001). The experimental results state that this system can automatically assess the motor function of the affected upper limb by measuring the posture and force distribution.

Psychometric validation of the Psoriasis Symptom Scale, Functional Assessment of Chronic Illness Therapy-Fatigue and pain-Visual Analogue Scale in patients with generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease associated with considerable patient burden. The Psoriasis Symptom Scale (PSS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and pain-Visual Analogue Scale (pain-VAS) are patient-reported outcomes (PROs) that have not yet been validated in patients with GPP. To evaluate the psychometric properties of the PSS, FACIT-Fatigue and pain-VAS using data from Effisayil 1, a randomised trial of spesolimab in patients with moderate-to-severe GPP. Inter-item correlations and confirmatory factor analysis (CFA) were performed using Week 1 data. Internal consistency was assessed with Cronbach's α coefficient using baseline and Week 1 data. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs); change data for the GPP Physician Global Assessment total score and pustulation subscore were used to define a stable population. Convergent validity was assessed at baseline and Week 1 using Spearman's rank-order correlations. Known-groups validity was measured by analysis of variance using Week 1 data. Ability to detect change from baseline to Week 1 was evaluated by analysis of covariance. Inter-item and item-to-total correlations were moderate or strong for most PSS and FACIT-Fatigue items. CFA demonstrated the unidimensionality of the PSS and FACIT-Fatigue, with high factor loadings for most items (PSS range, 0.75-0.94; FACIT-Fatigue range, 0.11-0.93) and acceptable fit statistics. Both scores demonstrated internal consistency (Cronbach's α, 0.71 and 0.95, respectively). The PSS, FACIT-Fatigue and pain-VAS demonstrated test-retest reliability (ICCs ≥0.70) and good evidence of convergent validity. Furthermore, the PROs could differentiate between known groups of varying symptom severity (range, p < 0.0001-0.0225) and detect changes in symptom severity from baseline to Week 1 (range, p < 0.0001-0.0002). Overall, these results support the reliability, validity and ability to detect change of the PSS, FACIT-Fatigue and pain-VAS as PROs in patients with GPP.

Characteristics and management of generalized pustular psoriasis (GPP): Experience from the Central and Eastern Europe (CEE) GPP Expert Network.

Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by widespread eruption of sterile pustules with or without systemic symptoms. This study aimed to describe the demographics of patients with GPP in Central and Eastern Europe (CEE), present the clinical characteristics of individual GPP flares and explore the current treatment landscape. Patient demographics were collected at the times of last observation and previous treatment. Characteristics of a patient's last (most recent) and most severe (from all documented episodes) flare were provided at clinician's discretion. Fifty-eight patients were recruited from 12 centres in nine CEE countries; median (range) age was 61 (16-92) years and 60.3% (35 out of 58) were female. The most common comorbidities were hypertension (43.1% [25 out of 58]) and hyperlipidaemia (32.8% [19 out of 58]). Thirty-four patients (58.6%) presented with concomitant plaque psoriasis before or during the course of GPP. Data from two separate flares were recorded in 26 individuals; in 32 patients, the most recent flare was reported as the most severe. Over 90% of patients with a flare episode classified as most severe by clinicians were hospitalized, with >75% of these individuals having a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 3 or 4. Systemic symptoms were more common in patients with a GPPGA score of 3 or 4 but were also manifest in individuals with a GPPGA score ≤2. A significant correlation was observed between a combined systemic disease score of clinical and laboratory features and both GPPGA total score (r = 0.385, p < 0.001) and GPPGA pustulation subscore (r = 0.305, p < 0.05). Considerable heterogeneity in the presentation of GPP flares was observed, both between patients and within-patient. All GPP flares were associated with a significant clinical burden, highlighting the unmet need for accurate and early diagnosis.

Dysfunction of the triple-network model is associated with cognitive impairment in patients with cerebral small vessel disease

PurposeThis study aimed to demonstrate the correlations between the altered functional connectivity patterns in the triple-network model and cognitive impairment in patients with cerebral small vascular disease (CSVD). MethodsResting-state functional magnetic resonance imaging data were obtained from 22 patients with CSVD and 20 healthy controls. The resting-state data were analyzed using independent component analysis and functional network connectivity (FNC) analysis to explore the functional alterations in the intrinsic triple-network model including the salience network (SN), default mode network (DMN), and central executive network (CEN), and their correlations with the cognitive deficits and clinical observations in the patients with CSVD. ResultsCompared to the healthy controls, the patients with CSVD exhibited increased connectivity patterns in the CEN-DMN and decreased connectivity patterns in the DMN-SN, CEN-SN, intra-SN, and intra-DMN. Significant negative correlations were detected between the intra-DMN connectivity pattern and the Montreal Cognitive Assessment (MoCA) total scores (r = −0.460, p = 0.048) and MoCA abstraction scores (r = −0.565, p = 0.012), and a positive correlation was determined between the intra-SN connectivity pattern and the MoCA abstraction scores (r = 0.491, p = 0.033). ConclusionsOur study findings suggest that the functional alterations in the triple-network model are associated with the cognitive deficits in patients with CSVD and shed light on the importance of the triple-network model in the pathogenesis of CSVD.

Increased Resting-State BOLD Turnover (TBOLD) is Associated With Decreased Cognitive Performance During Aging

Increasing evidence documents turnover of the resting-state blood-oxygen-level dependent signal (TBOLD) as a key measure of local cortical brain status. Here we evaluated contemporaneous and lagged associations between TBOLD and cognitive function in 711 participants in the Human Connectome Project on Aging (HCP-A; 316 males and 395 females, age range 36-90 years). We found that TBOLD was negatively associated with Montreal Cognitive Assessment (MoCA) Total scores and with performance on 2 subscales, Delayed Recall and Visuospatial/Executive Function, controlling for sex, age, and handedness. This negative association was largely documented across brain areas and was significantly stronger in the left hemisphere compared to the right. In addition, analyses evaluating forward lagged crosscorrelations between TBOLD and cognitive performance demonstrated that TBOLD predicted decrements in future performance on MoCA Total score, Delayed Recall, and Visuospatial/Executive Function subscales, controlling for sex and handedness. Taken together, we found that increased TBOLD is associated with decreased cognitive performance contemporaneously and in the future. On the hypothesis that increased TBOLD is the outcome of neuroinflammatory processes, these findings provide a mechanism linking neuroinflammation with decreased cognitive performance.

A novel biomarker of fibrofatty replacement in dystrophinopathies identified by integrating transcriptome, magnetic resonance imaging, and pathology data.

We aimed to analyse genome-wide transcriptome differences between Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients and identify biomarkers that correlate well with muscle magnetic resonance imaging (MRI) and histological fibrofatty replacement in both patients, which have not been reported. One hundred and one male patients with dystrophinopathies (55 DMD and 46 BMD) were enrolled. Muscle-derived genome-wide RNA-sequencing was performed in 31 DMD patients, 29 BMD patients, and 11 normal controls. Fibrofatty replacement was scored on muscle MRI and histological levels in all patients. A unique pipeline, single-sample gene set enrichment analysis combined with Spearman's rank correlations (ssGSEA-Cor) was developed to identify the most correlated gene signature for fibrofatty replacement. Quantitative real-time PCR (qRT-PCR) analysis, western blot analysis, and single-nucleus RNA-sequencing (snRNA-seq) were performed in the remaining patients to validate the most correlated gene signature. Comparative transcriptomic analysis revealed that 31 DMD muscles were characterized by a significant increase of inflammation/immune response and extracellular matrix remodelling compared with 29 BMD muscles (P<0.05). The ssGSEA-Cor pipeline revealed that the gene set of CDKN2A and CDKN2B was the most correlated gene signature for fibrofatty replacement (histological rs =0.744, P<0.001; MRI rs =0.718, P<0.001). Muscle qRT-PCR confirmed that CDKN2A mRNA expression in both 15 DMD (median=25.007, P<0.001) and 12 BMD (median=5.654, P<0.001) patients were significantly higher than that in controls (median=1.101), while no significant difference in CDKN2B mRNA expression was found among DMD, BMD, and control groups. In the 27 patients, muscle CDKN2A mRNA expression respectively correlated with muscle MRI (rs =0.883, P<0.001) and histological fibrofatty replacement (rs =0.804, P<0.001) and disease duration (rs =0.645, P<0.001) and North Star Ambulatory Assessment total scores (rs =-0.698, P<0.001). Muscle western blot analysis confirmed that both four DMD (median=2.958, P<0.05) and four BMD (median=1.959, P<0.01) patients had a significantly higher level of CDKN2A protein expression than controls (median=1.068). The snRNA-seq analysis of two DMD muscles revealed that CDKN2A was mainly expressed in fibro-adipogenic progenitors, satellite cells, and myoblasts. We identify CDKN2A expression as a novel biomarker of fibrofatty replacement, which might be a new target for antifibrotic therapy in dystrophinopathies.

Astrocyte reactivity moderates the effect of education on cognitive reserve

AbstractBackgroundCognitive reserve and resilience account for differential susceptibility to brain aging and disease across individuals. Previous data suggest that functional connectivity among different brain areas is associated with cognitive reserve. However, its neural basis is yet unclear. In this study, we investigated the moderating effect of astrocyte reactivity in cognitive reserve.MethodCognitively unimpaired individuals who had plasma GFAP analyzed were selected from ADNI at baseline (n = 130). Years of education were used as a proxy of cognitive reserve; the Montreal Cognitive Assessment (MoCA) total score was retrieved from all individuals. A moderation analysis was performed according to the most recent framework for reserve and resilience in aging concepts. The total MoCA score was the outcome, and we investigated the moderation of plasma GFAP in the association of years of education and MoCA. Data are shown as mean+‐SD.ResultA total of 130 individuals had complete data for all variables (72.3+‐6.3 years of age; 16.36+‐2.75 years of education; 43.1% females). A significant moderating effect was found in plasma GFAP and years of education (beta = 0.004, p = 0.0006) as a predictor of total MoCA scores (Model R2 = 0.37, p &lt; 0.0001) when correcting for age and gender. Plasma GFAP and sex were also predictors of total MOCA scores independently (p&lt;0.001 for both). Plasma GFAP was a moderator in individuals below 18 years of education (p = 0.003), but not above 18 years of education (p = 0.9).ConclusionAstrocyte reactivity may play a potential role in the neural basis of cognitive reserve. The neuroprotective effect of astrocytes in cognitive reserve may have a ceiling effect. Further studies may investigate the importance of glial interactions with brain regions and its ability to predict cognitive changes in a longitudinal analysis.

Circulating cell‐free mitochondrial DNA (ccf‐mtDNA) and memory in mild cognitive impairment (MCI) and Alzheimer’s disease (AD)

AbstractBackgroundCirculating cell‐free mitochondrial DNA (ccf‐mtDNA), a measure of mitochondrial dysfunction, is emerging as a potential biomarker for early Alzheimer’s disease (AD). Decreased levels of cerebrospinal fluid ccf‐mtDNA concentrations have been detected in early AD patients. Few studies have investigated peripheral ccf‐mtDNA in early AD or with cognitive measures, much less evaluating the role of physical activity within the relationships. Considering the hallmark of episodic memory impairment in early AD, we examined the association between serum ccf‐mtDNA and memory, while considering potential contributing factors, physical activity level and age.MethodsParticipants were diagnosed with mild cognitive impairment (MCI) or mild AD using the Diagnostic and Statistical Manual of Mental Disorders criteria for mild or major neurocognitive disorder. Serum ccf‐mtDNA concentration (copies/uL) was measured using quantitative polymerase chain reaction from circulating cell free DNA purified by spin columns with primer for the MT‐ND4 gene. Memory was assessed using the Word Recall Task from the Alzheimer’s Disease Assessment Scale‐Cog (ADAS‐Cog). Physical activity level was assessed by Leisure‐Time Exercise Questionnaire (LTEQ). Linear regression analyses were used to assess the association between ccf‐mtDNA levels and recall memory with a priori covariates, age and LTEQ score. Ccf‐mtDNA levels were log‐transformed prior to analyses due to significant departure from normality in Shapiro‐Wilk tests.ResultsOf 29 participants [17 (59%) male, 21 (72%) MCI], the mean (SD) age was 74.2 (8.7), years of education was 16.2 (2.2), Montreal Cognitive Assessment (MoCA) total score was 22.1 (3.3), LTEQ score was 36.2 (17.4), and ccf‐mtDNA levels were 2545.8 (2223.6) copies/uL. Higher ccf‐mtDNA was associated with worse recall [F(3,25) = 5.21, R2 = .39, p = .006]. Controlling for LTEQ and age, one log ccf‐mtDNA unit was associated with 1.87 (SE = .71) fewer words recalled (p = .01, f2 = .21).ConclusionIn this sample, higher serum ccf‐mtDNA concentrations were associated with worse recall, controlling for age and physical activity level. This relationship supports the potential involvement of mitochondrial dysfunction in cognitive functions and neurodegenerative diseases and suggest the need for further research to explore the role of physical activity and age with mitochondrial dysfunction and memory.

Effect of Spesolimab on Achieving Sustained Disease Remission in Patients with Generalized Pustular Psoriasis: Results from the Effisayil 2 Study

Introduction: Generalized pustular psoriasis (GPP) is a chronic, rare and potentially life-threatening disease characterized by flares of widespread skin pustulation. Sustained skin clearance is a key treatment objective. Intravenous (IV) spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved for GPP flare treatment; however, the optimal dosing and long-term efficacy of subcutaneous (SC) spesolimab treatment in patients with GPP has not yet been reported. We report the effect of SC spesolimab on achieving sustained disease remission over 48 weeks in Effisayil 2 (NCT04399837), a trial that evaluated the efficacy and safety of SC spesolimab in preventing GPP flares.&#x0D; Methods: Patients with a history of GPP were randomized (1:1:1:1) to receive placebo (n=31), low- (n=31, 300 mg loading dose [LD]; 150 mg every 12 weeks [q12w]), medium- (n=31, 600 mg LD; 300 mg q12w) or high-dose (n=30, 600 mg LD; 300 mg every 4 weeks [q4w]) SC spesolimab over 48 weeks. Sustained remission was defined as GPP Physician Global Assessment (GPPGA) total score of 0 or 1 at all visits up to Week 48, or GPPGA total score of 0 or 1 and all GPPGA subscores ≤2 at all visits up to Week 48. Sustained pustular clearance was defined as GPPGA pustulation subscore of 0 at all visits from Week 4 to Week 48. Any use of IV spesolimab or another standard of care for GPP worsening was considered a failure of remission. Missing data were imputed by a sequential logistic regression multiple imputation method. Adjusted risk differences (RD) were calculated by the Mantel−Haenszel type-weighted average of differences.&#x0D; Results: 31 patients received placebo, and 30 patients received high-dose spesolimab. Compared to placebo, more patients had sustained remission in the high-dose arm using both GPPGA total score 0 or 1 (63.3% vs 29.0%; RD [95% CI] 0.35 [0.10–0.59]), and GPPGA total score 0 or 1 and all GPPGA subscores ≤2 (60.4% vs 29.0%; RD [95% CI] 0.32 [0.07–0.56]). Compared to placebo, more patients in the high-dose arm had sustained pustular clearance over 48 weeks (63.6% vs 25.8%; RD [95% CI] 0.38 [0.14–0.62]).&#x0D; Conclusion: Overall, high-dose SC spesolimab q4w is effective for the long-term management of GPP skin symptoms.

Metoclopramide Nasal Spray in Women With Symptomatic Diabetic Gastroparesis: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study

Background & AimsMetoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but not men with diabetic gastroparesis. The aim of this phase 3 study was to further determine the safety and efficacy of MNS compared to placebo in reducing symptoms of diabetic gastroparesis in women. MethodsThis US multi-center, randomized, double-blind, parallel group study enrolled women aged 18 to 75 years with diabetic gastroparesis and delayed gastric emptying. Subjects were randomized 1:1 to receive placebo or MNS 10 mg. The primary efficacy endpoint was change in mean daily Gastroparesis Symptom Assessment (GSA) total score from baseline to week 4. The GSA daily diary is a validated patient-reported outcome instrument that averages scores of nausea, early satiety, prolonged fullness, bloating, and upper abdominal pain on a five-point ordinal scale. ResultsTwo-hundred-five subjects were randomized to receive placebo (n = 103) or MNS (n = 102). Overall, the MNS group did not experience a significant reduction in symptoms compared to the placebo group from baseline to week 4 (P = 0.881). However, subjects with moderate to severe symptoms at baseline had a significant treatment effect from weeks 1 to 3 (P < 0.05) and experienced a significant reduction in nausea and upper abdominal pain for all four weeks versus placebo (P < 0.05). Treatment-emergent adverse events were primarily mild to moderate with headache and abdominal pain reported most frequently. ConclusionsAlthough the primary endpoint was not met using all enrolled patients, treatment with MNS provided significant relief for women with moderate to severe diabetic gastroparesis symptoms. MNS was well tolerated and demonstrated a similar safety profile to placebo. ClinicalTrials.gov identifier: NCT02025725.

81 Assessment of Functional Capacity Interview (AFCI): A New Informant- Report Measure to Detect Disability Risk in Older Adults

Objective:Functional disability is a foreseeable consequence of neurodegenerative diseases affecting cognition, yet there are few validated instruments that assess functional capacity for use in pre-clinical and clinical dementia conditions. To our knowledge, the existing instruments do not comprehensively assess decision-making capacity across the numerous functional domains of daily life. We developed and evaluated the utility of an informant-report measure, the Assessment of Functional Capacity Interview (AFCI), within a sample of cognitively unimpaired and preclinical dementia groups.Participants and Methods:Based on a comprehensive literature review, analysis of existing measures, and clinical experience, we generated &gt;40 items consisting of open-ended questions assessing crucial aspects of daily functioning. These items were presented to 12 experts in the field of geriatrics and neuropsychology, through a graded approach (4 rounds of feedback and alterations), resulting in item modification or rejection, as well as addition of new items. The remaining items were piloted on three informants at the time of outpatient clinical evaluations, leading to further item refinement. The final version of the AFCI evaluated capacity across domains of financial affairs and management, medical affairs and healthcare management, home and personal safety, and social behaviors and community functioning. The AFCI contained 6 items per domain with response items that ranged from 0=no difficulty to 3=severe difficulty (scores ranged from 0 to 72).Results:Participants (N = 58; Agemean = 76; Educationmean = 16) were classified as cognitively unimpaired (CU, n = 17), subjective cognitive decline (SCD, n = 24), or mild cognitive impairment (MCI, n = 17) based on established criteria. All participants had a knowledgeable informant who completed the AFCI. We found statistically significant moderate to large correlations between the AFCI total score and an informant report measure of cognitive functioning (Brief Informant Form of Neurobehavioral Symptomatology total score), rs(42) = .73, p &lt; .001, Test of Practical Judgment-informant total score rs(42) = .87, p &lt; .001, and Montreal Cognitive Assessment total score rs(41) = -.34, p = .027. A Kruskal-Wallis H test revealed significant differences in AFCI total score between the three diagnostic groups, H(2) = 12.30, p = .002. Pairwise post-hoc analysis with Bonferroni correction showed a significant difference between CU and MCI (p = .001). The difference in AFCI total score between SCD and MCI was in the expected direction, but did not achieve statistical significance with correction, (p = .068). As expected, there was no statistically significant difference between CU and SCD (p =.353).Conclusions:In this pilot sample (data collection is ongoing), the AFCI showed promise as a brief, clinically useful functional capacity instrument that is easily administered during a clinical interview or completed by knowledgeable informants. Results can help identify compromised decision-making in at-risk older adults to aid the prevention of common safety issues within this vulnerable population. Ongoing research will extend preliminary investigation of validity and further inform the utility of AFCI in both diagnostic and interventional contexts

Association between neurodevelopmental impairments and motor function in Duchenne muscular dystrophy.

We explored various prognostic factors of motor outcomes in corticosteroid-naive boys with Duchenne Muscular Dystrophy (DMD). The associations between parent-reported neurodevelopmental concerns (speech delay, speech and language difficulties (SLD), and learning difficulties), DMD mutation location, and motor outcomes (6-minute walk distance (6MWD), North Star Ambulatory Assessment (NSAA) total score, 10-meter walk/run velocity, and rise from floor velocity) were studied in 196 corticosteroid-naive boys from ages 4 to less than 8 years. Participants with SLD walked 25.8 fewer meters in 6 minutes than those without SLD (p = 0.005) but did not demonstrate statistical differences in NSAA total score, 10-meter walk/run velocity, and rise from floor velocity. Participants with distal DMD mutations with learning difficulties walked 51.8 fewer meters in 6 minutes than those without learning difficulties (p = 0.0007). Participants with distal DMD mutations were slower on 10-meter walk/run velocity, and rise from floor velocity (p = 0.02) than those with proximal DMD mutations. Participants with distal DMD mutations, who reported speech delay or learning difficulties, were slower on rise from floor velocity (p = 0.04, p = 0.01) than those with proximal DMD mutations. The mean NSAA total score was lower in participants with learning difficulties than in those without (p = 0.004). Corticosteroid-naive boys with DMD with distal DMD mutations may perform worse on some timed function tests, and that those with learning difficulties may perform worse on the NSAA. Pending confirmatory studies, our data underscore the importance of considering co-existing neurodevelopmental symptoms on motor outcome measures.

P140 Predicting long-term trajectories of the North Star Ambulatory Assessment (NSAA) total score in Duchenne muscular dystrophy (DMD): an updated model

P140 Predicting long-term trajectories of the North Star Ambulatory Assessment (NSAA) total score in Duchenne muscular dystrophy (DMD): an updated model

P242 Understanding North Star Ambulatory Assessment total scores and their implications for standards of care

P242 Understanding North Star Ambulatory Assessment total scores and their implications for standards of care

Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged ≥4 to

Delandistrogene moxeparvovec is approved in the USA for the treatment of ambulatory patients (4-5 years) with Duchenne muscular dystrophy. ENDEAVOR (SRP-9001-103; NCT04626674) is a single-arm, open-label study to evaluate delandistrogene moxeparvovec micro-dystrophin expression, safety, and functional outcomes following administration of commercial process delandistrogene moxeparvovec. In cohort 1 of ENDEAVOR (N = 20), eligible ambulatory males, aged ≥4 to <8 years, received a single intravenous infusion of delandistrogene moxeparvovec (1.33 × 1014 vg/kg). The primary endpoint was change from baseline (CFBL) to week 12 in delandistrogene moxeparvovec micro-dystrophin by western blot. Additional endpoints evaluated included: safety; vector genome copies; CFBL to week 12 in muscle fiber-localized micro-dystrophin by immunofluorescence; and functional assessments, including North Star Ambulatory Assessment, with comparison with a propensity score-weighted external natural history control. The 1-year safety profile of commercial process delandistrogene moxeparvovec in ENDEAVOR was consistent with safety data reported in other delandistrogene moxeparvovec trials (NCT03375164 and NCT03769116). Delandistrogene moxeparvovec micro-dystrophin expression was robust, with sarcolemmal localization at week 12; mean (SD) CFBL in western blot, 54.2% (42.6); p < 0.0001. At 1 year, patients demonstrated stabilized or improved North Star Ambulatory Assessment total scores; mean (SD) CFBL, +4.0 (3.5). Treatment versus a propensity score-weighted external natural history control demonstrated a statistically significant difference in least squares mean (standard error) CFBL in North Star Ambulatory Assessment, +3.2 (0.6) points; p < 0.0001. Results confirm efficient transduction of muscle by delandistrogene moxeparvovec. One-year post-treatment, delandistrogene moxeparvovec was well tolerated, and demonstrated stabilized or improved motor function, suggesting a clinical benefit for patients with Duchenne muscular dystrophy. ANN NEUROL 2023;94:955-968.

ChatGPT versus human in generating medical graduate exam multiple choice questions-A multinational prospective study (Hong Kong S.A.R., Singapore, Ireland, and the United Kingdom).

Large language models, in particular ChatGPT, have showcased remarkable language processing capabilities. Given the substantial workload of university medical staff, this study aims to assess the quality of multiple-choice questions (MCQs) produced by ChatGPT for use in graduate medical examinations, compared to questions written by university professoriate staffs based on standard medical textbooks. 50 MCQs were generated by ChatGPT with reference to two standard undergraduate medical textbooks (Harrison's, and Bailey & Love's). Another 50 MCQs were drafted by two university professoriate staff using the same medical textbooks. All 100 MCQ were individually numbered, randomized and sent to five independent international assessors for MCQ quality assessment using a standardized assessment score on five assessment domains, namely, appropriateness of the question, clarity and specificity, relevance, discriminative power of alternatives, and suitability for medical graduate examination. The total time required for ChatGPT to create the 50 questions was 20 minutes 25 seconds, while it took two human examiners a total of 211 minutes 33 seconds to draft the 50 questions. When a comparison of the mean score was made between the questions constructed by A.I. with those drafted by humans, only in the relevance domain that the A.I. was inferior to humans (A.I.: 7.56 +/- 0.94 vs human: 7.88 +/- 0.52; p = 0.04). There was no significant difference in question quality between questions drafted by A.I. versus humans, in the total assessment score as well as in other domains. Questions generated by A.I. yielded a wider range of scores, while those created by humans were consistent and within a narrower range. ChatGPT has the potential to generate comparable-quality MCQs for medical graduate examinations within a significantly shorter time.

Counterparty Risk Contagion Model of Carbon Quota Based on Asset Price Reduction

Driven by the “double carbon” goal, the sale of financial assets at reduced prices by firms due to carbon emission constraints is bound to aggravate the uncertainty and volatility of carbon trading among firms, and potentially create counterparty risk contagion. In view of this, this paper considers the sensitivity of the transaction of corporate financial assets, the transaction price of carbon quotas, and corporate carbon performance; constructs a network model for the risk contagion of carbon quota counterparties; theoretically discusses the risk formation and infection mechanism of carbon quota counterparties; and calculates and simulates the evolutionary characteristics of the risk contagion of carbon quota counterparties. The main research conclusions are as follows. (1) In the interfirm debt network, the sensitivity to the price of selling the financial asset, the probability of credit risk contagion of carbon quotas among firms, the cumulative proportion of assets sold, and the proportion of rational investors in the financial market exert a decreasing phenomenon on the risk of carbon quota counterparties. In addition, the corporate carbon performance shows a marginal increasing phenomenon. (2) When multiple factors intersect, the proportion of rational investors in the financial market has the greatest influence on the formation of the carbon quota counterparty risk, whereas the effect of corporate carbon performance has the least. Corporate carbon risk awareness has the greatest effect on the risk contagion of carbon quota counterparties, whereas the trading price of the carbon quota has the least influence. In addition, the total score of the interfirm assessment has a great impact on the trend and range of the risk contagion of carbon quota counterparties. (3) Corporate carbon risk awareness and the carbon quota trading price have a marginally decreasing effect on the risk contagion of carbon quota counterparties, and corporate carbon performance and the total score of interfirm assessment have a marginally increasing effect. This study has important theoretical and practical significance for preventing interfirm counterparty risk contagion under the double carbon target.