Total Assessment Score Research Articles

Improving Access to Dementia Care in the Era of Monoclonal Antibody Treatments for Alzheimer's Disease: a Pilot Clinical Protocol Using Abbreviated Neuropsychological Assessment.

To meet the growing demand for timely diagnosis in the new era of disease-modifying medications for Alzheimer's disease (AD), the present study aimed to reduce clinic wait times by developing and refining an abbreviated neuropsychological battery to assess individuals with a suspected amnestic process (i.e., Early-Stage AD Pathway). Early-Stage AD Pathway patients were referred by an internal neurology provider who determined that the patient had: (1) an amnestic clinical presentation, (2) a normal neurological examination, and (3) a Montreal Cognitive Assessment total score between 18 and 25. These patients were scheduled for a 2-h neuropsychological evaluation, including a brief clinical interview and an abbreviated testing battery. We evaluated n = 19 patients in the Early-Stage AD Pathway and compared them to 114 older adults referred via traditional clinic procedures (i.e., General Clinic). Most individuals evaluated via the Early-Stage AD Pathway were diagnosed with mild cognitive impairment (MCI; 68.4%) or mild dementia (21.1%) through the neuropsychological evaluation. Rate of diagnosis of MCI/dementia was comparable between groups. The average number of days between initial referral and completion of the neuropsychological evaluation was significantly lower (Mdiff = 145.8days, U = 1867.500, p < 0.001) for the Early-Stage AD Pathway group than for the General Clinic group, as the former could be scheduled more flexibly. Implementing an abbreviated neuropsychological assessment process significantly reduced the time between referral and evaluation to identify individuals who may be eligible for emerging pharmacological treatments for AD and/or non-pharmacological interventions in a timely manner.

Four-weekly dosing intervals with subcutaneous spesolimab appear to be required for optimal prevention of generalized pustular psoriasis flares: Data from the EFFISAYIL® 2 and EFFISAYIL® ON trials

Generalized pustular psoriasis (GPP) is a rare chronic skin disease characterized by recurrent, acute, and often life-threatening flares of widespread neutrophilic sterile pustules and systemic inflammation. Spesolimab, an anti-interleukin-36 receptor antibody, is approved in adults and adults and pediatric patients 12 years of age and older and weighing at least 40 kg, as a subcutaneous dosage for treatment of GPP when not experiencing a flare, and as an intravenous dosage for GPP flare treatment. In Effisayil 2, a randomized, placebo-controlled trial (NCT04399837), subcutaneous spesolimab was superior to placebo and well tolerated for flare prevention when administered as a 600-mg subcutaneous loading dose followed by 300 mg every 4 weeks (q4w) over 48 weeks. In Effisayil 2, 3/30 (10.0%) patients receiving subcutaneous spesolimab 300 mg q4w had flares, and there were no flares after Week 4 until the end of the study. We assessed the effect on flare recurrence of a longer (q12w) interval between subcutaneous spesolimab doses in Effisayil 2 and Effisayil ON (NCT03886246), an ongoing open-label extension trial. Flares were defined as a ≥2-point increase in GPP Physician Global Assessment total score with pustulation subscore of ≥2, or intravenous spesolimab or standard of care treatment due to GPP worsening. In Effisayil 2, 9/31 (29.0%) patients who received subcutaneous spesolimab 300 mg q12w had a flare; of those, 7/9 (77.8%) experienced a flare before their second subcutaneous dose (Week 12), and 5/7 (71.4%) flares occurred during Weeks 4–12, indicating the need for q4w dosing. In Effisayil ON, 36/108 (33.3%) patients who started q12w dosing were either escalated to a q4w regimen (n=24) or experienced a flare (n=12). These observations suggest that subcutaneous spesolimab 300 mg q4w is the optimal dosing regimen for prevention of GPP flares.

Successful Treatment of Pediatric Generalized Pustular Psoriasis (GPP) with Spesolimab: 5 Case Reports and Evaluations of Circulating IL-36 Levels.

Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory cutaneous disease. IL-36 is a key treatment target in GPP. Spesolimab, a humanized monoclonal antibody of the IL-36 receptor, has demonstrated a good efficacy and a favorable safety profile in adults with GPP. However, data on its use in children are scarce. We treated patients aged 4-12 years with GPP with a single dose of spesolimab. The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score, GPPGA pustulation sub-score, Generalized Pustular Psoriasis Area and Severity Index (GPPASI), and the Japanese Dermatological Association severity index for GPP were evaluated. The levels of IL-36α, IL-36β, and IL-36γ were detected by the magnetic bead-based immunoassays, and the levels of IL-17A, IL-17C, IFN-γ, TNF, IL-6, and IL-8 were measured by the Olink proximity extension assay technology. We included five patients (four boys and one girl) with a median age was 6.9 years old (range: 4.8 to 10.6 years), and a median age of onset of 1.7 years (range: 3 months-10 years and 5 months). After 1week of spesolimab administration, all patients had a total GPPGA score of 0/1 and pustulation subscore of 0, all patients had a GPPASI of 50, and four patients had a GPPASI of 75. Meanwhile, plasma levels of IL-36α, IL-36β, IL-36γ, IL-17A, IL-17C, IFN-γ, TNF, IL-6, IL-8 all decreased, and those of IL-36α, IL-36β, IL-17A, IL-17C, and IL-6 were statistically significant. There was no recurrence after 2 to 8 months of treatment. No other adverse event was recorded apart from one patient who experienced an upper respiratory infection in the first week. Spesolimab might be a prospective option for children aged 4 to 12 years.

Characterization of patients with Duchenne muscular dystrophy across previously developed health states.

Project HERCULES has developed a natural history model (NHM) of disease progression in Duchenne muscular dystrophy (DMD) that comprises eight ordered health states (two ambulatory states, one transfer state indicating increased caregiver burden in which patients cannot walk/run 10m or rise from floor but can still support their own weight, and five non-ambulatory states). The current study used data from nine sources (clinical trial placebo arms, one real-world dataset, and three natural history datasets) to further characterize patients with DMD according to these health states. The study included 1,173 patients across 5,306‬ visits. Patients were on average older and exhibited worse ambulatory, pulmonary, upper limb, and cardiac functions with each successive health state. Mean±SE ages increased monotonically across health states, starting with 8.47±0.07 for early ambulatory, 10.86±0.13 for late ambulatory, 11.65±0.35 for transfer state, and ranging from 13.17±0.32 to 16.84±0.37 for the non-ambulatory states. North Star Ambulatory Assessment (NSAA) total score, which measures motor function and ranges from 34 (best) to 0 (worst), was 23.7 (interquartile range [IQR]: 20-30) for early ambulatory patients, 12.7 (IQR: 9-16) for late ambulatory patients, and 3.9 (IQR: 2-5) for transfer patients. Pulmonary function as measured by mean±SE of forced vital capacity percent predicted (FVC%p) was 94.5±0.8 for early ambulatory, 89.1±1.4 for late ambulatory, and 80.2±2.8 for transfer states, and decreased from 77.2±1.7 to 20.6±1.6 across the five non-ambulatory health states. In summary, these findings further characterize health states and their interpretation in economic modeling and decision-making in DMD management.

Understanding North Star Ambulatory Assessment total scores and their implications for standards of care using observational data

NorthStar Ambulatory Assessment (NSAA) total score (TS) is an ordinal scale to evaluate disease progression and treatment response in ambulatory Duchenne Muscular Dystrophy individuals. Clinical management according to standard of care could be enhanced by understanding how changes in the TS could inform standards of care. Here we describe the associated item performance patterns in the NorthStar Database for ranges of NSAA TS and its timed tests (10 m walk/run and rise from floor). We then compare these patterns depending on whether a participant is on an improving/stable (≤2-point loss in the prior year) or declining (>2-point loss in the prior year) trend. These TS and trends are subsequently linked and referenced to therapy standards of care. We included 761 participants from the UK NorthStar observational clinical database between 5 and 16 years, who were on steroids. Differences and trends in item ability, compensations, and times can suggest specific disease complications and lead towards anticipatory therapy recommendations. Families and therapists can benefit from using the TS and trend to guide therapy management.

Glymphatic function assessment with diffusion tensor imaging along the perivascular space in patients with major depressive disorder and its relation to cerebral white-matter alteration.

The link between glymphatic system function in the brain and alterations in white-matter microstructure among individuals with major depressive disorder (MDD) remains unclear. This study aimed to examine the assessment of glymphatic system function in patients with MDD using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and to evaluate its association with cerebral-white-matter abnormalities and neuropsychological scores. From February 2023 to November 2023, this cross-sectional study recruited 35 patients with MDD from the Psychosomatic Diseases Department of the First Affiliated Hospital of Dalian Medical University. In this time period, 23 healthy controls (HCs) were enlisted from the community and matched with the MDD cohort in terms of years of education, gender, and age. All participants underwent magnetic resonance imaging, depression, anxiety, and cognitive assessments. The tract-based spatial statistics (TBSS) analyzed DTI parameters and identified significant clusters. Automated fiber quantification (AFQ) was used to automatically identify fiber bundles with statistical differences. Mann-Whitney tests or two-sample t-tests were used for comparisons. Interobserver consistency of the DTI-ALPS measurements was evaluated using the interclass correlation coefficient (ICC). Partial correlation analyses and linear regression analyses were used to examine relationships. A comparison of the DTI-ALPS index was made between the two groups. Correlations among diffusion characteristics, neuropsychological scores, and the DTI-ALPS index were analyzed. Compared to HCs, patients with MDD exhibited a lower DTI-ALPS score (P=0.001). According to using linear regression analysis, the ALPS index was found to be an independent predictor of the Hamilton Depression Rating Scale [B=-25.32; P=0.001; 95% confidence interval (CI): -40.35 to -11.55], Hamilton Anxiety Rating Scale (B=-33.48; P=0.003; 95% CI: -55.38 to -11.24), and Montreal Cognitive Assessment total score (B=8.59; P=0.008; 95% CI: 2.38 to 14.79). According to the TBSS analysis, there were clusters of increased axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in patients with MDD as compared to HCs (all P values <0.05). A lower DTI-ALPS score was correlated with higher AD (r=-0.592; P<0.001), MD (cluster 1: r=-0.567, P=0.001; cluster 2: r=-0.581, P<0.001), and RD (r=-0.491; P=0.004) values. AFQ analysis identified the significantly different diffusion indicators in the left cingulum bundle (CB_L), left inferior longitudinal fasciculus (ILF_L), and left uncinate fasciculus (UF_L) between the two groups (all false discovery rate P values <0.05). DTI-ALPS score was negatively correlated with the AD value of CB_L (r=-0.304; P=0.024), ILF_L (r=-0.35; P=0.008), and UF_L (r=-0.354; P=0.008) in AFQ tract-level analysis. In point-wise analysis, the MD value of CB_L at nodes 33 to 36 was negatively correlated with DTI-ALPS score (r ranging from -0.504 to -0.535; P<0.01). Our results indicated a decrease in DTI-ALPS index score in patients with MDD. DTI-ALPS score was associated with depression, anxiety, declined cognitive ability, and white-matter microstructural abnormalities and may thus be a promising biomarker for the partial evaluation of glymphatic system function in patients with MDD.

Reductions in functional muscle mass and ability to ambulate in Duchenne muscular dystrophy from ages 4 to 24 years.

Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12month, longitudinal, observational study. Here, we report the baseline data. A 20mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4-25years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r=0.517, P<0.0001 and r=0.764, P<0.0001 respectively). The age-associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non-ambulant subjects, suggesting a threshold of 18-22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D3Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. KEY POINTS: The non-invasive D3creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non-ambulant patients. The difference in %MM between ambulant and non-ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM. The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability.

Meaningful changes in motor function in Duchenne muscular dystrophy (DMD): A multi-center study.

Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the 'meaningfulness' of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to <18 years and receiving steroids. Minimal clinically important differences (MCIDs) for worsening were also estimated. Estimated MDC thresholds for >80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD.

RANCANGAN DAN ANALISIS KELAYAKAN PEMENUHAN GIZI IBU HAMIL MELALUI APLIKASI MENU GIZI IBU HAMIL (AMEZI BUMIL)

Nutritional intake during pregnancy is crucial for the health of pregnant women and optimal fetal development. The Pregnancy Nutrition Menu Application (AMEZI BUMIL) was developed to ensure balanced nutritional intake. The research aims to analyze the Pregnancy Nutrition Menu Application (AMEZI BUMIL). This study uses the Research and Development (R&amp;D) method to analyze the feasibility of AMEZI BUMIL. This Android application goes through the planning, validation, design revision, and testing stages. The educational media for the pregnancy nutrition menu application (AMEZI BUMIL) was validated by 6 competent nutrition experts and 3 competent IT media experts. Identifying the deficiencies of this application, the researchers conducted revisions based on the validation by media and content experts. The final stage in the product design is product testing, which was carried out by 10 pregnant women in the Telaga Biru Health Center area in Pontianak City. The sampling technique used purposive sampling with sample determination based on small group testing conducted on 10 individuals. This research collected primary data using questionnaires for validation and small-scale testing. Total assessment scores can be calculated using the Likert Scale formula. Data is presented descriptively, and results are presented in descriptive and tabular forms. This application achieves significant acceptance levels from users, healthcare professionals, and media experts, with positive ratings exceeding 80% for users and healthcare professionals and over 55% for media experts, indicating good suitability. This success reflects the potential for widespread public adoption of AMEZI BUMIL as it has met user expectations.

Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial.

Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery. To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo. ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial. 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living. Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset. Matching placebo plus standardized rehabilitation. The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events. The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study.

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.

Factors Associated With Early Motor Function Trajectories in DMD After Glucocorticoid Initiation: Post Hoc Analysis of the FOR-DMD Trial.

Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak. This was a prospective 18-month analysis of the Finding the Optimum Corticosteroid Regimen for Duchenne Muscular Dystrophy study. Four COAs were investigated: rise from supine velocity (RFV), 10-meter walk/run velocity (10MWRV), North Star Ambulatory Assessment (NSAA) total score, and 6-minute walk test distance (6MWT). The relationships of baseline age (4-5 vs 6-7 years), COA baseline performance, genotype, and glucocorticoid regimen (daily vs intermittent) with the COA trajectories were evaluated using linear mixed-effects models. One hundred ninety-six glucocorticoid-naïve boys with DMD aged 4-7 years were enrolled. The mean age at baseline was 5.9 ± 1.0 years, 66% (n = 130) were on daily regimens, 55% (n = 107) showed a 6MWT distance >330 metres; 41% (n = 78) showed RFV >0.2 rise/s; 76% (n = 149) showed 10MWRV >0.142 10m/s, and 41.0% (n = 79) showed NSAA total score >22 points. Mean COA trajectories differed by age at glucocorticoid initiation (p < 0.01 for RFV, 10MWRV, and NSAA; p < 0.05 for 6MWT) and regimen (p < 0.01 for RFV, 10MWRV, and NSAA). Boys younger than 6 years reached their peak performance 12-18 months after glucocorticoid initiation. Boys aged 6 years or older on a daily regimen peaked between months 9 and 12 and those on an intermittent regimen by 9 months. The baseline COA performance was associated with the NSAA (p < 0.01) and the 6MWT trajectory in boys younger than 6 years on a daily regimen (p < 0.01). Differences in the mean trajectories by genotype were not significant. Glucocorticoid regimen, age, duration of glucocorticoid exposure, and baseline COA performance need to be considered in the design and analysis of clinical trials in young boys with DMD.

Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) in Chronic Myeloproliferative Neoplasms with Relation to Genetic Burden and Thrombosis

The Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) is a surrogate marker for symptom evaluation in chronic myeloproliferative neoplasms (MPNs). However, insufficient data are available regarding the relationship among the MPN-SAF TSS, JAK2 mutation allele burden, and thrombosis. In this retrospective analysis, we aimed to determine the genetic burdens, clinical features, and relationships with MPN-SAF TSS in MPN patients. One hundred thirty JAK2V617F-positive patients with MPNs were included in our study. We calculated the MPN-SAF TSS for all patients and compared it with their clinical characteristics. Patients with higher JAK2V617F mutation allele burden had higher MPN-SAF TSS values (p=0.008). Patients with thrombosis had higher MPN-SAF TSS than patients without thrombosis (p=0.003). The mean MPN-SAF TSS was higher in patients with primary myelofibrosis compared to those with polycythemia vera and essential thrombocythemia. Thrombosis was associated with increased symptom severity in several domains, including fatigue, abdominal discomfort, inactivity, night sweats, pruritus, weight loss, and early satiety. Additionally, an increase in JAK2 allele burden was observed with higher symptom scores. The MPN-SAF TSS proved to be a reliable tool for assessing symptom burden in Turkish MPN patients. Furthermore, the significant association between thrombosis occurrence and symptom severity suggests that thrombotic events may contribute to symptom development. Notably, increasing JAK2 allele burden was correlated with more severe symptoms, highlighting its potential role in predicting disease burden. This study emphasizes the importance of symptom assessment in MPN patients and supports the incorporation of the MPN-SAF TSS in routine clinical practice to enhance patient care and management.

The Effect of Calcitonin Gene-Related Peptide Monoclonal Antibodies on Quality of Life among Migraine Patients: Pilot Study at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics.

Migraine has a negative impact on patients' quality of life, with the frequency of attacks being associated with greater disability and poorer health status. Frequent migraine-type headaches require prophylactic treatment, which has so far been of limited effectiveness until advent of calcitonin gene-related peptide (CGRP) monoclonal antibody. A prospective analysis was conducted of data from 41 migraine patients who experienced 4 or more monthly migraine days (MMD) longer than three months. At the beginning of the study, treatment with monoclonal antibodies against CGRP (fremanezumab 225 mg or erenumab 70 or 140 g per month) was prescribed according to the indications. The effect of the medications was evaluated after 3-month period. The mean age of patients was 37.17 (±11.78) years. It was found that 17 patients (41.5%) had episodic migraine (EM) and 24 (58.5%) had chronic migraine (CM). Fremanezumab was prescribed to 26 patients (63.4%) and erenumab to 15 patients (36.6%); among the latter, 13 patients used 70 mg/month and 2 patients used 140 mg/month. Three months after treatment, CM changed to EM for 19 patients (79.2%), 27 patients (65.9%) had ≥50% reduction in the number of MMD and total migraine disability assessment (MIDAS) score was reduced by >50% in 31 patients (75.6%). Also, all areas of quality of life of patients were improved after 3 months continued treatment compared to baseline. For more than half the patients using fremanezumab or erenumab after 3-month period, MMD decreased by ≥50% and total MIDAS score by >50 points. All areas of quality of life were improved after prophylactic treatment of migraine.

Effectiveness and feasibility of 5G-based remote interactive ultrasound training in critical care

BackgroundUltrasound has widely used in various medical fields related to critical care. While online and offline ultrasound trainings are faced by certain challenges, remote ultrasound based on the 5G cloud platform has been gradually adopted in many clinics. However, no study has used the 5G remote ultrasound cloud platform operating system for standardized critical care ultrasound training. This study aimed to evaluate the feasibility and effectiveness of 5G-based remote interactive ultrasound training for standardized diagnosis and treatment in critical care settings.MethodsA 5G-based remote interactive ultrasound training system was constructed, and the course was piloted among critical care physicians. From July 2022 to July 2023, 90 critical care physicians from multiple off-site locations were enrolled and randomly divided into experimental and control groups. The 45 physicians in the experimental group were trained using the 5G-based remote interactive ultrasound training system, while the other 45 in the control group were taught using theoretical online videos. The theoretical and practical ultrasonic capabilities of both groups were evaluated before and after the training sessions, and their levels of satisfaction with the training were assessed as well.ResultsThe total assessment scores for all of the physicians were markedly higher following the training (80.7 ± 11.9) compared to before (42.1 ± 13.4) by a statistically significant margin (P < 0.001). Before participating in the training, the experimental group scored 42.2 ± 12.5 in the critical care ultrasound competency, and the control group scored 41.9 ± 14.3—indicating no significant differences in their assessment scores (P = 0.907). After participating in the training, the experimental group’s assessment scores were 88.4 ± 6.7, which were significantly higher than those of the control group (72.9 ± 10.8; P < 0.001). The satisfaction score of the experimental group was 42.6 ± 2.3, which was also significantly higher than that of the control group (34.7 ± 3.1, P < 0.001).ConclusionThe 5G-based remote interactive ultrasound training system was well-received and effective for critical care. These findings warrant its further promotion and application.

An analysis of factors influencing cognitive dysfunction among older adults in Northwest China based on logistic regression and decision tree modelling

BackgroundCognitive dysfunction is one of the leading causes of disability and dependence in older adults and is a major economic burden on the public health system. The aim of this study was to investigate the risk factors for cognitive dysfunction and their predictive value in older adults in Northwest China.MethodsA cross-sectional study was conducted using a multistage sampling method. The questionnaires were distributed through the Elderly Disability Monitoring Platform to older adults aged 60 years and above in Northwest China, who were divided into cognitive dysfunction and normal cognitive function groups. In addition to univariate analyses, logistic regression and decision tree modelling were used to construct a model to identify factors that can predict the occurrence of cognitive dysfunction in older adults.ResultsA total of 12,494 valid questionnaires were collected, including 2617 from participants in the cognitive dysfunction group and 9877 from participants in the normal cognitive function group. Univariate analysis revealed that ethnicity, BMI, age, educational attainment, marital status, type of residence, residency status, current work status, main economic source, type of chronic disease, long-term use of medication, alcohol consumption, participation in social activities, exercise status, social support, total scores on the Balanced Test Assessment, total scores on the Gait Speed Assessment total score, and activities of daily living (ADL) were significantly different between the two groups (all P < 0.05). According to logistic regression analyses, ethnicity, BMI, educational attainment, marital status, residency, main source of income, chronic diseases, annual medical examination, alcohol consumption, exercise status, total scores on the Balanced Test Assessment, and activities of daily living (ADLs) were found to influence cognitive dysfunction in older adults (all P < 0.05). In the decision tree model, the ability to perform activities of daily living was the root node, followed by total scores on the Balanced Test Assessment, marital status, educational attainment, age, annual medical examination, and ethnicity.ConclusionsTraditional risk factors (including BMI, literacy, and alcohol consumption) and potentially modifiable risk factors (including balance function, ability to care for oneself in daily life, and widowhood) have a significant impact on the increased risk of cognitive dysfunction in older adults in Northwest China. The use of decision tree models can help health care workers better assess cognitive function in older adults and develop personalized interventions. Further research could help to gain insight into the mechanisms of cognitive dysfunction and provide new avenues for prevention and intervention.

Impaired Standing Balance in Older Adults with Cognitive Impairment after a Severe Fall

Introduction: Fall-related sequelae as well as balance and gait impairments are more pronounced in older adults who are cognitively impaired (OACI) compared to older adults who are cognitively healthy (OACH). Evidence is scarce about differences in standing balance and gait in OACH and OACI after a fall, even though these are major risks for recurrent falls. Thus, the aim of this study was to investigate early impairments in gait and balance, by adding inertial measurement units (IMUs) to a functional performance test in OACH and OACI after a severe fall with a presentation to the emergency department (ED) and immediate discharge. Methods: The study sample was stratified into participants with and without probable cognitive impairment using the result of the Montreal Cognitive Assessment total score (maximum of 30 points). The cutoff for probable cognitive impairment was set at ≤ 24. Standing balance and gait parameters were measured using three IMUs in n = 69 OACH (72.0 ± 8.2 years) and n = 76 OACI (78.7 ± 8.1 years). Data were collected at participants’ homes as part of a comprehensive geriatric assessment in the “SeFallED” study within 4 weeks after presentation to the ED after a severe fall (German Clinical Trials Register ID: 00025949). ANCOVA was used for statistical analysis, adjusted for age. Results: The data indicated significantly more sway for OACI compared to OACH during balance tasks, whereas no differences in gait behavior were found. In detail, differences in standing balance were revealed for mean velocity (m/s) during parallel stance with eyes open (ηp2 = 0.190, p < 0.001) and eyes closed on a balance cushion (ηp2 = 0.059, p = 0.029), as well as during tandem stance (ηp2 = 0.034, p = 0.044) between OACI and OACH. Further differences between the two groups were detected for path length (m/s2) during parallel stance with eyes open (ηp2 = 0.144, p < 0.001) and eyes closed (ηp2 = 0.044, p < 0.027) and for range (m/s2) during tandem (ηp2 = 0.036, p = 0.036) and parallel stance with eyes closed (ηp2 = 0.045, p = 0.032). Conclusion: Even though both groups have experienced a severe fall with presentation to the ED in the preceding 4 weeks, balance control among OACI indicated a higher fall risk than among OACH. Therefore, effective secondary fall prevention efforts have to be established, particularly for OACI.

Exploring Cognitive Dysfunction in Long COVID Patients: Eye Movement Abnormalities and Frontal-Subcortical Circuits Implications via Eye-Tracking and Machine Learning

BackgroundCognitive dysfunction is regarded as one of the most severe aftereffects following coronavirus disease 2019 (COVID-19). Eye movements, controlled by several brain areas, such as the dorsolateral prefrontal cortex and frontal-thalamic circuits, provide a potential metric for assessing cortical networks and cognitive status. We aimed to examine the utility of eye movement measurements in identifying cognitive impairments in long COVID patients. MethodsWe recruited 40 long COVID patients experiencing subjective cognitive complaints and 40 healthy controls and used a certified eye-tracking medical device to record saccades and antisaccades. Machine learning was applied to enhance the analysis of eye movement data. ResultsPatients did not differ from the healthy controls regarding age, sex, and years of education. However, the patients' Montreal Cognitive Assessment total score was significantly lower than healthy controls. Most eye movement parameters were significantly worse in patients. These included the latencies, gain (computed as the ratio between stimulus amplitude and gaze amplitude), velocities, and accuracy (evaluated by the presence of hypermetric or hypometria dysmetria) of both visually and memory-guided saccades; the number of correct memory saccades; the latencies and duration of reflexive saccades; and the number of errors in the antisaccade test. Machine learning permitted distinguishing between long COVID patients experiencing subjective cognitive complaints and healthy controls. ConclusionOur findings suggest impairments in frontal subcortical circuits among long COVID patients who report subjective cognitive complaints. Eye-tracking, combined with machine learning, offers a novel, efficient way to assess and monitor long COVID patients' cognitive dysfunctions, suggesting its utility in clinical settings for early detection and personalized treatment strategies. Further research is needed to determine the long-term implications of these findings and the reversibility of cognitive dysfunctions.

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 disease characterized by flares of widespread skin pustulation. 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 in Effisayil 2 (NCT04399837), a 48-week 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.

Measuring GPPGA, Pain, Symptom, and Quality of Life Index Scores in Untreated Generalized Pustular Psoriasis: Results from the Placebo Group of the Effisayil-2 Trial

Introduction &amp; Objectives: Generalized pustular psoriasis (GPP) is a chronic inflammatory, and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab is approved to treat GPP flares in adults. Effisayil 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report on the underlying disease burden of untreated GPP by longitudinally analyzing patients in the placebo group who did not experience a GPP flare.&#x0D; Materials &amp; Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to receive one of three subcutaneous spesolimab regimens or placebo for 48 weeks. Patients were assessed for measures of chronic disease burden through the use of Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) Total Score, Pain Visual Analog Scale (VAS), and Psoriasis Symptom Scale (PSS) at baseline and at 4-week intervals during the trial, and Dermatology Quality of Life Index (DLQI) at baseline and weeks 4, 8, 12, 24, 36, and 48.&#x0D; Results: 16/31 placebo-treated patients experienced a GPP flare over the 48-week observational period of the trial, defined as an increase in GPPPGA score by ≥2 from baseline and the pustular component of GPPPGA ≥2. Of the remaining (“non-flaring”) 15 patients, 40% (6/15) had at least one GPPPGA Total Score value of 2 (skin not clear or almost clear); 4/6 reported such score at ≥4 visits. Pain scores ranged from 0 to 92.47, with 47% (7/15) and 20% (3/15) of patients having at least one “moderate” and “severe” VAS score over 48 weeks, respectively. Most of the 7 patients’ pain scores fluctuated with episodic peaks and valleys. 47% (7/15) and 13% (2/15) of patients had at least one “moderate” and “severe” PSS score, respectively. “Moderate” and “very large” effect on quality of life was reported, at least once, in 67% (10/15) and 40% (6/15) of patients, respectively.&#x0D; Conclusion: Acute flare was reported in more than 50% (16/31) of patients in the placebo group over 48 weeks. Despite not meeting the trial’s definition of GPP flare, most of the 15 “non-flaring” placebo-treated patients showed clear evidence of underlying GPP disease activity – nearly half did not have “clear” or “almost clear” skin and had moderate pain and symptoms; a small subset reported severe pain and symptoms. Majority of patients experienced a moderate to very large impact on quality of life over the 48 weeks. These findings suggest that untreated GPP negatively affects patients even in the absence of acute flare events.