Measures Of Disease Severity Research Articles

Factors Associated With Treatment Escalation for Psoriasis: An Analysis of Electronic Health Records Data

Background Electronic health records (EHRs) offer the possibility of using data entry templates to simultaneously document routine clinical care and capture disease-specific measures as discrete data elements that can be used for health services research (HSR). The objective of this study was to determine factors associated with meaningful treatment escalation (MTE) of psoriasis as a pilot study for future real-world HSR studies. Methods We conducted a retrospective, observational cohort study of psoriasis patients by using data collected during routine clinical care from an EHR using EpiCare® SmartForms. The psoriasis SmartForm records psoriasis disease severity measures and descriptive findings to generate visit notes. These data were extracted and analyzed to identify factors associated with MTE, defined as changing or adding, phototherapy, systemic, or biologic therapy. Results 473 psoriasis patients met study criteria; 239 underwent MTE between their first and third observed visits. Patients who experienced MTE had more severe disease at Visit 1—assessed by BSA, pPGA, oPGA, and a patient-reported disease severity measure--than patients who did not experience MTE. Other factors associated with MTE included use of topicals only or no active treatment at Visit 1, palmoplantar disease, and involvement of other difficult-to-treat body areas. Patients who underwent MTE experienced larger improvements in disease severity than those who did not. Conclusions This study highlights how data collected during routine clinical practice can be readily used for real-world retrospective HSR when disease measures are captured as discrete elements. This approach could provide a cost-effective platform to conduct real-world HSR.

Evaluation of Post-Swallow Residue with Visual Analysis of Swallowing Efficiency and Safety in Patients with Idiopathic Parkinson's Disease.

Objectives: Dysphagia is common in idiopathic Parkinson's disease (IPD) and is associated with impairments in both swallowing safety and swallowing efficiency. The goals of this study were to define post-swallow residue patterns in people with IPD and describe pathophysiological endoscopic findings affecting residue accumulation. Methods: This was a prospective single-blinded cross-sectional cohort study of patients with the diagnosis of IPD recruited from a Movement Disorder Clinic. Clinical variables included patient age, cognitive function, and measures of disease severity, and laryngoscopic examinations with a flexible endoscopic evaluation of swallowing (FEES) were completed for each patient. Visual Analysis of Swallowing Efficiency and Safety (VASES) was used to analyze FEES. Post-swallow residue outcomes and non-residue endoscopic outcomes including the Bowing index, Penetration Aspiration Scale (PAS) score, premature leakage, and build-up phenomenon were evaluated. Multiple regression models were used to evaluate factors affecting the residue at different anatomic levels. Results: Overall 53 patients completed the study. The multiple regression analyses showed a relation between (1) the presence of residue at the level of oropharynx and epiglottis with premature leakage, (2) the presence of residue at the level of the laryngeal vestibule and vocal folds with build-up phenomenon, and (3) the presence of residue at the level of the hypopharynx, laryngeal vestibule, and subglottis with airway invasion. Conclusion: Residue pattern during FEES is associated with specific swallow dysfunctions in IPD. Using residue localization and quantification may be a helpful tool in assessing the impact of targeted swallowing interventions in patients with IPD and dysphagia.

Commensal Oral Microbiota, Disease Severity, and Mortality in Fibrotic Lung Disease.

Rationale: Oral microbiota associate with diseases of the mouth and serve as a source of lung microbiota. However, the role of oral microbiota in lung disease is unknown. Objectives: To determine associations between oral microbiota and disease severity and death in idiopathic pulmonary fibrosis (IPF). Methods: We analyzed 16S rRNA gene and shotgun metagenomic sequencing data of buccal swabs from 511 patients with IPF in the multicenter CleanUP-IPF (Study of Clinical Efficacy of Antimicrobial Therapy Strategy Using Pragmatic Design in IPF) trial. Buccal swabs were collected from usual care and antimicrobial cohorts. Microbiome data were correlated with measures of disease severity using principal component analysis and linear regression models. Associations between the buccal microbiome and mortality were determined using Cox additive models, Kaplan-Meier analysis, and Cox proportional hazards models. Measurements and Main Results: Greater buccal microbial diversity associated with lower FVC at baseline (mean difference, -3.60; 95% confidence interval [CI], -5.92 to -1.29% predicted FVC per 1-unit increment). The buccal proportion of Streptococcus correlated positively with FVC (mean difference, 0.80; 95% CI, 0.16 to 1.43% predicted per 10% increase) (n = 490). Greater microbial diversity was associated with an increased risk of death (hazard ratio, 1.73; 95% CI, 1.03-2.90), whereas a greater proportion of Streptococcus was associated with a reduced risk of death (HR, 0.85; 95% CI, 0.73 to 0.99). The Streptococcus genus was mainly composed of Streptococcus mitis species. Conclusions: Increasing buccal microbial diversity predicts disease severity and death in IPF. The oral commensal S. mitis spp associates with preserved lung function and improved survival.

Comparing benefit and detriment from medical diagnostic radiation exposure using disability-adjusted life years: towards quantitative justification

Justification of medical radiation exposure is one of the main elements of radiation protection for patients. For a medical exposure to proceed, the benefit from the procedure must have been determined to be greater than the detriment. It is rare, however, that justification can be stated quantitatively as a ratio of benefit to detriment, or as a net benefit, and this is particularly true for medical diagnostic exposures associated with non-fatal diseases where survival statistics do not apply. The concept of the disability-adjusted life year (DALY) is well established as a measure of disease severity in public health, and there have been calls to revise the international system of radiation protection dosimetry to employ the DALY as a measure of radiation detriment. This paper looks at possible routes to quantify the benefit and detriment aspects of justification based on initial published results for the use of the DALY as a measure of radiation detriment, together with established values of DALY for a range of diseases. Although spreadsheet-style solutions for the calculation of a justification factor based on statistical life tables can be devised, these will be shown to have some limitations. A justification factor based on the rate of change of benefit divided by the rate of change of detriment following medical exposure is proposed. This factor is simple to calculate, is age independent, can apply to non-fatal diseases and is argued to have logical and ethical advantages for the explanation of the relative benefits and detriments of radiological procedures to patients.

Passively monitored smartphone battery percentage relates to disease severity in frontotemporal dementia: A proof‐of‐concept study

AbstractBackgroundFrontotemporal dementia (FTD) is a leading cause of dementia in individuals under age 65. Due to limitations in access to in‐person evaluations, there is an urgent need to examine remote, accessible, and low‐burden assessment techniques for FTD. Unobtrusive monitoring of at‐home computer use in older adults has shown that those with mild cognitive impairment (MCI) have significant declines in computer use over time. To extend these findings, we characterized daily trajectories in smartphone battery percentage, a proxy of smartphone use, and examined relationships with clinical indicators of disease severity in FTD.MethodParticipants included 250 adults enrolled in the ALLFTD Mobile App study (mean age = 53.9 [SD = 14.9]; 59% women; 94% White). To assess clinical disease severity, all participants completed the FTLD Clinical Dementia Rating scale (CDR®+NACC FTLD), a brief neuropsychological battery, the Neuropsychiatric Inventory Questionnaire (NPI‐Q), and brain MRI. The ALLFTD Mobile App was installed onto participants’ smartphones for remote, passive, continuous monitoring of smartphone use (average days of monitoring = 82 [range = 7‐541]). Battery percentage was collected every 15 minutes. Linear mixed effects models examined linear, quadratic, and cubic effects of time of day (i.e., hour; modeled as person‐specific random effects) and their interactions with each measure of disease severity on battery percentage. Models covaried for age.Result57% of participants were clinically normal, 21% had MCI, and 22% had dementia. CDR®+NACC FTLD Global score interacted with hour such that participants with MCI and dementia had flatter battery curves (i.e., less change in battery percentage throughout the day – a proxy of less smartphone use) than clinically normal participants (ps<0.001). Additional models showed that worse memory (hour3 x memory score: 𝛃 = 0.59, p<0.001) and executive functioning (hour3 x executive score: 𝛃 = 0.64, p<0.001), more neuropsychiatric symptoms (hour3 x NPI‐Q: 𝛃 = ‐0.22, p = 0.004), and smaller gray matter volumes (controlling for intracranial volume; hour3 x volume: 𝛃 = 0.49, p<0.001) were also statistically significantly related to less battery usage throughout the day.ConclusionThese findings are proof‐of‐concept that passively acquired smartphone data, specifically battery usage, can provide insights about disease progression in FTD. Results support future research focusing on the development of passively collected digital metrics sensitive to clinical declines in neurodegenerative disease.

Examining longitudinal changes of disease severity scores in familial forms of frontotemporal dementia within the GENFI cohort

AbstractBackgroundThe CDR®+NACC FTLD Sum of Boxes (SB) score is a well‐established measure of disease severity in frontotemporal dementia (FTD), however, few studies have assessed longitudinal changes in score within familial forms of FTD.Method343 participants from the Genetic FTD Initiative (77 mutation‐negative controls, 109 C9orf72 expansion carriers, 105 GRN mutation carriers, and 52 MAPT mutation carriers), with available scores on the CDR®+NACC FTLD‐SB and the FTD Rating Scale (FRS) at baseline and follow‐up, were examined. Using the baseline FRS percentage scores, mutation carriers were stratified into four groups: asymptomatic/very mild (100‐97%), mild (96‐80%), moderate (79‐41%), and severe (40‐0%). Linear regression models with bootstrapping were used to assess annualised change in CDR®+NACC FTLD‐SB scores across genetic groups between participants' first and follow‐up visit.Result C9orf72 and GRN mutation carriers in the moderate and severe groups, as well as mild GRN carriers, showed significantly greater change than controls (p < 0.050). No significant differences in change scores were observed between MAPT mutation carriers and controls. Comparisons within genetic groups revealed that both the moderate and severe GRN and C9orf72 expansion carriers showed larger annualised change relative to their asymptomatic/very mild counterparts (p < 0.001 and p = 0.037; p = 0.028 and p < 0.001, respectively). The moderate GRN and severe C9orf72 groups also demonstrated greater annualised score changes than their respective mild counterparts (p < .001; p = 0.001). For MAPT mutation carriers, no significant changes were observed. Between genetic group comparisons revealed significant change score differences between the moderate individuals, with GRN mutation carriers showing a greater change than the C9orf72 and MAPT groups (both p < 0.001), and the C9orf72 group showing a larger annualised change than the MAPT mutation carriers (p = 0.041).ConclusionThe CDR®+NACC FTLD‐SB detects significant changes in disease severity from baseline to a first follow‐up visit in familial forms of FTD, with GRN mutation carriers showing the greatest annualised change.

Application of a Validated Method for Quantifying Circulating Protoporphyrin IX to the Beacon Trial of Bitopertin in Erythropoietic Protoporphyria

Introduction: Accumulation of the photoreactive heme precursor protoporphyrin IX (PPIX) is a signature of the disease pathophysiology for both erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP), and PPIX levels correlate with disease severity and light tolerance. Additionally, an elevated ratio of circulating metal-free PPIX vs. metal-bound PPIX is observed in patients with protoporphyrias, and the extent of metal-free elevation is distinguishable between EPP (85-100%) and XLP (50-85%). Therefore, the accurate determination of metal-free PPIX and metal-bound PPIX is of particular interest in patients with EPP or XLP. Methods: Novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were developed and validated to quantify circulating metal-free and zinc (Zn)-complexed PPIX in whole blood and plasma. Each of the four assays were developed and validated according to applicable regulatory guidance for bioanalytical assay validation with regard to accuracy, precision, sensitivity, and selectivity. The minimum required sample volume for each assay was 200 µL, compared to >1 mL for most currently available protoporphyria-related assays. During bioanalytical method development, rapid degradation of metal-free PPIX (≥90%) and Zn-PPIX (up to 96%) was observed in plasma samples within 24 hours under ambient light conditions. In contrast, whole blood was less susceptible to photodegradation (i.e., ≤20% for both metal-free PPIX and Zn-PPIX) under the same conditions. The most effective method for maintaining sample integrity was reduction of light exposure during sample collection, handling, and processing. Implementation of light-reduction controls was used during method validation and facilitated improved stability of metal-free PPIX and Zn-PPIX in plasma and whole-blood samples. For the metal-free PPIX plasma assay validation, the effect of hemolysis was evaluated due to the apparent sequestration of metal-free PPIX in red blood cells. The bioanalytical work informed specific sample-collection procedures to mitigate instability and hemolysis, such as the use of opaque consumables for sample collection, controls for plasma aliquoting, and operating under low-light conditions for all sample handling and processing. BEACON is a Phase 2, randomized, open-label, parallel-arm trial (ACTRN12622000799752) of approximately 22 participants who will receive oral, once-daily administration of 20 or 60 mg of bitopertin for 6 months. Baseline light tolerance was assessed using 2 patient-reported outcomes measures during a 2- to 4-week screening period. Participants were asked to conduct weekly sun exposure challenges and time to first prodromal symptom (itching, burning, tingling, etc.) was averaged for the screening period. Results: More than 600 clinical samples from 17 participants in the BEACON study have been collected as of 06 June 2023 and analyzed using the validated porphyrin assays. Measured metal-free PPIX baseline values ranged from 1440 - 34,100 ng/mL (2.6 - 61 µM) in whole blood and 177 - 2560 ng/mL (0.31 - 4.5 µM) in plasma ( n=16). Baseline percentage of intra-patient plasma/whole-blood concentrations ranged from 2.5 - 16%. Each participant's baseline values were converted to erythrocyte metal-free PPIX concentrations using measured hematocrit levels and ranged from 3590 - 88400 ng/mL (6.4 - 157 µM). These values were comparable to data previously reported in the literature (6-139 µM 1). Additionally, higher baseline whole-blood metal-free PPIX concentrations were associated with decreased averages for time to prodrome (Table 1). Conclusion: Fully-validated LC-MS/MS assays to quantify metal-free PPIX and Zn-PPIX in plasma and whole blood were used to analyze clinical samples from the BEACON study evaluating bitopertin in EPP. PPIX values were consistent with previously reported values for patients with EPP. The methods also provided improved accuracy and specificity for metal-free vs. metal-complexed PPIX and reduced sample volume requirements. In addition, higher baseline whole-blood PPIX values were associated with decreased light tolerance within the trial population, supporting its use as a measure of disease severity in EPP.

Screening of Rice Genotypes for Resistance Against Bacterial Blight Disease

A study was undertaken at V. C. Farm, Mandya, Karnataka, India during 2020 to screen the genotypes against BLB under natural field conditions. Host Plant resistance is an important component of an integrated management program for this disease. Among the 102 rice genotypes screened under natural epiphytotic condition at Zonal Agricultural Station, V. C. Farm, Mandya, none of them were found immune against bacterial leaf blight. So, in the study, plants were assessed by measuring disease severity (% of leaf diseased) and area under the disease progress curve (AUDPC). The pathogenicity of Xoo was tested on IRRI rice cultivars, inoculation was conducted at the maximum tillering stage, and the lesion length was measured after 14 days of inoculation. An attempt was made to phenotypically characterize a set of 102 Genotypes from IRRI for BLB resistance by artificially inoculaton using clipping method. Out of the 102 genotypes and two checks tested, it was observed that five entries viz., IRGC 125853, IRGC 126264, IRGC 132357, IRGC 122088 IRGC 125658 and Improved Samba Mahsuri were highly resistant with score of 1. Only one entry (IRGC 125754) was resistant with score of 3, 33 lines being moderately resistant with score of 5 and 43 lines were susceptible with score of 7. 20 lines and also the susceptible check Jyothi-PTB 39, had the highest susceptibility with a phenotypic score of 9.

Use of Antipseudomonal Antibiotics is Not Associated With Lower Rates of Postoperative Drainage Procedures or More Favorable Culture Profiles in Children With Complicated Appendicitis: Results From a Multicenter Regional Research Consortium.

To compare rates of postoperative drainage and culture profiles in children with complicated appendicitis treated with the 2 most common antibiotic regimens with and without antipseudomonal activity [piperacillin-tazobactam (PT) and ceftriaxone with metronidazole (CM)]. Variation in the use of antipseudomonal antibiotics has been driven by a paucity of multicenter data reporting clinically relevant, culture-based outcomes. A retrospective cohort study of patients with complicated appendicitis (7/2015-6/2020) using NSQIP-Pediatric data from 15 hospitals participating in a regional research consortium. Operative report details, antibiotic utilization, and culture data were obtained through supplemental chart review. Rates of 30-day postoperative drainage and organism-specific culture positivity were compared between groups using mixed-effects regression to adjust for clustering after propensity matching on measures of disease severity. In all, 1002 children met the criteria for matching (58.9% received CM and 41.1% received PT). In the matched sample of 778 patients, children treated with PT had similar rates of drainage overall [PT: 11.8%, CM: 12.1%; odds ratio (OR): 1.44 (OR: 0.71-2.94)] and higher rates of drainage associated with the growth of any organism [PT: 7.7%, CM: 4.6%; OR: 2.41 (95% CI: 1.08-5.39)] and Escherichia coli [PT: 4.6%, CM: 1.8%; OR: 3.42 (95% CI: 1.07-10.92)] compared to treatment with CM. Rates were similar between groups for drainage associated with multiple organisms [PT: 2.6%, CM: 1.5%; OR: 3.81 (95% CI: 0.96-15.08)] and Pseudomonas [PT: 1.0%, CM: 1.3%; OR: 3.42 (95% CI: 0.55-21.28)]. The use of antipseudomonal antibiotics is not associated with lower rates of postoperative drainage procedures or more favorable culture profiles in children with complicated appendicitis.

Assessment of the disease severity in patients hospitalized for COVID-19 based on the National Early Warning Score (NEWS) using statistical and machine learning methods: An electronic health records database analysis.

The coronavirus disease 2019 (COVID-19) was a cause of concern in the healthcare system and increased the need for disease severity indicators. However, they still vary in use to evaluate in-hospital outcomes and severity. The National Early Warning Score (NEWS) is routinely used to evaluate patient health status at the hospital. Further research is needed to ensure if NEWS can be a good instrument for an overall health status assessment with or without additional information like laboratory tests, intensive care needs, and history of chronic diseases. To evaluate if NEWS can be an indicator to measure COVID-19 patient status in-hospital. We used the fully anonymized Electronic Health Records (EHR) characterizing patients admitted to the hospital with COVID-19. Data was obtained from Vilnius University Hospital Santaros Klinikos EHR system (SANTA-HIS) from 01-03-2020 to 31-12-2022. The study sample included 3875 patients. We created several statistical and machine learning models for discrimination between in-hospital death/discharge for evaluation NEWS as a disease severity measure for COVID-19 patients. In these models, two variable sets were considered: median NEWS and its combination with clinical parameters and medians of laboratory test results. Assessment of models' performance was based on the scoring metrics: accuracy, sensitivity, specificity, area under the ROC curve (AUC), and F1-score. Our analysis revealed that NEWS predictive ability for describing patient health status during the stay in the hospital can be increased by adding the patient's age at hospitalization, gender, clinical and laboratory variables (0.853 sensitivity, 0.992 specificity and F1-score - 0.859) in comparison with single NEWS (0.603, 0.995, 0.719, respectively). A comparison of different models showed that stepwise logistic regression was the best method for in-hospital mortality classification. Our findings suggest employing models like ours for advisory routine usage. Our model demonstrated incremental value for COVID-19 patient's status evaluation.

Efficacy of Secukinumab in Patients With Mild to Moderate Psoriasis: A Pooled Analysis of 6 Phase 3 Studies

Introduction: Secukinumab has demonstrated sustained long-term efficacy for the treatment of patients with moderate to severe plaque psoriasis, but efficacy in mild to moderate psoriasis has not been rigorously evaluated. The secukinumab phase 3 clinical trial program included patients with mild to moderate psoriasis among populations with active psoriatic arthritis (EXCEED and FUTURE 2-5; NCT02745080, NCT01752634, NCT01989468, NCT02294227, and NCT02404350), and among patients with moderate to severe palmoplantar psoriasis (GESTURE; NCT01806597). Here, we report efficacy and safety of secukinumab in a pooled population of patients with mild to moderate psoriasis.
 Methods: This post hoc analysis included patients from the phase 3 EXCEED, FUTURE 2-5, and GESTURE trials, with mild to moderate psoriasis defined as either a baseline affected body surface area (BSA) of 3%-10% or a baseline Investigator’s Global Assessment modified 2011 score (IGA) of 2 or 3. Patients were pooled by treatment received through Week 16 (treatment period 1) and from Weeks 16 to 52 (treatment period 2), according to the following groups: treatment period 1 (secukinumab 300 mg, secukinumab 150 mg, or placebo) and treatment period 2 (secukinumab 300 mg or secukinumab 150 mg). Efficacy was assessed by the proportion of patients achieving 75% improvement in the Psoriasis Area and Severity Index (PASI75), PASI90, and PASI100 among patients with a BSA 3%-10%; and by IGA 0/1 response with ≥2-point improvement among patients with baseline IGA score of 2 or 3. Descriptive statistics were reported for each outcome. Missing data were imputed using non-responder imputation.
 Results: Overall, 654 patients and 971 patients had mild to moderate psoriasis at baseline as defined by a BSA of 3%-10% or IGA score of 2 or 3, respectively. Demographics and baseline disease characteristics were similar between populations defined by BSA and by IGA. Among patients with a baseline BSA of 3%-10%, secukinumab resulted in greater achievement of PASI75/90/100 vs placebo at Week 12 (secukinumab 300 mg: 62.8%/44.4%/33.1%; secukinumab 150 mg: 48.0%/29.1%/19.4%; placebo: 11.7%/9.0%/8.0%), with increased responses at Week 52 (secukinumab 300 mg: 65.7%/56.5%/47.3%; secukinumab 150 mg: 58.1%/40.5%/31.3%). The proportion of patients with baseline IGA=2 or 3 achieving IGA 0/1 response with ≥2-point improvement was greater among patients receiving secukinumab 300 mg (46.6%) or 150 mg (37.2%) than placebo (8.6%) at Week 12, with increased responses at Week 52 (secukinumab 300 mg: 52.5%; secukinumab 150 mg: 44.4%).
 Conclusions: Secukinumab led to improvements in measures of disease severity among patients with mild to moderate psoriasis after 12 weeks of treatment vs placebo in a pooled analysis of patients with psoriatic arthritis or palmoplantar psoriasis. Both doses of secukinumab showed increased efficacy from Week 12 to Week 52.

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Moderate to Severe Plaque Psoriasis: Efficacy by Baseline Body Surface Area (BSA) Involvement and Baseline Psoriasis Area and Severity Index (PASI)

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. In the phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials, deucravacitinib was significantly more efficacious than placebo and apremilast. This analysis evaluated deucravacitinib efficacy by two measures of baseline disease severity, BSA involvement and PASI scores.
 Methods: Patients were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily in both trials, which included 16-week placebo-controlled and 24-week apremilast-controlled periods from Day 1. Of patients randomized to deucravacitinib, those in PSO-1 were treated continuously for 52 weeks; in PSO-2, Week 24 PASI 75 responders were rerandomized to continued deucravacitinib or placebo. Patients randomized to placebo crossed over to deucravacitinib at Week 16 and were treated through Week 52. Efficacy outcomes, including ≥75%/≥90%/100% reductions from baseline in PASI (PASI 75/90/100) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1), were evaluated using nonresponder imputation in disease severity subgroups defined by baseline BSA involvement (10%-<15%, 15%-<20%, 20%-<30%, ≥30%) and PASI score (12-<15, ≥15). Results are reported through Week 24 in the pooled PSO-1/PSO-2 population (apremilast-controlled) and through Week 52 in the PSO-1 population (continuous deucravacitinib treatment).
 Results: In the pooled PSO-1/PSO-2 population (N=1686), 391 (23.2%) had baseline BSA involvement of 10%-<15% (deucravacitinib, n=194), 371 (22.0%) had 15%-<20% (deucravacitinib, n=183), 391 (23.2%) had 20%-<30% (deucravacitinib, n=198), and 533 (31.6%) had ≥30% (deucravacitinib, n=268). For baseline PASI scores, 387 (23.0%) had a score of 12-<15 (deucravacitinib, n=183) and 1298 (77.0%) had a score of ≥15 (deucravacitinib, n=660). Deucravacitinib-treated patients had comparable PASI 75 response rates across all subgroups at Week 16 (BSA subgroups, 50.5%-58.2%; PASI subgroups, 48.6%-57.0%) and at Week 24 (BSA subgroups, 62.0%-64.1%; PASI subgroups, 59.9%-63.8%), with superior responses versus those in patients receiving placebo or apremilast evaluated in each subgroup. Similar findings were observed for all other efficacy measures. In PSO-1, efficacy was maintained through Week 52 with continuous deucravacitinib treatment across BSA (PASI 75, 67.1%-75.7%; sPGA 0/1, 52.1%-61.2%) and PASI subgroups (PASI 75, 65.6%-73.1%; sPGA 0/1, 54.7%-58.8%).
 Conclusion: Deucravacitinib was efficacious in patients with moderate or severe plaque psoriasis regardless of extent of baseline BSA involvement or PASI scores.

Myocardial T1 dispersion in fabry disease: comprehensive evaluation of a novel measurement of cardiovascular disease severity

Abstract Background The cardiovascular manifestations of Fabry disease are common and represent the leading cause of death. Myocardial T1 dispersion has recently emerged as a robust predictor of adverse cardiac outcome in Fabry disease but the relationship between T1 dispersion and other cardiovascular manifestations has not been studied. Objective To evaluate the relationship between myocardial T1 dispersion and other cardiovascular manifestations of Fabry disease, and identify its determinants. Methods Prospective longitudinal cohort study including 181 participants with Fabry disease and 30 controls undergoing clinical cardiovascular magnetic resonance. T1 dispersion was assessed in relation to other structural and functional cardiovascular biomarkers and examined in Pre-hypertrophic, Hypertrophic and Fibrotic phenotypic sub-groups. Determinates of T1 dispersion were investigated using multivariable linear regression. Results T1 dispersion was similar in the Control, Pre-hypertrophic and Hypertrophic sub-groups, but was significantly elevated in the Fibrotic sub-group. Independent determinates of T1 dispersion were age, body surface area-indexed left ventricular mass, indexed left ventricular end diastolic volume, global longitudinal strain, native myocardial T1, non-ischaemic late gadolinium enhancement, and extracellular volume fraction (R2 0.414). T1 dispersion was consistently higher in females than males. Conclusions Myocardial T1 dispersion appears sensitive to both the T1 shortening effect of globotriaosylceramide accumulation and T1 lengthening effect of fibrosis, and accordingly increases as Fabry disease progresses. In conjunction with recent data showing it to be a robust predictor of adverse cardiac outcome, myocardial T1 dispersion is advocated as a key cardiovascular biomarker in Fabry disease.Figure 1Figure 2

Abstract 15424: Phase-to-Phase Short Phenomenon in a Left Ventricular Assist Device: Navigating Through Clinical and Ethical Challenges

Description of Case A 59-year-old male with an axial continuous-flow left ventricular assist device (CF-LVAD) presented asymptomatically after noticing low-flow alarms. He reported extensive external driveline damage that accumulated over one year. The CF-LVAD was connected to an ungrounded cable and the driveline was repaired by the manufacturer. However, low-flow alarms continued. Log files revealed pump stoppages on all modes of power which was compatible with phase-to-phase short phenomenon (PtPSP). The patient was cannulated in case of emergent need for ECMO and upgraded to UNOS status 1 for heart transplant. Because PtPSP was considered unrepairable, the patient underwent emergent cardiac transplantation. Discussion The CF-LVAD driveline consists of three phases, each of which is formed by two electrical wires, connected to six motor stators. PtPSP causes driveline dysfunction due to a loss of insulation between the three phases owing to multiple breaches of the insulator, causing the pump to lose power when the damaged phases come into contact. Pump stoppages are likely and unpredictable even on batteries or an ungrounded cable. Patients may notice alarms associated with low flow, pump speed drops, or pump arrest. PtPSP is unrepairable, and pump exchange or urgent heart transplantation are the only viable treatment options.This case highlights the ethical complexity of the care of patients with advanced heart failure, whereby subjective treatment decisions often translate to objectively different levels of priority on the heart transplantation waiting list without intrinsic measures of disease severity, which may incentivize more aggressive care. Conclusions: CF-LVAD driveline dysfunction due to PtPSP is a clinically asymptomatic ominous scenario often uncovered by pump-controller alarms. Given the high risk of abrupt pump stoppage, a diagnosis of PtPSP necessitates emergent device exchange or explant with an orthotopic heart transplantation.

6 Remote Smartphone Cognitive and Motor Testing in Frontotemporal Dementia Research: Feasibility, Reliability, and Validity

Objective:Therapeutics targeting frontotemporal dementia (FTD) are entering clinical trials. There are challenges to conducting these studies, including the relative rarity of the disease. Remote assessment tools could increase access to clinical research and pave the way for decentralized clinical trials. We developed the ALLFTD Mobile App, a smartphone application that includes assessments of cognition, speech/language, and motor functioning. The objectives were to determine the feasibility and acceptability of collecting remote smartphone data in a multicenter FTD research study and evaluate the reliability and validity of the smartphone cognitive and motor measures.Participants and Methods:A diagnostically mixed sample of 207 participants with FTD or from familial FTD kindreds (CDR®+NACC-FTLD=0 [n=91]; CDR®+NACC-FTLD=0.5 [n=39]; CDR®+NACC-FTLD>1 [n=39]; unknown [n=38]) were asked to remotely complete a battery of tests on their smartphones three times over two weeks. Measures included five executive functioning (EF) tests, an adaptive memory test, and participant experience surveys. A subset completed smartphone tests of balance at home (n=31) and a finger tapping test (FTT) in the clinic (n=11). We analyzed adherence (percentage of available measures that were completed) and user experience. We evaluated Spearman-Brown split-half reliability (100 iterations) using the first available assessment for each participant. We assessed test-retest reliability across all available assessments by estimating intraclass correlation coefficients (ICC). To investigate construct validity, we fit regression models testing the association of the smartphone measures with gold-standard neuropsychological outcomes (UDS3-EF composite [Staffaroni et al., 2021], CVLT3-Brief Form [CVLT3-BF] Immediate Recall, mechanical FTT), measures of disease severity (CDR®+NACC-FTLD Box Score & Progressive Supranuclear Palsy Rating Scale [PSPRS]), and regional gray matter volumes (cognitive tests only).Results:Participants completed 70% of tasks. Most reported that the instructions were understandable (93%), considered the time commitment acceptable (97%), and were willing to complete additional assessments (98%). Split-half reliability was excellent for the executive functioning (r’s=0.93-0.99) and good for the memory test (r=0.78). Test-retest reliabilities ranged from acceptable to excellent for cognitive tasks (ICC: 0.70-0.96) and were excellent for the balance (ICC=0.97) and good for FTT (ICC=0.89). Smartphone EF measures were strongly associated with the UDS3-EF composite (ß's=0.6-0.8, all p<.001), and the memory test was strongly correlated with total immediate recall on the CVLT3-BF (ß=0.7, p<.001). Smartphone FTT was associated with mechanical FTT (ß=0.9, p=.02), and greater acceleration on the balance test was associated with more motor features (ß=0.6, p=0.02). Worse performance on all cognitive tests was associated with greater disease severity (ß's=0.5-0.7, all p<.001). Poorer performance on the smartphone EF tasks was associated with smaller frontoparietal/subcortical volume (ß's=0.4-0.6, all p<.015) and worse memory scores with smaller hippocampal volume (ß=0.5, p<.001).Conclusions:These results suggest remote digital data collection of cognitive and motor functioning in FTD research is feasible and acceptable. These findings also support the reliability and validity of unsupervised ALLFTD Mobile App cognitive tests and provide preliminary support for the motor measures, although further study in larger samples is required.

Silent Airway Mucus Plugs in COPD and Clinical Implications

BackgroundAirway mucus plugs are frequently identified on computed tomography (CT) scans of patients with COPD with a smoking history without mucus-related symptoms, i.e., cough and phlegm (“silent mucus plugs”). Research QuestionsIn patients with COPD, what are risk and protective factors associated with silent airway mucus plugs? Are silent mucus plugs associated with functional, structural, and clinical measures of disease? Study Design and MethodsWe identified mucus plugs on chest CT scans of participants with COPD from the COPDGene study. The mucus plug score was defined as the number of pulmonary segments with mucus plugs, ranging from 0 to 18, and categorized into three groups (0, 1-2, and 3+). We determined risk and protective factors for silent mucus plugs and the associations of silent mucus plugs with measures of disease severity using multivariable linear and logistic regression models. ResultsOf 4,363 participants with COPD, 1,739 had no cough or phlegm. Among the 1,739 participants, 627 (36%) had airway mucus plugs identified on CT. Risk factors of silent mucus plugs (compared to symptomatic mucus plugs) were older age (Odds ratio, OR=1.02), female sex (OR=1.40), and Black race (OR=1.93) (all P values < 0.01). Among those without cough or phlegm, silent mucus plugs (vs. absence of mucus plugs) were associated with worse 6-MWD, resting SpO2, FEV1% predicted, greater emphysema, thicker airway walls, and higher odds of severe exacerbation in the past year in adjusted models. InterpretationMucus plugs are common in COPD patients without mucus-related symptoms. Silent mucus plugs are associated with worse functional, structural and clinical measures of disease. CT-identified mucus plugs can complement the evaluation of patients with COPD.

Functional proportional hazards mixture cure model with applications in cancer mortality in NHANES and post ICU recovery.

We develop a functional proportional hazards mixture cure model with scalar and functional covariates measured at the baseline. The mixture cure model, useful in studying populations with a cure fraction of a particular event of interest is extended to functional data. We employ the expectation-maximization algorithm and develop a semiparametric penalized spline-based approach to estimate the dynamic functional coefficients of the incidence and the latency part. The proposed method is computationally efficient and simultaneously incorporates smoothness in the estimated functional coefficients via roughness penalty. Simulation studies illustrate a satisfactory performance of the proposed method in accurately estimating the model parameters and the baseline survival function. Finally, the clinical potential of the model is demonstrated in two real data examples that incorporate rich high-dimensional biomedical signals as functional covariates measured at the baseline and constitute novel domains to apply cure survival models in contemporary medical situations. In particular, we analyze (i) minute-by-minute physical activity data from the National Health And Nutrition Examination Survey 2003-2006 to study the association between diurnal patterns of physical activity at baseline and all cancer mortality through 2019 while adjusting for other biological factors; (ii) the impact of daily functional measures of disease severity collected in the intensive care unit on post intensive care unit recovery and mortality event. Our findings provide novel epidemiological insights into the association between daily patterns of physical activity and cancer mortality. Software implementation and illustration of the proposed estimation method are provided in R.

Using Computer Vision to Improve Endoscopic Disease Quantification in Therapeutic Clinical Trials of Ulcerative Colitis

Endoscopic assessment of ulcerative colitis (UC) typically reports only the maximum severity observed. Computer vision methods may better quantify mucosal injury detail, which varies among patients. Endoscopic video from the UNIFI clinical trial (A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis) comparing ustekinumab and placebo for UC were processed in a computer vision analysis that spatially mapped Mayo Endoscopic Score (MES) to generate the Cumulative Disease Score (CDS). CDS was compared with the MES for differentiating ustekinumab vs placebo treatment response and agreement with symptomatic remission at week 44. Statistical power, effect, and estimated sample sizes for detecting endoscopic differences between treatments were calculated using both CDS and MES measures. Endoscopic video from a separate phase 2 clinical trial replication cohort was performed for validation of CDS performance. Among 748 induction and 348 maintenance patients, CDS was lower in ustekinumab vs placebo users at week 8 (141.9 vs 184.3; P < .0001) and week 44 (78.2 vs 151.5; P < .0001). CDS was correlated with the MES (P < .0001) and all clinical components of the partial Mayo score (P < .0001). Stratification by pretreatment CDS revealed ustekinumab was more effective than placebo (P < .0001) with increasing effect in severe vs mild disease (-85.0 vs -55.4; P < .0001). Compared with the MES, CDS was more sensitive to change, requiring 50% fewer participants to demonstrate endoscopic differences between ustekinumab and placebo (Hedges' g= 0.743 vs 0.460). CDS performance in the JAK-UC replication cohort was similar to UNIFI. As an automated and quantitative measure of global endoscopic disease severity, the CDS offers artificial intelligence enhancement of traditional MES capability to better evaluate UC in clinical trials and potentially practice.

Automated Disease Severity Measurement Using Image Processing

Apple orchards are vital to the agricultural industry, but they face constant threats from diseases like apple scab, powdery mildew, rust, and rot. Traditional methods for measuring disease severity in apple leaves are labour-intensive, subjective, and prone to errors, limiting their practicality for large-scale agriculture. This paper introduces an innovative approach leveraging image processing techniques to automate disease severity measurement in apple leaves, offering a transformative solution for orchard management. The research aims to provide an efficient and accurate method for assessing disease severity, addressing the critical need for precise disease management and improved crop yields. Current methods relying on visual inspections by human experts are inefficient and unreliable. In contrast, the proposed method automates the measurement process, saving time and resources, enabling frequent monitoring, and enhancing early disease detection. This automation, in turn, leads to more effective disease management and increased crop yield and quality. The methodology involves image preprocessing, grayscale conversion, histogram equalization, thresholding, and defect area extraction, ultimately resulting in a quantitative disease severity index. The study utilizes a diverse dataset of apple leaf images, allowing for robust model development capable of accurate disease detection under varying conditions. This research holds significant implications for disease management and crop yield optimization, with broader applicability across agriculture. It paves the way for precision agriculture by enabling data-driven decisions on disease control measures while reducing the environmental impact of chemical inputs. Furthermore, the image processing techniques developed here can be adapted to other crops and plant diseases, promising efficient and accurate disease severity measurement methods across agricultural domains.

The effect of COVID-19 vaccination status on all-cause mortality in patients hospitalised with COVID-19 in Hungary during the delta wave of the pandemic.

The high mortality of patients with coronavirus disease 2019 (COVID-19) is effectively reduced by vaccination. However, the effect of vaccination on mortality among hospitalised patients is under-researched. Thus, we investigated the effect of a full primary or an additional booster vaccination on in-hospital mortality among patients hospitalised with COVID-19 during the delta wave of the pandemic. This retrospective cohort included all patients (n = 430) admitted with COVID-19 at Semmelweis University Department of Medicine and Oncology in 01/OCT/2021-15/DEC/2021. Logistic regression models were built with COVID-19-associated in-hospital/30day-mortality as outcome with hierarchical entry of predictors of vaccination, vaccination status, measures of disease severity, and chronic comorbidities. Deceased COVID-19 patients were older and presented more frequently with cardiac complications, chronic kidney disease, and active malignancy, as well as higher levels of inflammatory markers, serum creatinine, and lower albumin compared to surviving patients (all p < 0.05). However, the rates of vaccination were similar (52-55%) in both groups. Based on the fully adjusted model, there was a linear decrease of mortality from no/incomplete vaccination (ref) through full primary (OR 0.69, 95% CI: 0.39-1.23) to booster vaccination (OR 0.31, 95% CI 0.13-0.72, p = 0.006). Although unadjusted mortality was similar among vaccinated and unvaccinated patients, this was explained by differences in comorbidities and disease severity. In adjusted models, a full primary and especially a booster vaccination improved survival of patients hospitalised with COVID-19 during the delta wave of the pandemic. Our findings may improve the quality of patient provider discussions at the time of admission.