Severity Index Research Articles

Insomnia treatment effects on negative emotionality among veterans in treatment for alcohol use disorder.

Insomnia symptoms are pervasive and persistent in alcohol use disorder (AUD), though little is known about the mechanisms that underlie this association. We previously found that cognitive behavioral therapy for insomnia (CBT-I) reduced alcohol-related problems among veterans by improving insomnia severity (NCT03806491). In this planned secondary analysis of the same clinical trial data, we tested negative emotionality as one potential mechanism to explain this effect. Specifically, we tested the change in negative emotionality as a mediator of the association between change in insomnia symptoms and alcohol-related outcomes (craving, heavy drinking frequency, and alcohol-related problems). Participants were 67 veterans in treatment for AUD who also met the criteria for insomnia disorder (91% male, 84% White, average age = 46.3 years). Participants were randomized to five sessions of CBT-I or a single-session sleep hygiene control. Assessments occurred at baseline, immediately posttreatment (~6 weeks after baseline), and at 6-week follow-up. Measures included the Insomnia Severity Index, Penn Alcohol Craving Scale, Timeline Followback, and Short Inventory of Problems. We created a latent negative emotionality indicator based on five validated and reliable measures of negative emotionality. Contrary to hypotheses, CBT-I did not improve negative emotionality relative to sleep hygiene control. However, across both treatment conditions, decreases in insomnia symptoms from baseline to posttreatment were associated with concurrent decreases in negative emotionality, which in turn predicted reductions in alcohol craving and heavy drinking. Negative emotionality may help explain links between insomnia symptoms and alcohol-related outcomes.

Admitting clinical department effect on outcomes for acute pulmonary embolism

Abstract Background Pulmonary embolism (PE) is the third most fatal cardiovascular disease and its management is often complex requiring multidisciplinary involvement. Aims To investigate whether there are differences between patient populations with acute PE and associated outcomes admitted to different clinical departments based on a German nationwide inpatient population. Methods We used the German nationwide inpatient sample to identify hospitalizations of patients with acute PE within the period 2005-2020. Patients were classified according to the department were they spent the longest duration of hospitalization (cardiology, general internal medicine, or pulmonology/critical care medicine). Patients admitted and treated to other departments were excluded from the analysis. Temporal trends of hospitalizations, as well as the impact of admitting departments on case-fatality were investigated with the cardiology department used as reference and after multivariable adjustment for age, sex, and comorbidities (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). Results During the investigated period a total of 759,115 patients with acute PE were identified; of those 117,501 (15.5%) were admitted to cardiology, 37,726 (5.0%) were admitted to pulmonology/critical care, while the majority of 603,888 (79.5%) were admitted to internal medicine (Table 1). A trend towards increasing number of patients admitted to cardiology in recent years was observed as opposed to being admitted to internal medicine. The number of patients admitted to pulmonology/critical care appeared stable (Figure 1A). Patients admitted to cardiology were more likely to be younger (Figure 1B) and had less risk factors for acute PE, such as cancer and recent surgery. The PE severity indices were higher in patients admitted to cardiology with a higher prevalence of tachycardia, syncope, signs of right ventricular dysfunction and shock (Table 1). There was an overall trend towards decrease in systemic thrombolysis and increase in catheter-directed thrombolysis independent of the admitting department. Catheter-directed thrombectomy has increased when patients were admitted to cardiology and internal medicine, but not when patients were admitted to pulmonology/critical care. Trends for in-hospital mortality were decreasing linearly over time independent of the admitting clinical service. In the multivariable adjustment, admission to cardiology was associated with significantly reduced rates of in-hospital mortality (OR 0.73, 95% CI 0.71-0.74). Conclusion In this nationwide analysis, the majority of patients with PE were hospitalized in an internal medicine ward, while notably, cardiology admissions demonstrated unique patient characteristics compared to other departments and were associated with decreased in-hospital mortality, suggesting specialized care's potential benefits in PE management.Table 1Figure 1

Evaluating a mobile application based intervention for insomnia in college students: a preliminary study

Objective: This study examined the feasibility, acceptability, and efficacy of a self-guided, mobile application for Cognitive Behavioral Therapy for Insomnia (CBT-I Coach) in a sample of college students. Participants: Data was collected from 55 students, who mostly identified as women (82%) and white (84%) and reported at least moderate insomnia symptoms based on the Insomnia Severity Index. Methods: Participants were randomized to either an intervention condition (i.e., 4 wk of CBT-I Coach) or a wait-list condition and completed self-report measures biweekly across the 8-week study period. Results: Nearly 70% of participants found the app moderately to extremely effective. The intervention group experienced a larger reduction in insomnia symptoms from baseline to post-treatment compared to the control group (g = 0.88). Conclusions: These findings provide preliminary evidence that utilizing a self-guided mobile intervention for insomnia among college students is feasible and components of the app were perceived to be moderately to highly effective.

Evaluation of naples prognostic score to predict long-term mortality in patients with pulmonary embolism

Abstract Background/Introduction APE mortality rates are still not satisfactory despite new diagnosis and treatment methods (1). Thus, risk classification is crucial due to the wide range of clinical presentations. Several risk stratifications have been developed such as simplified Pulmonary Embolism Severity Index (sPESI) (2). Nonetheless, there remains a need for an optimal indicator that can be conveniently measured with a high degree of precision to predict clinical outcomes. Naples prognostic score (NPS) is a newly defined index that is developed to determine the prognosis of cancer patients and reflects the inflammatory and nutritional status of the patients (3). Purpose The aim of our study was to determine the long-term prognostic value of NPS in APE patients. Methods Two hundred ninety-three patients diagnosed with APE between November 2016 and February 2022 were included in the study. NPS consists of 4 parameters: serum albumin, total cholesterol (TC) concentration, neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Naples scores of all patients were calculated and the patients were divided into 2 groups according to their NPS and their long-term mortality was compared. The primary endpoint of the study was long-term mortality. Results The long-term mortality was observed in 38 patients out of 293 patients in the mean follow-up of 24 (16-42) months. In the low-Naples risk group (group 1), there were 215 patients, while the high-Naples risk group (group 2) had 78 patients. Multivariate analysis showed that NPS as a categorical parameter (HR: 3.458, 95%CI:1.734-6.896, p<0.001), NPS as a numerical parameter, (HR:1.651, 95%CI:1.217-2.241, p=0.001) and simplified pulmonary embolism severity index (sPESI) (HR:1.887, 95%CI:1.223-2.911), p=0.004) score were independent predictors of long-term mortality. The receiver operating characteristic curve analysis showed that the model 2 with NPS as continuous had higher discriminative ability than the baseline model for detecting patients with mortality (Area under curve (AUC) values = 0.791 vs. 0.723, respectively, p=0.04) (Figure 1A). The long-term predictive capability of NPS was non-inferior than the sPESI score (Figure 1B). Conclusions The current study highlights that NPS, which reflects systemic inflammation and nutritional status may have potential to predict long-term mortality in APE patients. To our knowledge, this is the first study to show the relationship between long-term mortality and NPS in APE patients.

Efficacy of Subdermal Poly-d,l-Lactic Acid Injections for the Treatment of Melasma.

Melasma is a chronic, recurrent skin disorder with limited long-term treatment success using conventional therapies like hydroquinone and laser treatments, which primarily target epidermal components while leaving dermal aspects untreated. To evaluate the efficacy and safety of poly-d,l lactic acid (PDLLA) subdermal injections for treating moderate melasma. Three female patients (age range: 45-59 years) with Fitzpatrick skin types III and IV received three PDLLA injection sessions at 3-week intervals. Treatment outcomes were assessed using the Melasma Area and Severity Index (MASI) and patient satisfaction scores at 12-week follow-up. All patients showed significant MASI score improvements (reduction range: 3.60-6.30 points). Patient satisfaction ratings ranged from 3 to 4 out of 4. Temporary side effects included mild edema and bruising, resolving within 72 h. PDLLA subdermal injections showed promising results in melasma treatment, potentially due to its biostimulatory effects on collagen production and dermal remodeling. Further research, including histopathological analysis, is needed to confirm long-term efficacy and safety, and understand underlying mechanisms.

Identification and Functional Analysis of Git3 G Protein-Coupled Receptors in Ganoderma boninense PER71

G protein-coupled receptors (GPCRs) are integral components of eukaryotic heterotrimeric G proteins, playing crucial roles in detecting extracellular signals and initiating the activity of signaling proteins within cells to activate cellular responses to these signals. The objectives of this study are to identify and characterize the function of Git3, a Class III GPCR protein, in the oil palm pathogen Ganoderma boninense. To identify the potential genes encoded for GPCR in this fungus, intensive data mining on the genome and transcriptome data has been carried out. A total of six classes of GPCRs have been identified. These include Class II pheromone detectors, Class III carbon detectors, Class IV nitrogen detectors, Class VII proteins similar to glycosyltransferase, Class VIII proteins similar to hemolysin, and Class X protein receptors. Among these, the Class III protein Git3, postulated to be involved in glucose sensing and fungal pathogenicity, was selected for gene knockdown using RNA interference (RNAi). A plasmid, designated pUChph-GIT3, was constructed, to target git3 silencing by incorporating a hygromycin resistance gene cassette and antisense sequences of git3. Transformation of G. boninense PER71 with pUChph-GIT3 produced five potential Δgit3 gene-silenced mutants. PCR analysis confirmed the integration of the RNAi expression cassette into the fungal genome. Quantitative PCR (qPCR) analysis revealed significant reductions in git3 expression in three G. boninense mutants, M42, M66, and M5 by 47%, 23%, and 13%, respectively. The Disease Severity Index (DSI) indicated slower disease progression in oil palm plantlets infected with Δgit3 mutants compared to those infected with wild-type G. boninense PER71. In conclusion, this study successfully isolated and characterized the git3 GPCR from G. boninense and demonstrated that it might play a role during the early stages of infection, as the mutants were able to slow the progression of infection in oil palm plantlets.

Clinical features and effects of cyclosporine in the treatment of psoriasis: a systemic review and meta-analysis.

To systematically evaluate clinical features and effects of cyclosporine in the treatment of psoriasis. Databases including Web of Science, PubMed, The Cochrane Library, Embase, CNKI, Wan Fang, and VIP were electronically searched for studies on the use of cyclosporine in the treatment of psoriasis, from inception to March 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. A meta-analysis was then performed. A total of 12 randomised controlled trial (RCT) studies were included. Compared with the control group, there were statistically significant differences in the effective rate, recurrence rate, erythema regression time, pustular resolution time, fever resolution time, and Psoriasis Area Severity Index (PASI) score of cyclosporine in the treatment of psoriasis. Moreover, the sub-group analysis showed that the effective rate of patients aged less than 40 years was significantly higher than that of the control group and the recurrence rate was significantly lower than that of the control group. The effective rate of psoriasis patients without nail lesions was significantly higher than that of control group. The effective rate of cyclosporin was significantly higher than that of dexamethasone acetate. There was no significant change in pooled sensitivity and specificity after each study was excluded one by one, indicating the stability of the meta-analysis. Cyclosporine had a high effective rate and low recurrence rate in the treatment of psoriasis, but it still had similar rate of adverse reactions compared to other drugs. This study systematically evaluated the effect of cyclosporine in the treatment of psoriasis and provided reference for clinical practice.

Evaluation of the effectiveness of cognitive–behavioural therapy for insomnia delivered by nurses and physicians for patients in primary care (the NPD study): protocol for a cluster randomised controlled trial

IntroductionInsomnia is the most common sleep disorder, and it adversely impacts daily living and increases the risk of chronic and acute health problems. Of the few individuals who seek treatment...

The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials

Regulatory T cell (Treg) impairment is implicated in the pathogenesis of chronic inflammatory diseases, but relatively little is known about the therapeutic potential of Treg restoration. Here we present clinical evidence for the Treg-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). Key inclusion criteria for AD included an Eczema Area and Severity Index (EASI) score ≥ 16 and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and for PsO included a Psoriasis Area and Severity Index (PASI) score of ≥ 12 and a static Physician’s Global Assessment (sPGA) score of ≥ 3. REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 µg/kg or 24 µg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives, respectively. AD patients receiving the higher dose demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These exploratory clinical improvements are accompanied by sustained increases in CD25bright Tregs. REZPEG thus represents a homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control.

Matching-Adjusted Indirect Comparison of Risankizumab Versus Deucravacitinib in Patients with Moderate-to-Severe Plaque Psoriasis.

Despite advancements in the treatment of psoriasis (PsO), there are few head-to-head studies assessing comparative effectiveness of the newest therapies approved to treat PsO. Our objective was to assess the comparative clinical effectiveness of risankizumab and deucravacitinib in patients with moderate-to-severe PsO. This placebo-anchored matching-adjusted indirect comparison (MAIC) analysis utilized data from UltIMMa-1/2 risankizumab and POETYK PSO-1/2 deucravacitinib trials. Individual patient data from UltiMMA-1/2 were weighted via propensity score to match POETYK PSO-1/2 published summary data. Rate differences between risankizumab and deucravacitinib were assessed for Psoriasis Area and Severity Index (PASI) 75/90/100, the Static Physician Global Assessment (sPGA = 0 or 0/1), and the Dermatology Life Quality Index (DLQI) 0/1. At 16weeks, risankizumab-treated patients demonstrated statistically significantly higher rates of skin clearance and greater improvement in quality of life (QoL) compared to those treated with deucravacitinib. Across all outcomes, risankizumab demonstrated a lower number needed to treat compared to deucravacitinib. Limitations are potential bias due to unobserved/unmeasurable differences and limited generalizability of the results. This indirect comparison demonstrates that risankizumab has higher rates of skin clearance and greater improvements in QoL than deucravacitinib. This study will help inform healthcare providers in their treatment and management strategy of PsO.

Long-term efficacy and safety of stapokibart for moderate-to-severe atopic dermatitis: 52-week results from a phase 3 trial.

Management of moderate-to-severe atopic dermatitis (AD) needs long-term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin-4 receptor α subunit (IL-4Rα), a shared receptor for IL-4 and IL-13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75; 66.9% vs. 25.8%) and Investigator's Global Assessment (IGA) score of 0/1 with ≥2-point reduction (44.2% vs. 16.1%) at Week 16. Herein, we report long-term (52 weeks) efficacy and safety of stapokibart from this trial. After 16-week double-blind treatment completed, patients in both stapokibart and placebo groups entered a 36-week maintenance treatment period and received stapokibart 300 mg every 2 weeks. Concomitant use of topical medications for AD was permitted throughout the maintenance period. Of 476 patients entering maintenance period, 430 completed the treatment. At Week 52, EASI-75 was achieved in 92.5% of patients continuing stapokibart and 88.7% of those switching from placebo to stapokibart, respectively; an IGA score of 0 or 1 with a ≥2-point reduction was achieved in 67.3% and 64.2% of patients, respectively; a ≥4-point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale (PP-NRS) was achieved in 67.3% and 60.5% of patients, respectively. Over the 52-week treatment period, 88.1% of patients reported treatment-emergent adverse events, most were mild or moderate. Long-term treatment with stapokibart demonstrated a sustained efficacy and favorable safety profile in adults with moderate-to-severe AD.

Balancing Objective Markers and Subjective Experience in Eating Disorder Diagnoses: Commentary on Dang et al. (2024).

The results of Dang et al.'s recent systematic review and meta-analysis suggested that individuals diagnosed with other specified feeding or eating disorder (OSFED) and those diagnosed with specified eating disorders (EDs, such as bulimia nervosa) endorse similar, elevated levels of ED-related cognitions (but not behaviors). The DSM has traditionally conceptualized EDs primarily as disturbances in eating behavior, and the diagnostic boundaries for EDs are based on objective markers, such as behavioral frequencies and weight. Although focusing on objective markers for ED diagnoses and severity indices has advantages (e.g., clinical communication, measurement), pitfalls include diagnostic migration and low emphasis on ED cognitions. Dang et al.'s findings provide a basis for rethinking DSM's conceptualization of EDs as primarily behavioral. This commentary discusses the potential merits and challenges of emphasizing subjective cognitions when assigning ED diagnoses. We explore how objective markers (e.g., behavioral frequency, weight) and subjective experience (e.g., fear of weight gain) may be balanced to improve the clinical utility of ED diagnoses. In all, research that more deeply phenotypes the subjective experiences of people with EDs across contexts, identities, and cultures will enrich our understanding of eating pathology and may inform diagnostic revisions.

Evaluation of the spatial responses in vegetation phenology to drought and the analysis of their driving factors in China

The warming and drying trend accompanying climate change challenges global ecosystem stability. Vegetation phenology, which can serve as a sensitive indicator of climate change, is crucial in understanding ecosystem carbon cycling and climate-carbon cycle feedback. Therefore, assessing the phenological responses to drought is essential for addressing climate change. In this study, vegetation phenology data [including the start and end of season (SOS, EOS) and length of growing season (LOS)] and the Palmer drought severity index (PDSI) were employed to analyze the impacts of drought on plant phenology in China by maximum Pearson correlation coefficients and partial least squares regression. The findings showed that drought significantly affected the timing of phenology, delaying senescence in approximately 62% of China and extending the growing season in about 53% of the country, indicating the critical role of water availability in vegetation biomass. Preseason nocturnal warming was found to advance SOS, delay EOS, and extend LOS across China, with significant effects observed in approximately 60% of the country. Meanwhile, daytime warming delayed SOS, delayed EOS and extended LOS in 50∼60% of the regions. Moreover, preseason precipitation is conducive to advanced SOS, delayed EOS and extended LOS in northern China and areas susceptible to drought. It is suggested that vegetation management should be strengthened to mitigate the impact of climate change in temperate and drought-prone regions in China since climate warming will lead to frequent droughts.

Early prediction of sepsis in emergency department patients using various methods and scoring systems.

Early recognition of sepsis, a common life-threatening condition in intensive care units (ICUs), is beneficial for improving patient outcomes. However, most sepsis prediction models were trained and assessed in the ICU, which might not apply to emergency department (ED) settings. To establish an early predictive model based on basic but essential information collected upon ED presentation for the follow-up diagnosis of sepsis observed in the ICU. This study developed and validated a reliable model of sepsis prediction among ED patients by comparing 10 different methods based on retrospective electronic health record data from the MIMIC-IV database. In-ICU sepsis was identified as the primary outcome. The potential predictors encompassed baseline demographics, vital signs, pain scale, chief complaints and Emergency Severity Index (ESI). 80% and 20% of the total of 425 737 ED visit records were randomly selected for the train set and the test set for model development and validation, respectively. Among the methods evaluated, XGBoost demonstrated an optimal predictive performance with an area under the curve (AUC) of 0.90 (95% CI: 0.90-0.91). Logistic regression exhibited a comparable predictive ability to XGBoost, with an AUC of 0.89 (95% CI: 0.89-0.90), along with a sensitivity and specificity of 85% (95% CI: 0.83-0.86) and 78% (95% CI: 0.77-0.80), respectively. Neither of the five commonly used severity scoring systems demonstrated satisfactory performance for sepsis prediction. The predictive ability of using ESI as the sole predictor (AUC: 0.79, 95% CI: 0.78-0.80) was also inferior to the model integrating ESI and other basic information. The use of ESI combined with basic clinical information upon ED presentation accurately predicted sepsis among ED patients, strengthening its application in ED. The proposed model may assist nurses in risk stratification management and prioritize interventions for potential sepsis patients, even in low-resource settings.

Assessing systemic inflammatory markers in psoriasis: A retrospective study.

Psoriasis is a chronic inflammatory disease often associated with serious cardiovascular comorbidities. The aim of this study was to investigate the systemic inflammatory burden in psoriasis by examining various inflammatory markers and to assess the relationship between these markers and the severity of the disease. This retrospective study was conducted on medical records of patients who visited the dermatology outpatient clinic between 1 January 2016 and 31 December 2022. The study included patients with psoriasis vulgaris and healthy volunteers. Demographic data, Psoriasis Area and Severity Index score, C-reactive protein, monocyte-high-density lipoprotein cholesterol ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, and Systemic Inflammation Response Index were analysed and compared. A total of 278 psoriasis patients and 90 healthy volunteers were analysed. Compared to the control group, psoriasis patients showed significantly higher systemic immune-inflammation index, Systemic Inflammation Response Index, neutrophil-to-lymphocyte ratio, monocyte-high-density lipoprotein cholesterol ratio, serum C-reactive protein levels, neutrophil count, monocyte count, body mass index, and waist circumference (p < 0.001, p = 0.001, p < 0.001, p = 0.014, p < 0.001, p < 0.001, p = 0.046, p < 0.001, and p = 0.011, respectively). Among patients with severe psoriasis (Psoriasis Area and Severity Index >10), systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and serum C-reactive protein levels were significantly higher compared to patients with mild/moderate psoriasis (Psoriasis Area and Severity Index ≤10). In the ROC curve analysis, the optimal cut-off (AUC, sensitivity, specificity) values for neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, and platelet-to-lymphocyte ratio were found to be 2.11 (0.592, 62%, 57%), 552.9 (0.579, 61%, 58%), and 111.9 (0.578, 64%, 46%), respectively. The inflammatory parameters that showed correlation with Psoriasis Area and Severity Index were systemic immune-inflammation index, Systemic Inflammation Response Index, neutrophil-to-lymphocyte ratio, monocyte-high-density lipoprotein cholesterol ratio, monocyte-to-lymphocyte ratio, and C-reactive protein. The findings of this study suggest that systemic immune-inflammation index, Systemic Inflammation Response Index, neutrophil-to-lymphocyte ratio, monocyte-high-density lipoprotein cholesterol ratio, and C-reactive protein values have the potential to serve as simple and cost-effective markers for assessing the inflammatory burden in individuals with psoriasis.

Effectiveness of the Emergency Severity Index in Early Identification of Sepsis in a Tertiary Care Hospital of a Low-resource Setting

Background: Sepsis is life-threatening organ dysfunction, and a global issue, with incidence and mortality are around 49 M cases in 2017. Annual sepsis incidence from Pakistan is around 1600-2500 per 100, 000 cases with high mortality of approx. 30%. This huge mortality among sepsis and septic shock cases from low-income settings it is necessary to implement a focused and effective triage tool to prioritize and categorize the sick patients from huge bulk of sick patients who attend the ED and to identify those who need to be seen and manage accordingly. Emergency severity index (ESI), a widely acceptable tool that was developed to assess illness severity, hence able to identify the sick patients that need immediate attention at triage. Objectives: Our objective is to determine the effectiveness of ESI triage acuity in early recognition of patient with sepsis and septic shock at triage in a busy ED. Methods: This was a single center, cross sectional and observational study, we include 240 cases who present to the ED of a tertiary care hospital. We follow ESI v. 4.0. All cases presenting to the ED with suspected diagnosis of sepsis or septic shock were included. Data was collected on a predesigned data sheet. Participants were followed by their electronic medical record number through patient care information software where patient’s medical diagnosis and discharge diagnosis are present. Results: Total of 240 patients in the inclusion criteria, area under curve (AUC) for the ESI score I, for septic shock was 0.943 [0.921 - 0.964] with the optimal cutoff value of 2.0, sensitivity of 88.5% and specificity 100%. Similarly, the receiver operating curve (ROC) with area under the curve of ESI Score II for sepsis is found 0.2 [0.129-0.270] with sensitivity 23% and specificity was 12.7%. Conclusion: ESI is a reliable tool which is both sensitive and specific in screening patients with septic shock in a busy emergency department.

Prognostic performance of the Bova, sPESI, and Qanadli scores in patients with acute pulmonary embolism.

Acute pulmonary embolism (PE) is a disease with a serious prognosis and a high probability of death in the emergency department. To investigate the prediction of PE-related mortality and intensive care admission (ICU) of Qanadli (Qscore), Bova, and simplified Pulmonary Embolism Severity Index (sPESI) scores. This retrospective observational study consisted of all patients diagnosed with acute PE who were imaged under computed tomography pulmonary angiography (CTPA) for a total of 5 years between 1 June 2018 and 1 June 2023. The prediction of radiological and clinical scores for mortality and ICU admission was examined. A total of 95 patients were analyzed. Patients who died and those who were admitted to the ICU had a significantly higher frequency of being found to have a high-risk (≥1) sPESI score (P = 0.04 and P = 0.016, respectively). For mortality, the sPESI score was found to be significant; the sensitivity and specificity were observed as 54% and 66% (area under the curve [AUC]=0.670, 95% confidence interval [CI]=0.527-0.814; P = 0.020). For ICU admission, the sensitivity and specificity of the Qscore, sPESI, and Bova scores were 35%, 77%, and 58%, and 78%, 65%, and 84% respectively (AUC=0.626, 95% CI=0.511-0.740, P = 0.031; AUC=0.769, 95% CI=0.674-0.865, P < 0.001; and AUC=0.767, 95% CI=0.671-0.862, P < 0.001, respectively). It was found that the sPESI score was effective at predicting mortality in patients with acute PE. Qscore, sPESI, and Bova scores have been shown to be useful in predicting ICU admission.

Effect of iberdomide on cutaneous manifestations in systemic lupus erythematosus: a randomized phase 2 clinical trial

Iberdomide, a cereblon modulator, promotes degradation of transcription factors Ikaros and Aiolos. Evaluate iberdomide efficacy and safety in cutaneous lupus erythematosus (CLE) in a phase 2 study. Patients were randomized (2:2:1:2) to iberdomide 0.45 (n=81), 0.30 (n=82), or 0.15 mg (n=42) or placebo (n=83) daily while continuing background lupus medications. The mean (SD) baseline Cutaneous Lupus Area and Severity Index Activity (CLASI-A) score was 6.9 (7.0); 28% of patients had a score ≥8; 56% had acute CLE, 29% chronic CLE, and 16% subacute CLE. Mean CLASI-A improvement in patients with baseline score ≥8 was 39.7% for iberdomide 0.45 mg versus 20.1% for placebo at week 4 (P=0.032), with continued improvement through week 24 (66.7% vs 54.2%; P=0.295). Proportions of patients achieving ≥50% CLASI-A reduction from baseline at week 24 were significantly greater for iberdomide 0.45 mg versus placebo for patients with subacute (91.7% vs 52.9%, P=0.035) and chronic (62.1% vs 27.8%; P=0.029) CLE but not for the overall population (55.6% vs 44.6%) or patients with baseline CLASI-A ≥8 (66.7% vs 50.0%). Small patient subgroups of CLE subtypes. Iberdomide showed beneficial effects when added to background lupus medications in patients with subacute and chronic CLE.

Efficacy and safety of the ustekinumab biosimilar ABP 654 in patients with moderate-to-severe plaque psoriasis: a randomized, double-blinded, active-controlled, comparative clinical study over 52 weeks.

ABP 654 is a biosimilar to ustekinumab reference product (RP). ABP 654 has been shown to have an amino acid sequence identical to ustekinumab RP and they are similar in structure, purity, and potency as well as clinical pharmacokinetics and safety in healthy volunteers. This randomized, double-blinded, active-controlled, single-transition, comparative clinical study (ClinicalTrials.gov ID NCT04607980) was conducted to compare the efficacy, safety, and immunogenicity of ABP 654 and ustekinumab RP in patients with moderate-to-severe plaque psoriasis. Patients were randomized in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a weight-based dose of 45 mg or 90 mg administered subcutaneously on day 1 (week 0), week 4, and week 16. At week 28, patients with a ≥75% improvement in Psoriasis Area and Severity Index (PASI) were re-randomized such that those initially randomized to ABP 654 continued to receive ABP 654 and those initially randomized to ustekinumab RP were re-randomized to either continue on ustekinumab RP or transition to ABP 654. The primary efficacy endpoint was PASI percent improvement from baseline to week 12. Secondary endpoints included additional efficacy measurements as well as an assessment of adverse events and antidrug antibodies. At week 12, the observed mean (SD) PASI percent improvement from baseline was 81.9 (19.9) and 81.9 (19.6) for the ABP 654 and ustekinumab RP treatment groups, respectively. The point estimate of the mean difference in PASI percent improvement from baseline to week 12 between the treatment groups was 0.14 with a 2-sided 90% confidence interval (CI) of (-2.6, 2.9), well within the prespecified similarity margin of (-10, +10). In addition, throughout the study, secondary efficacy analyses and safety and immunogenicity profiles were similar across the treatment groups. These results indicate that ABP 654 and ustekinumab RP are clinically similar in efficacy, safety, and immunogenicity in patients with moderate-to-severe plaque psoriasis. Further, a single transition from ustekinumab RP to ABP 654 at week 28 had no impact on the efficacy, safety, or immunogenicity results for the remainder of the 52-week study, supporting a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP.

Long-term management of moderate-to-severe atopic dermatitis with lebrikizumab and concomitant topical corticosteroids: a 68-week, randomized, double-blind, placebo-controlled phase III trial in Japan (ADhere-J).

Moderate-to-severe atopic dermatitis (AD) impacts patients' quality of life (QOL). More treatment options are urgently needed to manage this chronic disease. Lebrikizumab is a monoclonal antibody that binds to IL-13, a key mediator in AD pathogenesis. In Japanese patients, lebrikizumab has been evaluated through week (W) 16 in the randomized, placebo-controlled, phase III ADhere-J study. To evaluate long-term efficacy and safety of lebrikizumab in combination with topical corticosteroids (TCS) in the ADhere-J study. Patients aged ≥12 years and weighing ≥40 kg with moderate-to-severe AD, and receiving either subcutaneous lebrikizumab 250 mg every 2 weeks (Q2W)/every 4 weeks (Q4W) or placebo during the 16-week induction period, were evaluated during the long-term maintenance period from W16 to W68. Responders achieved co-primary endpoints at W16: Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with ≥2-point improvement from baseline, and/or ≥75% improvement from baseline in Eczema Area and Severity Index (EASI 75). In this analysis, W16 responders received lebrikizumab 250 mg Q2W or Q4W combined with TCS during the maintenance period (maintenance primary population; MPP); W16 per-protocol nonresponders received lebrikizumab Q2W with TCS (maintenance escape population; MEP). Major endpoints included IGA (0,1) with ≥2-point improvement from baseline and EASI 75 through W68. Other outcomes included QOL, itch, and serum thymus and activation-regulated chemokine. At W68, 66-81% of 103 patients in the MPP and 32-38% of 168 patients in the MEP achieved IGA (0,1) with ≥2-point improvement from baseline. EASI 75 was maintained by 83-89% of patients in the MPP, while 71-80% of patients in the MEP achieved this outcome by W68. Across treatment arms, patients in the MPP tended to maintain improvements recorded at W16, while patients in the MEP steadily improved across the maintenance period. No new safety signals were reported, and most treatment-emergent adverse events were mild or moderate in severity in both populations. Safety outcomes were consistent with previous reports for lebrikizumab treatment in global studies. These results support the use of lebrikizumab in combination with TCS for moderate-to-severe AD in the Japanese population over the long term. ClinicalTrials.gov (NCT04760314).