Benefits Of Treatment Research Articles

Physical Activity and Exercise Interventions in Abdominal Wall Hernia Patients: Impact on Quality of Life and Health Outcomes - A Systematic Review and Meta-Analysis

ABSTRACT Objective Abdominal wall hernias are a common pathology in the surgical field, often leading to symptoms such as pain and tightness that can significantly reduce quality of life. Some studies have suggested that exercise and physical activity may improve both quality of life and health outcomes. This study aimed to evaluate the impact of exercise on quality of life and health outcomes in abdominal wall hernia patients through a qualitative systematic review and a quantitative meta-analysis. Design The systematic review identified six studies (n = 2409) that met the inclusion criteria, all demonstrating that exercise and physical activity positively affected health outcomes in abdominal wall hernia patients. Due to the limited number of studies available, the meta-analysis focused specifically on the effects of exercise and physical activity on quality of life and pain. Results The meta-analysis results indicated significant improvements in quality of life between pre- and postsurgery after a physical exercise intervention. However, no significant differences were found in pain levels between pre- and postsurgery following the exercise program. Conclusion This systematic review and meta-analysis offer promising insights into the potential benefits of physical activity and exercise interventions on health outcomes for AWH patients.

Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer’s disease

AbstractDisease-modifying therapies for Alzheimer’s disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating mutation carriers from non-carrier controls 10-20 years before the estimated onset of clinical symptoms, depending on the statistical model used. However, after symptom onset the rate of change in CSF NfL continued to increase steadily, whereas the rate of change in plasma NfL leveled off. Both plasma and CSF NfL changes were associated with grey-matter atrophy, but not with Aβ-PET changes, supporting a temporal decoupling of Aβ deposition and neurodegeneration. These observations support NfL in both CSF and blood as an early marker of neurodegeneration but suggest that NfL measured in the CSF may be better suited for monitoring clinical trial outcomes in symptomatic AD patients.

Early Adoption of Sodium-Glucose Cotransporter-2 Inhibitor in Patients Hospitalized With Heart Failure With Mildly Reduced or Preserved Ejection Fraction

ImportanceSodium-glucose cotransporter-2 inhibitors (SGLT2is) are the first therapy shown to improve clinical outcomes for patients with heart failure (HF) and a left ventricular ejection fraction (LVEF) greater than 40%. Nationwide adoption of SGLT2is in the US since publication of the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) in August 2021 is unknown.ObjectiveTo examine trends and hospital-level variation in SGLT2i adoption.Design, Setting, and ParticipantsThis cohort study included patients with LVEF greater than 40% who were hospitalized for decompensated HF at 1 of 557 sites in the US between July 1, 2021, and September 30, 2023, from the Get With The Guidelines–Heart Failure registry.Main Outcomes and MeasuresPatient-level trends and site-level variation in prescription rates of SGLT2i at hospital discharge. Site-level variation was quantified using the median odds ratio, which describes the average odds that a patient being treated at one vs another randomly selected hospital would receive SGLT2i therapy at discharge.ResultsOf 158 849 patients (median [IQR] age, 76 [66-85] years; 89 816 females [56.5%]), 22 126 eligible patients (13.9%) with HF and an LVEF greater than 40% were prescribed an SGLT2i at hospital discharge. Quarterly prescription rates increased from 4.2% in July to September 2021 to 23.5% in July to September 2023 (P for trend < .001). SGLT2i prescription was more likely among patients with HF with mildly reduced LVEF (41%-49%) than in those with preserved LVEF (≥50%; 5127 of 27 712 patients [18.5%] vs 16 999 of 131 137 patients [13.0%]; absolute standardized difference, 16.7%). After adjustment for patient characteristics, there was a high variance between hospitals in the rate of SGLT2i prescription (median odds ratio, 2.12; 95% CI, 2.02-2.25). Among 518 hospitals with 10 or more eligible discharges, 11 hospitals (2.1%) discharged 50% or more of their patients with an SGLT2i prescription, while 232 (44.8%) discharged fewer than 10% of eligible patients with an SGLT2i prescription.Conclusion and RelevanceFor patients with HF and an LVEF greater than 40%, discharge prescription of SGLT2is increased from 4.2% to 23.5% during the first 2 years after the EMPEROR-Preserved trial demonstrating treatment benefits; however, these rates varied across US hospitals.

Will the Intervention Benefit My Client? Helping Social Workers to Answer the Question Using Indicators of Clinically Meaningful Change

AbstractSocial workers strive to provide the best support to each client, making it crucial to consider not just group-level effects of interventions but also individual outcomes. While empirical evidence often stems from group-based analyses, these offer limited insights into individual change, which is key for tailoring interventions. The aim of this study is to highlight the importance of individual-level analyses, an underexplored area in social work, using four indicators of “clinically meaningful change” (CMC). We compare these analyses with group-level analyses using a dataset of 146 Swedish families undergoing Functional Family Therapy (FFT), an intervention with strong empirical support. While group-level analyses confirmed FFT’s general effectiveness in reducing adolescent psychosocial symptoms, individual-level analyses revealed a more nuanced picture, showing variations in outcomes—positive, negative, and neutral. The study thus demonstrates the value of CMC indicators for generating individual-level information that social workers can harness to find optimal solutions for their individual clients.

Effect of an 18-month meditation training on cardiovascular risk in older adults: a secondary analysis of the Age-Well randomized controlled trial.

Cardiovascular risk factors represent an important health issue in older adults. Previous findings suggest that meditation training could have a positive impact on these risk factors. The objective of this study was to investigate the effects of an 18-month meditation-based intervention on cardiovascular health. Age-Well was a randomized, controlled superiority trial with blinded end point assessment, including community-dwelling cognitively unimpaired adults 65years and older enrolled between November 24, 2016, and March 5, 2018, in France. One hundred and thirty-four participants were included in this secondary analysis. Participants were randomly affected to an intervention group that received an 18-month meditation-based program or to comparison groups (active control group i.e. non-native language training or passive control group i.e. no intervention). The main outcome was change in the Framingham Risk Score (FRS); other outcomes were changes in cardiovascular and metabolic risk factors. There was no difference in FRS change after 18months between trial arms (p = .38). When assessing individual cardiovascular or metabolic risk factors, meditation training was associated with a greater reduction in diastolic blood pressure than the comparison group in participants with intermediate to high cardiovascular risk (FRS > 10%) at baseline (p = .03). An 18-month meditation training was not effective to increase overall cardiovascular health in older adults, but improved diastolic blood pressure in a subgroup analysis including at-risk participants. These results suggest a potential benefit of a long-term meditation intervention in older adults at-risk of cardiovascular diseases, and highlights the need for future research in more targeted populations. ClinicalTrials.gov Identifier: NCT02977819.

VSD Surgical Closure in Colombia in Children with Secondary Pulmonary Hypertension. Does Altitude Influence Postoperative Pulmonary Pressure?

A retrospective, cross-sectional, descriptive, observational study was carried out to describe the history of pulmonary hypertension in pediatric patients living at different altitudes following surgical correction of ventricular septal defect. Data from 40 patients who underwent surgery in La Fundacion Cardioinfantil was collected and used for our analysis. Bivariate analysis showed no significant relationship between altitude and pulmonary hypertension after ventricular septal defect closure. Unrelated to the main objective of our study, our investigation revealed that our population underwent surgical correction of VSD at older ages than expected. While previous publications demonstrate the benefit of intervention at 4years of age or younger (19, 20), the average age in our studied population was found to be 7.8years old. These patients had unfavorable hemodynamic parameters for ventricular septal defect closure, but our study showed that our patients benefited from surgery with an immediate satisfactory postoperative result. Patients transitioned from parameters indicating severe PH to mild PH within the first 24-48h after surgery.

Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire: A Patient-Level Meta-Analysis.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a commonly used outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean treatment effects do not necessarily reflect the clinical benefit experienced by individual patients. To evaluate the association between mean KCCQ treatment effects and the proportions of patients experiencing clinically important improvements across a range of clinical trials and heart failure etiologies. A patient-level analysis of 11 randomized clinical trials, including 9977 patients, was performed to examine the association between mean treatment effects and the KCCQ Overall Summary Score (OSS) and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate to large (≥10 points) improvements. There was no target date range, and included studies were those for which patient-level data were available. Validation was performed in 7 additional trials. The data were analyzed between July 1 and September 15, 2023. Proportion of patients experiencing an improvement of 5 or more and 10 or more points in their KCCQ score (with each domain transformed to a range of 0 to 100 points, where higher scores represent better health status). Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI], 4.0%-8.1%) in the proportion of patients improving 5 or more points and 5.0% (95% PI, 3.1%-7.0%) in the proportion improving 10 or more points, corresponding to a number needed to treat of 17 (95% PI, 12-25) and 20 (95% PI, 14-33), respectively. Inferences about clinical impacts based on population-level mean treatment effects may be misleading, since even small between-group differences may reflect clinically important treatment benefits for individual patients. Results of this study suggest that clinical trials should explicitly describe the distributions of KCCQ change at the patient level within treatment groups to support the clinical interpretation of their results.

Identifying thresholds for meaningful improvements in NTDT-PRO scores to support conclusions about treatment benefit in clinical studies of patients with non-transfusion-dependent beta-thalassaemia: analysis of pooled data from a phase 2, double-blind, placebo-controlled, randomised trial

ObjectivesTo estimate thresholds for defining meaningful within-patient improvement from baseline to weeks 13–24 and interpreting meaningfulness of between-group difference for the non-transfusion-dependent beta-thalassaemia patient-reported outcome (NTDT-PRO) tiredness/weakness (T/W) and shortness...

Real-world mepolizumab treatment in eosinophilic granulomatosis with polyangiitis reduces disease burden in the United States.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, chronic inflammatory disease characterized by asthma and small/medium vessel vasculitis. Mepolizumab is approved for use in EGPA disease management alongside oral corticosteroids (OCS), but evidence of its real-world impact is limited. To compare real-world treatment patterns and health outcomes, particularly OCS use, EGPA-related hospitalizations/relapses, and asthma exacerbations pre- and post-mepolizumab initiation in US patients with EGPA. Patients with EGPA receiving ≥2 mepolizumab doses were identified using administrative claims data from Komodo Health's Comprehensive Dataset (December 2016-March 2020). Outcomes assessed pre- and post-mepolizumab initiation included corticosteroid/other medication use, EGPA-related hospitalizations/relapses, and asthma exacerbations. Overall, 114 patients were identified; of these, 60 (53%) received mepolizumab 300 mg at index. Average daily OCS dose per dispensing was significantly lower post- versus pre-mepolizumab initiation (21.2 vs 26.8 mg/day, 21% relative reduction, P<0.001); mean number of OCS bursts also decreased (0.9 vs 1.8, 50% relative reduction, P<0.001). Patients experienced significantly lower rates of EGPA-related hospitalization (0.86 vs 1.55 per person-year [PPY], 49% relative reduction, P=0.004) and EGPA relapse (3.18 vs 3.94 PPY, 19% relative reduction, P=0.004) post- versus pre-initiation. Most patients (91%) had an asthma diagnosis at baseline; among these patients, asthma exacerbation rates were significantly lower post- versus pre-initiation (1.05 vs 1.84 PPY, 42% relative reduction, P=0.004). Mepolizumab was associated with significant steroid-sparing benefits and significantly reduced rates of EGPA-related hospitalizations, EGPA relapses, and asthma exacerbations in this real-world study of US patients with EGPA, confirming the benefits of mepolizumab treatment seen in clinical trials.

Self-rated costs and benefits of conventional and alternative adult ADHD treatments.

Conventional treatments offered by healthcare providers for adult ADHD include pharmacological and non-pharmacological approaches or a combination of both. Both treatment types may have downsides like side effects or low efficacy, potentially leading to treatment dissatisfaction. Also, adults with ADHD explore non-prescribed, complementary and/or alternative medicine (CAM) on their initiative, including substances such as dietary supplements and activities such as physical exercise. This survey study aimed to investigate the types of conventional and CAM treatments adults with ADHD use and their self-rated effectiveness. Also, lifetime experience of negative effects across all treatment types and the motives to use CAM were explored. In total, 227 adults diagnosed with ADHD or reporting clinically elevated ADHD symptoms (without official ADHD diagnosis) were included in the analyses. Both lifetime and current use and experiencing negative effects were highest for conventional pharmacological treatments, followed by CAM activities, CAM substances, and conventional non-pharmacological approaches. The most common reason for using CAM was overall well-being. Conventional treatments were rated more effective in influencing cognition than CAM, but their self-rated effectiveness did not differ in other assessed domains. CAM activities were rated more effective than CAM substances in all assessed domains. This study highlights the high prevalence of CAM use by adults with ADHD, implying that some patients find value in such alternative treatments. Future studies should consider investigating alternative and/or complementary treatments for adult ADHD, alone or in combination with conventional treatments.

EGS SO26 - Back Under the Knife: Unveiling the Fate of non-trauma Patients Returning to the Emergency Theatre

Abstract Background Offering a planned or unplanned second operation in emergency general surgery is not uncommon. However, there is a scarcity of data in this context. This study aims to evaluate the outcomes of patients who were offered two emergency operations to those who required one operation, focusing on complications, increased level of care at discharge and mortality rates. Method We identified those patients who underwent planned and unplanned revisits to the emergency theatre between July 2020 and July 2023. Inclusion criteria were consistent with the established UK National Emergency Laparotomy Audit (NELA at our centre over three years.. We examined demographics, ASA (American Society of Anesthesiologists) classification, indications and outcomes in terms of complications, increased post-operative care levels and mortality rates. Results 390 patients (89.3%) required one operation (1OP) and 47 (10.7%)patients underwent two operations (2OP) . The median age was 70 years for 1OP and 71 years for 2OP, with a male-to-female ratio of 192:198 in 1OPG and 22:25 in 2OP. The median ASA score (2 vs. 3), median frailty score (3 vs. 4) and the median Clavien-Dindo classification (2 vs. 4), and length of stay in days (12 vs. 21) were significantly higher for the 2OP. The increase in the level of care at discharge (30.6% vs. 59%) and the mortality (7.4% vs. 32%) were higher in the 2OP. Conclusion Our study shows that non-trauma patients requiring a second emergency operation face significantly worse outcomes compared to those undergoing only one surgery. Specifically, the group needing two operations experienced higher rates of complications, increased levels of post-operative care, and significantly higher mortality rates. These findings underscore the critical need for close monitoring and a multidisciplinary approach perioperatively. Moreover, these insights can help provide patients and their families with informed decision-making regarding the potential risks and benefits of additional surgical interventions. A prospective multicentre study would be valuable in providing further insights into this subgroup of patients.

Abstract B044: Fragmentomic features of cell-free DNA predict late-stage melanoma treatment benefit and survival

Abstract The levels of circulating tumour DNA (ctDNA) in cancer patients are associated with response and survival outcomes. Analysis of ctDNA generally requires knowledge of tumour mutations or the application of expensive next generation targeted sequencing. Here we utilize a cutting-edge approach, combining cell-free DNA molecules (cfDNA) fragmentomics and machine learning, to infer the presence of ctDNA to predict response and survival to immune checkpoint inhibitors in stage III unresectable and IV melanoma patients. Genome libraries were constructed from cfDNA derived from 48 (discovery cohort) and 96 (validation cohort) stage III unresectable and IV melanoma patients prior to the commencement of immune-checkpoint inhibitors. The discovery cohort included any-line therapy, patients had a median age of 66, 69% were male, 33% were BRAF V600 mutant, and 88% had an ECOG of 0-1. The validation cohort included first-line therapy, patients had a median age of 69, 59% were male, 22% were BRAF V600 mutant, and 89% had an ECOG of 0-1. Genome libraries were subjected to shallow whole genome sequencing (8x) and the following metrics were calculated: tumour content prediction, aneuploidy levels, various proportions of fragments ranging from 20 bp to 320 bp, the proportion of mitochondrial DNA, and the amplitude of 10 bp size oscillations between 75-150 bp, and the Shannon diversity of trinucleotide motifs at each end of the read. Non-penalized logistic modelling was used to predict clinical benefit, and the resulting logistic model was transformed into a “white-box” model. The white-box model was applied to the cohorts and used to test progression-free and overall survival. The removal of reads with inserts &amp;lt;90 and &amp;gt;150 bp greatly improved chromosome aneuploidy detection from 19% to 31%. Logistic modelling of the fragmentomic features of cfDNA yielded an AUROC of 0.83 for prediction of clinical benefit in the discovery cohort. A cutoff was set for the fragmentomic model score and used to stratify groups for survival analysis. Patients with a low score showed significantly worse progression- free (mPFS 931 vs 286 days, HR 3.4, 95% CI 1.55-7.46, p&amp;lt;0.002) and overall (mOS NR vs 363 days, HR 8.1, 95% CI 2.7-24.3, p&amp;lt;0.001) survival. These results were replicated in the validation cohort with an AUROC of 0.78 for prediction of clinical benefit and significant associations with progression-free (mPFS 1986 vs 926 days, HR 2.33 95% CI 1.27-3.92, p=0.005) and overall (mOS NR vs 1238 days, HR 4.51 95% CI 1.7-11.96, p=0.002) survival. Fragmentomic features of plasma cfDNA enable the prediction of clinical benefit, progression-free, and overall survival in stage IV melanoma patients treated with immune-checkpoint inhibitors. Citation Format: Aaron B Beasley, Leslie Calapre, Ashleigh Stewart, Anna L Reid, Russell Diefenbach, Wei Yen Chan, Rebecca Auzins, Luisa Pinnel, Sanjeev Adhikari, Muhammad A Khattak, Peter Lau, Tarek M Meniawy, Jenny H Lee, Lydia Warburton, Michael Millward, Alexander M Menzies, Richard A Scolyer, Georgina V Long, Helen Rizos, Elin S Gray. Fragmentomic features of cell-free DNA predict late-stage melanoma treatment benefit and survival [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B044.

The Utilization of the Accelerated Approval Pathway in Oncology: A Case Study of Pembrolizumab.

The accelerated approval (AA) pathway was established by the United States Food and Drug Administration (FDA) to provide earlier access to therapies for patients with serious medical conditions and unmet medical needs. Since its inception, the AA pathway has been used for novel treatments across different therapeutic areas, but most prominently in oncology, including the immune checkpoint inhibitor class. This review article describes the history of regulatory approvals for pembrolizumab, an immunotherapy agent targeting programmed death receptor-1 (PD-1), and use of the AA pathway and the corresponding regulatory decisions made by the FDA. From its first AA in September 2014 to February 2024, pembrolizumab has used the accelerated pathway for roughly 40% of the approved indications listed in the US Prescribing Information and was the first oncology therapy to receive an AA for an alternate dosing regimen and a tissue-agnostic indication. As of February 2024, 14 of the 18 indication-specific AAs and 1 post-marketing requirement (PMR) for the alternate dosing regimen AA were converted to traditional approvals. Accelerated approvals for two indications were withdrawn, and the remaining ongoing PMRs are not due until later in 2024 or 2025. The median conversion time from AA to traditional approval was 2.6 years, which is roughly 6 months earlier than the median time reported for oncology AAs. While FDA was the first agency to establish an expedited approval pathway, regulators from other countries have established similar pathways. For pembrolizumab, approximately half of the datasets that supported US AAs also supported expedited approval, or sometimes full approval, in Canada, EU, Australia or Japan. Ultimately, the AA pathway balances the provision of earlier access to therapies with overcoming uncertainty about potential effectiveness, and therefore it is important to confirm treatment benefit and withdraw indications that do not confirm benefit in a timely manner. The regulatory strategy and use of this expedited program for pembrolizumab highlights the importance of the AA pathway in providing oncology patients with earlier access to life-saving medications.

Prenatal Acetaminophen Exposure and its Associated Risk for Attention Deficit Hyperactivity Disorder

Acetaminophen is one of the most commonly used over-the-counter antipyretic and analgesic drugs on the market and has been relevant in the medical world for almost a hundred years. It has maintained an excellent reputation as a safe therapeutic in several types of patient profiles. However, the number of children diagnosed with neurodevelopmental disorders, namely ADHD, have been on the rise. Recent findings have indicated an association between in utero exposure to acetaminophen and an increased risk of developing neurodevelopmental disorders such as ADHD in offspring. The mechanism by which this potential side effect occurs is difficult to pinpoint. However, it is known that the metabolism of acetaminophen is known to cause oxidative stress, which has been shown to influence the developing fetus. This review highlights the epidemiological data indicating the correlation between prenatal acetaminophen exposure and ADHD and discusses several proposed theories by which this phenomenon may occur. While there is not yet enough clinical evidence to prove that acetaminophen may cause ADHD, there is a strong enough correlation to indicate a warning to pregnant patients of the potential risks. The risks and benefits of treatment should be considered so that the patient may continue with the course of action with the most favorable outcome. This review was mainly based on manuscripts pulled from Google Scholar and PubMed. The purpose of this literature review is to assist clinicians to better understand lesser-known risks in acetaminophen usage in pregnant patients.

Impact of a multifaceted intervention programme on antibiotic prescribing and dispensing in four patient-centred settings in five European countries. The HAPPY PATIENT project.

The primary cause of antimicrobial resistance is excessive and non-indicated antibiotic use. To evaluate the impact of a multifaceted intervention aimed at various healthcare professionals (HCPs) on antibiotic prescribing and dispensing for common infections. Before-and-after study set in general practice, out-of-hours services, nursing homes, and community pharmacies in France, Greece, Lithuania, Poland, and Spain. Following the Audit Project Odense method, HCPs from these four settings self-registered encounters with patients related to antibiotic prescribing and dispensing before and after an intervention (February-April 2022 and February-April 2023). Prior to the second registration, the HCPs undertook a multifaceted intervention, which included reviewing and discussing feedback on the first registration's results, enhancing communication skills, and providing communication tools. Indicators to identify potentially unnecessary prescriptions and non-first-line antibiotic choices were developed, and the results of the two registrations were compared. A total of 345 HCPs registered 10 744 infections in the first registration period and 10 207 infections in the second period. In general practice, participants showed a significant 9.8% reduction in unnecessary antibiotic prescriptions in the second period, whereas limited or no effect was observed in out-of-hours services and nursing homes (0.8% reduction and 4.5% increase, respectively). Pharmacies demonstrated an 18% increase in safety checks, and correct advice in pharmacies rose by 17%. External factors like COVID-19, antibiotic shortages, and a streptococcal epidemic impacted the intervention's benefits. Despite this, the intervention successfully improved antibiotic use in both settings.

Rocatinlimab Improves Patient-Reported Outcomes in Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Double-Blind Placebo-Controlled Phase2b Study.

In adults with moderate-to-severe atopic dermatitis (AD), rocatinlimab demonstrated significant and progressive improvement in clinical measures of disease severity compared with placebo. This post hoc analysis of a phase2b study was undertaken to understand the disease burden and to assess the impact of rocatinlimab on patient-reported outcomes (PROs). This analysis used baseline data from a multicenter, randomized, double-blind study of adults with moderate-to-severe AD, who completed a Worst Pruritus numerical rating scale (NRS), Sleep Disturbance NRS, and the Dermatology Life Quality Index (DLQI). A mixed model for repeated measures was used to estimate changes in PRO scores from baseline; scores were also compared with clinically meaningful change benchmarks. The analysis included 267 subjects, mean (SD) age 37.9 (14.7) years, 40.8% female; 55.1% grade3 and 44.9% grade4 Investigator Global Assessment for AD. Mean (SD) scores were: Worst Pruritus NRS 7.5 (1.9), Sleep Disturbance NRS 5.5 (2.9), DLQI total score 12.6 (7.1). Worst Pruritus and Sleep NRS scores had low positive correlations with SCORing AD (SCORAD) score (r = 0.44, r = 0.45 respectively) and negligible correlations with Eczema Area and Severity Index (EASI) score and area affected (r < 0.30). DLQI score varied by sex, study country, race, age, longer disease duration, disease severity (EASI and SCORAD), presence of asthma, and Worst Pruritus NRS, Sleep disturbance NRS, and DLQI scores. Rocatinlimab showed benefit on all three PROs, with significant improvements from baseline at the end of the double-blind period (week18) and active treatment extension (week36). Benefits were maintained over 20weeks' post-treatment follow-up. The benefit of rocatinlimab treatment on PROs is rapid and maintained for at least 20weeks following treatment completion. This analysis demonstrates the importance of characterizing the burden of moderate-to-severe AD from the patient's perspective, alongside clinical disease measures, to develop a fuller picture of treatment benefit. ClinicalTrials.gov identifier, NCT03703102.

Abstract 4124675: Deep Learning Screening of Cardiac MRIs Uncovers Undiagnosed Hypertrophic Cardiomyopathy in the UK BioBank

Introduction: The prevalence of hypertrophic cardiomyopathy (HCM) in the UK Biobank based on ICD-10 codes (.07%) is lower than global estimates of disease prevalence (0.2 - 0.5%). Prior studies using this data have remarked on the limitations of findings given likely underdiagnosis. The availability of cardiac MRI scans on a fraction of the participants offers an opportunity to identify missed diagnoses. Aims: This study seeks to utilize a generalizable deep learning model to detect likely cases of undiagnosed hypertrophic cardiomyopathy from cardiac MRIs in the UK Biobank. Methods: The foundational model was trained on a multi-institutional dataset of 14,073 cardiac MRIs via a self-supervised contrastive learning approach that sought to minimize the divergence between scans and their associated radiology reports. The pre-trained model was fine-tuned to diagnose hypertrophic cardiomyopathy on a distinct cohort of 4,870 MRIs with 368 cases of HCM, achieving an AUC of 0.94. The fine-tuned model was applied to the UK Biobank cardiac MRI dataset to ascertain predicted probabilities of HCM. Cases exceeding a threshold of 95% – correlating to the top 0.5% of cases (expected specificity of 97% and sensitivity of 60%) – were screened in for manual reading. In a blinded fashion, a board-certified radiologist was tasked with diagnosing HCM on a sample of cases composed of high and low predicted probabilities. Results: Of the 43,017 patients with cardiac MRIs, only 9 (.02%) had an ICD diagnosis of HCM. 266 cardiac MRIs were manually reviewed: 216 had greater than 95% predicted probability of HCM; 50 negative controls were randomly selected amongst cases with predicted probability less than 10%. The radiologist concurred with an HCM diagnosis for 115 cases (sensitivity 53%, specificity 98%), 112 of which were previously undiagnosed. The prevalence of hypertension and aortic stenosis did not significantly differ between the cohort of true positives (69.2%) and false positives (76.6%). The corrected prevalence of HCM in the UK BioBank MRI cohort is estimated at 0.28%. Conclusions: The findings of this study illustrate the remarkable ability of a generalizable deep learning model to detect undiagnosed cases of a rare disease process from cardiac MRIs. This is an important milestone that may allow for widespread screening of hypertrophic cardiomyopathy while minimizing demand for radiologist labor, and thereby allow patients to reap the substantial benefits of earlier treatment.

Antioxidant Therapies in the Treatment of Aminoglycoside-Induced Ototoxicity: A Meta-Analysis.

A feared complication of aminoglycoside treatment is ototoxicity, which is theorized to be attributed to the production of aminoglycoside-induced reactive oxygen species. Previous studies using animal models have suggested that numerous therapies targeting reducing oxidative stress may prevent ototoxicity from aminoglycosides. However, few clinical studies have been conducted on these antioxidants. This systematic review and meta-analysis examines the effectiveness of antioxidant therapies in the treatment of aminoglycoside-induced ototoxicity. PubMed, Embase, Web of Science, and ClinicalTrials.gov. A literature search was conducted in August 2024. This review sought randomized controlled trials to be conducted on humans to examining otologic outcomes in aminoglycoside-induced ototoxicity following administration of medications intended to reduce oxidative stress. A systematic review yielded 2037 results, of which seven studies met inclusion criteria. N-acetylcysteine (NAC) was investigated in four studies, aspirin in two studies, and vitamin E in one study. Six studies examined the benefit of antioxidant treatments for up to 8 weeks after administration while one study tested subjects' hearing after 1 year. In pooled analysis, two studies assessing NAC showed the greatest reduction in ototoxicity (RR 0.112, 95% CI, 0.032-0.395; p = 0.0007; I2 = 18%), followed by two studies examining aspirin (RR 0.229, 95% CI, 0.080-0.650; p = 0.0057; I2 = 0%). One study performed with vitamin E did not find a reduction in ototoxicity compared to the placebo (RR 0.841, 95% CI, 0.153-4.617; p = 0.8416). Multiple studies have shown that NAC and aspirin are effective in reducing ototoxicity from treatment with aminoglycosides. However, there is a lack of high-quality evidence. Additional studies should examine whether aspirin and N-acetylcysteine provide long-term benefit, and which of the other promising antioxidants translate from animal models. N/A Laryngoscope, 2024.

Unhealthy Alcohol Use: Screening and Behavioral Counseling Interventions.

Despite the increase in daily alcohol intake in recent decades and the implementation of national health screenings, effective management strategies for alcohol consumption remain outdated. This review evaluates intervention studies on screening and behavioral counseling for unhealthy alcohol use, with the aim of enhancing the effectiveness of interventions and improving health outcomes. On the basis of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation)- ADOLOPMENT framework, systematic reviews and randomized controlled trials were examined to investigate the effectiveness of screening and counseling interventions in reducing unhealthy alcohol use. Five key questions were generated, and an evaluation and quality assessment of existing systematic reviews and new evidence related to each key question were conducted. Updating the U.S. Preventive Services Task Force and Cochrane 2018 reviews, we identified five new randomized trials that evaluated screening and counseling interventions for unhealthy alcohol use. For Key Question 2, the sensitivity and specificity of the new screening studies were consistent with those of prior research. Brief interventions were confirmed to reduce alcohol use (Key Question 4a), although additional research is required for a wider array of health outcomes. One study highlighted the benefits of counseling interventions for newborn health indicators in pregnant women (Key Question 4b). No new evidence was found regarding the harms of screening (Key Question 3) or alcohol use reduction interventions (Key Question 5). This review supports the continued use of brief interventions to reduce alcohol consumption in highrisk groups and highlights the need for culturally tailored research in Korea.

Ruptured pancreatic carcinosarcoma - A case of extended survival following surgical resection and chemotherapy.

We present a rare case of ruptured pancreatic carcinosarcoma in a 56-year-old male who underwent radical surgery and adjuvant chemotherapy. Despite the typical poor prognosis associated with this aggressive tumor, the patient achieved an overall survival of 20 months postoperatively. This case emphasizes the challenges in diagnosing and managing pancreatic carcinosarcoma and highlights the potential benefits of aggressive surgical and chemotherapeutic interventions in achieving extended survival.