Meaningful Improvements In Symptoms Research Articles

Efgartigimod: A Review in Generalised Myasthenia Gravis.

Efgartigimod (Vyvgart®; Vyvgart® Hytrulo) is a neonatal fragment crystallizable receptor (FcRn) antagonist indicated for the treatment of generalised myasthenia gravis (gMG) in adults who are acetylcholine receptor (AChR) antibody positive (Ab+). Efgartigimod is approved for both intravenous (IV) and subcutaneous (SC) use. In a pivotal phaseIII trial, IV efgartigimod was associated with significant and clinically meaningful improvements in myasthenia gravis symptoms and reductions in disease burden. The beneficial effects of IV efgartigimod were reproducible, durable and maintained over the long term. IV efgartigimod also improved health-related quality of life (HRQOL). In another phaseIII trial, SC efgartigimod PH20 was noninferior to IV efgartigimod in reducing total immunoglobulin G levels. Clinical improvement with SC efgartigimod PH20 was consistent with that of IV efgartigimod and was reproducible over the long term. Efgartigimod was generally well tolerated; the most common adverse events were headache and infections (with IV efgartigimod) and injection-site reactions (with SC efgartigimod PH20). Although further long-term data are required, IV and SC formulations of efgartigimod provide effective, generally well-tolerated and flexible treatment options for adults with AChR Ab+ gMG.

Personalised Health Behaviour Support Programme in Adults With Post-COVID Syndrome: A Randomised, Controlled Pilot Feasibility Trial.

We investigated whether a novel 8-week personalised health behaviour support programme, focusing on the stability of symptoms and strategies to improve activities of daily living, was feasible and acceptable in adults with post-COVID syndrome. In this randomised, controlled, pilot feasibility trial, 32 adults with post-COVID syndrome (continued symptoms for ≥ 12 weeks) were randomised 1:1 to receive personalised health behaviour support (self-reported physical activity and symptom diaries, plus seven one-to-one remotely delivered personalised self-management support sessions), once weekly for 8-weeks, or usual care (referral to online 'your COVID-19 recovery' programme). The primary outcome was the feasibility of recruiting and randomising adults with post-COVID syndrome. The secondary outcomes were to assess the acceptability and safety of the intervention and various outcome measures. Of the 48 adults who expressed interest in the study, 32 (67%) were eligible and completed the baseline assessment. All 32 adults were willing to be randomised to either the personalised health behaviour support programme (n = 17) or usual care (n = 15) and 27 (age: 45 ± 12 years) adults completed follow-up at 9 weeks. The intervention was deemed feasible, with high adherence (92% and 94% completion rates for the physical activity and symptom diaries, respectively) and excellent acceptability rates (94% 'liked the intervention a lot'). The intervention was deemed safe, with no symptom exacerbations reported. An 8-week personalised health behaviour support programme was feasible for adults with post-COVID syndrome, with good adherence and acceptability rates. Early pilot data from this small sample also suggests meaningful improvements in physical activity, fatigue and respiratory symptoms. People living with post-COVID syndrome were involved from the outset with the study design, review of study documentation and interpretation of the data following completion. Furthermore, several participants have supported the local dissemination of findings following the completion of the study.

Effectiveness of Vortioxetine Treatment on Depression and Cognitive Functions in Patients with Alzheimer's Disease: A 12-Month, Retrospective, Observational Study.

This study aimed to assess the effectiveness of vortioxetine for improving depressive symptoms, cognitive performance, daily and global functioning in patients with Alzheimer's disease (AD) and major depressive disorder (MDD) in real-world clinical practice. We retrospectively identified 46 AD patients who had received treatment for 12 months with vortioxetine. Drug effects were evaluated at baseline, 4, 8, and 12 months. The primary endpoint was change from baseline in the Hamilton Depression Rating Scale (HDRS) and in the Cornell Scale for Depression in Dementia (CSDD) to month 12. Cognitive and daily and global functioning changes were also evaluated. Significant baseline-to-endpoint improvement in depressive symptom severity was observed (p < 0.0001). At month 12, the least-square mean (standard error) change score from baseline was -10.48 (±0.42) on the HDRS and -9.04 (±0.62) on the CSDD. Significant improvements in cognitive performance were observed for the Rey Auditory Verbal Learning Test, the Symbol Digit Modalities Test, the Letter Fluency Test, the Category Fluency Test, and the Trail Making Test-A. Patients also experienced significant improvements in daily and global functioning. Vortioxetine was safe and well tolerated. Patients with AD and MDD receiving vortioxetine showed meaningful improvements in depressive symptoms, cognitive performance, and daily and global functioning over the 12-month treatment period.

Brief Report: Baseline HRV Time Domain Parameters Predict Trauma and Depression Symptom Change in Veterans with PTSD Undergoing Biofeedback.

Heart rate variability (HRV) is an index of cardiac autonomic function and an objective biomarker for stress and health. Improving HRV through biofeedback has proven effective in reducing symptoms of posttraumatic stress disorder (PTSD) and depression in veteran populations. Brief protocols involving fewer sessions can better maximize limited clinic resources; however, there is a dearth of knowledge on the number of clinical sessions needed to significantly reduce trauma and depression symptoms. We conducted a series of linear regression models using baseline, post-intervention, and follow-up data from intervention group participants (N = 18) who engaged in a pilot waitlist-controlled study testing the efficacy of a 3-session mobile app-adapted HRV biofeedback intervention for veterans with PTSD. Based on Nunan et al. (Pacing and Clinical Electrophysiology 33:1407-1417, 2010) short-term norms, we found that pre-intervention RMSSD in the normal range significantly predicted PTSD and depression symptom improvement. Findings suggest the utility of baseline RMSSD as a useful metric for predicting HRV biofeedback treatment outcomes for veterans with PTSD and comorbid depression. Those with below-normal baseline RMSSD may likely need additional sessions or an alternative treatment to show clinically meaningful symptom improvement.

A Randomized Controlled Trial of the Safety and Efficacy of Systemic Enzyme Supplementation on Symptoms and Quality of Life in Patients with Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) imposes a substantial symptom burden that adversely impacts patients' quality of life. Current anti-fibrotic treatments for IPF provide limited symptomatic relief, necessitating the implementation of complementary disease management strategies to enhance health-related quality of life (HRQOL). Serracor-NK® and Serra Rx260, systemic enzyme supplements, improved symptoms and HRQOL with favorable safety profiles in a proof-of-concept study in PF patients. This prospective, double-blind randomized placebo-controlled trial enrolled 100 IPF patients from six institutions. The supplement group (n = 50) received the oral systemic enzyme supplements Serracor-NK® and Serra Rx260 in addition to standard care for 6 months, while the placebo group (n = 50) received standard care alone. The primary objective was to evaluate the regimen's impact on symptoms, QOL, and well-being using the UCSD shortness of breath (UCSD-SOB) questionnaire, St. George's respiratory questionnaire (SGRQ), and WHO well-being index (WHO-5). Safety evaluation was a secondary objective. A significantly higher proportion of patients in the supplement group demonstrated meaningful improvement in symptoms as compared to the placebo group, as assessed by the UCSD-SOB (p < 0.05) and SGRQ questionnaires (p < 0.05). Additionally, a significantly greater proportion of patients in the supplement group showed improved QOL and well-being (p < 0.05) and reduced health impairment (p < 0.05), as assessed by SGRQ. Mental well-being (WHO-5) and physical activity (SGRQ activity domain) did not differ significantly between the groups. Safety assessments, including liver function tests and vital signs, indicated that the supplement regimen was well tolerated. To conclude, Serracor-NK® and Serra Rx260 alleviate symptoms and enhance HRQOL in IPF patients with a favorable safety profile (Clinical Trials Registry India registration number: CTRI/2020/05/025374).

Bronchial Rheoplasty for Chronic Bronchitis: Results from a Canadian Feasibility Study with RheOx®.

Chronic bronchitis (CB), a chronic obstructive pulmonary disease (COPD) phenotype defined by persistent mucus hypersecretion and cough, is associated with poor quality of life, exacerbations, and lung function impairment. Bronchial Rheoplasty (BR) delivers non-thermal pulsed electric fields to airway epithelium and submucosa. Preliminary studies demonstrated reduced airway goblet cell hyperplasia and symptom improvement in response to BR. This study aimed to further assess the safety and clinical feasibility of BR in the setting of CB. This 3-center, single-arm study evaluated the safety and feasibility of BR in Canadian patients. The major inclusion criteria were the sum of CAT first 2 questions (cough and mucus) ≥ 7 out of 10 and FEV1 ≥ 30% predicted. Right-sided airways were treated first; left, 1 month later. Serious adverse events (SAEs) were tabulated through 12 months. Outcomes were evaluated using the SGRQ and CAT. Ten patients with CB were enrolled and followed for 12 months. The BR procedure was successful in all patients (mean age 69 ± 5.8 years, post-BD FEV1 77.1 ± 28.3, SGRQ 56.2 ± 8.8, CAT 25.4 ± 4.7). Only one SAE, a COPD exacerbation 13 days following the BR procedure, was considered device related. No additional SAEs occurred through 12 months, and 90% of the patients were CAT responders (≥ 2-point improvement) at 3 and 6 months. Similar results were observed in SGRQ. BR was safe and well-tolerated. Meaningful symptom improvement was observed through 12 months, suggesting BR may be a viable treatment option for patients with CB.

Acupuncture for hot flashes in hormone receptor-positive breast cancer: A pooled analysis of individual patient data from parallel randomized trials.

Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence. Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)-Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT-Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models. In total, 158 women with stage 0-III breast cancer were randomized (United States, n=78; China, n=40; South Korea, n=40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change±standard error: 5.1±0.9 vs. 0.2±1.0; p=.0003), the hot flash score (-5.3±0.9 vs. -1.4±0.9; p<.003), and the FACT-Breast total score (8.0±1.6 vs. -0.01±1.6; p=.0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p=.005). Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea.

Responder analysis using clinically meaningful thresholds: Post hoc analyses from randomized dupilumab clinical trials in patients with prurigo nodularis.

Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient-reported outcome (PRO) instruments, Worst Itch-Numeric Rating Scale (WI-NRS), Skin Pain-NRS, Sleep-NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within-patient improvement thresholds (responder definition) have been established through data pooled from the two Phase-3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies. To estimate the proportion of dupilumab-treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials. The patient-level data pooled from the two Phase-3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within-patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI-NRS and Skin Pain-NRS), 2 (Sleep-NRS) and 9 points (DLQI). The proportion of dupilumab-treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs. Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI-NRS (58.8% vs. 19.0%, p < 0.0001), Skin Pain-NRS (49.7% vs. 20.9%, p < 0.0001), Sleep-NRS (42.5% vs. 23.4%, p < 0.0001) and DLQI (64.7% vs. 22.8%, p < 0.0001). Proportion of patients achieving simultaneous improvement in symptoms and QoL (24.8% vs. 6.3%, p < 0.0001) were significantly higher in dupilumab-treated patients versus placebo. The time needed for achieving clinically meaningful improvement in symptoms were significantly lower in dupilumab-treated patients, versus placebo. Significantly greater proportion of dupilumab-treated patients with PN, versus placebo, demonstrated clinically meaningful improvements in PRO measures of symptoms and QoL.

Clinician Burnout and Effectiveness of Guideline-Recommended Psychotherapies

Clinician burnout has been associated with clinician outcomes, but the association with patient outcomes remains unclear. To evaluate the association between clinician burnout and the outcomes of patients receiving of guideline-recommended trauma-focused psychotherapies for posttraumatic stress disorder (PTSD). This cohort study was set at the US Veterans Affairs Health Care System and included licensed therapists who provided trauma-focused psychotherapies and responded to an online survey between May 2 and October 8, 2019, and their patients who initiated a trauma-focused therapy during the following year. Patient data were collected through December 31, 2020. Data were analyzed from May to September 2023. Therapists completing the survey reported burnout with a 5-point validated measure taken from the Physician Worklife Study. Burnout was defined as scores of 3 or more. The primary outcome was patients' clinically meaningful improvement in PTSD symptoms according to the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Patient dropout, therapist adherence, and session spacing was assessed through electronic health records. Multivariable random-effects logistic regression examined the association of therapist burnout and clinically meaningful improvement, adjusted for case-mix. In this study, 165 of 180 (91.7%) therapists (89 [53.9%] female) completed the burnout measure and provided trauma-focused psychotherapies to 1268 patients (961 [75.8%] male) with outcome data. Fifty-eight (35.2%) therapists endorsed burnout. One third of patients (431 [34.0%]) met criterion for clinically meaningful improvement. Clinically meaningful improvement in PTSD symptoms was experienced by 120 (28.3%) of the 424 patients seen by therapists who reported burnout and 311 (36.8%) of the 844 patients seen by therapists without burnout. Burnout was associated with lower odds of clinically meaningful improvement (adjusted odds ratio [OR],0.63; 95% CI, 0.48-0.85). The odds of clinically meaningful improvement were reduced for patients who dropped out (OR, 0.15; 95% CI, 0.11-0.20) and had greater session spacing (OR, 0.80; 95% CI, 0.70-0.92). Therapist adherence was not associated with therapy effectiveness. Adjusting for dropout or session spacing did not meaningfully alter the magnitude of the association between burnout and clinically meaningful improvement. In this prospective cohort study, therapist burnout was associated with reduced effectiveness of trauma-focused psychotherapies. Studying when and how burnout affects patient outcomes may inform workplace interventions.

A systematic review of randomised controlled trials on topical nasal steroids.

Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most frequently used is beclomethasone dipropionate (BDP). Over the years many studies have evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and allergic rhinitis (AR) along with nasal washes, which seems to be very well tolerated. To analyse the data in the literature regarding the various therapeutic regimens of BDP in different sinonasal disease and their efficacy and tolerability. Using different search engines, the posology, efficacy, and tolerability of BDP were reviewed and a total of 64 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, 4 articles were reviewed. BDP is among the group of INCs with significant improvement of nasal symptoms and has good efficacy and safety. BDP nasal spray is one of the most frequently prescribed INC for rhinitis and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and the safety profile is similar to that of placebo in most patients. These results, in conjunction with the significant benefit reported in subjects with CRS and AR, provide convincing evidence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal disease.

490 Unilateral Subthalamic Nucleus Deep Brain Stimulation Improves Motor Symptoms Without Neurocognitive Worsening in Parkinsons Disease

INTRODUCTION: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical intervention for patients with medically refractory Parkinson’s disease (PD). Numerous reports have described adverse nonmotor side effects, such as declines in verbal fluency and working memory, following bilateral implantation. Unilateral STN DBS is a possible alternative; however, it remains unclear whether unilateral implantation meaningfully reduces harmful effects on cognition. METHODS: This retrospective cohort study utilized chart review to collect pre- and postoperative Unified Parkinson’s Disease Rating Scale (UPDRS)-III, Levodopa Equivalent Daily Dosage (LEDD), imaging, and neurocognitive test results from 32 patients (unilateral, n = 12; bilateral, n = 20). For all statistical comparisons, p-values less than or equal to 0.05 were considered statistically significant. Student’s unpaired and paired T-tests were used to assess for differences between groups and within groups, respectively. RESULTS: There was no difference across 17 preoperative neurocognitive tests. Both unilateral and bilateral STN DBS resulted in significant decreases in postoperative UPDRS-III and LEDD (unilateral: p &lt; 0.0001; bilateral: p &lt; 0.0001) scores. There were no differences in the absolute decreases in UPDRS (p=0.055) and LEDD (p=0.120) scores between the groups. The bilateral STN DBS group had a significant deterioration in verbal fluency (COWAT FAS, p = 0.002; COWAT Animals, p = 0.014) and attention/executive function (Trails A, p=0.049 and Trails B, p = 0.011) compared to the unilateral group. CONCLUSIONS: Unilateral STN DBS is an effective and safe treatment option for patients with advanced PD. Particularly for patients with asymmetric motor symptoms, unilateral implantation provides a meaningful improvement in motor symptoms and reductions in dopaminergic medications without the risk of neurocognitive decline seen in bilateral implantation.

Impact of a private sector residential early parenting program on clinically significant postnatal depressive symptoms experienced by women: Audit of routinely collected data.

Early parenting services in Australia offer brief structured residential programs to address moderate to severe non-psychotic mental health problems among women and unsettled infant/toddler behaviours. The aims were to (1) estimate the immediate and medium-term impact of a five-night psychoeducational residential early parenting program on postpartum depressive symptoms and (2) identify the factors associated with improvement or worsening of postpartum depressive symptoms after completing the program and six weeks post-discharge. Audit of routinely collected medical record data from pre-admission, pre-discharge and post-discharge assessments of a consecutive cohort of women admitted, with their infants/toddlers in a 15-month period to Masada Private Hospital Early Parenting Centre. Data included structured questions assessing: demographic characteristics, access to family and social support, past and current mental health problems, reproductive and obstetric health, chronic health conditions, breastfeeding problems, coincidental major life events, health risk behaviours and infant/toddler feeding, sleeping and crying behaviours. Standardised instruments included the Partner Interaction after Birth Scale (PIBS), the MacLean Screening Instrument for Borderline Personality Disorder (MSI-BPD), Modified Fatigue Assessment Scale (FAS) and selected items from the Karitane Parenting Confidence Scale. The primary outcomes were Edinburgh Postnatal Depression Scale scores at pre-discharge and follow up assessments. Data were analysed using multinomial logistic regression models in which individual and psychosocial characteristics at pre-admission were included as predictors of the likelihood of the changes of the outcomes from pre-admission to pre-discharge and follow up. Complete data from 1220 of 1290 (95%) eligible women were available to assess pre-admission to pre-discharge and from 559 (45.8%) to assess pre-discharge to six-week follow-up changes. The mean pre-admission EPDS score was 11.7 (95% CI: 11.5; 12.0), pre-discharge it was 7.1 (95% CI: 6.9; 7.4) and at six-week follow up it was 5.7 (95% CI: 5.3; 6.1). We found that almost all women experienced a clinically meaningful and rapid improvement in depressive symptoms of at least this magnitude (reduction in mean EPDS scores of 4.6 points from pre-admission to pre-discharge (five nights) and a further reduction of 1.2 points pre-discharge to follow up) (six weeks) and we identified an interpretable set of risk factors for symptoms that did not improve or worsened. The adverse outcomes were associated with having symptoms of borderline personality disorder, a partner experienced as lacking kindness and care, coincidental adverse events and having a child younger than six months. Residential early parenting programs, which take a psycho-educational approach to strengthening caregiving skills, maximising agency, and reducing helplessness, have a rapid beneficial effect on women's postpartum depressive symptoms. These programs provide a valuable and effective component of comprehensive mental health services. Long-term dialectical behaviour therapy is indicated for women with borderline personality disorder traits for whom early parenting programs alone are insufficient to improve depressive symptoms.

A pilot randomized controlled trial of online written exposure therapy delivered by peer coaches to veterans with posttraumatic stress disorder.

This pilot randomized clinical trial (RCT) sought to examine the preliminary efficacy of an internet-based version of written exposure therapy delivered to veterans through an online program supported by peer coaches. Veterans (N = 124) with clinically significant posttraumatic stress disorder (PTSD) symptoms were randomly assigned to imaginal exposure either via writing (written exposure) or verbal recounting (verbal exposure). The online treatment involved four to eight sessions of imaginal exposure preceded and followed by an online chat with a peer coach. Participants completed assessments at baseline, posttreatment, and 3-month follow-up. Half of the participants never started treatment; among those who started treatment, the mean number of sessions completed was 4.92. At posttreatment, participants in both conditions reported clinically meaningful improvements in PTSD symptoms, d = 1.35; depressive symptoms, d = 1.10; and functioning, d = 0.39. Although participants in both treatment conditions demonstrated significant improvements in PTSD symptom severity, equivalence results were inconclusive, as the 95% confidence interval of the change score difference exceeded the specified margin and overlapped with 0. Estimated mean change scores demonstrated that both conditions showed significant reductions at posttreatment and follow-up. Although engagement with the online program was a significant challenge, the findings suggest that written exposure therapy is effective for improving PTSD symptoms, depressive symptoms, and functioning when adapted for internet-based delivery and facilitated by peer coaches. Using technology to deliver exposure therapy and task-shifting the role of the therapist to peer coaches are promising strategies to increase access to effective PTSD care.

P237 Cognitive debriefing of a patient-reported outcome measure for abdominal pain and loose stool frequency in Crohn’s disease

Abstract Background Abdominal pain (AP) and loose stools are key symptoms of Crohn’s disease (CD). Patient-reported AP and loose stool frequency (SF) items comprise two of the three patient-reported items included in the Crohn’s Disease Activity Index. These AP and SF items are referred to as "the PRO" in Lilly’s clinical trials. This study aimed to elicit in-depth information on how patients understand and respond to the PRO. Methods Cognitive debriefing interviews were conducted in adults and adolescents (aged 15–17 years) with moderately to severely active CD. Eligible participants self-reported disease severity but had to provide proof that they were diagnosed with CD ≥6 months ago. Participants must have received biologic and/or conventional therapy for CD and must not have had surgery to treat CD. Participants provided feedback on the PRO and described what PRO response options or score changes would reflect meaningful improvement in symptoms or denote successful treatment. Interview transcripts and field notes were analysed using a standard thematic analysis approach. Results 17 adults and 3 adolescents participated during May–July 2023. Participants had a mean age of 38 (range=17–60) years; 70% (n=14) were female; 70% (n=14) were White. Participants had been diagnosed, on average, 10 (range=0.5–29) years ago. Most participants (n=13, 65%) reported moderate CD severity. All participants interpreted the AP item as intended, found the response options clear and easy to use, and reported that it would be easy to recall their AP severity over 24 hours. Of the 13 participants reporting AP (mild: n=6, 30%; moderate: n=7, 35%), nearly all (n=11, 85%) would consider a 1-level improvement (e.g., ‘mild’ to ‘none’ on the four-level scale) as meaningful. Most participants (n=11, 55%) would consider a treatment successful if their AP was ‘mild’; while many others (n=8, 40%) would need their AP to be completely resolved (i.e., ‘none’). All participants easily understood the SF item, interpreted it as intended, and reported that it would be easy to recall how many very soft or liquid stools they had experienced in a 24-hour period. Participants generally considered a 35.5% decrease in the number of very soft or liquid stools to be a meaningful improvement. On average, participants would consider a treatment successful if they had 1.7 (range=0–5, median=1) very soft or liquid stools per day. Conclusion Participants understood and easily completed the PRO. These findings support the content validity of the PRO in adults and adolescents with moderately to severely active CD and provide insights on the amount of change in AP and SF that patients would consider meaningful.

Korean Medicine Treatment for a Patient with Post-COVID-19 Pulmonary Fibrosis: A Case Report

Background: Post-COVID-19 pulmonary fibrosis (PCPF) is a common complication in severe COVID-19 cases, often associated with acute respiratory distress syndrome or mechanical ventilation. Patients with PCPF frequently experience a decline in their quality of life due to persistent COVID-19 sequelae, including cough and chest pain. However, there is currently no established standard treatment, and the efficacy of existing medications remains uncertain.Case Report: A 65-year-old female patient presenting with cough, dyspnea, chest pain, and fatigue due to PCPF received Korean medicine treatment for 25 days. Symptom evaluation utilized the modified Medical Research Council scale, the Leicester Cough Questionnaire, and the Numeral Rating Scale. Quality of life and functional status were assessed using the Post-COVID-19 Functional Status and the EuroQol 5-Dimensional 5-Level. The extent of pulmonary fibrosis was assessed by comparing chest computed tomography (chest CT) scans before and after hospitalization. Following treatment, the patient demonstrated clinically meaningful improvement in clinical symptoms, enhanced quality of life, and decreased fibrotic lesions on CT scans.Conclusion: This case report suggests that Korean medicine treatment may be effective in improving clinical symptoms, such as cough and dyspnea caused by PCPF, while also enhancing post-COVID-19 quality of life and ameliorating pulmonary fibrotic lesions.

Exploring the Number of Web-Based Behavioral Health Coaching Sessions Associated With Symptom Improvement in Youth: Observational Retrospective Analysis.

Rates of anxiety and depression have been increasing among children and adolescents for the past decade; however, many young people do not receive adequate mental health care. Digital mental health interventions (DMHIs) that include web-based behavioral health coaching are widely accessible and can confer significant improvements in youth anxiety and depressive symptoms. However, more research is necessary to determine the number of web-based coaching sessions that confer clinically significant improvements in anxiety and depressive symptoms in youth. This study uses data from a pediatric DMHI to explore the number of web-based coaching sessions required to confer symptom improvements among children and adolescents with moderate or moderately severe symptoms of anxiety and depression. We used retrospective data from a pediatric DMHI that offered web-based behavioral health coaching in tandem with self-guided access to asynchronous chat with practitioners, digital mental health resources, and web-based mental health symptom assessments. Children and adolescents who engaged in 3 or more sessions of exclusive behavioral health coaching for moderate to moderately severe symptoms of anxiety (n=66) and depression (n=59) were included in the analyses. Analyses explored whether participants showed reliable change (a decrease in symptom scores that exceeds a clinically established threshold) and stable reliable change (at least 2 successive assessments of reliable change). Kaplan-Meier survival analyses were performed to determine the median number of coaching sessions when the first reliable change and stable reliable change occurred for anxiety and depressive symptoms. Reliable change in anxiety symptoms was observed after a median of 2 (95% CI 2-3) sessions, and stable reliable change in anxiety symptoms was observed after a median of 6 (95% CI 5-8) sessions. A reliable change in depressive symptoms was observed after a median of 2 (95% CI 1-3) sessions, and a stable reliable change in depressive symptoms was observed after a median of 6 (95% CI 5-7) sessions. Children improved 1-2 sessions earlier than adolescents. Findings from this study will inform caregivers and youth seeking mental health care by characterizing the typical time frame in which current participants show improvements in symptoms. Moreover, by suggesting that meaningful symptom improvement can occur within a relatively short time frame, these results bolster the growing body of research that indicates web-based behavioral health coaching is an effective form of mental health care for young people.

Improvements in Patient-Reported Outcomes in Relapsed or Refractory Large B-Cell Lymphoma Patients Treated With Epcoritamab

BackgroundPatient-reported outcomes were evaluated in EPCORE NHL-1 in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with epcoritamab monotherapy (NCT03625037). Materials and MethodsAdults with R/R CD20+ LBCL and ≥2 prior systemic antilymphoma therapies, including anti-CD20, completed the Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) and EQ-5D-3L. A subgroup of patients provided additional feedback in one-on-one qualitative interviews. FACT-Lym and EQ-5D-3L score changes from baseline (CFB) to cycle 9 or end of treatment were interpreted using published minimally important differences (MID). ResultsIn total, 157 patients (88.5% with diffuse LBCL) were treated (median age, 64 years). In total, 70.7% had ≥3 prior treatments, 61.1% had primary refractory disease, and 82.8% were refractory to last systemic therapy. FACT-Lym scores exceeded MID thresholds: mean (SD) CFB were 4.4 (15.2), MID 3.0 to 7.0 (FACT-General); 5.9 (7.6), MID 2.9 to 5.4 (FACT-Lymphoma subscale); 8.4 (15.2), MID 5.5 to 11.0 (FACT-Trial Outcome Index); 10.3 (20.2), MID 6.5 to 11.2 (FACT-Lym total score). EQ-5D-3L index scores, 0.09 (0.20), MID 0.08, and EQ-VAS scores, 16.6 (22.8), MID 7.0, improved. In 20 qualitative interviews, 88.2% reported symptom improvements; 80.0% were “very satisfied” or “satisfied” with epcoritamab. ConclusionsR/R LBCL patients reported consistent, clinically meaningful improvements in symptoms and HRQoL and satisfaction with epcoritamab.

Longitudinal Assessment of Transfusion Intensity in Patients with JAK Inhibitor-Naive or -Experienced Myelofibrosis Treated with Momelotinib in the Phase 3 Simplify-1 and Momentum Trials

Introduction: Anemia is a cardinal feature of myelofibrosis (MF), along with splenomegaly and constitutional symptoms. Red blood cell (RBC) transfusions, often used to manage anemia in patients (pts) with MF, are a negative prognostic factor for overall survival and are associated with diminished quality of life and increased healthcare-related economic burden. Momelotinib (MMB), a Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor, has demonstrated clinically meaningful and durable improvements in anemia, splenomegaly, and symptoms. Prespecified anemia endpoints in MMB phase 3 studies prioritized achievement of a strict transfusion independence response, defined as no transfusions for ≥12 wk immediately before the end of wk 24, with all hemoglobin levels ≥8 g/dL. Longitudinal analysis of transfusion intensity (units per 28 days) in a phase 2 trial of MMB in pts with transfusion-dependent MF demonstrated a reduction in transfusion burden in most (85%) pts (Harrison C, et al. EHA 2023). Here, we further characterize the impact of MMB and comparators on transfusion burden in pts with JAK inhibitor-naive and -experienced MF from the phase 3 SIMPLIFY-1 and MOMENTUM trials. Methods: This analysis evaluated time-dependent transfusion burden in pts enrolled in the phase 3 SIMPLIFY-1 (NCT01969838) and MOMENTUM (NCT04173494) trials. SIMPLIFY-1 included pts with JAK inhibitor-naive MF randomized (1:1) to receive MMB or ruxolitinib (RUX). In MOMENTUM, pts with symptomatic (Myelofibrosis Symptom Assessment Form Total Symptom Score ≥10), anemic (hemoglobin &amp;lt;10 g/dL), JAK inhibitor-experienced MF were randomized (2:1) to receive MMB or danazol (DAN). All RBC units transfused were collected during the 24-wk randomized treatment period of each study and during the 84 days before receipt of randomized treatment on study for baseline assessment. Time-dependent transfusion burden was quantified by number of RBC units administered, in a tabular display of baseline- and treatment-period intensity. Pts were grouped jointly based on the baseline- and treatment-period intensity of RBC units per 28 days into ordinal bins: exactly zero units, &amp;gt;0 to 1 unit, &amp;gt;1 to 2 units, &amp;gt;2 to 3 units, &amp;gt;3 to 4 units, and &amp;gt;4 units. Results: In SIMPLIFY-1 (JAK inhibitor-naive pts), 150 of 213 evaluable pts (70%) in the MMB arm and 163 of 216 evaluable pts (76%) in the RUX arm required zero units of RBC transfusion per 28 days at baseline. Of pts who required zero units of transfusion at baseline, a higher proportion in the MMB arm (142 of 150 [95%]) maintained a requirement of zero RBC transfusions during randomized treatment of 24 wks vs the RUX arm (93 of 163 [57%]). Overall, the mean RBC transfusion burden per 28 days declined 0.10 units (SD, 0.701) from baseline to randomized treatment in the MMB arm and increased 0.39 units (SD, 1.016) in the RUX arm. Using ordinal bins, 87% of pts in the MMB arm maintained (144 [67.6%]) or improved (41 [19.2%]) RBC transfusion intensity during randomized treatment compared with baseline vs 54% in the RUX arm (maintained, 94 [43.5%]; improved, 23 [10.6%]) (Figure). In MOMENTUM (JAK inhibitor-experienced pts), most pts had some transfusion requirement at baseline, with 26 of 130 (20%) in the MMB arm and 11 of 65 (17%) in the DAN arm requiring zero units of RBC transfusion per 28 days. During randomized treatment, a higher proportion of pts in the MMB arm (46 of 130 [35%]) required zero units of RBC transfusion vs the DAN arm (11 of 65 [17%]), including a higher proportion of those who had zero RBC transfusion requirement at baseline who maintained zero RBC transfusion requirement during randomized treatment (MMB, 92%; DAN, 64%). The mean RBC transfusion burden per 28 days declined 0.86 units (SD, 1.748) from baseline to randomized treatment in the MMB arm and declined 0.28 units (SD, 1.584) in the DAN arm. Using ordinal bins, 85% of pts in the MMB arm maintained (25 [19.2%]) or improved (85 [65.4%]) RBC transfusion intensity compared with baseline vs 63% in the DAN arm (maintained, 7 [10.8%]; improved, 34 [52.3%]). Conclusions: These data demonstrate that MMB was associated with better maintenance of RBC transfusion intensity and zero RBC transfusion status vs RUX in pts with MF who were JAK inhibitor naive and showed greater reduction in RBC transfusion burden from baseline vs DAN in pts with MF who were JAK inhibitor experienced. Across both trials, ≥85% of pts treated with MMB maintained or improved transfusion intensity.

Clinical Effectiveness and Safety of Momelotinib Compared with Continued Ruxolitinib or Best Available Therapy in Patients with Myelofibrosis Who Required RBC Transfusions: Subgroup Analysis of the Phase 3 Simplify-2 Study

Introduction: Splenomegaly, constitutional symptoms, and anemia are key clinical features of myelofibrosis (MF); approximately one-third of patients (pts) are anemic at diagnosis, and most develop anemia over time. While Janus kinase (JAK) inhibitors such as ruxolitinib (RUX) and fedratinib (FED) may address symptoms and splenomegaly, they do not manage and may exacerbate anemia. Treatments for anemia include erythropoiesis-stimulating agents (ESAs), often in combination with RUX or FED, and androgens such as danazol; however, these have shown limited efficacy. Red blood cell (RBC) transfusions are the mainstay of anemia management in MF, but transfusion dependency is associated with diminished quality of life and is a negative prognostic factor for survival. Treatments that address anemia as well as spleen volume and symptoms are needed. Momelotinib (MMB), a JAK1/JAK2/activin A receptor type 1 inhibitor, has demonstrated clinically meaningful and durable improvements in anemia, splenomegaly, and symptoms in pts with MF across 3 phase 3 trials. To evaluate outcomes in pts who switched to MMB vs continuing RUX or best available therapy (BAT) despite transfusion requirement, we present a descriptive subgroup analysis of pts enrolled in SIMPLIFY-2 (NCT02101268) who were considered transfusion dependent (TD; ≥4 units of RBC transfusions in the previous 8 wk or hemoglobin [Hb] level &amp;lt;8 g/dL) or transfusion requiring (TR; receiving transfusions but not meeting TD criteria) at baseline (BL). Methods: SIMPLIFY-2 was an international, multicenter, open-label, phase 3 clinical trial investigating the efficacy and safety of MMB vs BAT in pts with MF who had suboptimal responses or hematologic toxicities while receiving RUX. Pts (N=156) were randomized 2:1 to receive open-label MMB or BAT, which was RUX in 88.5% of pts. Treatment washout from prior RUX was not permitted before study enrollment. The primary endpoint was spleen volume reduction ≥35% (SVR35). Total Symptom Score (TSS) response rate (≥50% reduction; TSS50) and transfusion independence response (TI-R; no RBC transfusions for ≥12 wk immediately before the end of wk 24, with all Hb levels ≥8 g/dL) were key secondary endpoints. This post hoc, descriptive analysis focused on pts treated with either MMB or BAT, who were considered non-transfusion-independent (non-TI), defined as either TD or TR, at BL. Results: In SIMPLIFY-2, 72 of 104 pts (69%) in the MMB arm and 33 of 52 pts (63%) in the BAT arm were non-TI at BL, and BL characteristics were balanced between both patient groups. Mean duration of prior treatment with RUX was 64.6 and 59.5 wk in non-TI pts in the MMB and RUX arms, respectively. Average BL TSS for this subpopulation was 18.6. All pts randomized to the MMB arm received a starting dose of 200 mg daily. In the BAT arm, 29 of 33 pts (88%) were treated with RUX, with 59% receiving a BL dose of ≤20 mg daily. ESAs were administered to 5 pts in the BAT arm. At wk 24, SVR35 was observed in 7 of 72 pts (10%) treated with MMB and 1 of 33 pts (3%) treated with BAT. TSS50 was achieved in 21 of 72 pts (29%) treated with MMB, but there were no responses in the BAT arm. Additionally, TI-R was achieved in 25 of 72 pts (35%) treated with MMB compared with only 1 of 33 (3%) treated in the BAT arm on RUX. Many responders with MMB achieved 2 or all 3 endpoints (16 of 36 responders [44%]) (Figure); there were no dual or triple responses in the BAT arm. Of the 5 pts in the BAT arm who received ESAs, only 1 pt each (different pts per response) achieved SVR35, TSS50, or TI. Safety outcomes were consistent with those previously reported for the intent-to-treat (ITT) population. Conclusions: In RUX/BAT-treated pts with MF who required RBC transfusions, continued treatment with RUX/BAT in most pts resulted in poor treatment outcomes compared with MMB. Specifically, treatment with MMB demonstrated an ability to deliver higher SVR, TI, and TSS response rates. The lower SVR35 rate in both arms, similar to the overall ITT population, was likely a result of lack of washout from prior JAK inhibitor treatment. While pt numbers were limited, similar findings were observed compared with pts who received ESAs. Overall, these data support MMB as a potential alternative treatment option for pts with MF who require RBC transfusions. Figure. Responses at Week 24 for Non-TI Patients at Baseline

Efficacy and safety of apremilast in patients with moderate-to-severe genital psoriasis: Results from DISCREET, a phase 3 randomized, double-blind, placebo-controlled trial

Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. To assess the efficacy and safety of apremilast 30mg twice daily in patients with genital psoriasis. DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. Patients were randomized to apremilast (n=143) or placebo (n=146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P=.0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. Lack of active-comparator. Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis.