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Abstract Objectives This study aimed to investigate the procedural characteristics, efficacy, and safety of atrioventricular junction (AVJ) ablation for atrial tachyarrythmia (AT) in patients with congenital heart disease (CHD). Background Although AVJ ablation is an established treatment option for intractable AT in the general population, there is no existing data on this treatment in patients with CHD. Methods Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Eleven centers contributed baseline, procedural and longitudinal data, including vital status, echocardiographic data, QRS duration, and NYHA class. Outcomes were assessed at early (3 months-1 year), and late follow-up (≥2 years) after AVJ ablation. Results A total of 66 patients (46.7 ± 20.2 years) underwent 71 AVJ ablations. In total, 58.5% had moderate or complex CHD, including 17.1% patients with a systemic RV or single ventricular circulation. The cumulative AVJ ablation success rate was 98.5%. An abnormal location of the atrioventricular conduction pathway was successfully targeted in 20.0% of the patients, which was significantly more common in patients with complex CHD compared to moderate or mild CHD (44.4%, 15.8%, and 3.6%, respectively; both P<0.05). Thirty-six patients (54.5%) underwent primary pacemaker implantation as part of the ‘pace and ablate’ strategy; final pacing modes were VVI pacing in 60.9%, and CRT/CSP in 39.1%. The transplant-free survival rates at 2, 5 and 10 years after AVJ ablation were 91.5%, 84.3%, and 69.0%, respectively. The acute and long-term complication rates were 3.0% and 13.6%, respectively. Conclusions AVJ ablation can be successfully performed in CHD patients with a high acute success rate and low complication rate. Anatomical challenges were common, which underscores the need for careful planning and operator experience. Given the acceptable long-term survival, these findings support the consideration of a ‘pace and ablate’ strategy in CHD patients with intractable AT.

Individuals with inflammatory bowel disease (IBD) experience overlooked deficits in objectively measured cognitive functioning; however, there is limited knowledge about self-reported cognitive symptoms in this group. Sleep characteristics, such as insomnia, poor sleep quality, or fragmented sleep, may be key modifiable factors that are associated with cognitive symptoms among individuals with IBD. This study aimed to describe cognitive symptoms and examine the relationship between these symptoms and sleep characteristics among adults with IBD. We conducted a descriptive, cross-sectional study using the Pittsburgh Sleep Quality Index, wrist actigraphy, the Insomnia Severity Index, and the FACT-Cog Perceived Cognitive Impairments subscale. Bivariate statistics were used to evaluate relationships between variables. The sample included 83 participants (mean age 40.44 years [standard deviation 10.7], 71% female). Over 77% ( n = 60) had poor self-reported sleep quality, and 69.5% ( n = 57) had clinically meaningful insomnia. The most frequently reported cognitive symptoms (experienced two or more times a week) were trouble concentrating (51.3%), forgetting names (43.8%), forgetting intended tasks (38.9%), and slow thinking (37.6%). Insomnia severity was moderately correlated with three out of the four most common cognitive symptoms (trouble concentrating: r s = .51, p < .01; forgetting intended tasks: r s = .38, p < .01; slow thinking: r s = .46, p < .01). Future research is needed to examine relationships between objective cognitive measures and sleep characteristics and to test the effects of insomnia treatment on daytime cognitive symptoms in this complex patient population.

Objective Despite promising outcomes from pilot initiatives, the transition to widespread adoption and upscaling of eHealth solutions in the hospital context remains challenging. This study aims to explore the barriers and facilitators influencing the implementation of eCoaches from the perspective of professionals. Methods A qualitative research design was employed, involving individual semi-structured interviews with management and healthcare professionals ( n = 10) who were involved with an eCoach either for heart failure (HF) or inflammatory bowel disease (IBD). Both eCoaches supported remote monitoring, advisory, educational, and interactive care activities. Interview topics were guided by the Consolidated Framework for Implementation Research (CFIR), including the original five domains and the added domain Patients′ needs and Resources. Data were analyzed thematically. Results Barriers and facilitators were identified across all CFIR domains: eCoach design and licensing costs (Intervention Characteristics); financial compensation (Outer Setting); integration into care pathways, Information and Communication Technology (ICT) infrastructure, team dynamics, and task reallocation (Inner Setting); intrinsic motivation, beliefs, and competencies of professionals (Characteristics of Individuals); patient resources and digital literacy (Patients’ Needs and Resources); and availability of evidence and management information (Process of Implementation). Conclusion This study underscores the complex nature of implementing eCoaches within the hospital setting, where barriers and facilitators span multiple interrelated domains. To overcome “pilotitis” and achieve the sustainable integration of blended care for patients with chronic conditions, comprehensive implementation strategies that concurrently address all relevant domains are essential. By illuminating the experiences of healthcare professionals, this study offers actionable insights to guide the design, implementation, and upscaling of eCoaches and related eHealth technologies.

Abstract Background Research is limited on the impacts of menopause, defined as the permanent cessation of ovarian function and decline of reproductive hormones, on gastrointestinal symptom severity and disease progression in women with inflammatory bowel disease (IBD). This review synthesizes current evidence on the impact of menopause, menopause transition, and hormonal therapy (HT) on disease activity, IBD and menopause symptom severity, and disease progression among individuals with IBD. Methods A systematic literature review was reported following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and preregistered at PROSPERO (CRD42024564901). Five databases were searched without date restrictions. Data extraction and risk-of-bias assessment were performed independently by multiple reviewers. Results were qualitatively synthesized. Results Of 1667 records, 15 studies met inclusion criteria (5 cohort, 3 case-control, 7 cross-sectional) with IBD sample sizes from 37 to 1367. Evidence on HT and IBD risk was mixed: some studies linked HT to increased ulcerative colitis risk while others found no significant association after adjusting for confounders. Women with IBD experience earlier menopause than healthy control subjects. While most women reported no change in IBD symptoms postmenopause, a minority reported symptom worsening. HT may reduce flare severity. Women with IBD reported more severe vulvovaginal symptoms and had distinct vaginal microbiome profiles compared with healthy control subjects. Conclusions Few studies have explored the relationship between menopause and IBD. There is a need for continued research on the relationship between IBD disease activity and menopause symptoms to create tailored interventions to improve women’s health with IBD across the lifespan.

Limited studies have explored the effects of individual and environmental factors on sleep disturbance in individuals with inflammatory bowel disease (IBD), which is vital for informing future sleep interventions. Thus, the purpose of this study was to explore the possible mediated effects of potential precipitating and/or perpetuating factors on the relationship between sleep disturbance and symptoms in adults with IBD. This is a correlational study of adults with IBD recruited from ResearchMatch. Survey questions asked about demographics, clinical characteristics, sleep hygiene, sleep beliefs and attitudes, sleep environment, sleep control, and symptoms (sleep disturbance, abdominal pain, anxiety, depression, fatigue). Data analysis included descriptive statistics, Pearson correlations, and mediation analysis. We included 250 adults with IBD ( M = 37.9 years old, 64.8% female, 72.4% white). Fifty-four percent of the sample self-reported having a diagnosed sleep disorder. Sleep hygiene and sleep beliefs and attitudes significantly mediated the relationship between sleep disturbance and symptoms (i.e., fatigue, depression, anxiety, and abdominal pain). Whereas the sleep environment and sleep control did not significantly mediate the relationship between sleep disturbance and symptoms. Individuals with IBD experience sleep disturbances, alongside symptoms of anxiety, depression, abdominal pain, and fatigue. Mediation analysis identified sleep hygiene and sleep beliefs, and attitudes as partial mediators. Considering cognitive-behavioral therapy for insomnia is recommended for restructuring these mediating factors. Participants also faced moderate environmental disturbances, suggesting a need for further investigation in this population.

Abstract Introduction The majority of adults with inflammatory bowel disease (IBD) experience disability which is not fully explained by disease activity. Up to 80% of adults with IBD experience poor sleep health, which is associated with disability in other populations; however, the relationship between disability and sleep health among patients with IBD is largely unexamined. The purpose of this study was to compare the sleep health characteristics of those with and without IBD-related disability. Methods We recruited adults (18 to 59 years old) with IBD from a single academic medical center from 2022 to 2024. We measured disease activity using the Manitoba IBD Index and sleep using the PROMIS Sleep Disturbance and PROMIS Sleep-Related Impairment scales, the Insomnia Severity Index, and 14 days of wrist-worn actigraphy (Phillips Spectrum Plus, Phillips Respironics). We asked participants how many days they missed or had at least 50% reduced productivity in paid work or household work or missed leisure activities in the last 3 months related to their IBD. Disability was defined as missing six or more day over three months. We conducted bivariate analyses and logistic regressions to study associations. Results Among 83 adults with IBD [mean age = 40.4 years (SD 10.7), 59 (71.1%) were female, 56 (71.1%) had Crohn’s disease], and 49 (62.0%) had IBD-related disability. Patients with disability had more severe sleep disturbance (56.4 vs. 51.0, p &lt;.001), sleep-related impairment (58.3 vs 50.3, p &lt;.001), more severe insomnia (12.7 vs. 9.4, p =.029), and actigraph-measured higher wake after sleep onset (41.6 minutes vs. 34.0 minutes, p = 0.012) and lower sleep efficiency (85.1% vs. 87.9%, p = 0.032) compared to those without disability. After controlling for age and disease activity, sleep-related impairment (OR = 1.1, 95% CI 1.03, 1.15) was independently associated with disability. Conclusion Patients with IBD-related disability experience poor sleep health. Sleep related daytime impairment uniquely contributed to disability when controlling for disease activity. Sleep interventions need to be tested in adults with IBD to determine if they are effective at addressing disability in this population. Support (if any) Mayo Clinic Bonner Fund

ImportanceMyeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.ObjectiveTo determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.Design, Settings, and ParticipantsVerdiperstat was tested as a regimen of the HEALEY ALS Platform Trial, a multicenter, double-blind, perpetual platform design, randomized clinical trial, with sharing of trial infrastructure and placebo data across multiple regimens. The study was conducted at 54 ALS referral centers across the US from July 2020 to April 2022. Adult participants with a diagnosis of clinically possible, probable, laboratory-supported probable, or definite ALS defined by the revised El Escorial criteria were randomized to verdiperstat or regimen-specific placebo. An additional group of participants concurrently randomized to placebo from other regimens was included in the analyses.InterventionsEligible participants were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily or matching placebo for a planned placebo-controlled duration of 24 weeks.Main Outcomes and MeasuresThe primary efficacy outcome was change from baseline through week 24 in disease severity, as measured by a joint model of ALS Functional Rating Scale–Revised and survival, with the treatment effect quantified by the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression of verdiperstat relative to placebo.ResultsA total of 167 participants (mean [SD] age, 58.5 [11.4] years; 59 [35.3%] female; 108 [64.6%] male) were randomized to either verdiperstat (126 [75.4%]) or to placebo (41 [25.6%]). Among the participants randomized to the verdiperstat regimen, 130 (78%) completed the trial. The estimated DRR was 0.98 (95% credible interval, 0.77-1.24; posterior probability = 0.57 for slowing of disease progression [DRR &amp;lt;1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, −23% to 24%; posterior probability 0.57). Verdiperstat was overall safe and well tolerated. Common adverse events in the verdiperstat group were nausea, insomnia, and elevated thyrotropin levels.Conclusions and RelevanceResults demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS.Trial RegistrationClinical Trial Identifiers: NCT04297683 and NCT04436510

ImportanceAmyotrophic lateral sclerosis (ALS) is a fatal disease. The sigma-1 (σ1) receptor emerged as a target for intervention.ObjectiveTo determine the effects of pridopidine, a σ1-receptor agonist, in ALS.Design, Settings, and ParticipantsPridopidine was tested as a regimen of the HEALEY ALS Platform Trial, a phase 2/3, multicenter, randomized, double-blind, platform trial. The study was conducted at 54 sites in the US from January 2021 to July 2022 (final follow-up, July 14, 2022). A total of 163 participants with ALS were randomized to receive pridopidine or placebo. An additional 122 concurrently randomized participants were assigned to receive placebo in other regimens and included in the analyses.InterventionsEligible participants were randomized 3:1 to receive oral pridopidine 45 mg twice daily (n = 121) or matching oral placebo (n = 42) for a planned duration of 24 weeks.Main Outcomes and MeasuresThe primary efficacy outcome was change from baseline through week 24 in ALS disease severity, analyzed using a bayesian shared parameter model, which has components for function (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]) and survival that were linked through an integrated estimate of treatment-dependent disease slowing across these 2 components. This was denoted as the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression on pridopidine relative to placebo. There were 5 key secondary end points: time to 2-point or greater reduction in ALSFRS-R total score among participants with bulbar dysfunction at baseline, rate of decline in slow vital capacity among participants with bulbar dysfunction at baseline, percentage of participants with no worsening in the ALSFRS-R bulbar domain score, time to 1-point or greater change in the ALSFRS-R bulbar domain score, and time to death or permanent assisted ventilation.ResultsAmong 162 patients (mean age, 57.5 years; 35% female) who were randomized to receive the pridopidine regimen and included in the primary efficacy analysis, 136 (84%) completed the trial. In the primary analysis comparing pridopidine vs the combined placebo groups, there was no significant difference between pridopidine and placebo in the primary end point (DRR, 0.99 [95% credible interval, 0.80-1.21]; probability of DRR &amp;lt;1, 0.55) and no differences were seen in the components of ALSFRS-R or survival. There was no benefit of pridopidine on the secondary end points. In the safety dataset (pridopidine, n = 121; placebo, n = 163), the most common adverse events were falls (28.1% vs 29.3%, respectively) and muscular weakness (24.0% vs 31.7%, respectively).Conclusions and RelevanceIn this 24-week study, pridopidine did not impact the progression of ALS.Trial RegistrationClinicalTrials.gov Identifiers: NCT04297683, NCT04615923

Importance The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression. Objective To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS. Design, Setting, and Participants Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens. Interventions Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing. Main Outcomes and Measures The primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; &amp;lt;1 indicating treatment benefit). The study included prespecified rules for early stopping for futility. Outcome analyses were performed in the full analysis set comparing the zilucoplan group with the total shared placebo group (n = 164). Results Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified. Conclusions and Relevance In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources. Trial Registration ClinicalTrials.gov Identifier: NCT04297683