Pandemic restrictions impacted healthcare, particularly during the first year. We evaluated the impact of the pandemic on quality of life and clinical care among patients with primary biliary cholangitis (PBC). This mixed-methods study administered quality of life surveys (Fear of COVID-19 Scale [FCV-19S], EuroQol 5-dimension 3-level [EQ-5D-3L], 29-item Patient-Reported Outcomes Measurement Instrument Survey [PROMIS-29]) and a PBC Care Delivery questionnaire to 348 Canadian PBC patients, followed by two focus groups with patients (n = 14) and stakeholders (n = 3). Quality of life scores were compared among sub-groups (i.e., care delays and pandemic appointment type) and with various reference populations. Most participants were female (94.0%) and Caucasian (88.2%), with a median age of 63.0 years (IQR: 55.9-71.2). During the pandemic, 75.8% had the majority (≥ 50%) of their hepatologist appointments virtually, but only 22.4% preferred to continue with virtual care post-pandemic. Participants with care delays had worse scores on the FCV-19S (p = 0.014), EQ-5D-3L (p = 0.009), and PROMIS-29 (i.e., fatigue, anxiety, sleep disturbance, ability to participate in social roles and activities, p < 0.01), compared to those without care delays. PBC patients had worse PROMIS-29 scores compared to a general population (p < 0.01). Both patients and stakeholders stressed the importance of in-person appointments, while recognizing a role for virtual appointments post-pandemic. PBC patients' quality of life worsened during the pandemic, especially those with delayed care. Most PBC patients expressed a preference for in-person appointments post-pandemic.

Individuals living with chronic illness commonly experience co-occurring physical, psychological, and existential symptoms that cluster and reinforce one another, contributing to functional decline and distress. Yet, frailty and existential distress have rarely been examined alongside psychological and physical symptoms, and few studies have mapped how these symptoms interrelate across chronic conditions. This study used baseline patient-reported outcome measures (PROMs) from the eMPower randomized controlled trial to examine interconnections among symptoms across physical, psychological, and existential domains in adults living with chronic medical conditions. Adults aged ≥18 years (n = 825) were enrolled in the 12-week eMPower digital mind-body program (breathwork/meditation practices, movement, psychology-based coping skills curriculum based on acceptance and commitment therapy (ACT)). Baseline PROMs included the Hospital Anxiety and Depression Scale (HADS), Modified Fatigue Impact Scale (MFIS), EQ-5D-5L, SF-12, Edmonton Frail Scale Acute Care version (EFS-AC), online Fried Frailty Phenotype (online FFP), Demoralization Scale-II (DS-II), and PROMIS Sleep Disturbance SF-8a. Network analysis of pooled baseline data using LASSO-regularized partial correlations identified clusters and central symptoms. Participants had a mean age 55.6 ± 12.7 years and were predominantly female (84%). Across the cohort, symptom burden was high, frailty was prevalent, and quality of life was impaired. Network analysis identified three clusters: (i) mental health; (ii) fatigue and frailty; and (iii) quality of life, with physical fatigue emerging as the most central node linking psychological and functional domains. These findings suggest that fatigue, demoralization, and frailty are interconnected drivers of symptom burden in chronic illness. Targeting fatigue may represent an important strategy for improving mental health and functional outcomes in people living with chronic medical conditions.

Background Anxiety, depression, and fatigue affect >50% of adults across a range of chronic medical conditions, leading to reductions in quality of life. Digital symptom management interventions may address this burden, but clinical trial evidence across diverse conditions is limited, and the added value of human support remains uncertain. This study aimed to determine whether a multicomponent digital intervention, delivered with or without human support, reduces anxiety and depression compared with usual care at 12 weeks in adults with chronic medical conditions, and whether human-supported delivery outperforms self-directed delivery. Methods and findings A three-arm parallel-group open-label randomized controlled trial was conducted from February 2023 to December 2024, with online recruitment and delivery across 13 countries. 825 adults (≥18 years) with self-reported chronic medical conditions and internet access were allocated by computer-generated stratified block randomization (1:1:1) to: (i) waitlist control ( n = 274); (ii) eMPower, a self-directed digital program integrating video-guided movement, breathwork, and meditation practices, a psychology-based coping skills curriculum, and disease education ( n = 275); or (iii) eMPower + human support consisting of weekly telephone check-ins (≤15 min) from trained nonclinicians ( n = 276). The primary outcome was change in Hospital Anxiety and Depression Scale (HADS) total score from baseline to 12 weeks in the eMPower + human support arm compared with the control arm, adjusted for baseline score, chronic condition type, age, and sex. Secondary outcomes included HADS anxiety and depression subscales, fatigue (Modified Fatigue Impact Scale [MFIS]), and health-related quality of life (Short Form-12 [SF-12] mental and physical component scores and EQ-5D-5L index score). Twelve-week assessments were completed by 695 participants (84.2%). Primary outcome data were available for 222 participants in the eMPower + human support arm, 214 in the self-directed eMPower arm, and 259 in the control arm. Analyses followed the intention-to-treat principle. In the prespecified primary comparison, eMPower + human support improved HADS total score by 2.9 points (95% CI [2.0, 3.8]; p < 0.001). In prespecified exploratory analyses, the self-directed eMPower arm also significantly improved HADS total score, compared with control (mean difference 2.6 points; 95% CI [1.8, 3.5]; p < 0.001). No significant differences were observed between intervention arms for any outcome (all p > 0.05). Both intervention arms were associated with improvements across prespecified secondary outcomes compared with control. No intervention-related adverse events were reported in any arm. Key limitations include the use of a waitlist control design, which does not control for nonspecific intervention effects; reliance on self-reported diagnoses for most participants; the 12-week follow-up period; and a predominantly female and highly educated sample, which may limit generalizability. Additional registered process-oriented secondary outcomes and exploratory outcomes will be reported in companion publications. Conclusions A multicomponent digital intervention with human support significantly reduced anxiety and depression symptoms compared with usual care in adults with chronic medical conditions. Comparable effects between self-directed and human-supported delivery in exploratory analyses highlight potential for scalable, low-resource implementation. Longer-term follow-up and cost-effectiveness analyses are warranted. Trial registration: ClinicalTrials.gov: NCT05786482.

Primary biliary cholangitis (PBC) is a rare cholestatic autoimmune liver disease. We aimed to generate evidence of the signs, symptoms, and impacts of PBC considered important by patients through interviews with clinicians and patients. This noninterventional, qualitative study involved a targeted literature review (TLR), clinician interviews, and patient interviews. The TLR identified relevant signs, symptoms, and impacts of PBC, as well as their reported prevalence data. This information was developed into a preliminary conceptual model (PCM) of PBC and refined via interviews with gastroenterology/hepatology clinicians, focusing on patients’ experiences. Next, PBC-related concepts were captured through patient interviews, and the PCM was finalized. A thematic approach was used to analyze data, and descriptive statistics were used to assess symptom and impact salience, ensuring a representative sample and achieving concept saturation. Fatigue and pruritus were confirmed as the most prevalent symptoms. Clinician interviews (n = 4) provided insights into biochemical abnormalities used for diagnosis and common symptoms. Patient interviews (n = 20) revealed 41 unique PBC signs and symptoms. Patients reported mental and/or physical fatigue, with both impacting daily activities and overall health-related quality of life. They also reported that pruritus interfered with sleep and social engagements. The final conceptual model could distinguish between salient and non-salient signs, symptoms, and impacts, reflecting patients’ attributions to PBC and its treatment. PBC imposes a significant burden on patients’ lives. This study highlights unmet patient needs, contributing valuable qualitative evidence to support clinical and observational studies in PBC. Primary biliary cholangitis (PBC) is a rare disease where the immune system attacks and damages small bile ducts in the liver. PBC can get worse with time and can be potentially life-threatening. The main symptoms are tiredness and itchy skin (pruritus). We examined how people with PBC experience their condition, to better understand how it can be managed in the most useful way for patients. First, we used published studies to gather information on PBC, such as symptoms and ways in which PBC affects patients’ lives (impacts), allowing us to develop a model of PBC. Then, we interviewed medical professionals and patients to understand which symptoms and life impacts matter most to those living with PBC. The medical professionals discussed methods for diagnosing PBC. They reported that patients’ tiredness became worse as the day progressed. Medical professionals said that patients mostly had itchy skin on the soles of the feet or palms and found it to be very bothersome, greatly affecting patients’ daily lives and mental health. When interviewed, patients reported 41 different signs and symptoms, most commonly tiredness and itchy skin. Patients said they experienced mental and physical tiredness, making everyday tasks difficult, and they described how the itching disturbed their sleep and social lives. This study showed how much PBC affects patients’ quality of life. Our model of the most important symptoms and impacts for patients can guide research and improve care by helping us focus on what patients find most difficult about PBC.

Abstract Background: Fibroblast growth factor receptor 1 (FGFR1) gene amplification and overexpression is associated with an adverse prognosis in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) breast cancer and is observed in ~10% of all invasive breast cancers. The phase 2 FOENIX-MBC2 study (NCT04024436) was designed to evaluate the effect of futibatinib, a highly selective and potent irreversible covalent inhibitor of FGFR1–4 (FDA-approved for intrahepatic cholangiocarcinoma), used either alone or in combination with fulvestrant in patients with metastatic breast cancer. Here, we report final efficacy and safety data for the cohort of patients receiving futibatinib plus fulvestrant for HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification. Methods: Patients were eligible if they had disease progression after prior therapy for advanced/metastatic disease, had measurable disease per RECIST v1.1, had an ECOG performance status of 0 or 1, were fulvestrant-naïve, and had previously received 1–2 endocrine-containing therapies, ≤1 chemotherapy regimen, and a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor for advanced cancer (unless ineligible). High-level FGFR1 gene amplification, determined in tumor tissue using next-generation sequencing, fluorescence in situ hybridization (FISH), or similar assays, was defined as FGFR1/centromere 8 ratio ≥5 or FGFR1 copy number ≥10 signals per cell. Local FGFR1 determination results were confirmed in tumor tissue by a central laboratory using FISH. Patients received oral futibatinib 20 mg once daily and standard fulvestrant dosing until disease progression, unacceptable toxicity, or other discontinuation criteria were met. The primary endpoint was the 6-month progression-free survival (PFS) rate. Key secondary endpoints included objective response rate (ORR), PFS, and overall safety. Results: Overall, 22 female patients were enrolled in this cohort. Patients were a median age of 58 years, had received a median of 3 lines of any prior systemic anticancer therapy, and had all received CDK4/6 inhibitor pretreatment. PFS at 6 months was observed in 10 (45.5%) patients (95% CI: 24.4, 67.8) and the median PFS was 7.2 (95% confidence interval [CI]: 2.1, 7.6) months. Four patients had a confirmed partial response (ORR: 18.2%; 95% CI: 5.2, 40.3). The median duration of response was 6.3 (range: 3.3–12.8) months. All patients had ≥1 treatment-related adverse event (TRAE), the most common being hyperphosphatemia (95.5%), alopecia (54.5%), constipation (45.5%), and dry mouth (40.9%). There were 5 (22.7%) patients with a Grade 3 TRAE (no Grade 4 or 5). TRAEs leading to study treatment interruption or reduction were seen in 9 (40.9%) and 15 (68.2%) patients, respectively. There were 2 (9.1%) patients who had TRAEs leading to study treatment discontinuation. No treatment-related serious adverse events were reported. Conclusions: Futibatinib plus fulvestrant showed antitumor activity in patients with advanced HR+/HER2− breast cancer with FGFR1 amplification progressing on prior CDK4/6 inhibitors, with a numerically higher ORR and doubling in PFS relative to historical fulvestrant results in post-CDK4/6 patients. The safety profile was consistent with those of the individual study drugs. Further biomarker work is ongoing. Citation Format: Senthil Damodaran, Fabrice André, Nisha Unni, Marta Ferreira, Karthik Giridhar, Brooke Daniel, Marco Colleoni, Luis Costa, Thomas Bachelot, Ciara O’Brien, Gail Wright, Masashi Shimura, Gareth Tomlinson, Maciej Gil, Nicholas Turner. Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF01-04.

Background: Symptoms of depression and anxiety are prevalent among adults with chronic health conditions, contributing to reduced quality of life, morbidity, and mortality. Mind-body wellness interventions (i.e. psychology programming, mindful movement, breathwork, meditation) may impact mental health symptoms, with online delivery offering access and scalability. Whether online mind-body wellness interventions are effective in improving patient outcomes across a broad range of chronic conditions remains uncertain. Methods: This three-armed, pragmatic, randomized controlled trial will use a nested mixed methods approach to assess the effectiveness of an online mind-body wellness intervention (eMPower), offered at two levels of personnel support, on symptoms of anxiety and depression in adults with chronic health conditions. Inclusion criteria require a self-reported chronic condition and access to an internet-connected device. Eligible participants will be randomized 1:1:1 to [1] waitlist control; [2] eMPower; [3] eMPower + weekly 1-to-1 check-in. The primary analysis will compare the Hospital and Anxiety Depression Scale (HADS) total score between eMPower + weekly 1-to-1 check-in versus controls, with secondary and exploratory outcomes including HADS subscales, health-related quality of life, fatigue, program engagement, and frailty. Conclusion: With online intervention delivery, a range of outcomes, mixed method evaluation, and automated intervention tracking, findings are anticipated to enhance our understanding of how individuals living with chronic health conditions engage with and are impacted by online mind-body wellness programming. Six hundred and fifty-six participants have been enrolled as of April 5, 2024, and 598 patients have completed 12week follow-up.

BACKGROUND: Persons with primary biliary cholangitis (PBC) experience significantly higher rates of mental distress and impaired health related quality of life (HrQoL) than the general population. Given limited evidence, but a high need, our primary aim was to assess feasibility and acceptability of a 12-week, online, mind-body wellness program in people with PBC. METHODS: This was a single-group, sequential mixed-methods, pre-post feasibility, and acceptability study. Core program components included follow-along movement, meditation and breathwork videos, and cognitive behavioural therapy informed activities. This was supplemented by weekly phone check-ins. Feasibility was assessed by recruitment, adherence, and retention. The pre-post exploratory efficacy assessment included surveys for fatigue, perceived stress, anxiety, depression, HrQoL, and resilience. A qualitative descriptive approach with semi-structured interviews evaluated study experiences. RESULTS: Thirty-two participants were recruited within 30 days and 29 (91%) were retained to end-of-study. Of these, 25 (86%) adhered to carrying out the mind-body practice at least 2-3 days per week. Feedback supported acceptability (satisfaction score 90%). Significant improvements were observed in fatigue (13%, p = 0.004), anxiety (30%, p = 0.005), depression (28%, p = 0.004), and five PBC-40 domains (itch, fatigue, cognitive, emotional, general symptoms). Qualitative interviews revealed improved stress management, better coping, and a more positive mindset. Fatigue and self-sabotaging thoughts were cited as barriers to participation. CONCLUSIONS: These findings suggest that a 12-week online mind-body intervention is feasible and acceptable in patients with PBC. After iterative refinement, a randomized controlled trial will be designed using this feedback.

Background and Aims: People with primary biliary cholangitis (PBC) experience high rates of mental distress and fatigue despite standard of care therapy. We aimed to assess the impact of an online mind-body intervention on these symptoms. Methods: This 12-week RCT used sequential mixed-methods evaluation. Alongside standard of care, participants with primary biliary cholangitis were randomized to receive weekly countdown emails, or the intervention consisting of (i) a weekly 20-30 minute-mind-body follow-along video, (ii) weekly 5-10-minute psychology-based "managing chronic disease skills videos," and (iii) 10-minute telephone check-ins. The primary outcome was a change in the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes evaluated changes in fatigue, perceived stress, resilience, and health-related quality of life. ANCOVA determined between-group differences. Results: Of the 87 randomized patients (control group: n = 44, intervention group: n = 43), the between-group HADS total score improved by 20.0% (95% CI 4.7, 35.2, p = 0.011). Significant improvements were seen in depression (25.8%), perceived stress (15.2%), and 2 primary biliary cholangitis-40 domains [emotional symptoms (16.3%) and social symptoms (11.8%)] with a mean satisfaction of 82/100. This corresponded with end-of-study qualitative findings. Although no improvements were observed in fatigue in the main analysis, a significant benefit was observed in the subgroup of intervention participants (20/36;56%) who completed the mind-body video routine at least 3 times per week. Conclusion: This intervention improved measures of mental wellness and quality of life with high satisfaction and reasonable adherence. Future studies could explore strategies to optimize adherence and target fatigue

Abstract Background: Chemotherapy treatments with robust efficacy that preserve quality of life are needed. Tesetaxel is a novel, oral taxane that has potential advantages over currently available taxanes, including: oral administration with a low pill burden and once every 3 week (Q3W) dosing; no observed hypersensitivity reactions; preclinical evidence of central nervous system (CNS) penetration; and improved activity against chemotherapy-resistant tumors. More than 600 patients have been treated with tesetaxel in clinical studies. Tesetaxel had robust monotherapy activity in a Phase 2 study in 38 patients with HER2-, HR+ MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45%. Preclinical and clinical studies suggest that reducing the dose of capecitabine in combination with a taxane may result in reduced toxicity without a reduction in efficacy. CONTESSA 2 investigates tesetaxel plus a reduced dose of capecitabine as an all-oral regimen in taxane-naïve patients with HER2-, HR+ MBC. Trial design: CONTESSA 2 is a 125-patient, multinational, multicenter, single-arm, Phase 2 study of tesetaxel (27 mg/m2 on Day 1 of a 21-day cycle) plus a reduced dose of capecitabine (1,650 mg/m2/day for 14 days of each 21-day cycle) in patients with HER2-, HR+ MBC who have received no more than one chemotherapy regimen for advanced disease and have not previously been treated with a taxane in any setting. Patients with CNS metastases are eligible. The primary endpoint is confirmed ORR assessed by an Independent Radiologic Review Committee (IRC). A sample size of 125 will allow the ORR to be estimated with a maximum standard error of < 5%. Secondary endpoints include duration of response, pharmacokinetics (PK) of tesetaxel and potential for a PK interaction between tesetaxel and capecitabine. Enrollment was initiated in January 2019. For further information on this trial, email joconnell@odonate.com or visit clinicaltrials.gov (NCT03858972). Citation Format: Lee Schwartzberg, Jamil Asselah, Igor Bondarenko, YeeSoo Chae, Noshir DaCosta, Yin-Hsun Feng, Yann Izarzugaza, Julie Lemieux, Mei-Ching Liu, Gavin Marx, Joyce O'Shaughnessy, Mafalda Oliveira, Hope Rugo, Andrew Seidman, Gail Wright, Joseph O'Connell, Thomas Wei, Sung-Bae Kim. CONTESSA 2: A multinational, multicenter, phase 2 study of tesetaxel plus a reduced dose of capecitabine in patients with HER2-, HR+ metastatic breast cancer (MBC) who have not previously received a taxane [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-07.

inflation-adjusted total hospitalization charges increased by 9.9% (from $47,996 to $52,739).Compared to non-Hispanic whites, significantly longer hospital LOS was observed in African Americans (6.31 vs. 5.48 days; OR 1.08, 95% CI 1.02-1.13,p<0.01) and Asians (7.41 vs. 5.48 days; OR 1.11, p<0.01).When evaluating hospitalization charges, compared to non-Hispanic whites, higher charges were observed in Hispanics ($68,362 vs. $48,692; OR 1.07, 95% CI 1.02-1.21,p<0.01) and Asians ($79,121 vs. $48,692; OR 1.14, 95% CI 1.04-1.25,p<0.01).Among all patients combined, the estimated national economic burden of PBC hospitalizations increased from $94.6 million in 2007 to $120.8 million in 2014.Conclusions: The inpatient economic burden of PBC-related hospitalizations increased significantly from 2007 to 2014, accounting for over $120 million in 2014.This increasing economic burden is multi-factorial and reflects increasing number of hospitalizations, increasing hospitalization LOS, and increasing charges.While the majority of PBC hospitalizations were among non-Hispanic whites, significantly longer hospital LOS and significantly higher mean total hospitalization charges were observed among ethnic minorities.