Disease-related Symptoms Research Articles

BELLWAVE-011: Phase 3 randomized trial of nemtabrutinib versus ibrutinib or acalabrutinib in untreated chronic lymphocytic leukemia/small lymphocytic lymphoma.

TPS7088 Background: Bruton tyrosine kinase (BTK) inhibitors have significantly improved survival in patients (pts) with chronic lymphocytic leukemia (CLL). Nemtabrutinib is a reversible noncovalent inhibitor of wild-type and C481-mutated BTK that has shown promising antitumor activity in pts with CLL (Woyach JA et al. Cancer Discovery 2023). In this ongoing trial, we evaluate the efficacy and safety of nemtabrutinib versus investigator’s choice of ibrutinib or acalabrutinib in pts with untreated CLL/small lymphocytic lymphoma (SLL) requiring therapy (NCT06136559). Methods: This randomized, open-label, parallel group, active-controlled phase 3 trial will enroll approximately 1200 pts aged ≥18 years. Eligible pts will have confirmed CLL/SLL with active disease based on the IWCLL criteria, which include one of the following: 1) progressive marrow failure or lymphocytosis, 2) massive, progressive, or symptomatic splenomegaly or lymphadenopathy, 3) autoimmune complications, 4) extranodal involvement, or 5) disease-related symptoms. The study will enroll patients who are treatment naïve, with an ECOG performance status 0-2, adequate organ function, and provide blood, bone marrow, and/or a lymph node sample. Pts are excluded if they have Richter Transformation, central nervous system (CNS) involvement by CLL/SLL, an active second malignancy, or a severe bleeding disorder. Pts will be randomized 1:1 to receive oral nemtabrutinib 65 mg QD, or investigator’s choice of oral ibrutinib 420 mg QD or acalabrutinib 100 mg BID. Randomization will be stratified by TP53aberration, clinical stage, investigator’s choice of comparator, and region. Treatment will continue on both arms until unacceptable toxicity, disease progression, or withdrawal. Disease response assessments by physical examination, constitutional symptoms, imaging, and evaluation of blood and bone marrow will be performed Q12W up to week 97, and Q24W thereafter. Primary efficacy endpoints are objective response (OR) and progression free survival (PFS) by BICR per iwCLL 2018 criteria. Secondary endpoints are overall survival (OS), duration of response (DOR) by BICR per iwCLL 2018, and safety. OR will be tested via a non-inferiority comparison, while PFS and OS will be tested for superiority. Adverse events will be monitored throughout the trial and graded per NCI CTCAE v5.0 and iwCLL scales. Enrollment in this trial is ongoing. Clinical trial information: NCT06136559 .

Understanding breast cancer (BC) from the patient (pt) perspective: A qualitative study of symptoms, impacts and health-related quality of life (HRQoL) in hormone receptor-positive, HER2-negative (HR+, HER2–) BC.

e23184 Background: HR+, HER2– is the predominant BC subtype. Treatment (tx) options across stages are broad; however, there are limited published qualitative data providing insights on pt disease and tx experiences to inform healthcare decision-making. This study aimed to identify the most important disease- and tx-related symptoms and impacts on HRQoL, including exploring how bothersome and worrisome symptoms were, and attribution to tx and disease, in HR+, HER2– early (e) and metastatic (m)BC. Methods: This was an international qualitative study with pt steering committee input. Individual pt concept elicitation interviews were conducted (until saturation). Interviews were audio-recorded, translated into English, transcribed, and anonymized. Transcripts were coded and analyzed thematically. Two pt-centered conceptual models were developed to summarize data for eBC and mBC. Results: Twenty-four female pts (12 eBC; 12 mBC), aged 33–70 yrs old, were interviewed; 17 were postmenopausal. The most common tx was hormone therapy (n = 10) in eBC and cyclin-dependent kinase 4/6 inhibitors (n = 7) in mBC. The most frequently reported symptoms were fatigue (eBC n = 11; mBC n = 10) and pain (eBC n = 9; mBC n = 11). In eBC, fatigue was ranked most bothersome (n = 3) and pain most worrisome (n = 3). In mBC, pain was ranked most bothersome and worrisome (n = 7). In eBC, sleep problems, hot flashes, and difficulty concentrating/brain fog were also frequently reported (≥50% of pts) and ranked most bothersome. In mBC, sleep problems and hot flashes were also frequently reported (≥50% of pts), with hot flashes ranked most bothersome; nausea was less frequently reported but ranked most bothersome by two pts. The majority of pts with eBC attributed their most frequently reported symptoms to tx, whereas pts with mBC attributed them to tx alone or tx and their disease. The most frequently reported impacts in eBC were limited exercise/strenuous activity (n = 10), and fatigue, difficulty concentrating, and anxiety (n = 9 each). The most frequently reported impacts in mBC were limited participation in social activities (n = 10), and difficulties with activities of daily living, trouble with mobility, anxiety, and frustration (n = 9 each). Conclusions: These qualitative data highlight similarities in pt symptoms across eBC and mBC (pain and fatigue), with differences in symptom attribution. Compared with eBC, pts with mBC had greater physical functioning impairment and may have experienced more disease-related symptoms. Overall, these data improve understanding of pts’ experience in HR+, HER2– BC, identify the distinct and clinically relevant concepts most important to them, and can help to optimize the selection and development of pt-reported outcomes in research and clinical practice to further inform treatment decision-making.

The effects of myofascial release in combined with task-oriented circuit training on balance in people with Parkinson’s disease: a randomized pilot trial

ABSTRACT Objectives Task-oriented circuit training (TOCT) has been used to improve balance in people with Parkinson’s disease (pwPD). To investigate the effectiveness of TOCT on balance, quality of life, and disease symptoms when combined with myofascial release in pwPD. Methods Twenty-six pwPD were randomized into two groups for this randomized controlled study. The groups received TOCT three days a week for eight weeks. At the end of each session, the myofascial release was applied to the neck, trunk, and lumbar region with three sets of 60-s foam rolling body weight (Intervention group-IG) and perceived discomfort level 0/10 (Control group-CG) using a numeric rating scale. Primary outcome measures were measured by the Berg Balance Scale (BBS), Parkinson’s Disease Questionnaire (PDQ-8), and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Secondary outcome measures included posturographic assessment, timed-up and go test (TUG), Trunk Impairment Scale (TIS), and rolling time. Results Data obtained from 26 pwPDs in equal numbers in both groups were analyzed. All groups reported a significant change in MDS-UPDRS, MDS-UPDRS-III, PDQ-8, TIS, and rolling time after treatment compared to pretreatment. Post-hoc analyses showed that IG significantly improved motor symptoms, TUG, and TIS dynamics compared to CG. The mediolateral limits of stability and anterioposterior limits of stability distances of IG increased (p < 0.05). Discussion Myofascial release, when combined with TOCT, may help to reduce disease-related motor symptoms and improve dynamic balance in pwPD. These findings suggest that myofascial release can be a beneficial addition to TOCT programs for pwPD. Clinical Trial Number: NCT05900934 (ClinicalTrials.gov).

Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma.

In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here. Participants were randomly assigned to receive STRIDE, durvalumab, or sorafenib. PROs were assessed (preplanned secondary outcome) using the European Organization for Research and Treatment of Cancer 30-item Quality of Life Questionnaire and the 18-item HCC module. Time to deterioration (TTD), change from baseline and improvement rate in global health status/quality of life (GHS/QoL), functioning, and disease-related symptoms were analyzed. In total, 1,171 participants were randomly assigned to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389) and were evaluable for PRO assessments. Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms. TTD in GHS/QoL, physical functioning, fatigue, appetite loss, and abdominal pain was numerically longer for both STRIDE and durvalumab versus sorafenib. Clinically meaningful deterioration in PROs was not observed in any treatment arm. However, TTD in nausea and abdominal swelling was numerically longer for STRIDE versus sorafenib, and the likelihood of clinically meaningful improvement in GHS/QoL, role, emotional and social functioning, and disease-related symptoms was greater with STRIDE and durvalumab versus sorafenib. PROs with STRIDE and durvalumab were generally similar. Compared with sorafenib, STRIDE and durvalumab were associated with clinically meaningful, patient-centered GHS/QoL, functioning, and symptom benefits in people with uHCC. These findings support the benefits of the STRIDE regimen compared with sorafenib for a diverse population reflective of the global uHCC population.

The Potential Role of the Ketogenic Diet in Serious Mental Illness: Current Evidence, Safety, and Practical Advice.

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics the physiological state of fasting. The potential therapeutic effects in many chronic conditions have led to the gaining popularity of the KD. The KD has been demonstrated to alleviate inflammation and oxidative stress, modulate the gut microbiota community, and improve metabolic health markers. The modification of these factors has been a potential therapeutic target in serious mental illness (SMI): bipolar disorder, major depressive disorder, and schizophrenia. The number of clinical trials assessing the effect of the KD on SMI is still limited. Preliminary research, predominantly case studies, suggests potential therapeutic effects, including weight gain reduction, improved carbohydrate and lipid metabolism, decrease in disease-related symptoms, increased energy and quality of life, and, in some cases, changes in pharmacotherapy (reduction in number or dosage of medication). However, these findings necessitate further investigation through larger-scale clinical trials. Initiation of the KD should occur in a hospital setting and with strict care of a physician and dietitian due to potential side effects of the diet and the possibility of exacerbating adverse effects of pharmacotherapy. An increasing number of ongoing studies examining the KD's effect on mental disorders highlights its potential role in the adjunctive treatment of SMI.

Abstract PS02-02: Patient-reported outcomes from the Phase 3 CAPItello-291 trial investigating capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR-positive/HER2-negative advanced breast cancer

Abstract Background: In the Phase 3 CAPItello-291 trial, adding capivasertib (C), a pan-AKT inhibitor, to fulvestrant (F) in patients (pts) with aromatase inhibitor-resistant, HR+/HER2− (HER2− defined as IHC 0, or 1+ or IHC2+/ISH–) advanced breast cancer significantly improved PFS vs placebo (P) + F in the overall (HR 0.60, 95% CI 0.51, 0.71, p&amp;lt; 0.001) and AKT pathway-altered populations (HR 0.50, 95% CI 0.38, 0.65, p&amp;lt; 0.001). The safety profile of C-F was manageable; diarrhea (mostly grade 1) was the most frequent adverse event. Global health status (GHS)/health-related quality of life (HRQoL) was maintained from baseline in both arms; time to deterioration (TTD) favored C-F. We report results from additional patient-reported outcomes (PRO). Methods: Pts were randomized 1:1 to receive F (500 mg IM on days 1 and 15 of cycle 1 and day 1 of each subsequent 28-day cycle) with either P or C (400 mg BID; 4 days on, 3 days off). PRO measures assessed HRQoL, disease-related symptoms, functioning, and patient-reported treatment tolerability using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC QLQ Breast Cancer 23 items (EORTC QLQ-BR23), PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Patient Global Impression of Treatment Tolerability (PGI-TT). PROs were assessed at pre-specified timepoints. Change from baseline was assessed using Mixed Model Repeat Measures (on-treatment scores) for EORTC QLQ-C30 and summarized for EORTC QLQ-BR23; TTD was assessed using the stratified log-rank test for both. Results: Overall, 708 pts were randomized to C-F (n=355) or P-F (n=353). Overall compliance rates with EORTC QLQ-C30 and PGI-TT were 84.5% and 80.6% with C-F and 81.8% and 81.7% with P-F, respectively. Baseline compliance rates with the EORTC QLQ-C30 and PGI-TT were 88.2% and 82.8% with C-F and 87.3% and 83.1% with P-F, respectively. Mean changes from baseline in EORTC QLQ-C30 functional and symptom domain scores were maintained with C-F and P-F, except for diarrhea in the C-F arm, where scores worsened by &amp;gt;10 points (table). TTD analysis showed that HRs favored C-F vs P-F for all functional and symptom domains, except diarrhea (HR 2.75; 95% CI 2.01, 3.81), which favored P-F (table). Median TTD of diarrhea was shorter with C-F vs P-F in line with the C-F safety profile. Diarrhea with C-F was generally manageable, and discontinuations due to diarrhea were low (2.0%; n=7/355). For PGI-TT, most pts reported that they were ‘not at all’ or ‘a little bit’ bothered by the side effects of cancer therapy. Over the first 6 months, the proportion of pts reporting to be ‘somewhat’, ‘quite a bit’, or ‘very much’ bothered by side effects was higher for C-F vs P-F, with between-arm differences being highest in the first 2 cycles. Results from EORTC QLQ-BR23 domains will be presented at the meeting. Conclusions: Pts treated with C-F maintained HRQoL for longer than pts treated with P-F on all EORTC QLQ-C30 functional and symptom domain scores, except diarrhea. Worsening of diarrhea was observed with C-F, consistent with the safety profile of C, but events appeared tolerable and did not negatively impact GHS/HRQoL. Together with the clinical efficacy and manageable safety profile of C-F, the PRO results from the CAPItello-291 trial further support a positive benefit–risk profile of the combination in this population. https://clinicaltrials.gov/: NCT04305496. Funding: CAPItello-291 is sponsored by AstraZeneca. Editorial acknowledgment: AstraZeneca-funded medical writing support was provided by Suzanne Patel, Ph.D., from BOLDSCIENCE Inc. Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited). Citation Format: Hope Rugo, Mafalda Oliveira, Sacha Howell, Florence Dalenc, Javier Cortés, Henry Gómez, Xichun Hu, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Yeon Park, Joo Hyuk Sohn, Eriko Tokunaga, Masakazu Toi, Samih Yousef, Lyudmila Zhukova, Marta Fulford, Haylee Andrews, Ian Wadsworth, Celina D’Cruz, Nicholas Turner. Patient-reported outcomes from the Phase 3 CAPItello-291 trial investigating capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR-positive/HER2-negative advanced breast cancer [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 PS02-02.

Special issue PRO] A demonstration of estimands and sensitivity analyses for time-to-deterioration of patient reported outcomes

ABSTRACT In oncology trials, health-related quality of life (HRQoL), specifically patient-reported symptom burden and functional status, can support the interpretation of survival endpoints, such as progression-free survival. However, applying time-to-event endpoints to patient-reported outcomes (PRO) data is challenging. For example, in time-to-deterioration analyses clinical events such as disease progression are common in many settings and are often handled through censoring the patient at the time of occurrence; however, disease progression and HRQoL are often related leading to informative censoring. Special consideration to the definition of events and intercurrent events (ICEs) is necessary. In this work, we demonstrate time-to-deterioration of PRO estimands and sensitivity analyses to answer research questions using composite, hypothetical, and treatment policy strategies applied to a single endpoint of disease-related symptoms. Multiple imputation methods under both the missing-at-random and missing-not-at-random assumptions are used as sensitivity analyses of primary estimands. Hazard ratios ranged from 0.52 to 0.66 over all the estimands and sensitivity analyses modeling a robust treatment effect favoring the treatment in time to disease symptom deterioration or death. Differences in the estimands include how people who experience disease progression or discontinue the randomized treatment due to AEs are accounted for in the analysis. We use the estimand framework to define interpretable and principled approaches for different time-to-deterioration research questions and provide practical recommendations. Reporting the proportions of patient events and patient censoring by reason helps understand the mechanisms that drive the results, allowing for optimal interpretation.

Prevalence and Predictors of Follow-up Endoscopic Biopsy in Patients With Celiac Disease in the United States.

To characterize the frequency and predictors of follow-up endoscopic biopsy in patients with celiac disease. The utility of routine follow-up biopsy in patients after a diagnosis of celiac disease is uncertain, especially in patients whose symptoms resolve on the gluten-free diet. Using the Merative MarketScan U.S. commercial insurance and Medicare databases, we identified 30,737 patients with biopsy-diagnosed celiac disease. We followed them until they had a second duodenal biopsy (our primary outcome) or insurance coverage ended. Among the patients with celiac disease we identified, 5976 (19.4%) underwent a follow-up biopsy. The median time between initial and follow-up biopsies was 16.8 months. Compared with younger patients, those aged 20 years or older had an increased likelihood of undergoing a follow-up biopsy (cumulative incidence rate at 5y for patients age ≥20y was 36.0%, 95% CI: 35.0%-37.1% vs 21.9%, 95% CI: 20.5%-23.4% in patients age ≤19y). Follow-up biopsies occurred less frequently in more recent calendar years. Follow-up biopsy was more common among patients with an Elixhauser Comorbidity Index of 1 (hazard ratio: 1.09; 95% CI: 1.01-1.17) or ≥2 (hazard ratio: 1.28; 95% CI: 1.20-1.37) compared with patients with an index of zero. Among patients who had a follow-up biopsy, 57% had a celiac disease-related symptom recorded in the 30 days before the procedure. Follow-up duodenal biopsy is performed in a substantial minority of U.S. patients with celiac disease. Adult age and increased comorbidity burden were associated with a greater likelihood of follow-up biopsy. Just under half of follow-up biopsies are performed for routine surveillance, in the absence of persistent symptoms.

Sex differences in Parkinson’s disease-related non motor symptoms: a focus on sleep problems

Parkinson’s disease (PD) symptomatology differs between females and males, yet the contribution of sex on sleep problems needs further analysis. Here, we aimed to investigate sex-specific patterns in the relationship between sleep problems, assessed using the Parkinson’s disease sleep scale (PDSS-2), non motor symptoms (NMS), measured by the NMS scale (NMSS), and health-related quality of life (HR-QoL), evaluated by the Parkinson’s disease questionnaire (PDQ-39), in a large cohort of PD patients. One-hundred-fifty-four PD patients were included in the study. Female PD patients (n = 62) exhibited a higher prevalence of sleep problems than males (n = 92), with nocturnal motor-related sleep issues being the most frequent. Sleep disturbances differently correlated with a range of NMS between the two sexes. In females, sleep problems mostly correlated with pain; on the other hand, sleep disturbances were linked to a frailer phenotype characterized by global dysautonomia, perception disturbances, and impaired cognitive function in males. Whether female PD patients experienced a lower HR-QoL than males, sleep disturbances were associated with a worse HR-QoL in both sexes. In conclusion, sleep problems in PD differently burden the two sexes, suggesting possible different etiopathogenesis, diagnostic investigations, and possibly tailored approaches.

Association between Sense of Coherence, Disease-Specific Symptoms, and Health-Related Quality of Life among Japanese Patients with Ulcerative Colitis: A Cross-Sectional Study

Introduction: We examined the associations among disease-related symptoms, health-related quality of life (HRQOL), and sense of coherence (SOC) in Japanese patients with ulcerative colitis (UC). Methods: This cross-sectional survey involved patients and physicians at 23 hospitals specializing in UC treatment in Japan (December 2019–December 2020). Multiple linear regression analysis was performed using scores on the Mental Health and General Health subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey as outcomes and SOC as the main independent variable. Scores on the Inflammatory Bowel Disease Questionnaire (IBDQ) and Fecal Incontinence Quality of Life Scale (FIQL) were used to measure the effect of disease-related symptoms. The moderating effect of symptoms on the association between HRQOL and SOC was also tested. Results: SOC was positively and independently associated with HRQOL (Mental Health: β = 0.43, 95% confidence interval [CI] = 0.24–0.61, p < 0.001; General Health: β = 0.41, 95% CI = 0.23–0.59, p < 0.001). The association of SOC with Mental Health scores did not differ by symptoms, whereas its association with General Health was attenuated by symptoms (interaction term of IBDQ by SOC: β = −0.0082, 95% CI = −0.017 to 0.00064, p = 0.07; that of FIQL by SOC: β = −0.0052, 95% CI = −0.011 to 0.0010, p = 0.10). Conclusions: SOC affected mental health independently, and its protective association with general health perception was affected by symptoms. Further research is required to determine the most effective use of SOC in interventions to improve HRQOL in patients with UC.

The Beneficial Impact of Pulmonary Rehabilitation in Idiopathic Pulmonary Fibrosis: A Review of the Current Literature.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible fibrotic disease whose natural history is characterised by a progressive worsening of the pulmonary function, exertional dyspnoea, exercise intolerance, reduced physical activity, and health-related quality of life (HRQOL) impairment. Pulmonary rehabilitation (PR) is a comprehensive, multi-disciplinary programme that uses a combination of strength training, teaching, counselling, and behaviour modification techniques to reduce symptoms and optimise functional capacity in patients with chronic lung disease. Based on the well-documented effectiveness of PR in chronic obstructive pulmonary disease (COPD), over the years supportive evidence of its benefits for other respiratory diseases has been emerging. Although the latest rehabilitation guidelines recognised PR's efficacy for interstitial lung disease (ILD) and IPF in particular, this comprehensive approach remains underused and under-resourced. In this review, we will discuss the advantages and beneficial effects of PR on IPF, analysing its impact on exercise capacity, disease-related symptoms, cardiovascular outcomes, body composition, and HRQOL.

Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study

BackgroundPhysical active lifestyles are essential throughout growth and maturation and may offer potential preventive and therapeutic benefit in patients with juvenile idiopathic arthritis (JIA). Insufficient physical activity (PA), in contrast, can lead to aggravation of disease-related symptoms. This study aimed to i) examine PA levels in children and adolescents with JIA compared to general population controls and ii) investigate correlates of pronounced physical inactivity in order to identify risk groups for sedentary behaviour.MethodsData from children and adolescents with JIA and population controls aged 3 to 17 years documented in the National Pediatric Rheumatologic Database (NPRD) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were used. Self-reported PA was collected from parents/guardians of children up to 11 years of age or adolescents 12 years of age and older. To compare PA-related data, age- and sex-specific pairwise analyses were conducted considering NPRD/KiGGS participants' data from 2017. Correlates of physical inactivity among patients were identified using a linear regression model.ResultsData of 6,297 matched-pairs (mean age 11.2 ± 4.2 years, female 67%, patients’ disease duration 4.5 ± 3.7 years, persistent oligoarthritis 43%) were available for evaluation. Almost 36% of patients aged 3–17 years (vs. 20% of controls) achieved the WHO recommended amount of PA, while PA steadily decreased with age (18% of patients aged ≥ 12 years) and varied between JIA categories. Female adolescents and patients with enthesitis-related arthritis were least likely to achieve the minimum recommended level of PA. Physical inactivity was associated with female sex, higher age at disease onset, longer disease duration, more functional disability (C-HAQ) and higher disease activity (cJADAS-10).ConclusionsDepending on JIA category, children and adolescents with JIA were similarly or even more likely to achieve the WHO recommended minimum level of PA compared to general population controls. However, since a large proportion of young JIA patients appear to be insufficiently physically active, engagement in targeted efforts to promote PA is urgently needed.

Identifying antinuclear antibody positive individuals at risk for developing systemic autoimmune disease: development and validation of a real-time risk model.

Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas forclinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. Wedeveloped and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals. Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples. We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set. We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals.

Fear of disease in patients with epilepsy - a network analysis.

Disease-related fear among patients with epilepsy has significantly impacted their quality of life. The Disease-Related Fear Scale (D-RFS), comprising three dimensions, serves as a relatively well-established tool for assessing fear in these patients. However, certain problems potentially exist within the D-RFS's attribution of items, and its internal structure is still unclear. To establish an appropriate dimensional structure and gain deeper comprehension of its internal structure-particularly its core variables-is vital for developing more effective interventions aimed at alleviating disease-related fear among patients with epilepsy. This study employed a cross-sectional survey involving 609 patients with epilepsy. All participants underwent assessment using the Chinese version of the D-RFS. We used exploratory network analysis to discover a new structure and network analysis to investigate the interrelationships among fear symptom domains. In addition to the regularized partial correlation network, we also estimated the node and bridge centrality index to identify the importance of each item within the network. Finally, it was applied to analyze the differences in network analysis outcomes among epilepsy patients with different seizure frequencies. The research findings indicate that nodes within the network of disease-related fear symptoms are interconnected, and there are no isolated nodes. Nodes within groups 3 and 4 present the strongest centrality. Additionally, a tight interconnection exists among fear symptoms within each group. Moreover, the frequency of epileptic episodes does not significantly impact the network structure. In this study, a new 5-dimension structure was constructed for D-RFS, and the fear of disease in patients with epilepsy has been conceptualized through a network perspective. The goal is to identify potential targets for relevant interventions and gain insights for future research.

Brazilin-7-2-butenoate inhibits amyloid β-protein aggregation, alleviates cytotoxicity, and protects Caenorhabditis elegans

The fibrillogenesis of amyloid β-protein (Aβ) gradually accumulates to form neurotoxic Aβ aggregates in the human brain, which is the direct cause of Alzheimer's disease (AD) related symptoms. There are currently no effective therapies for AD. Brazilin, a natural polyphenol, inhibits Aβ fibrillogenesis, disrupts the mature fibrils and alleviates the corresponding cytotoxicity, but it also has the high toxic. Therefore, brazilin-7-2-butenoate (B-7-2-B), a brazilin derivative, was designed and synthesized. B-7-2-B exhibited lower toxicity and stronger inhibitory effect on Aβ aggregation than brazilin. B-7-2-B could prevent the formation of Aβ fibrils and oligomers, and depolymerize pre-formed aggregates in a dose-dependent manner. Furthermore, B-7-2-B prominently alleviated the cytotoxicity and the oxidative stress induced by Aβ aggregates in PC12 cells. The protective impacts of B-7-2-B were further demonstrated by using the Caenorhabditis elegans model, including decreasing the extent of Aβ aggregation, improving the motility and sensation disorders. Eventually, B-7-2-B was proven to be no apparent damage to worms. In summarize, it can be concluded that B-7-2-B has the potential as a drug for treating AD.

ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options

Interferon-based therapies, such as ropeginterferon alfa-2b have emerged as promising disease-modifying agents for myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). Current ET treatments aim to normalize hematological parameters and reduce the thrombotic risk, but they do not modify the natural history of the disease and hence, have no impact on disease progression. Ropeginterferon alfa-2b (trade name BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval, has demonstrated a robust and sustained efficacy in polycythemia vera (PV) patients. Given the similarities in disease pathophysiology and treatment goals, ropeginterferon alfa-2b holds promise as a treatment option for ET. The ROP-ET trial is a prospective, multicenter, single-arm phase III study that includes patients with ET who are intolerant or resistant to, and/or are ineligible for current therapies, such as hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman, leaving these patients with limited treatment options. The primary endpoint is a composite response of hematologic parameters and disease-related symptoms, according to modified European LeukemiaNet (ELN) criteria. Secondary endpoints include improvements in symptoms and quality of life, molecular response and the safety profile of ropeginterferon alfa-2b. Over a 3-year period the trial assesses longer term outcomes, particularly the effects on allele burden and clinical outcomes, such as disease-related symptoms, vascular events and disease progression. No prospective clinical trial data exist for ropeginterferon alfa-2b in the planned ET study population and this study will provide new findings that may contribute to advancing the treatment landscape for ET patients with limited alternatives.Trial registrationEU Clinical Trials Register; EudraCT, 2023-505160-12-00; Registered on October 30, 2023.

Investigation of Serum Albumin as a Dynamic Treatment-Specific Surrogate for Outcomes in Patients With Myelofibrosis Treated With Ruxolitinib.

Ruxolitinib improves splenomegaly and disease-related symptoms in most patients with myelofibrosis (MF), and it has been associated with a survival benefit in higher-risk patients with splenomegaly. Spleen volume reduction has been associated with a survival benefit in ruxolitinib-treated patients; however, its use as a surrogate is limited. We hypothesized that an anti-inflammatory response to ruxolitinib would correlate with improved patient outcomes. We interrogated serum albumin, an acute phase reactant and marker of nutritional status in 590 patients with MF and analyzed differential trajectories of albumin on the basis of ruxolitinib treatment. Additionally, we assessed the prognostic role of baseline albumin and change in albumin. We found that serum albumin levels tend to decrease in patients with MF; however, this tendency is abrogated by ruxolitinib treatment. To that end, baseline serum albumin level correlates with overall survival (OS) in patients with MF, independent of the variables that comprise the dynamic international prognostic scoring system; however, this correlation is limited to ruxolitinib-naïve patients. In ruxolitinib-treated patients, the change in serum albumin after ruxolitinib treatment, rather than the baseline value, is associated with improved OS, a finding not seen in ruxolitinib-naïve patients. These findings suggest that serum albumin, a ubiquitously available laboratory value, has specific relevance in patients with MF and reflects therapeutic response to ruxolitinib.

Sleep Patterns, Pain, and Emotional Functioning in Youth with Inflammatory Bowel Disease.

Youth with inflammatory bowel disease (IBD) may be at increased risk for sleep difficulties due to the painful and inflammatory nature of their disease. Moreover, children and adolescents with IBD experience impairment across a variety of psychosocial domains. However, researchers have yet to investigate the complex interplay between sleep, disease-related symptoms, and psychosocial factors in this population. The purpose of this study was to examine sleep patterns, pain, and mood in pediatric IBD. A sample of 25 children and adolescents with IBD (Mage = 14.24, Range = 10-18 years; 56% male) were recruited from a pediatric gastroenterology clinic. Youth wore an actigraphy watch and completed daily measures of affect and pain over the course of 14 days. Statistical analyses involved repeated measures general estimating equations. No significant association for sleep with negative affect was demonstrated. Despite majority of this sample being in disease remission, results revealed that increased sleep onset latency was associated with presence of next day pain and pain was associated with better next night sleep efficiency. Findings of the current study suggest youth with IBD experience poor sleep quality, which is significantly related to the pain they experience. Consequently, healthcare providers should screen for and address sleep quality to optimize outcomes in their pediatric patients. Objectively assessing sleep patterns (e.g., actigraphy) may prove useful for pediatric IBD samples; however, additional research is needed to determine actigraphy's feasibility and efficacy in assessing sleep patterns in real world settings (e.g., pediatric medical clinics).

Factors influencing health-related quality of life in women with endometriosis: A cross-sectional study.

This study aimed to assess the health-related quality of life and identify its associated factors in women with endometriosis. A cross-sectional correlation study design and convenience sampling were conducted in the gynecological outpatient clinic of a teaching hospital in northern Taiwan. A total of 216 women with endometriosis were recruited. The data were collected using structured questionnaires and analyzed using descriptive and inferential statistics. Participants reported a moderate level of health-related quality of life. The most significant impact of endometriosis on health-related quality of life was emotional well-being, followed by feeling of control or powerless, pain, social support, and self-image. Educational attainment, menstrual cycle, period length, perceived menstrual flow, symptom distress, and self-management strategies explained 66% of the variance in health-related quality of life. Factors influencing health-related quality of life in women with endometriosis play a key role in promoting women's well-being. Interventions based on these related factors should be developed and taken into practice to effectively manage the disease-related symptoms for women with endometriosis and thereby improve their overall health-related quality of life.

Cross-cultural validation of the Portuguese version of the Dialysis Symptom Index for haemodialysis patients.

Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) are associated with low quality of life (QoL) and high disease-related symptoms. The patient self-report instruments can assess the burden of physical and psychological symptoms. The Dialysis Symptom Index (DSI) is a specific instrument to evaluate the multidimensional reported symptoms by patients undergoing HD. To translate, validate and assess the psychometric properties of the Portuguese version of the DSI. A cross-cultural adaptation process from English to Portuguese and a validation study (n = 156) were conducted. Reliability, validity and responsiveness were assessed. The patients' most reported symptoms were, nausea (n = 86, 55%), muscle cramps (n = 92, 59%), feeling tired or lack of energy (n = 92, 59%), bone or joint pain (n = 88, 56%) and trouble staying asleep (n = 95, 60%). Cronbach's alpha of the DSI was 0.87, and intraclass correlation coefficient was 0.868 (95%CI 0.836-0.896). The smallest detectable change was 28.32. The Portuguese DSI demonstrates excellent psychometric properties for assessing HD patients' reported symptoms. It highlights symptom severity and impact, providing valuable insights for healthcare practitioners. Nurses can use the DSI to tailor interventions and enhance patient-centred care.