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Tenosynovial giant cell tumor (TGCT), a rare locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, inflammation, pain, and swelling, in part due to colony-stimulating factor 1 receptor–bearing macrophages recruited to the tumor by genetic elevation of colony-stimulating factor 1 activity. The most common treatment is surgery, although promising pharmacologic treatments are in development. Patient-reported outcome (PRO) instruments are critical end points in demonstrating the clinical relevance of standard oncologic outcome measures and the overall impact of novel pharmacologic therapies in nonmalignant neoplastic conditions such as TGCT. The content validity of PROs relevant to patients with TGCT has not been formally investigated, and instruments to evaluate such outcomes do not exist for this condition. PRO instruments of potential relevance were evaluated by using a literature review and by clinical and PRO experts. Patients with TGCT were recruited through clinical sites and the Internet for participation in qualitative research interviews to identify predominant symptoms and to test the relevance and content validity of several PRO measures. Select PRO measures were included in a Phase I clinical trial, and preliminary results of the PRO end points are reported descriptively. Of the 22 subjects who participated in qualitative interviews, 73% were female, and their mean age was 42.5 years (range, 27–56 years). The TGCTs (19 diffuse and 3 localized) were located in the knee (n = 15), hip (n = 3), ankle (n = 2), elbow (n = 1), and forearm (n = 1). The most common symptoms cited were pain (82%), swelling (86%), stiffness (73%), reduced range of motion (64%), and joint instability (64%), which were consistent with clinical expert input and with the content of instruments chosen by PRO experts. The worst pain numeric rating scale, Patient Reported Outcomes Measurement Information System physical functioning items, and the Western Ontario and McMaster Universities Osteoarthritis Index, as well as a worst stiffness numeric rating scale developed for TGCT, were confirmed as meaningful measures of TGCT patient symptoms and were well understood in qualitative interviews. Results from the Phase I trial showed trends of improvement in both pain and stiffness over time. This study is the first to gather information directly from patients with TGCT regarding their symptom experiences. Pain, stiffness, and physical functioning are important treatment outcomes in patients with TGCT. We have identified content-valid PRO measures of these concepts, which are included in an ongoing Phase III TGCT clinical trial with pexidartinib (PLX3397) (NCT02371369).

Introduction: Responder endpoints are often used in clinical trial design to evaluate treatment efficacy, but positive responder-endpoint results are not necessarily associated with quality-of-life improvements. We evaluate the relationship between clinical responder endpoints and health-related quality of life (HRQOL) measures in patients with persistent gastroesophageal reflux disease (pGERD). Methods: Patients with pGERD - characterized by continued heartburn and regurgitation symptoms despite ongoing proton pump inhibitor (PPI) treatment-were enrolled in an 8-week, randomized, double-blinded, placebo-controlled phase 2b trial of IW-3718, an investigational gastric-retentive formulation of a bile acid sequestrant. Each patient completed a symptom assessment e-dairy (mRESQ-eD) daily, degree of relief assessments weekly, and the EQ-5D HRQOL at week 0 (baseline), 4, & 8. Heartburn and regurgitation responders were defined as having a >45% reduction in the mean daily heartburn severity or mean daily regurgitation frequency score, respectively, for >4 of 8 weeks, including >1 of the last 2 weeks. Degree of relief responders (heartburn, regurgitation, and overall GERD symptoms) were patients who reported significant or moderate relief for >4 of 8 weeks. Least-square mean changes from baseline to week 8 in EQ-5D were obtained for responders vs. non-responders using a mixed model for repeated measures (MMRM) with week (categorical), responder status, and week-by-responder status as fixed-effect terms and baseline EQ-5D as a covariate. Results: Patient demographics are shown in the Table. Responders showed better improvement in EQ-5D at week 8 compared with non-responders across all responder endpoints (p<0.05 for heartburn, regurgitation, and degree of GERD relief responder endpoints, Figure). Conclusion: Patients with persistent GERD symptoms who achieved clinical response also showed improvement in health-related quality of life as measured by the EQ-5D utility index; the heartburn, regurgitation, and GERD relief responders show significant improvement in EQ-5D results compared to non-responders. The clinical responder endpoints used in the IW-3718 phase 2b trial may yield results useful to payers as well as clinicians.

ObjectiveThere is an increase in patient-reported outcome assessments to gain information on new drug candidates from the patient’s perspective. A data gap remains in patient-reported outcome measurements for anti-programmed death 1 (anti-PD-1) therapies in endometrial cancer. We present patient-reported outcome measures collected from patients with mismatch repair-deficient/microsatellite instability-high advanced or recurrent endometrial cancer treated with dostarlimab, an anti-PD-1 monoclonal antibody, in an expansion cohort of the GARNET trial.MethodsGARNET (NCT02715284) is a phase I single-arm study of dostarlimab monotherapy in multiple tumor types. Patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer were treated with 500 mg of intravenous dostarlimab once every 3 weeks for four cycles, then 1000 mg of intravenous dostarlimab every 6 weeks. Patient-reported outcome assessments were an exploratory endpoint, measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30).ResultsAt data cut-off, 88 patients with mismatch repair-deficient endometrial cancer were included in the analysis. Patient-reported outcome assessment completion was >95.5% throughout cycle 7 of the trial, with no individual domain completion <90.9%. Quality of life, emotional functioning, and social functioning showed improvement compared with baseline. All symptom scores showed either improvement or stability from baseline through cycle 7. Categorical change in response across all symptom scales and single-item response scores showed stability or improvement for most patients. For patients who saw a worsening of their categorical change in response, ≤7.4% experienced a 2-category worsening and ≤2.5% experienced a 3-category worsening.ConclusionsMost patients remained stable or had improved quality of life while receiving dostarlimab for the treatment of recurrent or advanced mismatch repair-deficient endometrial cancer.Trial registration number NCT02715284.

Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS). Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week). Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was -1.9 vs -1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%). Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.

Introduction/BackgroundPatient preference on treatment options following frontline platinum-based chemotherapy for epithelial ovarian cancer (EOC) remains unstudied. Multiple treatment options are available, including PARP inhibitors, so understanding patient preference is critical.MethodologyA cross-sectional survey was completed by US patients with newly-diagnosed EOC eligible for frontline maintenance therapy. Maintenance preference was assessed via time trade-off simulation. Patients selected their preferred post-chemotherapy treatment approach: surveillance, oral daily (QD), oral twice daily (BID), intravenous every 3 weeks (IV-Q3W), or combination IV-Q3W/BID, assuming equivalent efficacy (for all scenarios) and safety (medication scenarios only). Patients were asked to select between a series of maintenance scenarios comparing decreased time to progression (TTP) on their preferred option with constant TTP with alternative options. Relative disutility of each scenario was calculated.Abstract 2022-RA-949-ESGO Table 1Patient (N=153) preferences for formulation and dosing frequency of frontline maintenance for EOCResults153 patients completed the survey, median age was 52.3 years; 30% were non-White, and 83% had health insurance covering full EOC treatment. Of all medication strategies, QD treatment was preferred (38%, table 1); patients were willing to trade the least amount of time (2.3 months) without progression on this scenario versus other choices. For patients who preferred to take a medication even when surveillance offered the same amount of time without progression (n=86), the most common reason was a feeling of taking an active approach to treatment (66%), having a reason to regularly visit a doctor/hospital (30%), being cared for/monitored more regularly and carefully (28%), and because taking medication is reassuring (24%).ConclusionPatients preferred QD treatment more than other medication strategies for EOC maintenance following frontline platinum-based chemotherapy; patients who preferred medication felt they were taking an active approach to treatment. Patient preferences should be considered in treatment decisions and further studied.Previously submitted to the IGCS Global Meeting (29 Sept–1 Oct 2022; New York City, USA)Funding statementGSK (214511/NCT02655016).

INTRODUCTION:Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS).METHODS:Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week).RESULTS:Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was −1.9 vs −1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%).DISCUSSION:Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.

INTRODUCTION:GERD is a common disorder often treated with proton pump inhibitors (PPIs). However, many patients experience persistent GERD symptoms despite PPI treatment. The objective of this study was to estimate the prevalence of persistent GERD symptoms despite PPI treatment and to describe the characteristics of these patients in the US adult population.METHODS:The Acumen Health Research Institute survey is a cross-sectional health survey of US adults in which a subgroup of participants self-identified as having GERD (GERD patients). Participants aged ≥ 18 years were recruited in 2018 using sampling framework that ensured a composition representative of the US population. Patients were asked about their GERD history, treatments, and symptoms using the GERD Symptom Assessment Scale. Health-related quality of life (HRQoL) was assessed using the Veterans RAND 12-item (VR-12) physical component summary (PCS), mental component summary (MCS), and health utility (VR-6D). Work productivity and sleep disturbance due to GERD were also assessed. Persistent GERD was defined a priori as the presence of bothersome symptoms on at least 2 days in the preceding week despite taking PPIs for at least 25 days per month. Effectiveness of PPI treatment was rated as “a little” or “a lot.” GERD patients with and without persistent GERD symptoms were compared using descriptive statistics.RESULTS:Of 12,348 survey respondents, 1566 (12.7%) self-identified as GERD patients; 855 (54.6%) reported taking PPIs. Of those, 301 (35.2%) met the definition for persistent GERD. Patients with persistent GERD had decreased HRQoL (36.2 vs. 40.5 PCS, 41.6 vs. 45.7 MCS, and 0.60 vs. 0.66 VR-6D) and greater impairment in work productivity (3.2 vs. 2.1 work hours/week missed due to health) than those without. GERD patients with persistent GERD were more likely to take antacids (50.2%) and H2-receptor antagonists (17.9%) in addition to their PPI than those without (30.9% and 13.4%, respectively). GERD patients with persistent symptoms had more difficulty with sleep than those without. In the preceding week, 38.2% and 14.4%, respectively, reported difficulty falling asleep because of GERD symptoms on > 2 nights, and 29.3% and 10.6%, respectively, woke because of GERD symptoms on > 2 nights.CONCLUSION:Among GERD patients taking PPIs, more than one-third had persistent symptoms. Patients with persistent GERD symptoms had decreased HRQoL, greater impairment of work productivity, and greater sleep disturbance than those without.

Purpose Past traumatic experiences are common among older adults with substance use disorders. Services supporting this population must be sensitive and equipped to address possible past trauma and associated post-traumatic stress disorder (PTSD) amongst service users. This commentary aims to explore past traumatic experiences and associated PTSD among older adults with substance use disorders. The focus is on defining trauma and PTSD, discussing their manifestation in older populations and examining the links between trauma and substance use disorders within the older age group. Design/methodology/approach We drew insights from authors’ lived experiences and experiences in practice within services supporting older people with substance use problems and trauma and findings from the CO-ACT study, exploring alcohol and mental health problems in older adults. This commentary is supplemented with findings and guidance from relevant research and key bodies involved with older substance users. Findings The analysis highlights the importance of services supporting older substance users to be sensitive to past trauma and equipped to address PTSD. The authors focus on the relevance of trauma-informed care and access to trauma-specific interventions in addressing PTSD within this demographic. We shed light on the specific challenges faced by care services in the United Kingdom, while emphasising that the recommendations presented are pertinent to other care systems. Originality/value This commentary responds to calls by people with lived experience aiming to inform research on substance use and mental health in older adults. By raising awareness of trauma amongst older substance users, the authors aim to contribute to a more comprehensive understanding of their unique needs. This paper provides insights into the manifestation of trauma and PTSD in older populations and offers recommendations to enhance care services supporting this vulnerable demographic.

This study aimed to examine the validity of the modified Reflux Symptom Questionnaire-electronic Diary (mRESQ-eD) through patient input and psychometric testing of the questionnaire to support use in clinical trials in patients with persistent gastroesophageal reflux disease (GERD) and in accordance with Food and Drug Administration guidance on patient-reported outcome instruments. Cognitive interviews were conducted with patients (n = 30) to evaluate the interpretability and content validity of draft mRESQ-eD items. Patient data from a phase 2b clinical study (ClinicalTrials.gov identifier: NCT02637557) on persistent GERD served to aid in the construction of weekly scores for heartburn severity, regurgitation severity, and total GERD severity. These scores' psychometric properties were also evaluated. Minor modifications were made to the draft mRESQ-eD based on patient feedback to improve interpretability and clarity of the instrument. Psychometric analysis suggested that an 8-item version of the mRESQ-eD was best suited to the clinical data. The internal consistency was found to be high (Coefficient ω = 0.95). Retest reliability and convergent validity were strong for a heartburn weekly severity score, regurgitation weekly severity score, and total GERD severity score. The final 8-item mRESQ-eD is a reliable and valid instrument with good psychometric properties for use in clinical trials in patients with persistent GERD. The mRESQ-eD may be considered for inclusion in clinical trials for persistent GERD and potentially positioned, in consultation with Food and Drug Administration, as endpoints to characterize treatment benefit.