Patient interpretations of patient-reported outcome measures to assess bowel urgency: qualitative interviews in ulcerative colitis.

OBJECTIVES: Bowel urgency is an impactful core symptom of ulcerative colitis (UC). Patient-reported outcome (PRO) questionnaires have been developed and used to assess the patient experience of this important symptom. The objective of this paper is to present evidence from qualitative research conducted to support the use and interpretation of select PRO questionnaires to assess bowel urgency related to the UC patient experience. METHODS: Qualitative interviews were conducted with ten adults with a clinician-confirmed diagnosis of moderately to severely active UC. Interviews aimed to document patient interpretation of modified recall periods for the Urgency Numeric Rating Scale (Urgency NRS), two global assessments (i.e., the Patient Global Impression of Severity [PGIS] and Patient Global Impression of Change [PGIC]), and four items (Items 11, 16, 23, and 26) of the Inflammatory Bowel Disease Questionnaire (IBDQ), and explore the patient perspective of meaningful change on these questionnaires. RESULTS: Both modified Urgency NRS versions (with 7-day or 3-day recall period) were interpreted as intended by most patients (≥ 88.9%), and slightly more than half of patients (60.0%) reported that the 7-day recall period was more relevant to their bowel urgency experience. Patients reported thinking of bowel urgency (≥ 80.0%) or bowel urgency-related accidents (70.0% of patients) when interpreting the global assessments and IBDQ items. Most patients reported a 1- to 3-point change as the smallest meaningful improvement that would be meaningful on the Urgency NRS (similar to findings on other questionnaires). CONCLUSION: Adults with UC can understand and respond to the Urgency NRS with modified recall periods (i.e., 7-day or 3-day), interpret the conceptual content of the PGIS, PGIC, and select IBDQ items to be inclusive of bowel urgency and bowel urgency-related accidents, and select answers representing meaningful improvements on the Urgency NRS, PGIS, PGIC, and IBDQ item response scales. These results further contribute patient-centered data to existing UC and bowel urgency research.

Patient Perspectives of Bowel Urgency and Bowel Urgency-Related Accidents in Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Bowel urgency is bothersome in patients with ulcerative colitis (UC) or Crohn's disease (CD) and impacts their well-being but remains underappreciated in clinical trials and during patient-healthcare provider interactions. This study explored the experiences of bowel urgency and bowel urgency-related accidents to identify the concepts most relevant and important to patients. METHODS: Adults with a diagnosis of moderate-to-severe UC or CD for ≥6 months and experience of bowel urgency in the past 6 months were included. Qualitative, semi-structured interviews were conducted via telephonic/Web-enabled teleconference. Interview transcripts were coded and analyzed in ATLAS.ti 9 using a systematic thematic analysis. RESULTS: In total, 30 participants with UC or CD (n = 15 each) (mean age 52 and 50 years, respectively) participated in the interviews. The majority of participants were receiving biologic and/or conventional therapy (80% and 87%, respectively). Most participants with UC (87%) and all with CD experienced bowel urgency-related accidents. The most frequently reported symptoms co-occurring with bowel urgency were abdominal pain, fatigue, and abdominal cramping. Abdominal pain and abdominal cramping were the most bothersome co-occurring symptoms of bowel urgency and bowel urgency-related accidents. In both groups, participants reported decreased frequency of bowel urgency and not wanting to experience bowel urgency-related accidents at all as a meaningful improvement. CONCLUSIONS: Participants with UC or CD expressed bowel urgency and bowel urgency-related accidents to be bothersome and impactful on their daily lives despite use of biologic and/or conventional therapy. These findings underscore the need for development of patient-reported outcome measures to assess bowel urgency in clinical settings.

Bowel urgency and bowel urgency-related accidents are accompanied by several bothersome symptoms and considerably impact patients' quality of life, highlighting the need to develop a patient-reported outcome measure for assessing and addressing bowel urgency in clinical settings.

Interleukin-1 Trap Rilonacept Improved Health-Related Quality of Life and Sleep in Patients With Recurrent Pericarditis: Results From the Phase 3 Clinical Trial RHAPSODY.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health-related quality of life. RHAPSODY (rilonacept inhibition of interleukin-1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL-1α and -ß cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient-reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient-reported outcome (PRO) questionnaires assessing pericarditis pain, health-related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run-in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run-in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run-in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health-related quality of life. All PRO scores significantly improved (P<0.001) on rilonacept treatment during the run-in period. For the randomized withdrawal period, PRO scores were maintained for participants receiving rilonacept. For those receiving placebo and who experienced a recurrence, PRO scores deteriorated at the time of recurrence and then improved following rilonacept bailout. At randomized withdrawal Week 24/End of Study, scores of participants who received bailout rilonacept were similar to those of participants who had continued rilonacept. Conclusions These results demonstrate the burden of pericarditis recurrences and the improved physical and emotional health of patients with recurrent pericarditis while on rilonacept treatment. These findings extend prior rilonacept efficacy results, demonstrating improvements in patient-reported health-related quality of life, sleep, pain, and global symptom severity while on treatment. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

A Systematic Review of Conversion to Resectability in Unresectable Metastatic Colorectal Cancer Chemotherapy Trials.

OBJECTIVES: Metastasectomy in patients with metastatic colorectal cancer (mCRC) confers a significant survival benefit. We hypothesized that conversion to resectability (C2R) correlates with superior overall survival (OS) in patients with unresectable mCRC. METHODS: A prospectively registered systematic review (PROSPERO CRD42015024104) of randomized clinical trials published after 2003 was conducted. Exposure of interest was C2R with a primary outcome of OS. Clinical trials were classified based on difference in C2R between study arms (<2%, 2% to 2.9%, ≥3%). Generalized estimating equations were used to measure associations while adjusting for multiple observations from the same trial. RESULTS: Of 2902 studies reviewed, 30 satisfied selection criteria (n=13,618 patients). Median C2R was 7.3% (interquartile range [IQR]: 5% to 12.9%), with maximum C2R in the FOLFOX/FOLFIRI+cetuximab arm (28.6%). The median difference in C2R between 2 arms of the same study was 2.3% (IQR: 1.3% to 3.4%) with a maximum difference of 15.4% seen in FOLFOX/FOLFIRI+cetuximab versus FOLFOX/FOLFIRI. Median OS for the entire patient cohort was 20.7 months (IQR: 18.9 to 22.7 mo), with a between group difference of 1.3 months (IQR: -1.2 to 3.6 mo). The median survival difference between the 2 study arms with <2% C2R difference was 0.8 months versus 1.6 months with ≥3% C2R rates . Increasing C2R had an incremental dose-effect response on OS ( P =0.021), and higher response rates correlated with C2R rates ( P =0.003). CONCLUSIONS: C2R occurs infrequently and variably in clinical trials enrolling patients with unresectable mCRC. Prioritization of chemotherapeutic agents that enhance C2R might improve OS of patients.

Developmental potential of immature human oocytes aspirated after controlled ovarian stimulation.

PURPOSE: Intracytoplasmic sperm injection (ICSI) for initially immature oocytes that mature in vitro is controversial and practice varies widely. While it may increase the number of usable embryos, it may also be time-intensive and potentially low-yield. This study sought to elucidate which patients may benefit from ICSI of initially immature oocytes that matured in vitro. METHODS: A retrospective study comparing fertilization, cleavage, blastulation, and embryo usage rates between sibling initially immature and mature oocytes that underwent ICSI between 2015 and 2019 was performed. Outcomes of initially immature oocytes were stratified by initial maturation stage, timing of progression to metaphase II (MII) in vitro, percentage of mature oocytes in the cycle, and female age. RESULTS: Ten thousand eight hundred seventeen oocytes from 889 cycles were included. Of 3137 (29.0%) initially immature oocytes, 418 (13.3%) reached MII later on the day of retrieval (day 0) and 1493 (47.6%) on day 1. Overall, embryos originating from initially immature oocytes had lower cleavage and blastulation rates compared to those from initially mature oocytes (P<0.05, all groups). However, embryos from oocytes that matured later on day 0 comprised a unique subset that had clinically similar cleavage (75% vs 80%, RR 0.93, P=0.047) and blastulation rates (41% vs 50%, RR 0.81, P=0.024) compared to initially mature oocytes. Women with low percentages of mature oocytes in the cycle overall and women ≥40 in cleavage cycles derived the highest relative benefit from the use of immature oocytes. CONCLUSION: ICSI of immature oocytes, particularly those that mature later on the day of retrieval, may improve numbers of usable embryos. This study supports routine reassessment of immature oocytes for progression to MII and ICSI on day 0. An additional reassessment on day 1 may also be of use in older women or those with low percentage of mature oocytes.

Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept.

BACKGROUND: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1ß cytokine trap) to treat RP. METHODS: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n = 16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n = 9). All participants received rilonacept weekly during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept. RESULTS: Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline (mean PROMIS Global Physical Health [GPH] and Global Mental Health [GMH], were lower than population norm average). In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved during EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP). CONCLUSION: This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to CS. TRIAL REGISTRATION: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522 .

Content validity of the National Comprehensive Cancer Network - Functional Assessment of Cancer Therapy - Breast Cancer Symptom Index (NFBSI-16) and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form with advanced breast cancer patients.

BACKGROUND: The purpose of this study is to evaluate the content validity of the National Comprehensive Cancer Network - Functional Assessment of Cancer Therapy - Breast Cancer Symptom Index (NFBSI-16) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b among patients with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. METHODS: Cognitive debriefing interviews sought to evaluate patients' ability to read, understand, and meaningfully respond to the questionnaires, as well as to evaluate the questionnaires' relevance in the target patient population. Interviews were conducted by telephone and lasted approximately 90 min. Audio recordings were transcribed, anonymized, and analyzed using qualitative data analysis software. RESULTS: Fifteen cognitive debriefing interviews were conducted with women (mean age 66.0 years [standard deviation = 12.4]). Patients reported metastases in the bone (86.7%), liver (20.0%), lung (13.3%), skin (6.7%), and lymph node (6.7%) (not mutually exclusive). All patients for whom data were available demonstrated understanding of the instructions and the recall period of the NFBSI-16 (n = 14/14, 100.0%) and the PROMIS (n = 14/14, 100.0%). Greater than 90% of patients demonstrated understanding of each of the items in the NFBSI-16 and the PROMIS. Greater than 70% of patients demonstrated understanding of the response options of the NFBSI-16, > 90% understood response options of PROMIS Items 1-6, and ≥ 50% understood response options of PROMIS Items 7-10. Conceptual relevance was supported for most items in both questionnaires based on patients' reports of experiencing the concepts as part of their breast cancer experience. CONCLUSIONS: The results of the cognitive debriefing interviews provide evidence that the NFBSI-16 and PROMIS Physical Function Short Form 10b have content validity in the HR+/HER2- advanced breast cancer patient population. Patients may benefit from additional instructions at the point the response options reverse direction in the PROMIS.

Understanding key symptoms, side effects, and impacts of HR+/HER2- advanced breast cancer: qualitative study findings.

BACKGROUND: Patients with breast cancer experience a variety of disease symptoms and treatment-related side effects that can adversely affect functioning. The breast cancer experience may differ across disease stages and biomarker subtypes. This study identified relevant disease symptoms, treatment-related side effects, and physical functioning impacts in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. METHODS: One-on-one concept elicitation interviews were conducted with 15 patients with HR+/HER2- advanced breast cancer. Open-ended questions about patient experience with breast cancer and its treatment were drawn from a semi-structured interview guide. All interviews were audio-recorded and transcribed verbatim, and codes were used to document and organize patient descriptions of their experiences. Coded concepts were defined, supported by exemplary patient quotes, and analyzed for frequency of mention and saturation. Five interviews with experienced oncologists were conducted to supplement the concept elicitation interviews. RESULTS: The average age of the patients was 66 years. Most (53%) self-identified as White/Caucasian; 40%, as Black/African American. Patients were reported to have metastases to bone (87%), liver (20%), lung (13%), skin (7%), and lymph nodes (7%). The most frequently reported disease-related concepts were fatigue and lump in breast (47% each) and pain (40%), while the most frequently reported treatment-related side effects were hair loss (67%), fatigue/tiredness (47%), and nausea (40%). Patients identified 10 concepts associated with both breast cancer and its treatment, including fatigue/tiredness, shortness of breath, weakness, and nausea. The most frequently reported impacts on physical function included working around home (73%), walking (73%), and cooking (53%). The most frequently reported symptoms and side effects from the expert perspective included fatigue, pain, and hot flashes (n = 5 each, 100%), while the ability to work (n = 5, 100%) and walk (n = 3, 60%) were reported impacts, aligning with those concepts reported by patients. The resulting concepts were organized into a patient-based conceptual model. CONCLUSIONS: Patients have varied experiences due to HR+/HER2- advanced breast cancer and its treatment, and commonly experience fatigue/tiredness, hair loss, general pain, lump in breast, and nausea, as well as impacts to physical functioning (specifically, activities of daily living and mobility).

Elective Regional Therapy Treatment for Hepatic Adenoma.

BACKGROUND: Locoregional therapy treatments for hepatic adenoma (HA) are typically limited to selective hepatic arterial embolization (HAE) to control acute hemorrhage. This systematic review sought to report the utilization of HAE and ablation for non-emergent treatment of HA. METHODS: A PubMed query identified studies reporting ablation or embolization for HA patients. Abstracts were screened to exclude studies with only patients managed for acute hemorrhage. Outcomes of interest included rate of success, complications, and repeat procedures. RESULTS: Of 209 initial search results, 33 full-text publications were reviewed, and 10 were selected after applying the exclusion criteria. All were published from 2005 to 2016. A total of 105 patients were included, of which 66 patients with 138 adenomas underwent elective locoregional therapy treatment. The mean size of treated adenomas was 2.9 (range 0.8-8.3) cm. HAE was utilized in 25 patients with 58 adenomas, whereas 35 patients with 68 adenomas underwent radiofrequency ablation. Six patients with 12 adenomas received microwave ablation. Most patients were female (89/105), and adenomas were associated with oral contraceptive use or hormonal therapies in 49 of 105 patients. Success was reported in 115 of 138 first-time procedures, and repeat procedures were needed after 18 of 138. Mean follow-up time was 36.4 months, with two complications. CONCLUSIONS: Reports of elective locoregional therapy for the treatment of HA are limited to case reports and small institutional series. In the select patients treated, outcomes are acceptable, with low rates of repeat procedures or complications. This systematic review warrants further discussion and broader consideration for the treatment of HA.

Is long-term survival possible after margin-positive resection of retroperitoneal sarcoma (RPS)?

BACKGROUND/OBJECTIVES: For various reasons, some patients undergo a gross margin positive resection (R2) leading to a dilemma in care. We hypothesized that there is a subset of patients who have long-term survival (LTS, ≥5 years) after R2 resection for retroperitoneal sarcoma (RPS). METHODS: National Cancer Database data from 1998 to 2011 were reviewed to identify patients with RPS who had R2 resections. Logistic and Cox regression models were used to compare LTS with short-term survival. RESULTS: Of 12,028 patients, R2 resection rate was 3.28% (4.9% in 1998; 2.5% in 2011). Median survival for RPS with R2 resection was 21 months versus 69 months for those with R0/R1 resections (P < 0.001). Of 272 patients with available survival, 24% (n = 64) survived ≥5 years with 64% alive at follow-up. LTS was most often seen in younger patients (<65 years) with well-differentiated liposarcoma. Chemotherapy appeared to improve survival in the first 3 postoperative years, but paradoxical effects were seen in LTS (Hazards Ratio [HR] 0.69, 95%CI: 0.50-0.95, P = 0.024) in first 3 years versus (HR 2.15, 95%CI: 1.21-3.81, P = 0.009). CONCLUSION: Long-term survival is possible for a subset of patients after an R2 resection for RPS, especially with favorable histology characteristics. Benefits of chemotherapy in margin positive settings need to be investigated. J. Surg. Oncol. 2016;113:823-827. © 2016 Wiley Periodicals, Inc.

Impact of surgical volume of centers on post-operative outcomes from cytoreductive surgery and hyperthermic intra-peritoneal chemoperfusion.

Complex surgical operations performed at centers of high volume have improved outcomes due to improved surgical proficiency, and betters systems of care including avoidance of errors. Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemoperfusion (HIPEC), which has been shown to be an oncologically effective strategy for peritoneal carcinomatosis (PC), is one such procedure with significant morbidity and mortality. The learning curve to reach technical proficiency in CRS + HIPEC is about 140-220 cases for a center. Focus on improving surgical proficiency through training, improving systems of care through partnerships and reporting mechanisms for quality could reduce the time to proficiency.