Cost-Effectiveness of eRAPID eHealth Intervention for Symptom Management During Chemotherapy.

PURPOSE: A randomized controlled trial of online symptom monitoring during chemotherapy with electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) system found improved symptom control and patient self-efficacy, without increasing hospital admissions and visits. The aim of this study was to evaluate the cost-effectiveness of the eRAPID eHealth intervention compared with usual care for patients receiving systemic treatment for colorectal, breast, or gynecologic cancers in the United Kingdom. METHODS: An embedded economic evaluation was conducted alongside the trial evaluating the effectiveness of eRAPID from health care provider and societal perspectives. Costs and quality-adjusted life-years (QALYs) of patients were compared over 18 weeks of the trial. Incremental cost-effectiveness ratios (ICERs) were estimated and compared with the National Institute for Health and Care Excellence cost-effectiveness threshold. Uncertainty around the ICER was explored using nonparametric bootstrapping and sensitivity analyses. Follow-up data were collected 12-months after random assignment for a subset of the study sample to conduct exploratory analysis of potential longer-term effects. RESULTS: Patients in the eRAPID group had the highest QALY gain and lowest costs over 18 weeks. Although differences were small and not statistically significant, eRAPID had a 55%-58% probability of being more cost-effective than usual care. Patient out-of-pocket costs were lower in the eRAPID group, indicating eRAPID may help patients access support needed within the National Health Service. Exploratory 12-months analysis showed small differences in costs and QALYs, with higher QALY gains in the eRAPID group but also higher costs. Exploratory subgroup analysis by disease status indicated that the eRAPID intervention was cost-effective for patients with early-stage cancers but not for patients with metastatic disease. CONCLUSION: Despite small differences in QALYs and costs, the analyses show potential cost-effectiveness of online symptom monitoring, when added to usual care, particularly during adjuvant systemic treatment for early-stage cancers.

Online Symptom Monitoring During Pelvic Radiation Therapy: Randomized Pilot Trial of the eRAPID Intervention.

PURPOSE: Radiation therapy (RT) and chemoRT for pelvic cancers increase survival but are associated with serious treatment-related symptoms. Electronic-patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is a secure online system for patients to self-report symptoms, generating immediate advice for hospital contact or self-management. This pilot study aimed to establish feasibility and acceptability of the system. METHODS AND MATERIALS: In a prospective 2-center randomized parallel-group pilot study, patients undergoing radical pelvic RT for prostate cancer (prostateRT) or chemoRT for lower gastrointestinal and gynecological cancers were randomized to usual care (UC) or eRAPID (weekly online symptom reporting for 12, 18, and 24 weeks). Primary outcomes were recruitment/attrition, study completion, and patient adherence. Secondary outcomes were effect on hospital services and performance of patient outcome measures. Missing data, floor/ceiling effects, and mean change scores were examined for Functional Assessment of Cancer Therapy (FACT-G), European Organisation for Research and Treatment of Cancer, Quality of Life (EORTC QLQ C-30), self-efficacy, and EuroQol (EQ5D). RESULTS: From 228 patients approached, 167 (73.2%) were consented and randomized (83, eRAPID; 84, UC; 87, prostateRT; 80, chemoRT); 150 of 167 completed 24 study weeks. Only 16 patients (9.6%) withdrew (10, eRAPID; 6, UC). In the eRAPID arm, completion rates were higher in patients treated with prostateRT compared with chemoRT (week 1, 93% vs 69%; week 2, 93% vs 68%; week 12, 69% vs 55%). Overall, over 50% of online reports triggered self-management advice for milder adverse events. Unscheduled hospital contact was low, with no difference between eRAPID and UC. Return rates for outcome measures were excellent in prostateRT (97%-91%; 6-24 weeks) but lower in chemoRT (95%-55%; 6-24 weeks). Missing data were low (1%-4.1%), ceiling effects were evident in EQ5D-5L, self-efficacy-scale, and FACT-Physical Wellbeing. At 6 weeks, the chemoRT-eRAPID group showed less deterioration in FACT-G, EORTC QLQ-C30, and EQ5D-Visual Analogue Scale than UC, after baseline adjustment. CONCLUSIONS: eRAPID was successfully added to UC at 2 cancer centers in different patient populations. Acceptability and feasibility were confirmed with excellent adherence by prostate patients, but lower by those undergoing chemoRT for gynecological cancers.

Effect of a Patient Decision Aid on Preferences for Colorectal Cancer Screening Among Older Adults: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Guidelines recommend individualized decision-making for colorectal cancer (CRC) screening among adults aged 76 to 84 years, a process that includes a consideration of health state and patient preference. Objective: To determine whether a targeted patient decision aid would align older adults' screening preference with their potential to benefit from CRC screening. Design, Setting, and Participants: This is a prespecified secondary analysis from a randomized clinical trial. Participants aged 70 to 84 years who were not up to date with screening and had an appointment within 6 weeks were purposively sampled by health state (poor, intermediate, or good) at 14 community-based primary care practices and block randomized to receive the intervention or control. Patients were recruited from March 1, 2012, to February 28, 2015, and these secondary analyses were performed from January 15 to March 1, 2022. Interventions: Patient decision aid targeted to age and sex. Main Outcomes and Measures: The primary outcome of this analysis was patient preference for CRC screening. The a priori hypothesis was that the decision aid (intervention) group would reduce the proportion preferring screening among those in poor and intermediate health compared with the control group. Results: Among the 424 participants, the mean (SD) age was 76.8 (4.2) years; 248 (58.5%) of participants were women; and 333 (78.5%) were White. The proportion preferring screening in the intervention group was less than in the control group for those in the intermediate health state (34 of 76 [44.7%] vs 40 of 73 [54.8%]; absolute difference, -10.1% [95% CI, -26.0% to 5.9%]) and in the poor health state (24 of 62 [38.7%] vs 33 of 61 [54.1%]; absolute difference, -15.4% [95% CI, -32.8% to 2.0%]). These differences were not statistically significant. The proportion of those in good health who preferred screening was similar between the intervention and control groups (44 of 74 [59.5%] for intervention vs 46 of 75 [61.3%] for control; absolute difference, -1.9% [95% CI, -17.6% to 13.8%]). Conclusions and Relevance: The findings of this secondary analysis of a clinical trial did not demonstrate statistically significant differences in patient preferences between the health groups. Additional studies that are appropriately powered are needed to determine the effect of the decision aid on the preferences of older patients for CRC screening by health state. Trial Registration: ClinicalTrials.gov Identifier: NCT01575990.

Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during allergic airway disease.

The NADPH oxidase DUOX1 contributes to epithelial production of alarmins, including interleukin (IL)-33, in response to injurious triggers such as airborne protease allergens, and mediates development of mucus metaplasia and airway remodeling in chronic allergic airways diseases. DUOX1 is also expressed in non-epithelial lung cell types, including macrophages that play an important role in airway remodeling during chronic lung disease. We therefore conditionally deleted DUOX1 in either lung epithelial or monocyte/macrophage lineages to address its cell-specific actions in innate airway responses to acute airway challenge with house dust mite (HDM) allergen, and in chronic HDM-driven allergic airway inflammation. As expected, acute responses to airway challenge with HDM, as well as type 2 inflammation and related features of airway remodeling during chronic HDM-induced allergic inflammation, were largely driven by DUOX1 with the respiratory epithelium. However, in the context of chronic HDM-driven inflammation, DUOX1 deletion in macrophages also significantly impaired type 2 cytokine production and indices of mucus metaplasia. Further studies revealed a contribution of macrophage-intrinsic DUOX1 in macrophage recruitment upon chronic HDM challenge, as well as features of macrophage activation that impact on type 2 inflammation and remodeling.

Vacuolar H+-ATPase and Na+/K+-ATPase energize Na+ uptake mechanisms in the nuchal organ of the hyperregulating freshwater crustacean Daphnia magna.

The nuchal organ of the embryos and neonates of the cladoceran, Daphnia magna, has been shown to be a site of Na+ influx and H+, NH4+ and Cl- efflux. This study combines the scanning ion-selective electrode technique with application of inhibitors of specific transporters to assess the mechanisms of Na+ transport across the nuchal organ. Na+ influx across the nuchal organ was inhibited both by inhibitors of the Na+/K+-ATPase (ouabain, bufalin) and by inhibitors of the vacuolar H+-ATPase (bafilomycin, N-ethylmaleimde, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, KM91104, S-nitrosoglutathione). Na+ influx was unaffected by the epithelial Na+ channel blocker benzamil, but was sensitive to ethylisopropyl amiloride and elevated external ammonium concentrations, consistent with roles for Na+/H+ and Na+/NH4+ exchangers in the apical membrane but not Na+ channels. Transport across the basolateral membrane into the haemolymph is proposed to involve the Na+/K+-ATPase and a thiazide-sensitive Na+/Cl- cotransporter.

Phase III Randomized Controlled Trial of eRAPID: eHealth Intervention During Chemotherapy.

PURPOSE: Electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is an online eHealth system for patients to self-report symptoms during cancer treatment. It provides automated severity-dependent patient advice guiding self-management or medical contact and displays the reports in electronic patient records. This trial evaluated the impact of eRAPID on symptom control, healthcare use, patient self-efficacy, and quality of life (QOL) in a patient population treated predominantly with curative intent. METHODS: Patients with colorectal, breast, or gynecological cancers commencing chemotherapy were randomly assigned to usual care (UC) or the addition of eRAPID (weekly online symptom reporting for 18 weeks). Primary outcome was symptom control (Functional Assessment of Cancer Therapy-General, Physical Well-Being subscale [FACT-PWB]) assessed at 6, 12, and 18 weeks. Secondary outcomes were processes of care (admissions or chemotherapy delivery), patient self-efficacy, and global quality of life (Functional Assessment of Cancer Therapy-General, EQ5D-VAS, and EORTC QLQ-C30 summary score). Multivariable mixed-effects repeated-measures models were used for analyses. Trial registration: ISRCTN88520246. RESULTS: Participants were 508 consenting patients (73.6% of 690 eligible) and 55 health professionals. eRAPID compared to UC showed improved physical well-being at 6 (P = .028) and 12 (P = .039) weeks and no difference at 18 weeks (primary end point) (P = .69). Fewer eRAPID patients (47%) had clinically meaningful physical well-being deterioration than UC (56%) at 12 weeks. Subgroup analysis found benefit in the nonmetastatic group at 6 weeks (P = .0426), but not in metastatic disease. There were no differences for admissions or chemotherapy delivery. At 18 weeks, patients using eRAPID reported better self-efficacy (P = .007) and better health on EQ5D-VAS (P = .009). Average patient compliance with weekly symptom reporting was 64.7%. Patient adherence was associated with clinician's data use and improved FACT-PWB at 12 weeks. CONCLUSION: Real-time monitoring with electronic patient-reported outcomes improved physical well-being (6 and 12 weeks) and self-efficacy (18 weeks) in a patient population predominantly treated with curative intent, without increasing hospital workload.

Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial.

BACKGROUND: We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial. METHODS: FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1-3, pN0-1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132. FINDINGS: Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were -0·3% (-1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and -0·7% (-1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1-5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy. INTERPRETATION: 26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Individualized Colorectal Cancer Screening Discussions Between Older Adults and Their Primary Care Providers: A Cross-Sectional Study.

Introduction. Discussions of colorectal cancer (CRC) screening with older adults should be individualized to maximize appropriate screening. Our aim was to describe CRC screening discussions and explore their associations with patient characteristics and screening intentions. Methods. Cross-sectional survey of 422 primary care patients aged ≥70 years and eligible for CRC screening, including open-ended questions about CRC screening discussions. Primary outcomes were the frequency with which CRC screening discussions occurred, who had those discussions, and the domains that emerged from thematic analysis of participants' brief reports of their discussions. We also examined the associations between 1) patient characteristics and whether a screening discussion occurred and 2) the domains discussed and what screening decisions were made. Results. Of 422 participants, 209 reported having discussions and 201 responded to open-ended questions about CRC discussions. In a regression analysis, several factors were associated with increased odds of having a discussion: participants' preference to pursue screening (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3, 3.9), good health (OR 2.9, 95% CI 1.7, 4.8), and receipt of the decision aid (OR 2.1, 95% CI 1.4, 3.2). Our thematic analysis identified five domains related to discussion content and three related to discussion process. The CRC screening-related information domain was the most commonly discussed content domain, and the timing/frequency domain was associated with increased odds of intent to pursue screening. Decision-making role, the most commonly discussed process domain, was associated with increased odds of the intent to forgo CRC screening. Conclusions and Relevance. CRC screening discussions varied by type of participant and content. Future work is needed to determine if interventions focused on specific domains alters the appropriateness of participants' colorectal cancer screening intentions.

Blind spots in telemedicine: a qualitative study of staff workarounds to resolve gaps in diabetes management.

BACKGROUND: Novel telemedicine platforms have expanded access to critical retinal screening into primary care settings. This increased access has contributed to improved retinal screening uptake for diabetic patients, particularly those treated in Federally Qualified Health Centers ('safety net' clinics). The aim of this study was to understand how the implementation of telemedical screening for diabetic retinopathy within primary care settings is improving the delivery of critical preventative services, while also introducing changes into clinic workflows and creating additional tasks and responsibilities within resource-constrained clinics. METHODS: A qualitative approach was employed to track workflows and perspectives from a range of medical personnel involved in the telemedicine platform for diabetic retinopathy screening and subsequent follow-up treatment. Data were collected through semi-structured interviews and participant observation at three geographically-dispersed Federally Qualified Health Centers in California. Qualitative analysis was performed using standard thematic analytic approaches within a qualitative data analysis software program. RESULTS: The introduction of telemedicine platforms, such as diabetic retinopathy screening, into primary care settings is creating additional strain on medical personnel across the diabetes eye care management spectrum. Central issues are related to scheduling patients, issuing referrals for follow-up care and treatment, and challenges to improving adherence to treatment and diabetes management. These issues are overcome in many cases through workarounds, or when medical staff work outside of their job descriptions, purview, and permission to move patients through the diabetes management continuum. CONCLUSIONS: This study demonstrates how the implementation of a novel telemedical platform for diabetic retinopathy screening contributes to the phenomenon of workarounds that account for additional tasks and patient volume. These workarounds should not be considered a sustainable model of health care delivery, but rather as an initial step to understanding where issues are and how clinics can adapt to the inclusion of telemedicine and ultimately increase access to care. The presence of workarounds suggests that as telemedicine is expanded, adequate resources, as well as collaborative, cross-sectoral co-design of new workflows must be simultaneously provided. Systematic bolstering of resources would contribute to more consistent success of telemedicine screening platforms and improved treatment and prevention of disease-related complications.

eRAPID electronic patient self-Reporting of Adverse-events: Patient Information and aDvice: a pilot study protocol in pelvic radiotherapy.

BACKGROUND: An estimated 17,000 patients are treated annually in the UK with radical radiotherapy (RT) for pelvic cancer. New treatment approaches in RT have increased survivorship and changed the subjective toxicity profile for patients who experience acute and long-term pelvic-related adverse events (AE). Multi-disciplinary follow-up creates difficulty for monitoring and responding to these events during treatment and beyond. Originally developed for use in systemic oncology therapy eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is an online system for patients to report AEs from home. eRAPID enables patient data to be integrated into the electronic patient records for use in clinical practice, provides patient management advice for mild and moderate AE and advice to contact the hospital for severe AE. The system has now been developed for pelvic RT patients, and we aim to test the intervention in a pilot study with staff and patients to inform a future randomised controlled trial (RCT). METHODS: Eligible patients are those attending St James's University hospital cancer centre and The Christie Hospital Manchester undergoing pelvic radiotherapy+/-chemotherapy/hormonotherapy for prostate, lower gastrointestinal and gynaecological cancers. A prospective 1:1 randomised (intervention or usual care) parallel group design with repeated measures and mixed methods will be employed. We aim to recruit 168 patients following recommendations for sample size estimates for pilot studies. Participants using eRAPID will report AE (at least weekly) from home weekly for 6 weeks and 6 weeks post-treatment (12-week total) then at 18 and 24 weeks. Hospital staff will review eRAPID reports and use information during consultations. Notifications will be sent to the relevant clinical team when severe symptoms are reported. We will measure patient-reported outcomes using validated questionnaires (Functional Assessment in Cancer Therapy Scale-General (FACT-G), European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC-QLQ-C30), process of care impact (hospital records of patient contacts and admissions) and economic variables (EQ5D-5L, patient use of resources)). Staff and patient experiences will be explored via semi-structured interviews. DISCUSSION: The objectives are to establish feasibility, recruitment, integrity of the system and attrition rates, determine effect sizes and aid selection of the primary outcome measure for a future RCT. We will also refine the intervention by exploring staff and patient views. The overall goal of this complex intervention is to improve the safe delivery of cancer treatments, enhance patient care and standardise documentation of AE within the clinical datasets. TRIAL REGISTRATION: ClinicalTrials.gov NCT02747264.

A Decision Aid to Promote Appropriate Colorectal Cancer Screening among Older Adults: A Randomized Controlled Trial.

BACKGROUND: Concerns have been raised about both over- and underutilization of colorectal cancer (CRC) screening in older patients and the need to align screening behavior with likelihood of net benefit. OBJECTIVE: The purpose of this study was to test a novel use of a patient decision aid (PtDA) to promote appropriate CRC screening in older adults. METHODS: A total of 424 patients ages 70 to 84 y who were not up to date with CRC screening participated in a double-blinded randomized controlled trial of a PtDA targeted to older adults making decisions about whether to undergo CRC screening from March 2012 to February 2015. INTERVENTION: Patients were randomized to a targeted PtDA or an attention control. The PtDA was designed to facilitate individualized decision making-helping patients understand the potential risks, benefits, and uncertainties of CRC screening given advanced age, health state, preferences, and values. OUTCOMES: Two composite outcomes, appropriate CRC screening behavior 6 mo after the index visit and appropriate screening intent immediately after the visit, were defined as completed screening or intent for patients in good health, discussion about screening with their provider for patients in intermediate health, and no screening or intent for patients in poor health. Health state was determined by age and Charlson Comorbidity Index. RESULTS: Four hundred twelve (97%) and 421 (99%) patients were analyzed for the primary and secondary outcomes, respectively. Appropriate screening behavior at 6 mo was higher in the intervention group (55% v. 45%, P = 0.023) as was appropriate screening intent following the provider visit (61% v. 47%, P = 0.003). LIMITATIONS: The study took place in a single geographic region. The appropriate CRC screening classification system used in this study has not been formally validated. CONCLUSIONS: A PtDA for older adults promoted appropriate CRC screening behavior and intent. TRIAL REGISTRATION: Clinicaltrials.gov, registration number NCT01575990. https://clinicaltrials.gov/ct2/show/NCT01575990?term=epic-d&rank=1.

Adjuvant endocrine therapy after breast cancer: a qualitative study of factors associated with adherence.

INTRODUCTION: Despite evidence of the efficacy of adjuvant endocrine therapy (AET) in reducing the risk of recurrence and mortality after treatment for primary breast cancer, adherence to AET is suboptimal. This study aimed to explore factors that influence adherence and nonadherence to AET following breast cancer to inform the development of supportive interventions. METHODS: Interviews were conducted with 32 women who had been prescribed AET, 2-4 years following their diagnosis of breast cancer. Both adherers (n=19) and nonadherers (n=13) were recruited. The analysis was conducted using the Framework approach. RESULTS: Factors associated with adherence were as follows: managing side effects including information and advice on side effects and taking control of side effects, supportive relationships, and personal influences. Factors associated with nonadherence were as follows: burden of side effects, feeling unsupported, concerns about long-term AET use, regaining normality, including valuing the quality of life over length of life, and risk perception. CONCLUSION: Provision of timely information to prepare women for the potential side effects of AET and education on medication management strategies are needed, including provision of timely and accurate information on the efficacy of AET in reducing breast cancer recurrence and on potential side effects and ways to manage these should they arise. Trust in the doctor-patient relationship and clear patient pathways for bothersome side effects and concerns with AET are important. Training and education on AET for GPs should be considered alongside novel care pathways such as primary care nurse cancer care review and community pharmacist follow-up.

Can the Sum of Adenoma Diameters (Adenoma Bulk) on Index Examination Predict Risk of Metachronous Advanced Neoplasia?

BACKGROUND: Recent data suggest that adenoma size and number are more important predictors of metachronous colorectal neoplasia than advanced histology. Furthermore, there is poor reproducibility in diagnosing advanced histology; high-grade dysplasia and villous histology. Therefore we developed a new metric, adenoma bulk, the sum of diameters of all baseline adenomas, regardless of advanced features. GOAL: Compare the predictive value for metachronous advanced neoplasia of adenoma bulk to conventional paradigm. STUDY: Data were collected prospectively in a multicenter adenoma-chemoprevention trial (2004 to 2013). For the conventional paradigm, high-risk baseline findings were defined as ≥3 adenomas, large adenomas (≥1 cm) or adenomas with villous components or high-grade dysplasia. Adenoma bulk was examined across quartiles and as a continuous variable. Predictive characteristics (sensitivities, specificities, c-statistics) for metachronous advanced neoplasia using conventional criteria and adenoma bulk were calculated. receiver operator characteristic curves were computed using logistic regression. RESULTS: In total, 1948 adults had index and follow-up colonoscopies (mean follow-up, 45.2 mo). Those with an adenoma bulk ≥10 mm (4th quartile) had a higher metachronous advanced neoplasia risk (14.4% vs. 6.9-8.2% in lower 3 quartiles; P=0.0002). The c-statistics and sensitivities (specificity fixed at 0.73) for the adenoma bulk and conventional models were 0.587 and 0.563 (P=0.17) and 0.396 and 0.390, respectively. CONCLUSIONS: Categorizing sporadic adenoma patients as high versus low risk for metachronous advanced neoplasia by adenoma bulk of

Design of a randomized clinical trial of a colorectal cancer screening decision aid to promote appropriate screening in community-dwelling older adults.

BACKGROUND: Appropriate colorectal cancer screening in older adults should be aligned with the likelihood of net benefit. In general, patient decision aids improve knowledge and values clarity, but in older adults, they may also help patients identify their individual likelihood of benefit and foster individualized decision-making. We report on the design of a randomized clinical trial to understand the effects of a patient decision aid on appropriate colorectal cancer screening. This report includes a description of the baseline characteristics of participants. METHODS: English-speaking primary care patients aged 70-84 years who were not currently up to date with screening were recruited into a randomized clinical trial comparing a tailored colorectal cancer screening decision aid with an attention control. The intervention group received a decision aid that included a values clarification exercise and individualized decision-making worksheet, while the control group received an educational pamphlet on safe driving behaviors. The primary outcome was appropriate screening at 6 months based on chart review. We used a composite measure to define appropriate screening as screening for participants in good health, a discussion about screening for patients in intermediate health, and no screening for patients in poor health. Health state was objectively determined using patients' Charlson Comorbidity Index score and age. RESULTS: A total of 14 practices in central North Carolina participated as part of a practice-based research network. In total, 424 patients were recruited to participate and completed a baseline visit. Overall, 79% of participants were White and 58% female, with a mean age of 76.8 years. Patient characteristics between groups were similar by age, gender, race, education, insurance coverage, or work status. Overall, 70% had some college education or more, 57% were married, and virtually all had Medicare insurance (90%). The three primary medical conditions among the cohort were a history of diabetes, pneumonia, and cancer (28%, 26%, and 21%, respectively). CONCLUSION: We designed a randomized clinical trial to test a novel use of a patient decision aid to promote appropriate colorectal cancer screening and have recruited a diverse study population that seems similar between the intervention and control groups. The study should be able to determine the ability of a patient decision aid to increase individualized and appropriate colorectal cancer screening.

Unmetabolized Folic Acid, Tetrahydrofolate, and Colorectal Adenoma Risk.

In a randomized trial of folic acid supplementation for the prevention of colorectal adenomas, we previously found indications of increased risk during later treatment and follow-up. This could have been due to the unmetabolized folic acid (UFA) or natural reduced and methylated folates (mF) to which it is metabolized. In post hoc analyses, we measured mF (the sum of 5-methyl-tetrahydrofolate and 4-alfa-hydroxy-5-methyl-THF) and UFA concentrations in the serum of 924 participants. Using binomial regression models with a log link, we assessed the associations between plasma mF or UFA and adenoma occurrence. We found no association between plasma mF or UFA and overall adenoma risk. However, during later follow-up, the prespecified, composite endpoint of high-risk findings (advanced or multiple adenomas) was positively associated with plasma mF (Plinear trend = 0.009), with a 58% increased risk for participants in the upper versus lowest quartile. An irregular association was seen with plasma UFA, with suggestions of an inverse trend (Plinear trend=0.049). A modest, significant inverse association was also seen between mF and risk of serrated lesions, with a 39% lower risk for upper versus lower quartile participants (Plinear trend = 0.03). In conclusion, during the later follow-up period in which folic acid supplementation was previously seen to increase the risk of advanced and multiple adenomas, higher serum mF was associated with a higher risk of multiple and/or advanced adenomas, but no clear indication that UFA played a direct role. There were indications that higher mF was associated with reduced risk of serrated polyps. Cancer Prev Res; 10(8); 451-8. ©2017 AACR.

Electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID): a randomised controlled trial in systemic cancer treatment.

BACKGROUND: eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is an internet based system for patients to self-report symptoms and side effects (adverse events or AE) of cancer treatments. eRAPID allows AE reporting from home and patient reported data is accessible via Electronic Patient Records (EPR) for use in routine care. The system can generate alerts to clinical teams for severe AE and provides patient advice on managing mild AEs. The overall aims of eRAPID are to improve the safe delivery of cancer treatments, enhance patient care and standardise AE documentation. METHODS: The trial is a prospective randomised two-arm parallel group design study with repeated measures and mixed methods. Participants (adult patients with breast cancer on neo-adjuvant or adjuvant chemotherapy, colorectal and gynaecological cancer receiving chemotherapy) are randomised to receive the eRAPID intervention or usual care over 18 weeks of treatment. Participants in the intervention arm receive training in using the eRAPID system to provide routine weekly adverse event reports from home. Hospital staff can access eRAPID reports via the EPR and use the information during consultations or phone calls with patients. Prior to commencing the full trial an internal pilot phase was conducted (N = 87 participants) to assess recruitment procedures, consent and attrition rates, the integrity of the intervention information technology and establish procedures for collecting outcome data. The overall target sample for the trial is N = 504. The primary outcome of the trial is quality of life (FACT-G) with secondary outcomes including health economics (costs to patients and the NHS), process of care (e.g. contacts with the hospital, number of admissions, clinic appointments and changes to treatment/medications) and patient self-efficacy. Outcome data is collected at baseline, 6, 12, 18 weeks and 12 months. The intervention is also being evaluated via end of study interviews with patient participants and clinical staff. DISCUSSION: The pilot phase was completed in February 2016 and recruitment and attrition rates met criteria for continuing to the full trial. Recruitment recommenced in May 2016 and is planned to continue until December 2017. Overall findings will determine the value of the eRAPID intervention for supporting the care of patients receiving systemic cancer treatment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88520246 . Registered 11 September 2014.

Psychometric properties of the Beliefs about Medicine Questionnaire-adjuvant endocrine therapy (BMQ-AET) for women taking AETs following early-stage breast cancer.

This study evaluated the Beliefs about Medicine Questionnaire to explore adherence to adjuvant endocrine therapy after treatment for breast cancer (BMQ-AET). Factor structure of the BMQ-AET was explored alongside internal consistency, convergent validity and acceptability. The BMQ-AET Specific Scale fitted the original 10 item model. Internal consistency of the BMQ-AET was much improved compared to the original BMQ and convergent validity showed predicted direction of correlation, although correlation with BMQ-AET concerns scale was low. Acceptability was good. The evaluation of the BMQ-AET is encouraging, and could facilitate future research around adherence to AET.

Asking the right questions to get the right answers: using cognitive interviews to review the acceptability, comprehension and clinical meaningfulness of patient self-report adverse event items in oncology patients.

BACKGROUND: Standardized reporting of treatment-related adverse events (AE) is essential in clinical trials, usually achieved by using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) reported by clinicians. Patient-reported adverse events (PRAE) may add value to clinician assessments, providing patient perspective on subjective toxicity. We developed an online patient symptom report and self-management system for real-time reporting and managing AE during cancer treatment integrated with electronic patient records (eRAPID). As part of this program we developed a patient version of the CTCAE (version 4.0), rephrasing terminology into a self-report format. We explored patient understanding of these items via cognitive interviews. MATERIAL AND METHOD: Sixty patients (33 female, 27 male) undergoing treatment were purposively sampled by age, gender and tumor group (median age 61.5, range 35-84, 12 breast, 12 gynecological, 13 colorectal, 12 lung and 11 renal). Twenty-one PRAE items were completed on a touch-screen computer. Subsequent audio-recorded cognitive interviews and thematic analysis explored patients' comprehension of items via verbal probing techniques during three interview rounds (n = 20 patients/round). RESULTS: In total 33 item amendments were made; 29% related to question comprehension, 68% response option and 3% order effects. These amendments to phrasing and language improved patient understanding but maintained CTCAE grading and key medical information. Changes were endorsed by members of a patient advisory group (N = 11). CONCLUSION: Item adaptations resulted in a bank of consistently interpreted self-report AE items for use in future research program. In-depth analysis of items through cognitive interviews is an important step towards developing an internationally valid system for PRAE, thus improving patient safety and experiences during cancer treatment.

A web-based intervention (RESTORE) to support self-management of cancer-related fatigue following primary cancer treatment: a multi-centre proof of concept randomised controlled trial.

PURPOSE: Cancer-related fatigue (CRF) is a frequent and distressing symptom experienced after cancer treatment. RESTORE is the first web-based resource designed to enhance self-efficacy to manage CRF following curative-intent treatment. The aim of this study is to test the proof of concept and inform the design of an effectiveness trial. METHODS: A multi-centre parallel-group two-armed (1:1) exploratory randomised controlled trial (RCT) with qualitative process evaluation was employed in the study. Participants (≥18 years; ≤5 years post treatment with moderate to severe fatigue) were recruited and randomly assigned to RESTORE or a leaflet. Feasibility and acceptability were measured by recruitment, attrition, intervention adherence, completion of outcome measures and process evaluation. Change in self-efficacy to manage CRF was also explored. Outcome measures were completed at baseline (T0), 6 weeks (T1) and 12 weeks (T2). Data were analysed using mixed-effects linear regression and directed content analysis. RESULTS: One hundred and sixty-three people participated in the trial and 19 in the process evaluation. The intervention was feasible (39 % of eligible patients consented) and acceptable (attrition rate 36 %). There was evidence of higher fatigue self-efficacy at T1 in the intervention group vs comparator (mean difference 0.51 [-0.08 to 1.11]), though the difference in groups decreased by 12 weeks. Time since diagnosis influenced perceived usefulness of the intervention. Modifications were suggested. CONCLUSION: Proof of concept was achieved. The RESTORE intervention should be subject to a definitive trial with some adjustments. Provision of an effective supportive resource would empower cancer survivors to manage CRF after treatment completion. TRIAL REGISTRATION: ISRCTN67521059.

Results of a transparent expert consultation on patient and public involvement in palliative care research.

BACKGROUND: Support and evidence for patient, unpaid caregiver and public involvement in research (user involvement) are growing. Consensus on how best to involve users in palliative care research is lacking. AIM: To determine an optimal user-involvement model for palliative care research. DESIGN: We hosted a consultation workshop using expert presentations, discussion and nominal group technique to generate recommendations and consensus on agreement of importance. A total of 35 users and 32 researchers were approached to attend the workshop, which included break-out groups and a ranking exercise. Descriptive statistical analysis to establish consensus and highlight divergence was applied. Qualitative analysis of discussions was completed to aid interpretation of findings. SETTING/PARTICIPANTS: Participants involved in palliative care research were invited to a global research institute, UK. RESULTS: A total of 12 users and 5 researchers participated. Users wanted their involvement to be more visible, including during dissemination, with a greater emphasis on the difference their involvement makes. Researchers wanted to improve productivity, relevance and quality through involvement. Users and researchers agreed that an optimal model should consist of (a) early involvement to ensure meaningful involvement and impact and (b) diverse virtual and face-to-face involvement methods to ensure flexibility. CONCLUSION: For involvement in palliative care research to succeed, early and flexible involvement is required. Researchers should advertise opportunities for involvement and promote impact of involvement via dissemination plans. Users should prioritise adding value to research through enhancing productivity, quality and relevance. More research is needed not only to inform implementation and ensure effectiveness but also to investigate the cost-effectiveness of involvement in palliative care research.