Mild cognitive impairment in long-term brain tumor survivors following brain irradiation.

INTRODUCTION: There is no accepted classification of cognitive impairment in cancer survivors. We assess the extent of mild cognitive impairment (MCI) syndrome in brain tumor survivors using criteria adapted from the National Institute on Aging and the Alzheimer's Association (NIA-AA). METHODS: We retrospectively reviewed the cognitive data of brain tumor survivors post-radiation therapy (RT) enrolled from 2008 to 2011 in a randomized trial of donepezil versus placebo for cognitive impairment. One hundred and ninety eight adult survivors with primary or metastatic brain tumors who were ≥ 6 months post RT were recruited at 24 sites in the United States. Cognitive function was assessed at baseline, 12 and 24 weeks post-randomization. For this analysis, we used baseline data to identify MCI and possible dementia using adapted NIA-AA criteria. Cases were subtyped into four groups: amnestic MCI-single domain (aMCI-sd), amnestic MCI-multiple domain (aMCI-md), non-amnestic MCI-single domain (naMCI-sd), and non-amnestic MCI-multiple domain (naMCI-md). RESULTS: One hundred and thirty one of 197 evaluable patients (66%) met criteria for MCI. Of these, 13% were classified as aMCI-sd, 58% as aMCI-md, 19% as naMCI-sd, and 10% as naMCI-md. Patients with poorer performance status, less education, lower household income and those not working outside the home were more likely to be classified as MCI. CONCLUSION: Two-thirds of post-RT brain tumor survivors met NIA-AA criteria for MCI. This taxonomy may be useful when applied to brain tumor survivors because it defines cognitive phenotypes that may be differentially associated with course, treatment response, and risk factor profiles.

Effect of a Digital Health Intervention on Receipt of Colorectal Cancer Screening in Vulnerable Patients: A Randomized Controlled Trial.

Background: Screening for colorectal cancer (CRC) reduces mortality, yet more than one third of age-eligible Americans are unscreened. Objective: To examine the effect of a digital health intervention, Mobile Patient Technology for Health-CRC (mPATH-CRC), on rates of CRC screening. Design: Randomized clinical trial. (ClinicalTrials.gov: NCT02088333). Setting: 6 community-based primary care practices. Participants: 450 patients (223 in the mPATH-CRC group and 227 in usual care) scheduled for a primary care visit and due for routine CRC screening. Intervention: An iPad application that displays a CRC screening decision aid, lets patients order their own screening tests, and sends automated follow-up electronic messages to support patients. Measurements: The primary outcome was chart-verified completion of CRC screening within 24 weeks. Secondary outcomes were ability to state a screening preference, intention to receive screening, screening discussions, and orders for screening tests. All outcome assessors were blinded to randomization. Results: Baseline characteristics were similar between groups; 37% of participants had limited health literacy, and 53% had annual incomes less than $20 000. Screening was completed by 30% of mPATH-CRC participants and 15% of those receiving usual care (logistic regression odds ratio, 2.5 [95% CI, 1.6 to 4.0]). Compared with usual care, more mPATH-CRC participants could state a screening preference, planned to be screened within 6 months, discussed screening with their provider, and had a screening test ordered. Half of mPATH-CRC participants (53%; 118 of 223) "self-ordered" a test via the program. Limitation: Participants were English speakers in a single health care system. Conclusion: A digital health intervention that allows patients to self-order tests can increase CRC screening. Future research should identify methods for implementing similar interventions in clinical care. Primary Funding Source: National Cancer Institute.

Phase II study of Ginkgo biloba in irradiated brain tumor patients: effect on cognitive function, quality of life, and mood.

UNLABELLED: Ginkgo biloba has been reported to improve cognitive function in older adults and patients with Alzheimer's disease and multi-infarct dementia. We conducted an open-label phase II study of this botanical product in symptomatic irradiated brain tumor survivors. Eligibility criteria included: life expectancy ≥30 weeks, partial or whole brain radiation ≥6 months before enrollment, no imaging evidence of tumor progression in previous 3 months, or stable or decreasing steroid dose, and no brain tumor treatment planned while on study. The Ginkgo biloba dose was 120 mg/day (40 mg t.i.d.) for 24 weeks followed by a 6-week washout period. Assessments performed at baseline, 12, 24 (end of treatment), and 30 weeks (end of washout) included KPS, Functional Assessment of Cancer Therapy-Brain (FACT-Br), Profile of Mood States, Mini-Mental Status Exam, Trail Making Test Parts A (TMT-A) and B (TMT-B), Digit Span Test, Modified Rey Osterrieth Complex Figure (ROCF), California Verbal Learning Test Part II, and the F-A-S Test. RESULTS: Of the 34 patients enrolled on study, 23 (68 %) completed 12 weeks of treatment and 19 (56 %) completed 24 weeks of treatment. There were significant improvements at 24 weeks in: executive function (TMT-B) (p = 0.007), attention/concentration (TMT-A) (p = 0.002), and non-verbal memory (ROCF-immediate/delayed recall) (p = 0.001/0.002), mood (p = 0.002), FACT-Br subscale (p = 0.001), and the FACT physical subscale (p = 0.003). CONCLUSIONS: Some improvement in quality of life and cognitive function were noted with Ginkgo biloba. However, treatment with Ginkgo biloba was associated with a high dropout rate.

Effect of a Digital Health Intervention on Decreasing Barriers and Increasing Facilitators for Colorectal Cancer Screening in Vulnerable Patients.

BACKGROUND: Colorectal cancer is the second leading cause of cancer-related death in the United States, in part, because one third of Americans fail to get screened. In a prior randomized controlled trial, we found that an iPad patient decision aid called Mobile Patient Technology for Health-CRC (mPATH-CRC) doubled the proportion of patients who completed colorectal cancer screening. METHODS: All data for the current analysis were collected as part of a randomized controlled trial to determine the impact of mPATH-CRC on receipt of colorectal cancer screening within 24 weeks. Participants were enrolled from six community-based primary care practices between June 2014 and May 2016 and randomized to either usual care or mPATH-CRC. Six potential mediators of the intervention effect on screening were considered. The Iacobucci method was used to assess the significance of the mediation. RESULTS: A total of 408 patients had complete data for all potential mediators. Overall, the potential mediators accounted for approximately three fourths (76.3%) of the effect of the program on screening completion. Perceived benefits, self-efficacy, ability to state a screening decision, and patient-provider discussion were statistically significant mediators. Patient-provider discussion accounted for the largest proportion of the effect of mPATH-CRC (70.7%). CONCLUSIONS: mPATH-CRC increased completion of colorectal cancer screening by affecting patient-level and system-level mediators. However, the most powerful mediator was the occurrence of a patient-provider discussion about screening. Digital interventions like mPATH-CRC are an important adjunct to the patient-provider encounter. IMPACT: Understanding the factors that mediated mPATH-CRC's success is paramount to developing other effective interventions.

The Reach and Feasibility of an Interactive Lung Cancer Screening Decision Aid Delivered by Patient Portal.

OBJECTIVE: Health systems could adopt population-level approaches to screening by identifying potential screening candidates from the electronic health record and reaching out to them via the patient portal. However, whether patients would read or act on sent information is unknown. We examined the feasibility of this digital health outreach strategy. METHODS: We conducted a single-arm pragmatic trial in a large academic health system. An electronic health record algorithm identified primary care patients who were potentially eligible for lung cancer screening (LCS). Identified patients were sent a patient portal invitation to visit a LCS interactive Web site which assessed screening eligibility and included a decision aid. The primary outcome was screening completion. Secondary outcomes included the proportion of patients who read the invitation, visited the interactive Web site, and completed the interactive Web site. RESULTS: We sent portal invitations to 1,000 patients. Almost all patients (86%, 862/1,000) read the invitation, 404 (40%) patients visited the interactive Web site, and 349 patients (35%) completed it. Of the 99 patients who were confirmed screening eligible by the Web site, 81 made a screening decision (30% wanted screening, 44% unsure, 26% declined screening), and 22 patients had a chest computed tomography completed. CONCLUSION: The digital outreach strategy reached the majority of patient portal users. While the study focused on LCS, this digital outreach approach could be generalized to other health needs. Given the broad reach and potential low cost of this digital strategy, future research should investigate best practices for implementing the system.

ACES (Accelerated Chest Pain Evaluation With Stress Imaging) Protocols Eliminate Testing Disparities in Patients With Chest Pain.

BACKGROUND: Patients from racial and ethnic minority groups presenting to the Emergency Department (ED) with chest pain experience lower odds of receiving stress testing compared with nonminorities. Studies have demonstrated that care pathways administered within the ED can reduce health disparities, but this has yet to be studied as a strategy to increase stress testing equity. METHODS: A secondary analysis from 3 randomized clinical trials involving ED patients with acute chest pain was performed to determine whether a care pathway, ACES (Accelerated Chest pain Evaluation with Stress imaging), reduces the racial disparity in index visit cardiac testing between African American (AA) and White patients. Three hundred thirty-four participants with symptoms and findings indicating intermediate to high risk for acute coronary syndrome were enrolled in 3 clinical trials. Major exclusions were ST-segment elevation, initial troponin elevation, and hemodynamic instability. Participants were randomly assigned to receive usual inpatient care, or ACES. The ACES care pathway includes placement in observation for serial cardiac markers, with an expectation for stress imaging. The primary outcome was index visit objective cardiac testing, compared among AA and White participants. RESULTS: AA participants represented 111/329 (34%) of the study population, 80/220 (36%) of the ACES group and 31/109 (28%) of the usual care group. In usual care, objective testing occurred less frequently among AA (22/31, 71%) than among White (69/78, 88%, P = 0.027) participants, primarily driven by cardiac catheterization (3% vs. 24%; P = 0.012). In ACES, testing rates did not differ by race [AA 78/80 (98%) vs. White 138/140 (99%); P = 0.623]. At 90 days, death, MI, and revascularization did not differ in either group between AA and White participants. CONCLUSIONS: A care pathway with the expectation for stress imaging eliminates the racial disparity among AA and White participants with chest pain in the acquisition of index-visit cardiovascular testing.

Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population.

Purpose This study examined an inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), in radiotherapy (RT)-induced early adverse skin reactions or toxicities in breast cancer. Patients and Methods Between 2011 and 2013, 1,000 patients with breast cancer who underwent RT were evaluated prospectively for skin toxicities through the National Cancer Institute-funded Wake Forest University Community Clinical Oncology Program Research Base. Pre- and post-RT plasma hsCRP levels and Oncology Nursing Society skin toxicity criteria (0 to 6) were used to assess RT-induced skin toxicities. Multivariable logistic regression analyses were applied to ascertain the associations between hsCRP and RT-induced skin toxicities after adjusting for potential confounders. Results The study comprised 623 white, 280 African American, 64 Asian/Pacific Islander, and 33 other race patients; 24% of the patients were Hispanic, and 47% were obese. Approximately 42% and 15% of patients developed RT-induced grade 3+ and 4+ skin toxicities, respectively. The hsCRP levels differed significantly by race and body mass index but not by ethnicity. In multivariable analysis, grade 4+ skin toxicity was significantly associated with obesity (odds ratio [OR], 2.17; 95% CI, 1.41 to 3.34], post-RT hsCRP ≥ 4.11 mg/L (OR, 1.61; 95% CI, 1.07 to 2.44), and both factors combined (OR, 3.65; 95% CI, 2.18 to 6.14). Above-median post-RT hsCRP (OR, 1.93; 95% CI, 1.03 to 3.63), and change in hsCRP (OR, 2.80; 95% CI, 1.42 to 5.54) were significantly associated with grade 4+ skin toxicity in nonobese patients. Conclusion This large prospective study is the first to our knowledge of hsCRP as an inflammatory biomarker in RT-induced skin toxicities in breast cancer. We demonstrate that nonobese patients with elevated RT-related change in hsCRP levels have a significantly increased risk of grade 4+ skin toxicity. The outcomes may help to predict RT responses and guide decision making.

Usability of a Novel Mobile Health iPad App by Vulnerable Populations.

BACKGROUND: Recent advances in mobile technologies have created new opportunities to reach broadly into populations that are vulnerable to health disparities. However, mobile health (mHealth) strategies could paradoxically increase health disparities, if low socioeconomic status individuals lack the technical or literacy skills needed to navigate mHealth programs. OBJECTIVE: The aim of this study was to determine whether patients from vulnerable populations could successfully navigate and complete an mHealth patient decision aid. METHODS: We analyzed usability data from a randomized controlled trial of an iPad program designed to promote colorectal cancer (CRC) screening. The trial was conducted in six primary care practices and enrolled 450 patients, aged 50-74 years, who were due for CRC screening. The iPad program included a self-survey and randomly displayed either a screening decision aid or a video about diet and exercise. We measured participant ability to complete the program without assistance and participant-rated program usability. RESULTS: Two-thirds of the participants (305/450) were members of a vulnerable population (limited health literacy, annual income < US $20,000, or black race). Over 92% (417/450) of the participants rated the program highly on all three usability items (90.8% for vulnerable participants vs 96.6% for nonvulnerable participants, P=.006). Only 6.9% (31/450) of the participants needed some assistance to complete the program. In multivariable logistic regression, being a member of a vulnerable population was not associated with needing assistance. Only older age, less use of text messaging (short message service, SMS), and lack of Internet use predicted needing assistance. CONCLUSIONS: Individuals who are vulnerable to health disparities can successfully use well-designed mHealth programs. Future research should investigate whether mHealth interventions can reduce health disparities.

Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial.

PURPOSE: Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. PATIENTS AND METHODS: A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. RESULTS: Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. CONCLUSION: Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments.

Effectiveness of a web-based colorectal cancer screening patient decision aid: a randomized controlled trial in a mixed-literacy population.

BACKGROUND: Colorectal cancer (CRC) screening reduces mortality yet remains underutilized. Low health literacy may contribute to this underutilization by interfering with patients' ability to understand and receive preventive health services. PURPOSE: To determine if a web-based multimedia CRC screening patient decision aid, developed for a mixed-literacy audience, could increase CRC screening. DESIGN: RCT. Patients aged 50-74 years and overdue for CRC screening were randomized to the web-based decision aid or a control program seen immediately before a scheduled primary care appointment. SETTING/PARTICIPANTS: A large community-based, university-affiliated internal medicine practice serving a socioeconomically disadvantaged population. MAIN OUTCOME MEASURES: Patients completed surveys to determine their ability to state a screening test preference and their readiness to receive screening. Charts were abstracted by masked observers to determine if screening tests were ordered and completed. RESULTS: Between November 2007 and September 2008, a total of 264 patients enrolled in the study. Data collection was completed in 2009, and data analysis was completed in 2010. A majority of participants (mean age=57.8 years) were female (67%), African-American (74%), had annual household incomes of <$20,000 (76%), and had limited health literacy (56%). When compared to control participants, more decision-aid participants had a CRC screening preference (84% vs 55%, p<0.0001) and an increase in readiness to receive screening (52% vs 20%, p=0.0001). More decision-aid participants had CRC screening tests ordered (30% vs 21%) and completed (19% vs 14%), but no statistically significant differences were seen (AOR=1.6, 95% CI=0.97, 2.8, and AOR=1.7, 95% CI=0.88, 3.2, respectively). Similar results were found across literacy levels. CONCLUSIONS: The web-based decision aid increased patients' ability to form a test preference and their intent to receive screening, regardless of literacy level. Further study should examine ways the decision aid can be combined with additional system changes to increase CRC screening.

Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment: a prospective study.

BACKGROUND: The incidence of chemotherapy-induced amenorrhea (CIA) and the time to subsequent menstrual bleeding in premenopausal breast cancer patients treated with current standard chemotherapy regimens was examined. METHODS: Four hundred sixty-six women ages 20 to 45 years at the time of diagnosis of a stage I to III breast cancer were recruited between January 1998 and July 2002. Patients completed monthly bleeding calendars from the time of study recruitment. Updated medical history data were obtained at 6-month intervals. RESULTS: Most women received doxorubicin and cyclophosphamide (AC); doxorubicin, cyclophosphamide, and paclitaxel (ACT); or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Approximately 41% of women experienced an initial 6 months of CIA, and an additional 29% had at least 1 year of CIA. Approximately half of the women with 6 months of CIA and 29% of those with 1 year of CIA resumed bleeding within the subsequent 3 years, usually in the year after their amenorrheic episode. Resumption of bleeding differed significantly by treatment regimen after 6 months of CIA (P = .002; 68% with AC, 57% with ACT, and 23% with CMF), but not after 1 year of CIA (P = .5). Of the 23% of women who experienced an initial 2-year period of CIA, 10% resumed bleeding within the ensuing 3 years after their amenorrheic episode, but none had regular menses. CONCLUSIONS: A considerable proportion of women treated with chemotherapy will experience periods of CIA, but many will resume bleeding. Newer treatment regimens such as ACT appear to have a higher resumption of bleeding compared with CMF. This finding may have implications for choice of anti-estrogen treatment and for future potential pregnancies/fertility.