Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial.

IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful. OBJECTIVE: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah. INTERVENTIONS: Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months. MAIN OUTCOMES AND MEASURES: The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden. RESULTS: Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P < .001). Only 2 participants experienced grade 3 adverse events. [table: see text]. CONCLUSIONS AND RELEVANCE: Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 01187901.

Perspectives on physical activity and exercise among Appalachian youth.

BACKGROUND: Most children in the United States receive far less physical activity (PA) than is optimal. In rural, under resourced areas of Appalachian Kentucky, physical inactivity rates are significantly higher than national levels. We sought to understand children's perceptions of PA, with the goal of developing culturally appropriate programming to increase PA. METHODS: During 11 focus groups, we explored perspectives on PA among 63 Appalachian children, ages 8-17. Sessions were tape recorded, transcribed, content analyzed, and subjected to verification procedures. RESULTS: Several perspectives on PA emerged among these rural Appalachian youth, including the clear distinction between PA (viewed as positive) and exercise (viewed as negative) and an emphasis on time and resource factors as barriers to adequate PA. Additional PA determinants expressed in the focus groups are similar to those of other populations. We include children's recommendations for appealing PA programs. CONCLUSIONS: Appalachian and other rural residents contend with the loss of rural health advantages (due to declines in farming/other occupational and avocational transitions). At the same time, Appalachian residents have not benefitted from urban PA facilitators (sidewalks, recreational facilities, clubs and organized leisure activities). Addressing low PA levels requires extensive community input and creative programming.

Perceptions of healthful eating and influences on the food choices of Appalachian youth.

OBJECTIVE: Patterns of overweight and obesity have an unequal geographic distribution, and there are elevated rates in Appalachia. Perceptions of Appalachian youth toward healthful eating and influences on food choice were examined as part of formative research to address these disparities. METHODS: Eleven focus groups, averaging 6 youth (n = 68) and moderated by experienced local residents, were conducted with participants aged 8-17. Session transcripts were coded for thematic analysis, using measures to enhance rigor and transferability. RESULTS: Participants discussed numerous internal and external factors affecting dietary choices. They expressed confidence in their own nutritional knowledge, and they stressed the importance of taste preferences, cost, convenience, social influences, and advertising on diet. CONCLUSIONS AND IMPLICATIONS: Appalachian youth awareness of the multiple influences on diet may create opportunities for multifaceted, ecologically based interventions. In particular, participants stressed the importance of social influences on diet and on successful nutrition programming.

Formative research conducted in rural Appalachia to inform a community physical activity intervention.

PURPOSE: Despite the well-established benefits of physical activity (PA), most Americans, especially those in rural, traditionally underserved areas, engage in considerably less PA than recommended. This study examines perceived barriers to and facilitators of PA and promising organized PA programs among rural Appalachians. DESIGN: Eight focus groups and seven group key informant interviews were conducted. SETTING: This study was conducted in eastern Kentucky, in central Appalachia. SUBJECTS: One hundred and fourteen rural Appalachian residents (74% female, 91% white) participated. MEASURES: Open-ended, semistructured, and structured questions regarding perceptions of, barriers to/facilitators of, and examples of successful/failed PA programs were asked. ANALYSIS: Qualitative data analysis was conducted, including codebook development and steps taken to ensure rigor and transferability. Interrater reliability was over 94%. RESULTS: In addition to barriers that are consistent with those found in other populations, rural Appalachian residents indicated that travel time, family commitments, and inadequate community resources undermine PA. Suggested avenues to increase PA include partnership with churches and the U.S. Department of Agriculture's Cooperative Extension Service; programs that include families, are well advertised, and focus on health rather than appearance; and, underlying all suggestions, culturally relevant yet nonstereotyping activities. CONCLUSIONS: When developing PA interventions in rural Appalachia, it is important to employ community-based participatory approaches that leverage unique assets of the population and show potential in overcoming challenges to PA.

Perceptions of smoking cessation programs in rural Appalachia.

OBJECTIVES: To identify perspectives on smoking cessation programs in Appalachian Kentucky, a region with particularly high smoking rates and poor health outcomes. METHODS: Insufficient existing research led us to conduct 12 focus groups (smokers and nonsmokers) and 23 key informant interviews. RESULTS: Several findings previously not described in this high-risk population include (1) transition from pro-tobacco culture toward advocacy for tobacco cessation approaches, (2) region-specific challenges to program access, and (3) strong and diverse social influences on cessation. CONCLUSIONS: To capitalize on changes from resistance to support for smoking cessation, leaders should incorporate culturally appropriate programs and characteristics identified here.