Epigenome-Wide Study Identifies Epigenetic Outliers in Normal Mucosa of Patients with Colorectal Cancer.

Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as "Outlier Methylation Phenotype" (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development. PREVENTION RELEVANCE: Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.

Pilot Testing Fall TIPS (Tailoring Interventions for Patient Safety): a Patient-Centered Fall Prevention Toolkit.

BACKGROUND: Patient falls during an acute hospitalization cause injury, reduced mobility, and increased costs. The laminated paper Fall TIPS Toolkit (Fall TIPS) provides clinical decision support at the bedside by linking each patient's fall risk assessment with evidence-based interventions. Strategies were needed to integrate this evidence into clinical practice. METHODS: The Institute for Healthcare Improvement's Framework for Spread is the conceptual model for pilot implementation of Fall TIPS at Brigham and Women's Hospital (BWH; Boston) and Montefiore Medical Center (MMC; Bronx, New York). The key to translating the evidence into practice was engaging stakeholders by leveraging existing shared governance structures, identifying unit champions, holding training sessions for all staff, and implementing auditing to assess and provide feedback on protocol adherence and patient outcomes. RESULTS: BWH unit compliance with using Fall TIPS averaged 82%, the mean fall rate decreased from 3.28 to 2.80 falls per 1,000 patient-days from January through June 2015 versus 2016, and the mean fall with injury rate for these periods decreased from 1.00 to 0.54 per 1,000 patient-days. At MMC, compliance averaged 91%, but the mean fall rate increased marginally from 3.04 to 3.10, while the mean fall with injury rate decreased from 0.47 to 0.31 per 1,000 patient-days. Patient knowledge survey results show improvement in knowledge of the risks for falls and the ways to prevent falls. CONCLUSION: Engaging hospital and clinical leadership is critical in translating evidence-based care into clinical practice. Barriers to adoption of the protocol have been addressed and detailed to provide guidance for spread to other institutions.