A weekly in depth discussion of two pre-selected relevant recent publications from the biomedical literature
Martin T. Zanni, Ph.D. (U Wisconsin, Madison) "TBA"
"What is your colon worth to you? Changing the way we look at ulcerative colitis"
Meenakshi Bewtra, MD, MPH PhD Candidate Division of Epidemiology University of Pennsylvania Perelman School of Medicine
Dissertation Advisor: James Lewis, MD, MSCE Dissertation Committee Chair: David Margolis, MD, PhD
Abstract: Treatment options for mesalamine-refractory ulcerative colitis (UC) include chronic immunosuppressive medications or colectomy surgery. Current treatment paradigms presume the patients' foremost desire is to avoid surgery; and therefore view surgery as a consequence of medication failure. However, immunosuppressive therapy may not be ideal for all patients due to unclear durable efficacy and potential lethal adverse events. While current practice views surgery as an option of last resort, no previous studies have quantified UC patients' willingness to accept the risks of chronic immunosuppression to avoid colectomy. Such information can improve UC patient autonomy and facilitate shared-decision making and informed consent. It can also inform physicians, drug manufacturers and regulators when contemplating appropriate indications for existing and new medical therapies.
We first examined all-cause and cause-specific mortality in inflammatory bowel disease (IBD). Evidence addressing mortality in IBD has been conflicting and debate exists over appropriate study design to examine these important outcomes. We conduct a comprehensive meta-analysis of all-cause and cause-specific mortality in both Crohn's disease (CD) and UC, and additionally examined various effects of study design (inception-based versus population-based studies) on this outcome. In UC, we find statistically increased colorectal-, pulmonary- and non-alcoholic liver disease-related relative mortality; and in CD, we find a statistically increased pulmonary- and non-alcoholic liver disease-related relative mortality. We found little evidence of significant differences in all-cause relative mortality summary estimates by study type. This is the first study demonstrating an elevated relative mortality for UC patients.
We next conducted a study examining the reliability of a simple two-item non-invasive non-physician driven index, the 6-Point Mayo score, for measuring UC disease activity. Currently, there is no gold-standard for disease severity assessment in UC; and current non-invasive patient-driven disease assessment tools are cumbersome for patient-reported disease assessment. We found the 6-Point Mayo to strongly correlate with more extensive disease assessment tools with a similar sensitivity, specificity and ROC area under the curve for patient-defined clinical remission.
With these insights, we subsequently conducted a discrete choice experiment (DCE) to quantify the UC patients' tolerance for life-threatening serious adverse events (SAEs) in exchange for specific treatment benefits. We estimated the mean maximum acceptable risk (MAR) for SAEs associated with immunosuppressant therapy that UC patients are willing to accept to avoid colectomy with ostomy, ileal pouch anal anastomosis (IPAA) or IPAA complicated by fecal incontinence. We also evaluated how clinical characteristics affect risk tolerances. Using DCE, we were able to show that UC tolerances for medical and surgical risks do not conform to conventional preference-elicitation methodology assumptions of linear preferences across probabilities. UC patients were willing to accept very high levels of fatal SAEs to avoid an ostomy. However, if a durable clinical remission could not be achieved with medical therapy, patients were equally satisfied with J-pouch surgery. Finally, we found that several important clinical phenotypes impacted patient risk tolerances for medical and surgical therapy in UC including some modifiable patient characteristics such as surgical education about surgical options. This is the first empirical demonstration that UC patients view a well-functioning J-pouch as equivalent to mild clinical disease. It further demonstrates that these patients value medication efficacy and suggests that clinical remission, rather than response, be the preferred outcome for therapy efficacy trials and treatment algorithms. Our findings underline the need for rigorous methodologies to accurately measure patient-preferences; and suggest potential avenues to enhance UC patient autonomy and facilitate shared decision-making.
This event will begin in the morning from 9:00am - 12:00 pm with a session designed for postdocs called, Making Sense of Proposals. followed by lunch with postdocs and a selected group of faculty members. The afternoon session will be a roundtable for faculty members called, Competing Emphases in Science - Because the Facts Never Speak for Themselves.
Department of Radiation OncologyRadiation Biology Research DivisionRBI Meeting Speaker: Dr. Jerry Glickson, Research Professor of RadiologyTitle: "The use of Lonidamine to selectively sensitize tumors to chemotherapy, radiation therapy, and hyperthermia.” 12am-1pm in Room 8-146A; Lunch will be served at 11:45am
Mark A. Lemmon, PhD - Diversity of receptor tyrosine kinase (RTK) activation mechanisms in health and disease
Rodebaugh Diabetes Center Conference Series Presents: