Stacy A. Kahn

Fecal bacteriotherapy for ulcerative colitis: patients are ready, are we?

Background: Fecal bacteriotherapy (FB) has been proposed as a safe and effective alternative treatment for a number of gastrointestinal conditions including ulcerative colitis (UC). We performed a qualitative study to explore the attitudes and concerns of adult patients and parents of children with UC regarding FB as a potential treatment. Methods: We conducted six focus groups for adult patients with UC and parents of children with UC or indeterminate colitis. Participants were asked about their perceptions of and interest in FB as a treatment for UC. Sessions were recorded, transcribed, and reviewed to identify domains, themes, and major concepts. Results: The focus groups included 15 adult patients and seven parents of children with colitis. We identified five major domains pertaining to FB: impressions of treatment, benefits, risks, potential mechanisms, and social concerns. All but one participant expressed interest in FB and several wished it were already available. Participants compared FB to probiotics, felt it was “natural,” easier than current therapies, and with donor screening would be safe. Although initial distaste and the “yuck factor” were uniformly mentioned, these concerns were outweighed by perceived benefits. Conclusion: This is the first study to examine important ethical and social issues surrounding FB as a treatment for UC. Given adequate supporting research, donor selection, and screening, adult patients and parents of children with UC will consider FB and are eager for it to become available. These findings have important implications for future microbiome‐based treatments. (Inflamm Bowel Dis 2011;)

Patient Perceptions of Fecal Microbiota Transplantation for Ulcerative Colitis

Background:Fecal microbiota transplantation (FMT), the delivery of stool from a healthy prescreened donor to an individual with disease, is gaining increasing recognition as a potential treatment for inflammatory bowel diseases. Our objective was to describe patient interest in and social concerns around FMT. Methods:We conducted a survey of adults with ulcerative colitis (UC) seen in outpatient clinic at the University of Chicago IBD Center. All English-speaking patients ≥18 years of age were eligible. Subjects completed a written survey in clinic. Ninety-five participants, median age 39 years, 53% female, were enrolled in the study. Results:Forty-four percent and 49% reported excellent or good/satisfactory medical management of their UC, respectively. Forty-six percent participants were willing to undergo FMT as a treatment of UC, 43% were unsure, and 11% were unwilling to undergo FMT. Subjects who had been hospitalized were more willing to undergo FMT, 54% versus 34%, P = 0.035. Primary concerns included the following: adequate screening for infections (41%), cleanliness (24%), and potential to worsen UC (18%); 21% reported no specific concerns. For donor selection, an equal number of participants (46%) preferred whomever their doctor recommended or family member/spouse. Conclusions:In our center despite reporting satisfactory to excellent disease control with their treatments, the vast majority of patients with UC are interested in or willing to consider FMT. Proof of safety and effectiveness, and failure of other medical therapies are key issues in considering FMT. Strong interest in this as-yet unproven therapy warrants attention and is a pressing priority for clinical research and education.

Genetic and Metabolic Signals during Acute Enteric Bacterial Infection Alter the Microbiota and Drive Progression to Chronic Inflammatory Disease

Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

Colonoscopic Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in a Child

Colonoscopic Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in a Child

Studying the Enteric Microbiome in Inflammatory Bowel Diseases: Getting through the Growing Pains and Moving Forward.

In this commentary, we will review some of the early efforts aimed at understanding the role of the enteric microbiota in the causality of inflammatory bowel diseases. By examining these studies and drawing on our own experiences bridging clinical gastroenterology and microbial ecology as part of the NIH-funded Human Microbiome Project (Turnbaugh et al., 2007), we hope to help define some of the “growing pains” that have hampered these initial efforts. It is our sincere hope that this discussion will help advance future efforts in this area by identifying current challenges and limitations and by suggesting strategies to overcome these obstacles.

What's in a name generator? Choosing the right name generators for social network surveys in healthcare quality and safety research

Background Interest in the use of social network analysis (SNA) in healthcare research has increased, but there has been little methodological research on how to choose the name generators that are often used to collect primary data on the social connection between individuals for SNA. Objective We sought to determine a minimum set of name generators sufficient to distinguish the social networks of a target population of physicians active in quality improvement (QI). Methods We conducted a pilot survey including 8 name generators in a convenience sample of 25 physicians active in QI to characterize their social networks. We used multidimensional scaling to determine what subset of these name generators was needed to distinguish these social networks. Results We found that some physicians maintain a social network organized around a specific colleague who performed multiple roles while others maintained highly differentiated networks. We found that a set of 5 of the 8 name generators we used was needed to distinguish the networks of these physicians. Conclusions Beyond methodology for selecting name generators, our findings suggest that QI networks may require 5 or more generators to elicit valid sets of relevant actors and relations in this target population.

Can You Teach a Teen New Tricks? Problem Solving Skills Training Improves Oral Medication Adherence in Pediatric Patients with Inflammatory Bowel Disease Participating in a Randomized Trial.

Background:Medication nonadherence is associated with higher disease activity, greater health care utilization, and lower health-related quality of life in pediatric inflammatory bowel diseases (IBD). Problem solving skills training (PSST) is a useful tool to improve adherence in patients with chronic diseases but has not been fully investigated in IBD. This study assessed feasibility, acceptability, and preliminary efficacy of PSST in pediatric IBD. Methods:Recruitment occurred during outpatient clinic appointments. After completion of baseline questionnaires, families were randomized to a treatment group or wait-list comparison group. The treatment group received either 2 or 4 PSST sessions. Youth health-related quality of life was assessed at 3 time points, and electronic monitoring of oral medication adherence occurred for the study duration. Results:Seventy-six youth (ages 11–18 years) on an oral IBD maintenance medication participated. High retention (86%) and treatment fidelity rates (95%) supported feasibility. High satisfaction ratings (mean values ≥4.2 on 1–5 scale) supported intervention acceptability. Modest increases in adherence occurred after 2 PSST sessions among those with imperfect baseline adherence (d = 0.41, P < 0.10). Significant increases in adherence after 2 PSST sessions were documented for participants aged 16 to 18 years (d = 0.95, P < 0.05). Improvements in health-related quality of life occurred after 2 PSST sessions. No added benefit of 4 sessions on adherence was documented (d = 0.05, P > 0.05). Conclusions:Phone-delivered PSST was feasible and acceptable. Efficacy estimates were similar to those of lengthier interventions conducted in other chronic illness populations. Older adolescents benefited more from the intervention than their younger counterparts.

Feeling Fine: Anxiety and Depressive Symptoms in Youth with Established IBD.

Background:Previous research is discrepant with respect to the prevalence of internalizing symptoms (i.e., depressive and anxiety symptoms) in pediatric inflammatory bowel disease (IBD) samples. Moreover, few studies have examined the combined influence of demographic and disease-related risk factors for internalizing symptoms. This study described rates of depressive, anxiety, and overall internalizing symptomatology in a multisite sample of youth with established IBD diagnoses. Additionally, the study examined risk factors for elevated depressive, anxiety, and internalizing symptoms, including those in demographic (i.e., family income and sex) and disease (i.e., disease activity and functional disability) domains. Methods:One hundred sixty-one youth (aged 11–18 yr) with established IBD diagnoses, primarily inactive disease, prescribed oral medications, and who were not taking corticosteroids were recruited from outpatient Gastroenterology Clinics at 3 childrens hospitals. This article reflects a secondary analysis of data collected from 2 larger studies examining oral medication adherence and psychosocial functioning in pediatric IBD. After providing written consent/assent, participants completed questionnaires assessing demographics, functional disability, and internalizing symptoms. Medical records were reviewed for disease information and clinical disease activity ratings. Results:Only 13% of the sample reported clinically elevated anxiety or depressive symptoms. Perceived functional disability, but not clinical disease activity, was associated with higher depressive and anxiety symptoms, and higher overall internalizing symptomatology. Conclusions:Current results highlight the need to look beyond disease severity and examine the perception of functional disability of patients with IBD when seeking to identify youth at risk for internalizing symptoms such as depression and anxiety.

Whole-exome Sequence Analysis Implicates Rare Il17REL Variants in Familial and Sporadic Inflammatory Bowel Disease

Background:Rare variants (<1%) likely contribute significantly to risk for common diseases such as inflammatory bowel disease (IBD) in specific patient subsets, such as those with high familiality. They are, however, extraordinarily challenging to identify. Methods:To discover candidate rare variants associated with IBD, we performed whole-exome sequencing on 6 members of a pediatric-onset IBD family with multiple affected individuals. To determine whether the variants discovered in this family are also associated with nonfamilial IBD, we investigated their influence on disease in 2 large case–control (CC) series. Results:We identified 2 rare variants, rs142430606 and rs200958270, both in the established IBD-susceptibility gene IL17REL, carried by all 4 affected family members and their obligate carrier parents. We then demonstrated that both variants are associated with sporadic ulcerative colitis (UC) in 2 independent data sets. For UC in CC 1: rs142430606 (odds ratio [OR] = 2.99, Padj = 0.028; minor allele frequency [MAF]cases = 0.0063, MAFcontrols = 0.0021); rs200958270 (OR = 2.61, Padj = 0.082; MAFcases = 0.0045, MAFcontrols = 0.0017). For UC in CC 2: rs142430606 (OR = 1.94, P = 0.0056; MAFcases = 0.0071, MAFcontrols = 0.0045); rs200958270 (OR = 2.08, P = 0.0028; MAFcases = 0.0071, MAFcontrols = 0.0042). Conclusions:We discover in a family and replicate in 2 CC data sets 2 rare susceptibility variants for IBD, both in IL17REL. Our results illustrate that whole-exome sequencing performed on disease-enriched families to guide association testing can be an efficient strategy for the discovery of rare disease-associated variants. We speculate that rare variants identified in families and confirmed in the general population may be important modifiers of disease risk for patients with a family history, and that genetic testing of these variants may be warranted in this patient subset.

What Teens Do Not Know Can Hurt Them: An Assessment of Disease Knowledge in Adolescents and Young Adults with IBD

Background: Although adequate disease-related knowledge is recognized as an important component of transition readiness, little empirical attention has been directed toward understanding the levels of disease knowledge of adolescents and young adults (AYAs) with inflammatory bowel diseases (IBDs) or factors associated with higher levels of knowledge. This study described disease knowledge in a sample of AYAs with IBDs and examined individual, family, and patient–provider relationship factors associated with higher knowledge. Methods: Seventy-five AYAs (ages 16–20) and their parents participated. AYAs and parents reported on demographics, parent autonomy granting behaviors, health care satisfaction, patient–provider transition-related communication, and disease knowledge. AYAs self-reported on disease self-efficacy. Disease information was abstracted from the medical record. Results: On average, AYAs answered 8.20 (SD = 1.75) of 12 knowledge questions correctly. Over 85% of AYAs correctly identified their type of IBD, number and type of IBD–related surgeries, and name of their current IBD medical provider. In contrast, knowledge about frequency of medication refills, effects of drugs and alcohol on IBD, and number to call to schedule medical appointments was suboptimal (i.e., 50% or fewer provided a correct response). Older AYA age, greater AYA health care satisfaction, higher AYA self-efficacy, and more frequent patient–provider transition-related communication were each associated with higher IBD-related knowledge. Conclusions: To promote disease knowledge, providers should foster AYA self-efficacy by encouraging age-appropriate involvement in IBD management and make discussion of transition-related issues a priority during clinical appointments. Moreover, fostering collaborative and positive relationships with patients will improve satisfaction and may also enhance knowledge.