Ashish Atreja

Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook.

The community of microorganisms within the human gut (or microbiota) is critical to health and functions with a level of complexity comparable to that of an organ system. Alterations of this ecology (or dysbiosis) have been implicated in a number of disease states, and the prototypical example is Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to durably alter the gut microbiota of the recipient and has shown efficacy in the treatment of patients with recurrent CDI. There is hope that FMT may eventually prove beneficial for the treatment of other diseases associated with alterations in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Although relatively simple to perform, questions regarding both short-term and long-term safety as well as the complex and rapidly evolving regulatory landscape has limited widespread use. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current whole-stool transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future.

Antibiotics Associated With Increased Risk of New-Onset Crohn's Disease But Not Ulcerative Colitis: A Meta-Analysis

OBJECTIVES:The objective of this study was to perform a meta-analysis investigating antibiotic exposure as a risk factor for developing inflammatory bowel disease (IBD).METHODS:A literature search using Medline, Embase, and Cochrane databases was performed to identify studies providing data on the association between antibiotic use and newly diagnosed IBD. Included studies reported Crohn’s disease (CD), ulcerative colitis (UC), or a composite of both (IBD) as the primary outcome and evaluated antibiotic exposure before being diagnosed with IBD. A random-effects meta-analysis was conducted to determine overall pooled estimates and 95% confidence intervals (CIs).RESULTS:A total of 11 observational studies (8 case–control and 3 cohort) including 7,208 patients diagnosed with IBD were analyzed. The pooled odds ratio (OR) for IBD among patients exposed to any antibiotic was 1.57 (95% CI 1.27–1.94). Antibiotic exposure was significantly associated with CD (OR 1.74, 95% CI 1.35–2.23) but was not significant for UC (OR 1.08, 95% CI 0.91–1.27). Exposure to antibiotics most markedly increased the risk of CD in children (OR 2.75, 95% CI 1.72–4.38). All antibiotics were associated with IBD, with the exception of penicillin. Exposure to metronidazole (OR 5.01, 95% CI 1.65–15.25) or fluoroquinolones (OR 1.79, 95% CI 1.03–3.12) was most strongly associated with new-onset IBD.CONCLUSIONS:Exposure to antibiotics appears to increase the odds of being newly diagnosed with CD but not UC. This risk is most marked in children diagnosed with CD.

Safety and efficacy of endoscopic dilation for primary and anastomotic Crohn's disease strictures.

BACKGROUNDnLiterature on endoscopic dilation of Crohns disease (CD) strictures, especially for primary (non-anastomotic) strictures is limited.nnnMETHODSnA historical cohort study was performed on patients who underwent endoscopic stricture dilations for CD in our IBD center. Primary endpoint was the efficacy of first endoscopic dilation in preventing the need for surgery in primary strictures compared to anastomotic strictures. Cox proportional hazards models using robust sandwich covariance matrix estimate were used to evaluate the need for surgery and any further endoscopic intervention.nnnRESULTSnIn our study cohort (mean age 42.2 ± 13.1 years, 57% females, 16.4% current smokers, and median follow-up 1.8 years), 128 patients underwent a total of 430 endoscopic stricture dilations for 169 strictures (88 primary, 81 secondary). Forty-two patients (32.8%) required surgery in the follow-up period, with a mean interval period between first dilation and surgery of 33 months. There was no difference between primary or anastomotic strictures with respect to the need for surgery (34.1% vs. 29.6%, p=0.53), redilation (59.1% vs. 58%, p=0.89) or total interventions (surgery+redilations, 71.6% vs. 72.8%, p=0.86). Multivariable analysis did not show any significant difference between patients who received and did not receive intralesional steroid injections, biologics or immunomodulators with respect to the need for repeat intervention or surgery.nnnCONCLUSIONnEfficacy and safety of endoscopic dilation are similar between primary and anastomotic CD strictures. Intralesional steroid injection or use of biologics did not decrease the need for re-intervention or surgery for either primary or anastomotic strictures.

Fecal microbiota transplantation for recurrent C difficile infection: Ready for prime time?

Recurrent Clostridium difficile infection has been a major challenge for patients and clinicians. Recurrence of infection after treatment with standard antibiotics is becoming more common with the emergence of more-resistant strains of C difficile. Fecal microbiota transplantation is an alternative treatment for recurrent C difficile infection, but it is not yet widely used. If you had a serious disease, would you agree to an alternative treatment that is cheap, safe, and effective—but seems disgusting? Would you recommend it to patients?

Impact of the Mobile HealthPROMISE Platform on the Quality of Care and Quality of Life in Patients With Inflammatory Bowel Disease: Study Protocol of a Pragmatic Randomized Controlled Trial

Background Inflammatory bowel disease (IBD) is a chronic condition of the bowel that affects over 1 million people in the United States. The recurring nature of disease makes IBD patients ideal candidates for patient-engaged care that is centered on enhanced self-management and improved doctor-patient communication. In IBD, optimal approaches to management vary for patients with different phenotypes and extent of disease and past surgical history. Hence, a single quality metric cannot define a heterogeneous disease such as IBD, unlike hypertension and diabetes. A more comprehensive assessment may be provided by complementing traditional quality metrics with measures of the patient’s quality of life (QOL) through an application like HealthPROMISE. Objective The objective of this pragmatic randomized controlled trial is to determine the impact of the HealthPROMISE app in improving outcomes (quality of care [QOC], QOL, patient adherence, disease control, and resource utilization) as compared to a patient education app. Our hypothesis is that a patient-centric self-monitoring and collaborative decision support platform will lead to sustainable improvement in overall QOL for IBD patients. Methods Participants will be recruited during face-to-face visits and randomized to either an interventional (ie, HealthPROMISE) or control (ie, education app). Patients in the HealthPROMISE arm will be able to update their information and receive disease summary, quality metrics, and a graph showing the trend of QOL (SIBDQ) scores and resource utilization over time. Providers will use the data for collaborative decision making and quality improvement interventions at the point of care. Patients in the control arm will enter data at baseline, during office visits, and at the end of the study but will not receive any decision support (trend of QOL, alert, or dashboard views). Results Enrollment in the trial will be starting in first quarter of 2015. It is intended that up to 300 patients with IBD will be recruited into the study (with 1:1 allocation ratio). The primary endpoint is number of quality indicators met in HealthPROMISE versus control arm. Secondary endpoints include decrease in number of emergency visits due to IBD, decrease in number of hospitalization due to IBD, change in generic QOL score from baseline, proportion of patients in each group who meet all eligible outpatient quality metrics, and proportion of patients in disease control in each group. In addition, we plan to conduct protocol analysis of intervention patients with adequate HealthPROMISE utilization (more than 6 log-ins with data entry from week 0 through week 52) achieving above mentioned primary and secondary endpoints. Conclusions HealthPROMISE is a unique cloud-based patient-reported outcome (PRO) and decision support tool that empowers both patients and providers. Patients track their QOL and symptoms, and providers can use the visual data in real time (integrated with electronic health records [EHRs]) to provide better care to their entire patient population. Using pragmatic trial design, we hope to show that IBD patients who participate in their own care and share in decision making have appreciably improved outcomes when compared to patients who do not. Trial Registration ClinicalTrials.gov NCT02322307; https://clinicaltrials.gov/ct2/show/NCT02322307 (Archived by WebCite at http://www.webcitation.org/6W8PoYThr).

A Pooled Analysis of Efficacy, Safety, and Long-term Outcome of Endoscopic Balloon Dilation Therapy for Patients with Stricturing Crohn's Disease.

Background: Endoscopic balloon dilation (EBD) is widely used to manage Crohns disease–associated strictures. However, most studies of the safety and efficacy are small and heterogenous. We performed a combined analysis of published studies and evaluated 676 comprehensive individual participant data sets to determine the overall effects of EBD. Methods: Citations from the Embase, MEDLINE, and the Cochrane library from 1991 through 2013 were systematically reviewed, and references of cited articles were assessed for relevant publications. We collected data from studies including ≥15 patients and additionally generated a unique individual patient database containing 676 individual data sets derived from 12 studies. Technical feasibility, short-term and long-term efficacies, and safety were evaluated. Results: In 1463 patients with Crohns disease who underwent 3213 EBD procedures, 98.6% of strictures were ileal and 62% anastomotic. The technical success rate of the EBDs was 89.1% with a clinical efficacy of 80.8%. Complications occurred in 2.8% per procedure. After 24 months of follow-up, 73.5% of subjects underwent redilation and 42.9% surgical resection. In a multivariate analysis of 676 individual patients, a stricture length of ⩽5 cm was associated with a surgery-free outcome; every 1 cm increase of stricture length increased the hazard of need for surgery by 8% (P = 0.008). Inflammation did not affect outcomes or rate of complications. Conclusions: Based on a systematic literature review and analysis of data sets from 676 patients, EBD has a high rate of short-term technical and clinical efficacies, with substantial long-term efficacy and acceptable rates of complication.

Challenges in designing a national surveillance program for inflammatory bowel disease in the United States

Abstract:This review describes the history of U.S. government funding for surveillance programs in inflammatory bowel diseases (IBD), provides current estimates of the incidence and prevalence of IBD in the United States, and enumerates a number of challenges faced by current and future IBD surveillance programs. A rationale for expanding the focus of IBD surveillance beyond counts of incidence and prevalence, to provide a greater understanding of the burden of IBD, disease etiology, and pathogenesis, is provided. Lessons learned from other countries are summarized, in addition to potential resources that may be used to optimize a new form of IBD surveillance in the United States. A consensus recommendation on the goals and available resources for a new model for disease surveillance are provided. This new model should focus on “surveillance of the burden of disease,” including (1) natural history of disease and (2) outcomes and complications of the disease and/or treatments.

Personalized Technologies in Chronic Gastrointestinal Disorders: Self-monitoring and Remote Sensor Technologies

With increased access to high-speed Internet and smartphone devices, patients have started to use mobile applications (apps) for various health needs. These mobile apps are now increasingly used in integration with telemedicine and wearables to support fitness, health education, symptom tracking, and collaborative disease management and care coordination. More recently, evidence (especially around remote patient monitoring) has started to build in some chronic diseases, and some of the digital health technologies have received approval from the Food and Drug Administration. With the changing healthcare landscape and push for value-based care, adoption of these digital health initiatives among providers is bound to increase. Although so far there is a dearth of published evidence about effectiveness of these apps in gastroenterology care, there are ongoing trials to determine whether remote patient monitoring can lead to improvement in process metrics or outcome metrics for patients with chronic gastrointestinal diseases.

White Paper AGA: The Impact of Mental and Psychosocial Factors on the Care of Patients With Inflammatory Bowel Disease

&NA; Patients with chronic medically complex disorders like inflammatory bowel diseases (BD) often have mental health and psychosocial comorbid conditions. There is growing recognition that factors other than disease pathophysiology impact patients health and wellbeing. Provision of care that encompasses medical care plus psychosocial, environmental and behavioral interventions to improve health has been termed “whole person care” and may result in achieving highest health value. There now are multiple methods to survey patients and stratify their psychosocial, mental health and environmental risk. Such survey methods are applicable to all types of IBD programs including those at academic medical centers, independent health systems and those based within independent community practice. Once a practice determines that a patient has psychosocial needs, a variety of resources are available for referral or co‐management as outlined in this paper. Included in this white paper are examples of psychosocial care that is integrated into IBD practices plus innovative methods that provide remote patient management.

Statins Associated with Decreased Risk of New Onset Inflammatory Bowel Disease

Objectives:Prior studies suggest that medication exposures may be associated with new onset inflammatory bowel disease (IBD). The aim of this study was to determine the effect of statins on the risk of new onset IBD in a large United States health claims database.Methods:We conducted a retrospective matched case–control study with a national medical claims and pharmacy database from Source Healthcare Analytics LLC. We included any patient aged 18 or older with ICD-9 code 555.x for Crohn’s disease (CD) or 556.x for ulcerative colitis (UC) between January 2008 and December 2012. IBD patients diagnosed in 2012 were compared with the age group, gender, race, and geographically matched controls. Controls had no ICD-9 codes for CD, UC, or IBD-associated diseases and no prescriptions for IBD-related medications. New onset IBD patients were defined as having at least three separate CD or UC ICD-9 codes and no IBD-related ICD-9 or prescription before first IBD ICD-9. Statin exposure was assessed by Uniform System of Classification level 5 code. To account for diagnostic delay, exposures within 6 months of first ICD-9 were excluded. Exposures within 12 and 24 months were excluded in sensitivity analyses. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for new onset IBD, CD, and UC.Results:A total of 9,617 cases and 46,665 controls were included in the analysis. Any statin exposure was associated with a significantly decreased risk of IBD (OR 0.68, 95% CI 0.64–0.72), CD (0.64, 95% CI 0.59–0.71), and UC (OR 0.70, 95% CI 0.65–0.76). This effect was similar for most specific statins and regardless of intensity of therapy. The protective effect against new onset CD was strongest among older patients. Statins’ association with a lower risk of IBD was similar after adjusting for antibiotics, hormone replacement therapy, oral contraceptives, comorbidities, and cardiovascular medications.Conclusions:Statins may have a protective effect against new onset IBD, CD, and UC. This decreased risk is similar across most statins and appears to be stronger among older patients, particularly in CD.