Huiping Xu

Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease

Background:New treatments are needed as Clostridium difficile infection (CDI) is becoming increasingly formidable. Fecal microbiota transplantation (FMT) has a 90% success rate in the treatment of recurrent CDI. However, evidence regarding its safety, efficacy, and effect on disease activity in patients with inflammatory bowel disease (IBD) is lacking. Methods:This cohort study used data from 8 national and international academic centers. Patients with established IBD who underwent FMT for recurrent CDI were followed for a minimum of 3 months. The primary outcome was CDI recurrence at 3 months after FMT. The secondary outcomes were (1) IBD activity and severity at 3 months based on the judgment of the treating physician, endoscopic findings, and clinical disease activity scores; and (2) safety. Results:Sixty-seven patients were included in the analysis. Thirty-five (52%) had Crohns disease, 31 (46%) ulcerative colitis, and one indeterminate colitis with 43 (64%) patients on an immunosuppressive agent at the time of FMT. The initial FMT was successful in 53 (79%) patients. After the FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%), and worse in 9 (13%) patients. Serious adverse events included colectomy (1.4%), hospitalization for CDI (2.9%), hospitalization for IBD flare (2.9%), small bowel obstruction (1.4%), CMV colitis (1.4%), and pancreatitis (1.4%). Discussion:The overall CDI cure rates were high, with a large percentage of patients experiencing clinical improvement of their IBD after FMT. A minority of patients developed an IBD flare. No severe adverse events directly attributable to FMT were found in this largest reported series of recurrent or refractory CDI patients with concurrent IBD.

Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution: A Randomized Clinical Trial

IMPORTANCE Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution. OBJECTIVE To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution. DESIGN, SETTING, AND PARTICIPANTS Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded. INTERVENTIONS Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence. MAIN OUTCOMES AND MEASURES Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of -15%. RESULTS There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, -3.0% to ∞; P < .001). Given the prespecified noninferiority margin of -15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46; P < .001). CONCLUSIONS AND RELEVANCE Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01221311.

Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study.

OBJECTIVES:Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10–20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure.METHODS:Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model.RESULTS:Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4±19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26–15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55–9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18–1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1–2 indicating moderate risk, and ≥3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66±18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort.CONCLUSIONS:Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.

Effect of oral capsule– vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: A randomized clinical trial

Importance Fecal microbiota transplantation (FMT) is effective in preventing recurrent Clostridium difficile infection (RCDI). However, it is not known whether clinical efficacy differs by route of delivery. Objective To determine whether FMT by oral capsule is noninferior to colonoscopy delivery in efficacy. Design, Setting, and Participants Noninferiority, unblinded, randomized trial conducted in 3 academic centers in Alberta, Canada. A total of 116 adult patients with RCDI were enrolled between October 2014 and September 2016, with follow-up to December 2016. The noninferiority margin was 15%. Interventions Participants were randomly assigned to FMT by capsule or by colonoscopy at a 1:1 ratio. Main Outcomes and Measures The primary outcome was the proportion of patients without RCDI 12 weeks after FMT. Secondary outcomes included (1) serious and minor adverse events, (2) changes in quality of life by the 36-Item Short Form Survey on a scale of 0 (worst possible quality of life) to 100 (best quality of life), and (3) patient perception on a scale of 1 (not at all unpleasant) to 10 (extremely unpleasant) and satisfaction on a scale of 1 (best) to 10 (worst). Results Among 116 patients randomized (mean [SD] age, 58 [19] years; 79 women [68%]), 105 (91%) completed the trial, with 57 patients randomized to the capsule group and 59 to the colonoscopy group. In per-protocol analysis, prevention of RCDI after a single treatment was achieved in 96.2% in both the capsule group (51/53) and the colonoscopy group (50/52) (difference, 0%; 1-sided 95% CI, −6.1% to infinity; P < .001), meeting the criterion for noninferiority. One patient in each group died of underlying cardiopulmonary illness unrelated to FMT. Rates of minor adverse events were 5.4% for the capsule group vs 12.5% for the colonoscopy group. There was no significant between-group difference in improvement in quality of life. A significantly greater proportion of participants receiving capsules rated their experience as “not at all unpleasant” (66% vs 44%; difference, 22% [95% CI, 3%-40%]; P = .01). Conclusions and Relevance Among adults with RCDI, FMT via oral capsules was not inferior to delivery by colonoscopy for preventing recurrent infection over 12 weeks. Treatment with oral capsules may be an effective approach to treating RCDI. Trial Registration clinicaltrials.gov Identifier: NCT02254811

Volume of home- and community-based Medicaid waiver services and risk of hospital admissions.

OBJECTIVES: To evaluate whether type and volume of Medicaid Home‐ and Community‐Based Services (HCBS) waiver program are associated with risk of hospitalization and whether this association changes over time.

A Probit Latent Class Model with General Correlation Structures for Evaluating Accuracy of Diagnostic Tests

Traditional latent class modeling has been widely applied to assess the accuracy of dichotomous diagnostic tests. These models, however, assume that the tests are independent conditional on the true disease status, which is rarely valid in practice. Alternative models using probit analysis have been proposed to incorporate dependence among tests, but these models consider restricted correlation structures. In this article, we propose a probit latent class model that allows a general correlation structure. When combined with some helpful diagnostics, this model provides a more flexible framework from which to evaluate the correlation structure and model fit. Our model encompasses several other PLC models but uses a parameter-expanded Monte Carlo EM algorithm to obtain the maximum-likelihood estimates. The parameter-expanded EM algorithm was designed to accelerate the convergence rate of the EM algorithm by expanding the complete-data model to include a larger set of parameters and it ensures a simple solution in fitting the PLC model. We demonstrate our estimation and model selection methods using a simulation study and two published medical studies.

Lower provider volume is associated with higher failure rates for endoscopic retrograde cholangiopancreatography

Background:Among physicians who perform endoscopic retrograde cholangiopancreatography (ERCP), the relationship between procedure volume and outcome is unknown. Objective:Quantify the ERCP volume-outcome relationship by measuring provider-specific failure rates, hospitalization rates, and other quality measures. Research Design:Retrospective cohort. Subjects:A total of 16,968 ERCPs performed by 130 physicians between 2001 and 2011, identified in the Indiana Network for Patient Care. Measures:Physicians were classified by their average annual Indiana Network for Patient Care volume and stratified into low (<25/y) and high (≥25/y). Outcomes included failed procedures, defined as repeat ERCP, percutaneous transhepatic cholangiography or surgical exploration of the bile duct⩽7 days after the index procedure, hospitalization rates, and 30-day mortality. Results:Among 15,514 index ERCPs, there were 1163 (7.5%) failures; the failure rate was higher among low (9.5%) compared with high volume (5.7%) providers (P<0.001). A second ERCP within 7 days (a subgroup of failure rate) occurred more frequently when the original ERCP was performed by a low-volume (4.1%) versus a high-volume physician (2.3%, P=0.013). Patients were more frequently hospitalized within 24 hours when the ERCP was performed by a low-volume (28.3%) versus high-volume physician (14.8%, P=0.002). Mortality within 30 days was similar (low=1.9%, high=1.9%). Among low-volume physicians and after adjusting, the odds of having a failed procedure decreased 3.3% (95% confidence interval, 1.6%–5.0%, P<0.001) with each additional ERCP performed per year. Conclusions:Lower provider volume is associated with higher failure rate for ERCP, and greater need for postprocedure hospitalization.

Insufficient Help for Activity of Daily Living Disabilities and Risk of All‐Cause Hospitalization

To determine whether insufficient help for activity of daily living (ADL) disability, a potentially modifiable condition, significantly increases disabled older adults’ risk of future hospital admissions.

Multi-center colonoscopy quality measurement utilizing natural language processing

Background:An accurate system for tracking of colonoscopy quality and surveillance intervals could improve the effectiveness and cost-effectiveness of colorectal cancer (CRC) screening and surveillance. The purpose of this study was to create and test such a system across multiple institutions utilizing natural language processing (NLP).Methods:From 42,569 colonoscopies with pathology records from 13 centers, we randomly sampled 750 paired reports. We trained (n=250) and tested (n=500) an NLP-based program with 19 measurements that encompass colonoscopy quality measures and surveillance interval determination, using blinded, paired, annotated expert manual review as the reference standard. The remaining 41,819 nonannotated documents were processed through the NLP system without manual review to assess performance consistency. The primary outcome was system accuracy across the 19 measures.Results:A total of 176 (23.5%) documents with 252 (1.8%) discrepant content points resulted from paired annotation. Error rate within the 500 test documents was 31.2% for NLP and 25.4% for the paired annotators (P=0.001). At the content point level within the test set, the error rate was 3.5% for NLP and 1.9% for the paired annotators (P=0.04). When eight vaguely worded documents were removed, 125 of 492 (25.4%) were incorrect by NLP and 104 of 492 (21.1%) by the initial annotator (P=0.07). Rates of pathologic findings calculated from NLP were similar to those calculated by annotation for the majority of measurements. Test set accuracy was 99.6% for CRC, 95% for advanced adenoma, 94.6% for nonadvanced adenoma, 99.8% for advanced sessile serrated polyps, 99.2% for nonadvanced sessile serrated polyps, 96.8% for large hyperplastic polyps, and 96.0% for small hyperplastic polyps. Lesion location showed high accuracy (87.0–99.8%). Accuracy for number of adenomas was 92%.Conclusions:NLP can accurately report adenoma detection rate and the components for determining guideline-adherent colonoscopy surveillance intervals across multiple sites that utilize different methods for reporting colonoscopy findings.

Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach

ABSTRACT Severe and severe-complicated Clostridium difficile infection (CDI) is associated with high morbidity and mortality. Colectomy is standard of care; however, post-surgical mortality rates approach 50%. Case reports suggest fecal microbiota transplant (FMT) is a promising treatment of severe and severe-complicated disease but there is a paucity of data. Here, we present a single center experience with a novel sequential FMT protocol for patients refractory to maximal medical therapy. This approach consists of at least one FMT delivered via colonoscopy with criteria for repeat FMT and continued vancomycin therapy based on clinical response and pseudomembranes. Our cohort included 57 consecutive inpatients diagnosed with severe or severe-complicated CDI and treated with FMT. Overall, 91% (52/57) experienced clinical cure at 1 month with a 100% cure rate among severe CDI (n = 19) patients and an 87% cure rate for severe-complicated CDI (n = 33) patients. For the cohort, the survival rate was 94.7% at 1 month and 78.6% at 3 months. There were no serious adverse events related to FMT including no procedure-related complications or perforation. There was no difference in outcome between fresh or frozen fecal material. Sequential FMT for inpatients with severe or severe-complicated CDI is promising and may be preferred over colectomy in certain patients.