Yecheskel Schneider

Association Between Cirrhosis and Stroke in a Nationally Representative Cohort

Importance Cirrhosis is associated with hemorrhagic and thrombotic extrahepatic complications. The risk of cerebrovascular complications is less well understood. Objective To investigate the association between cirrhosis and various stroke types. Design, Setting, and Participants We performed a retrospective cohort study using inpatient and outpatient Medicare claims data from January 1, 2008, through December 31, 2014, for a random 5% sample of 1 618 059 Medicare beneficiaries older than 66 years. Exposures Cirrhosis, as defined by a validated diagnosis code algorithm. Main Outcomes and Measures The primary outcome was stroke, and secondary outcomes were ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage as defined by validated diagnosis code algorithms. Results Among 1 618 059 beneficiaries, 15 586 patients (1.0%) had cirrhosis (mean [SD] age, 74.1 [6.9] years; 7263 [46.6%] female). During a mean (SD) of 4.3 (1.9) years of follow-up, 77 268 patients were hospitalized with a stroke. The incidence of stroke was 2.17% (95% CI, 1.99%-2.36%) per year in patients with cirrhosis and 1.11% (95% CI, 1.10%-1.11%) per year in patients without cirrhosis. After adjustment for demographic characteristics and stroke risk factors, patients with cirrhosis had a higher risk of stroke (hazard ratio [HR], 1.4; 95% CI, 1.3-1.5). The magnitude of association appeared to be higher for intracerebral hemorrhage (HR, 1.9; 95% CI, 1.5-2.4) and subarachnoid hemorrhage (HR, 2.4; 95% CI, 1.7-3.5) than for ischemic stroke (HR, 1.3; 95% CI, 1.2-1.5). Conclusions and Relevance In a nationally representative sample of Medicare beneficiaries, cirrhosis was associated with an increased risk of stroke, particularly hemorrhagic stroke. A potential explanation of these findings implicates the mixed coagulopathy observed in cirrhosis.

Single Delivery of High-diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis.

Background: Recent trials suggest fecal microbiota transplantation (FMT) with repeated enemas and high-diversity FMT donors is a promising treatment to induce remission in ulcerative colitis. Methods: We designed a prospective, open-label pilot study to assess the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active ulcerative colitis using a 2-donor fecal microbiota preparation (FMP). Safety and clinical endpoints of response, remission, and mucosal healing at week 4 were assessed. Fecal DNA and rectal biopsies were used to characterize the microbiome and mucosal CD4+ T cells, respectively, before and after FMT. Results: Of the 20 patients enrolled in this study, 7 patients (35%) achieved a clinical response by week 4. Three patients (15%) were in remission at week 4 and 2 of these patients (10%) achieved mucosal healing. Three patients (15%) required escalation of care. No serious adverse events were observed. Microbiome analysis revealed that restricted diversity of recipients pre-FMT was significantly increased by high-diversity 2-donor FMP. The microbiome of recipients post-transplant was more similar to the donor FMP than the pretransplant recipient sample in both responders and nonresponders. Notably, donor composition correlated with clinical response. Mucosal CD4+ T-cell analysis revealed a reduction in both Th1 and regulatory T-cells post-FMT. Conclusions: High-diversity, 2-donor FMP delivery by colonoscopy seems safe and effective in increasing fecal microbial diversity in patients with active ulcerative colitis. Donor composition correlated with clinical response and further characterization of immunological parameters may provide insight into factors influencing clinical outcome.

Discharge Disposition After Stroke in Patients With Liver Disease

Background and Purpose— Liver disease is associated with both hemorrhagic and thrombotic processes, including an elevated risk of intracranial hemorrhage. We sought to assess the relationship between liver disease and outcomes after stroke, as measured by discharge disposition. Methods— Using administrative claims data, we identified a cohort of patients hospitalized with stroke in California, Florida, and New York from 2005 to 2013. The predictor variable was liver disease. All diagnoses were defined using validated diagnosis codes. Ordinal logistic regression was used to analyze the association between liver disease and worsening discharge disposition: home, nursing/rehabilitation facility, or death. Secondarily, multiple logistic regression was used to analyze the association between liver disease and in-hospital mortality. Models were adjusted for demographics, vascular risk factors, and comorbidities. Results— We identified 121u2009428 patients with intracerebral hemorrhage and 703u2009918 with ischemic stroke. Liver disease was documented in 13u2009584 patients (1.7%). Liver disease was associated with worse discharge disposition after both intracerebral hemorrhage (global odds ratio, 1.28; 95% confidence interval, 1.19–1.38) and ischemic stroke (odds ratio, 1.23; 95% confidence interval, 1.17–1.29). Similarly, liver disease was associated with in-hospital death after both intracerebral hemorrhage (odds ratio, 1.33; 95% confidence interval, 1.23–1.44) and ischemic stroke (odds ratio, 1.60; 95% confidence interval, 1.51–1.71). Conclusions— Liver disease was associated with worse hospital discharge disposition and in-hospital mortality after stroke, suggesting worse functional outcomes.

Delays in Initiating Post-operative Prophylactic Biologic Therapy Are Common Among Crohn’s Disease Patients

BackgroundStudies have shown that prophylactic biologic therapy can reduce post-surgical Crohn’s disease recurrence.AimsWe aimed to identify the frequency of delay and risk factors associated with a delay in the initiation of prophylactic post-surgical biologic therapy in high-risk patients.MethodsWe performed a cohort study of Crohn’s disease patients who underwent a bowel resection. We identified those at risk of recurrence and explored multiple characteristics for those with and without a delay post-operatively.ResultsA total of 84 patients were included in our analysis of which 69.0% had a greater than 4-week delay and 56.0% a greater than 8-week delay in post-surgical biologic prophylaxis. Publicly insured patients had a 100% delay in post-surgical prophylaxis initiation (pu2009=u20090.039, pu2009=u20090.003 at 4 and 8xa0weeks, respectively). Patients on a biologic pre-surgery were less likely to have a delay (pu2009<u20090.001) in post-operative prophylaxis. Care at an inflammatory bowel disease (IBD) center was associated with timely therapy when considering a post-operative immunomodulator or biologic strategy.ConclusionsThere are a substantial number of delays in initiating post-operative prophylactic biologic therapy in high-risk patients. Identifying susceptible patients by insurance type or absence of pre-operative therapy can focus future improvement efforts. Additionally, consultation with IBD-specialized providers should be considered in peri-surgical IBD care.

Premedication Use in Preventing Acute Infliximab Infusion Reactions in Patients with Inflammatory Bowel Disease: A Single Center Cohort Study

Background: Infliximab (IFX) is commonly used in patients with inflammatory bowel disease. One common side effect of IFX is an acute infusion reaction. Despite the lack of evidence supporting their use, clinicians use various premedications to prevent acute reactions. We evaluated the effectiveness of premedications in the prevention of acute IFX infusion reactions. Methods: A retrospective cohort study was performed identifying patients with a diagnosis of inflammatory bowel disease who received IFX at our institution. Information about each IFX infusion was recorded, including the dose, infusion rate, use of premedications, and any reactions. Infusions were stratified into low and high risk. In the high- and low-risk groups, the relative risk was calculated for each premedication combination used in our institution. Results: Seven hundred seventy-three patients were identified; 578 patients (7090 infusions) met inclusion criteria and were included for analysis. Nine hundred eighty-six high-risk infusions were isolated; 620 (62.8%) of these infusions were administered with premedications (diphenhydramine and/or hydrocortisone) and 53 (5.4%) reactions occurred. Six thousand one hundred four low-risk infusions were identified; 2253 (36.9%) of these infusions had premedications and 61 (1.0%) reactions occurred. In both groups, none of the premedications used resulted in a significantly lower reaction rate compared with no premedication use. Conclusions: In both the high- and low-risk cohorts in this study, premedication use was not effective in reducing the rate of acute IFX reactions. Given this, routine premedication use is not recommended without future randomized control trials to demonstrate efficacy.

P-057 Harvey-Bradshaw Index Captures Clinical Efficacy of Vedolizumab Induction Therapy for Active Crohnʼs Disease

Background:Vedolizumab, a humanized monoclonal antibody that specifically recognizes the &agr;4&bgr;7 integrin, is currently indicated for achieving clinical response and remission in adult patients with moderately to severely active Crohns disease (CD). Recent results from the GEMINI 2 trial revealed the efficacy of vedolizumab in inducing and maintaining remission (CDAI <150), but not clinical response (CDAI-100) at week 6 and week 52. Subsequent analysis of patients who failed anti-TNF&agr; treatment (GEMINI 3) revealed statistically significant changes in CDAI-100 at weeks 6 and 10. Validation of these data are difficult given the cumbersome nature of CDAI recording in clinical practice. The Harvey-Bradshaw Index (HBI), which correlates strongly with CDAI, provides a clinically validated disease activity score that allows physicians to rapidly capture disease activity index in a clinical setting; however data evaluating the efficacy of the HBI in capturing clinical response in CD is limited. The aim of this study is to use the HBI to evaluate the clinical efficacy of vedolizumab in moderate to severe Crohns patients following induction therapy. Methods:A retrospective cohort analysis was conducted in moderate to severe CD patients treated with vedolizumab at the Jill Roberts Center for IBD at Weill Cornell Medical College from July 2014 through May 2015. Vedolizumab induction therapy was administered at 0, 2, and 6 weeks. HBI was recorded at week 0 and at the first post-induction visit (week 10 or 14) to assess clinical efficacy. Clinical response was defined as a decrease in the HBI ≥3 and clinical remission as HBI ⩽4. Results:Thirty patients were included in the study (47% male, average disease duration 17.5 years). The majority of patients, 83%, were anti-TNF&agr; failures. At the first post-induction visit, 60% (18/30) and 37% (11/30), achieved clinical response and clinical remission with an average decrease in HBI of 3.7 (P = 0.0001). No significant decreases in the HBI subscore of extra-intestinal complications (53% versus 43%, P = 0.2) or ESR and CRP were observed in the first post-induction visit (ESR 26.5 versus 22.6, P = 0.53; CRP 2.48 versus 3.28, P = 0.54) suggesting potential discordance with extra-intestinal manifestations and conventional systemic biomarkers. Conclusions:These data support the efficacy of vedolizumab in anti-TNF&agr; experienced patients and suggest that HBI is an effective clinical disease index to use in monitoring improvement following vedolizumab induction therapy.