Health Literacy Burden Is Associated With Access to Liver Transplantation.

BACKGROUND: Getting listed for liver transplantation is a complex process. Institutional health literacy may influence the ability of patients with limited educational attainment (EA) to list. As an easily accessible indicator of institutional health literacy, we measured the understandability of liver transplant center education websites and assessed whether there was any association with the percentage of low EA patients on their waitlists. METHODS: Patients on the waitlist for liver transplantation 2007-2016 were identified in Scientific Registry of Transplant Recipients. Understandability of patient education websites was assessed using the Clear Communication Index (CCI). The Centers for Disease Control and Prevention has set itself a goal CCI of 90 as being easy to understand. Low EA was defined as less than a high school education. We adjusted for center case-mix, Donor Service Area characteristics, and EA of the general population. RESULTS: Patients (84 774) were listed across 112 liver transplant centers. The median percent of waitlisted patients at each center with low EA was 11.0% (IQR, 6.6-16.8). CCI ranged from 53 to 88 and correlated with the proportion of low EA patients on the waitlist. However, CCI was not associated with the percentage of low EA in the general population. For every 1-point improvement in CCI, low EA patients increase by 0.2% (P < 0.05), translating to a 3.6% increase, or additional 3000 patients, if all centers improved their websites to CCI of 90. CONCLUSIONS: Educational websites that are easier to understand are associated with increased access to liver transplantation for patients with low EA. Lowering the health literacy burden by transplant centers may improve access to the liver transplant waitlist.

Mucosal Gene Expression in Pediatric and Adult Patients With Ulcerative Colitis Permits Modeling of Ideal Biopsy Collection Strategy for Transcriptomic Analysis.

Background: Transcriptional profiling has been performed on biopsies from ulcerative colitis patients. Limitations in prior studies include the variability introduced by inflammation, anatomic site of biopsy, extent of disease, and medications. We sought to more globally understand the variability of gene expression from patients with ulcerative colitis to advance our understanding of its pathogenesis and to guide clinical study design. Methods: We performed transcriptional profiling on 13 subjects, including pediatric and adult patients from 2 hospital sites. For each patient, we collected 6 biopsies from macroscopically inflamed tissue and 4 biopsies from macroscopically healthy-appearing tissue. Isolated RNA was used for microarray gene expression analysis utilizing Affymetrix Human Primeview microarrays. Ingenuity pathway analysis was used to assess over-representation of gene ontology and biological pathways. RNAseq was also performed, and differential analysis was assessed to compare affected vs unaffected samples. Finally, we modeled the minimum number of biopsies required to reliably detect gene expression across different subject numbers. Results: Transcriptional profiles co-clustered independently of the hospital collection site, patient age, sex, and colonic location, which parallels prior gene expression findings. A small set of genes not previously described was identified. Our modeling analysis reveals the number of biopsies and patients per cohort to yield reliable results in clinical studies. Conclusions: Key findings include concordance, including some expansion, of previously published gene expression studies and similarity among different age groups. We also established a reliable statistical model for biopsy collection for future clinical studies.

Pediatric kidney transplantation and mortality: Distance to transplant center matters.

Distance from pediatric kidney transplant centers may be a significant barrier in accessing care for patients and families, particularly due to the lower number of pediatric kidney transplant centers compared with the number of adult centers. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients to determine the effect of distance on pediatric kidney transplant waitlist outcomes. We found that distance did not play a role in the likelihood of transplantations for patients who were placed on the waitlist. However, living a greater distance from the transplant center was associated with a greater risk of death while on the waitlist. Larger volume centers attracted patients from greater distances, many of whom had other centers closer to their home. Further investigation on the role of distance to transplant center and the likelihood of being evaluated and listed for a kidney transplant would elucidate whether there are additional barriers these patients face.

Sequential Combination Therapy Versus Monotherapy: A Lack of Benefit in Time to Inflammatory Bowel Disease-Related Surgery.

BACKGROUND: The benefits of combination therapy with infliximab and azathioprine have been demonstrated in clinical trials of patients with ulcerative colitis (UC) and Crohn's disease (CD). Concerns remain regarding the ideal duration and benefits of adding therapies in a sequential manner. AIMS: We aim to compare long-term outcomes among patients with inflammatory bowel disease (IBD) treated with sequentially added combination therapy or monotherapy strategies . METHODS: We performed a retrospective cohort study involving adult patients with UC and CD. One cohort included patients treated with infliximab, adalimumab, or a thiopurine as monotherapy. A second cohort included patients treated with sequentially added combination therapy including infliximab or adalimumab and a thiopurine. The primary outcome was the rate of IBD-related surgery. RESULTS: Among 462 patients, 181 (39 %) were treated with combination therapy. 12 % of patients treated with combination therapy underwent an IBD-related surgery compared to 18 % of patients treated with monotherapy (p = 0.091), with no overall difference in time to IBD-related surgery demonstrated (log-rank test, p = 0.063). When evaluating the subtypes of IBD, there was a significant benefit in time to IBD-related surgery among patients with CD treated with sequentially added combination therapy (HR 0.46, 95 % CI 0.25-0.85) but not UC (HR 0.82, 95 % CI 0.30-2.22). CONCLUSIONS: The benefits of sequentially added combination therapy seem blunted when evaluating long-term clinical outcomes. This may be due to a decreased effectiveness of sequential combination therapy, a loss of benefit over time, or a differential effect between subtypes of IBD.

Risk Factors for Rehospitalization Within 90 Days in Patients with Inflammatory Bowel Disease.

BACKGROUND: Care of patients with inflammatory bowel disease (IBD) poses a significant burden to the health-care system. Repeat hospitalization in subgroups of IBD patients seems to be a large part of this issue; however, there are limited data examining the characteristics of these patients. The aim of this study was to characterize admission patterns in patients with IBD at a tertiary-care center and to identify preventable risk factors of 90-day readmission after an index IBD admission. METHODS: Retrospective analysis was performed extracting data from an electronic medical record over a 2-year period. RESULTS: Three hundred fifty-six patients were admitted at least once during the 2-year study period for an unplanned IBD-related reason. Of these, 48.9% were admitted once, 38.2% were admitted 2 to 4 times, and 12.9% were admitted 5 or more times during the study period. Patients with any admission within 90 days before index were excluded; n = 33. One hundred two patients had experienced a readmission by 90 days after index admission. Numerous demographic and medical factors were examined for association with readmission. The final Cox model included 3 variables: depression (HR = 1.99, 1.33-3.00), chronic pain (HR = 1.88, 1.14-3.10), and steroid use in the previous 6 months (HR = 1.33, 0.92-2.04). CONCLUSIONS: Our findings suggest that patients with depression and chronic pain are at greatest risk for a readmission within 90 days after an initial IBD admission. Disease activity, represented by steroid use in the previous 6 months, was not related to readmission. Addressing these problems in the outpatient setting may reduce future hospitalizations.

An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease.

There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD.