Feasibility and acceptability of patient- and clinician-level antithrombotic stewardship interventions to reduce gastrointestinal bleeding risk in patients using warfarin (Anticoagulation with Enhanced Gastrointestinal Safety): a factorial randomized controlled pilot trial.

Background: Overuse of antiplatelet therapy and underuse of gastroprotection contribute to preventable bleeding in patients taking anticoagulants. Objectives: (1) Determine the feasibility of a factorial trial testing patient activation and clinician outreach to reduce gastrointestinal (GI) bleeding risk in patients prescribed warfarin-antiplatelet therapy without proton pump inhibitor gastroprotection and (2) assess intervention acceptability. Methods: Pragmatic 2 × 2 factorial cluster-randomized controlled pilot comparing (1) a patient activation booklet vs usual care and (2) clinician notification vs clinician notification plus nurse facilitation was performed. The primary feasibility outcome was percentage of patients completing a structured telephone assessment after 5 weeks. Exploratory outcomes, including effectiveness, were evaluated using chart review, surveys, and semistructured interviews. Results: Among 47 eligible patients, 35/47 (74.5%; 95% CI, 58.6%-85.7%) met the feasibility outcome. In the subset confirmed to be high risk for upper GI bleeding, 11/29 (37.9%; 95% CI, 16.9%-64.7%) made a medication change, without differences between intervention arms. In interviews, few patients reported reviewing the activation booklet; barriers included underestimating GI bleeding risk, misunderstanding the booklet's purpose, and receiving excessive health communication materials. Clinicians responded to notification messages for 24/47 patients (51.1%; 95% CI, 26.4%-75.4%), which was lower for surgeons than nonsurgeons (22.7% vs 76.0%). Medical specialists but not surgeons viewed clinician notification as acceptable. Conclusion: The proposed trial design and outcome ascertainment strategy were feasible, but the patient activation intervention is unlikely to be effective as designed. While clinician notification appears promising, it may not be acceptable to surgeons, findings which support further refinement and testing of a clinician notification intervention.

Nausea, Vomiting, and Dyspepsia Following Solid Organ Abdominal Transplant.

Background and objective Multiple comorbidities may contribute to high readmission rates post-transplant procedures. In this study, we aimed to assess the rates and factors associated with hospital readmissions for dyspeptic symptoms among transplant patients. Methods This was a retrospective analysis of adult patients who underwent solid organ transplants at our institution. Pregnant patients or those patients with preexisting gastroparesis were excluded from the study. Readmissions associated with the International Classification of Diseases (ICD) codes for nausea/vomiting, weight loss, failure to thrive, abdominal pain, and/or bloating were included. Factors associated with 30-day and frequent readmissions (two or more) were explored. Results A total of 931 patients with solid organ transplants were included; 54% had undergone kidney transplants while 34% were liver transplants. Of note, 30% were readmitted within the first 30 days after discharge following transplant while 32.3% had frequent readmissions. A post-transplant upper endoscopy (EGD) was performed in 34% with food residue discovered in 19% suggesting gastroparesis. However, since only 22% of these patients had a gastric emptying study, only 6% were formally diagnosed with gastroparesis, which was independently associated with both 30-day [odds ratios (OR): 2.58, 95% confidence intervals (CI): 1.42-4.69] and frequent readmissions (OR: 6.71, 95% CI: 3.45-13.10). The presence of pre-transplant diabetes (35%) was significantly associated with a diagnosis of gastroparesis following transplant (OR: 5.17, 95% CI: 2.79-9.57). The use of belatacept (OR: 0.63, 95% CI: 0.42-0.94, p=0.023) was associated with a decrease in the odds of 30-day readmissions. Conclusion A significant number of patients were readmitted due to dyspeptic symptoms after solid organ transplants. Diabetes and gastroparesis were significantly associated with higher odds of readmissions while the use of belatacept appeared to be a protective factor.

Utilizing functional lumen imaging probe in directing treatment for post-fundoplication dysphagia.

BACKGROUND: Esophagogastric junction obstruction (EGJO) post-fundoplication (PF) is difficult to identify with currently available tests. We aimed to assess the diagnostic accuracy of EGJ opening on functional lumen imaging probe (FLIP) and dilation outcome in FLIP-detected EGJO in PF dysphagia. METHODS: We prospectively collected data on PF patients referred to Esophageal Clinic over 18 months. EGJO diagnosis was made by (a) endoscopist's description of a narrow EGJ/wrap area, (b) appearance of wrap obstruction or contrast/tablet retention on esophagram, or (c) EGJ-distensibility index (DI) < 2.8 mm2/mmHg on real-time FLIP. In patients with EGJO and dysphagia, EGJ dilation was performed to 20 mm, 30 mm, or 35 mm in a stepwise fashion. Outcome was assessed as % dysphagia improvement during phone call or on brief esophageal dysphagia questionnaire (BEDQ) score. RESULTS: Twenty-six patients were included, of whom 17 (65%) had a low EGJ-DI. No patients had a hiatal hernia greater than 3 cm. Dysphagia was the primary symptom in 17/26 (65%). In 85% (κ = 0.677) of cases, EGJ assessment (tight vs. open) was congruent between the combination of endoscopy (n = 26) and esophagram (n = 21) vs. EGJ-DI (n = 26) on FLIP. Follow-up data were available in 11 patients who had dilation based on a low EGJ-DI (4 with 20 mm balloon and 7 with ≥ 30 mm balloon). Overall, the mean % improvement in dysphagia was 60% (95% CI 37.7-82.3%, p = 0.0001). Nine out of 11 patients, including 6 out of 7 undergoing pneumatic dilation, had improvement ≥ 50% in dysphagia (mean % improvement 72.2%; 95% CI 56.1-88.4%, p = 0.0001). CONCLUSIONS AND INFERENCES: Functional lumen imaging probe is an accurate modality for evaluating for EGJ obstruction PF. FLIP may be used to select patients who may benefit from larger diameter dilation.

Recalcitrant Esophageal Stricture Secondary to Mycophenolate Mofetil.

Mycophenolate mofetil (MMF) is associated with various gastrointestinal toxicities. However, limited literature studies exist reporting MMF-related gastrointestinal toxicity manifesting as esophageal strictures. We report a case of a 62-year-old male with kidney transplant on MMF, tacrolimus, and prednisone, presenting with progressive dysphagia and odynophagia. Esophagogastroduodenoscopy revealed severe esophageal stricturing with near food bolus impaction, requiring dilations, esophageal stent, and ultimately gastrostomy tube. Biopsies revealed nonspecific inflammation with no evidence of infectious/neoplastic process; thus, our multidisciplinary esophageal group determined that the process was secondary to MMF. This case demonstrates that, though rare, MMF can result in severe esophageal strictures causing significant morbidity.

Effect of the ASCENT Intervention to Increase Knowledge of Kidney Allocation Policy Changes Among Dialysis Providers.

INTRODUCTION: The Allocation System Changes for Equity in Kidney Transplantation (ASCENT) trial was a cluster-randomized pragmatic, effectiveness-implementation study designed to test whether a multicomponent educational intervention targeting leadership, clinic staff, and patients in dialysis facilities improved knowledge and awareness of the 2014 Kidney Allocation System (KAS) change. METHODS: Participants included 690 dialysis facility medical directors, nephrologists, social workers, and other staff within 655 US dialysis facilities, with 51% (n = 334) in the intervention group and 49% (n = 321) in the control group. Intervention activities included a webinar targeting medical directors and facility staff, an approximately 10-minute educational video targeting dialysis staff, an approximately 10-minute educational video targeting patients, and a facility-specific audit and feedback report of transplant performance. The control group received a standard United Network for Organ Sharing brochure. Provider knowledge was a secondary outcome of the ASCENT trial and the primary outcome of this study; knowledge was assessed as a cumulative score on a 5-point Likert scale (higher score = greater knowledge). Intention-to-treat analysis was used. RESULTS: At baseline, nonintervention providers had a higher mean knowledge score (mean ± SD, 2.45 ± 1.43) than intervention providers (mean ± SD, 2.31 ± 1.46). After 3 months, the average knowledge score was slightly higher in the intervention (mean ± SD, 3.14 ± 1.28) versus nonintervention providers (mean ± SD, 3.07 ± 1.24), and the estimated mean difference in knowledge scores between the groups at follow-up minus the mean difference at baseline was 0.25 (95% confidence interval [CI], 0.11-0.48; P = 0.039). The effect size (0.41) was low to moderate. CONCLUSION: Dialysis facility provider education could help extend the impact of a national policy change in organ allocation.

Racial and Ethnic Differences in Diagnostic Imaging Utilization During Adult Emergency Department Visits in the United States, 2005 to 2014.

OBJECTIVE: To compare the use of medical imaging (x-ray [XR], CT, ultrasound, and MRI) in the emergency department (ED) for adult patients of different racial and ethnic groups in the United States from 2005 to 2014. METHODS: We performed a multilevel stratified regression analysis of the National Hospital Ambulatory Medical Care Survey ED Subfile, a nationally representative database of hospital-based ED visits. We examined race (white, black, Asian, other) and ethnicity (Hispanic versus non-Hispanic) as the primary exposures for the outcomes of ED medical imaging use (XR, CT, ultrasound, MRI, and any imaging). We controlled for other potential patient-level and facility-level determinants of ED imaging use. RESULTS: Approximately half (48.8%) of the 225,037 adult patient ED visits underwent imaging; 36.1% underwent XR, 16.4% CT, 4.1% ultrasound, and 0.8% MRI. White patients received imaging during 51.3% of their encounters, black patients received imaging during 43.6% of their encounters, Asians received imaging during 50.8% of their encounters, and other races received imaging during 46% of their encounters. As compared with white patients, black patients had decreased adjusted odds of receiving imaging in the ED (odds ratio [OR] = 0.86, 95% confidence interval [CI]: 0.84-0.89). Comparatively, black patients had a lower odds of CT scan (OR = 0.80, 95% CI: 0.77-0.83) or MRI (OR = 0.74, 95% CI: 0.65-0.85). Hispanic patients and Asian patients had a higher odds of receiving ultrasound (OR = 1.36, 95% CI: 1.27-1.44 and OR = 1.25, 95% CI: 1.10-1.42), respectively. IMPLICATIONS: We observed significant racial and ethnic differences in medical imaging use in the ED even after controlling for patient- and facility-level factors.

Awareness of Racial Disparities in Kidney Transplantation among Health Care Providers in Dialysis Facilities.

BACKGROUND AND OBJECTIVES: Despite the important role that health care providers at dialysis facilities have in reducing racial disparities in access to kidney transplantation in the United States, little is known about provider awareness of these disparities. We aimed to evaluate health care providers' awareness of racial disparities in kidney transplant waitlisting and identify factors associated with awareness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a cross-sectional analysis of a survey of providers from low-waitlisting dialysis facilities (n=655) across all 18 ESRD networks administered in 2016 in the United States merged with 2014 US Renal Data System and 2014 US Census data. Awareness of national racial disparity in waitlisting was defined as responding "yes" to the question: "Nationally, do you think that African Americans currently have lower waitlisting rates than white patients on average?" The secondary outcome was providers' perceptions of racial difference in waitlisting at their own facilities. RESULTS: Among 655 providers surveyed, 19% were aware of the national racial disparity in waitlisting: 50% (57 of 113) of medical directors, 11% (35 of 327) of nurse managers, and 16% (35 of 215) of other providers. In analyses adjusted for provider and facility characteristics, nurse managers (versus medical directors; odds ratio, 7.33; 95% confidence interval, 3.35 to 16.0) and white providers (versus black providers; odds ratio, 2.64; 95% confidence interval, 1.39 to 5.02) were more likely to be unaware of a national racial disparity in waitlisting. Facilities in the South (versus the Northeast; odds ratio, 3.05; 95% confidence interval, 1.04 to 8.94) and facilities with a low percentage of blacks (versus a high percentage of blacks; odds ratio, 1.86; 95% confidence interval, 1.02 to 3.39) were more likely to be unaware. One quarter of facilities had >5% racial difference in waitlisting within their own facilities, but only 5% were aware of the disparity. CONCLUSIONS: Among a limited sample of dialysis facilities with low waitlisting, provider awareness of racial disparities in kidney transplant waitlisting was low, particularly among staff who may have more routine contact with patients.

Awareness of the New Kidney Allocation System among United States Dialysis Providers with Low Waitlisting.

It is unknown whether dialysis facility staff are aware of the new kidney allocation system implemented in December 2014, which changed how deceased donor kidneys are allocated and waiting time is calculated. U.S. dialysis facilities with low annual waitlisting (<15.2%) were surveyed as part of a large randomized study. Among 653 facilities, 57.9% of staff were aware of the policy change, with medical directors (84.4%) being more aware than social workers (73.3%), facility administrators (53.1%), nurse managers (46.4%), and other staff (43.8%). Targeted education among dialysis facilities with low waitlisting may help extend the reach of the new policy.

Mutations in palmitoyl-protein thioesterase 1 alter exocytosis and endocytosis at synapses in Drosophila larvae.

Infantile-onset neuronal ceroid lipofuscinosis (INCL) is a severe pediatric neurodegenerative disorder produced by mutations in the gene encoding palmitoyl-protein thioesterase 1 (Ppt1). This enzyme is responsible for the removal of a palmitate group from its substrate proteins, which may include presynaptic proteins like SNAP-25, cysteine string protein (CSP), dynamin, and synaptotagmin. The fruit fly, Drosophila melanogaster, has been a powerful model system for studying the functions of these proteins and the molecular basis of neurological disorders like the NCLs. Genetic modifier screens and tracer uptake studies in Ppt1 mutant larval garland cells have suggested that Ppt1 plays a role in endocytic trafficking. We have extended this analysis to examine the involvement of Ppt1 in synaptic function at the Drosophila larval neuromuscular junction (NMJ). Mutations in Ppt1 genetically interact with temperature sensitive mutations in the Drosophila dynamin gene shibire, accelerating the paralytic behavior of shibire mutants at 27 °C. Electrophysiological work in NMJs of Ppt1-deficient larvae has revealed an increase in miniature excitatory junctional potentials (EJPs) and a significant depression of evoked EJPs in response to repetitive (10 hz) stimulation. Endocytosis was further examined in Ppt1-mutant larvae using FM1-43 uptake assays, demonstrating a significant decrease in FM1-43 uptake at the mutant NMJs. Finally, Ppt1-deficient and Ppt1 point mutant larvae display defects in locomotion that are consistent with alterations in synaptic function. Taken together, our genetic, cellular, and electrophysiological analyses suggest a direct role for Ppt1 in synaptic vesicle exo- and endocytosis at motor nerve terminals of the Drosophila NMJ.