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"Alexander, Jeffrey A"
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Accuracy and Safety of the Cytosponge for Assessing Histologic Activity in Eosinophilic Esophagitis: A Two-Center Study
2017
Management of eosinophilic esophagitis (EoE) requires repeated endoscopic mucosal sampling to assess disease activity. A less invasive and expensive means of monitoring of EoE is required. The objective of this study was to assess the accuracy, safety, and tolerability of the cytosponge compared to endoscopy and biopsy for histologic assessment of EoE.
In this prospective two-center cross-sectional study, patients with known EoE underwent cytosponge sampling followed by endoscopy and biopsy. Sample adequacy and eosinophil counts (eos/HPF) were determined for both cytosponge and endoscopic samples. The cytosponge was assessed for diagnostic accuracy, safety, and patient preference as compared to endoscopy.
Six patients (7%) failed to swallow the sponge. One hundred and five procedures were successfully performed in 80 patients (66% male, 100% white, 19% stricture). The cytosponge sample was adequate in 102 and the biopsy in 104; 101 procedures had adequate samples by both techniques. Fifty-seven biopsies were graded as active EoE with ≥15 eos/HPF as the gold standard. Eosinophil counts highly correlated between the biopsy and cytosponge (r=0.78, P<0.0001). Using a cutoff of ≤15 eos/HPF for inactive disease, the sensitivity and specificity of the cytosponge was 75% and 86%, respectively. Six patients had active EoE on cytosponge not found on biopsy. For biopsies with inactive EoE, the cytosponge identified 38/44. No complications occurred, and cytosponge endoscopic abrasion scores were low (0.34/4). Patients preferred cytosponge to endoscopy with higher rating scores (7.27 vs. 6.11, P=0.002).
Compared to endoscopy with biopsy, cytosponge provided a minimally invasive, safe, well tolerated, and accurate method to assess EoE histologic activity. (ClinicalTrial.gov number NCT01585103).
Journal Article
Effect of Maintenance Therapy for Eosinophilic Esophagitis on Need for Recurrent Dilation
2021
BackgroundEosinophilic esophagitis is an inflammatory condition in which eosinophil infiltration leads to esophageal remodeling and stricturing, with dilation therapy often needed. Achieving histologic remission reduces the need for repeat dilation, although little is known about the effects of long-term maintenance therapy.AimsTo further assess the relationship between short-term histologic remission and maintenance therapy on need for repeat dilation in eosinophilic esophagitis.MethodsA total of 77 patients with eosinophilic esophagitis (59.7% male; mean age 41.6 years) seen at a single medical center from June 2000 to August 2017 were included. Information on history of dilation and therapy [proton pump inhibitors (PPIs), steroids, elimination diet] was collected. Mean follow-up was 164 weeks. Fifty-one patients achieved histologic remission and 42 of these remained on maintenance therapy (23 PPIs, 14 topical steroids, and 5 dietary therapy). Standard phone interview was completed in cases with lack of follow-up. Only patients who underwent esophageal dilation to ≥ 17 mm were included.ResultsA significantly lower proportion of patients on maintenance therapy required repeat dilation (12/42) compared with patients not on maintenance therapy (8/9) (hazard ratio 0.12; p < 0.001). Of patients who received maintenance therapy, 9.1% required re-dilation. The difference in need for repeat dilation in patients who achieved histologic remission on therapy (14/26) versus those who did not (20/51) was not significant (hazard ratio 1.34; p = 0.45).ConclusionIn a retrospective analysis of patients with eosinophilic esophagitis, we found that a significantly lower proportion who received maintenance therapy (PPIs, steroids, or dietary exclusions) required repeat dilation.
Journal Article
Three-to-six month post-POEM timed barium esophagram can predict esophageal contents and may stratify aspiration risk on follow-up EGD
2025
Background
Peroral endoscopic myotomy (POEM) is an increasingly utilized endoscopic therapy for achalasia. When undergoing esophagogastroduodenoscopy (EGD), patients with a diagnosis of achalasia may receive endotracheal intubation (EI) to reduce the risk of aspiration. The risk of aspiration on post-POEM EGD should be reduced due to improved esophageal emptying. Despite history of myotomy, treated achalasia patients frequently receive EI on follow-up EGD increasing costs, procedural time, and potential risks from anesthesia. We determined if timed barium esophagram (TBE) findings three to six months after POEM predict the presence of esophageal contents on follow up endoscopy which may indicate aspiration risk.
Methods
We identified achalasia patients who underwent POEM from September 2021 to October 2023 and had both a follow-up TBE and EGD three to six months later. At our institution, all achalasia patients are instructed to avoid solid oral intake (liquids allowed) for 2 days prior to pre-and post-POEM EGD. Predictors of esophageal contents were identified and receiver operating characteristic (ROC) curves were constructed to determine column heights that correspond to the presence of esophageal contents.
Results
We identified 48 patients meeting inclusion criteria. Increasing barium column height at 5 min was associated with liquid/solid esophageal contents on EGD (OR: 1.36;
p
= 0.004). The receiver operating characteristics curve for esophageal contents demonstrated an area under the curve of 0.85 at 7 cm. Passage of a 13 mm tablet was inversely associated with the presence of esophageal contents (OR: 0.03;
p
= 0.002).
Conclusion
In post-POEM achalasia patients, follow-up TBE at 3–6 months demonstrating a 5-minute barium column height of less than 7.0 cm and passage of a 13 mm barium tablet may predict an esophagus free of liquid/solids during follow-up EGD after a 2-day solid fast. This study adds to our knowledge that TBE findings are a good predictor of esophageal emptying post-POEM, and may be used to predict which patients may be at risk of having residual esophageal contents and therefore need EI.
Journal Article
Methods and metrics challenges of delivery-system research
by
Alexander, Jeffrey A
,
Hearld, Larry R
in
Analysis
,
Debate
,
Delivery of Health Care - organization & administration
2012
Background
Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned). This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not) into the operating context of the delivery system.
Methods
The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1) modeling intervention context; (2) measuring readiness for change; (3) assessing intervention fidelity and sustainability; (4) assessing complex, multicomponent interventions; and (5) incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges.
Results and conclusions
We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory) and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the \"why\" and \"how\" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs.
A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services for presentation and discussion at a meeting on \"The Challenge and Promise of Delivery System Research,\" held in Sterling, VA, on February 16-17, 2011. The opinions in the paper are those of the author and do not represent the views or recommendations of AHRQ or the US Department of Health and Human Services.
1
Journal Article
Proton Pump Inhibitors: Review of Emerging Concerns
by
Alexander, Jeffrey A.
,
Nehra, Vandana
,
Loftus, Conor G.
in
Analysis
,
Chronic kidney failure
,
Clostridium
2018
First introduced in 1989, proton pump inhibitors (PPIs) are among the most widely utilized medications worldwide, both in the ambulatory and inpatient clinical settings. The PPIs are currently approved by the US Food and Drug Administration for the management of a variety of gastrointestinal disorders including symptomatic peptic ulcer disease, gastroesophageal reflux disease, and nonulcer dyspepsia as well as for prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy. PPIs inhibit gastric acid secretion, and the most commonly associated adverse effects include abdominal pain, diarrhea, and headache. Although PPIs have had an encouraging safety profile, recent studies regarding the long-term use of PPI medications have noted potential adverse effects, including risk of fractures, pneumonia, Clostridium difficile diarrhea, hypomagnesemia, vitamin B12 deficiency, chronic kidney disease, and dementia. These emerging data have led to subsequent investigations to assess these potential risks in patients receiving long-term PPI therapy. However, most of the published evidence is inadequate to establish a definite association between PPI use and the risk for development of serious adverse effects. Hence, when clinically indicated, PPIs can be prescribed at the lowest effective dose for symptom control.
Journal Article
A decreased abundance of clostridia characterizes the gut microbiota in eosinophilic esophagitis
2019
Abnormalities in the gut microbiome are associated with suppressed Th2 response (Belizario et al., 2018 Mediators Inflamm. 2018:2037838) and predisposition to atopic disease such as asthma and eczema. We investigated if this applies to eosinophilic esophagitis (EoE). Stool bacterial DNA was extracted and followed by 16S rRNA amplification from 12 patients with eosinophilic esophagitis and 12 controls. Alpha‐ and beta‐diversity were analyzed. Only two patients had asthma or atopy and one patient was on budesonide. No patients were on PPIs. Patients with EoE had lower gut microbiota alpha diversity (species richness, P = 0.09; Shannon index, P = 0.01). The microbial composition was distinct as evidenced by significantly different beta diversity (P = 0.03) when compared to healthy controls. There were also significant differences in relative abundance at multiple taxonomic levels when comparing the two communities; at the phylum level, we observed a marked decrease in Firmicutes and increase in Bacteroidetes and at the order and family level there were significant decreases in Clostridia and Clostridiales in patients with EoE (q ≤ 0.1). We conclude that there are significant differences in microbial community structure, microbial richness, and evenness and a significant decrease in taxa within the Clostridia in patients with EoE. Our data suggest that Clostridia based interventions could be tested as adjuncts to current therapeutic strategies in EoE. We investigated if abnormalities in the gut microbiome associated with suppressed Th2 response are present in patients with eosinophilic esophagitis. Patients with EoE had lower gut microbiota alpha diversity and a distinct microbial composition as evidenced by significantly different beta diversity, marked decrease in Firmicutes, Clostridiales and an increase in Bacteroidetes. We conclude that there are significant differences in microbial community structure, microbial richness, and evenness and a significant decrease in taxa within the Clostridia in patients with EoE. Our data suggest that Clostridia based interventions could be tested as adjuncts to current therapeutic strategies in EoE.
Journal Article
Low Grade Esophageal Eosinophilia in Adults: An Unrecognized Part of the Spectrum of Eosinophilic Esophagitis?
by
Arora, Amindra S.
,
Alexander, Jeffrey A.
,
Smyrk, Thomas C.
in
Adrenal Cortex Hormones - therapeutic use
,
Adult
,
Adults
2011
Background
Eosinophilic esophagitis (EoE) is defined by a minimum of 15 eosinophils (eos) per high-powered field (HPF) on esophageal biopsy, along with esophageal symptoms and the exclusion of gastroesophageal reflux (GERD). The clinical significance of fewer eosinophils is unknown.
Methods
Fifty-nine adult patients without a previous diagnosis of EoE with esophageal biopsies containing 1–14 eos per HPF (low grade eosinophilia) and 418 adult patients with ≥15 eos per HPF were identified by retrospective review. Patients were divided into group A (1–9 eos per HPF), group B (10–14 eos per HPF), and group C (≥15 eos per HPF) with a chart review of clinical and demographic data.
Results
While dysphagia and atopy (asthma and allergic rhinitis) were more common in patients with ≥15 eos per HPF (group C) than those with low grade esophageal eosinophilia (groups A and B) (93 vs. 88%,
P
= 0.02), food impaction and heartburn occurred at an equal frequency across all patient groups. Endoscopic findings were likewise similar between groups. Of the 14 patients with low grade esophageal eosinophilia who underwent repeat endoscopy a mean interval of 42 weeks (range 8–118 weeks) later, five (36%) met conventional diagnostic criteria for EoE of 15 or greater eos per HPF. Follow-up in ten patients treated with topical corticosteroids noted improvement in nine, with mean follow-up of 8 weeks (range 4–12 weeks).
Conclusion
Some adult patients with dysphagia and less than 15 eos per HPF have similar endoscopic findings and clinical course to patients meeting the consensus definition of EoE. Further evaluation of patients with low grade esophageal eosinophilia is needed.
Journal Article
Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse
by
Tholen Crystal
,
Ravi Karthik
,
Geno Debra
in
Autoimmune diseases
,
Esophageal diseases
,
Esophagus
2021
BackgroundIdentification of clinical predictors of response to first-line therapies for EoE is needed to guide initial medical management.Study DesignA retrospective analysis of patients diagnosed with EoE from 2011 to 2018 was conducted. Clinical and diagnostic variables including demographics, endoscopic, and esophagram findings were compared between PPI responders and PPI nonresponders. All patients underwent a standard 8-week twice-daily PPI trial, with PPI responsiveness defined as < 15 eos/hpf on repeat EGD. Univariate and multivariable analyses were conducted to identify risk factors for nonresponse, and ROC curves were created to identify cutoff values.ResultsA total of 223 EoE patients (135 male, median age 39 (29–51)) were identified, with PPI nonresponse (PPI-NR) in 71% of patients. PPI-NR was seen in all 10 patients with failure of scope passage, with an OR of 9.06 by univariate analysis (P = 0.1485). In a multivariable model, age per 10 years (OR 0.71; P = 0.007), BMI per 1 kg/m2 (OR 0.94; P = 0.03), and peripheral eosinophil count per 100 per mm3 (OR 1.37; P = 0.003) were independent risk factors. Dichotomization to maximize sensitivity and specificity identified age ≤ 36 years old, BMI ≤ 25.2 kg/m2, and peripheral eos > 460 per mm3 as predictive thresholds for PPI-NR. The probability of PPI-NR was 72.4–84.5% with 1 risk factor, 87.9–93.8% with 2 risk factors, and 97.2% with all 3 risk factors.ConclusionsYoung age, reduced BMI, elevated peripheral eosinophil count, and likely inability to pass an endoscope predict lack of response to PPIs in patients with EoE.
Journal Article
The Science of Quality Improvement Implementation: Developing Capacity to Make a Difference
by
Alexander, Jeffrey A.
,
Hearld, Larry R.
in
Benchmarking - organization & administration
,
Data collection
,
Delivery of Health Care - organization & administration
2011
Background: Quality improvement (QI) holds promise to improve quality of care; however, organizations often struggle with its implementation. It has been recommended that practitioners, managers, and researchers attempt to increase systematic understanding of the structure, practices, and context of organizations that facilitate or impede the implementation of QI innovations. Objectives: To critically review the empirical research on QI implementation in health care organizations. Research Design: A literature review of 107 studies that examined the implementation of QI innovations in health care organizations. Studies were classified into 4 groups based on the types of predictors that were assumed to affect implementation (content of QI innovation, organizational processes, internal context, and external context). Results: Internal context and organizational processes were the most frequently studied categories. External context and organizational process categories exhibited the highest rate of positive effects on QI implementation. Conclusions: The review revealed several important gaps in the QI implementation literature. Studies often lacked clear conceptual frameworks to guide the research, which may hinder efforts to compare relationships across studies. Studies also tended to adopt designs that were narrowly focused on independent effects of predictors and did not include holistic frameworks to capture interactions among the many factors involved in implementation. Other design limitations included the use of cross-sectional designs, single-source data collection, and potential selection bias among study participants.
Journal Article
Diagnostic and Therapeutic Long-term Management of Eosinophilic Esophagitis—Current Concepts and Perspectives for Steroid Use
by
Straumann, Alex
,
Greuter, Thomas
,
Katzka, David A
in
Autoimmune diseases
,
Endoscopy
,
Esophageal diseases
2018
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which requires short- and long-term treatment. In addition, patients under long-term treatment for any chronic condition should have a structured follow-up. The mainstays in EoE treatment are drugs (such as swallowed topical corticosteroids [STC] and proton pump inhibitors), dietary exclusions, and endoscopic dilations. STC are the most widely used treatment and have proven efficacy in inducing clinical, endoscopic and histological remission in active EoE. However, data regarding maintaining disease remission and long-term management are limited. Ongoing disease activity and relapses despite STC treatment are frequently observed. This sheds light on the urgent need for adequate maintenance strategies, which have not been well defined. In terms of follow-up concepts, to date neither guidelines nor consensus recommendations have been published. To summarize the current knowledge on long-term diagnostic and therapeutic STC management of EoE, we conducted a literature search using PubMed and Embase applying the following key search items: Eosinophilic esophagitis, eosinophils, esophagus, swallowed topical corticosteroids, fluticasone, budesonide, long-term, treatment, therapy, and follow-up. In addition, we present empirically developed long-term management concepts applied at two large EoE centers, with a special focus on STC treatments. Finally, we highlight areas of future research and perspectives regarding the long-term management of EoE.
Journal Article