Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage.

Heart development is exquisitely sensitive to the precise temporal regulation of thousands of genes that govern developmental decisions during differentiation. However, we currently lack a detailed understanding of how chromatin and gene expression patterns are coordinated during developmental transitions in the cardiac lineage. Here, we interrogated the transcriptome and several histone modifications across the genome during defined stages of cardiac differentiation. We find distinct chromatin patterns that are coordinated with stage-specific expression of functionally related genes, including many human disease-associated genes. Moreover, we discover a novel preactivation chromatin pattern at the promoters of genes associated with heart development and cardiac function. We further identify stage-specific distal enhancer elements and find enriched DNA binding motifs within these regions that predict sets of transcription factors that orchestrate cardiac differentiation. Together, these findings form a basis for understanding developmentally regulated chromatin transitions during lineage commitment and the molecular etiology of congenital heart disease.

Esophageal Self-Dilation in Benign Refractory Esophageal Strictures: Outcomes from a Randomized Controlled Trial and a Prospective Observational Study.

BACKGROUND: Patients with benign esophageal strictures may not maintain a response to endoscopic dilation, stenting, incisional or injectional therapies. For patients with these refractory esophageal strictures, esophageal self-dilation therapy (ESDT), performed to maintain luminal patency, may provide persistent symptomatic benefit while reducing patients' reliance on healthcare services and the risk associated with repeated endoscopic procedures. AIMS: The aim of this study was to evaluate the efficacy and safety of EDST in a randomized controlled trial and prospective observational study. METHODS: Twenty-five patients with refractory benign esophageal strictures were recruited at two esophageal clinics between November 2018 and June 2021. Twelve patients participated in the randomized trial and 13 in the prospective observational study. The number of endoscopic dilations, impact of therapy on dysphagia, adverse events, and complications were recorded. RESULTS: In the randomized study, 50% of patients performing ESDT and 100% of controls required endoscopic dilation during follow-up (P = 0.02). In the observational study, the median (IQR) number of endoscopic dilations fell from 7 [7-10] in the 6 months prior to commencing ESDT to 1 [0-2] in the 6 months after (P < 0.0001). Most patients (22/25) were able to learn self-dilation. Few serious adverse events were noted. Dysphagia severity remained unchanged or improved. CONCLUSIONS: ESDT appears to be a safe effective therapy for benign esophageal strictures refractory to endoscopic treatment. CLINICAL TRIAL NUMBER: NCT03738566.

Use of the Esophageal Sponge in Directing Food Reintroduction in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Dietary therapy is successful in eosinophilic esophagitis (EoE) but requires multiple upper endoscopies. The aim of this study was to determine if food reintroduction in EoE can be directed by minimally-invasive esophageal sponge cytology. METHODS: In this prospective non-blinded trial, 22 responders to 6-food elimination diets underwent sequential food reintroduction guided by esophageal sponge cytology. Foods were reintroduced followed by unsedated esophageal sponge cytology assessment. A food trigger was defined by sponge cytology peak eosinophil count of ≥15 eos/high-powered field (hpf). Symptoms (EoE symptom activity index [EEsAI]), endoscopic score (EoE endoscopic reference score [EREFS]), and biopsy histology (peak eosinophil count) were collected pre-dietary therapy and post-dietary therapy, and then 4 weeks post food reintroduction. RESULTS: The EEsAI and EREFS were similar post-dietary therapy to post-food reintroduction: 12.0 (interquartile range [IQR], 0.0-27.0) vs 16.5 (IQR, 9.0-28.8) (P = .265) and 1.5 (IQR, 0.2-3.0) vs 1.0 (IQR, 0.0-2.0) (P = .185). However, the peak eosinophil count was increased post-food reintroduction compared with post-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 2.0 (IQR, 1.0-4.0) (P < .001), suggesting a failure of identification of all food triggers. The peak eosinophil count was lower post-food reintroduction compared with pre-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 52.0 (IQR, 30.8-76.2) (P = .008). At the post food reintroduction evaluation, sponge cytology and biopsy histology were in agreement in 59% (13/22) of cases using a cutoff of <15 eos/hpf and 68% (15/22) of cases using a cutoff of <6 eos/hpf. CONCLUSIONS: In the first study to evaluate a non-endoscopic technique in the clinical management of EoE, the esophageal sponge was moderately successful at guiding food reintroduction in EoE dietary responders in the outpatient setting. CLINICALTRIALS: gov, Number NCT02599558.

A novel blood-sensing capsule for rapid detection of upper GI bleeding: a prospective clinical trial.

BACKGROUND AND AIMS: Upper GI bleeding (UGIB) is a common medical emergency associated with high resource utilization, morbidity, and mortality. Timely EGD can be challenging from personnel, resource, and access perspectives. PillSense (EnteraSense Ltd, Galway, Ireland) is a novel swallowed bleeding sensor for the detection of UGIB, anticipated to aid in patient triage and guide clinical decision-making for individuals with suspected UGIB. METHODS: This prospective, open-label, single-arm comparative clinical trial of a novel bleeding sensor for patients with suspected UGIB was performed at a tertiary care center. The PillSense system consists of an optical sensor and an external receiver that processes and displays data from the capsule as "Blood Detected" or "No Blood Detected." Patients underwent EGD within 4 hours of capsule administration; participants were followed up for 21 days to confirm capsule passage. RESULTS: A total of 126 patients were accrued to the study (59.5% male; mean age, 62.4 ± 14.3 years). Sensitivity and specificity for detecting the presence of blood were 92.9% (P = .02) and 90.6% (P < .001), respectively. The capsule's positive and negative predictive values were 74.3% and 97.8%, and positive and negative likelihood ratios were 9.9 and .08. No adverse events or deaths occurred related to the PillSense system, and all capsules were excreted from patients on follow-up. CONCLUSIONS: The PillSense system is safe and effective for detecting the presence of blood in patients evaluated for UGIB before upper GI endoscopy. It is a rapidly deployed tool, with easy-to-interpret results that will affect the diagnosis and triage of patients with suspected UGIB. (Clinical trial registration number: NCT05385224.).

Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

BACKGROUND: The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. AIMS: (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). METHODS: Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. RESULTS: EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. CONCLUSION: The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

6K1, NIa-VPg, NIa-Pro, and CP of Wheat Streak Mosaic Virus Are Collective Determinants of Wheat Streak Mosaic Disease in Wheat.

Wheat streak mosaic virus (WSMV; genus Tritimovirus, family Potyviridae) is the causal agent of the most economically important wheat streak mosaic disease of wheat (Triticum aestivum) in the Great Plains region of the United States. WSMV determinants responsible for wheat streak mosaic disease in wheat are unknown. Triticum mosaic virus (TriMV), a wheat-infecting virus, was used as an expression vector for the transient expression of each of the WSMV-encoded cistrons in wheat. WSMV-encoded 6K1, NIa-VPg, NIa-Pro, and CP cistrons in TriMV elicited symptoms specific to different stages of wheat streak mosaic disease without significantly affecting the genomic RNA accumulation. WSMV 6K1 produced early wheat streak mosaic disease-like symptoms of severe chlorotic streaks and patches. NIa-VPg and CP caused severe chlorotic streaks, followed by moderate stunting (only with NIa-VPg) of wheat, mimicking early- and mid-stage symptoms of wheat streak mosaic disease. WSMV NIa-Pro caused mild chlorotic streaks, followed by dark green leaves with severe stunting, representing the late symptoms of wheat streak mosaic disease. Collectively, these data suggest that cumulative effects of WSMV-encoded 6K1, NIa-VPg, NIa-Pro, and CP are responsible for different stages of wheat streak mosaic disease symptoms in wheat. Furthermore, deletion analysis of wheat streak mosaic disease determinants revealed that complete 6K1 and NIa-Pro, amino acids 3 to 60 and 121 to 197 of NIa-VPg, and amino acids 101 to 294 of CP are responsible for wheat streak mosaic disease-like symptoms in wheat. This study suggests that management strategies for wheat streak mosaic disease in wheat should target WSMV determinants of the disease phenotype.

Flexible endoscopic Zenker's diverticulotomy - A retrospective review of outcomes in 75 patients.

OBJECTIVE: Flexible endoscopic Zenker's diverticulotomy (FEZD) is a procedure performed primarily by gastroenterologists for treatment of symptomatic Zenker's diverticulum (ZD). Given the lack of prior investigations with large sample sizes, we report on one of the largest series of patients who underwent FEZD. METHODS: A review of patients who underwent FEZD at our institution from 2006 to 2021 was performed. Data were abstracted for patient demographics, clinical features, procedural characteristics, adverse events, and outcomes. RESULTS: A total of 75 patients (37 women) with mean age of 77.9 (33-102) years and mean (range) follow-up of 1.1 (0-13.2) years were identified. 67.9 % of FEZD cases were performed under general anesthesia. The mean procedure time was 37.1 min. Same day discharge and resumption of oral intake was seen in 56.4 % and 57.1 % of cases, respectively. Adverse events included intraprocedural bleeding (15.7 %) controlled with endoscopic means, infection (4.8 %) exclusively managed with antibiotics in all but one case, subcutaneous emphysema (2.4 %), and perforation (10.7 %) conservatively managed in all but one case. 97.6 % of patients had sustained subjective improvement in symptoms following their procedure. Fifteen patients (20 %) experienced recurrence after undergoing initial FEZD-26.7 % percent of whom were sufficiently treated with repeat FEZDs. Younger age was associated with recurrence (p < 0.01). CONCLUSION: FEZD is an effective, safe procedure for the management of symptomatic ZD. It is a viable alternative for patients in whom otorhinolaryngological procedures via rigid endoscopy are not an option.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Reliability and responsiveness of endoscopic disease activity assessment in eosinophilic esophagitis.

BACKGROUND AND AIMS: Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. METHODS: Modified Research and Development/University of California Los Angeles appropriateness methods and a panel of 15 international EoE experts identified endoscopic items and definitions with face validity that were used in a 2-round voting process to define simplified (all items graded as absent or present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intrarater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]) were evaluated using paired endoscopy video assessments of 2 blinded central readers in patients before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). RESULTS: The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions and grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs of .472-.736 and .469-.763, respectively) and moderate-to-almost perfect intrarater reliability (ICCs of .580-.828 and .581-.828, respectively). Strictures were least reliably assessed (ICC, .072-.385). The original EREFS was highly responsive (SES, 1.126 [95% confidence interval {CI}, .757-1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows: SES, 1.229 [95% CI, .858-1.643]; all items expanded: SES, 1.252 [95% CI, .880-1.667]). The EREFS and its modifications were not more reliably scored by segment and also not more responsive when proximal and distal EREFSs were summed. CONCLUSIONS: EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness.

Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference.

Endoscopy plays a critical role in caring for and evaluating the patient with eosinophilic esophagitis (EoE). Endoscopy is essential for diagnosis, assessment of response to therapy, treatment of esophageal strictures, and ongoing monitoring of patients in histologic remission. To date, less-invasive testing for identifying or grading EoE severity has not been established, whereas diagnostic endoscopy as integral to both remains the criterion standard. Therapeutic endoscopy in patients with adverse events of EoE may also be required. In particular, dilation may be essential to treat and attenuate progression of the disease in select patients to minimize further fibrosis and stricture formation. Using a modified Delphi consensus process, a group of 20 expert clinicians and investigators in EoE were assembled to provide guidance for the use of endoscopy in EoE. Through an iterative process, the group achieved consensus on 20 statements yielding comprehensive advice on tissue-sampling standards, gross assessment of disease activity, use and performance of endoscopic dilation, and monitoring of disease, despite an absence of high-quality evidence. Key areas of controversy were identified when discussions yielded an inability to reach agreement on the merit of a statement. We expect that with ongoing research, higher-quality evidence will be obtained to enable creation of a guideline for these issues. We further anticipate that forthcoming expert-generated and agreed-on statements will provide valuable practice advice on the role and use of endoscopy in patients with EoE.

Histologic response to steroids in eosinophilic esophagitis is dependent on delivery compound.

Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study.

BACKGROUND & AIMS: Data evaluating efficacy of different doses of swallowed topical corticosteroids (STC) in the long-term management of eosinophilic esophagitis (EoE) are lacking. We assessed long-term effectiveness and safety of different STC doses for adults with EoE after achievement of histological remission. METHODS: We performed a retrospective multicenter study at five EoE referral centers (US and Switzerland). We analyzed data on 82 patients with EoE in histological remission and ongoing STC treatment with therapeutic adherence of ≥75% (58 males; mean age at diagnosis, 37.2±14.4 years). Patients were followed for a median of 2.2 years (interquartile range [IQR], 1.0-3.8 years). We collected data from 217 follow-up endoscopy visits. The primary endpoint was time to histological relapse. RESULTS: Histological relapse occurred in 67% of patients. Relapse rates were comparable in patients taking low dose (≤0.5 mg per day, n = 58) and high dose STC (>0.5 mg per day, n = 24) with 72 vs 54% (ns). However, histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030). There was no difference regarding rates of and time to stricture formation for low vs high dose STC. Esophageal candidiasis was observed in 6% of patients (5% for low dose, 8% for high dose, ns). No dysplasia or mucosal atrophy was detected. CONCLUSION: Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small.

Effect of Maintenance Therapy for Eosinophilic Esophagitis on Need for Recurrent Dilation.

BACKGROUND: Eosinophilic 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. AIMS: To further assess the relationship between short-term histologic remission and maintenance therapy on need for repeat dilation in eosinophilic esophagitis. METHODS: A 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. RESULTS: A 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). CONCLUSION: In 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.

Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse.

BACKGROUND: Identification of clinical predictors of response to first-line therapies for EoE is needed to guide initial medical management. STUDY DESIGN: A 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. RESULTS: A 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. CONCLUSIONS: Young age, reduced BMI, elevated peripheral eosinophil count, and likely inability to pass an endoscope predict lack of response to PPIs in patients with EoE.

Management and treatment of HIV: are primary care clinicians prepared for their new role?

BACKGROUND: Current literature suggests the number of HIV clinicians in the United States is diminishing. There are 294,834 primary care providers (PCP) in the United States, and, of these, 3101 provide care to HIV-positive patients. More PCPs to treat and manage HIV patients may be the solution to alleviate the HIV provider shortage. However, PCPs also face challenges, including workforce shortages. We surveyed PCPs to determine perceived barriers, beliefs, and attitudes about their readiness to manage and treat HIV patients. METHODS: Following a quantitative, descriptive, cross-sectional survey design, currently practicing clinicians in primary care (physicians, residents, physician assistants, family nurse practitioners) were emailed a link to the study survey. Three hundred forty-seven family medicine clinicians from 47 states met the study inclusion criteria. RESULTS: Most (245/347, 70.6%) of the PCPs agreed that PCPs should take care of HIV patients. PCPs practicing HIV medicine (n = 171) were more likely than those not practicing HIV medicine (n = 176) to agree that PCPs should help with the HIV provider shortage (U = 10,384, p < 0.001) and that PCPs are the best solution to the HIV provider shortage (U = 10,294, p < 0.001). The majority (206, 59.4%) believed PCPs are the best solution for the HIV provider shortage. Of 133 physician assistants (PAs) and family nurse practitioners (NPs), seventy (52.6%) believed they could be ready to manage HIV patients with some training. CONCLUSION: The HIV provider shortage in the United States is likely to continue. To alleviate the provider shortage, PCPs should be offered additional training, decreased workload, and increased compensation when treating and managing HIV patients. Also, encouraging PAs and family NPs to be involved with HIV medicine may be a solution.

Sustaining participation in multisector health care alliances: The role of personal and stakeholder group influence.

BACKGROUND: Cross-sectoral collaborative organizations (e.g., alliances, coalitions) bring together members from different industry sectors to ameliorate multifaceted problems in local communities. The ability to leverage the diverse knowledge and skills of these members is predicated on their sustained participation, which research has shown to be a significant challenge. PURPOSE: The purpose of this study was to investigate how alliance member perceptions of decision-making influence relate to sustained participation in the alliance and its activities. METHODOLOGY: An Internet-based survey of 638 members of 15 multistakeholder health care alliances participating in the Robert Wood Johnson Foundation's Aligning Forces for Quality program was conducted. Ordinal logistic regression path analysis was used to estimate the relationship between two types of influence (personal influence and general stakeholder influence), perceived value of alliance participation, and intentions regarding future participation. FINDINGS: Alliance members saw less participation value when their personal influence was believed to be lower than the influence of other alliance members (b = -0.09, p < .05). This type of influence was not significantly associated with the anticipated level of future participation. In contrast, imbalances in general stakeholder group influence was not significantly associated with perceived value, but greater imbalances were associated with a decreased likelihood of future participation (OR = 0.52, 95% CI [0.32, 0.83]). PRACTICE IMPLICATIONS: Our findings highlight the important yet complicated task of balancing perceptions of influence; leaders must keep the desired outcomes in mind when considering what type of influence to attend to.

How different governance models may impact physician-hospital alignment.

BACKGROUND: Hospitals utilize three ideal type models for governing relationships with their physicians: the traditional medical staff, strategic alliances, and employment. Little is known about how these models impact physician alignment. PURPOSE: The study compares the level of physician-hospital alignment across the three models. APPROACH: We used survey data from 1,895 physicians in all three models across 34 hospitals in eight systems to measure several dimensions of alignment. We used logistic equations to predict survey nonresponse and differential physician selection into the alliance and employment models. Controlling for these selection effects, we then used multiple regression to estimate the effects of alliance and employment models on alignment. RESULTS: Physicians in employment models express greater alignment with their hospital on several dimensions, compared to physicians in alliances and the traditional medical staff. There were no differences in physician alignment between the latter two models. CONCLUSIONS: Employment models promote greater alignment on some (but not all) dimensions, controlling for physician selection. The impact of employment on alignment is not large, however. PRACTICE IMPLICATIONS: Hospitals and accountable care organizations that rely on employment may achieve higher physician alignment compared to the other two models. It is not clear that the gain in alignment is worth the cost of employment. Given the small impact of employment on alignment, it is also clear that they are not identical. Hospitals may need to go beyond structural models of integration to achieve alignment with their physicians.

Measurement of Observed Eating Behaviors in Patients With Active and Inactive Eosinophilic Esophagitis.

Subjective measures of eating difficulties in eosinophilic esophagitis (EoE) such as the presence of dysphagia, food modifications, and prolonged eating times are well documented. Although it is assumed that these measures reflect adaptive measures for eating with EoE, this is not well studied. The aim of this study was to directly observe and measure eating behaviors in patients with EoE and assess the degree of correlation to subjective assessment and validated EoE scoring systems.

Variation in Endoscopic Activity Assessment and Endoscopy Score Validation in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is assessed endoscopically (endoscopic activity), based on grades of edema, rings, exudates, furrows, and strictures (EREFS). We examined variations in endoscopic assessments of severity, developed and validated 3 EREFS-based scoring systems, and assessed responsiveness of these systems using data from a randomized placebo-controlled trial of patients with EoE. METHODS: For the development set, 5 gastroenterologists reviewed EREFS findings from 266 adults with EoE and provided endoscopist global assessment scores (EndoGA, scale of 0 to 10); variation (ΔEndoGA) was assessed using linear regression. We evaluated simple scores (features given arbitrary values from 0 to 3) and developed 2 scoring systems (adjusted score range, 0-100). We then fitted our linear regression model with mean EndoGA to data from 146 adults recruited in centers in Switzerland and the United States between April 2011 and December 2012. For the validation set, we collected data from 120 separate adults (recruited in centers in Switzerland and the United States between May 2013 and July 2014), assessing regression coefficient-based scores using Bland-Altman method. We assessed the responsiveness of our scoring systems using data from a randomized trial of patients with EoE given fluticasone (n=16) or placebo (n=8). RESULTS: The distribution of EndoGA values differed among endoscopists (mean ΔEndoGA, 2.6±1.8; range 0-6.6). We developed 2 regression-based scoring systems to assess overall and proximal and distal esophageal findings; variation in endoscopic features accounted for more than 90% of the mean EndoGA variation. In the validation group, differences between mean EndoGA and regression-based scores were small (ranging from -4.70 to 2.03), indicating good agreement. In analyses of data from the randomized trial, the baseline to end of study change in patients given fluticasone was a reduction of 24.3 in simple score (reduction of 4.6 in patients given placebo, P=.052); a reduction of 23.5 in regression-based overall score (reduction of 6.56 in patients given placebo, P=.12), and a reduction of 23.8 (reduction of 8.44 in patients given placebo, P=.11). CONCLUSION: Assessments of endoscopic activity in patients with EoE vary among endoscopists. In an analysis of data from a randomized controlled trial, we found that newly developed scoring systems are no better than simple scoring system in detecting changes in endoscopic activity. These results support the use of a simple scoring system in evaluation of endoscopic activity in patients with EoE. clinicaltrials.gov no: NCT00939263 and NCT01386112.