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Purpose: Severe asthma poses a significant health burden in those with the disease, therefore a timely diagnosis can ensure patients receive specialist care and appropriate medication management. This study qualitatively explored the patient experience of adult Australians with severe asthma regarding specialist referral, to identify potential opportunities to streamline the process of severe asthma diagnosis and treatment and optimise referral pathways. Patients and Methods: Adults currently being treated with medication for severe asthma were invited to participate in this study. Participants were interviewed and asked to describe initial diagnosis of their asthma or severe asthma, and how they came to be referred to secondary care. Interviews were transcribed verbatim, coded by two members of the research team and thematically analysed. Results: Thirty-two people completed the study; 72% were female. Mean interview length was 33 minutes. The major themes generated were patient-related factors contributing to seeking a severe asthma diagnosis; perceptions of health care provision; diagnosis of severe asthma and the referral journey. Key findings were that both patient and healthcare provider attitudes contributed to participants' willingness to seek or receive a referral, and referral to respiratory specialists was often delayed. Contributing factors included a mismatch between patient expectations and general practice, lack of continuity of primary care, and a lack of patient understanding of the role of the respiratory specialist. Conclusion: Timely severe asthma diagnosis in Australia appears to be hampered by an absence of a clear referral process, lack of general practitioner (GP) knowledge of additional treatment options, underutilisation of pharmacists, and multiple specialists treating patient comorbidities. Directions for future research might include interviewing healthcare providers regarding how well the referral process works for severe asthma patients, and researching the time between referral and when a patient sees the respiratory specialist.

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The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.

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Introduction: Non-bacterial thrombotic endocarditis is well documented in the literature to occur in patients with known malignancies. It is, however, much less common for patients to be diagnosed with marantic endocarditis as the presenting sign of an unknown primary malignancy. Case Presentation: We discuss a case in which a patient was undergoing routine surveillance for his known heart failure with a transthoracic echocardiogram when an aortic valve vegetation was discovered. After further investigation, he was found to have metastatic adenocarcinoma of the lung. Next-generation sequencing was utilized to identify an EGFR mutation, which led to the patient being treated with osimertinib. Conclusion: Adequate treatment of his primary malignancy, along with anticoagulation, led to overall clinical improvement of the patient.

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A preliminary report from the recent phase 3 trial of benralizumab, a monoclonal antibody that binds to interleukin-5 receptor alpha (IL5Rα), in patients with EoE revealed that medication use led to tissue eosinophil eradication but did not meet the clinical endpoint of symptom resolution. Here, we characterized the clinical, endoscopic, histologic, and transcriptional changes in patients with active EoE following benralizumab treatment. We retrospectively examined patients with EoE treated with benralizumab at the University of Utah (n = 11) and reviewed reported clinical symptoms, circulating and tissue eosinophilia, and endoscopic and histologic scores. Gene expression profiles from available esophageal tissue from benralizumab-treated patients were compared to those from patients with remission EoE (n = 5), active EoE (n = 10), and controls (n = 22). Benralizumab treatment resulted in partial symptom improvement and significant reduction in tissue eosinophilia, and endoscopic and histologic disease scoring (P < 0.01). Histologic score reductions were driven by eosinophil feature scores, while scores for epithelial features (basal cell hyperplasia and dilated intercellular spaces) were similar to those in active EoE. The gene signatures in benralizumab-treated patients mimicked those of active EoE (e.g. upregulation of POSTN, CDH26, CCL26, and downregulation of DSG1). RNA profiles and pathways support histologic findings of impaired epithelial function that persists despite benralizumab treatment. In conclusion, despite eosinophil eradication, patients treated with benralizumab had persistent epithelial injury at the histologic and transcriptional level. In this cohort, benralizumab therapy failed to eradicate inflammation and epithelial dysfunction showing that interleukin-5 receptor alpha blockade monotherapy is insufficient to control EoE.

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BACKGROUND: Anticholinergic and sedative medications affect cognition among older adults. The Drug Burden Index (DBI) is a validated measure of exposure to these medications, with higher DBI scores indicating higher drug burden. This ancillary analysis investigated the association between DBI and cognition assessed by the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSST). METHODS: The Health, Aging, and Body Composition Study was a prospective study of community-dwelling adults aged 70-79 years at enrollment. Using data from years 1, 5, and 10, DBI was calculated using medication data per participant. Linear mixed modeling was used to assess cross-sectional and longitudinal effects of DBI on 3MS and DSST. Adjusted models included biological sex, race, education level, APOE status, and death. Sensitivity analyses included testing the strength of the associations for each year and testing attrition due to death as a possible confounding factor via Cox-Proportional Hazard models. RESULTS: After adjustment, DBI was inversely associated with 3MS and DSST scores. These associations became stronger in each subsequent year. Neither DBI at year 1 nor within-person change in DBI were predictive of longitudinal declines in either cognitive measure. Sensitivity analyses indicated that DBI, 3MS, and DSST were associated with a greater risk of attrition due to death. CONCLUSIONS: Results suggest that in years when older adults had a higher DBI scores, they had significantly lower global cognition and slower processing speed. These findings further substantiate the DBI as a useful pharmacological tool for assessing the effect of medication exposure.

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Despite the rising prevalence and incidence of eosinophilic esophagitis (EoE), the etiology and pathophysiology remain unknown. Studies to date suggest that complex interactions between genetic and environmental risk factors result in the development and presentation of disease. Examining environmental factors both in the early life and later life exposures offers potential clues for the development of EoE, although challenges exist in making causal inferences due to diagnostic delay and access, ascertainment biases, and misclassification of cases. The authors review studies supporting early life factors as etiologic factors in the development of EoE.

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BACKGROUND & AIMS: Current approaches to managing digestive disease in older adults fail to consider the psychosocial factors contributing to a person's health. We aimed to compare the frequency of loneliness, depression, and social isolation in older adults with and without a digestive disease and to quantify their association with poor health. METHODS: We conducted an analysis of Health and Retirement Study data from 2008 to 2016, a nationally representative panel study of participants 50 years and older and their spouses. Bivariate analyses examined differences in loneliness, depression, and social isolation among patients with and without a digestive disease. We also examined the relationship between these factors and health. RESULTS: We identified 3979 (56.0%) respondents with and 3131 (44.0%) without a digestive disease. Overall, 60.4% and 55.6% of respondents with and without a digestive disease reported loneliness (P < .001), 12.7% and 7.5% reported severe depression (P < .001), and 8.9% and 8.7% reported social isolation (P = NS), respectively. After adjusting for covariates, those with a digestive disease were more likely to report poor or fair health than those without a digestive disease (odds ratio [OR], 1.25; 95% CI, 1.11-1.41). Among patients with a digestive disease, loneliness (OR, 1.43; 95% CI, 1.22-1.69) and moderate and severe depression (OR, 2.93; 95% CI, 2.48-3.47; and OR, 8.96; 95% CI, 6.91-11.63, respectively) were associated with greater odds of poor or fair health. CONCLUSIONS: Older adults with a digestive disease were more likely than those without a digestive disease to endorse loneliness and moderate to severe depression and these conditions are associated with poor or fair health. Gastroenterologists should feel empowered to screen patients for depression and loneliness symptoms and establish care pathways for mental health treatment.

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BACKGROUND & AIMS: Tools that can automatically predict incident esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using electronic health records to guide screening decisions are needed. METHODS: The Veterans Health Administration (VHA) Corporate Data Warehouse was accessed to identify Veterans with 1 or more encounters between 2005 and 2018. Patients diagnosed with EAC (n = 8430) or GCA (n = 2965) were identified in the VHA Central Cancer Registry and compared with 10,256,887 controls. Predictors included demographic characteristics, prescriptions, laboratory results, and diagnoses between 1 and 5 years before the index date. The Kettles Esophageal and Cardia Adenocarcinoma predictioN (K-ECAN) tool was developed and internally validated using simple random sampling imputation and extreme gradient boosting, a machine learning method. Training was performed in 50% of the data, preliminary validation in 25% of the data, and final testing in 25% of the data. RESULTS: K-ECAN was well-calibrated and had better discrimination (area under the receiver operating characteristic curve [AuROC], 0.77) than previously validated models, such as the Nord-Trøndelag Health Study (AuROC, 0.68) and Kunzmann model (AuROC, 0.64), or published guidelines. Using only data from between 3 and 5 years before index diminished its accuracy slightly (AuROC, 0.75). Undersampling men to simulate a non-VHA population, AUCs of the Nord-Trøndelag Health Study and Kunzmann model improved, but K-ECAN was still the most accurate (AuROC, 0.85). Although gastroesophageal reflux disease was strongly associated with EAC, it contributed only a small proportion of gain in information for prediction. CONCLUSIONS: K-ECAN is a novel, internally validated tool predicting incident EAC and GCA using electronic health records data. Further work is needed to validate K-ECAN outside VHA and to assess how best to implement it within electronic health records.

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BACKGROUND: Challenging eating behaviors or feeding difficulties, commonly displayed in children with Down syndrome (DS), may amplify perceived stress in caregivers. If caregivers lack resources on how to accommodate the needs of the child with DS, they may find feeding the child stressful and resort to negative coping strategies. OBJECTIVE: The aim of this study was to understand the feeding stressors, resources, and coping strategies used by caregivers of children with DS. DESIGN: A qualitative analysis of interview transcripts was undertaken, framed around the Transactional Model of Stress and Coping. PARTICIPANTS/SETTING: Between September to November 2021, 15 caregivers of children (aged 2 through 6 years) with DS, were recruited from 5 states located in the Southeast, Southwest, and West regions of the United States. ANALYSIS: Interviews were audio-recorded, transcribed verbatim, and analyzed using deductive thematic analysis and content analysis approaches. RESULTS: Thirteen caregivers reported increased stress around feeding the child with DS. Stressors identified included concern about adequacy of intake and challenges associated with feeding difficulties. Stress related to feeding was higher among caregivers whose child was learning a new feeding skill or in a transitional phase of feeding. Caregivers used both professional and interpersonal resources in addition to problem- and emotion-based coping strategies. CONCLUSIONS: Caregivers identified feeding as a stressful event with higher stress reported during transitional phases of feeding. Caregivers reported that speech, occupational, and physical therapists were beneficial resources to provide support for optimizing nutrition and skill development. These findings suggest that caregiver access to therapists and registered dietitian nutritionists is warranted.

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Dietary therapy for short- and long-term management of eosinophilic esophagitis is an effective yet poorly understood and underutilized treatment strategy. Despite several prospective trials demonstrating the efficacy of dietary therapies, successful clinical implementation is hampered by the need for a multidisciplinary approach including dietitian support and provider expertise. The availability of these resources is not readily available to most gastroenterologists. Without standardized guidance on starting or completing the diet for gastrointestinal providers and/or consulting dietitians, provider attitudes toward dietary therapy vary greatly depending on familiarity and knowledge gaps in using diet therapy. This review aims to summarize evidence in support of dietary therapy in eosinophilic esophagitis while providing guidance on initiation and implementation of dietary therapy for providers.

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The family environment, which involves parent eating behaviors and feeding practices, influences child intake and eating behaviors. Specifically, parental emotional eating or emotional feeding practices may lead to emotional eating in the child. Mindful eating practices may decrease emotional eating behaviors. The purpose of this narrative review was to investigate the influence of parental mindful eating on emotional eating behaviors of their children or adolescents. A secondary purpose of this review was to determine whether a family-based or child mindful eating intervention improves child emotional eating directly or through the improvements of the parent and parental role modeling. EBSCOhost was used to simultaneously search 5 databases. The search was limited to full-text, peer-reviewed articles in the English language. Seven studies, 4 cross-sectional studies and 3 intervention studies, were identified. Across studies, measures of mindful and emotional eating differed. Among the cross-sectional studies, parental mindful eating/feeding or mindful parenting were either directly or indirectly related to decreased emotional eating in the child or adolescent. The effect was unclear among the intervention studies; however, these were pilot feasibility studies. Overall, parental mindful eating is associated with emotional eating behaviors among children and adolescents. Additional studies with a randomized controlled design are needed to evaluate parent mindful eating interventions on child and adolescent eating behaviors. Additionally, future trials need to use similar validated measures to ensure consistent quality data collection and allow for comparison of findings across studies.

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INTRODUCTION: Guidelines suggest 1-time screening with esophagogastroduodenoscopy (EGD) for Barrett's esophagus (BE) in individuals at an increased risk of esophageal adenocarcinoma (EAC). We aimed to estimate the yield of repeat EGD performed at prolonged intervals after a normal index EGD. METHODS: We conducted a national retrospective analysis within the U S Veterans Health Administration, identifying patients with a normal index EGD between 2003 and 2009 who subsequently had a repeat EGD. We tabulated the proportion with a new diagnosis of BE, EAC, or esophagogastric junction adenocarcinoma (EGJAC) and conducted manual chart review of a sample. We fitted logistic regression models for the odds of a new diagnosis of BE/EAC/EGJAC. RESULTS: We identified 71,216 individuals who had a repeat EGD between 1 and 16 years after an index EGD without billing or cancer registry codes for BE/EAC/EGJAC. Of them, 4,088 had a new billing or cancer registry code for BE/EAC/EGJAC after the repeat EGD. On manual review of a stratified sample, most did not truly have new BE/EAC/EGJAC. A longer duration between EGD was associated with greater odds of a new diagnosis (adjusted odds ratio [aOR] for each 5 years 1.31; 95% confidence interval [CI] 1.19-1.44), particularly among those who were younger during the index EGD (ages 19-29 years: aOR 3.92; 95% CI 1.24-12.4; ages 60-69 years: aOR 1.19; 95% CI 1.01-1.40). DISCUSSION: The yield of repeat EGD for BE/EAC/EGJAC seems to increase with time after a normal index EGD, particularly for younger individuals. Prospective studies are warranted to confirm these findings.

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Objectives: The purpose of this qualitative study was to explore factors associated with the ability of people with PD to perform food-related activities (FRAs). Methods: Eleven dyads, older adults with Parkinson disease (PD) and their care-partners (n = 22), completed virtual semi-structured interviews guided by the Social Cognitive Theory (SCT) that were independently analyzed by two coders via directed content analysis. Results: The following themes were identified-(1) Personal: perception of a healthy diet, perception of how nutrition influences PD, confidence in following a healthy diet, and barriers to performing FRA; (2) Environmental: previous sources of nutrition information and willingness to changing their diet with a registered dietitian; and (3) Behavioral: modifications to FRA due to food-medication interactions, and skills necessary to maintain a healthy diet. Discussion: Findings from this study highlight the need for nutrition intervention research to inform evidence-based guidelines in order to provide tailored education for people with PD and care-partners.

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There is a need for more Registered Dietitian Nutritionists (RDNs) trained to provide nutritional care to older adults with dementia who experience mealtime difficulties. The purpose of this single-arm, pre/post pilot study was to adapt a generalized dementia care curriculum to the learning needs of RDNs who work with individuals with dementia and to determine the feasibility and acceptability of the adapted program. Using an existing evidence-based dementia care curriculum, the research team identified learning objectives and content pertinent to the scope of RDNs. The adapted program was piloted with RDNs who work with older adults with dementia. Twenty-five RDNs registered for the training while 80% (20) attended the training and completed the post-training survey. All participants agreed that the module met the learning needs of RDNs who work with older adults with dementia, the two-hour workshop was a good use of their time, and the experience and skills gained would be useful in their work as an RDN. Implementation costs totaled $1,310. Based on the post-training feedback, the adapted program was deemed feasible and acceptable by RDN participants, who also expressed interest in using the module to train other caregivers on providing mealtime assistance to older adults with dementia.

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PURPOSE OF REVIEW: As the rising prevalence and incidence of eosinophilic esophagitis (EoE) has quickly outpaced the rate of esophageal biopsies, particularly in Westernized countries, several studies have suggested a link between intrinsic genetic and extrinsic environmental risk factors and the development, presentation, and diagnosis of EoE. This review aims to critically assess existing studies describing the role of the environment on the development, symptomatic presentation, and diagnosis of this recently recognized chronic immune-mediated disease. RECENT FINDINGS: We present and critically evaluate the working hypotheses and supportive studies thus far on environmental factors on EoE, describe sources of potential bias in diagnosis due to socioeconomic factors and thus undermining studies of EoE etiology, and highlight opportunities for future research. As genetics alone do not explain the rapid rise of EoE, we must look to environmental, or extrinsic, factors both in the early-life period which shape the development of the gut microbiome, as well as later life contributing to diagnosis of this new disease. Future etiologic studies linking risk factors to EoE development in individual patients are needed.

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The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene PMM2, which affect protein N-linked glycosylation. The yeast gene SEC53 encodes a homolog of human PMM2. We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, sec53-V238M and sec53-F126L, or wild-type SEC53. We find that after 1000 generations, most populations compensate for the slow-growth phenotype associated with the sec53 human-disease-associated alleles. Through whole-genome sequencing we identify compensatory mutations, including known SEC53 genetic interactors. We observe an enrichment of compensatory mutations in other genes whose human homologs are associated with Type 1 CDG, including PGM1, which encodes the minor isoform of phosphoglucomutase in yeast. By genetic reconstruction, we show that evolved pgm1 mutations are dominant and allele-specific genetic interactors that restore both protein glycosylation and growth of yeast harboring the sec53-V238M allele. Finally, we characterize the enzymatic activity of purified Pgm1 mutant proteins. We find that reduction, but not elimination, of Pgm1 activity best compensates for the deleterious phenotypes associated with the sec53-V238M allele. Broadly, our results demonstrate the power of experimental evolution as a tool for identifying genes and pathways that compensate for human-disease-associated alleles.

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INTRODUCTION: Despite effective dietary treatments, physicians prefer medications for eosinophilic esophagitis (EoE). METHODS: We conducted a web-based survey of providers to assess the perceived effectiveness, practice patterns, and barriers to EoE dietary therapy. RESULTS: Providers view diet as the least effective treatment. The greatest barrier was the belief that patients are disinterested and unlikely to adhere (58%). With less access to dietitians (56%), nonacademic providers often manage diets without dietitian guidance (41%). DISCUSSION: Given high patient acceptance for diets and multiple treatment options for EoE, clinicians need evidence-based knowledge on EoE diets, access to dietitians, and awareness of patient preferences.

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OBJECTIVE: The purpose of this mixed methods study was to explore the impact of COVID-19 on the ability of people with Parkinson disease (PwPs) and their care-partners to perform food-related activities (FRA) and PwPs' overall diet quality. METHODS: Using a convergent parallel mixed methods design, PwPs and their care-partners completed virtual dyadic semi-structured interviews about their FRA during the COVID-19 pandemic. PwPs completed Food Frequency Questionnaires (FFQ) to quantify their dietary intake in the previous 12 months. Qualitative data were analyzed by two coders using thematic analysis, and quantitative data from FFQs were descriptively analyzed to calculate diet quality scores. RESULTS: Eleven dyadic interviews revealed the following key themes: cooking more at home; changes with grocery shopping; less meals with non-household members. These changes were described to increase the care-partners' responsibilities and overall burden. Diet scores among PwPs were 73.0 ± 6.3 for the Healthy Eating Index 2015 (scale of 0-100), 29.2 ± 6.6 for the Mediterranean diet (scale of 0-55), and 10.4 ± 1.8 for the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet (scale 0-15). CONCLUSIONS: Diet scores revealed that PwPs consumed a high-quality diet during the pandemic. Findings from this study highlight the need for tailored nutrition education to support PwPs' care-partners.

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Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease of the oesophagus and is clinically characterized by upper gastrointestinal (GI) symptoms including dysphagia and esophageal food impaction. Histopathologic manifestations, which include intraepithelial eosinophilic inflammation and alterations of the esophageal squamous epithelium, such as basal zone hyperplasia (BZH) and dilated intercellular spaces (DIS), are thought to contribute to esophageal dysfunction and disease symptoms. Corroborative clinical and discovery science-based studies have established that EoE is characterized by an underlying allergic inflammatory response, in part, related to the IL-13/CCL26/eosinophil axis driving dysregulation of several key epithelial barrier and proliferative regulatory genes including kallikrein (KLK) serine proteases, calpain 14 (CAPN14) and anoctamin 1 (ANO1). The contribution of these inflammatory and proliferative processes to the clinical and histological manifestations of disease are not fully elucidated. Herein, we discuss the immune molecules and cells that are thought to underlie the clinical and pathologic manifestations of EoE and the emerging therapeutics targeting these processes for the treatment of EoE.

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