Progressive stridor: extraintestinal airway manifestations in a pediatric patient with inflammatory bowel disease.

Airway manifestations of inflammatory bowel disease are rare in pediatrics. This case describes a nine-year-old female with ulcerative colitis (UC) with progressive stridor and dyspnea for two months. Severe upper airway obstruction was noted on spirometry. CatScan (CT) of the neck and chest revealed tracheal narrowing with circumferential, heterogeneous soft tissue thickening, and posterior wall nodularity. Bronchoscopy visualized the granulation tissue of the large airways and an ulcerative lesion to the right mainstem. Consultation and evaluation by gastroenterology, oncology, and rheumatology determined a diagnosis of extraintestinal manifestations of UC. Systemic steroids led to symptom resolution and improvement in lung function

Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial

BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia. METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. RESULTS: In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥ 1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died during the 30 days after randomization. Among patients with severe COVID-19 pneumonia, the median time to recovery with Auxora was 5 days versus 12 days with SOC; the recovery rate ratio was 1.87 (95% CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction = 32%; 95% CI, - 0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO(2)/FiO(2) = 101-200. CONCLUSIONS: Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from the early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04345614

The Patient\u27s Perspective: A Qualitative Study of Patient Perceptions of Teamwork Competencies

Purpose: To examine patients’ ability to evaluate the interprofessional core competencies of their healthcare teams using the Jefferson Teamwork Observation Guide (JTOG). Background: It is widely regarded that interprofessional team-based care improves patient outcomes and satisfaction.[i] To investigate that claim, the JTOG, a validated survey tool mapped to the Interprofessional Education Collaborative (IPEC) Core Competencies for Interprofessional Collaborative Practice (CP)[ii], was adapted to collect patients’ feedback on teamwork behaviors in the domains of: Communication, Values/Ethics, Roles/Responsibilities, and Teamwork. Description of Intervention or Program: Trained research assistants surveyed inpatients and outpatients about their perceptions of their health care providers’ teamwork. Patients were asked one qualitative and eight quantitative questions. Of all 302 qualitative responses, a small sample was coded by consensus and then all were coded by a trained research assistant for themes relating to the core competencies. Results: Of the 302 comments, 210 (70%) centered on communication and 134 (44%) focused on teamwork. 185 (61%) responses reflected multiple competencies, with 90 (30%) including both communication and teamwork and 85 (28%) highlighting communication and patient-centeredness, a sub-domain of values/ethics. Conclusion: Patients can perceive interprofessional core competencies displayed by their healthcare teams using the JTOG. Communication skills, especially combined with teamwork and values/ethics, were commonly articulated by patients when explaining their positive experiences. These findings support the interrelation of the IPEC domains, including some difficulty in distinguishing them from one another. Relevance to interprofessional education or practice: Growing evidence supports the importance of CP and of having standardized core competencies for CP education. Studying real-life interactions of CP teams is useful for further understanding of such concepts. 2-3 measurable learning objectives relevant to conference goals: Describe patients’ ability to evaluate their care team using the Jefferson Teamwork Observation Guide Discuss the extent to which patients identify the IPEC competencies in evaluating their care teams Identify the importance of patients’ perspectives in improving interprofessional team-based care [i] World Health Organization. (2010). Framework for action on interprofessional education & collaborative practice. Geneva, Switzerland: WHO Department of Human Resources for Health. http://whqlibdoc.who.int/hq/2010/WHO_HRH_HPN_10.3_eng.pdf. [ii] Interprofessional Education Collaborative Expert Panel. (2011). Core competencies for interprofessional collaborative practice: Report of an expert panel. Washington, DC: Interprofessional Education Collaborative. http://www.aacn.nche.edu/education-resources/ipecreport.pdf

Impairing oral tolerance promotes allergy and anaphylaxis: a new murine food allergy model

a Chicago, Ill Background: Food allergy is a disorder in which antigenic food proteins elicit immune responses. Animal models of food allergy have several limitations that influence their utility, including failure to recapitulate several key immunologic hallmarks. Consequently, little is known regarding the pathogenesis and mechanisms leading to food allergy. Staphylococcus aureusderived enterotoxins, a common cause of food contamination, are associated with antigen responses in atopic dermatitis. Objective: We hypothesized that S aureus-derived enterotoxins might influence the development of food allergy. We examined the influence of administration of staphylococcal enterotoxin B (SEB) with food allergens on immunologic responses and compared these responses with those elicited by a cholera toxindriven food allergy model. Methods: Oral administration of ovalbumin or whole peanut extract with or without SEB was performed once weekly. After 8 weeks, mice were challenged with oral antigen alone, and the physiologic and immunologic responses to antigen were studied. Results: SEB administered with antigen resulted in immune responses to the antigen. Responses were highly T H 2 polarized, and oral challenge with antigen triggered anaphylaxis and local and systemic mast cell degranulation. SEB-driven sensitization induced eosinophilia in the blood and intestinal tissues not observed with cholera toxin sensitization. SEB impaired tolerance specifically by impairing expression of TGF-b and regulatory T cells, and tolerance was restored with high-dose antigen. Conclusions: We demonstrate a new model of food allergy to oral antigen in common laboratory strains of mice that recapitulates many features of clinical food allergy that are not seen in other models. We demonstrate that SEB impairs oral tolerance and permits allergic responses. (J Allergy Clin Immunol 2009;123:231-8.

Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis

Background: Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. Methods: We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). Findings: Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9–65·4) were blind (crude prevalence 0·48%; 80% UI 0·17–0·87; 56% female), 216·6 million (80% UI 98·5–359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34–4·89; 55% female), and 188·5 million (80% UI 64·5–350·2) had mild visual impairment (2·57%, 80% UI 0·88–4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1–1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9–997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9–57·3) in 1990 to 36·0 million (80% UI 12·9–65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (–36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3–270·0) in 1990 to 216·6 million (80% UI 98·5–359·1) in 2015. Interpretation: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world’s population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels

Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis

Background: Contemporary data on causes of vision impairment and blindness form an important basis for recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modeling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020. Methods: Published and unpublished population-based data on the causes of vision impairment and blindness from 1980 to 2015 were systematically analysed. A series of regression models were fit to estimate the proportion of moderate and severe vision impairment (MSVI; defined as presenting visual acuity <6/18 but ≥3/60 in the better eye) and blindness (presenting visual acuity <3/60 in the better eye) by cause by age, region, and year. Findings: Among the projected global population with MSVI (216.6 million; 80% uncertainty intervals [UI] 98.5-359.1), in 2015 the leading causes thereof are uncorrected refractive error (116.3 million; UI 49.4-202.1), cataract (52.6 million; UI 18.2-109.6), age-related macular degeneration (AMD; 8.4 million; UI 0.9-29.5), glaucoma (4.0 million; UI 0.6-13.3) and diabetic retinopathy (2.6 million; UI 0.2-9.9). In 2015, the leading global causes of blindness were cataract (12.6 million; UI 3.4-28.7) followed by uncorrected refractive error (7.4 million; UI 2.4-14.8) and glaucoma (2.9 million; UI 0.4-9.9), while by 2020, these numbers affected are anticipated to rise to 13.4 million, 8.0 million and 3.2 million, respectively. Cataract and uncorrected refractive error combined contributed to 55% of blindness and 77% of MSVI in adults aged 50 years and older in 2015. World regions varied markedly in the causes of blindness, with a relatively low prevalence of cataract and a relatively high prevalence of AMD as causes for vision loss in the High-income subregions. Blindness due to cataract and diabetic retinopathy was more common among women, while blindness due to glaucoma and corneal opacity was more common among men, with no gender difference related to AMD. Conclusions: The numbers of people affected by the common causes of vision loss have increased substantially as the population increases and ages. Preventable vision loss due to cataract and refractive error (reversible with surgery and spectacle correction respectively), continue to cause the majority of blindness and MSVI in adults aged 50+ years. A massive scale up of eye care provision to cope with the increasing numbers is needed if one is to address avoidable vision loss

Establishment Failure in Biological Invasions: A Case History of Littorina littorea in California, USA

The early stages of biological invasions are rarely observed, but can provide significant insight into the invasion process as well as the influence vectors have on invasion success or failure.We characterized three newly discovered populations of an introduced gastropod, Littorina littorea (Linné, 1758), in California, USA, comparing them to potential source populations in native Europe and the North American East Coast, where the snail is also introduced. Demographic surveys were used to assess spatial distribution and sizes of the snail in San Francisco and Anaheim Bays, California. Mitochondrial DNA was sequenced and compared among these nascent populations, and various populations from the North American East Coast and Europe, to characterize the California populations and ascertain their likely source. Demographic and genetic data were considered together to deduce likely vectors for the California populations. We found that the three large California L. littorea populations contained only adult snails and had unexpectedly high genetic diversity rather than showing an extreme bottleneck as typically expected in recent introductions. Haplotype diversity in Californian populations was significantly reduced compared to European populations, but not compared to East Coast populations. Genetic analyses clearly suggested the East Coast as the source region for the California introductions.The California L. littorea populations were at an early, non-established phase of invasion with no evidence of recruitment. The live seafood trade is the most likely invasion vector for these populations, as it preferentially transports large numbers of adult L. littorea, matching the demographic structure of the introduced California L. littorea populations. Our results highlight continued operation of live seafood trade vectors and the influence of vectors on the demographic and genetic structure of the resulting populations, especially early stages of the invasion process

Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection

IMPORTANCE Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. OBJECTIVES To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. EXPOSURE SARS-CoV-2 detected via nucleic acid testing. MAIN OUTCOMES AND MEASURES Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. RESULTS Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference. 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; >= 7 symptoms: aOR, 4.59 [95% CI, 2.50 8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321[2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391[10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). CONCLUSIONS AND RELEVANCE In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.This studywas supported by grants from the Canadian Institutes of Health Research (operating grant: COVID-19-clinical management); the Alberta Health Services-University of Calgary-Clinical Research Fund; the Alberta Children's Hospital Research Institute; the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis; and the Cincinnati Children's Hospital Medical Center Division of Emergency Medicine Small Grants Program. Dr Funk is supported by the University of Calgary Eyes-High PostDoctoral Research Fund. Dr Freedman is supported by the Alberta Children's Hospital Foundation Professorship in Child Health andWellness