Krista L. Harrison

The H1 histamine receptor regulates allergic lung responses

Histamine, signaling via the type 1 receptor (H1R), has been shown to suppress Th2 cytokine production by in vitro cultured T cells. We examined the role of H1R in allergic inflammation in vivo using a murine asthma model. Allergen-stimulated splenic T cells from sensitized H1R-/- mice exhibited enhanced Th2 cytokine production. Despite this Th2 bias, allergen-challenged H1R-/- mice exhibited diminished lung Th2 cytokine mRNA levels, airway inflammation, goblet cell metaplasia, and airway hyperresponsiveness (AHR). Restoration of pulmonary Th2 cytokines in H1R-/- mice by intranasal IL-4 or IL-13 restored inflammatory lung responses and AHR. Further investigation revealed that histamine acts as a T cell chemotactic factor and defective T cell trafficking was responsible for the absence of lung inflammation. Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R. In vivo, allergen-specific WT but not H1R-/- CD4+ T cells were recruited to the lungs of naive recipients following inhaled allergen challenge. H1R-/- T cells failed to confer airway inflammation or AHR observed after transfer of WT T cells. Our data establish a role for histamine and H1R in promoting the migration of Th2 cells into sites of allergen exposure.

IgE Influences the Number and Function of Mature Mast Cells, but Not Progenitor Recruitment in Allergic Pulmonary Inflammation

Studies performed using cultured cells indicate that IgE functions not only to trigger degranulation of mast cells following allergen exposure, but also to enhance their survival. Such an influence of IgE on mast cell homeostasis during allergic responses in vivo has not been established. In this study, we show that inhalation of Aspergillus fumigatus extract in mice induced a dramatic rise in IgE accompanied by an increase in airway mast cells. These had an activated phenotype with high levels of FcεRI. Plasma mast cell protease-1 was also increased, indicating an elevated systemic mast cell load. In addition, enhanced levels of IL-5 and eosinophils were observed in the airway. Both mast cell expansion and activation were markedly attenuated in IgE−/− animals that are incapable of producing IgE in response to A. fumigatus. The recruitment of eosinophils to the airways was also reduced in IgE−/− mice. Analyses of potential cellular targets of IgE revealed that IgE Abs are not required for the induction of mast cell progenitors in response to allergen, but rather act by sustaining the survival of mature mast cells. Our results identify an important role for IgE Abs in promoting mast cell expansion during allergic responses in vivo.

Developmental expression patterns of the zebrafish small heat shock proteins

Small heat shock proteins (sHSPs), or α‐crystallins, are low‐molecular weight proteins found in every kingdom and nearly every species examined to date. Many, if not all, sHSPs act as molecular chaperones. Several also have functions independent of their chaperone activity, and at least a few are expressed in specific spatiotemporal patterns during embryonic and/or juvenile stages, suggesting specific roles during development. To date, however, no one has systematically characterized the expression patterns of all of the sHSPs during development in any organism. We have characterized the normal heat shock‐induced expression patterns of all 13 zebrafish sHSPs during development. Seven of the sHSPs are expressed in a tissue‐specific manner during development, and five are upregulated by heat shock. The results of these studies provide a foundation for analysis of sHSP function during normal development and their roles in protecting cells from the effects environmental stressors. Developmental Dynamics 237:454–463, 2008.

How patients view probiotics: Findings from a multicenter study of patients with inflammatory bowel disease and irritable bowel syndrome

Background Patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) have access to a growing number of probiotic products marketed to improve digestive health. It is unclear how patients make decisions about probiotics and what role they expect their gastroenterologists to play as they consider using probiotics. Understanding patients’ knowledge, attitudes and expectations of probiotics may help gastroenterologists engage patients in collaborative discussions about probiotics. Study Focus groups were conducted with patients with IBD and IBS at the Cleveland Clinic, Mayo Clinic, and Johns Hopkins University. Inductive analytic methods were used to identify common themes and draw interpretations from focus group narratives. Results One hundred thirty-six patients participated in 22 focus groups between March and August 2009. Patients viewed probiotics as an appealing alternative to pharmaceutical drugs and understood probiotics as a more “natural,” low-risk therapeutic option. Many patients were hesitant to use them without consulting their gastroenterologists. Patients would weigh the risks and benefits of probiotics, their disease severity and satisfaction with current treatments when considering probiotic use. Conclusions Patients are interested in probiotics but have many unanswered questions about their use. Our findings suggest that patients with IBD and IBS will look to gastroenterologists and other clinicians as trustworthy advisors regarding the utility of probiotics as an alternative or supplement to pharmaceutical drugs. Gastroenterologists and other clinicians who care for patients with these diseases should be prepared to discuss the potential benefits and risks of probiotics and assist patients in making informed decisions about their use.

Low Completion and Disparities in Advance Care Planning Activities Among Older Medicare Beneficiaries

Letters Chicago; Ann Thomas, MD, MPH, Oregon Public Health Division, Portland; Teri Moser Woo, PhD, Pacific Lutheran University, Tacoma, Washington; Rachel M. Zetts, The Pew Charitable Trusts, Washington, DC. Conflict of Interest Disclosures: Dr Hersh has received funding from the CDC, the Agency for Healthcare Research and Quality, Pfizer/Joint Commission, and Merck. No other conflicts are reported. Funding/Support: This project was made possible through a partnership with the CDC Foundation. Support for this project was provided by Pew Charitable Trusts. Role of the Funder/Sponsor: The CDC participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The Pew Charitable Trusts participated in the interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The Pew Charitable Trusts sponsored in-person and telephone author meetings and supported some author travel to in-person meetings. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. Additional Contributions: Tia Carter, MS, Allan Coukell, BSc Pharm, and Elizabeth Jungman, JD, MPH, of The Pew Charitable Trusts assisted in convening author meetings. They did not receive any compensation for their role in the study. 1. The White House. National action plan for combating antibiotic resistant bacteria. https://www.whitehouse.gov/sites/default/files/docs/national_action _plan_for_combating_antibotic-resistant_bacteria.pdf. Accessed August 3, 2015. 2. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 3. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259-273. 4. Piccirillo JF, Mager DE, Frisse ME, Brophy RH, Goggin A. Impact of first-line vs second-line antibiotics for the treatment of acute uncomplicated sinusitis. JAMA. 5. Capra AM, Lieu TA, Black SB, Shinefield HR, Martin KE, Klein JO. Costs of otitis media in a managed care population. Pediatr Infect Dis J. 2000;19(4): Table 1. Characteristics of Participants Participants, No. (%) a Variable Sociodemographic characteristics Age, y Sex Female Male Race/ethnicity White Black/African American Hispanic/Latino English-speaking Spanish-speaking Other Education High school diploma or less Greater than high school Annual income, b

Ethical challenges in the care of children and families affected by life-limiting neuromuscular diseases.

Health-related characteristics Self-rated health Excellent or very good Good Fair or poor Dementia c None Possible or probable dementia Low Completion and Disparities in Advance Care Planning Activities Among Older Medicare Beneficiaries Advance care planning (ACP) is an iterative process that in- cludes discussions about preferences for end-of-life (EOL) care, completion of advance directives (AD), and designation of a surrogate decision maker in a durable power of attorney for health care (DPOA). 1,2 Engagement in ACP has increased over time. 3 However, the rising tide of ACP may not have lifted all boats equally. Minorities, those with lower levels of educa- tional attainment, and the poor may not have benefited from rising rates of ACP to the same extent that white, highly edu- cated, affluent individuals have. Rates of ACP by older Lati- nos in particular are unknown. Further, we do not know if ACP uptake is greater among those in worse health and with poorer prognoses. Methods | We used data from the National Health and Aging Trends Study (NHATS), a longitudinal cohort study using a nationally representative sample of community-dwelling Medi- care beneficiaries ages 65 years and older (2011 round 1 re- sponse rate, 71%; 2012 round 2 response rate, 86%). 4 This cross- sectional analysis used a random one-third sample of 2015 d Number of chronic medical conditions None Number of ADLs requiring help e 1 or 2 (continued) participants who responded to a supplemental module on ACP fielded in 2012. This study was considered exempt by the institutional review board of the University of California, San Francisco. Outcome variables included 3 self-reported elements of ACP: (1) discussing with any individual the medical treat- ment desired if seriously ill in the future (EOL discussion), (2) having legal arrangements for a proxy to make decisions about medical care (DPOA), or (3) having written instructions about JAMA Internal Medicine December 2016 Volume 176, Number 12 (Reprinted) jamainternalmedicine.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/935892/ by a UCSF LIBRARY User on 06/15/2017

EPPM and willingness to respond: the role of risk and efficacy communication in strengthening public health emergency response systems.

Objective: We sought to understand how neuromuscular clinicians respond to the ethical challenges that arise in caring for children with life-limiting neuromuscular diseases. Methods: We conducted a national survey of interdisciplinary professionals who care for children with Duchenne Muscular Dystrophy and Spinal Muscular Atrophy Type-1 to document their knowledge, attitudes, beliefs and reported practices with regard to prominent ethical challenges, and their suggestions for ethics interventions that would assist them in improving clinical practice. Results: 157 participants completed paper or electronic surveys for an overall participation rate of 24%. A significant minority of respondents were either unaware of or chose not to adopt relevant ethical guidelines, and reported experiencing crises of conscience in the care of their patients. In response to 8 ethical dilemmas, there was variability in how often respondents encountered them, their comfort in addressing them, and their reported practices, including only 24% who have requested ethics consultation. Conclusion: Training of interdisciplinary clinicians is needed to improve their adoption of relevant ethical guidelines, cultivate greater awareness of diverse attitudes regarding the ethical permissibility of different treatment options and the utility of ethics consultation, and foster greater confidence and competence in responding to ethical challenges that arise in pediatric neuromuscular practice.

Improving the Quality of Palliative Care Through National and Regional Collaboration Efforts.

This study examines the attitudinal impact of an Extended Parallel Process Model (EPPM)-based training curriculum on local public health department (LHD) workers’ willingness to respond to representative public health emergency scenarios. Data are from 71 U.S. LHDs in urban and rural settings across nine states. The study explores changes in response willingness and EPPM threat and efficacy appraisals between randomly assigned control versus intervention health departments, at baseline and 1 week post curriculum, through an EPPM-based survey/resurvey design. Levels of response willingness and emergency response-related attitudes/beliefs are measured. Analyses focus on two scenario categories that have appeared on a U.S. government list of scenarios of significant concern: a weather-related emergency and a radiological “dirty” bomb event (U.S. Department of Homeland Security, 2007). The greatest impact from the training intervention on response willingness was observed among LHD workers who had low levels of EPPM-related threat and efficacy perceptions at baseline. Self-efficacy and response efficacy and response willingness increased in intervention LHDs for both scenarios, with greater response willingness increases observed for the radiological “dirty” bomb terrorism scenario. Findings indicate the importance of building efficacy versus enhancing threat perceptions as a path toward greater response willingness, and suggest the potential applicability of such curricular interventions for boosting emergency response willingness among other cadres of health providers.

‘Someone should oversee it’: patient perspectives on the ethical issues arising with the regulation of probiotics

BACKGROUND The measurement and reporting of the quality of care in the field of palliation has become a required task for many health care leaders and specialists in palliative care. Such efforts are aided when organizations collaborate together to share lessons learned. METHODS The authors reviewed examples of quality-improvement collaborations in palliative care to understand the similarities, differences, and future directions of quality measurement and improvement strategies in the discipline. RESULTS Three examples were identified that showed areas of robust and growing quality-improvement collaboration in the field of palliative care: the Global Palliative Care Quality Alliance, Palliative Care Quality Network, and Project Educate, Nurture, Advise, Before Life Ends. These efforts exemplify how shared-improvement activities can inform improved practice for organizations participating in collaboration. CONCLUSIONS National and regional collaboratives can be used to enhance the quality of palliative care and are important efforts to standardize and improve the delivery of palliative care for persons with serious illness, along with their friends, family, and caregivers.

First Medicare Demonstration of Concurrent Provision of Curative and Hospice Services for End-of-Life Care

Although many probiotic products are currently available in yogurt or pill form in the United States (US), there is uncertainty surrounding the structure of regulation of these products. As more therapeutic probiotics are developed, changes to existing regulatory process in the United States may be required to meet the needs of patients and users in the population.