The Goblet Cell Is the Cellular Source of the Anti-Microbial Angiogenin 4 in the Large Intestine Post Trichuris muris Infection

Mouse angiogenin 4 (Ang4) has previously been described as a Paneth cell-derived antimicrobial peptide important in epithelial host defence in the small intestine. However, a source for Ang4 in the large intestine, which is devoid of Paneth cells, has not been defined.Analysis was performed on Ang4 expression in colonic tissue by qPCR and immunohistochemistry following infection with the large intestine dwelling helminth parasite Trichuris muris. This demonstrated an increase in expression of the peptide following infection of resistant BALB/c mice. Further, histological analysis of colonic tissue revealed the cellular source of this Ang4 to be goblet cells. To elucidate the mechanism of Ang4 expression immunohistochemistry and qPCR for Ang4 was performed on colonic tissue from T. muris infected mouse mutants. Experiments comparing C3H/HeN and C3H/HeJ mice, which have a natural inactivating mutation of TLR4, revealed that Ang4 expression is TLR4 independent. Subsequent experiments with IL-13 and IL-4 receptor alpha deficient mice demonstrated that goblet cell expression of Ang4 is controlled either directly or indirectly by IL-13.The cellular source of mouse Ang4 in the colon following T. muris infection is the goblet cell and expression is under the control of IL-13

Surrogate Markers of Cardiovascular Risk and Chronic Obstructive Pulmonary Disease: A Large Case-Controlled Study.

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid-femoral (aortic) pulse wave velocity, augmentation index, and carotid intima-media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima-media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease

Functional analysis of the role of interferon gamma through the characterisation of conditional interferon gamma receptor two mouse mutants

The data presented within this thesis shows the generation and characterisation of a complete-, macrophage/granulocyte- and T cell-specific IFNγR2 deficient mouse mutant. This mutant mouse is a valuable tool in dissecting the mechanism of action of the pleiotrophic cytokine IFNγ.The global mutant mouse was tested in three models in vivo - DSS induced colitis, Trichuris muris infection and EAE. The aim of the DSS-induced colitis model was to test the role of IFNγ in the innate immune system and, despite previous reports demonstrating IFNγ deficient mice are protected from DSS-colitis, our IFNγR2 deficient mice displayed equal or more severe colitis than control mice. We hypothesise that this discrepancy is due to differences in the gut microbiota.The Trichuris muris model was utilised as a method of examining the role of IFNγ in the adaptive immune system. The complete IFNγR2 mutant was resistant to a low dose T. muris infection; however, neither the T cell specific nor the macrophage/granulocyte specific mutant duplicated the resistant phenotype observed in the global knock-out mice. Analysis of a double conditional T cell and macrophage/granulocyte specific IFNγR2 mutant produced inconsistent results. Initial experiments suggested that, in combination, these deficiencies are sufficient to duplicate the resistant phenotype observed in the global mutant mice, but this was not reproducible.The final in vivo model that we used to analyse IFNγR2 mutant mice was EAE. This model was chosen as, for a long time, the mechanism of action and the involvement of IFNγ in EAE has been a matter of uncertainty. These results demonstrated that global IFNγR2 mutant mice demonstrate an atypical phenotype, with no signs of recovery. In contrast, control mice develop classical EAE symptoms with almost complete recovery prior to the termination of the experiment. The IFNγ receptor mutant mouse generated will be of great value to the scientific community as IFNγ has been demonstrated to play a role in multiple diseases and this tool allows the mechanism of action of this cytokine to be unravelled.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Proceedings of the 8th Annual Conference on the Science of Dissemination and Implementation

A1 Introduction to the 8(th) Annual Conference on the Science of Dissemination and Implementation: Optimizing Personal and Population Health David Chambers, Lisa Simpson D1 Discussion forum: Population health D&I research Felicia Hill-Briggs D2 Discussion forum: Global health D&I research Gila Neta, Cynthia Vinson D3 Discussion forum: Precision medicine and D&I research David Chambers S1 Predictors of community therapists’ use of therapy techniques in a large public mental health system Rinad Beidas, Steven Marcus, Gregory Aarons, Kimberly Hoagwood, Sonja Schoenwald, Arthur Evans, Matthew Hurford, Ronnie Rubin, Trevor Hadley, Frances Barg, Lucia Walsh, Danielle Adams, David Mandell S2 Implementing brief cognitive behavioral therapy (CBT) in primary care: Clinicians' experiences from the field Lindsey Martin, Joseph Mignogna, Juliette Mott, Natalie Hundt, Michael Kauth, Mark Kunik, Aanand Naik, Jeffrey Cully S3 Clinician competence: Natural variation, factors affecting, and effect on patient outcomes Alan McGuire, Dominique White, Tom Bartholomew, John McGrew, Lauren Luther, Angie Rollins, Michelle Salyers S4 Exploring the multifaceted nature of sustainability in community-based prevention: A mixed-method approach Brittany Cooper, Angie Funaiole S5 Theory informed behavioral health integration in primary care: Mixed methods evaluation of the implementation of routine depression and alcohol screening and assessment Julie Richards, Amy Lee, Gwen Lapham, Ryan Caldeiro, Paula Lozano, Tory Gildred, Carol Achtmeyer, Evette Ludman, Megan Addis, Larry Marx, Katharine Bradley S6 Enhancing the evidence for specialty mental health probation through a hybrid efficacy and implementation study Tonya VanDeinse, Amy Blank Wilson, Burgin Stacey, Byron Powell, Alicia Bunger, Gary Cuddeback S7 Personalizing evidence-based child mental health care within a fiscally mandated policy reform Miya Barnett, Nicole Stadnick, Lauren Brookman-Frazee, Anna Lau S8 Leveraging an existing resource for technical assistance: Community-based supervisors in public mental health Shannon Dorsey, Michael Pullmann S9 SBIRT implementation for adolescents in urban federally qualified health centers: Implementation outcomes Shannon Mitchell, Robert Schwartz, Arethusa Kirk, Kristi Dusek, Marla Oros, Colleen Hosler, Jan Gryczynski, Carolina Barbosa, Laura Dunlap, David Lounsbury, Kevin O'Grady, Barry Brown S10 PANEL: Tailoring Implementation Strategies to Context - Expert recommendations for tailoring strategies to context Laura Damschroder, Thomas Waltz, Byron Powell S11 PANEL: Tailoring Implementation Strategies to Context - Extreme facilitation: Helping challenged healthcare settings implement complex programs Mona Ritchie S12 PANEL: Tailoring Implementation Strategies to Context - Using menu-based choice tasks to obtain expert recommendations for implementing three high-priority practices in the VA Thomas Waltz S13 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Siri, rate my therapist: Using technology to automate fidelity ratings of motivational interviewing David Atkins, Zac E. Imel, Bo Xiao, Doğan Can, Panayiotis Georgiou, Shrikanth Narayanan S14 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Identifying indicators of implementation quality for computer-based ratings Cady Berkel, Carlos Gallo, Irwin Sandler, C. Hendricks Brown, Sharlene Wolchik, Anne Marie Mauricio S15 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Improving implementation of behavioral interventions by monitoring emotion in spoken speech Carlos Gallo, C. Hendricks Brown, Sanjay Mehrotra S16 Scorecards and dashboards to assure data quality of health management information system (HMIS) using R Dharmendra Chandurkar, Siddhartha Bora, Arup Das, Anand Tripathi, Niranjan Saggurti, Anita Raj S17 A big data approach for discovering and implementing patient safety insights Eric Hughes, Brian Jacobs, Eric Kirkendall S18 Improving the efficacy of a depression registry for use in a collaborative care model Danielle Loeb, Katy Trinkley, Michael Yang, Andrew Sprowell, Donald Nease S19 Measurement feedback systems as a strategy to support implementation of measurement-based care in behavioral health Aaron Lyon, Cara Lewis, Meredith Boyd, Abigail Melvin, Semret Nicodimos, Freda Liu, Nathanial Jungbluth S20 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Common loop assay: Methods of supporting learning collaboratives Allen Flynn S21 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Innovating audit and feedback using message tailoring models for learning health systems Zach Landis-Lewis S22 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Implementation science and learning health systems: Connecting the dots Anne Sales S23 Facilitation activities of Critical Access Hospitals during TeamSTEPPS implementation Jure Baloh, Marcia Ward, Xi Zhu S24 Organizational and social context of federally qualified health centers and variation in maternal depression outcomes Ian Bennett, Jurgen Unutzer, Johnny Mao, Enola Proctor, Mindy Vredevoogd, Ya-Fen Chan, Nathaniel Williams, Phillip Green S25 Decision support to enhance treatment of hospitalized smokers: A randomized trial Steven Bernstein, June-Marie Rosner, Michelle DeWitt, Jeanette Tetrault, James Dziura, Allen Hsiao, Scott Sussman, Patrick O’Connor, Benjamin Toll S26 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A patient-centered approach to successful community transition after catastrophic injury Michael Jones, Julie Gassaway S27 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - Conducting PCOR to integrate mental health and cancer screening services in primary care Jonathan Tobin S28 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A comparative effectiveness trial of optimal patient-centered care for US trauma care systems Douglas Zatzick S29 Preferences for in-person communication among patients in a multi-center randomized study of in-person versus telephone communication of genetic test results for cancer susceptibility Angela R Bradbury, Linda Patrick-Miller, Brian Egleston, Olufunmilayo I Olopade, Michael J Hall, Mary B Daly, Linda Fleisher, Generosa Grana, Pamela Ganschow, Dominique Fetzer, Amanda Brandt, Dana Farengo-Clark, Andrea Forman, Rikki S Gaber, Cassandra Gulden, Janice Horte, Jessica Long, Rachelle Lorenz Chambers, Terra Lucas, Shreshtha Madaan, Kristin Mattie, Danielle McKenna, Susan Montgomery, Sarah Nielsen, Jacquelyn Powers, Kim Rainey, Christina Rybak, Michelle Savage, Christina Seelaus, Jessica Stoll, Jill Stopfer, Shirley Yao and Susan Domchek S30 Working towards de-implementation: A mixed methods study in breast cancer surveillance care Erin Hahn, Corrine Munoz-Plaza, Jianjin Wang, Jazmine Garcia Delgadillo, Brian Mittman Michael Gould S31Integrating evidence-based practices for increasing cancer screenings in safety-net primary care systems: A multiple case study using the consolidated framework for implementation research Shuting (Lily) Liang, Michelle C. Kegler, Megan Cotter, Emily Phillips, April Hermstad, Rentonia Morton, Derrick Beasley, Jeremy Martinez, Kara Riehman S32 Observations from implementing an mHealth intervention in an FQHC David Gustafson, Lisa Marsch, Louise Mares, Andrew Quanbeck, Fiona McTavish, Helene McDowell, Randall Brown, Chantelle Thomas, Joseph Glass, Joseph Isham, Dhavan Shah S33 A multicomponent intervention to improve primary care provider adherence to chronic opioid therapy guidelines and reduce opioid misuse: A cluster randomized controlled trial protocol Jane Liebschutz, Karen Lasser S34 Implementing collaborative care for substance use disorders in primary care: Preliminary findings from the summit study Katherine Watkins, Allison Ober, Sarah Hunter, Karen Lamp, Brett Ewing S35 Sustaining a task-shifting strategy for blood pressure control in Ghana: A stakeholder analysis Juliet Iwelunmor, Joyce Gyamfi, Sarah Blackstone, Nana Kofi Quakyi, Jacob Plange-Rhule, Gbenga Ogedegbe S36 Contextual adaptation of the consolidated framework for implementation research (CFIR) in a tobacco cessation study in Vietnam Pritika Kumar, Nancy Van Devanter, Nam Nguyen, Linh Nguyen, Trang Nguyen, Nguyet Phuong, Donna Shelley S37 Evidence check: A knowledge brokering approach to systematic reviews for policy Sian Rudge S38 Using Evidence Synthesis to Strengthen Complex Health Systems in Low- and Middle-Income Countries Etienne Langlois S39 Does it matter: timeliness or accuracy of results? The choice of rapid reviews or systematic reviews to inform decision-making Andrea Tricco S40 Evaluation of the veterans choice program using lean six sigma at a VA medical center to identify benefits and overcome obstacles Sherry Ball, Anne Lambert-Kerzner, Christine Sulc, Carol Simmons, Jeneen Shell-Boyd, Taryn Oestreich, Ashley O'Connor, Emily Neely, Marina McCreight, Amy Labebue, Doreen DiFiore, Diana Brostow, P. Michael Ho, David Aron S41 The influence of local context on multi-stakeholder alliance quality improvement activities: A multiple case study Jillian Harvey, Megan McHugh, Dennis Scanlon S42 Increasing physical activity in early care and education: Sustainability via active garden education (SAGE) Rebecca Lee, Erica Soltero, Nathan Parker, Lorna McNeill, Tracey Ledoux S43 Marking a decade of policy implementation: The successes and continuing challenges of a provincial school food and nutrition policy in Canada Jessie-Lee McIsaac, Kate MacLeod, Nicole Ata, Sherry Jarvis, Sara Kirk S44 Use of research evidence among state legislators who prioritize mental health and substance abuse issues Jonathan Purtle, Elizabeth Dodson, Ross Brownson S45 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 1 designs Brian Mittman, Geoffrey Curran S46 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 2 designs Geoffrey Curran S47 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 3 designs Jeffrey Pyne S48 Linking team level implementation leadership and implementation climate to individual level attitudes, behaviors, and implementation outcomes Gregory Aarons, Mark Ehrhart, Elisa Torres S49 Pinpointing the specific elements of local context that matter most to implementation outcomes: Findings from qualitative comparative analysis in the RE-inspire study of VA acute stroke care Edward Miech S50 The GO score: A new context-sensitive instrument to measure group organization level for providing and improving care Edward Miech S51 A research network approach for boosting implementation and improvement Kathleen Stevens, I.S.R.N. Steering Council S52 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - The value of qualitative methods in implementation research Alison Hamilton S53 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Learning evaluation: The role of qualitative methods in dissemination and implementation research Deborah Cohen S54 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Qualitative methods in D&I research Deborah Padgett S55 PANEL: Maps & models: The promise of network science for clinical D&I - Hospital network of sharing patients with acute and chronic diseases in California Alexandra Morshed S56 PANEL: Maps & models: The promise of network science for clinical D&I - The use of social network analysis to identify dissemination targets and enhance D&I research study recruitment for pre-exposure prophylaxis for HIV (PrEP) among men who have sex with men Rupa Patel S57 PANEL: Maps & models: The promise of network science for clinical D&I - Network and organizational factors related to the adoption of patient navigation services among rural breast cancer care providers Beth Prusaczyk S58 A theory of de-implementation based on the theory of healthcare professionals’ behavior and intention (THPBI) and the becker model of unlearning David C. Aron, Divya Gupta, Sherry Ball S59 Observation of registered dietitian nutritionist-patient encounters by dietetic interns highlights low awareness and implementation of evidence-based nutrition practice guidelines Rosa Hand, Jenica Abram, Taylor Wolfram S60 Program sustainability action planning: Building capacity for program sustainability using the program sustainability assessment tool Molly Hastings, Sarah Moreland-Russell S61 A review of D&I study designs in published study protocols Rachel Tabak, Alex Ramsey, Ana Baumann, Emily Kryzer, Katherine Montgomery, Ericka Lewis, Margaret Padek, Byron Powell, Ross Brownson S62 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Model simulation techniques to estimate the cost of implementing foundational public health services Cezar Brian Mamaril, Glen Mays, Keith Branham, Lava Timsina S63 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Inter-organizational network effects on the implementation of public health services Glen Mays, Rachel Hogg S64 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Implementation fidelity, coalition functioning, and community prevention system transformation using communities that care Abigail Fagan, Valerie Shapiro, Eric Brown S65 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Expanding capacity for implementation of communities that care at scale using a web-based, video-assisted training system Kevin Haggerty, David Hawkins S66 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Effects of communities that care on reducing youth behavioral health problems Sabrina Oesterle, David Hawkins, Richard Catalano S68 When interventions end: the dynamics of intervention de-adoption and replacement Virginia McKay, M. Margaret Dolcini, Lee Hoffer S69 Results from next-d: can a disease specific health plan reduce incident diabetes development among a national sample of working-age adults with pre-diabetes? Tannaz Moin, Jinnan Li, O. Kenrik Duru, Susan Ettner, Norman Turk, Charles Chan, Abigail Keckhafer, Robert Luchs, Sam Ho, Carol Mangione S70 Implementing smoking cessation interventions in primary care settings (STOP): using the interactive systems framework Peter Selby, Laurie Zawertailo, Nadia Minian, Dolly Balliunas, Rosa Dragonetti, Sarwar Hussain, Julia Lecce S71 Testing the Getting To Outcomes implementation support intervention in prevention-oriented, community-based settings Matthew Chinman, Joie Acosta, Patricia Ebener, Patrick S Malone, Mary Slaughter S72 Examining the reach of a multi-component farmers’ market implementation approach among low-income consumers in an urban context Darcy Freedman, Susan Flocke, Eunlye Lee, Kristen Matlack, Erika Trapl, Punam Ohri-Vachaspati, Morgan Taggart, Elaine Borawski S73 Increasing implementation of evidence-based health promotion practices at large workplaces: The CEOs Challenge Amanda Parrish, Jeffrey Harris, Marlana Kohn, Kristen Hammerback, Becca McMillan, Peggy Hannon S74 A qualitative assessment of barriers to nutrition promotion and obesity prevention in childcare Taren Swindle, Geoffrey Curran, Leanne Whiteside-Mansell, Wendy Ward S75 Documenting institutionalization of a health communication intervention in African American churches Cheryl Holt, Sheri Lou Santos, Erin Tagai, Mary Ann Scheirer, Roxanne Carter, Janice Bowie, Muhiuddin Haider, Jimmie Slade, Min Qi Wang S76 Reduction in hospital utilization by underserved patients through use of a community-medical home Andrew Masica, Gerald Ogola, Candice Berryman, Kathleen Richter S77 Sustainability of evidence-based lay health advisor programs in African American communities: A mixed methods investigation of the National Witness Project Rachel Shelton, Lina Jandorf, Deborah Erwin S78 Predicting the long-term uninsured population and analyzing their gaps in physical access to healthcare in South Carolina Khoa Truong S79 Using an evidence-based parenting intervention in churches to prevent behavioral problems among Filipino youth: A randomized pilot study Joyce R. Javier, Dean Coffey, Sheree M. Schrager, Lawrence Palinkas, Jeanne Miranda S80 Sustainability of elementary school-based health centers in three health-disparate southern communities Veda Johnson, Valerie Hutcherson, Ruth Ellis S81 Childhood obesity prevention partnership in Louisville: creative opportunities to engage families in a multifaceted approach to obesity prevention Anna Kharmats, Sandra Marshall-King, Monica LaPradd, Fannie Fonseca-Becker S82 Improvements in cervical cancer prevention found after implementation of evidence-based Latina prevention care management program Deanna Kepka, Julia Bodson, Echo Warner, Brynn Fowler S83 The OneFlorida data trust: Achieving health equity through research & training capacity building Elizabeth Shenkman, William Hogan, Folakami Odedina, Jessica De Leon, Monica Hooper, Olveen Carrasquillo, Renee Reams, Myra Hurt, Steven Smith, Jose Szapocznik, David Nelson, Prabir Mandal S84 Disseminating and sustaining medical-legal partnerships: Shared value and social return on investment James Teufe

Effect of prehospital high-dose glucocorticoid on hemodynamics in patients resuscitated from out-of-hospital cardiac arrest:a sub-study of the STEROHCA trial

Background: Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients. Methods: The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times. Results: A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference − 0.04 mcg/kg/min, 95% CI − 0.07 to − 0.01, p = 0.02). Moreover, after 12–24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from − 4.2 to − 3.8, 95% CIs from − 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from − 0.10 to − 0.07, 95% CIs from − 0.16 to − 0.01), while there were no major differences in heart rate (mean differences from − 4 to − 3, 95% CIs from − 11 to 3). These treatment differences between groups were also present 30–48 h post-admission but to a smaller extent and with increased statistical uncertainty. No differences were found in pulmonary artery catheter measurements between groups. Conclusions: Prehospital treatment with high-dose glucocorticoid was associated with reduced norepinephrine use in resuscitated OHCA patients. Trial registration: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT04624776. Graphic Abstract: [Figure not available: see fulltext.]</p

OveRcoming Adverse ChiLdhood Experiences (ORACLE):A Mixed Methods Intervention Co-design Study to Improve Outcomes for Children and Young People Experiencing or at Risk of Adversity

Childhood exposures to adversity are common and increase risk for negative health and social outcomes throughout the life course. There is limited evidence regarding interventions to prevent or reduce the impact of adverse childhood experiences (ACEs), particularly for families with multiple adversities. Here we present the findings of mixed methods research to co-design a complex intervention to prevent adverse childhood experiences, and their impacts. Using established research methods, and the framework of the Medical Research Council (MRC) complex interventions development guidance, the work was conducted in four stages, shaped by stakeholder engagement and input at every stage. The first stage, Discover, was exploratory and employed evidence synthesis and quantitative (n = 11,564) and qualitative (n = 31) research methods to understand needs, experiences, and evidence gaps. The Define stage developed three intervention principles and identified intervention options, through a series of six co-design workshops with 41 participants and an academic research team workshop. The Develop and Deliver stages were undertaken through a Policy Lab (22 participants), and developed options for intervention design, before converging on a defined intervention that could be delivered and tested. Through this process, we developed a 'village-style' intervention, which functions at three levels: individual service users, operational, and system/strategy. Central to this are link or community health workers who would build relationships with family members, and act as a single point of contact. They should develop an understanding of family needs and the interaction of multiple complex adversities, and advocate for families, facilitating access to services. Crucially, they should use this understanding to work at and feed into operational and strategic levels to reshape services and enhance access for all families at risk of or experiencing adversity. Entry into the intervention through assessments at existing universal touch points, for example at routine perinatal or newborn appointments, should provide a prevention focus and follow the principles of proportionate universalism. Sensitive enquiry regarding financial stress may be a component of the assessment, in response to the findings of this work regarding the contexts created through the interaction of poverty and other adversities. The proposed intervention is designed to improve individual and family outcomes, and generate positive system-level changes. A feasibility study and evaluation will be required in future work, to assess the effects, costs and benefits. The processes and frameworks we developed and used may provide an adaptable template for future intervention co-design work

Surrogate Markers of Cardiovascular Risk and Chronic Obstructive Pulmonary Disease: A Large Case-Controlled Study.

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid-femoral (aortic) pulse wave velocity, augmentation index, and carotid intima-media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima-media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease

Reparación y garantía de no repetición en Wallmapu: la brecha entre la aplicación de justicia a las víctimas mapuche y las normas internacionales

L'article parteix del treball de litigació i de observacions realitzades en els tribunals del sud de Chile aquests últims anys i, en particular, en 2021. Dona compte de la "dilatació" dels judicis quan es tracta de sancionar agents de l'estat que han comès delictes en contra de persones maputxe, com en els casos Huracan o Lemun. Aquest tipus de situacions afecten principis claus del dret com són la reparació del dellicte i la garantia de no repetició. S'exposa com la lentitud i passivitat del sistema judicial xilè provoca un major sentiment d'injustícia per al poble maputxe. Després d'haver presentat aquests principis vinculats amb els Drets Humans, i els seus fonaments en l'àmbit legal i psicosocial, s'analitzaran dos casos de vulneració de drets comesos per agents de l'estat encara vigents per a millor aprehendre les seves diverses conseqüènciesThe article is based on the litigation work and observations made in the courts of southern Chile in recent years and, in particular, in 2021. It gives an account of the "delay" of the trials when it comes to punishing state agents who have committed crimes against Mapuche people, as in the Huracan or Lemun cases. This type of situation affects key principles of law, such as reparation for the crime and the guarantee of non-repetition. It exposes how the slowness and passivity of the Chilean judicial system causes a greater feeling of injustice for the Mapuche people. After having presented these principles related to Human Rights, and their foundations in the legal and psychosocial field, two cases of violation of rights committed by state agents still in force will be analyzed to better apprehend their various consequences.El artículo parte del trabajo de litigación y de observaciones realizadas en los tribunales del sur de Chile en estos últimos años y, en particular, en 2021. Da cuenta de la "dilatación" de los juicios cuando se trata de sancionar agentes del estado que han cometidos delitos en contra de personas mapuche, como en los casos Huracan o Lemun. Este tipo de situaciones afectan principios claves del derecho, como son la reparación del delito y la garantía de no repetición. Se expone cómo la lentitud y pasividad del sistema judicial chileno provoca un mayor sentimiento de injusticia para el pueblo mapuche. Después de haber presentado estos principios vinculados con los Derechos Humanos, y sus fundamentos en el ámbito legal y psicosocial, se analizarán dos casos de vulneración de derechos cometidos por agentes del estado aún vigentes para mejor aprehender sus diversas consecuencias