Aryl hydrocarbon receptor activation alters immune cell populations in the lung and bone marrow during coronavirus infection.

Respiratory viral infections are one of the major causes of illness and death worldwide. Symptoms associated with respiratory infections can range from mild to severe, and there is limited understanding of why there is large variation in severity. Environmental exposures are a potential causative factor. The aryl hydrocarbon receptor (AHR) is an environment-sensing molecule expressed in all immune cells. Although there is considerable evidence that AHR signaling influences immune responses to other immune challenges, including respiratory pathogens, less is known about the impact of AHR signaling on immune responses during coronavirus (CoV) infection. In this study, we report that AHR activation significantly altered immune cells in the lungs and bone marrow of mice infected with a mouse CoV. AHR activation transiently reduced the frequency of multiple cells in the mononuclear phagocyte system, including monocytes, interstitial macrophages, and dendritic cells in the lung. In the bone marrow, AHR activation altered myelopoiesis, as evidenced by a reduction in granulocyte-monocyte progenitor cells and an increased frequency of myeloid-biased progenitor cells. Moreover, AHR activation significantly affected multiple stages of the megakaryocyte lineage. Overall, these findings indicate that AHR activation modulates multiple aspects of the immune response to a CoV infection. Given the significant burden of respiratory viruses on human health, understanding how environmental exposures shape immune responses to infection advances our knowledge of factors that contribute to variability in disease severity and provides insight into novel approaches to prevent or treat disease.NEW & NOTEWORTHY Our study reveals a multifaceted role for aryl hydrocarbon receptor (AHR) signaling in the immune response to coronavirus (CoV) infection. Sustained AHR activation during in vivo mouse CoV infection altered the frequency of mature immune cells in the lung and modulated emergency hematopoiesis, specifically myelopoiesis and megakaryopoiesis, in bone marrow. This provides new insight into immunoregulation by the AHR and extends our understanding of how environmental exposures can impact host responses to respiratory viral infections.

Substance Use Research with Indigenous Communities: Exploring and Extending Foundational Principles of Community Psychology.

Many Indigenous communities are concerned with substance use (SU) problems and eager to advance effective solutions for their prevention and treatment. Yet these communities also are concerned about the perpetuation of colonizing, disorder-focused, stigmatizing approaches to mental health, and social narratives related to SU problems. Foundational principles of community psychology-ecological perspectives, empowerment, sociocultural competence, community inclusion and partnership, and reflective practice-provide useful frameworks for informing ethical community-based research pertaining to SU problems conducted with and by Indigenous communities. These principles are explored and extended for Indigenous community contexts through themes generated from seven collaborative studies focused on understanding, preventing, and treating SU problems. These studies are generated from research teams working with Indigenous communities across the United States and Canada-inclusive of urban, rural, and reservation/reserve populations as well as adult and youth participants. Shared themes indicate that Indigenous SU research reflects community psychology principles, as an outgrowth of research agendas and processes that are increasingly guided by Indigenous communities. At the same time, this research challenges these principles in important ways pertaining to Indigenous-settler relations and Indigenous-specific considerations. We discuss these challenges and recommend greater synergy between community psychology and Indigenous research.

Screening and Management of Substance Use in Pregnancy: A Review.

Substance use during pregnancy has important implications for health care providers, policy makers, and can negatively impact a woman's health and the health of her children. Understanding trends, patterns of use and outcomes are critical to prevention campaigns, building awareness, and providing effective care. This review will discuss the current therapeutic approaches and recommendations for screening and patient management for substance use in pregnancy and during the postpartum period, and it is geared towards any care providers who care for patients or those who may care for patients who may be at risk for substance use during pregnancy.

Epidemiology and Effects of Substance Use in Pregnancy.

Substance use during pregnancy has important implications for health care providers and policymakers and can negatively affect a woman's health and the health of her children. Understanding trends, patterns of use, and outcomes are critical to developing prevention campaigns, building awareness, and providing effective care. This review critically examines the current literature on substance use in pregnancy and during the postpartum period in terms of epidemiology, risk factors, and implications. The risk factors for substance use in pregnancy, the challenges associated with reporting these cases, and the adverse effects of common substances on maternal and fetal health are discussed.

Harm reduction in name, but not substance: a comparative analysis of current Canadian provincial and territorial policy frameworks.

BACKGROUND: In Canada, funding, administration, and delivery of health services-including those targeting people who use drugs-are primarily the responsibility of the provinces and territories. Access to harm reduction services varies across jurisdictions, possibly reflecting differences in provincial and territorial policy commitments. We examined the quality of current provincial and territorial harm reduction policies in Canada, relative to how well official documents reflect internationally recognized principles and attributes of a harm reduction approach. METHODS: We employed an iterative search and screening process to generate a corpus of 54 provincial and territorial harm reduction policy documents that were current to the end of 2015. Documents were content-analyzed using a deductive coding framework comprised of 17 indicators that assessed the quality of policies relative to how well they described key population and program aspects of a harm reduction approach. RESULTS: Only two jurisdictions had current provincial-level, stand-alone harm reduction policies; all other documents were focused on either substance use, addiction and/or mental health, or sexually transmitted and/or blood-borne infections. Policies rarely named specific harm reduction interventions and more frequently referred to generic harm reduction programs or services. Only one document met all 17 indicators. Very few documents acknowledged that stigma and discrimination are issues faced by people who use drugs, that not all substance use is problematic, or that people who use drugs are legitimate participants in policymaking. A minority of documents recognized that abstaining from substance use is not required to receive services. Just over a quarter addressed the risk of drug overdose, and even fewer acknowledged the need to apply harm reduction approaches to an array of drugs and modes of use. CONCLUSIONS: Current provincial and territorial policies offer few robust characterizations of harm reduction or go beyond rhetorical or generic support for the approach. By endorsing harm reduction in name, but not in substance, provincial and territorial policies may communicate to diverse stakeholders a general lack of support for key aspects of the approach, potentially challenging efforts to expand harm reduction services.

Honoring Indigenous culture-as-intervention: Development and validity of the Native Wellness AssessmentTM.

There is a need for Indigenous-centered research to appraise culture's role in wellness. Researchers described the development and validity of the Native Wellness Assessment (NWATM). The NWA has culture-as-intervention at its apex. Wellness, culture, and cultural intervention practices (CIPs) are explored from an Indigenous perspective. Indigenous clients completed matching self-report and observer versions of the NWA at three time points during addictions treatment. Statistically and psychometrically, the NWA content and structure performed well, demonstrating that culture is an effective and fair intervention for Indigenous peoples with addictions. The NWA can inform Indigenous health and community-based programs and policy.

Insulin dependent apolipoprotein B degradation and phosphatidylinositide 3-kinase activation with microsomal translocation are restored in McArdle RH7777 cells following serum deprivation.

Previous studies in rat hepatocytes demonstrated that insulin-dependent apolipoprotein (apo) B degradation (IDAD) is lost when cells are maintained for 3 d under enriched culture conditions. Loss of IDAD correlates with increased expression of protein tyrosine phosphatase 1B (PTP1B) known to be associated with resistance to insulin signaling in the liver. McArdle RH7777 hepatoma (McA) cells cultured in serum containing medium are resistant to IDAD; demonstrate a 30% increase in apo B secretion, and express increased levels of PTP1B protein and mRNA. In addition, insulin-stimulated Class I phosphatidylinositide 3-kinase (PI3K) activity of anti-pY immunoprecipitates is severely blunted. IDAD resistance in McA cells correlates with diminished translocation of insulin-stimulated pY-IRS1 to intracellular membranes. Incubation of McA cells with RK682, a protein tyrosine phosphatase inhibitor, is sufficient to restore IDAD in resistant McA cells. Overall, results further support the importance of Class I PI3K activity in IDAD, and suggest that loss of this activity is sufficient to cause resistance. Although other factors are involved in downstream events including sortilin binding to apo B, autophagy, and lysosomal degradation, loss of signal generation and reduced localization of Class I PI3K to intracellular membranes plays a significant role in IDAD resistance.

Reflections on How a University Binge Drinking Prevention Initiative Supports Alcohol Screening, Brief Intervention, and Referral for Student Alcohol Use.

What's Your Cap: Know When to Put a Lid on Drinking (WYC) is a student-led and research-based binge-drinking prevention campaign at the University of Saskatchewan, Canada. It was formed to encourage a culture of alcohol moderation on the university campus through peer-to-peer engagement that emphasizes promotional items and activities of interest to students. Since its development in 2011, WYC has been guided by a logic model that promotes: 1) perceived and actual student drinking norms on campus; 2) benefits of a student-led initiative; and 3) merits of working with community partners. With the release of a clinical guide in Canada for alcohol screening, brief intervention, and referral (SBIR) in 2013, WYC was prompted to consider whether it is a form of population-based SBIR. SBIR is commonly undertaken in the substance use field by health care practitioners, and this paper shares the potential for a student-based SBIR modification on a university campus.

Predictors of research use among staff in aboriginal addiction treatment programs serving women.

The objective of this study was to identify the predictors of research use among staff from Aboriginal addiction programs serving women. A total of 89 staff from 26 Aboriginal addiction programs completed an online survey that included items assessing the theory of planned behavior constructs (attitudes, subjective norms, perceived behavioral control), intent to use research, and research use. Consistent with the theory of planned behavior, research use was predicted by attitudes, subjective norms, and perceived behavioral control. Intent to use research was not a mediator, demonstrating partial applicability of the theory of planned behavior to staff in Aboriginal addiction programs serving women.

Insulin-dependent apolipoprotein B degradation is mediated by autophagy and involves class I and class III phosphatidylinositide 3-kinases.

Insulin acutely stimulates the degradation of apolipoprotein B (apo B) which decreases very low density lipoprotein (VLDL) secretion by liver. Insulin-dependent apo B degradation (IDAD) occurs following phosphatidylinositide 3-kinase (PI3K) activation and involves lysosomal degradation. Insulin suppression of apo B secretion is blocked by over-expression of phosphatase and tensin homologue (PTEN) in McArdle RH7777 (McA) cells suggesting the importance of Class I PI3K generated PI (3,4,5) triphosphate (PIP3) in IDAD. Classical autophagy inhibitors including 3-methyladenine, L-asparagine and bafilomycin A1 also blocked the ability of insulin to suppress apo B secretion by rat hepatocytes (RH) suggesting that IDAD occurs through an autophagy-related mechanism. IDAD is also blocked following over-expression in McA cells of a dominant negative kinase-defective Vps34, a class III PI3K that generates PI 3-monophosphate required for autophagy. Vps34 inhibition of IDAD occurs without altering insulin-dependent S473 phosphorylation of Akt indicating PI3K/PIP3/Akt signaling is intact. Cellular p62/SQSTM1, an inverse indicator of autophagy, is increased with insulin treatment consistent with the known ability of insulin to inhibit autophagy, and therefore the role of insulin in utilizing components of autophagy for apo B degradation is unexpected. Thapsigargan, an inducer of endoplasmic reticulum (ER) stress, and a recently demonstrated autophagy inhibitor, blocked apo B secretion which contrasted with other autophagy inhibitors and mutant Vps34 results which were permissive with respect to apo B secretion. Pulse chase studies indicated that intact B100 and B48 proteins were retained in cells treated with thapsigargan consistent with their accumulation in autophagosomal vacuoles. Differences between IDAD and ER stress-coupled autophagy mediated by thapsgargin suggest that IDAD involves an unique form of autophagy. Insulin action resulting in hepatic apo B degradation is novel and important in understanding regulation of hepatic VLDL metabolism.

Insulin suppression of apolipoprotein B in McArdle RH7777 cells involves increased sortilin 1 interaction and lysosomal targeting.

Insulin suppresses secretion of very low density lipoprotein (VLDL) apolipoprotein (apo) B in primary rodent hepatocytes (RH) by favoring the degradation of B100, the larger form of apo B, through post-endoplasmic reticulum proteolysis. Sortilin 1 (sort1), a multi-ligand sorting receptor, has been proposed as a mediator of lysosomal B100 degradation by directing B100 in pre-VLDL to lysosomes rather than allowing maturation to VLDL and secretion. The purpose of our studies was to investigate the role of sort1 in insulin-dependent degradation of apo B. Using liver derived McArdle RH7777 (McA) cells, we demonstrate that insulin suppresses VLDL B100 secretion via a phosphatidylinositide 3-kinase (PI3K) dependent process that is inhibitable by wortmannin in a fashion similar to RH. Using McA cells and in situ cross-linking, we demonstrate that insulin acutely (30min) stimulates the interaction of B100 with sort1. The insulin-induced interaction of sort1-B100 is markedly enhanced when lysosomal degradation is inhibited by Bafilomycin A1 (BafA1), an inhibitor of lysosomal acidification. As BafA1 also prevents insulin suppressive effects on apo B secretion, our results suggest that sort1-B100 interaction stimulated by insulin transiently accumulates with BafA1 and favors B100 secretion by default.

Outcome assessment of a triangular clinic as a harm reduction intervention in Rajaee-Shahr Prison, Iran.

BACKGROUND: Transmission of the human immunodeficiency virus (HIV) among incarcerated injection drug users (IDU) is a health epidemic in the Islamic Republic of Iran. Triangular clinics (TCs) were established in prisons as a harm reduction measure to decrease the risk of HIV transmission and other blood-borne infections. The objective of this study was to assess the immediate outcomes of one TC among male IDUs in Iran's Rajaee-Shahr prison. METHODS: This study was conducted in two stages between 2003 and 2005. In the preparatory stage, focus group data was collected to update the prison's TC education and medical interventions and construct the self-report questionnaire. In stage two, 150 male IDUs were recruited in a closed cohort study design to assess the immediate outcome of the TC. Participants were measured at baseline and followed up to six months to measure their drug use, attitude toward and knowledge of high risk behaviours, serological conversion for HIV, HBV and HCV, and engagement in risky behaviors. The TC outcomes were determined through random urine analysis testing, a self-administered questionnaire and behaviour report cards, and viral infection testing. RESULTS: The findings of the urine analyses indicated a minimal yet consistent decrease in drug use over the six months. The pre and post- self-administered questionnaire data relayed a modest change in IDU risky behaviours associated with sexual practices; this was greater in comparison to the knowledge and attitude measures. It was determined that age may have a detrimental effect as may viral infections (HIV and HBV) on knowledge, attitude and behavior change. Both education and employment may have a protective effect. Data collected from the self-report behaviour cards similarly showed a modest reduction in high risk practices. At the six month follow-up, only one case became HIV positive, 9 HCV and 17 HBV. CONCLUSIONS: Considering that HIV is concentrated among Iranian prisoners who inject drugs at a high level, the results of this study indicate that TCs are a possible effective intervention. However, many prisoners continued with risky behaviors even if they were participating in harm reduction measures, such as methadone maintenance therapy.

Remotely and collaboratively evaluating a campus-based therapy dog program during the COVID-19 pandemic.

The COVID-19 pandemic adversely affected the wellbeing of university students and adults in general, emphasizing the need for mental health programming that was compliant with physical distancing mandates. The present evaluation investigated mental health and social connection within the context of COVID-19 by remotely evaluating a virtual animal-assisted activity at the University of Saskatchewan - PAWS Your Stress. The purpose of this article is to outline our evaluation methods and findings, while calling specific attention to the collaborative strategies that were implemented within a remote, time-sensitive context. The evaluation findings revealed that remote animal-assisted programming can facilitate connections with humans and animals, and promote multiple mental health benefits, despite the lack of physical interaction with the animals. Our lessons learned indicate that remote program logic modelling workshops are feasible when suited to audience demographics. Further, our experience suggests that the Most Significant Change technique (a qualitative, participatory, storytelling method that elicits outcome data) can be useful in time-restricted evaluations, and the necessity of central steps in the process may vary depending on evaluation goals. This project has implications for future evaluation work, by demonstrating the effective use of remote methods that allowed for successful stakeholder collaboration.

Recognizing Zooeyia to Promote Companion Animal Welfare in Urban Bangladesh.

The One Health concept of zooeyia refers to the benefits of companion animals in human health and is gaining global research attention. This exploratory study aimed to understand contemporary experiences and perceptions of the social benefits and challenges of living with a companion animal in urban Bangladesh. Thirty-five qualitative interviews were conducted with companion animal owners (20), animal sellers (10), and livestock service department officers (5) from two major cities in Bangladesh, Dhaka and Khulna. Thematic analysis found that historically, animals had a utilitarian purpose, such as livestock for food and dogs for security. The role and perceptions of companion animals began to change for some around the turn of the century. Today, companion animal caretakers report social, psychological and physical health benefits from integrating companion animals into their lives. They also report that companion animal ownership can contribute to social problems due to the prevailing stigma against companion animals. This is rooted in the continued utilitarian role attached to companion animals by the majority of the Bangladesh population as well as religious-based non-acceptance. As a result, the Animal Welfare Act (2019) is not well implemented, posing a key concern for companion animal welfare. To tackle this, we propose various ways in which the emerging concept of zooeyia can help promote the welfare of companion animals by challenging the stigma associated with them in Bangladesh.

Insights into Canadians' Perceptions of Service Dogs in Public Spaces.

Service Dogs (SDs) are an increasingly common type of working dog supporting people with disabilities in Canada. One of the groups being paired with SDs is Veterans diagnosed with posttraumatic stress injuries (PTSIs). In past research, Veterans have expressed stress over negative interactions with people in public spaces because an SD brings attention to their disability. There is a dearth of research exploring perceptions of SDs in public settings. METHODS: A total of 485 Canadians were surveyed via an online questionnaire about their demographic information and beliefs about SDs in public spaces. Data were analyzed using robust ordinary least squares (OLS) regression to determine which demographic features, if any, contribute to perceptions. RESULTS: Generally, the Canadian public holds highly positive perceptions of SDs being in public spaces. Our analysis found that women, people who currently have pets, and Indigenous people were more supportive of SDs in public spaces than others. People with certain cultural heritages were less receptive. CONCLUSION: These findings are an important beginning contribution to the growing SD and Veteran health field.

An Experiential Approach to Canine-Assisted Learning in Corrections for Prisoners Who Use Substances.

ABSTRACT: Canine-assisted interventions are a promising approach to help address substance use and mental health issues in prisons. However, canine-assisted interventions in prisons have not been well explored in relation to experiential learning (EL) theory, despite canine-assisted interventions and EL aligning in many ways. In this article, we discuss a canine-assisted learning and wellness program guided by EL for prisoners with substance use issues in Western Canada. Letters written by participants to the dogs at the conclusion of the program suggest that such programming can help shift relational dynamics and the prison learning environment, benefit prisoners' thinking patterns and perspectives, and help prisoners generalize and apply key learnings to recovery from addiction and mental health challenges. Implications are discussed in relation to clinicians' practices, prisoners' health and wellness, and prison programming.

Unleashing compassionate care: canine-assisted intervention as a promising harm reduction approach to prisonization in Canada and its relevance to forensic psychiatry.

In recent years, there has been a global advancement in the offering of canine-assisted interventions (CAI) in prisons. However, these programs have focused primarily on the benefits to the dogs involved and not on the impact on the participants. The authors of this perspective study have been running a CAI program with therapy dogs, called PAWSitive Support, in a Canadian federal prison since 2016. Thoughts from the program facilitators and interviews with prison staff indicate that the program, and specifically the therapy dogs, provides a unique and integrated source of comfort, support, and love for participants. These benefits are consistent with those seen in CAI programs outside of prisons. Unique to the prison setting appears to be an improvement in participant-staff relations. The therapy dogs have helped participants to experience comfort and consequently express their emotions. This seems to contribute to their recognition of support within the prison system and specifically developing trust with staff. Additionally, the dogs have helped to create an experience of the feeling of love within the prison, interpreted as the feeling of being cared for, which is rare for this population. The authors suggest that the integration of a therapy dog intervention in prison could be a novel harm reduction strategy to address issues related to prisonization and associated mental health concerns, including substance use. This consideration can offer unique insight into the field of forensic psychiatry about providing compassionate care to patients.

Case report: A community case study of the human-animal bond in animal-assisted therapy: the experiences of psychiatric prisoners with therapy dogs.

Prisoners frequently experience chronic loneliness and lack social support, which can exacerbate their struggles with incarceration. According to attachment theory, individuals who are insecurely attached may be more likely to develop unstable relationships and engage in antisocial behavior as adults. In 2015 an animal-assisted therapy (AAT) program was implemented in a Canadian forensic psychiatric facility/prison, a "hybrid" facility that adheres to federal legislation regarding correctional services but follows provincial mental health legislation. The program centers on the development of a human-animal bond (HAB), which serves as a connection between the animals and prisoners. The HAB also addresses issues related to toxic masculinity, which are often present among men incarcerated in correctional facilities, including psychiatric prisons. An instrumental community case study design involving 6 prisoners at a forensic psychiatric facility/prison over 24 AAT sessions between 2015-2019 was undertaken. Interviews with the prisoners and their mental health clinicians were thematically analyzed to explore how the HAB was experienced as a form of attachment. Four themes emerged: safety, physical touch, reciprocity, and acceptance. These themes suggest that the therapy dogs have the potential to serve as a surrogate attachment figure for prisoners, mitigating their experiences of disconnection and fostering their development of interpersonal connections. This suggests attachment theory underpins the HAB and highlights the contribution of AAT practice and research in forensic psychiatric facilities/prisons. This study also suggests that the program's offering of prosocial support and nurturance/caring aligns with the specific criminogenic risks and needs identified within Correctional Service Canada's Risk-Need-Responsivity (RNR) model for rehabilitation. Continued research and attention should be paid to AAT programs as a valuable addition to the range of support networks available to prisoners in psychiatric or non-psychiatric institutions.

Perceptions and experiences of health care professionals and staff with animal-assisted interventions in health care settings: a qualitative systematic review protocol.

OBJECTIVE: The objective of this review is to examine the perceptions and experiences of health care professionals and staff in implementing or coordinating animal-assisted interventions in health care settings. INTRODUCTION: Animal-assisted interventions are applied in the areas of health, education, and human services to help improve individuals' health and wellness. The positive effects of animal-assisted interventions on individuals have been shown in multiple health disciplines, from pediatrics to long-term care, and include outcomes such as decreased feelings of loneliness and increased feelings of support. The increase of animal-assisted interventions in human health has initiated growing research on health care professionals' perceptions and experiences of these interventions. No current qualitative systematic reviews have focused solely on health care professionals' and staff's perceptions of animal-assisted interventions. Conducting such a review will advance understanding of how these providers perceive and engage with animal-assisted interventions as well as their influence and role in coordinating these interventions. INCLUSION CRITERIA: This review will consider qualitative primary studies that address the perceptions and experiences of health care professionals and staff in implementing or coordinating animal-assisted interventions in health care settings. METHODS: Nine bibliographic databases will be systematically searched for published and unpublished studies by employing a three-step search strategy. Studies published from database inception to present and in English will be considered. Two reviewers will independently appraise the studies and extract qualitative data using the standardized JBI critical appraisal and data extraction instruments. Findings from the review will be categorized according to similarity in meaning, and categories will be subjected to a meta-synthesis to produce a single comprehensive set of synthesized findings. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021258909.

Outcomes of a controlled trial with visiting therapy dog teams on pain in adults in an emergency department.

CONTEXT: Pain is a primary reason individuals attend an Emergency Department (ED), and its management is a concern. OBJECTIVES: Change in symptoms and physiologic variables at 3 time points pre-post a ten-minute St. John Ambulance therapy dog team visit compared to no visit in ED patients who experienced pain. DESIGN, SETTING AND PARTICIPANTS: Using a controlled clinical trial design, pain, anxiety, depression and well-being were measured with the Edmonton Symptom Assessment System (revised version) (ESAS-r) 11-point rating scales before, immediately after, and 20 minutes post- therapy dog team visit with Royal University Hospital ED patients participating in the study (n = 97). Blood pressure and heart rate were recorded at the time points. Control data was gathered twice (30 minutes apart) for comparison (n = 101). There were no group differences in age, gender or ethnicity among the control and intervention groups (respectively mean age 59.5/57.2, ethnicity 77.2% Caucasian/87.6%, female 43.6% /39.2%, male 56.4%/60.8%,). INTERVENTION: 10 minute therapy dog team visit in addition to usual care. MAIN OUTCOME MEASURES: Change in reported pain from pre and post therapy dog team visit and comparison with a control group. RESULTS: A two-way ANOVA was conducted to compare group effects. Significant pre- post-intervention differences were noted in pain for the intervention (mean changeint. = -0.9, SD = 2.05, p = .004, 95% confidence interval [CI] = [0.42, 1.32], ηp2 = 04) but not the control group. Anxiety (mean changeint. = -1.13, SD = 2.80, p = .005, 95% CI = [0.56, 1.64], ηp2 = .04), depression (mean changeint. = -0.72, SD = 1.71, p = .002, 95% CI = [0.39, 1.11], ηp2 = .047), and well-being ratings (mean changeint. = -0.87, SD = 1.84, p < .001, 95% CI = [0.49, 1.25], ηp2 = .07) similarly improved for the intervention group only. There were no pre-post intervention differences in blood pressure or heart rate for either group. Strong responders to the intervention (i.e. >50% reduction) were observed for pain (43%), anxiety (48%), depression (46%), and well-being (41%). CONCLUSIONS: Clinically significant changes in pain as well as significant changes in anxiety, depression and well-being were observed in the therapy dog intervention compared to control. The findings of this novel study contribute important knowledge towards the potential value of ED therapy dogs to affect patients' experience of pain, and related measures of anxiety, depression and well-being. TRIAL REGISTRATION: This controlled clinical trial is registered with ClinicalTrials.gov, registration number NCT04727749.