Dysregulation of the leukocyte signaling landscape during acute COVID-19

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation was tightly correlated with circulating IL-6 levels and high levels of phospho-STAT3 was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-γ production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19

Preference for hotline versus mobile application/countdown-based mobile overdose response services: a qualitative study

Abstract Background In response to the exacerbated rates of morbidity and mortality associated with the overlapping overdose and COVID-19 epidemics, novel strategies have been developed, implemented, operationalized and scaled to reduce the harms resulting from this crisis. Since the emergence of mobile overdose response services (MORS), two strategies have aimed to help reduce the mortality associated with acute overdose including staffed hotline-based services and unstaffed timer-based services. In this article, we aim to gather the perspectives of various key interest groups on these technologies to determine which might best support service users. Methods Forty-seven participants from various interested groups including people who use substances who have and have not used MORS, healthcare workers, family members, harm reduction employees and MORS operators participated in semi-structured interviews. Transcripts were coded and analyzed using a thematic analysis approach. Results Four major themes emerged regarding participant perspectives on the differences between services, namely differences in connection, perceived safety, privacy and accessibility, alongside features that are recommended for MORS in the future. Conclusions Overall, participants noted that individuals who use substances vary in their desire for connection during a substance use session offered by hotline and timer-based service modalities. Participants perceived hotline-based approaches to be more reliable and thus potentially safer than their timer-based counterparts but noted that access to technology is a limitation of both approaches

Feasibility and acceptability of inserts promoting virtual overdose monitoring services (VOMS) in naloxone kits: a qualitative study

Abstract Background In response to the ongoing opioid epidemic, there have been efforts to develop novel harm reduction strategies alongside scaling of currently implemented programs. Virtual overdose monitoring services (VOMS) are a novel intervention which aims to reduce substance-related mortality through technology for those who are out of reach of current supervised consumption sites. Scaling of naloxone programs presents a unique opportunity to promote VOMS to people at risk of substance-related mortality. This study aims to explore the feasibility and acceptability of naloxone kit inserts in promoting awareness of VOMS. Method We used purposive and snowball sampling to recruit 52 key informants, including people who use drugs (PWUD) with experience using VOMS (n = 16), PWUD with no prior experience using VOMS (n = 9), family members of PWUD (n = 5), healthcare and emergency services professionals (n = 10), community-based harm reduction organizations (n = 6), and VOMS administrators/peer support workers (n = 6). Two evaluators completed semi-structured interviews. Interview transcripts were analyzed using thematic analysis informed to identify key themes. Results Four key interrelated themes emerged, including the acceptability of naloxone kit inserts to promote VOMS, best practices for implementation, key messaging to include within promotional materials and facilitators to dissemination of harm reduction material. Participants highlighted that messaging should be promoted both inside and outside the kits, should be concise, provide basic information about VOMS and can be facilitated through current distribution streams. Messaging could further be used to draw attention to local harm reduction services and could be promoted on other supplies, including lighters and safer consumption supplies. Conclusion Findings demonstrate that it is acceptable to promote VOMS within naloxone kits and highlight interviewees preferred ways to do so. Key themes that emerged from interviewees can be used to inform the dissemination of harm reduction information, including VOMS and bolster current strategies for reducing illicit drug overdose

A cost benefit analysis of a virtual overdose monitoring service/mobile overdose response service: the national overdose response service

Abstract Background The overdose crisis continues across Canada which calls for novel harm reduction strategies. Previous research indicates that a majority of eHealth solutions are cost-effective however current literature on the cost-benefit of eHealth for harm reduction is sparse. The National Overdose Response Service (NORS) is a Canada-wide telephone-based harm reduction service. Service users can call the phone number and connect to a peer who can virtually monitor the substance use session and dispatch appropriate interventions in the case of overdose. Objectives of the research/project We aim to assess the cost-benefit of NORS by comparing the estimated cost-savings from prevented overdose mortality to the operating costs of the program, alongside healthcare costs associated with its operation. Methods Data around systems costs and operational costs were gathered for our calculations. Our primary outcome was cost-benefit ratios, derived from estimates and models of mortality rates in current literature and value of life lost. We presented our main results across a range of values for costs and the probability of death following an unwitnessed overdose. These values were utilized to calculate cost-benefit ratios and value per dollar spent on service provision by NORS over the length of the program’s operation (December 2020–2022). Results Over the total funded lifespan of the program, and using a Monte Carlo estimate, the benefit-to-cost ratio of the NORS program was 8.59 (1.53–15.28) per dollar spent, depending on estimated mortality rates following unwitnessed overdose and program operation costs. Further, we conservatively estimate that early community-based naloxone intervention results in healthcare system savings of $4470.82 per overdose response. Conclusions We found the NORS program to have a positive benefit-to-cost ratio when the probability of death following an unwitnessed overdose was greater than 5%. NORS and potentially other virtual overdose monitoring services have the potential to be cost-effective solutions for managing the drug poisoning crisis

Understanding the barriers and facilitators to implementing and sustaining Mobile Overdose Response Services from the perspective of Canadian key interest groups: a qualitative study

Abstract Introduction Unregulated supply of fentanyl and adulterants continues to drive the overdose crisis. Mobile Overdose Response Services (MORS) are novel technologies that offer virtual supervised consumption to minimize the risk of fatal overdose for those who are unable to access other forms of harm reduction. However, as newly implemented services, they are also faced with numerous limitations. The aim of this study was to examine the facilitators and barriers to the adoption of MORS in Canada. Methods A total of 64 semi-structured interviews were conducted between November 2021 and April 2022. Participants consisted of people who use substances (PWUS), family members of PWUS, health care professionals, harm reduction workers, MORS operators, and members of the general public. Inductive thematic analysis was used to identify the major themes and subthemes. Results Respondents revealed that MORS facilitated a safe, anonymous, and nonjudgmental environment for PWUS to seek harm reduction and other necessary support. It also created a new sense of purpose for operators to positively contribute to the community. Further advertising and promotional efforts were deemed important to increase its awareness. However, barriers to MORS implementation included concerns regarding privacy/confidentiality, uncertainty of funding, and compassion fatigue among the operators. Conclusion Although MORS were generally viewed as a useful addition to the currently existing harm reduction services, it’s important to monitor and tackle these barriers by engaging the perspectives of key interest groups

Association of drug overdoses and user characteristics of Canada’s national mobile/virtual overdose response hotline: the National Overdose Response Service (NORS)

Abstract Background Several novel overdose response technology interventions, also known as mobile overdose response services (MORS), have emerged as adjunct measures to reduce the harms associated with the drug poisoning epidemic. This retrospective observational study aims to identify the characteristics and outcomes of individuals utilizing one such service, the National Overdose Response Service (NORS). Methods A retrospective analysis was conducted using NORS call logs from December 2020 to April 2023 imputed by operators. A variety of variables were examined including demographics, substance use and route, location, and call outcomes. Odds ratios and 95% confidence intervals were calculated around variables of interest to test the association between key indicators and drug poisonings. Results Of the 6528 completed calls on the line, 3994 (61.2%) were for supervised drug consumption, 1703 (26.1%) were for mental health support, 354 (5.42%) were for harm reduction education or resources, and 477 (7.31%) were for other purposes. Overall, there were 77 (1.18%) overdose events requiring a physical/ in-person intervention. Of the total calls, 3235 (49.5%) were from women, and 1070 (16.3%) were from people who identified as gender diverse. Calls mostly originated from urban locations (n = 5796, 88.7%) and the province of Ontario (n = 4137, 63.3%). Odds ratios indicate that using opioids (OR 6.72, CI 95% 3.69–13.52), opioids in combination with methamphetamine (OR 9.70, CI 95% 3.24–23.06), multiple consumption routes (OR 6.54, CI 95% 2.46–14.37), and calls occurring in British Columbia (B.C) (OR 3.55, CI 95% 1.46–7.33) had a significantly higher likelihood of a drug poisoning. No deaths were recorded and only 3 false callouts had occurred. The overall drug poisoning event incidence to phone calls was 1.2%. Conclusion NORS presents a complimentary opportunity to access harm reduction services for individuals that prefer to use alone or face barriers to accessing in-person supervised consumption services especially gender minorities with high-risk use patterns

Beliefs, attitudes and experiences of virtual overdose monitoring services from the perspectives of people who use substances in Canada: a qualitative study

Abstract Background Solitary use of substances is a risk factor for substance use-related mortality. Novel e-health harm reduction interventions such as virtual overdose monitoring services (VOMS) have emerged in North America to improve access to emergency overdose support for people who use substances (PWUS). To date, little research has been published, and the perspectives of PWUS are needed to inform evaluation and policy efforts. Objective To explore the beliefs, values and perceptions of PWUS around using and accessing VOMS in Canada. Methods A qualitative study following grounded theory methodology was conducted. Using existing peer networks, purposive and snowball sampling was conducted to recruit PWUS (≥ 18 years) with previous experience with VOMS. Thematic analysis was used to analyze twenty-three interviews. Several methods were employed to enhance rigor, such as independent data coding and triangulation. Results Twenty-three one-on-one telephone interviews of PWUS with previous experience with VOMS were completed and analyzed. The following themes emerged: (1) feelings of optimism around VOMS to save lives; (2) privacy/confidentiality was highly valued due to stigma and fear of arrest; (3) concerns with reliable cell phones negatively impacting VOMS uptake; (4) concerns around emergency response times, specifically in rural/remote communities; (5) desire for trusting relationships with VOMS operators; (6) importance of mental health supports and referrals to psychosocial services; and (7) possible limited uptake due to low public awareness of VOMS. Conclusion This qualitative study provided novel insights about the VOMS from the perspectives of PWUS. PWUS generally felt optimistic about the potential of VOMS as a suitable harm reduction intervention, but several potential barriers around accessing VOMS were identified that may limit uptake. Future research is warranted

Additional file 1 of Association of drug overdoses and user characteristics of Canada’s national mobile/virtual overdose response hotline: the National Overdose Response Service (NORS)

Additional file 1. Figures of NORS uptake over time

Additional file 2 of Association of drug overdoses and user characteristics of Canada’s national mobile/virtual overdose response hotline: the National Overdose Response Service (NORS)

Additional file 2. Description of adverse events recorded