"It feels like I'm coming to a friend's house": an interpretive descriptive study of an integrated care site offering iOAT (Dr. Peter Centre).

BACKGROUND: Injectable opioid agonist treatment (iOAT) has proven to be a safe and effective treatment option for severe opioid use disorder (OUD). Yet, iOAT is often isolated from other health and social services. To align with a person-centered care approach, iOAT can be embedded in sites that combine systems and services that have been historically fragmented and that address multiple comorbidities (integrated care sites). The present study investigates the addition of iOAT at an integrated care in Vancouver, British Columbia. We aimed to capture what it means for service users and service providers to incorporate iOAT in an integrated care site and describe the processes by which the site keeps people engaged. METHODS: We conducted 22 interviews with 15 service users and 14 interviews with 13 service providers across two rounds of individual semi-structured interviews (Fall 2021, Summer 2022). The second interview round was precipitated by a service interruption in medication dispensation. Interview audio was recorded, transcribed, and then analysed in NVivo 1.6 following an interpretive description approach. RESULTS: The emergent themes from the analysis are represented in two categories: (1) a holistic approach (client autonomy, de-medicalized care, supportive staff relationships, multiple opportunities for engagement, barriers to iOAT integration) and (2) a sense of place (physical location, social connection and community belonging, food). CONCLUSION: Incorporating iOAT at an integrated care site revealed how iOAT delivery can be strengthened through its direct connection to a diverse, comprehensive network of health and social services that are provided in a community atmosphere with high quality therapeutic relationships.

Spotting as a risk mitigation method: A qualitative study comparing organization-based and informal methods.

OBJECTIVES: To explore the similarities and differences of organization-based and informal spotting (remote supervision of substance use) from the perspectives of spotters and spottees across Canada. METHODS: Spotters and spottees who spot informally and for organizations were recruited across Ontario and Nova Scotia. We interviewed 20 informal and 10 organization-based participants by phone using semi-structured interviews between 08/2020 and 11/2020. Participants were asked about each methods benefits and limitations. Interviews were audio-recorded, transcribed, and analyzed thematically. RESULTS: Benefits of informal spotting included its ability to strengthen social connections and foster autonomy in overdose response planning. The lack of support for informal spotters created stress and burnout. Organization-based spotters enjoyed the spotting training and support provided. However, regulations surrounding having to call ambulance in overdose events deterred many people from wanting to work for or call these services. CONCLUSIONS: Both organization-based and informal spotting have a role in mitigating harms associated with the overdose crisis. Moving forward, further research is needed on how to optimize these services for all people who use drugs in varying jurisdictions internationally.

A qualitative study on overdose response in the era of COVID-19 and beyond: how to spot someone so they never have to use alone.

BACKGROUND: Spotting is an informal practice among people who use drugs (PWUD) where they witness other people using drugs and respond if an overdose occurs. During COVID-19 restrictions, remote spotting (e.g., using a telephone, video call, and/or a social media app) emerged to address physical distancing requirements and reduced access to harm reduction and/or sexually transmitted blood borne infection (STBBI's) prevention services. We explored spotting implementation issues from the perspectives of spotters and spottees. METHODS: Research assistants with lived/living expertise of drug use used personal networks and word of mouth to recruit PWUD from Ontario and Nova Scotia who provided or used informal spotting. All participants completed a semi-structured, audio-recorded telephone interview about spotting service design, benefits, challenges, and recommendations. Recordings were transcribed and thematic analysis was used. RESULTS: We interviewed 20 individuals between 08/2020-11/2020 who were involved in informal spotting. Spotting was provided on various platforms (e.g., telephone, video calls, and through texts) and locations (e.g. home, car), offered connection and community support, and addressed barriers to the use of supervised consumption sites (e.g., location, stigma, confidentiality, safety, availability, COVID-19 related closures). Spotting calls often began with setting an overdose response plan (i.e., when and who to call). Many participants noted that, due to the criminalization of drug use and fear of arrest, they preferred that roommates/friends/family members be called instead of emergency services in case of an overdose. Both spotters and spottees raised concerns about the timeliness of overdose response, particularly in remote and rural settings. CONCLUSION: Spotting is a novel addition to, but not replacement for, existing harm reduction services. To optimize overdose/COVID-19/STBBI's prevention services, additional supports (e.g., changes to Good Samaritan Laws) are needed. The criminalization of drug use may limit uptake of formal spotting services.

Assessing the impact of food insecurity on HIV medication adherence in the context of an integrated care programme for people living with HIV in Vancouver, Canada.

OBJECTIVE: Food insecurity, or self-reports of inadequate food access due to limited financial resources, remains prevalent among people living with HIV (PLHIV). We examined the impact of food insecurity on combination antiretroviral therapy (cART) adherence within an integrated care programme that provides services to PLHIV, including two meals per day. DESIGN: Adjusted OR (aOR) were estimated by generalized estimating equations, quantifying the relationship between food insecurity (exposure) and cART adherence (outcome) with multivariable logistic regression. SETTING: We drew on survey data collected between February 2014 and March 2016 from the Dr. Peter Centre Study based in Vancouver, Canada. PARTICIPANTS: The study included 116 PLHIV at baseline, with ninety-nine participants completing a 12-month follow-up interview. The median (quartile 1-quartile 3) age was 46 (39-52) years at baseline and 87 % (n 101) were biologically male at birth. RESULTS: At baseline, 74 % (n 86) of participants were food insecure (≥2 affirmative responses on Health Canada's Household Food Security Survey Module) and 67 % (n 78) were adherent to cART ≥95 % of the time. In the adjusted regression analysis, food insecurity was associated with suboptimal cART adherence (aOR = 0·47, 95 % CI 0·24, 0·93). CONCLUSIONS: While food provision may reduce some health-related harms, there remains a relationship between this prevalent experience and suboptimal cART adherence in this integrated care programme. Future studies that elucidate strategies to mitigate food insecurity and its effects on cART adherence among PLHIV in this setting and in other similar environments are necessary.

"I'm Just Forgetting and I Don't Know Why": Exploring How People Living With HIV-Associated Neurocognitive Disorder View, Manage, and Obtain Support for Their Cognitive Difficulties.

HIV-associated neurocognitive disorder (HAND) is common, but the lived experience of HAND is not well-understood. In this descriptive qualitative study, we explored how adults with HAND view, manage, and obtain support for cognitive difficulties. We interviewed 25 participants (20% female; median age = 51 years) who were diagnosed with HAND using neuropsychological assessment and a clinical interview. Semistructured interviews, co-developed with community members living with HIV, focused on how cognitive difficulties manifested and progressed, impacted well-being, and were discussed with others. We analyzed interview transcripts using a team-based, thematic approach. Participants described concentration, memory, and multitasking difficulties that fluctuated over time, as well as potential risk factors, management strategies, and psychosocial consequences. They reported they seldom discussed cognitive impairment with health care professionals, and that receiving a HAND diagnosis was validating, informative, yet somewhat disconcerting. Conversations between health care professionals and people living with HIV about HAND may provide opportunities for education, assessment, and support.

Integrated HIV care and service engagement among people living with HIV who use drugs in a setting with a community-wide treatment as prevention initiative: a qualitative study in Vancouver, Canada.

INTRODUCTION: Social-structural inequities impede access to, and retention in, HIV care among structurally vulnerable people living with HIV (PLHIV) who use drugs. The resulting disparities in HIV-related outcomes among PLHIV who use drugs pose barriers to the optimization of HIV treatment as prevention (TasP) initiatives. We undertook this study to examine engagement with, and impacts of, an integrated HIV care services model tailored to the needs of PLHIV who use drugs in Vancouver, Canada - a setting with a community-wide TasP initiative. METHODS: We conducted qualitative interviews with 30 PLHIV who use drugs recruited from the Dr. Peter Centre, an HIV care facility operating under an integrated services model and harm reduction approach. We employed novel analytical techniques to analyse participants' service trajectories within this facility to understand how this HIV service environment influences access to, and retention in, HIV care among structurally vulnerable PLHIV who use drugs. RESULTS: Our findings demonstrate that participants' structural vulnerability shaped their engagement with the HIV care facility that provided access to resources that facilitated retention in HIV care and antiretroviral treatment adherence. Additionally, the integrated service environment helped reduce burdens associated with living in extreme poverty by meeting participants' subsistence (e.g. food, shelter) needs. Moreover, access to multiple supports created a structured environment in which participants could develop routine service use patterns and have prolonged engagement with supportive care services. Our findings demonstrate that low-barrier service models can mitigate social and structural barriers to HIV care and complement TasP initiatives for PLHIV who use drugs. CONCLUSION: These findings highlight the critical role of integrated service models in promoting access to health and support services for structurally vulnerable PLHIV. Complementing structural interventions with integrated service models that are tailored to the needs of structurally vulnerable PLHIV who use drugs will be pursuant to the goals of TasP.

"We're giving you something so we get something in return": Perspectives on research participation and compensation among people living with HIV who use drugs.

BACKGROUND: Compensation for participating in research has been a fundamental element of the research apparatus despite concerns about its impact on incentivising participation. Researchers and research ethics boards acknowledge that compensation may prompt structurally vulnerable populations, such as people who use drugs (PWUD), to engage in research primarily out of financial need. Thus, institutional restrictions around compensation have been implemented. This study explores the ethical implications of compensation practices aimed at 'protecting' structurally vulnerable people living with HIV (PLHIV) who use drugs within the context of individuals' lived realities. METHODS: We draw on five focus groups conducted in 2011 with 25 PLHIV who use drugs and access a community-based HIV care facility in Vancouver, Canada. This analysis focused on participants' perceptions of research compensation, which became the central point of discussion in each group. RESULTS: Participants viewed research as a transactional process through which they could challenge the underpinnings of bioethics and bargain for compensation. Research compensation was thus critical to attracting participants and positioned as a 'legitimate' form of income. Participants' medicalised identities, specifically living with HIV, were fundamental to justifying compensation. The type of compensation (e.g. gift card, cash) also significantly impacted whether participants were fully compensated and, at times, served to exacerbate their structural vulnerability. CONCLUSION: Research compensation is critical in shaping structurally vulnerable populations' participation and experiences with research and can further marginalize individuals. Practices surrounding research compensation, particularly for drug-using and HIV-positive populations, need to be evaluated to ensure participants are equitably compensated for the expertise they provide.

Enantioselective total synthesis of brevetoxin A: convergent coupling strategy and completion.

A highly convergent, enantioselective total synthesis of brevetoxin A is reported. The development of a [X+2+X] Horner-Wadsworth-Emmons/cyclodehydration/reductive etherification convergent coupling strategy allowed a unified approach to the synthesis of two advanced tetracyclic fragments from four cyclic ether subunits. The Horner-Wittig coupling of the two tetracyclic fragments provided substrates that were explored for reductive etherification, the success of which delivered a late-stage tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.

Enantioselective total synthesis of brevetoxin A: unified strategy for the B, E, G, and J subunits.

Brevetoxin A is a decacyclic ladder toxin that possesses 5-, 6-, 7-, 8-, and 9-membered oxacycles, as well as 22 tetrahedral stereocenters. Herein, we describe a unified approach to the B, E, G, and J rings based upon a ring-closing metathesis strategy from the corresponding dienes. The enolate technologies developed in our laboratory allowed access to the precursor acyclic dienes for the B, E, and G medium-ring ethers. The strategies developed for the syntheses of these four monocycles ultimately provided multigram quantities of each of the rings, supporting our efforts toward the completion of a convergent synthesis of brevetoxin A.

Access to a welwitindolinone core using sequential cycloadditions.

A concise approach to the core skeleton of the welwitindolinone alkaloids was developed on the basis of sequential cycloaddition reactions. First, a palladium catalyzed enantioselective [6 + 3] trimethylenemethane cycloaddition onto a tropone nucleus was used to generate the requisite bicyclo[4.3.1]decadiene. Subsequent modifications to the cycloadduct allowed for an intramolecular [4 + 2] cycloaddition to generate the oxindole and complete the core of the natural product family.

Total synthesis of brevetoxin A.

A total synthesis of brevetoxin A is reported. Two tetracyclic coupling partners, prepared from previously reported advanced fragments, were effectively united via a Horner-Wittig olefination. The resulting octacycle was progressed to substrates that were explored for reductive etherification, the success of which led to a penultimate tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.

Asymmetric synthesis of bicyclo[4.3.1]decadienes and bicyclo[3.3.2]decadienes via [6 + 3] trimethylenemethane cycloaddition with tropones.

The cyanosubstituted trimethylenemethane donor undergoes palladium-catalyzed [6 + 3] cycloaddition with a variety of tropones to yield bicyclo[4.3.1]decadienes in excellent regio-, diastereo-, and enantioselectivity. Products of the Pd-TMM [6 + 3] cycloaddition participate in a thermal [3,3] sigmatropic rearrangement to yield bicyclo[3.3.2]decadienes in good yield.

Improved synthesis of the ABCDE fragment of brevetoxin A.

A second-generation synthesis of the BCDE fragment of brevetoxin A is described. Novel reactions were developed that extend the utility of the asymmetric glycolate alkylation reaction and improve scale-up to provide gram quantities of the B and E subunits. Significant improvements to the convergent assembly of the tetracycle were also realized. In addition, formation of the A ring lactone was accomplished to complete the ABCDE pentacycle.

A convergent coupling strategy for the formation of polycyclic ethers: stereoselective synthesis of the BCDE fragment of brevetoxin A.

A stereoselective synthesis of the BCDE fragment of brevetoxin A has been completed. anti-Glycolate aldol, glycolate alkylation, and ring-closing metathesis reactions were employed as key bond-forming events. A convergent assembly strategy was employed that relied on a Horner-Wadsworth-Emmons union of two complex fragments. Subsequent cyclization and dehydration led to efficient generation of an intermediate endocyclic enol ether, which was advanced to a tetracyclic fragment. [reaction: see text]

Anti-selective aldol reactions with titanium enolates of N-glycolyloxazolidinethiones.

[reaction: see text] A highly diastereoselective anti aldol addition utilizing a variety of N-glycolyloxazolidinethiones has been developed. Enolization of an N-glycolyloxazolidinethione with titanium (IV) chloride and (-)-sparteine followed by addition of an aldehyde activated with additional TiCl(4) resulted in highly anti-selective aldol additions, typically with no observable syn isomers. Allyl-protected glycolates demonstrated the highest levels of selection and yields, although O-benzyl and O-methyl glycolyloxazolidinethiones also performed well.