Building Capacity for Injectable Diacetylmorphine and Hydromorphone for the Treatment of Opioid Use Disorder: Identifying Typical Doses.

Identifying typical doses of existing opioid use disorder medications, such as injectable opioid agonist treatment (iOAT), can support client and program needs, and potentially increase iOAT expansion. Longitudinal data from participants in a cohort study (n = 131), along with clinic dispensation records from August 2014 to April 2020, were used to examine physician prescribed as well as used doses of injectable diacetylmorphine and hydromorphone. Dosage groups, by medication and prescribed dose per session, were created for both hydromorphone and diacetylmorphine. A total of 534, 522 injections were registered during the study period among 129 participants. Mean received diacetylmorphine doses ranged from 106 to 989 mg per day, with most clients using 125-262 mg per session (mean 192.99 mg) and attending 2.40 sessions per day. Mean received hydromorphone doses ranged from 51.09 to 696.06 mg per day, with the majority using 88-154 mg per session (mean 121.32 mg; 2.43 sessions). Average daily doses remained stable overtime and, while mid-range doses were most typical, participants used the whole spectrum of allowable dose prescriptions. Evidence supporting typical doses of iOAT can be integrated into program planning to better allow providers and prescribers to anticipate program needs and engage in individualized care.

Retrospective Study of the Prevalence, Histopathology, Therapy, and Survival Time of Neoplastic Disease in Fish.

This study evaluated neoplasia in fish using medical records from zoos, aquariums, and exotic animal veterinarians. The parameters evaluated included geographic location, habitat type, signalment, anatomic location of neoplasia, type of neoplasia as confirmed with histologic examination, survival time, and treatments provided for each patient. These data were entered into the Exotic Species Cancer Research Alliance (ESCRA) database. Out of 455 cases from across the United States and England, most animals submitted were from zoologic parks or aquariums (62.9%), followed by private ownership (1.5%). The percent of female (19.3%) and male (17.8%) patients were similar, and the mean age at the time of diagnosis was 99.45 months, with a range of 12 to 300 months. The species with the highest neoplasia prevalence was koi (18.5%), followed by goldfish (10.8%). The eye was the most commonly reported site for a primary neoplasm (8.4%), and the most prevalent diagnosis across all organ systems was soft tissue sarcoma (26.2%). Only 13 patients in this study (2.9%) received any form of treatment, with a mean survival time of 8.85 months post-treatment. These data demonstrate that while information related to clinical therapy of cancer in fish species is lacking, surgical excision of tumors in fish, when feasible for the patient and client, may improve patient outcomes.

Shared decision-making and client-reported dose satisfaction in a longitudinal cohort receiving injectable opioid agonist treatment (iOAT).

BACKGROUND: Across different types of oral Opioid Agonist Treatment for people with Opioid Use Disorder, receiving a dose that meets their needs is associated with better outcomes. Evidence also shows patients are more likely to receive an "adequate dose" when their prescribers are involving them in decision making. Neither of these findings have been studied in the context of injectable Opioid Agonist Treatment, which is the purpose of this study. METHODS: This study was a retrospective analysis of an 18-month prospective longitudinal cohort study of 131 people receiving injectable Opioid Agonist Treatment. In the 18-month study, observations were collected every two months for one year, and then once more at 18 months. At 6 months, participants were asked whether their dose was satisfactory to them (outcome variable). Generalized Estimating Equations were used, to account for multiple observations from each participant. The final multivariate model was built using a stepwise approach. RESULTS: Five hundred forty-five participant-observations were included in the analysis. Participant-observations were grouped by "dose is satisfactory" and "wants higher dose". From unadjusted analyses, participants were less likely to report being satisfied with their dose if they: were Indigenous, had worse psychological or physical health problems, had ever attempted suicide, were younger when they first injected any drug, were a current smoker, felt troubled by drug problems, gave their medication a lower "drug liking" score, and felt that their doctor was not including them in decisions the way they wanted to be. In the final multivariate model, all previously significant associations except for "current smoker" and "troubled by drug problems" were no longer significant after the addition of the "drug liking" score. CONCLUSIONS: Patients in injectable Opioid Agonist Treatment who are not satisfied with their dose are more likely to: be troubled by drug problems, be a current smoker, and report liking their medication less than dose-satisfied patients. Prescribers' practicing shared decision-making can help patients achieve dose-satisfaction and possibly alleviate troubles from drug problems. Additionally, receiving a satisfactory dose may be dependent on patients being able to access an opioid agonist medication (and formulation) that they like.

Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression.

Importance: Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools. Objective: To identify a reproducible metabolomic biomarker signature in patient dried blood spots (DBSs) that differentiates BD from MDD during depressive episodes and assess its added value when combined with self-reported patient information. Design, Setting, and Participants: This diagnostic analysis used samples and data from the Delta study, conducted in the UK between April 27, 2018, and February 6, 2020. The primary objective was to identify BD in patients with a recent (within the past 5 years) diagnosis of MDD and current depressive symptoms (Patient Health Questionnaire-9 score of 5 or more). Participants were recruited online through voluntary response sampling. The analysis was carried out between February 2022 and July 2023. Main Outcomes and Measures: Patient data were collected using a purpose-built online questionnaire (n = 635 questions). DBS metabolites (n = 630) were analyzed using a targeted mass spectrometry-based platform. Mood disorder diagnoses were established using the Composite International Diagnostic Interview. Results: Of 241 patients in the discovery cohort, 170 (70.5%) were female; 67 (27.8%) were subsequently diagnosed with BD and 174 (72.2%) were confirmed as having MDD; and the mean (SD) age was 28.1 (7.1) years. Of 30 participants in the validation cohort, 16 (53%) were female; 9 (30%) were diagnosed with BD and 21 (70%) with MDD; and the mean (SD) age was 25.4 (6.3) years. DBS metabolite levels were assessed in 241 patients with depressive symptoms with a recent diagnosis of MDD, of whom 67 were subsequently diagnosed with BD by the Composite International Diagnostic Interview and 174 were confirmed as having MDD. The identified 17-biomarker panel provided a mean (SD) cross-validated area under the receiver operating characteristic curve (AUROC) of 0.71 (SD, 0.12; P < .001), with ceramide d18:0/24:1 emerging as the strongest biomarker. Combining biomarker data with patient-reported information significantly enhanced diagnostic performance of models based on extensive demographic data, PHQ-9 scores, and the outcomes from the Mood Disorder Questionnaire. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of MDD (n = 21) or BD (n = 9) during the study's 1-year follow-up period, with a mean (SD) AUROC of 0.73 (0.06; P < .001). Conclusions and Relevance: This study provides a proof of concept for developing an accessible biomarker test to facilitate the differential diagnosis of BD and MDD and highlights the potential involvement of ceramides in the pathophysiological mechanisms of mood disorders.

"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.

Robustness of performance during domain change in an esport: A study of within-expertise transfer.

Research on the transfer of skill from the circumstances in which it was learned to partially or completely novel tasks or situations is a foundational topic in the study of learning, memory, education, and expertise. A long history of transfer research has led to the conclusion that skill learning is generally domain specific. One important transfer problem occurs when a domain of expertise undergoes a fundamental shift, as when experts must adapt to changes in technology, rules, or professional practice. Here we examine skill maintenance in StarCraft 2, a video game of skills which undergoes frequent changes due to updates and includes a variety of gameplay options. Of particular interest are two competing predictions about how transfer will interact with expertise in this domain. The first approach emphasizes perceived similarity of the domains and predicts that skilled individuals will exhibit more favourable transfer than novices as these people will know enough to avoid processes, methods, and strategies which no longer apply after a domain change. The second emphasizes maximal adaptation to task constraints and predicts that experts will suffer the most during a domain change because of the loss of exploitable affordances. Neither approach did a good job explaining behaviour after the major game update called 'StarCraft 2: Heart of the Swarm,' perhaps because transfer was generally strong across all players. However, when examining transfer in the context of larger changes to gameplay, transfer seemed slightly better in more experienced players. The theoretical implications of this apparent interaction effect, and of the apparent resilience of more experienced StarCraft 2 players to transfer costs, are discussed.

The Impact of Injectable Opioid Agonist Treatment (iOAT) on Involvement in Criminalized Activities: A Secondary Analysis from a Clinical Trial in Vancouver, BC.

Purpose: A significant portion of the economic consequences of untreated Opioid Use Disorder (OUD) relate to individuals' involvement in the criminal justice system. The present study uncovers if treatment with iOAT is related to the number of criminal charges amongst participants, what type of crime participants were involved in, and the frequency with which participants were victims of crime. This study contributes to the body of research on the effectiveness of iOAT reducing criminal involvement. Patients and Methods: This is a secondary analysis of police record data obtained from the Vancouver Police Department over a three-year period during the Study to Assess Longer-term Opioid Medication Effectiveness clinical trial. The data was obtained from participants (N = 192) enrolled in the trial through a release of information form. Results: During the three-year period, most charges (45.6%) were property offences, and 25.5% of participants were victims of crime. Participants with no treatment prior to randomization into the SALOME trial were 2.61 (95% CI = 1.64-4.14) more likely to have been charged with a crime than during the iOAT state. Conclusion: IOAT can reduce individuals' involvement with the criminal justice system and is thus a crucial part of the continuum of care. Addiction should be conceptualized as a healthcare rather than criminal issue.

High fat diet reveals sex-specific fecal and liver metabolic alterations in C57BL/6J obese mice.

Obesity is a major health concern that poses significant risks for many other diseases, including diabetes, cardiovascular disease, and cancer. Prevalence of these diseases varies by biological sex. This study utilizes a mouse (C57BL/6J) model of obesity to analyze liver and fecal metabolic profiles at various time points of dietary exposure: 5, 9, and 12 months in control or high fat diet (HFD)-exposed mice. Our study discovered that the female HFD group has a more discernable perturbation and set of significant changes in metabolic profiles than the male HFD group. In the female mice, HFD fecal metabolites including pyruvate, aspartate, and glutamate were lower than control diet-exposed mice after both 9th and 12th month exposure time points, while lactate and alanine were significantly downregulated only at the 12th month. Perturbations of liver metabolic profiles were observed in both male and female HFD groups, compared to controls at the 12th month. Overall, the female HFD group showed higher lactate and glutathione levels compared to controls, while the male HFD group showed higher levels of glutamine and taurine compared to controls. These metabolite-based findings in both fecal and liver samples for a diet-induced effect of obesity may help guide future pioneering discoveries relating to the analysis and prevention of obesity in people, especially for females.

Identification of algal rich microbial blooms in the Sellafield Pile Fuel Storage Pond and the application of ultrasonic treatment to control the formation of blooms.

The presence of microorganisms in a range of nuclear facilities has been known for many years. In this study the microbial community inhabiting the Pile Fuel Storage Pond (PFSP), which is a legacy open-aired facility on the Sellafield nuclear site, Cumbria, UK, was determined to help target microbial bloom management strategies in this facility. The PFSP is currently undergoing decommissioning and the development of prolonged dense microbial blooms reduces the visibility within the water. Such impairment in the pond water visibility can lead to delays in pond operations, which also has financial implications. Efforts to control the microbial population within the PFSP are ongoing, with the installation of ultrasonic treatment units. Here next generation sequencing techniques focussing on broad targets for both eukaryotic and prokaryotic organisms were used to identify the microbial community. On-site monitoring of photosynthetic pigments indicated when microbial blooms formed and that eukaryotic algae were most likely to be responsible for these events. The sequencing data suggested that the blooms were dominated by members of the class Chrysophyceae, a group of golden algae, while evidence of cyanobacteria and other photosynthetic bacteria was limited, further supporting eukaryotic organisms causing the blooms. The results of sequencing data from 2018 was used to inform a change in the operational settings of the ultrasonic units, while monitoring of the microbial community and photosynthetic pigments trends was extended. Since the changes were made to the ultrasonic treatment, the visibility in the pond was significantly improved, with an absence of a spring bloom in 2020 and an overall reduction in the number of days lost due to microbial blooms annually. This work extends our knowledge of the diversity of microbes able to colonise nuclear fuel storage ponds, and also suggests that sequencing data can help to optimise the performance of ultrasonic treatments, to control algal proliferation in the PFSP facility and other inhospitable engineered systems.

The impact of relaxing restrictions on take-home doses during the COVID-19 pandemic on program effectiveness and client experiences in opioid agonist treatment: a mixed methods systematic review.

BACKGROUND: The COVID-19 pandemic led to an unprecedented relaxation of restrictions on take-home doses in opioid agonist treatment (OAT). We conducted a mixed methods systematic review to explore the impact of these changes on program effectiveness and client experiences in OAT. METHODS: The protocol for this review was registered in PROSPERO (CRD42022352310). From Aug.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, Cochrane Register of Controlled Trials, and the grey literature. We included studies reporting quantitative measures of retention in treatment, illicit substance use, overdose, client health, quality of life, or treatment satisfaction or using qualitative methods to examine client experiences with take-home doses during the pandemic. We critically appraised studies using the Mixed Methods Appraisal Tool. We synthesized quantitative data using vote-counting by direction of effect and presented the results in harvest plots. Qualitative data were analyzed using thematic synthesis. We used a convergent segregated approach to integrate quantitative and qualitative findings. RESULTS: Forty studies were included. Most were from North America (23/40) or the United Kingdom (9/40). The quantitative synthesis was limited by potential for confounding, but suggested an association between take-home doses and increased retention in treatment. There was no evidence of an association between take-home doses and illicit substance use or overdose. Qualitative findings indicated that take-home doses reduced clients' exposure to unregulated substances and stigma and minimized work/treatment conflicts. Though some clients reported challenges with managing their medication, the dominant narrative was one of appreciation, reduced anxiety, and a renewed sense of agency and identity. The integrated analysis suggested reduced treatment burden as an explanation for improved retention and revealed variation in individual relationships between take-home doses and illicit substance use. We identified a critical gap in quantitative measures of patient-important outcomes. CONCLUSION: The relaxation of restrictions on take-home doses was associated with improved client experience and retention in OAT. We found no evidence of an association with illicit substance use or overdose, despite the expansion of take-home doses to previously ineligible groups. Including patient-important outcome measures in policy, program development, and treatment planning is essential to ensuring that decisions around take-home doses accurately reflect their value to clients.

The mobilization of nurse-client therapeutic relationships in injectable opioid agonist treatment: Autonomy, advocacy and action.

INTRODUCTION: Injectable opioid agonist treatment (iOAT) is an evidence-based treatment that serves an important minority of people with opioid use disorder who require specialized care. Unique to iOAT care is the consistency with which clients access treatment (up to three times daily), a condition that creates repeated opportunities for health care engagement. To date, no study has examined therapeutic relationships in this life saving, nurse-led treatment that can have lasting implications in the equitable delivery of other forms of addictions care. METHODS: This study used grounded theory to generate a dynamic framework for therapeutic relationship building in iOAT. Researchers collected semi-structured interviews from registered nurses working in iOAT sites (n=24) form January 2020 through June 2022. The study analyzed collected data through a constant comparative analysis; explored through open, axial, and selective coding; and assessed in a conditional relationship matrix. The team reviewed key findings with stakeholders through formalized processes of engagement to confirm saturation of coding categories. Throughout data collection and analysis, researchers integrated feedback from additional knowledge users and member checking. Reported findings adhered to the COREQ1 standardized checklist. RESULTS: We identified five interrelated categories that created a distinct culture of care for iOAT nurses: Ways of Knowing, Personal Investment, Leveraging Empathy, Finding Flexibility, and Collaborating to Overcome. Through creating a safe, nonjudgmental environment, nurses establish therapeutic relationships that build trust to identify client needs outside of medication administration. In turn, nurses participate in team-based problem solving to advocate for client needs. If nurses cannot find flexibility within and outside of the health care system to improve client engagement, tensions can arise and therapeutic relationships can be strained. CONCLUSIONS: Therapeutic relationships are an integral part of building and maintaining trust with a population that has been precariously involved with other forms of health care. Nurses make a substantial effort to create a safe and nonjudgmental environment to manifest a culture of care that bridges client needs and program access. Without the expansion of access to iOAT programs and their embedded services, nurses are limited in their ability to provide individualized care for clients with diverse needs.

Clients' experiences on North America's first take-home injectable opioid agonist treatment (iOAT) program: a qualitative study.

BACKGROUND: To support public health measures during the COVID-19 pandemic, oral opioid agonist treatment (OAT) take-home doses were expanded in Western countries with positive results. Injectable OAT (iOAT) take-home doses were previously not an eligible option, and were made available for the first time in several sites to align with public health measures. Building upon these temporary risk-mitigating guidelines, a clinic in Vancouver, BC continued to offer two of a possible three daily doses of take-home injectable medications to eligible clients. The present study explores the processes through which take-home iOAT doses impacted clients' quality of life and continuity of care in real-life settings. METHODS: Three rounds of semi-structured qualitative interviews were conducted over a period of seventeen months beginning in July 2021 with eleven participants receiving iOAT take-home doses at a community clinic in Vancouver, British Columbia. Interviews followed a topic guide that evolved iteratively in response to emerging lines of inquiry. Interviews were recorded, transcribed, and then coded using NVivo 1.6 using an interpretive description approach. RESULTS: Participants reported that take-home doses granted them the freedom away from the clinic to have daily routines, form plans, and enjoy unstructured time. Participants appreciated the greater privacy, accessibility, and ability to engage in paid work. Furthermore, participants enjoyed greater autonomy to manage their medication and level of engagement with the clinic. These factors contributed to greater quality of life and continuity of care. Participants shared that their dose was too essential to divert and that they felt safe transporting and administering their medication off-site. In the future, all participants would like more accessible treatment such as access longer take-home prescriptions (e.g., one week), the ability to pick-up at different and convenient locations (e.g., community pharmacies), and a medication delivery service. CONCLUSIONS: Reducing the number of daily onsite injections from two or three to only one revealed the diversity of rich and nuanced needs that added flexibility and accessibility in iOAT can meet. Actions such as licencing diverse opioid medications/formulations, medication pick-up at community pharmacies, and a community of practice that supports clinical decisions are necessary to increase take-home iOAT accessibility.

Provider experiences with relaxing restrictions on take-home medications for opioid use disorder during the COVID-19 pandemic: A qualitative systematic review.

BACKGROUND: Historical restrictions on take-home medications for opioid use disorder have generated considerable debate. The COVID-19 pandemic shifted the perceived risks and benefits of daily clinic attendance and led to widespread policy reform, creating an unprecedented opportunity to explore the impact of more flexible prescribing. We conducted a qualitative systematic review to synthesize the evidence on providers' experiences with relaxing restrictions on take-home doses of medications prescribed for opioid use disorder during the COVID-19 pandemic. METHODS: The protocol for this systematic review was registered in PROSPERO (CRD42022360589; https://www.crd.york.ac.uk/prospero/). From Sept.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, the Cochrane Register of Controlled Trials, and the grey literature from 2020 onward. Studies were eligible for inclusion if they used qualitative methods to investigate providers' experiences with relaxed restrictions on take-home medications for opioid use disorder during the COVID-19 pandemic. We appraised study quality using the CASP qualitative checklist and used thematic synthesis and GRADE-CERQual to synthesize the results. RESULTS: We retrieved 13 articles representing 11 studies. Six were conducted in the United States and most focused on changes to methadone treatment. Providers' experiences with increased flexibilities around take-homes were broadly positive, despite widespread initial concern over client safety and the potential for medication misuse. For a small number of providers, concerns about diversion were a specific manifestation of more general unease with loss of control over clients and the treatment process. Most providers appreciated increased flexibilities and described them as enabling more individualized, person-centered care. CONCLUSION: Our findings support the continuation of flexibilities around take-homes and demonstrate that regulations and policies that reduce flexibility around take-homes conflict with person-centered approaches to care. Stronger guidance and support from professional regulatory agencies may help increase uptake of flexibilities around take-homes.

Changes in daily dose in open-label compared to double-blind: The role of clients' expectations in injectable opioid agonist treatment.

Introduction: Though double-blind studies have indicated that hydromorphone and diacetylmorphine produce similar effects when administered through injectable opioid agonist treatment (iOAT) programs, participant preference may influence some aspects of medication dispensation such as dose. Methods:  This is a retrospective longitudinal analysis. Participants (n = 131) were previously enrolled in a double-blind clinical trial for iOAT who continued to receive treatment in an open-label follow up study. Data included medication dispensation records from 2012 to 2020. Using linear regression and paired t-tests, average daily dose totals of hydromorphone and diacetylmorphine were examined comparatively between double-blind and open-label periods. A subgroup analysis explored dose difference by preference using the proxy, blinding guess, a variable used to facilitate the measurement of treatment masking during the clinical trial by asking which medication the participant thought they received. Results: During the open-label period, participants prescribed diacetylmorphine received 49.5 mg less than during the double-blind period (95% CI -12.6,-86.4). Participants receiving hydromorphone did not see a significant dose decrease. Participants who guessed they received hydromorphone during the clinical trial, but learned they were on diacetylmorphine during the open-label period, saw a decrease in total daily dose of 78.3 mg less (95% CI -134.3,-22.4) during the open-label period. Conclusion: If client preference is considered in the treatment of chronic opioid use disorder, clients may be able to better moderate their dose to suit their individual needs. Together with their healthcare providers, clients can participate in their treatment trajectories collaboratively to optimize client outcomes and promote person-centered treatment options.

"As long as that place stays open, I'll stay alive": Accessing injectable opioid agonist treatment during dual public health crises.

BACKGROUND: Since the onset of the COVID-19 pandemic, overdose rates in North America have continued to rise, with more than 100,000 drug poisoning deaths in the past year. Amidst an increasingly toxic drug supply, the pandemic disrupted essential substance use treatment and harm reduction services that reduce overdose risk for people who use drugs. In British Columbia, one such treatment is injectable opioid agonist treatment (iOAT), the supervised dispensation of injectable hydromorphone or diacetylmorphine for people with opioid use disorder. While evidence has shown iOAT to be safe and effective, it is intensive and highly regimented, characterized by daily clinic visits and provider-client interaction-treatment components made difficult by the pandemic. METHODS: Between April 2020 and February 2021, we conducted 51 interviews with 18 iOAT clients and two clinic nurses to understand how the pandemic shaped iOAT access and treatment experiences. To analyze interview data, we employed a multi-step, flexible coding strategy, an iterative and abductive approach to analysis, using NVivo software. RESULTS: Qualitative analysis revealed the ways in which the pandemic shaped clients' lives and the provision of iOAT care. First, client narratives illuminated how the pandemic reinforced existing inequities. For example, socioeconomically marginalized clients expressed concerns around their financial stability and economic impacts on their communities. Second, clients with health comorbidities recognized how the pandemic amplified health risks, through potential COVID-19 exposure or by limiting social connection and mental health supports. Third, clients described how the pandemic changed their engagement with the iOAT clinic and medication. For instance, clients noted that physical distancing guidelines and occupancy limits reduced opportunities for social connection with staff and other iOAT clients. However, pandemic policies also created opportunities to adapt treatment in ways that increased patient trust and autonomy, for example through more flexible medication regimens and take-home oral doses. CONCLUSION: Participant narratives underscored the unequal distribution of pandemic impacts for people who use drugs but also highlighted opportunities for more flexible, patient-centered treatment approaches. Across treatment settings, pandemic-era changes that increase client autonomy and ensure equitable access to care are to be continued and expanded, beyond the duration of the pandemic.

Diepoxybutane induces the p53-dependent transactivation of the CCL4 gene that mediates apoptosis in exposed human lymphoblasts.

Diepoxybutane (DEB) is the most toxic metabolite of the environmental chemical 1,3-butadiene. We previously demonstrated the occurrence of DEB-induced p53-mediated apoptosis in human lymphoblasts. The p53 protein functions as a master transcriptional regulator in orchestrating the genomic response to a variety of stress signals. Transcriptomic analysis indicated that C-C chemokine ligand 4 (CCL4) gene expression was elevated in a p53-dependent manner in DEB-exposed p53-proficient TK6 cells, but not in DEB-exposed p53-deficient NH32 cells. Thus, the objective of this study was to determine whether the CCL4 gene is a transcriptional target of p53 and deduce its role in DEB-induced apoptosis in human lymphoblasts. Endogenous and exogenous wild-type p53 transactivated the activity of the CCL4 promoter in DEB-exposed lymphoblasts, but mutant p53 activity on this promoter was reduced by ∼80% under the same experimental conditions. Knockdown of the upregulated CCL4 mRNA levels in p53-proficient TK6 cells inhibited DEB-induced apoptosis by ∼45%-50%. Collectively, these observations demonstrate for the first time that the CCL4 gene is upregulated by wild-type p53 at the transcriptional level, and this upregulation mediates apoptosis in DEB-exposed human lymphoblasts.

Measuring the preferences of injectable opioid agonist treatment (iOAT) clients: Development of a person-centered scale (best-worst scaling).

BACKGROUND: Injectable opioid agonist treatment (iOAT) is effective for opioid use disorder (OUD), yet little is known about client preferences for accessing iOAT (e.g., with diacetylmorphine, hydromorphone, buprenorphine, fentanyl, etc.). Best-worst scaling (BWS) is a preference elicitation method from health economics that has never been applied to addiction care broadly, or iOAT specifically. We describe the stages of developing a BWS scale that assesses iOAT clients' treatment delivery preferences to inform program planning and maximize healthcare efficiency. METHODS: We underwent several steps to reveal the relevant attributes/levels and design the scale structure. An initial list of potential attributes and levels was established from a literature review and prior qualitative data. Then, we conducted semi-structured interviews and focus groups with clients (n=21) on their iOAT preferences to confirm the attributes and prioritize/include new ones. Next, we conducted semi-structured interviews and focus groups with iOAT experts and stakeholders to receive their input on the draft list of attributes and levels. A BWS profile case design was piloted with iOAT clients (n=18) from different sites during a think aloud interview. After several rounds of revisions, the final version was tested by iOAT clients (n=2) before the scale was launched. RESULTS: We developed a person-centered scale that assesses current and former iOAT clients' most and least wanted aspects of iOAT delivery. The final version yielded 7 unique attributes: choice of medication, choice of dose, convenience, location & space, scheduling & routines, staff & training, and types of services offered. CONCLUSION: This scale can help expand iOAT programs in a way that is person-centered, rapid, and affordable. The methodology is a guide for other regions with similar populations who aim to develop strong quantitative methodologies that prioritize client collaboration.

Feasibility of Testing Client Preferences for Accessing Injectable Opioid Agonist Treatment (iOAT): A Pilot Study.

Purpose: Injectable opioid agonist treatment (iOAT) is an effective treatment for opioid use disorder (OUD). To our knowledge, no research has systematically studied client preferences for accessing iOAT. Incorporating preferences could help meet the heterogenous needs of clients and make addiction care more person-centred. This paper presents a pilot study of a best-worst scaling (BWS) preference elicitation survey that aimed to assess if the survey was feasible and accessible for our population and to test that the survey could gather sound data that would suit our planned analyses. Patients and Methods: Current and former iOAT clients (n = 18) completed a BWS survey supported by an interviewer using a think-aloud approach. The survey was administered on PowerPoint, and responses and contextual field notes were recorded manually. Think-aloud audio was recorded on Audacity. Results: Clients' feedback fell into five categories: framing of the task, accessibility, conceptualization of attributes and levels, formatting, and behaviour predicting questions. Survey repetitiveness was the most consistent feedback. The data simulation showed that 100 responses should provide an adequate sample size. Conclusion: This pilot demonstrates the type of analysis that can be done with BWS in our population, suggests that such analysis is feasible, and highlights the importance of the interviewer and participant working side-by-side throughout the task.

Connecting gut microbiomes and short chain fatty acids with the serotonergic system and behavior in Gallus gallus and other avian species.

The chicken gastrointestinal tract has a diverse microbial community. There is increasing evidence for how this gut microbiome affects specific molecular pathways and the overall physiology, nervous system and behavior of the chicken host organism due to a growing number of studies investigating conditions such as host diet, antibiotics, probiotics, and germ-free and germ-reduced models. Systems-level investigations have revealed a network of microbiome-related interactions between the gut and state of health and behavior in chickens and other animals. While some microbial symbionts are crucial for maintaining stability and normal host physiology, there can also be dysbiosis, disruptions to nutrient flow, and other outcomes of dysregulation and disease. Likewise, alteration of the gut microbiome is found for chickens exhibiting differences in feather pecking (FP) behavior and this alteration is suspected to be responsible for behavioral change. In chickens and other organisms, serotonin is a chief neuromodulator that links gut microbes to the host brain as microbes modulate the serotonin secreted by the host's own intestinal enterochromaffin cells which can stimulate the central nervous system via the vagus nerve. A substantial part of the serotonergic network is conserved across birds and mammals. Broader investigations of multiple species and subsequent cross-comparisons may help to explore general functionality of this ancient system and its increasingly apparent central role in the gut-brain axis of vertebrates. Dysfunctional behavioral phenotypes from the serotonergic system moreover occur in both birds and mammals with, for example, FP in chickens and depression in humans. Recent studies of the intestine as a major site of serotonin synthesis have been identifying routes by which gut microbial metabolites regulate the chicken serotonergic system. This review in particular highlights the influence of gut microbial metabolite short chain fatty acids (SCFAs) on the serotonergic system. The role of SCFAs in physiological and brain disorders may be considerable because of their ability to cross intestinal as well as the blood-brain barriers, leading to influences on the serotonergic system via binding to receptors and epigenetic modulations. Examinations of these mechanisms may translate into a more general understanding of serotonergic system development within chickens and other avians.

Comparing virtual reality, desktop-based 3D, and 2D versions of a category learning experiment.

Virtual reality (VR) has seen increasing application in cognitive psychology in recent years. There is some debate about the impact of VR on both learning outcomes and on patterns of information access behaviors. In this study we compare performance on a category learning task between three groups: one presented with three-dimensional (3D) stimuli while immersed in the HTC Vive VR system (n = 26), another presented with the same 3D stimuli while using a flat-screen desktop computer (n = 26), and a third presented with a two-dimensional projection of the stimuli on a desktop computer while their eye movements were tracked (n = 8). In the VR and 3D conditions, features of the object to be categorized had to be revealed by rotating the object. In the eye tracking control condition (2D), all object features were visible, and participants' gaze was tracked as they examined each feature. Over 240 trials we measured accuracy, reaction times, attentional optimization, time spent on feedback, fixation durations, and fixation counts for each participant as they learned to correctly categorize the stimuli. In the VR condition, participants had increased fixation counts compared to the 3D and 2D conditions. Reaction times for the 2D condition were significantly faster and fixation durations were lower compared to the VR and 3D conditions. We found no significant differences in learning accuracy between the VR, 3D, and 2D conditions. We discuss implications for both researchers interested in using VR to study cognition, and VR developers hoping to use non-VR research to guide their designs and applications.