PRimary Care Opioid Use Disorders treatment (PROUD) trial protocol: a pragmatic, cluster-randomized implementation trial in primary care for opioid use disorder treatment

BACKGROUND: Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. METHODS: PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be \u3e 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims ( electronic health records, [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. DISCUSSION: The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings

The Tangibility of Personalized 3D-Printed Feedback May Enhance Youths' Physical Activity Awareness, Goal Setting, and Motivation: Intervention Study

Background: In the United Kingdom, most youth fail to achieve the government guideline of 60 min of moderate to vigorous physical activity (MVPA) daily. Reasons that are frequently cited for the underachievement of this guideline include (1) a lack of awareness of personal physical activity levels (PALs) and (2) a lack of understanding of what activities and different intensities contribute to daily targets of physical activity (PA). Technological advances have enabled novel ways of representing PA data through personalized tangible three-dimensional (3D) models. Objective: The purpose of this study was to investigate the efficacy of 3D-printed models to enhance youth awareness and understanding of and motivation to engage in PA. Methods: A total of 39 primary school children (22 boys; mean age 7.9 [SD 0.3] years) and 58 secondary school adolescents (37 boys; mean age 13.8 [SD 0.3] years) participated in a 7-week fading intervention, whereby participants were given 3D-printed models of their previous week’s objectively assessed PALs at 4 time points. Following the receipt of their 3D model, each participant completed a short semistructured video interview (children, 4.5 [SD 1.2] min; adolescents, 2.2 [SD 0.6] min) to assess their PA awareness, understanding, and motivation. Data were transcribed verbatim and thematically analyzed to enable key emergent themes to be further explored and identified. Results: Analyses revealed that the 3D models enhanced the youths’ awareness of and ability to recall and self-evaluate their PA behaviors. By the end of the study, the youths, irrespective of age, were able to correctly identify and relate to the government’s PA guideline represented on the models, despite their inability to articulate the government's guideline through time and intensity. Following the fourth 3D model, 72% (71/97) of the youths used the models as a goal-setting strategy, further highlighting such models as a motivational tool to promote PA.Conclusions: The results suggest that 3D-printed models of PA enhanced the youths’ awareness of their PA levels and provided a motivational tool for goal setting, potentially offering a unique strategy for future PA promotion

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Adapting inpatient addiction medicine consult services during the COVID‑19 pandemic

An amendment to this paper has been published and can be accessed via the original article.Medicine, Faculty ofOther UBCNon UBCMedicine, Department ofReviewedFacult

Developing a Women’s Health track within addiction medicine fellowship: reflections and inspirations

Abstract Background Women who use drugs face sexism and intersectional stigma that influence their drug use experiences and treatment needs. There is a need to build the capacity of addiction medicine specialists who can deliver gender-responsive services and advance research and policy in women-focused addiction care. We describe the development of a Women’s Health track within an addiction medicine fellowship program and reflect on successes, challenges, and future directions. Main body The Women’s Health track was developed in collaboration between program leaders in Addiction Medicine and Obstetrics/Gynecology. Implementing the track led to the development of women-focused rotations and continuity clinics, as well as enrichment of women’s health didactic education for all fellows. The fellowship track spurred interdepartmental mentorship and collaboration on research and advocacy projects. Conclusion Addiction medicine fellowships can replicate this curriculum model to advance women-focused education, research, and policy. Future curricula should focus on structural sexism in drug use and addiction treatment throughout a woman’s life course

Study protocol for a pragmatic trial of the Consult for Addiction Treatment and Care in Hospitals (CATCH) model for engaging patients in opioid use disorder treatment

Abstract Background Treatment for opioid use disorder (OUD) is highly effective, yet it remains dramatically underutilized. Individuals with OUD have disproportionately high rates of hospitalization and low rates of addiction treatment. Hospital-based addiction consult services offer a potential solution by using multidisciplinary teams to evaluate patients, initiate medication for addiction treatment (MAT) in the hospital, and connect patients to post-discharge care. We are studying the effectiveness of an addiction consult model [Consult for Addiction Treatment and Care in Hospitals (CATCH)] as a strategy for engaging patients with OUD in treatment as the program rolls out in the largest municipal hospital system in the US. The primary aim is to evaluate the effectiveness of CATCH in increasing post-discharge initiation and engagement in MAT. Secondary aims are to assess treatment retention, frequency of acute care utilization and overdose deaths and their associated costs, and implementation outcomes. Methods A pragmatic trial at six hospitals, conducted in collaboration with the municipal hospital system and department of health, will be implemented to study the CATCH intervention. Guided by the RE-AIM evaluation framework, this hybrid effectiveness-implementation study (Type 1) focuses primarily on effectiveness and also measures implementation outcomes to inform the intervention’s adoption and sustainability. A stepped-wedge cluster randomized trial design will determine the impact of CATCH on treatment outcomes in comparison to usual care for a control period, followed by a 12-month intervention period and a 6- to 18-month maintenance period at each hospital. A mixed methods approach will primarily utilize administrative data to measure outcomes, while interviews and focus groups with staff and patients will provide additional information on implementation fidelity and barriers to delivering MAT to patients with OUD. Discussion Because of their great potential to reduce the negative health and economic consequences of untreated OUD, addiction consult models are proliferating in response to the opioid epidemic, despite the absence of a strong evidence base. This study will provide the first known rigorous evaluation of an addiction consult model in a large multi-site trial and promises to generate knowledge that can rapidly transform practice and inform the potential for widespread dissemination of these services. Trial registration: NCT0361133

Offering nurse care management for opioid use disorder in primary care: Impact on emergency and hospital utilization in a cluster-randomized implementation trial

Patients with opioid use disorder (OUD) have increased emergency and hospital utilization. The PROUD trial showed that implementation of office-based addiction treatment (OBAT) increased OUD medication treatment compared to usual care, but did not decrease acute care utilization in patients with OUD documented pre-randomization (clinicaltrials.gov/study/NCT03407638). This paper reports secondary emergency and hospital utilization outcomes in patients with documented OUD in the PROUD trial. This cluster-randomized implementation trial was conducted in 12 clinics from 6 diverse health systems (March 2015-February 2020). Patients who visited trial clinics and had an OUD diagnosis within 3 years pre-randomization were included in primary analyses; secondary analyses added patients with OUD who were new to the clinic or with newly-documented OUD post-randomization. Outcomes included days of emergency care and hospital utilization over 2 years post-randomization. Explanatory outcomes included measures of OUD treatment. Patient-level analyses used mixed-effect regression with clinic-specific random intercepts. Among 1988 patients with documented OUD seen pre-randomization (mean age 49, 53 % female), days of emergency care or hospitalization did not differ between intervention and usual care; OUD treatment also did not differ. In secondary analyses among 1347 patients with OUD post-randomization, there remained no difference in emergency or hospital utilization despite intervention patients receiving 32.2 (95 % CI 4.7, 59.7) more days of OUD treatment relative to usual care. Implementation of OBAT did not reduce emergency or hospital utilization among patients with OUD, even in the sample with OUD first documented post-randomization in whom the intervention increased treatment. •Treatment of opioid use disorder (OUD) has the potential to decrease emergency and hospital care.•This study evaluated implementation of a program in which nurses support medication treatment of OUD in primary care.•Although patients entering intervention clinics post-randomization had more OUD treatment but did not have decreased acute care

Luminescence sensing and imaging:general discussion

Faraday Discussion on Supramolecular Photochemistr