Improving Surgical Care and Outcomes in Older Cancer Patients Through Implementation of a Pre-Surgical Toolkit (OPTI-Surg)-Final Results of a Phase III Cluster Randomized Trial (Alliance A231601CD).

OBJECTIVE: To assess the effect of a practice-level preoperative frailty screening and optimization toolkit (OPTI-Surg) on postoperative functional recovery and complications in elderly cancer patients undergoing major surgery. SUMMARY BACKGROUND DATA: Frailty is common in older adults. it increases risk for poor postoperative functional recovery and complications. The potential for a practice-level screening/optimization intervention to improve outcomes is unknown. METHODS: Thoracic, gastrointestinal, and urologic oncological surgery practices within the NCI Community Oncology Research Program (NCORP) were randomized 1:1:1, to usual care (UC), OPTI-Surg, or OPTI-Surg with implementation coach. OPTI-Surg consisted of the Edmonton Frail Scale and guided recommendations for referral interventions. Patients ≥70 years old undergoing curative intent surgery were eligible. Primary outcome was 8 weeks postoperative function (kCal/week). Key secondary outcome was complications within 90 days. Mixed models were used to compare UC to the 2 OPTI-Surg arms combined. RESULTS: From 7/2019 to 9/2022, 325 patients were enrolled from 29 practices. 199 (64 UC, 135 OPTI-Surg) and 279 (78 UC, 201 OPTI-Surg) were evaluable for primary and secondary analysis, respectively. UC and OPTI-Surg patients did not significantly differ on total caloric expenditure (2.2 UC, 2.0 OPTI-Surg) after adjusting for baseline function (P=0.53). UC and OPTI-Surg patients did not significantly differ on postoperative complications (25.6% UC, 35.3% OPTI-Surg, P=0.5). CONCLUSIONS: Frailty assessment was successfully performed, but the OPTI-Surg intervention did not improve postoperative function nor reduce postoperative complications compared to UC. Future analysis will explore practice-level factors associated with toolkit implementation and differences between the coaching and non-coaching arms.

Defining Priorities in Value-Based Cancer Care: Insights From the Alliance for Clinical Trials in Oncology National Cooperative Group Survey.

PURPOSE: We determine how stakeholders prioritize the importance of oncologic outcomes, patient-reported outcomes (PROs), and cancer-related health care costs. METHODS: A survey was distributed to the National Clinical Trials Network Alliance for Clinical Trials in Oncology cooperative group membership from May 14 to June 30, 2022. Respondents were asked to rate (5-point Likert scale) and rank (1-9) evidence-based value domains: overall survival, treatment toxicities/complications, quality of life (QOL), financial toxicity, access to care, compliance with evidence-based care, health system performance, scientific discovery and innovation, and cost to the health care system. RESULTS: A total of 514 members responded, including researchers (24.7%), nurses (19.5%), medical oncologists (17.9%), administrators (9.3%), surgical and radiation oncologists (9.1%), patient advocates (3.1%), and nonphysician providers (16.4%). Participants represented various practice settings including National Cancer Institute-designated cancer centers (29.8%), university-affiliated academic cancer centers (21%), hospital-owned oncology practices (21.8%), and others (27.4%). There was agreement in how respondents prioritized value domains (W = 0.39, P < .001). Respondents ranked patient QOL (mean rank: 2.6 ± 1.9) as most important above all other metrics including survival (mean rank: 3.5 ± 0.3) and access to care (mean rank: 3.5 ± 2.1; P < .001). Members engaged in direct patient care also ranked access to care of higher importance than nonclinicians (P = .026). Cost to the health care system (mean rank: 7.5 ± 2.1) and health system performance (mean rank: 7 ± 2) were ranked as least important (P < .001). Inclusion of PROs into therapeutic assessment (59.3%) was the most frequently selected priority of future cooperative group initiatives. CONCLUSION: Oncology community stakeholders deemed patient-centered value domains as most important and considered patient QOL the highest priority. Inclusion of PROs into clinical trials was endorsed as an important component of therapeutic assessment. These findings can be taken into consideration when creating a value framework for inclusion in cancer clinical trials.

Educational role of nurse practitioners in a family practice centre: perspectives of learners and nurses.

OBJECTIVE: To examine the role of nurse practitioners (NPs) as educators of family medicine residents in order to better understand the interprofessional educational dynamics in a clinical teaching setting. DESIGN: A qualitative descriptive approach, using purposive sampling. SETTING: A family practice centre that is associated with an academic department of family medicine and is based in an urban area in southern Ontario. PARTICIPANTS: First-year (8 of 9) and second-year (9 of 10) family medicine residents whose training program was based at the family practice centre, and all NPs (4 of 4) who worked at the centre. METHODS: Semistructured interviews were conducted, which were audiotaped and transcribed. An iterative approach was used for coding and analysis. Data management software guided organization and analysis of the data. MAIN FINDINGS: Four interconnected themes were identified: role clarification, professional identity formation, factors that enhance the educational role of NPs, and factors that limit the educational role of NPs. Although residents recognized NPs' value in team functioning and areas of specialized knowledge, they were unclear about NPs' scope of practice. Depending on residents' level of training, residents tended to respond differently to teaching by NPs. More of the senior residents believed they needed to think like physicians and preferred clinical teaching from physician teachers. Junior residents valued the step-by-step instructional approach used by NPs, and they had a decreased sense of vulnerability when being taught by NPs. Training in teaching skills was helpful for NPs. Barriers to providing optimal education included opportunity, time, and physician attitudes. CONCLUSION: The lack of an intentional orientation of family medicine residents to NPs' scope of practice and educational role can lead to difficulties in interprofessional education. More explicit recognition of the evolving professional identity of family medicine residents might decrease resistance to teaching by NPs and ensure that interprofessional teaching and learning strategies are effective. Faculty development opportunities for all educators are required to manage these issues, both to ensure teaching competencies and to reinforce positive interprofessional collaboration.

Acute overactive endocannabinoid signaling induces glucose intolerance, hepatic steatosis, and novel cannabinoid receptor 1 responsive genes.

Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1). Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP), perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG) and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251) and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control), IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2), which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50%) the majority (303 of 533) of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1-dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and identify novel cannabinoid responsive genes.