Quality improvement projects conducted by interprofessional teams of learners: Implementation and impact.

Students in their second year of the Vanderbilt Program of Interprofessional Learning (VPIL) complete team-based quality improvement (QI) projects in their assigned clinic as part of the core curriculum. This report describes the creation and implementation of the student teams' QI curriculum and investigates how clinical preceptors view the project impact. Between 2012-2019, the VPIL teams designed and implemented 69 improvement projects. Improvement projects fell primarily into three categories: improving clinic care delivery (n = 25, 36%), patient education and health coaching (n = 21, 30%), and quality measures such as screening tests/prophylaxis (n = 10, 14%). Clinic preceptors received a survey about the sustainability and effectiveness of the projects. Survey feedback was received from 44/69 (64%) preceptors. Many (70%) projects resulted in perceived improvements, and some projects (34%) had improvements that are still in use. Despite barriers and challenges, interprofessional student teams can successfully learn the basics of QI and work together to design and implement a project. These projects have the potential to make meaningful changes in clinic practices and are helpful to the clinic preceptors.

Professionalism of Admitting and Consulting Services and Trauma Patient Outcomes.

OBJECTIVE: To determine whether trauma patients managed by an admitting or consulting service with a high proportion of physicians exhibiting patterns of unprofessional behaviors are at greater risk of complications or death. SUMMARY BACKGROUND DATA: Trauma care requires high-functioning interdisciplinary teams where professionalism, particularly modeling respect and communicating effectively, is essential. METHODS: This retrospective cohort study used data from 9 level I trauma centers that participated in a national trauma registry linked with data from a national database of unsolicited patient complaints. The cohort included trauma patients admitted January 1, 2012 through December 31, 2017. The exposure of interest was care by 1 or more high-risk services, defined as teams with a greater proportion of physicians with high numbers of patient complaints. The study outcome was death or complications within 30 days. RESULTS: Among the 71,046 patients in the cohort, 9553 (13.4%) experienced the primary outcome of complications or death, including 1875 of 16,107 patients (11.6%) with 0 high-risk services, 3788 of 28,085 patients (13.5%) with 1 high-risk service, and 3890 of 26,854 patients (14.5%) with 2+ highrisk services (P < 0.001). In logistic regression models adjusting for relevant patient, injury, and site characteristics, patients who received care from 1 or more high-risk services were at 24.1% (95% confidence interval 17.2% to 31.3%; P < 0.001) greater risk of experiencing the primary study outcome. CONCLUSIONS: Trauma patients who received care from at least 1 service with a high proportion of physicians modeling unprofessional behavior were at an increased risk of death or complications.

Front-Line innovation: Rapid implementation of a nurse-driven protocol for care of outpatients with COVID-19.

AIMS AND OBJECTIVES: Our objective was to rapidly adapt and scale a registered nurse-driven Coordinated Transitional Care (C-TraC) programme to provide intensive home monitoring and optimise care for outpatient Veterans with COVID-19 in a large urban Unites States healthcare system. BACKGROUND: Our diffuse primary care network had no existing model of care by which to provide coordinated result tracking and monitoring of outpatients with COVID-19. DESIGN: Quality improvement implementation project. METHODS: We used the Replicating Effective Programs model to guide implementation, iterative Plan-Do-Study-Act cycles and SQUIRE reporting guidelines. Two transitional care registered nurses, and a geriatrician medical director developed a protocol that included detailed initial assessment, overnight delivery of monitoring equipment and phone-based follow-up tailored to risk level and symptom severity. We tripled programme capacity in time for the surge of cases by training Primary Care registered nurses. RESULTS: Between 23 March and 15 May 2020, 120 Veterans with COVID-19 were enrolled for outpatient monitoring; over one-third were aged 65 years or older, and 70% had medical conditions associated with poor COVID-19 outcomes. All Veterans received an initial call within a few hours of the laboratory reporting positive results. The mean length of follow-up was 8.1 days, with an average of 4.2 nurse and 1.3 physician or advanced practice clinician contacts per patient. The majority (85%) were managed entirely in the outpatient setting. After the surge, the model was disseminated to individual primary care teams through educational sessions. CONCLUSION: A model based on experienced registered nurses can provide comprehensive, effective and sustainable outpatient monitoring to high-risk populations with COVID-19.

Interprofessional education between medical students and nurse practitioner students in a Global Health course.

BACKGROUND: Few global health experiences include intentionally-directed interprofessional training. We aim to prospectively evaluate the impact of a global health elective in facilitating interprofessional education (IPE) and promoting cultural sensitivity. METHODS: We included in our study, medical and nursing students who participated in the 2015 and 2016 cohorts of the Nicaragua Global Health course. The course consisted of a 12-week curriculum, and included an in-country immersion where students were organized into small-groups that participated in a variety of interprofessional activities. Students filled out pre- and post-course surveys. We performed quantitative analysis on numeric data and qualitative analysis on open-ended questions. RESULTS: Of 39 total students enrolled in the course, 26 (18 medical and 8 nursing students) participated in the study and filled out the pre- and post-course surveys. Mean competency scores increased for all questions between pre- and post-course surveys, and of these, 5 of 7 reached statistical significance. Qualitative themes identified included: 1) the importance of understanding other team member's roles and relative strengths; 2) the value provided by the breaking down of traditional power dynamics between clinicians. CONCLUSIONS: Global health experiences represent a unique and under-utilized opportunity for facilitating IPE.

Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis.

We have recently shown that non-viral gene therapy can stabilise the decline of lung function in patients with cystic fibrosis (CF). However, the effect was modest, and more potent gene transfer agents are still required. Fuson protein (F)/Hemagglutinin/Neuraminidase protein (HN)-pseudotyped lentiviral vectors are more efficient for lung gene transfer than non-viral vectors in preclinical models. In preparation for a first-in-man CF trial using the lentiviral vector, we have undertaken key translational preclinical studies. Regulatory-compliant vectors carrying a range of promoter/enhancer elements were assessed in mice and human air-liquid interface (ALI) cultures to select the lead candidate; cystic fibrosis transmembrane conductance receptor (CFTR) expression and function were assessed in CF models using this lead candidate vector. Toxicity was assessed and 'benchmarked' against the leading non-viral formulation recently used in a Phase IIb clinical trial. Integration site profiles were mapped and transduction efficiency determined to inform clinical trial dose-ranging. The impact of pre-existing and acquired immunity against the vector and vector stability in several clinically relevant delivery devices was assessed. A hybrid promoter hybrid cytosine guanine dinucleotide (CpG)- free CMV enhancer/elongation factor 1 alpha promoter (hCEF) consisting of the elongation factor 1α promoter and the cytomegalovirus enhancer was most efficacious in both murine lungs and human ALI cultures (both at least 2-log orders above background). The efficacy (at least 14% of airway cells transduced), toxicity and integration site profile supports further progression towards clinical trial and pre-existing and acquired immune responses do not interfere with vector efficacy. The lead rSIV.F/HN candidate expresses functional CFTR and the vector retains 90-100% transduction efficiency in clinically relevant delivery devices. The data support the progression of the F/HN-pseudotyped lentiviral vector into a first-in-man CF trial in 2017.

Loss of δ-GABAA receptor-mediated tonic currents in the adult prelimbic cortex following adolescent alcohol exposure.

Delayed maturation of the adolescent prefrontal cortex may render it particularly vulnerable to insults, including those associated with drugs of abuse. Using a rat model of binge alcohol exposure, the present study examined the effect of adolescent intermittent ethanol (AIE) exposure during postnatal days 28-42 on γ-aminobutyric acid (GABA)ergic neurotransmission in the prelimbic cortex. In control rats, patch-clamp electrophysiology in acute slices obtained at different postnatal ages revealed a developmental increase in the GABAA receptor-mediated tonic current in layer V pyramidal neurons but no change in layers II/III when measured in the adult. In slices from AIE-exposed rats, the amplitude of the tonic current was significantly reduced compared with controls when tested at postnatal days 45, 60 and 90-120. This AIE-induced reduction in tonic current was found to reflect attenuation of currents mediated by δ-subunit containing receptors. Consistent with this, facilitation of the tonic current by bath application of either ethanol or allopregnanolone was attenuated in slices from AIE-exposed adult rats compared with control rats. However, expression of this facilitation as a percent of the amplitude of the total current mediated by δ-GABAA receptors revealed that AIE did not alter their sensitivity to either agonist. Lastly, immunohistochemistry and Western blot analysis revealed no change in the expression of δ-GABAA subunits or their surface expression. Taken together, these studies reveal that AIE exposure results in persistent deficits in δ-GABAA tonic currents in the adult prelimbic cortex that may contribute to deficits in decision-making and behavioral control in adulthood.

How do we understand the determinants of health? An exploration of distributed knowledge and interprofessional health sciences education.

It is acknowledged that interprofessional communication and teamwork are foundational for high-quality, safe medical practice. The theory of distributed knowledge posits that each person has unique knowledge and experiences that can contribute to a broader group perspective. Patient care can be positively influenced by a robust and interprofessionally shared understanding of the complexities of health and illness. One would expect a variety of perspectives to be evident in all healthcare providers, including incoming health science students from different professional fields. To examine this notion, medical, nursing, and pharmacy students (n = 24) at the start of an interprofessional training experience were asked to write an essay on factors that contribute to health and/or illness. Their essays were thematically coded to generate a list of factors considered key to health/illness and compare responses across fields to better understand how knowledge is distributed across entering learners. Results show that students from different professional backgrounds emphasise some shared and some divergent factors. This distributed knowledge can be a rich source of understanding and shared thinking across professions. It is also a critical source of individual power to contribute to the construction of an ongoing, collaborative discourse about health.

Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.

Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity.

Chronic alcohol disrupts dopamine receptor activity and the cognitive function of the medial prefrontal cortex.

Dopamine (DA) receptors in the medial prefrontal cortex (mPFC) exert powerful effects on cognition by modulating the balance between excitatory and inhibitory neurotransmission. The present study examined the impact of chronic intermittent ethanol (CIE) exposure on cognitive function and DA receptor-mediated neurotransmission in the rat mPFC. Consistent with alterations in executive function in alcoholics, CIE-exposed rats exhibited deficits in behavioral flexibility in an operant set-shifting task. Since alterations in dopaminergic neurotransmission in the mPFC have been implicated in a number of behavioral disorders including addiction, studies were then performed in the adult acute slice preparation to examine changes in DA receptor function in the mPFC following CIE exposure. In slices obtained from control rats, DA receptor stimulation was observed to exert complex actions on neuronal firing and synaptic neurotransmission that were not only dependent upon the particular receptor subtype but also whether it was a pyramidal cell or a fast-spiking interneuron. In contrast to slices from control rats, there was a near complete loss of the modulatory actions of D2/D4 receptors on cell firing and neurotransmission in slices obtained immediately, 1 and 4 weeks after the last day of CIE exposure. This loss did not appear to be associated with changes in receptor expression. In contrast, CIE exposure did not alter D1 receptor function or mGluR1 modulation of firing. These studies are consistent with the suggestion that chronic alcohol exposure disrupts cognitive function at least in part through disruption of D2 and D4 receptor signaling in mPFC.

Evidence-based development in nurse-led interprofessional teams.

Team-based care is often described as the best way to provide health care. However the effective use of teams in primary care is not yet prevalent in the US and nurse-led interprofessional collaborative teams are rare. Over the past three years the US Department of Health and Human Services has put great emphasis on the development of nurse-led interprofessional teams and this article describes the development of one such team in a primary care setting and the evidence base behind it.

The role of ventral and dorsal striatum mGluR5 in relapse to cocaine-seeking and extinction learning.

Cocaine addiction is a chronic, relapsing disease characterized by an inability to regulate drug-seeking behavior. Here we investigated the role of mGluR5 in the ventral and dorsal striatum in regulating cocaine-seeking following both abstinence and extinction. Animals underwent 2 weeks of cocaine self-administration followed by 3 weeks of home-cage abstinence. Animals were then reintroduced to the operant chamber for a context-induced relapse test, followed by 7-10 days of extinction training. Once responding was extinguished, cue-primed reinstatement test was conducted. Both drug-seeking tests were conducted in the presence of either mGluR5 negative allosteric modulator, MTEP or vehicle infused into either the nucleus accumbens (NA) core or dorsolateral striatum (dSTR). We found that MTEP infused in the NA core attenuated both context-induced relapse following abstinence and cue-primed reinstatement following extinction training. Blocking dSTR mGluR5 had no effect on context- or cue-induced cocaine-seeking. However, the intra-dSTR MTEP infusion on the context-induced relapse test day attenuated extinction learning for 4 days after the infusion. Furthermore, mGluR5 surface expression was reduced and LTD was absent in dSTR slices of animals undergoing 3 weeks of abstinence from cocaine but not sucrose self-administration. LTD was restored by bath application of VU-29, a positive allosteric modulator of mGluR5. Bath application of MTEP prevented the induction of LTD in dSTR slices from sucrose animals. Taken together, this data indicates that dSTR mGluR5 plays an essential role in extinction learning but not cocaine relapse, while NA core mGluR5 modulates drug-seeking following both extinction and abstinence from cocaine self-administration.

Ceftriaxone normalizes nucleus accumbens synaptic transmission, glutamate transport, and export following cocaine self-administration and extinction training.

Decreased basal glutamate levels are observed in the rat nucleus accumbens (NA) core following cocaine self-administration. This disruption of glutamate homeostasis arises from a reduction in the export of glutamate via system x(C)(-) and is accompanied by a decrease in expression of xCT, the catalytic subunit of system x(C)(-). A second hallmark of disrupted homeostasis is a decrease in expression and function of the major glutamate transporter, GLT-1. We have previously shown that chronic treatment with the antibiotic ceftriaxone restores xCT and GLT-1 expression following cocaine self-administration and attenuates both cue- and cocaine-primed reinstatement. Here we used a (3)H-glutamate uptake assay and microdialysis to test the hypothesis that ceftriaxone restores the function of both GLT-1 and xCT (glutamate reuptake and export, respectively) in the NA core following cocaine self-administration. We also used electrophysiology to investigate the ability of ceftriaxone to normalize measures of synaptic plasticity following cocaine. We found that 5 d of ceftriaxone treatment following cocaine self-administration restores basal glutamate levels in the accumbens core, likely through an upregulation of system x(C)(-) function. We also found that ceftriaxone restores glutamate reuptake and attenuates the increase in synaptically released glutamate that accompanies cocaine-primed reinstatement. Ceftriaxone also reversed the cocaine-induced synaptic potentiation in the accumbens core, evidenced by normalized spontaneous EPSC amplitude and frequency and evoked EPSC amplitude. These data indicate that ceftriaxone normalizes multiple aspects of glutamate homeostasis following cocaine self-administration and thus holds the potential to reduce relapse in human cocaine addicts.

Implementation of Peer Messengers to Deliver Feedback: An Observational Study to Promote Professionalism in Nursing.

BACKGROUND: The Co-Worker Observation System (CORS) is a tool and a process to address disrespectful behavior through feedback from trained peer messengers. First used by physicians and advanced practice providers (APPs), CORS has been shown to decrease instances of unprofessional behaviors among physicians and APPs. The research team assessed the feasibility and fidelity of implementing CORS for staff nurses. METHODS: CORS was implemented at three academic medical centers using a project bundle with 10 essential implementation elements. Reports of unprofessional behavior among staff nurses that were submitted through the institution's electronic reporting system were screened through natural language processing software, coded by trained CORS coders using the Martinez taxonomy, and referred to a trained peer messenger to share the observations with the nurse. A mixed methods, observational design assessed feasibility and fidelity. RESULTS: A total of 590 reports from three sites were identified by the Center for Patient and Professional Advocacy from September 1, 2019, through August 31, 2021. Most reports included more than one problematic behavior, each of which was coded. Of the peer messages, 76.5% were successfully documented using the debriefing survey as complete, 2.2% as awaiting messenger feedback, and 0.2% as awaiting messenger assignments (total of 78.9 % considered delivered). A total of 21.1% were not shared; 4.7% of reports were intentionally not shared because the issue stemmed from a new system or policy implementation (4.0%) or because of known factors affecting the nurse (0.7%). CONCLUSION: CORS can be implemented with staff nurses efficiently when nursing infrastructure is adequate.

Differential global gene expression in cystic fibrosis nasal and bronchial epithelium.

Respiratory epithelium is the target of therapies, such as gene therapy, for cystic fibrosis (CF) lung disease. To determine the usefulness of the nasal epithelium as a pre-screen for lung-directed therapies, we profiled gene expression in CF and non-CF nasal and bronchial epithelium samples using Illumina HumanRef-8 Expression BeadChips. 863 genes were differentially expressed between CF and non-CF bronchial epithelium but only 15 were differentially expressed between CF and non-CF nasal epithelium (≥1.5-fold, P≤0.05). The most enriched pathway in CF bronchial epithelium was inflammatory response, whereas in CF nasal epithelium it was amino acid metabolism. We also compared nasal and bronchial epithelium in each group and identified differential expression of cellular movement genes in CF patients and cellular growth genes in non-CF subjects. We conclude that CF and non-CF nasal and bronchial epithelium are transcriptionally distinct and CF nasal epithelium is not a good surrogate for the lung respiratory epithelium.

Co-design of digital learning resources for care workers: reflections on the neurocare knowhow project.

Neurocare Knowhow is an online learning platform for care workers who support people with neurological conditions. Care workers often do not receive specialist training around neurological conditions and can experience anxiety and apprehension about caring for this group. Neurocare Knowhow aims to increase care workers' knowledge and confidence. Featuring flexible and personalisable digital features, in combination with documentary video and audio, it offers an alternative to traditional e-learning, moving away from longform didactic courses to flexible on-the-go learning. This co-design project worked closely with people with neurological conditions, their families, care workers and care organisation managers to validate the need and develop a proof of concept pilot. Co-design activity took place across multiple workshops in person and online. These gathered detailed insights into preferred features that support engaging online learning. The platform offers learning across diverse neurological conditions as a whole, with a focus on shared symptoms and challenges encountered by people with neurological conditions. Ongoing development to scale the pilot up to meet an anticipated national audience includes a focus on artificial intelligence to support searches at a moment of need and a range of personalisable features for individual and team learning.

Supporting the pursuit of professionalism during a crisis.

BACKGROUND: Crisis plans for healthcare organisations most often focus on operational needs including staffing, supplies and physical plant needs. Less attention is focused on how leaders can support and encourage individual clinical team members to conduct themselves as professionals during a crisis. METHODS: This qualitative study analysed observations from 79 leaders at 160 hospitals that participate in two national professionalism programmes who shared their observations in focus group discussions about what they believed were the essential elements of leading and addressing professional accountability during a crisis. RESULTS: Analysis of focus group responses identified six leadership practices adopted by healthcare organisations, which were felt to be essential for organisations to navigate the crisis successfully. Unique aspects of maintaining professionalism during each phase of the pandemic were identified and described. CONCLUSIONS: Leaders need a plan to support an organiation's pursuit of professionalism during a crisis. Leaders participating in this study identified practices that should be carefully woven into efforts to support the ongoing safety and quality of the care delivered by healthcare organisations before, during and after a crisis. The lessons learnt from the COVID-19 pandemic may be useful during subsequent crises and challenges that a healthcare organisation might experience.

Evaluation of Racial Microaggressions Experienced During Medical School Training and the Effect on Medical Student Education and Burnout: A Validation Study.

INTRODUCTION: Microaggressions in the learning environment have been documented at various levels of medical training. However, there is lack of data detailing the prevalence and effects of racial microaggressions in medical school. This limits interventions that might improve the learning environment for underrepresented minority medical students (URMMS). This study describes the creation and validation of a survey instrument characterizing the experience of microaggressions in medical school and their impact on medical student education and burnout. METHODS: An anonymous survey instrument was adapted for medical students from the validated Racial and Ethnic Microaggressions Scale (REMS) and distributed to the national listservs of the Student National Medical Association (SNMA), Latino Medical Student Association (LMSA), and the Asian Pacific American Medical Student Association. Responses were categorized into two cohorts: under-represented minority (URM) and non-URM based on self-reported race or ethnicity. RESULTS: A total of 217 responses were collected from medical students across the United States, with 148 (68.2%) students identifying as URM. URM respondents were significantly (p < 0.05) more likely to report experiencing race-related microaggressions during medical school (55% vs 31%), and to report that these microaggressions contributed to feelings of burnout (62% vs 29%) and compromised learning (64% vs 49%). URM students were significantly less likely to feel that adequate resources were available to address microaggressions (26% vs 39%, p < 0.05). CONCLUSIONS: Our results suggest that microaggressions experienced by URMMS can be evaluated using an adapted REMS. Additionally, the experience of microaggressions negatively impact the learning environment, and students feel the availability of sufficient resources to address microaggressions and their effects are lacking. Further research is needed to evaluate microaggressions and their impact on a larger scale. This should be followed by interventions to minimize the frequency and impact of these microaggressions.

Development of an observational tool to assess health coaching fidelity.

OBJECTIVE: This study describes the development of the Health Coaching Index (HCI), an observational tool for assessing fidelity to implementing health coaching practical skills. METHODS: Initial HCI items were developed, adapted following cognitive interviews, and refined during coding training. Participants (n = 42) were trainees who completed a National Board for Health and Wellness Coaching (NBHWC)-approved training program and coached a standardized patient. Interrater reliability for the HCI was determined by calculating interclass correlations from ten videos coded by three raters. Construct validity was evaluated from 42 recordings using Spearman's Rho between HCI and Roter Interaction Analysis System (RIAS) codes. RESULTS: The interclass correlation (ICC) for HCI total score was 0.81, considered an excellent level of inter-rater agreement. Some significant correlations between HCI and RIAS codes supported construct validity (e.g., patient activation: Rho = 0.32; empathy: Rho = 0.36). CONCLUSION: The HCI total score can reliably be used to assess fidelity to health coaching skills, and the HCI has construct validity similar to the RIAS as a measure of patient activation. PRACTICE IMPLICATIONS: Adoption and further study of the HCI tool will allow for a more consistent implementation of health coaching skills, and may facilitate more robust training of health coaches for clinical practice and research.

The Vanderbilt Program in Interprofessional Learning: Sustaining a Longitudinal, Clinical Experience That Aligns Practice With Education.

PROBLEM: Designing and sustaining a longitudinal, clinic-based interprofessional learning experience is logistically challenging, which has limited the educational opportunities available in health professions schools. The authors discuss the Vanderbilt Program in Interprofessional Learning (VPIL), which addresses some of the challenges facing clinic-based interprofessional experiences. APPROACH: VPIL places first- and second-year students from 4 professional degree programs (medicine, nursing, pharmacy, social work) in Nashville, Tennessee, on teams where they work and learn together in authentic clinical environments over a 2-year period. The program was implemented in 2010 and includes 3 components: a summer immersion experience, seminar-based classroom and simulation sessions, and a weekly clinical experience. Students also complete a capstone quality improvement project. VPIL administrators have set up structures at the institutional, clinic, faculty, and student levels that have contributed to the sustainability of the program. OUTCOMES: Between 2010 and 2019, VPIL admitted 398 students who participated on 91 clinical teams. In addition, 55 clinical preceptors and 12 core faculty trained students for future collaborative practice. The program has received consistently high ratings from students, who have produced 69 quality improvement projects at their clinics. These projects have addressed aspects of the care delivery process and produced durable materials, showing that the program has contributed to important innovations in the health system. NEXT STEPS: VPIL faculty continue to improve the curriculum and administrative structures and work to expand the program to reach a wider variety of health professions students. Going forward, lessons from the program could assist educators in creating opportunities for students to learn interprofessionally and deliver high value health care in increasingly complex delivery systems.

Telomere Maintenance Mechanisms Define Clinical Outcome in High-Risk Neuroblastoma.

Neuroblastoma is a childhood cancer with heterogeneous clinical outcomes. To comprehensively assess the impact of telomere maintenance mechanism (TMM) on clinical outcomes in high-risk neuroblastoma, we integrated the C-circle assay [a marker for alternative lengthening of telomeres (ALT)], TERT mRNA expression by RNA-sequencing, whole-genome/exome sequencing, and clinical covariates in 134 neuroblastoma patient samples at diagnosis. In addition, we assessed TMM in neuroblastoma cell lines (n = 104) and patient-derived xenografts (n = 28). ALT was identified in 23.4% of high-risk neuroblastoma tumors and genomic alterations in ATRX were detected in 60% of ALT tumors; 40% of ALT tumors lacked genomic alterations in known ALT-associated genes. Patients with high-risk neuroblastoma were classified into three subgroups (TERT-high, ALT+, and TERT-low/non-ALT) based on presence of C-circles and TERT mRNA expression (above or below median TERT expression). Event-free survival was similar among TERT-high, ALT+, or TERT-low/non-ALT patients. However, overall survival (OS) for TERT-low/non-ALT patients was significantly higher relative to TERT-high or ALT patients (log-rank test; P < 0.01) independent of current clinical and molecular prognostic markers. Consistent with the observed higher OS in patients with TERT-low/non-ALT tumors, continuous shortening of telomeres and decreasing viability occurred in low TERT-expressing, non-ALT patient-derived high-risk neuroblastoma cell lines. These findings demonstrate that assaying TMM with TERT mRNA expression and C-circles provides precise stratification of high-risk neuroblastoma into three subgroups with substantially different OS: a previously undescribed TERT-low/non-ALT cohort with superior OS (even after relapse) and two cohorts of patients with poor survival that have distinct molecular therapeutic targets. SIGNIFICANCE: These findings assess telomere maintenance mechanisms with TERT mRNA and the ALT DNA biomarker C-circles to stratify neuroblastoma into three groups, with distinct overall survival independent of currently used clinical risk classifiers.