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.

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.

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.

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.

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.

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.

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.

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.

Sex Differences in Depression as a Risk Factor for Alzheimer's Disease: A Systematic Review.

BACKGROUND AND OBJECTIVES: Depression is an important risk factor for Alzheimer's disease (AD) but little is known about the mechanisms of this association. Given sex differences in both AD and depression, we sought to conduct a systematic review and meta-analysis to examine whether there are sex differences in their association, as this may improve understanding of underlying mechanisms. RESEARCH DESIGN AND METHODS: MEDLINE, PsycINFO, and Cochrane Reviews were searched for observational studies including both sexes and examining the association between history of depression and AD. RESULTS: Forty studies, including 62,729 women and 47,342 men, were identified. Meta-analysis was not possible because only 3 studies provided sufficient data. Seven studies provided information about the influence of sex for a qualitative synthesis. Two found an association in men only, 2 in women only, and 3 reported no sex differences. The 2 studies finding an association in women only were unique in that they had the shortest follow-up periods, and were the only clinic-based studies. DISCUSSION AND IMPLICATIONS: The findings of our systematic review show that there are important methodological differences among the few studies providing data on the influence of sex on depression as a risk factor for AD. Had all 40 studies provided sex-segregated data, these methodological differences and their impact on sex effects could have been examined quantitatively. We encourage researchers to report these data, as well as potential moderating factors, so that the role of sex differences can be better understood.

Exploring perceptions of meaningfulness in visual representations of bivariate relationships.

Researchers often need to consider the practical significance of a relationship. For example, interpreting the magnitude of an effect size or establishing bounds in equivalence testing requires knowledge of the meaningfulness of a relationship. However, there has been little research exploring the degree of relationship among variables (e.g., correlation, mean difference) necessary for an association to be interpreted as meaningful or practically significant. In this study, we presented statistically trained and untrained participants with a collection of figures that displayed varying degrees of mean difference between groups or correlations among variables and participants indicated whether or not each relationship was meaningful. The results suggest that statistically trained and untrained participants differ in their qualification of a meaningful relationship, and that there is significant variability in how large a relationship must be before it is labeled meaningful. The results also shed some light on what degree of relationship is considered meaningful by individuals in a context-free setting.

Cognitive profile of non-demented Parkinson's disease: Meta-analysis of domain and sex-specific deficits.

INTRODUCTION: Better awareness of the cognitive domains affected in non-demented Parkinson's Disease (PD) should improve understanding of cognitive disease mechanisms. A complete understanding of the cognitive areas impaired in non-demented PD is hindered because most studies use small clinical samples without comparison to healthy controls. This meta-analysis examined cumulative evidence across studies to determine if there were impairments in non-demented PD in the three cognitive domains thought to be most widely affected in PD: frontal executive, visuospatial, and verbal memory. Because there are well-documented sex differences in PD, a second objective was to explore sex differences in these findings. METHODS: MEDLINE, EMBASE and PsycINFO databases were searched (1988-March 2017). Random effects models were used to compute and compare effect sizes of differences between PD patients and controls within cognitive domains. Sex differences in effect sizes were also examined in these comparisons. Moderating factors including age, disease duration, motor symptom severity, levodopa dosage, and depression were examined through meta-regression. RESULTS: PD patients showed deficits of moderate effect sizes in all three cognitive domains relative to controls. Significant sex differences were observed only for frontal executive abilities, with male PD patients showing greater deficits than female PD patients relative to controls. No moderators of effect sizes were identified in the domain specific overall or sex-segregated meta-analyses. CONCLUSIONS: Results indicate that non-demented PD patients have deficits of moderate magnitude in frontal executive, verbal memory, and visuospatial abilities. Our findings of greater frontal executive deficits in males warrant further confirmation.

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.

Corrigendum: Transcriptomic profiling of 39 commonly-used neuroblastoma cell lines.

This corrects the article DOI: 10.1038/sdata.2017.33.

A comprehensively characterized cell line panel highly representative of clinical ovarian high-grade serous carcinomas.

Recent literature suggests that most widely used ovarian cancer (OVCA) cell models do not recapitulate the molecular features of clinical tumors. To address this limitation, we generated 18 cell lines and 3 corresponding patient-derived xenografts predominantly from high-grade serous carcinoma (HGSOC) peritoneal effusions. Comprehensive genomic characterization and comparison of each model to its parental tumor demonstrated a high degree of molecular similarity. Our characterization included whole exome-sequencing and copy number profiling for cell lines, xenografts, and matched non-malignant tissues, and DNA methylation, gene expression, and spectral karyotyping for a subset of specimens. Compared to the Cancer Genome Atlas (TCGA), our models more closely resembled HGSOC than any other tumor type, justifying their validity as OVCA models. Our meticulously characterized models provide a crucial resource for the OVCA research community that will advance translational findings and ultimately lead to clinical applications.

Transcriptomic profiling of 39 commonly-used neuroblastoma cell lines.

Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or mRNA expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e.g., MYCN amplification status, ALK mutation status, chromosome arm 1p, 11q and/or 17q status, sensitivity to pharmacologic perturbation). Additionally, we designed this experiment to enable structural variant and/or long-noncoding RNA analysis across these cell lines. Finally, as more DNase/ATAC and histone/transcription factor ChIP sequencing is performed in these cell lines, our RNA-Seq data will be an important complement to inform transcriptional targets as well as regulatory (enhancer or repressor) elements in neuroblastoma.

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.

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.