Improved planning efficiency in multiple brain lesion SRS VMAT cases using Eclipse scripting.

Though dosimetry has a multitude of treatment modalities, software, and workflows to aid in the treatment planning process, treatment planners are still responsible for several tedious and monotonous tasks that could decrease their planning efficiency. The purpose of this study was to determine if scripting could improve treatment planning efficiency for multiple brain lesion stereotactic radiosurgery (SRS) volumetric arc therapy cases by reducing planning time commitment. A script was developed for multiple brain lesion SRS cases using Eclipse scripting application programming interface with the intention of improving treatment planning efficiency by creating optimization structures and importing prescription and suggested OS dose metrics to the optimizer. Nine treatment planners were each provided with 3 different multiple brain lesion, single-isocenter SRS cases. Each planner created 2 plans for each case. One of these 2 plans used the SRS script, and the other did not. There were 54 treatment plans developed, totaling 27 plan comparisons. Each of the 54 treatment plans were considered clinically acceptable based on the participating institution's plan quality guidelines. Statistical analyses of planning time commitment with and without the SRS script were performed using RStudio. The mean and median planning times with and without the SRS script were compared using a paired T-test and Wilcoxon Signed Rank test, respectively, and effect size was evaluated using Cohen's classification. Using the SRS script resulted in statistically significant reduction in total contouring time (11.3 vs 2.8 minutes, p < 0.001), optimizer preparation time (7.7 vs 2.1 minutes, p < 0.001), and overall planning time (105.1 vs 77.9 minutes, p < 0.001). This study concluded that scripts developed using Eclipse scripting application programming interface offer an opportunity to improve treatment planning efficiency by reducing the planning time commitment for treatment planners.

Implementing a Novel Interprofessional Caregiver Support Clinic: A Palliative Medicine and Social Work Collaboration.

BACKGROUND: High levels of burden and, in more severe instances, burnout represents a significant issue for caregivers of patients with advanced cancer. Early identification and management of caregiver distress and cultivating caregiver resiliency are seldom considered elements of routine care. AIM: To leverage the complementary expertise of palliative medicine and social work using an integrated model of care to assess and manage caregiver needs. METHODS: This quality improvement initiative involved the design and implementation of a novel and collaborative Caregiver Support Clinic (CSC), providing joint palliative medicine-social work encounters to caregivers of patients with advanced cancer. RESULTS: Caregivers felt the CSC provided a forum to discuss and review relevant, but previously neglected, care elements. The concerted collaborative efforts demonstrated by clinicians were found to be reassuring and comforting. Clinicians felt CSC visits prevented duplicative information gathering processes, enabled the ability to efficiently arrive at recommendations and both ensured continuity with, and avoided fragmentation of, care. CONCLUSIONS: By addressing the needs of caregivers through a dyadic, joint encounter, fragmentation and duplication in care can be reduced and both integrated and coordinated management can be efficiently provided. Caregiver and clinician experiences confirm this model of care for caregivers is likely to be beneficial and feasible.

Balloon-occluded retrograde transvenous obliteration (BRTO) of gastric varices using foam sclerosant and a reduced balloon inflation time: Feasibility and efficacy.

INTRODUCTION: Balloon-occluded retrograde transvenous obliteration (BRTO) is recommended for secondary prevention of gastric variceal bleeding in the American Association for the Study of Liver Disease (AASLD) guidelines, as an alternative to Transjugular intrahepatic portosystemic shunt (TIPS). However, there is significant heterogeneity in how BRTO is performed, including how and how long to occlude the outflow venous shunt amongst other variables such as variceal size, flow rate, agent used, and preparation technique. We propose a method using foam sclerotherapy and reducing balloon occlusion to as little as 30 min, with assessment of the efficacy of this shorter balloon inflation time. METHODS: Retrospective single-centre analysis of BRTO procedures between July 2015 and February 2019 for isolated gastric varices in a non-acute setting, where inflation time was 2 h or less. RESULTS: Six patients underwent BRTO with a short inflation time, with a mean age of 66 years. The median balloon inflation and thus 3% athoxysclerol foam contact time was 30 min (range 30-60 min). Four of the 6 patients showed complete resolution of varices, while 2 of the 6 showed a partial response. Mean follow-up was 27 months. There were no patients who did not show a response to treatment and no episodes of clinically significant upper gastrointestinal bleeding. CONCLUSIONS: This technique using a shortened balloon occlusion time resulted in complete or partial clinical and technical success in all patients and suggests that the threshold for initiation of gastric variceal thrombosis may be below 30 min. This timepoint may provide a balance between adequate balloon inflation, angiography room efficiency and hospital resource allocation with resultant procedural cost implications.

Operationalizing the Bridge Care Model-Advocating for At-Risk Students.

The inability to meet local, state, and federal health requirements for school entry can delay enrollment for uninsured, registering students. For at-risk, vulnerable students and families, limited access to health care providers, funding, and transportation, as well as inflexible work schedules, can create barriers to their ability to access required health services in a timely manner, thus delaying immediate student enrollment. This article focuses on the implementation of the Bridge Care Model through an innovative and unique partnership between an academic nurse-mananaged clinic network and a local school system. Through collaboration, data analysis, and process planning, these partners established a Memorandum of Agreement allowing each to address their programmatic missions, visions, and goals to meet the needs of at-risk, uninsured, vulnerable students and to remove barriers to school entry. Through this mutually beneficial approach, direct health services were provided at an on-site, central student registration location through a cost-effective, sustainable partnership. This article highlights how implementation of the Bridge Care model at a central student registration site allowed a local school system to reduce barriers to school entry for vulnerable at-risk students; provide access to medical navigation support for uninsured families; and create a streamlined communication system to allow school-based staff to support students with significant physical and behavioral health needs following enrollment.

Chief of Residents for Quality Improvement and Patient Safety: A Recipe for a New Role in Graduate Medical Education.

INTRODUCTION: The San Antonio Uniformed Services Health Education Consortium (SAUSHEC) is the largest group of residency programs in the Department of Defense. In an effort to provide improved Quality Improvement and Patient Safety (QI/PS) training for its residents, SAUSHEC created the position of Chief of QI/PS for Residents in the academic year 2014-2015. The Chief of QI/PS for Residents was based in the Internal Medicine residency program but also assisted with SAUSHEC-wide QI/PS projects. This is the first such job in the Department of Defense. METHODS: Here, we detail the accomplishments during this first academic year, including the alignment of the job with the stated QI/PS-related goals of the Accreditation Council for Graduate Medical Education Clinical Learning Environment Review. Efforts focused within the Internal Medicine residency program included QI/PS curriculum development, improvement upon monthly morbidity and mortality (M&M) conferences, and facilitating resident participation in QI projects. The 2014-2015 academic year Internal Medicine residency QI/PS project focused on increasing comfort and discussions with patients regarding advance directives; this also served to emphasize the humanistic side of potential QI/PS projects. The Chief of QI/PS for Residents also spearheaded hospital-wide initiatives, including the creation of a quarterly hospital-wide M&M conference, coordinating resident involvement in QI/PS-related committees, and facilitating feedback of patient safety report responses to trainees. RESULTS: We focus on the portion of the QI/PS curriculum involving the presentation of a mock Root Cause Analysis (RCA) and provide the results of a pre- and postpresentation survey of resident knowledge of RCAs. In order to quantify the efforts over the entire academic year, we also report the results of a resident self-assessment of QI/PS aptitude and competencies, including changes in these measures over the academic year. Finally, we discuss challenges faced and outline future goals for the position. CONCLUSION: The SAUSHEC Chief of QI/PS for Residents is the first such designated position in the Department of Defense. As QI/PS continues to increase as a focus area for physician training, we anticipate that other programs will create similar positions. We provide ideas for how a Chief of QI/PS for Residents can be involved at a program and hospital-wide level and quantify the success of different efforts.

Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone.

Protein kinase D (PKD) is a novel family of serine/threonine kinases targeted by the second messenger diacylglycerol. It has been implicated in many important cellular processes and pathological conditions. However, further analysis of PKD in these processes is severely hampered by the lack of a PKD-specific inhibitor that can be readily applied to cells and in animal models. We now report the discovery of the first potent and selective cell-active small molecule inhibitor for PKD, benzoxoloazepinolone (CID755673). This inhibitor was identified from the National Institutes of Health small molecule repository library of 196,173 compounds using a human PKD1 (PKCmu)-based fluorescence polarization high throughput screening assay. CID755673 suppressed half of the PKD1 enzyme activity at 182 nm and exhibited selective PKD1 inhibition when compared with AKT, polo-like kinase 1 (PLK1), CDK activating kinase (CAK), CAMKIIalpha, and three different PKC isoforms. Moreover, it was not competitive with ATP for enzyme inhibition. In cell-based assays, CID755673 blocked phorbol ester-induced endogenous PKD1 activation in LNCaP cells in a concentration-dependent manner. Functionally, CID755673 inhibited the known biological actions of PKD1 including phorbol ester-induced class IIa histone deacetylase 5 nuclear exclusion, vesicular stomatitis virus glycoprotein transport from the Golgi to the plasma membrane, and the ilimaquinone-induced Golgi fragmentation. Moreover, CID755673 inhibited prostate cancer cell proliferation, cell migration, and invasion. In summary, our findings indicate that CID755673 is a potent and selective PKD1 inhibitor with valuable pharmacological and cell biological potential.

Development, validation and implementation of immobilized metal affinity for phosphochemicals (IMAP)-based high-throughput screening assays for low-molecular-weight compound libraries.

This protocol describes assay development, validation and implementation of automated immobilized metal affinity for phosphochemicals (IMAP)-based fluorescence polarization (FP) and time-resolved fluorescence resonance energy transfer (TR-FRET) high-throughput screening (HTS) assays for identification of low-molecular-weight kinase inhibitors. Both procedures are performed in miniaturized kinase reaction volumes and involve the stepwise addition of test or control compounds, enzyme and substrate/ATP. Kinase reactions are stopped by subsequent addition of IMAP-binding buffer. Assay attributes of the IMAP FP and TR-FRET methodologies are described. HTS assays developed using these procedures should result in Z-factors and low assay variability necessary for robust HTS assays. Providing that the required reagents and equipment are available, one scientist should be able to develop a 384-well, miniaturized HTS assay in approximately 6-8 weeks. Specific automated HTS assay conditions will determine the number of assay plates processed in a screening session, but two scientists should expect to process between 100 and 150 assay plates in one 8-h screening day.

Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation.

Nucleic acid-binding innate immune receptors such as Toll-like receptor 7 (TLR7) and TLR9 have been implicated in the development of some autoimmune pathologies. The Y chromosome-linked genomic modifier Yaa, which correlates with a duplication of Tlr7 and 16 other genes, exacerbates lupus-like syndromes in several mouse strains. Here we demonstrated that duplication of the Tlr7 gene was the sole requirement for this accelerated autoimmunity, because reduction of Tlr7 gene dosage abolished the Yaa phenotype. Further, we described new transgenic lines that overexpressed TLR7 alone and found that spontaneous autoimmunity developed beyond a 2-fold increase in TLR7 expression. Whereas a modest increase in Tlr7 gene dosage promoted autoreactive lymphocytes with RNA specificities and myeloid cell proliferation, a substantial increase in TLR7 expression caused fatal acute inflammatory pathology and profound dendritic cell dysregulation. These results underscore the importance of tightly regulating expression of TLR7 to prevent spontaneous triggering of harmful autoreactive and inflammatory responses.