Multi-institutional evaluation of a Pareto navigation guided automated radiotherapy planning solution for prostate cancer.

BACKGROUND: Current automated planning solutions are calibrated using trial and error or machine learning on historical datasets. Neither method allows for the intuitive exploration of differing trade-off options during calibration, which may aid in ensuring automated solutions align with clinical preference. Pareto navigation provides this functionality and offers a potential calibration alternative. The purpose of this study was to validate an automated radiotherapy planning solution with a novel multi-dimensional Pareto navigation calibration interface across two external institutions for prostate cancer. METHODS: The implemented 'Pareto Guided Automated Planning' (PGAP) methodology was developed in RayStation using scripting and consisted of a Pareto navigation calibration interface built upon a 'Protocol Based Automatic Iterative Optimisation' planning framework. 30 previous patients were randomly selected by each institution (IA and IB), 10 for calibration and 20 for validation. Utilising the Pareto navigation interface automated protocols were calibrated to the institutions' clinical preferences. A single automated plan (VMATAuto) was generated for each validation patient with plan quality compared against the previously treated clinical plan (VMATClinical) both quantitatively, using a range of DVH metrics, and qualitatively through blind review at the external institution. RESULTS: PGAP led to marked improvements across the majority of rectal dose metrics, with Dmean reduced by 3.7 Gy and 1.8 Gy for IA and IB respectively (p < 0.001). For bladder, results were mixed with low and intermediate dose metrics reduced for IB but increased for IA. Differences, whilst statistically significant (p < 0.05) were small and not considered clinically relevant. The reduction in rectum dose was not at the expense of PTV coverage (D98% was generally improved with VMATAuto), but was somewhat detrimental to PTV conformality. The prioritisation of rectum over conformality was however aligned with preferences expressed during calibration and was a key driver in both institutions demonstrating a clear preference towards VMATAuto, with 31/40 considered superior to VMATClinical upon blind review. CONCLUSIONS: PGAP enabled intuitive adaptation of automated protocols to an institution's planning aims and yielded plans more congruent with the institution's clinical preference than the locally produced manual clinical plans.

Perianal Injury Prevention in Patients With Leukemia.

BACKGROUND: Perianal injuries in adults with hematologic malignancies can result in sepsis or death. Patients on a 36-bed acute care oncology unit experienced increased perianal injuries from 2018 to 2021 based on a chart review, which revealed that 24 patients with leukemia, all of whom had received cytarabine, developed perianal injuries. OBJECTIVES: This study examined whether a nurse-led educational intervention would decrease perianal injuries. METHODS: A survey examined baseline nurse knowledge on perianal injuries. Nurses received a 10-minute in-service education session about perianal injuries, their predisposing factors, and prevention strategies followed by a survey to test their knowledge. Twenty nurses completed the pre- and postintervention surveys. FINDINGS: After the intervention, staff knowledge increased by 33%. One year postintervention, perianal injuries had decreased by more than 50%. Nurse and patient education are vital to decrease perianal injuries in patients with leukemia.

Structural racism in healthcare and research: A community-led model of curriculum development and implementation.

Structural racism in the USA has roots that extend deep into healthcare and medical research, and it remains a key driver of illness and early death for Black, Indigenous, People of Color (BIPOC). Furthermore, the persistence of racism within academic medicine compels an interrogation of education and research within this context. In the spirit of this interrogation, this article highlights a unique model of community-engaged education that integrates cultural humility. As an individual and institutional stance, cultural humility denotes lifelong learning and self-critique, the mitigation of power imbalances, and accountability. The integration of cultural humility emphasizes that when space is created for BIPOC communities to lead the way, education regarding healthcare and research can be effectively reimagined. Demonstrating this effectiveness, six community partners led the development and implementation of a five-module Structural Racism in Healthcare and Research course. Using a cohort model approach, the pilot course enrolled 12 community members and 12 researchers. The curriculum covered topics such as history of racism in healthcare and research, and introduced participants to a cultural resilience framework. Evaluation results demonstrated a significant increase in participants' knowledge and ability to identify and take action to address inequities related to racism in healthcare and research.

Simvastatin and ML141 Decrease Intracellular Streptococcus pyogenes Infection.

BACKGROUND: Recurrent pharyngotonsillitis due to Streptococcus pyogenes develops regardless of whether infecting strains are resistant or susceptible to first-line antimicrobials. Causation for recurrent infection is associated with the use of first-line antimicrobials that fail to penetrate deep tissue and host cell membranes, enabling intracellular S. pyogenes to survive throughout repeated rounds of antimicrobial therapy. OBJECTIVE: To determine whether simvastatin, a therapeutic approved for use in the treatment of hypercholesterolemia, and ML141, a first-in-class small molecule inhibitor with specificity for human CDC42, limit host cell invasion by S. pyogenes. METHODS: Assays to assess host cell invasion, bactericidal activity, host cell viability, actin depolymerization, and fibronectin binding were performed using the RAW 267.4 macrophage cell line and Human Umbilical Vein Endothelial Cells (HUVEC) infected with S. pyogenes (90-226) and treated with simvastatin, ML141, structural analogs of ML141, or vehicle control. RESULTS: Simvastatin and ML141 decreased intracellular infection by S. pyogenes in a dose-dependent manner. Inhibition by simvastatin persisted following 1 h washout whereas inhibition by ML141 was reversed. During S. pyogenes infection, actin stress fibers depolymerized in vehicle control treated cells, yet remained intact in simvastatin and in ML141 treated cells. Consistent with the previous characterization of ML141, simvastatin decreased host cell binding to fibronectin. Structural analogs of ML141, designated as the RSM series, decreased intracellular infection through non-cytotoxic, nonbactericidal mechanisms. CONCLUSION: Our findings demonstrate the potential of repurposing simvastatin and of developing CDC42-targeted therapeutics for eradicating intracellular S. pyogenes infection to break the cycle of recurrent infection through a host-directed approach.

Clinical implementation of a knowledge based planning tool for prostate VMAT.

BACKGROUND: A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. METHODS: A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. RESULTS: Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. CONCLUSIONS: The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.

The effect of using different competence frameworks to audit the content of a masters program in public health.

OBJECTIVES: (1) To quantify the effect of using different public health competence frameworks to audit the curriculum of an online distance learning MPH program, and (2) to measure variation in the outcomes of the audit depending on which competence framework is used. STUDY DESIGN: Retrospective audit. METHODS: We compared the teaching content of an online distance learning MPH program against each competence listed in different public health competence frameworks relevant to an MPH. We then compared the number of competences covered in each module in the program's teaching curriculum and in the program overall, for each of the competence frameworks used in this audit. RESULTS: A comprehensive search of the literature identified two competence frameworks specific to MPH programs and two for public health professional/specialty training. The number of individual competences in each framework were 32 for the taught aspects of the UK Faculty of Public Health Specialist Training Program, 117 for the American Association of Public Health, 282 for the exam curriculum of the UK Faculty of Public Health Part A exam, and 393 for the European Core Competencies for MPH Education. This gave a total of 824 competences included in the audit. Overall, the online MPH program covered 88-96% of the competences depending on the specific framework used. This fell when the audit focused on just the three mandatory modules in the program, and the variation between the different competence frameworks was much larger. CONCLUSION: Using different competence frameworks to audit the curriculum of an MPH program can give different indications of its quality, especially as it fails to capture teaching considered to be relevant, yet not included in an existing competence framework. The strengths and weaknesses of using competence frameworks to audit the content of an MPH program have largely been ignored. These debates are vital given that external organizations responsible for accreditation specify a particular competence framework to be used. Our study found that each of four different competence frameworks suggested different levels of quality in our teaching program, at least in terms of the competences included in the curriculum. Relying on just one established framework missed some aspects of the curriculum included in other frameworks used in this study. Conversely, each framework included items not covered by the others. Thus, levels of agreement with the content of our MPH and established areas of competence were, in part, dependent on the competence framework used to compare its' content. While not entirely a surprising finding, this study makes an important point and makes explicit the challenges of selecting an appropriate competence framework to inform MPH programs, and especially one which recruits students from around the world.

Small Molecule Inhibitors Limit Endothelial Cell Invasion by Staphylococcus aureus.

Staphylococcus aureus is a leading causative agent in sepsis, endocarditis, and pneumonia. An emerging concept is that prognosis worsens when the infecting S. aureus strain has the capacity to not only colonize tissue as an extracellular pathogen, but to invade host cells and establish intracellular bacterial populations. In previous work, we identified host CDC42 as a central regulator of endothelial cell invasion by S. aureus. In the current work, we report that ML 141, a first-in-class CDC42 inhibitor, decreases invasion and resultant pathogenesis in a dose-dependent and reversible manner. Inhibition was found to be due in part to decreased remodeling of actin that potentially drives endocytic uptake of bacteria/fibronectin/integrin complexes. ML 141 decreased binding to fibronectin at these complexes, thereby limiting a key pathogenic mechanism used by S. aureus to invade. Structural analogs of ML 141 were synthesized (designated as the RSM series) and a subset identified that inhibit invasion through non-cytotoxic and non-bactericidal mechanisms. Our results support the development of adjunctive therapeutics targeting host CDC42 for mitigating invasive infection at the level of the host.

Immunization information systems national research and evaluation agenda.

Immunization Information Systems (IIS) are operational in most states and are useful in programmatic and clinical assessments. To ensure that IIS reach their technical and usability potential, and to promote their use, we conducted a Delphi survey to develop a national IIS research and evaluation agenda. Experts with a wide range of IIS knowledge were asked to generate research and evaluation topics that document their utility in achieving and sustaining clinical and public health goals. Topics were then collated by the authors into 13 main categories and were ranked by the survey experts in order of importance. Provider perspectives and needs was ranked as the top research priority. Both data quality and technical data exchange also ranked high, as well as increasing provider participation and IIS cost and cost savings. Lower-ranked research priorities included data sharing between states and factors affecting IIS population-based measurements. Development of an IIS research and evaluation agenda allows policy makers to ensure that their decisions coincide with expert views on national priorities and enables researchers to conduct studies addressing topics recognized as nationally important. It also allows for targeted funding decisions.

Designed to expedite: immunization registry information systems.

Nationally, more and more school nurses are encountering immunization registries or Immunization Information Systems as they search for immunization records on children attending their schools. Given the rise of immunization registries, the difficulty for parents to produce complete records, and the ongoing need of school nurses to gain access to this information, this is the time to bridge the gap between school nurses and immunization registries. The following article aims to help bring more information about immunization registries to school nurses. Following are excerpts taken from a special edition of Snapshots, the newsletter for the American Immunization Registry Association to help explain what registries are and how they might help.

Utility of an immunization registry in a pediatric emergency department.

OBJECTIVES: Determine prevalence of participation and underimmunization rate in a regional immunization registry (IR) among patients presenting to a university pediatric emergency department (PED). Rate of agreement between parental report and documented immunization status was also measured. METHODS: A convenience sample of parents of patients younger than 11 years registered in the PED were approached with a short questionnaire. When informed consent was obtained, the Central New York (CNY) IR was accessed via computer to see if the child was in the registry and to ascertain if their immunizations were up-to-date (UTD). Rate of agreement between parental report and immunization status documented in the IR was calculated. RESULTS: 698 (97%) of 720 patients consented to participate. Of these, 235 (34%, 95% CI, 30-37) were enrolled in the IR. Eighty-five (36%, 95% CI, 30-42) enrolled patients were under age 2. Sixty-seven (29%, 95% CI, 23-34) were from private group practices, 146 (62%, 95% CI, 56-68) were from university/community health center clinics and the source of primary care for 22 patients (9%) was unknown. Only 67 (29%, 95% CI, 23-34) parents of children in the IR were aware that they were enrolled. Of IR patients, 225 (96%, 95% CI, 93-98) stated they were UTD, while only 143 (61%, 95% CI, 55-67) were documented to be so. CONCLUSIONS: A significant number of patients seen in the PED were in the CNY IR. More than one-half of the parents of enrolled children did not recall that they had previously registered their child. Only 61% of patients were UTD, whereas parents reported that almost all were. In the PED, use of an IR would create an opportunity for intervention in a large number of patients who were not UTD.