Improvements in Interdisciplinary Communication Following the Implementation of a Standardized Handoff Curriculum: SAFETIPS (Statistics, Assessment, Focused Plan, Pertinent Exam findings, to Dos, If/Thens, Pointers/Pitfalls, and Severity of Illness).

Background Handoffs between medical providers serve a crucial patient safety function. While most published literature on the topic studies the handover process among physicians, robust literature is available on interdisciplinary medical communication. Little is known about the downstream effects of effective physician handover on subsequent physician and nursing interactions. Objective Our objective was to implement a handoff curriculum, SAFETIPS (Statistics, Assessment, Focused plan, pertinent Exam findings, To dos, If/thens, Pointers/pitfalls, and Severity of illness), for pediatric residents and to investigate its impact on nurses' perceptions of resident preparedness, efficiency, and competency. Methods Nurses were asked to score residents in five domains and describe the frequency of nurse-to-resident and resident-to-nurse interruptions. The survey was distributed before and after the SAFETIPS introduction. Results Statistical analysis revealed significant post-intervention mean score increases of one full point in four categories, namely organization and efficiency, communication, content, and clinical judgment. The percentage of nurses using the term "reasonable/relevant" to describe interactions with residents significantly increased from 45% to 76% (p = 0.004). The percentage of nurses reporting that residents gave "unsure response[s]," made decisions that differed from nurses' decisions, and made decisions without family/parental interests significantly decreased by 31 (p = 0.004), 22 (p = 0.034), and 30 (p = 0.002) percentage points, respectively. Conclusion The introduction of a structured handoff curriculum significantly improves communication among residents. This is then associated with improved interactions between residents and nurses.

Improving and Sustaining Resident Physician Handover.

Background Handoffs serve a critical patient safety function in the transition between caregivers. In 2006, the Joint Commission on Accreditation of Healthcare Organizations strongly recommended the implementation of "a standardized approach to 'handoff' communications, including an opportunity to ask and respond to questions." Numerous studies have investigated the quality and efficacy of patient handoffs and the utility of structured handoff curriculums, particularly in the context of patient safety and outcomes. Objective The pediatric residents at Penn State Health (PSH) did not utilize a formal written or verbal handoff tool. Our study facilitated the design of a comprehensive handoff curriculum, including verbal and written components, and the implementation of faculty and multidisciplinary care team involvement coupled with resident training and observations. We investigate the impact of this curriculum longitudinally utilizing validated tools completed by external observers as well as the residents themselves. Methods Prior to SAFETIPS being implemented, residents at a mid-sized Pediatric program were observed giving handovers at various intervals to understand baseline habits. Residents were then educated with the SAFETIPS curriculum and again observed. Trained observers of the handover process completed a validated evaluation form concentrating on seven key domains necessary for effective handover and communication; residents involved in the handover also completed a validated evaluation form. Consent for the project was implied with the observer's presence during the process and our study was exempt from full IRB consideration given its quality improvement design. A mix of summary statistics, stacked dot plots, mixed effects regression, and joint F tests were used to analyze data. Results Mean values on all sections of the handover evaluation Likert scale completed by trained observers tended to increase over time; the variance in responses was likewise much smaller at later time periods. Similarly, all sections of the evaluation tools completed by the resident physicians themselves showed significantly increased scores from pre- to post-implementation of our curriculum. Data revealed a plateauing of results toward later time points suggestive of skills mastery and sustained improvements. Conclusion Our findings suggest that the introduction of a structured handoff curriculum correlated with improved communication among residents, and such improvements were sustained over time.

Plasma and cerebrospinal fluid pharmacokinetics of select chemotherapeutic agents following intranasal delivery in a non-human primate model.

The blood-brain barrier (BBB) limits entry of most chemotherapeutic agents into the CNS, resulting in inadequate exposure within CNS tumor tissue. Intranasal administration is a proposed means of delivery that can bypass the BBB, potentially resulting in more effective chemotherapeutic exposure at the tumor site. The objective of this study was to evaluate the feasibility and pharmacokinetics (plasma and CSF) of intranasal delivery using select chemotherapeutic agents in a non-human primate (NHP) model. Three chemotherapeutic agents with known differences in CNS penetration were selected for intranasal administration in a NHP model to determine proof of principle of CNS delivery, assess tolerability and feasibility, and to evaluate whether certain drug characteristics were associated with increased CNS exposure. Intravenous (IV) temozolomide (TMZ), oral (PO) valproic acid, and PO perifosine were administered to adult male rhesus macaques. The animals received a single dose of each agent systemically and intranasally in separate experiments, with each animal acting as his own control. The dose of the agents administered systemically was the human equivalent of a clinically appropriate dose, while the intranasal dose was the maximum achievable dose based on the volume limitation of 1 mL. Multiple serial paired plasma and CSF samples were collected and quantified using a validated uHPLC/tandem mass spectrometry assay after each drug administration. Pharmacokinetic parameters were estimated using non-compartmental analysis. CSF penetration was calculated from the ratio of areas under the concentration-time curves for CSF and plasma (AUCCSF:plasma). Intranasal administration was feasible and tolerable for all agents with no significant toxicities observed. For TMZ, the degrees of CSF drug penetration after intranasal and IV administration were 36 (32-57) and 22 (20-41)%, respectively. Although maximum TMZ drug concentration in the CSF (Cmax) was lower after intranasal delivery compared to IV administration due to the lower dose administered, clinically significant exposure was achieved in the CSF after intranasal administration with the lower doses. This was associated with lower systemic exposure, suggesting increased efficiency and potentially lower toxicities of TMZ after intranasal delivery. For valproic acid and perifosine, CSF penetration after intranasal delivery was similar to systemic administration. Although this study demonstrates feasibility and safety of intranasal drug administration, further agent-specific studies are necessary to optimize agent selection and dosing to achieve clinically-relevant CSF exposures.

Measurements of the pons as a biomarker of progression for pediatric DIPG.

Treatment of pediatric diffuse intrinsic pontine glioma (DIPG) remains challenging, and reliable biomarkers of response are lacking. Radiographic response is a primary endpoint in many investigational studies of brain tumors, but there is no standard method of tumor measurement for DIPG, significant inter-observer variability exists given the invasive nature of these tumors, and tumor measurements are not predictive of outcome. Because DIPGs involve a significant portion of the pons, we evaluated the reliability and prognostic value of one-dimensional (1D) and two-dimensional (2D) pons measurements using anatomical landmarks rather than tumor boundaries. Patients with DIPG (n = 75) were evaluated longitudinally at our institution using MRI. Four readers independently performed 1D and 2D measurements of the pons using FLAIR images. Agreement and inter-reader variability were evaluated using differences among the six reader pairs and the coefficient of variation (CV). Prognostic value of pons measurements was calculated using Cox proportional hazards models, where relative hazard (RH) represents risk of death. Readers evaluated 384 exams. Agreement of readers' 1D and 2D measurements was strong (median difference between reader pairs 3.1 and 5.4%, respectively), with low inter-reader variability (median CV = 3.1% and median CV = 4.8%, respectively). Increases in 1D and 2D pons measurements over time indicated poorer prognosis (RH = 2.29, p = 0.0025 and RH = 1.13, p = 0.0016, respectively), with shorter overall survival. Pons measurements had low inter-reader variability compared to previously reported tumor measurement techniques and correlated with outcome in children with DIPG. Measurements of the pons (as opposed to direct measurements of tumor) are a viable in vivo biomarker for DIPG.

Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas.

Tumors of the central nervous system are the second most common malignancy in children. In particular, diffuse intrinsic pontine gliomas (DIPGs) are aggressive tumors with poor prognosis and account for 10% to 25% of pediatric brain tumors. The majority of DIPGs are astrocytic, infiltrative, and localized to the pons. Studies have shown median survival times of less than a year, with 90% of children dying within 2 years. We built multitissue arrays with 24 postmortem DIPG samples and analyzed the morphology and expression of several proteins (p53, EGFR, GFAP, MIB1, BMI1, ß-catenin, p16, Nanog, Nestin, OCT4, OLIG2, SOX2) with the goal of identifying potential treatment targets and improving our understanding of the biology of these tumors. The majority of DIPGs were high-grade gliomas (22), with 18 cases having features of glioblastoma (World Health Organization [WHO] grade IV) and 4 cases with high-grade features consistent with anaplastic astrocytoma (WHO grade III). One case was low grade (WHO grade II), and 1 case showed intermediate features between a grade II and grade III glioma (low mitotic rate but increased cellularity and cell atypia), being difficult to grade precisely. The majority of the tumors were positive for GFAP (24/24), MIB1 (23/24), OLIG2 (22/24), p16 (20/24), p53 (20/24), SOX2 (19/24), EGFR (16/24), and BMI1 (9/24). Our results suggest that dysregulation of EGFR and p53 may play an important role in the development of DIPGs. The majority of DIPGs express stem cell markers such as SOX2 and OLIG2, consistent with a role for tumor stem cells in the origin and maintenance of these tumors. Targeted therapies against these proteins could be beneficial in treatment.