bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug discovery and development: Biomarkers of neurotoxicity and neurodegeneration
Authors: Walker Abigail L , Imam Syed Z , Roberts Ruth A
Published: September 2018

The discovery and development of new drugs are vital if we are to improve and expand treatment options available to improve outcomes for patients. Overall, therapeutic strategies fall into two broad categories: small molecules and biologics, although more recently there has been a growth in novel platforms such as miRNAs and oligonucleotides. On average, the development of a small molecule drug takes around 12 years and costs around $50m. Despite this huge investment of time and money, attrition remains a major challenge and very few molecules actually make it through to the market. Here, we look at reasons for attrition in the small molecule field with a focus on neurotoxicology and efforts being made to improve success via the development of imaging and fluidic biomarkers. We also look at learnings from other models of CNS damage and degeneration such as Parkinson’s disease, traumatic brain injury, and multiple sclerosis since these may offer the opportunity to improve tools available to nonclinical toxicologists in the early detection of potential neurotoxicity. Reciprocally, learnings from studies of animal neurotoxicity may offer better ways to potentially monitor patients during clinical development of new drugs for neurodegeneration.
Classification of incoming calls for the capital city of Slovenia smart city 112 public safety system using open Internet of Things data
Authors: Grasic Valerij , Kos Andrej , Mileva-Boshkoska Biljana
Published: September 2018

There are many natural conditions in the world, such as floods and earthquakes that cause major accidents. The actual question is how to anticipate and predict such events, which enables us to prepare ourselves in advance. We are interested in the advance classification of incoming calls to the smart city 112 public safety system for Ljubljana, the capital city of Slovenia, and the whole country. We used open Internet of Things data for Ljubljana and the whole of Slovenia for the years 2013–2016. Using different classification methods, different models were obtained and compared with each other. We have provided a report on how accurate the forecasts are and what classification result differences occur when different models or data of the capital city or the whole of Slovenia are used. The results obtained are a sound basis for further work on improving the classification in advance of incoming calls to the smart city 112 public safety system.
Iran’s Aid Diplomacy in Afghanistan: The Role of Imam Khomeini Relief Committee
Authors: Kamal Abdol Moghset Bani , Ra’ees Wahabuddin
Published: September 2018

This study aims at examining the Islamic Republic of Iran’s “aid diplomacy” officially referred to as “support diplomacy” and focuses on the Imam Khomeini Relief Committee (IKRC), a charity organization which is functioning as the main vehicle. The IKRC is highly active in many poor countries and this study focuses on the activities, strategies, and achievements of the IKRC in Afghanistan. The study among others finds that Iran is using rigorous aid diplomacy to penetrate into the downtrodden layers of Afghan society. The foundational principles of the IKRC suggest that this institution is functioning in the direction of Ayatollah Khomeini’s doctrine of “Exporting the Revolution.” In line with this, the IKRC is tasked to nurture Afghan sympathizers for the Islamic Republic of Iran to enhance this country’s soft power in Afghanistan and the relief efforts are heavily influenced by its official ideology that is based on Shia belief system.
Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease
Authors: Swimm Alyson , Giver Cynthia R. , DeFilipp Zachariah , Rangaraju Sravanti , Sharma Akshay , Ulezko Antonova Alina , Sonowal Robert , Capaldo Christopher , Powell Domonica , Qayed Muna , Kalman Daniel , Waller Edmund K.
Published: September 2018

The intestinal microbiota in allogeneic bone marrow transplant (allo-BMT) recipients modulates graft-versus-host disease (GVHD), a systemic inflammatory state initiated by donor T cells that leads to colitis, a key determinant of GVHD severity. Indole or indole derivatives produced by tryptophan metabolism in the intestinal microbiota limit intestinal inflammation caused by diverse stressors, so we tested their capacity to protect against GVHD in murine major histocompatibility complex–mismatched models of allo-BMT. Indole effects were assessed by colonization of allo-BMT recipient mice with tryptophanase positive or negative strains of Escherichia coli, or, alternatively, by exogenous administration of indole-3-carboxaldehyde (ICA), an indole derivative. Treatment with ICA limited gut epithelial damage, reduced transepithelial bacterial translocation, and decreased inflammatory cytokine production, reducing GVHD pathology and GVHD mortality, but did not compromise donor T-cell-mediated graft-versus-leukemia responses. ICA treatment also led to recipient-strain-specific tolerance of engrafted T cells. Transcriptional profiling and gene ontology analysis indicated that ICA administration upregulated genes associated with the type I interferon (IFN1) response, which has been shown to protect against radiation-induced intestinal damage and reduce subsequent GVHD pathology. Accordingly, protective effects of ICA following radiation exposure were abrogated in mice lacking IFN1 signaling. Taken together, these data indicate that indole metabolites produced by the intestinal microbiota act via type I IFNs to limit intestinal inflammation and damage associated with myeloablative chemotherapy or radiation exposure and acute GVHD, but preserve antitumor responses, and may provide a therapeutic option for BMT patients at risk for GVHD.
UCH-L1 bypasses mTOR to promote protein biosynthesis and is required for MYC-driven lymphomagenesis in mice
Authors: Hussain Sajjad , Bedekovics Tibor , Liu Qiuying , Hu Wenqian , Jeon Haeseung , Johnson Sarah H. , Vasmatzis George , May Danielle G. , Roux Kyle J. , Galardy Paul J.
Published: September 2018

The mechanistic target of rapamycin (mTOR) is a central regulator of cellular proliferation and metabolism. Depending on its binding partners, mTOR is at the core of 2 complexes that either promote protein biosynthesis (mTOR complex 1; mTORC1) or provide survival and proliferation signals (mTORC2). Protein biosynthesis downstream of mTORC1 plays an important role in MYC-driven oncogenesis with translation inhibitors garnering increasing therapeutic attention. The germinal center B-cell oncogene UCHL1 encodes a deubiquitinating enzyme that regulates the balance between mTOR complexes by disrupting mTORC1 and promoting mTORC2 assembly. While supporting mTORC2-dependent growth and survival signals may contribute to its role in cancer, the suppression of mTORC1 activity is enigmatic, as its phosphorylation of its substrate 4EBP1 promotes protein biosynthesis. To address this, we used proximity-based proteomics to identify molecular complexes with which UCH-L1 associates in malignant B cells. We identified a novel association of UCH-L1 with the translation initiation complex eIF4F, the target of 4EBP1. UCH-L1 associates with and promotes the assembly of eIF4F and stimulates protein synthesis through a mechanism that requires its catalytic activity. Because of the importance of mTOR in MYC-driven oncogenesis, we used novel mutant Uchl1 transgenic mice and found that catalytic activity is required for its acceleration of lymphoma in the Eμ-myc model. Further, we demonstrate that mice lacking UCH-L1 are resistant to MYC-induced lymphomas. We conclude that UCH-L1 bypasses the need for mTORC1-dependent protein synthesis by directly promoting translation initiation, and that this mechanism may be essential for MYC in B-cell malignancy.
Nonlinear mixing law for magnetic resonance transverse-relaxation measurements of dispersed mixtures
Authors: Medellin David , Ravi Vivek R. , Torres-Verdín Carlos
Published: September 2018

Nuclear magnetic resonance (NMR) has been used to estimate the permeability of water-saturated rocks with uniform grain-surface composition. Geologic formations, however, usually consist of layers of rocks with different grain-surface compositions. In the absence of water diffusional coupling between adjacent layers, the NMR [Formula: see text] distribution measured by a borehole logging tool is a weighted average (i.e., it obeys a linear mixing law) of the [Formula: see text] distributions of each layer. However, when the layers are very thin (compared with the self-diffusion length of water) or the different grain types form a dispersed mixture (i.e., they are finely mixed), the resultant [Formula: see text] distribution does not obey a linear mixing law anymore. The question arises as to whether it is possible to differentiate between dispersed and layered formations using mixing laws. We have developed a nonlinear mixing law to calculate the NMR [Formula: see text] distribution of a water-saturated sample composed of a fine mixture of two different grain types from the [Formula: see text] distributions of the water-saturated samples for each grain type. Water-saturated mixtures of crushed Texas Cream limestone and white silica sand were prepared in different volume ratios; we used the new nonlinear mixing law to compute the [Formula: see text] distribution of the mixtures using the [Formula: see text] distributions of the pure water-saturated samples and their volume fractions. Conversely, we also applied the nonlinear mixing law to the mixture to calculate the volume fractions of pure components using the [Formula: see text] distributions of the pure components and the mixtures. Our results indicate that enough differences exist between the nonlinear and linear NMR mixing laws predictions that they can be used to establish whether in a given rock formation with two different grain types the pure components form layers or they are present in dispersed form.
Cost-effectiveness analysis of pembrolizumab in cancer therapy: A systematic review.
Authors: Donatien Claudette , Foster Lori-Ann , Loh F. Ellen
Published: September 2018

109

Background: Cancer treatment is very costly and is further complexed by barriers to healthcare such as the lack of health insurance. Cancer detected at a later stage is more expensive to treat and the outcome can be less successful. Pembrolizumab is an immunotherapy that can be given alone or with chemotherapy. Pembrolizumab, a monoclonal antibody, may be considered first-line treatment in cancer therapy with its increase in life expectancy and successful treatment rates. Methods: A systematic review was conducted to identify relevant studies of the cost-effectiveness of Pembrolizumab treatment in cancer patients. We included studies that compared pembrolizumab to previous treatments, treatment-naive patients, advance melanoma, and metastatic non-small-cell lung cancer. Results: Most of the studies reviewed concluded that pembrolizumab was more cost-effective despite its high drug acquisition cost and disease management costs. Treatment with pembrolizumab was most effective when it was limited to 2 years, however, costs increased when treatment went beyond the two years and disease progression did not cease in most trials. In fact, disease progression occurred in many of the trials and patients had to discontinue treatment with pembrolizumab or other treatment regimens for several reasons not limited to adverse event. Regardless, pembrolizumab, if used as first-line treatment, would reduce the chances of disease progression or costs in drug therapy. Conclusions: Improving a patient’s quality of life is important when choosing the right course of treatment for any type of disease. In these studies, the quality-adjusted life years (QALY) were continuously increased when using pembrolizumab as compared to standard of care treatments and other immunotherapies. In the US healthcare system, the main factors to consider are the Healthcare Budget and the Payers willingness to pay. The US has legislated against the explicit use of cost per QALY thresholds but the $50,000 mark is commonly referred to. More studies should be conducted in the US to further conclude the cost-effectiveness of pembrolizumab in the treatment of cancer.
Sustaining positive outcomes with a progressive upright mobility program protocol in cancer patients.
Authors: Gehringer Paul
Published: September 2018

126

Background: Critical illness associated with immobility leads to significant morbidity including increased intensive care unit (ICU) days, hospital lengths of stay (LOS), and prolonged deconditioning. Several prior studies have demonstrated improvements in LOS and ventilator days when early institution of mobility programs are utilized; however, malignancy and a short expected life span have been exclusions from all prior studies. The purpose of this retrospective investigation was to examine the safety and effectiveness of a progressive upright mobility program (PUM) in critically ill ventilated cancer patients. Methods: After twelve months of baseline data was collected investigating ventilator days, ICU LOS and hospital LOS, a stepwise multidisciplinary PUM protocol was developed and followed in all mechanically ventilated patients admitted to a single subspecialty cancer hospital ICU. Exclusions to protocol included hemodynamic instability, the need for continuous sedation, and neuromuscular blockade. Data from control period (pre) was compared to twelve-month post-intervention (post) data. To determine sustainability, an additional twelve months of data was collected and compared to the pre and post intervention groups. Compared data included demographics, severity of illness, ventilator days, and LOS. Results: Statistical analysis of the data included comparison of means and analysis of variance (ANOVA). The post protocol implementation group demonstrated statistically significant outcomes in the three areas measured; ventilator days reduced from 6.3 to 3.7 (p = 0.001755), ICU LOS 10.2 to 7.5 (p = 0.011016), and hospital LOS 20.9 to 14.1 (p = 0.000364). Conclusions: Despite oncology patients having a high severity of illness and likely functional decline, the patients continue to benefit from early mobilization as previously studied groups. The results reflect consistencies with current literature supporting the absence of complications in early mobilization of patients in the ICU. To our knowledge, this has been the first mobilization study conducted in an oncology critical care setting.
Flu fighters: Flu vaccine administrations in pediatric hematology oncology patients.
Authors: Beverley Mehgan , Lorenz Patricia , Kaplan Joel , Turner Nicole
Published: September 2018

131

Background: Influenza is a serious virus that affects millions of people every year. The CDC and AAP recommend all people starting 6 months of age get a yearly flu vaccine, especially the immunocompromised. Children receiving chemotherapy for cancer treatment are at heightened risk of severe influenza infection and resulting complications. (Goossen et al., 2013). Methods: An interdisciplinary team used the Model for Improvement with an aim statement, current and ideal process flow maps, and annotated run charts to monitor the impact of changes. Change ideas were tested via small-cycle PDSAs. Successful strategies included development of a flu form, targeting patients with pre-visit planning and phone calls, and escalation to physician intervention. Results: A p shewhart chart analyzed the percentage of target population receiving vaccines weekly. The goal was to vaccinate 95% of patients with leukemia or neuro-oncology on active chemotherapy who were older than 6 months of age without medical contraindications. At baseline, upper control limit (UCL) was 6%, mean was 2% and lower control limit (LCL) was 0%. After testing changes, the percentage of flu vaccines improved (special cause variation) to UCL 100%, mean 95%, LCL 87%. The goal was met and sustained through the end of 2018 flu season. This QI project also improved flu vaccinations given to all our patients as compared to the 2016/2017 flu season. During the 2016/2017 flu season, 295 flu vaccines were given. During the 2017/2018 flu season, 457 flu vaccines were given in a similar time frame, i.e. an increase of 155%. In addition to improving care delivered to our target population, this work facilitated greater distribution of flu vaccine to all at-risk populations in our clinic. Conclusions: This project shows a comprehensive and effective approach to reducing the risk of a serious health threat for some of our most vulnerable patients. By developing a well-defined process, standardizing messaging, and using data to inform next steps, our team surpassed benchmarks established by some of the best cancer care specialists in the country. The processes established here can be applied widely, offering hope that future flu seasons could be less devastating to vulnerable populations.
Creation and implementation of a chief fellow of quality improvement in an oncology fellowship program.
Authors: Jones Amy Little , Gulvin Joshua Michael , Butler-Gunn Catherin , Wolff Robert A. , Rieber Alyssa G.
Published: September 2018

152

Background: Educating oncology trainees in methods and practical applications of quality improvement (QI) is essential. QI is a key component of the ACGME core competency of systems based practice. Formal QI training helps oncologists deliver safe and effective cancer care. Creating a QI chief fellow position allows for patient safety and QI initiatives to be fellow-driven and focused on building lifelong, oncology specific, QI skills. Methods: Feedback was solicited from the fellowship’s executive committee and divisional leadership to establish the job description and funding. Nominations were sought from peer fellows, focusing on a fellow who has expressed interest in QI, patient safety, and/or value based healthcare. The chief fellow was tasked with implementing a QI educational curriculum, developing a fellowship-wide QI project, and representing the fellowship on institution-wide QI and patient safety committees. Results: 100% (14/14) graduating fellows completed the requirements for an institutional clinical QI certificate by the end of the second year of the QI chief implementation, compared to 0% before the start of the implementation. 100% (27/27) of 1st and 2nd year fellows completed online training modules in QI. Biannual root cause analyses for patient safety events were initiated as a standard part of educational curriculum. 4 separate fellow-initiated QI projects were completed: oral chemotherapy patient education, opioid use and documentation, survivorship care plans, and infusion center usage. Fellows’ selection to the institutional clinical safety and effectiveness course increased from 4.8% (2/42) to 9.8% (4/41) in since implementation of the QI chief fellow. Fellowship representation on institution-wide patient safety committee increased from 0 to 2. Conclusions: Implementing a QI chief fellow role in an oncology fellowship is a feasible way to integrate a QI curriculum and provide structure for fellows to obtain further certification in QI or patient safety during fellowship. Ongoing challenges include encouraging enthusiasm from the entire fellowship for QI projects, finding appropriate QI mentorship from faculty, and translating QI initiatives into academic products.
Sleep quality in hematopoietic stem cell transplant recipients and caregivers.
Authors: Badia Alonso Priscila , Hickey Victoria , Flesch Laura , Byerly Megan , Sensibaugh Chelsea , Potts Katherine , Michel Celia , Drozd Alisha , Dandoy Christopher Eugene
Published: September 2018

165

Background: Sleep is an essential biological function vital for physiological rest, healing and emotional well-being. Sleep disruption, defined as alterations to the normal sleeping patterns, is commonly seen in patients and caregivers with lengthy hospital stays. Sleep disruption in caregivers can lead to increased stress and fatigue, decrease quality of life and ultimately affect the caregiver ability to support their loved one. Methods: We studied through a longitudinal observational cohort study, the quality and quantity of sleep in pediatric patients undergoing hematopoietic stem cell transplant (HSCT) and their caregivers; we identified a high level of sleep disturbance utilizing actigraphy and recounted poor sleep through qualitative assessments. We then performed a cross sectional focus group analysis of patients/caregivers and medical staff to identify the factors associated with poor sleep. The global aim of our quality improvement initiative was to improve sleep quality in HSCT patients and caregivers through a reduction of the nighttime noise (9pm-7am) in the bone marrow transplant unit, from 46 decibels (dB) (mean baseline data) to 38dB (WHO recommends night outside noise of less than 40dB) in a 6 month period. Results: We identified the factors associated with sleep disruption; noisy room entries, overnight trash pulls, loud hallway noise and hospital staff. A simplified failure mode analysis identified four main key drivers; reliable nighttime awareness system, quiet nighttime nursing system, unobtrusive nighttime cleaning process and awareness maintenance system. Several PDSA (plan, do, study, and act) interventions took place and were adopted. After four months the overnight mean dB have decreased to 42dB (9% reduction). Overnight noise spikes above 60dB have decreased from a mean of 271 spikes to a mean of 151 spikes (44% reduction). By September 2018 we expect further decrease in spikes and overnight dB and follow up quantitative and qualitative sleep assessments. Conclusions: With a quality improvement initiative, we identified factors that negatively impact sleep and performed interventions that successfully mitigate these factors, leading to improve quality of sleep in HSCT patients and caregivers.
Promoting patient engagement in bladder cancer (BC) care through education.
Authors: Jaganathan Hamsa , Roc Anne , Turell Wendy , Chisolm Stephanie , Mohamed Nihal , Galsky Matthew
Published: September 2018

176

Background: BC is the 6th leading cause of cancer in the US and it is estimated that 81,190 Americans will be diagnosed this year. Promoting patient knowledge and involvement in BC care have led to successful management strategies. We offered 1 hour of online education to patients and their caregivers to provide clinical and supportive information that lends a sense of control, supports effective self-management, and promotes patient-physician communication. Methods: PlatformQ Health Education, in partnership with the Bladder Cancer Advocacy Network, developed and executed an interactive education program for patients with BC and their caregivers, which was broadcast live online on cancercoachlive.com on September 29, 2017 and on-demand through March 29, 2018. The program was viewed on cancercoachlive.com by 587 learners and attracted 533 additional learners through social media channels (e.g. Facebook). Education focused on treatment options and the accessibility of resources and support. Self-reported surveys, distributed to patients and caregivers 8 weeks after the program, were analyzed for improvements in perceived engagement in their cancer care. Results: After participating in the education, a majority of the learners reported they felt knowledgeable on treatment options to discuss with their HCPs (92%, n = 60) and resources and information they can use for self-care strategies (88%, n = 58). Follow-up survey results (n = 60) also indicated that the education helped 50% of learners enhance their communication with their HCP. Moreover, 54% of learners (n = 48) felt more in control of health care decisions, and 36% of learners (n = 59) reported improvements in their health-related behaviors. Write-in examples focused on staying informed of treatments and side effects, seeking support, and proactively asking questions to their HCPs. Conclusions: As ASCO guidelines note, providing patients with preoperative information and encouraging them to take an active part in the decision-making process are essential elements to achieving positive outcomes in BC. Results from the patient survey indicate that participating in an interactive, online education program enhanced knowledge and promoted patient engagement in BC care.
Evaluation of the implementation of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) across the province of Ontario.
Authors: Haji Farzana , Barbera Lisa Catherine , Amernic Heidi , Evans Jenna , Ismail Zahra , Brundage Michael Donald
Published: September 2018

188

Background: EPIC-CP, a prostate cancer Patient-Reported Outcome Measure (PROM), was implemented across Ontario’s 14 Regional Cancer Centres (RCCs) using a phased roll-out approach. This approach enabled implementation and evaluation in enrolled centres, with the aim of using the results to improve implementation in both the enrolled regions and those preparing to implement. The objective was to analyze formative evaluation results and identify opportunities for improvement in implementation. Methods: Surveys were developed for patients and providers to capture attitudes and experiences regarding EPIC-CP. Data collection was initiated approximately three months post-implementation, with three RCCs evaluated concurrently in ‘waves’. Descriptive analyses were performed to summarize the survey data. Results: To date, nine RCC’s have completed the formative evaluation with 104 providers and 517 patients responding to the surveys. Providers reported challenges with data flow (44% always or mostly received EPIC-CP results in a timely manner) and with responding to specific symptoms (27% and 29% reported that they are very confident in treating/managing sexual function and emotional issues respectively). Although 54% of providers acknowledged that using EPIC-CP should be part of their role, 46% indicated that it has added little or no value to their practice. In contrast, 75% of patients reported that EPIC-CP made it easier to communicate symptoms to their care team, which suggests that patients find EPIC adds value. Patient comments identified gaps such as educational resources for symptom management and additional support when completing the PROM. Conclusions: Opportunities to improve the patient and provider experience with EPIC-CP include: developing educational resources, addressing issues with technology and data flow, and identifying factors that influence provider uptake. These results will be used to design resources and support to improve the process for implementing EPIC-CP in later waves.
Feasibility of cancer clinical trial enrollment goals based on cancer incidence.
Authors: Tran George Nhat , Harker Matthew , Chiswell Karen , Unger Joseph M. , Fleury Mark , Hirsch Bradford Richard , Miller Kimberly , D'Almada Philip , Tibbs Sheri , Zafar Yousuf
Published: September 2018

20

Background: More than 20% of US clinical trials fail to accrue sufficient patients and terminate prematurely, impeding innovation and negating the valuable contributions of participating patients. The aim of this study is to estimate availability of patients for each trial opening in the national oncology clinical research portfolio to provide a benchmark for better understanding feasibility of clinical trial enrollment goals. Methods: The Database for Aggregate Analysis of ClinicalTrials.gov, up-to-date as of September 3, 2017, was used to identify actively-recruiting, interventional oncology trials at US sites. Observational studies were excluded as not all are registered. Trials were categorized via Medical Subject Headings or free text condition terms and sorted by cancer diagnosis. Trial slot availability was estimated between September 1, 2017, to August 31, 2018. Availability was estimated from total anticipated enrollment, assuming a constant recruitment rate. Estimates for studies with both foreign and US sites were pro-rated to calculate available enrollment in the US alone. The 2017 American Cancer Society cancer incidence estimates were used to approximate total US cancer diagnoses. Results: 4598 oncology trials were identified. Overall, an estimated 12.6 cancer patients are available for each clinical trial slot. The estimates by cancer diagnosis were: colorectal: 24.7 patients per trial slot; lung & bronchus: 20.1; prostate: 17.6; breast (female): 13.8; leukemia 11.6; and brain & other nervous system: 6.0. Conclusions: Across all diagnoses, 1 in 13 patients must enroll to meet accrual demands. This ratio varies by diagnosis. If cancer incidence is too low, trials with unrealistic accrual goals may be doomed at inception. In diagnoses with high disease burden, trial failure may be due to poor patient access or suboptimal design. [Table: see text]
Are real-world patient-reported outcomes associated with survival in patients with advanced pancreatic cancer?
Authors: Dai Wei Fang , Beca Jaclyn Marie , Guo Helen , Qiao Lucy , Isaranuwatchai Wanrudee , Schwartz Deborah , Naipaul Rohini , Arias Jessica , Gavura Scott , Barbera Lisa Catherine , Chan Kelvin K.
Published: September 2018

205

Background: Advanced pancreatic cancer (APC) patients often have a substantial symptom burden. In Ontario, patients visiting cancer clinics routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for 9 symptoms (scale: 0-10). Using ESAS, we explored the association between baseline patient-reported outcomes and overall survival (OS). Methods: APC Patients with ESAS records prior to receiving publicly-funded drugs from November 2008 to March 2016 were identified from Cancer Care Ontario’s New Drug Funding Program and Symptom Management databases. We examined 3 baseline composite ESAS scores: Total Symptom Distress Score (TSDS: all 9 symptoms), Physical Symptom Score (PHS: 6/9 symptoms), and Psychological Symptom Score (PSS: 2/9 symptoms); Composite scores greater than a threshold (defined as number of symptoms in composite score multiplied by clinically relevant score (≥4)) were categorized as High Symptom Burden (TSDS ≥ 36, PHS ≥ 24, PSS ≥ 8). The primary endpoint, OS, was assessed using Kaplan-Meier. Multivariable Cox models were used to adjust for age, gender, income, prior therapies (surgery, adjuvant gemcitabine, radiation), and Charlson's comorbidity. Analysis was repeated in a sub-cohort with identifiable ECOG status and stage. Results: We identified 2,199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving gemcitabine (54%), FOLFIRINOX (40%) or gemcitabine/nab-paclitaxel (6%). Crude median survival was 4.5 and 7.3 months for patients with high and low TSDS burden, respectively (HR = 1.50, 95% CI: 1.36, 1.66). After adjustment with multivariable Cox model, high TSDS burden was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). Similar trends were observed for PHS and PSS. When adjusting for both PHS and PSS in a Cox model, only the effect of PHS remained significant. In the sub-cohort (n = 393), high TSDS burden (HR = 1.34, 95% CI: 1.04, 1.73) was associated with lower OS, after adjusting for ECOG and stage. Conclusions: Among APC patients, a higher burden of patient-reported symptoms, via ESAS, at baseline was associated with reduced OS. The effect was prominent for physical symptoms, even after adjusting for treatment, stage and ECOG.
Creative strategies to address challenges in access.
Authors: Ruiz Carlos , Franco Susan
Published: September 2018

215

Background: The Cancer Center is structured across multiple campuses with clinics at three different locations. Patients, providers and referring offices encountered difficulty accessing services and encountered a fragmented structure and a non-standardized process. Patient and provider calls often resulted in multiple transfers. Referring providers and patients frequently left a voicemail for new patient appointments. There was no standardized process for addressing urgent clinical calls from patients. This led to delays in access for new patient appointments, delays in patient care and poor patient experience scores. Overall telephone statistics went untracked. Methods: A multidisciplinary team was organized and tasked with the creation of a centralized Cancer Contact Center (CCC). In August 2015 the CCC became a reality with the vision of “One Call Resolution” for anybody needing access to the services of the Cancer Center. Single telephone and fax numbers were created and all staff were placed together in one location. Three distinct job roles made up the CCC: Telephone Operators, as the main point of initial contact; New Patient Coordinators, to facilitate new patient referrals, record collection and scheduling; and Lead Nurses to provide clinical oversight and guidance. Processes were put in place to ensure standardization and consistent outcomes. Operator guidelines were conceived and an articulated approach to managing patient clinical concerns was planned. Clinical triage of these concerns initially involved the Telephone Operators, RN Case Managers and Lead Nurses. Later, clinical triage evolved into the creation of a specific triage line and Triage Nurses for clinical questions and to further ensure patient safety. Results: Patient experience scores relating to telephone accessibility for patients have increased from a 56.9 Top Box score to a 67.5 score. Telephone answer rates have been sustained above 95%. Conclusions: The creation of a centralized Cancer Contact Center has enabled all calls, referrals and clinical triage to be initially managed in one location under a standardized process with sustainable results.
Results from a pilot of an innovative 4R Cancer Care Delivery Model: Impact on patient self-management.
Authors: Trosman Julia Rachel , Weldon Christine B. , Perez Claudia B. , Kulkarni Swati , Khan Seema Ahsan , Hansen Nora M. , Nelson Valerie , Stein Jennifer , Simon Melissa A. , Spagnoli Cathy , Tepper Jennifer , Pearson Kay , Gradishar William John
Published: September 2018

224

Background: Under the “NCI ASCO Teams” Project, we proposed a 4R Model of teamwork and patient self-management (pSM) (Trosman JOP ’16). 4R is Right Info / Care / Patient / Time. It enables patient (pt) and care team to manage interdependent care along the care continuum with an innovative multimodality personalized 4R Care Project Plan. We piloted 4R at 3 centers (academic, community, safety net) and assessed its impact on pSM. Methods: 4R Plans were administered to breast cancer pts stage 0-III Sep ’16 – Aug ’17 (4R cohort). We surveyed the 4R cohort and a comparable historical cohort of pts who received care pre-4R, Jun ’15 – May ’16 (control). We used simple frequencies and Fisher’s exact test in analyses. Results: Survey response rates: 68%, 185/271 (4R cohort); 47%, 241/410 (control). 75% of 4R respondents reported 4R Plans very useful / useful in overall understanding and organizing their care; 68% found 4R’s novel “project” component, very useful / useful in managing timing & sequencing of interdependent care. Care complexity impacted 4R usefulness: 67% of pts who received > 6 care services found 4R very useful / useful vs. 47% of pts who received < = 6 services, p = .01. Pts with lower care complexity suggested how to make 4R more useful to them, eg focus on endocrine therapy. Table compares pSM metrics in the 4R and control cohort. Care complexity was a significant factor of feeling overwhelmed for pts in the control cohort (51% of pts receiving > 6 care services felt overwhelmed vs. 31% of pts receiving < = 6 services, p = .02), but not a significant factor for pts in the 4R cohort (30% vs. 28%, p = .9). Conclusions: The 4R model significantly improved pt self-management in early breast cancer and reduced the impact of care complexity on pts, but provider factors of pSM need improvement. A 4R pilot at additional 12 cancer centers across the U.S. is in progress.[Table: see text]
Nationwide utilization and costs of targeted anti-cancer drugs for elderly patients with solid tumors in the United States, 2004-2015.
Authors: Wilson Lauren E , Greiner Melissa , Altomare Ivy , Rotter Jason , Dinan Michaela Ann
Published: September 2018

23

Background: Studies of patients age < 65 suggest large increases in utilization and costs of targeted anti-cancer drugs (TADs). However, use and costs of TADs in patients age 65+ have not been examined in a national sample. Methods: We conducted a retrospective analysis of patients ≥ 65 years with invasive lung (LC), breast (BC), or colorectal (CC) cancer using Medicare 5% claims from 2004-2015. We identified the yearly proportion of cancer patients receiving an intravenous TAD and the proportion of Part D enrolled Medicare patients receiving an oral TAD. We examined yearly costs of TADs as a proportion of total Medicare cancer and all-cause spending. Using generalized linear models, we estimated yearly trends in mean cost per beneficiary for TADs, all cancer spending, and total Medicare cost with adjustment for age, sex, region and comorbidities. Costs were adjusted to 2015 dollars using the CPI medical cost index. Results: We observed higher uptake of IV TADs in the 65+ patient population for each of the three cancers compared to oral TADs. IV TAD utilization reached 9.8% in CC patients, 5.0% in lung cancer patients, and 3.7% of BC patients. Use of oral TADs remained lower than use of IV TADs (≤ 1% of patients across all three cancers). From 2005-2015, total and cancer-specific Medicare spending per beneficiary decreased slightly for CC and LC patients and remained stable for BC patients. However, adjusted mean IV TAD spending per beneficiary increased from $139 in 2005 to $897 in 2015 for LC, from $96 to $550 for BC, and from $384 to $455 for CC. For Part D patients, the combined contribution of IV and oral TADs to total yearly cancer spending increased significantly from 2006 to 2015 for LC (2 to 5%), BC (4 to 18%), and CC (6 to 12%) cancers. Conclusions: Use of IV TADs in the US elderly lung, breast, and colorectal cancer populations grew rapidly in the years following FDA approval and stabilized. Use of oral TADs remained low compared to IV agents. Against the backdrop of largely stable Medicare spending, TADs are increasingly responsible for a growing proportion of that spending, particularly in breast cancer patients where TADs accounted for nearly a fifth of all 2015 cancer spending for Part D patients.
Mitigating risk of preventable medical errors across a network through event sharing.
Authors: Denny, DBA Diane , Shinners Caitlyn
Published: September 2018

234

Background: Medical errors are the 4th leading cause of death in the US. Oncology providers are not immune to preventable medical errors occurring in the treatment of their patients. As a national network of five hospitals that specialize in the treatment of patients fighting complex or advanced-stage cancer, clinicians and quality professionals recognized an opportunity to encourage and formalize the process of sharing safety events, lessons learned, and action plans to mitigate the risk of repeat occurrence. Methods: An Alert Notification process was established consisting of an algorithm depicting two avenues for action when an event occurs. If the event is considered urgent, characterized by immediate high-risk of repeat occurrence or high-risk of severe harm, an alert is called. The hospital nursing officers and quality directors along with the corporate director of pharmacy and vice president of quality/safety convene within 24 hours of the event to: 1) resolve or “halt” the process; 2) escalate if needed; and 3) formulate a communication plan regarding any change in process. If the event does not meet urgent criteria, the hospital conducts a root cause analysis (RCA) or common cause analysis, depending upon the algorithm. A summary of RCAs conducted for events resulting in temporary or permanent severe harm or worse are presented at the network’s monthly safety meeting, with action plans implemented across sites. Results: The notification algorithm was implemented in September 2017. Since its inception, three events have been communicated using the Urgent Alert Notification, including a syringe recall that halted use at all sites until all lot numbers could be checked, and affected syringes pulled. Several events and near misses have been communicated using the non-urgent process, including for example, discussion of a retained foreign object which resulted in review of processes for orienting staff to new products. Conclusions: The process has promoted communication across the five centers as an error prevention strategy. The sharing allows all sites to cross-fertilize resolutions to minimize rework, reduce the risk of repeat events, and build collective knowledge ensuring patient safety is our first commitment.
Ongoing professional practice evaluation: An infrastructure for accountability.
Authors: Denny, DBA Diane , Gross Danielle , Bernstein Gary
Published: September 2018

239

Background: As a national network of five hospitals treating patients fighting complex cancers, continuous monitoring of clinical staff competence is a priority. Recognizing an opportunity for an enhanced structure for ongoing professional practice evaluation (OPPE), a process mandated by The Joint Commission, the network set out to create heightened accountability, reliability and understanding of the review of performance data. Methods: Two work groups were established. The first was charged with the selection of meaningful specialty specific measures applicable to the oncology patient population. The second tasked to leverage resources expended using existing software and limiting the need for manual intervention. This group was responsible for creation and implementation of a consistent workflow with defined roles for physicians, medical staff operations and quality reviewers. Results: Over 50 subspecialties were mapped to over 250 selected metrics, with overlap when applicable to more than one specialty. A standard network-wide policy was approved by each center’s medical executive team. A workflow was clearly defined to include responsibilities associated with (pre-review) analyst role, service chief and credential committee. The use of the network’s reporting tool was standardized for OPPE as well as additional sources of quality data identified outside of the tool as needed, specifically for low volume and non-patient facing providers. A review calendar was created to guide the process on a rolling basis. Lastly, an OPPE Toolkit was created to govern and educate on the process that includes a pocket guide, Q&A, and on-boarding materials for physicians to understand their data relevant to metrics for which they are accountable. Conclusions: This systemic and timely evaluation of practitioner specific data supports improvement of practitioner performance and provides objective information for credentialing and privileging decisions across the network. Physicians’ visibility into their own data has increased. Automating the majority of efforts associated with OPPE has reduced the time associated with fulfilling this external requirement and resulted in full compliance.
Developing and testing a novel hospital readmission score for patients with cancer.
Authors: Power Steve , Kamal Arif
Published: September 2018

244

Background: Up to 50% of cancer patients experience an unplanned hospitalization. This represents opportunities for both improvements in quality of care and utilization of low value resources. Hospital readmission scores, to best target post-discharge navigation and follow-up, are needed yet not widely available. Methods: We conducted a retrospective cohort study among oncology patients admitted to Duke University Hospitals in 2015. The readmissions risk test model was built using multivariate analysis to identify and ‘weight’ four key readmission predictors. The model was subsequently analyzed in a validation data set using 2016 & 2017 admission data. Results: Of the 4987 admissions in 2015, 55% were male, 73% were Caucasian, and mean age was 61 (SD 14.1 years). Common cancers were GI (31%), Thoracic (27%) and GU (24%). Factors used to build the readmission predictor model based on the relative Odds Ratios were race (1), length of stay (1), discharge disposition (2), and previous admission with < 90 days (2) or 91-180 days (1). The patient cohort used to test the model had 1926 admissions and each were assigned a point value according to the model specifications, see Figure 1. We found significant differences in risk for readmission among differences in scores (p < 0.05). We have subsequently launched a post-discharge navigation program, with frequency of contacts dictated by readmission risk from the model. Conclusions: Predictor models in the oncology setting can identify combinations of factors that are associated with readmission. Programs that integrate such models may identify cancer patients at high risk of readmission and thus tailor a personalized approach to preventing a subsequent admission.[Table: see text]
Standardization of inpatient CPR status discussions and documentation within the division of hematology-oncology at UPMC Shadyside: Results from PDSA cycle 1 and 2.
Authors: Garcia Christine Ann , Bhatnagar Mamta , Rodenbach Rachel , Chu Edward , Marks Stanley M. , Graham-Pardus Abigail , Kriner Jamie , Winfield Melissa , Minnier Christopher , Leahy Janet , Hanchett Sharon , Baird Emily , Levenson Joshua
Published: September 2018

257

Background: In December 2016, 49% of patients admitted to inpatient oncology services at UPMC Shadyside had CPR status discussion documentation prior to discharge. This project aims to improve quality and rates of CPR status conversations. Methods: During Plan-Do-Study-Act (PDSA) cycle 1, a stakeholder workgroup was formed in January 2017 by oncology faculty, fellows, nurses and advance practice providers (APPs), medicine house staff, and palliative care faculty. All oncology clinicians were reminded weekly to discuss and document CPR status preferences. APPs received communication training with palliative care specialists. Oncology leadership received a monthly update of CPR status documentation rates, and endorsed CPR status best practice guidelines developed by the workgroup. For PDSA cycle 2, patient charts without CPR status documentation in March 2018 were reviewed. Results: PDSA cycle 1 resulted in CPR status assessment rates increasing from 49% to > 80%. 1400+ more CPR status discussions were documented in 2017 than 2016. The percentage of patients discharged “Comfort Measures Only” or “Do Not Resuscitate” increased from 14.2 (S.D. 2.4) to 20.0 (S.D. 2.1). For PDSA cycle 2, 60 patients without CPR assessment were reviewed. Fifty-two percent were admitted overnight by nocturnists, 48% by daytime APPs, and none by housestaff. 55% (33/60) had metastatic disease. Fifty-three percent (31/60) of patients had prior CPR status documentation in the past 12 months. Fifteen percent (11/60) of patients were admitted for scheduled inpatient chemotherapy. Conclusions: PDSA 1 showed that standardization of CPR status assessment with formal training increased CPR status assessments. More patients wanted CMO or DNR when asked, which may indicate the need for earlier goals of care discussions. PDSA 2 indicated that focusing efforts on completing CPR assessment as part of the admission process, especially for scheduled inpatient chemotherapy admissions, is critical in further improving our rates.