Cell-specific imputation of drug connectivity mapping with incomplete data.

Drug repositioning allows expedited discovery of new applications for existing compounds, but re-screening vast compound libraries is often prohibitively expensive. "Connectivity mapping" is a process that links drugs to diseases by identifying compounds whose impact on expression in a collection of cells reverses the disease's impact on expression in disease-relevant tissues. The LINCS project has expanded the universe of compounds and cells for which data are available, but even with this effort, many clinically useful combinations are missing. To evaluate the possibility of repurposing drugs despite missing data, we compared collaborative filtering using either neighborhood-based or SVD imputation methods to two naive approaches via cross-validation. Methods were evaluated for their ability to predict drug connectivity despite missing data. Predictions improved when cell type was taken into account. Neighborhood collaborative filtering was the most successful method, with the best improvements in non-immortalized primary cells. We also explored which classes of compounds are most and least reliant on cell type for accurate imputation. We conclude that even for cells in which drug responses have not been fully characterized, it is possible to identify unassayed drugs that reverse in those cells the expression signatures observed in disease.

Co-created Mobile Apps for Palliative Care Using Community-Partnered Participatory Research: Development and Usability Study.

BACKGROUND: Open design formats for mobile apps help clinicians and stakeholders bring their needs to direct, co-creative solutions. Palliative care for patients with advanced cancers requires intensive monitoring and support and remains an area in high need for innovation. OBJECTIVE: This study aims to use community-partnered participatory research to co-design and pretest a mobile app that focuses on palliative care priorities of clinicians and patients with advanced cancer. METHODS: In-person and teleconference workshops were held with patient and family stakeholders, researchers, and clinicians in palliative care and oncology. Question prompts, written feedback, semistructured interviews, and facilitated group discussions identified the core palliative care needs. Using Chorus, a no-code app-building platform, a mobile app was co-designed with the stakeholders. A pretest with 11 patients was conducted, with semistructured interviews of clinician and patient users for feedback. RESULTS: Key themes identified from the focus groups included needs for patient advocacy and encouragement, access to vetted information, patient-clinician communication support, and symptom management. The initial prototype, My Wellness App, contained a weekly wellness journal to track patient-reported symptoms, goals, and medication use; information on self-management of symptoms; community resources; and patient and caregiver testimonial videos. Initial pretesting identified value in app-based communication for clinicians, patients, and caregivers, with suggestions for improving user interface, feedback and presentation of symptom reports, and gamification and staff coordinators to support patient app engagement. CONCLUSIONS: The development of a mobile app using community-partnered participatory research is a low-technology and feasible intervention for palliative care. Iterative redesign and user interface expertise may improve implementation.

Update in palliative care in gynecologic oncology.

PURPOSE OF REVIEW: This review summarizes research advances in quality of life, symptom management, and end-of-life practices within palliative care that can benefit patients with gynecologic cancers. RECENT FINDINGS: Addressing fertility issues, sexual side effects, and possible disease recurrence can promote quality of life in gynecologic cancer survivors. Cannabis can provide some benefit for nausea and neuropathic pain, yet for nonneuropathic pain presentations, it does not appear to provide significant benefit in reducing opioid usage. Lastly, palliative care outcomes, such as reduced aggressive care at the end of life and higher rates of hospice enrollment are augmented by the presence of an outpatient palliative care clinic. SUMMARY: Ongoing advances in palliative care research hold potential for improvement in systems delivery of palliative care as well as symptom management and psychosocial support.

Impact of a Palliative Care Nurse Practitioner in an Oncology Clinic: A Quality Improvement Effort.

PURPOSE: Guidelines support early integration of palliative care (PC) into standard oncology practice; however, little is known as to whether outcomes can be improved by modifying health care delivery in a real-world setting. METHODS: We report our 6-year experience of embedding a nurse practitioner in an oncology clinic (March 2014-March 2020) to integrate early, concurrent advance care planning and PC. RESULTS: Compared with patients with advanced cancer not enrolled in the palliative care nurse practitioner program, in March 2020, patients who are enrolled are more likely to have higher quality of PC (eg, goals of care note documentation [82% v 15%; P < .01], referral to the psychosocial oncology program [67% v 37%; P < .01], and referral to hospice [61% v 34%; P < .01]) and less inpatient utilization in the last 6 months of life (eg, hospital days [12 v 18; P < .01] and intensive care unit days [1.2 v 2.3; P < .01]). The program expanded over time with the support of faculty skills training for advance care planning and PC, supporting a shared mental model of PC delivery within the oncology clinic. CONCLUSION: Embedding a trained palliative care nurse practitioner in oncology clinics to deliver early integrated PC can lead to improved quality of care for patients with advanced cancer.

Needs assessment of current palliative care education in U.S. hematology/oncology fellowship programs.

BACKGROUND: Palliative care (PC) education for fellows in hematology/oncology (H/O) training programs is widely accepted, but no studies to date have assessed PC education practices and values among program leadership. METHODS: Program Directors and Associate Program Directors of active H/O fellowship programs in the U.S.A. were surveyed. RESULTS: Of 149 programs contacted, 84 completed the survey (56% response rate), of which 100% offered some form of PC education. The most frequently utilized methods of PC education were didactic lectures/conferences (93%), required PC rotations (68%), and simulation/role-playing (42%). Required PC rotations were ranked highest, and formal didactic seminars/conferences were ranked fifth in terms of perceived effectiveness. The majority felt either somewhat (60%) or extremely satisfied (30%) with the PC education at their program. Among specific PC domains, communication ranked highest, addressing spiritual distress ranked lowest, and care for the imminently dying ranked second lowest in importance and competency. Solid tumor oncologists reported more personal comfort with pain management (p = 0.042), non-pain symptom management (p = 0.014), ethical/legal issues (p = 0.029), reported their fellows were less competent in pain assessment/management (p = 0.006), and communication (p = 0.011), and were more satisfied with their program's PC education (p = 0.035) as compared with hematologists. CONCLUSIONS: Significant disparities exist between those modalities rated most effective for PC education and those currently in use. Clinical orientation of program leadership can affect both personal comfort with PC skills and estimations of PC curriculum effectiveness and fellows' competency. H/O fellowship programs would benefit from greater standardization and prioritization of active PC education modalities and content.

Lessons From the Development and Implementation of a Palliative Care Elective for Fourth-Year Medical Students: A Pilot Study.

BACKGROUND: Although palliative care is recognized as an important component of medical school curricula, the content and structure of education in the field is variable and often lacks outpatient exposure. We aimed to develop and implement a palliative care clinical elective for fourth-year medical students incorporating both inpatient and outpatient learning. METHODS: Fourteen medical students participated in a palliative care elective which included 2 weeks on an inpatient consult service and 1 week of outpatient clinic and home hospice visits. The elective was evaluated using a focus group and previously validated surveys assessing self-rated competency and attitudes toward caring for palliative care patients. Data were analyzed using paired t tests to compare survey response means before and after the elective. RESULTS: Of the 14 participating students, 7 completed both the pre- and postelective surveys. Significant improvements in self-rated competency were seen in pain and symptom management (P < .001), communication (P < .001), and advance care planning (P < .01). Survey results also showed improvement in attitudes toward caring for dying patients (P < .001), with lower scores at the end of the elective suggesting reduced emotional distress. Although the outpatient component was hypothesized to be a major benefit of the curriculum, qualitative data revealed the most highly valued component to be direct observation and feedback during inpatient time. CONCLUSION: Given the highlighted importance of direct observation and feedback as a unique and powerful learning experience, future work should be targeted toward enhancing the quality and timeliness of feedback delivered by the palliative care interdisciplinary team.

Prognostication Accuracy, Confidence, and Decisional Conflict Across Training Levels of Internal Medicine Providers.

CONTEXT: Providing patient care at the end of a patient's life is a humbling and sacred experience for both patient and provider. Without a truthful and meaningful conversation about end-of-life care preferences, the care that is delivered may not be the care that the patient prefers. OBJECTIVES: Determine if there is a relationship between level of training, confidence, and presence of decisional conflict in making an accurate prognosis for 2 standardized cases. Additionally, we evaluated the correctness of the prognosis as measured against survival outcomes for patients with similar diagnoses. METHODS: Decisional conflict was measured with the SURE tool, a validated 4-item tool that has been used in assessing for the presence of decisional conflict. RESULTS: Following analysis of data, it was found that providers with no decisional conflict were much more likely to be attendings with more than 5 years' experience. Providers were more conflicted overall when confronted with a case with a more grave prognosis. It was determined that providers with a lower level of training were more likely to have decisional conflict. CONCLUSIONS: Provider confidence increases and decisional conflict decreases as one increases their level of training. However, the degree in which the provider is correct in their prognosis does not change as one increases their level of training. These findings have broad implications on patients, providers, and the health-care system.

aTEMPO: Pathway-Specific Temporal Anomalies for Precision Therapeutics.

Dynamic processes are inherently important in disease, and identifying disease-related disruptions of normal dynamic processes can provide information about individual patients. We have previously characterized individuals' disease states via pathway-based anomalies in expression data, and we have identified disease-correlated disruption of predictable dynamic patterns by modeling a virtual time series in static data. Here we combine the two approaches, using an anomaly detection model and virtual time series to identify anomalous temporal processes in specific disease states. We demonstrate that this approach can informatively characterize individual patients, suggesting personalized therapeutic approaches.

Palliative care in gynecologic oncology.

PURPOSE OF REVIEW: Patients with gynecologic malignancies face many difficult issues in the course of their diseases, ranging from physical symptoms to advance care planning in light of a poor prognosis. This review examines the evidence supporting integration of palliative care early in the course of disease and symptom management, and provides a framework for difficult conversations. RECENT FINDINGS: Palliative care has been demonstrated to improve quality of life and promote survival if integrated early in the course of disease. An evidence-based approach should guide symptom management, such as pain and nausea. Advance care planning and goals of care discussions are enhanced by a framework guiding discussion and the incorporation of empathetic responses. SUMMARY: Palliative care is a diverse multidisciplinary field that can provide significant benefit for patients with gynecologic malignancies.

Palliative Care Professional Development for Critical Care Nurses: A Multicenter Program.

BACKGROUND: Integrating palliative care into intensive care units (ICUs) requires involvement of bedside nurses, who report inadequate education in palliative care. OBJECTIVE: To implement and evaluate a palliative care professional development program for ICU bedside nurses. METHODS: From May 2013 to January 2015, palliative care advanced practice nurses and nurse educators in 5 academic medical centers completed a 3-day train-the-trainer program followed by 2 years of mentoring to implement the initiative. The program consisted of 8-hour communication workshops for bedside nurses and structured rounds in ICUs, where nurse leaders coached bedside nurses in identifying and addressing palliative care needs. Primary outcomes were nurses' ratings of their palliative care communication skills in surveys, and nurses' identification of palliative care needs during coaching rounds. RESULTS: Each center held at least 6 workshops, training 428 bedside nurses. Nurses rated their skill level higher after the workshop for 15 tasks (eg, responding to family distress, ensuring families understand information in family meetings, all P < .01 vs preworkshop). Coaching rounds in each ICU took a mean of 3 hours per month. For 82% of 1110 patients discussed in rounds, bedside nurses identified palliative care needs and created plans to address them. CONCLUSIONS: Communication skills training workshops increased nurses' ratings of their palliative care communication skills. Coaching rounds supported nurses in identifying and addressing palliative care needs.

Effect and Efficiency of an Embedded Palliative Care Nurse Practitioner in an Oncology Clinic.

PURPOSE: To test a simultaneous care model for palliative care for patients with advanced cancer by embedding a palliative care nurse practitioner (NP) in an oncology clinic. METHODS: We evaluated the effect of the intervention in two oncologists' clinics beginning March 2014 by using implementation strategies, including use of a structured referral mechanism, routine symptom screening, integration of a psychology-based cancer supportive care center, implementation team meetings, team training, and a metrics dashboard for continuous quality improvement. After 1 year of implementation, we evaluated key process and outcome measures for supportive oncology and efficiency of the model by documenting tasks completed by the NP during a subset of patient visits and time-motion studies. RESULTS: Of approximately 10,000 patients with active cancer treated in the health system, 2,829 patients had advanced cancer and were treated by 42 oncologists. Documentation of advance care planning increased for patients of the two intervention oncologists compared with patients of the other oncologists. Hospice referral before death was not different at baseline, but was significantly higher for patients of intervention oncologists compared with patients of control oncologists (53% v 23%; P = .02) over the intervention period. Efficiency evaluation revealed that approximately half the time spent by the embedded NP potentially could have been completed by other staff (eg, a nurse, a social worker, or administrative staff). CONCLUSION: An embedded palliative care NP model using scalable implementation strategies can improve advance care planning and hospice use among patients with advanced cancer.

Use of a Shared Mental Model by a Team Composed of Oncology, Palliative Care, and Supportive Care Clinicians to Facilitate Shared Decision Making in a Patient With Advanced Cancer.

Our case describes the efforts of team members drawn from oncology, palliative care, supportive care, and primary care to assist a woman with advanced cancer in accepting care for her psychosocial distress, integrating prognostic information so that she could share in decisions about treatment planning, involving family in her care, and ultimately transitioning to hospice. Team members in our setting included a medical oncologist, oncology nurse practitioner, palliative care nurse practitioner, oncology social worker, and primary care physician. The core members were the patient and her sister. Our team grew organically as a result of patient need and, in doing so, operationalized an explicitly shared understanding of care priorities. We refer to this shared understanding as a shared mental model for care delivery, which enabled our team to jointly set priorities for care through a series of warm handoffs enabled by the team's close proximity within the same clinic. When care providers outside our integrated team became involved in the case, significant communication gaps exposed the difficulty in extending our shared mental model outside the integrated team framework, leading to inefficiencies in care. Integration of this shared understanding for care and close proximity of team members proved to be key components in facilitating treatment of our patient's burdensome cancer-related distress so that she could more effectively participate in treatment decision making that reflected her goals of care.

Cancer-related pain management in clinical oncology.

Uncontrolled pain is one of the most feared and debilitating symptoms among cancer patients, and many suffer unnecessarily from suboptimal pain control. Cancer-related pain is often multidimensional and can affect all aspects of a patient's life. Hence, achieving adequate pain relief among cancer patients involves a proper assessment of psychosocial, spiritual, and physical pain issues, matched with an individualized treatment plan involving pharmacologic, nonpharmacologic, and procedural therapies when appropriate. Providing effective pain relief can help ease the overall burden of disease among oncology patients while helping them tolerate cancer-directed therapies and achieve the most optimal quality of life throughout all phases of the disease continuum. In this review, the authors will discuss the syndromes, assessment of, and treatment for cancer-related pain in the outpatient setting.

New directions for diffusion-based network prediction of protein function: incorporating pathways with confidence.

MOTIVATION: It has long been hypothesized that incorporating models of network noise as well as edge directions and known pathway information into the representation of protein-protein interaction (PPI) networks might improve their utility for functional inference. However, a simple way to do this has not been obvious. We find that diffusion state distance (DSD), our recent diffusion-based metric for measuring dissimilarity in PPI networks, has natural extensions that incorporate confidence, directions and can even express coherent pathways by calculating DSD on an augmented graph. RESULTS: We define three incremental versions of DSD which we term cDSD, caDSD and capDSD, where the capDSD matrix incorporates confidence, known directed edges, and pathways into the measure of how similar each pair of nodes is according to the structure of the PPI network. We test four popular function prediction methods (majority vote, weighted majority vote, multi-way cut and functional flow) using these different matrices on the Baker's yeast PPI network in cross-validation. The best performing method is weighted majority vote using capDSD. We then test the performance of our augmented DSD methods on an integrated heterogeneous set of protein association edges from the STRING database. The superior performance of capDSD in this context confirms that treating the pathways as probabilistic units is more powerful than simply incorporating pathway edges independently into the network. AVAILABILITY: All source code for calculating the confidences, for extracting pathway information from KEGG XML files, and for calculating the cDSD, caDSD and capDSD matrices are available from http://dsd.cs.tufts.edu/capdsd

Pattern of malaria-specific T-cell responses in a cohort of Ugandan children.

Malaria is the leading cause of morbidity and mortality in children in Uganda. The mechanisms whereby malaria parasites are eliminated, or how they may avoid the immune response remain poorly understood. We examined malaria-specific T-cell responses in a well-characterized cohort of African children in an endemic area where malaria transmission occurs throughout the year. In studies of asymptomatic children, we found a low frequency of malaria-specific T-cell responses (15/117), and these appeared to be clustered in older children (> or =4 years old). Both CD4- and CD8-mediated T-cell responses were detected against circumsporozoite surface protein (CSP) and merozoite surface protein-1 (MSP-1). The presence of these T cells did not correlate with the frequency of prior episodes of parasitemia and 5 out of the 15 responders had no documented parasitemia within 8-12 months prior to immunologic evaluation. Our data supports focusing on high-risk children in future preventive vaccination efforts to ensure the generation and maintenance of effective anti-malarial cellular immune responses.