Perceptions Toward Naloxone Among Patients With Cancer Receiving Opioids.

CONTEXT: Naloxone nasal spray is recommended for patients with risk factors for opioid overdose. However, cancer patients' perceptions and beliefs regarding naloxone prescriptions and their self-perceived risks for overdose are understudied. OBJECTIVE: To determine the proportion of cancer patients at risk for overdose who perceived naloxone as beneficial. METHODS: Between July 2020 and April 2022, we surveyed 150 adult patients from the supportive care ambulatory clinic at a tertiary cancer center in the United States who received a co-prescription of naloxone nasal spray. We measured patients' knowledge of overdose risk-factors, attitudes, beliefs, and education received on naloxone. Risk-factors between beneficial vs. nonbeneficial groups were analyzed. The survey was administered on paper or via a telephone interview. RESULTS: Of the 150 patients, 55% were male, 70% were white, and 81% had advanced cancer. The majority of patients believed naloxone was beneficial (100/150, 67%). When compared to the nonbeneficial group, more patients from the beneficial group agreed that the concurrent use of alcohol (100% vs. 90%; P = 0.004) or sedating drugs (96% vs. 85%; P = 0.04) with opioids could result in overdoses and felt safe having naloxone at home (95% vs. 60%; P <0.0001). More patients from the nonbeneficial group associated naloxone prescription with being suspected of misusing opioids (12/50 vs. 8/100; P = 0.01), and fewer had confidence in their caregivers' ability to administer naloxone (69% vs. 95%; P < 0.0001). CONCLUSION: Most patients understood the benefits of naloxone and felt safe having one at home. More research is needed to identify knowledge gaps and develop educational strategies for those who find it nonbeneficial.

Deficiencies with CAGE-AID questionnaire in identifying nonmedical opioid use-a report of two cases.

BACKGROUND: The CAGE-AID questionnaire (Cut-down, Annoyed, Guilty, Eye-opener scale Adapted to Include Drugs) is used to screen patients for substance use disorder and nonmedical opioid use (NMOU). Major pain guidelines encourage using such screening tools for all patients including cancer patients before initiating opioids. We present two cases where the CAGE-AID results did not accurately identify the risk for NMOU. CASE DESCRIPTION: Patient 1 is a male in his 60s with metastatic prostate cancer was admitted for uncontrolled pain. Imaging revealed extensive spinal metastasis, needing initiation of methadone and hydromorphone. The CAGE-AID score was positive, placing him at risk for NMOU. This likely biased the providers, delaying opioid titration. Subsequently, doses were adjusted, and he was discharged with adequate pain control and no evidence of NMOU. Patient 2 is a male in his 40s with metastatic cholangiocarcinoma admitted for uncontrolled abdominal pain. The patient had multiple hospitalizations at different facilities with similar symptoms. The CAGE-AID score was negative. Despite this, the patient demonstrated behaviors such as demanding intravenous opioids, dose escalation, or interventions such as nerve blocks. The workup did not identify any etiology for the increased pain. The patient left the hospital against medical advice when his demands for intravenous opioids were not met. CONCLUSIONS: The CAGE-AID questionnaire alone does not accurately identify risks for NMOU. Screening tools must always be accompanied by a thorough clinical assessment of behaviors and pain mechanism. More research is needed to better characterize CAGE-AID false positives and negatives among patients with cancer pain.

Impact of an Institution-Wide Goals of Care Program on the Timing of Referrals to Outpatient Palliative Care.

CONTEXT: Palliative care has received increased interest since the COVID-19 pandemic due to its role in guiding goals of care (GOC) discussions. OBJECTIVES: We assessed the change in the timing of outpatient palliative care referrals before and after implementing an institution-wide multicomponent interdisciplinary GOC (myGOC) program. METHODS: We reviewed 200 random supportive care center (SCC) consult visits each from June to November 2019 (before myGOC) and June to November 2020 (after myGOC). Data regarding Edmonton Symptom Assessment Scale (ESAS) scores, time from hospital registration to SCC visit, SCC visit until death/last follow-up, and advance care planning (ACP) notes were collected. Kaplan-Meier curves were used to evaluate overall survival (OS). RESULTS: The median OS from the SCC consult visit was 15.2 months (95% CI:11.7-19.7) before and 14.0 months (95% CI:10.8-17.9) after the myGOC program (P = 0.646). There were no significant differences in the median time between the SCC consult visit to death/last follow-up (11.95 vs. 12.0 months after myGOC; P = 0.841) and the first visits to our cancer center and SCC (6.1 vs. 5.29 months after myGOC; P = 0.689). Patients seen after myGOC had significantly lower ESAS symptom scores, better performance status (2 [1-2] vs. 2 [1-3]; P = 0.018], and more ACP notes composed by medical oncology teams (25.5% vs. 4.5%; P < 0.001). CONCLUSION: There were no significant differences in OS among patients seen in the SCC before and after myGOC, likely related to a ceiling effect. More oncologists had ACP discussions with patients, and patients had lower symptom scores on ESAS after myGOC, likely indicating that more patients were referred for GOC discussions and ACP rather than for symptom distress.

Attitudes of Palliative Care Specialists Toward Assessing Sexual Dysfunction in Patients With Cancer.

CONTEXT: The sexual health of patients is frequently neglected. OBJECTIVES: To evaluate the attitudes and beliefs of palliative care providers toward discussing the presence of sexual dysfunction (SD) in patients with cancer METHODS: In this pilot study, an anonymous survey was conducted among palliative care professionals about their attitudes toward discussing SD RESULTS: Forty-nine (89%) palliative care providers completed the survey. Thirty-four (69%) responded that they rarely or never discussed sexuality with their patients and most believed it is the oncologist's responsibility. The top reasons for not discussing SD were that the patient did not raise the issue, lack of time and the presence of a third party. The majority acknowledged the need of more training and that printed materials would be helpful. CONCLUSION: Palliative care providers infrequently address the presence of SD among patients with cancer. Additional training and routine screening for SD might help addressing this problem.

High Flow Nasal Cannula in Patients With Cancer at the End of Life.

CONTEXT: High flow nasal cannula (HFNC) is frequently used to manage dyspnea in patients with cancer near the end of life. Because HFNC is restricted to the in-patient setting, patients on HFNC need to be liberated from it to be discharged from the hospital. OBJECTIVES: The purpose of this study is to assess the rate of successful liberation from HFNC in a palliative and supportive care unit (PSCU). METHODS: The study is a retrospective chart review of all 374 adult patients with cancer on HFNC admitted to a palliative and supportive care unit at a tertiary medical center from January 1, 2018 to December 31, 2020. We determined the proportion of patients who were liberated from HFNC (by day three and overall) and the proportion of patients discharged alive. RESULTS: The mean age of the patients was 64, 54% were male and 73% were white. Only 16% (95% CI: 13-20) of the patients were discharged alive. Liberation from HFNC by day three and overall was accomplished in 23% and 25% of the patients respectively. Comparing the patients who could be liberated from HFNC vs. those who could not by day three, 38% vs. 9% were discharged alive respectively; and overall, 62% vs. 1% respectively (P < 0.001 in both cases). CONCLUSION: Only a minority of patients with cancer at the end of life can be liberated from HFNC, and only a minority are discharged alive. This information is important when discussing goals of care with patients and their families before initiating HFNC.

Evaluation of a Daily Nine-Item "Handbook for Self-Care at Work" for Palliative Care Clinicians.

Context: A daily nine-item "Handbook for Self-Care at Work" was created to increase the well-being and satisfaction of the staff at the department of palliative care of a tertiary oncological center in the United States. Objectives: To evaluate the perceived usefulness of and adherence to the Handbook. Design, Setting and Participants: An anonymous survey was conducted among the palliative care staff asking for the frequency of utilization and the perception of usefulness of the Handbook. Additional data collected included demographics, satisfaction with professional life, frequency of burnout, and frequency of callousness toward people. We also compared the use and perception of the Handbook before and during the COVID-19 pandemic. Results: Of 52 palliative care clinicians, 39 (75%) completed the survey. Most participants were women and were <49 years. Most respondents (59%) found the Handbook useful or very useful. Offer help, ask for help, and hydration were perceived as the most useful items. The items most frequently achieved were movement, hydration, and eat light. The least useful perceived item was nap time, which was rarely achieved. During the COVID-19 pandemic, 32 (82%) respondents found the Handbook to be as/somewhat more/much more useful, and 29 (75%) were able to adhere to the items as/somewhat more/much more often than before. Conclusion: Most respondents found the Handbook useful and were able to accomplish the items most of the days. During the COVID-19 pandemic, the staff felt that the Handbook was more useful.

Delirium in Palliative Care.

Delirium, a widespread neuropsychiatric disorder in patients with terminal diseases, is associated with increased morbidity and mortality, profoundly impacting patients, their families, and caregivers. Although frequently missed, the effective recognition of delirium demands attention and commitment. Reversibility is frequently not achievable. Non-pharmacological and pharmacological interventions are commonly used but largely unproven. Palliative sedation, although controversial, should be considered for refractory delirium. Psychological assistance should be available to patients and their families at all times.

Animal-related motorcycle collisions in North Dakota.

OBJECTIVE: To study the epidemiology and mortality of animal-motorcycle collisions. METHODS: A retrospective study of all motorcycle collisions recorded in the North Dakota Department of Transportation Crash Reporting System from January 2007 to December 2009 was conducted. Mortality was designated as the main outcome measure. RESULTS: Seven hundred sixty-six collisions involving 798 motorcycles were included in this study; 48 of these collisions were with animals (6.3% of all motorcycle collisions). Deer were the most common animal involved (81%). Most animal-motorcycle collisions took place during nighttime with clear weather and on straight rural roads. Drivers were older in animal collisions compared with nonanimal collisions (median of 44 vs 30 years old, respectively, P < .0001). Most drivers were males, whereas most passengers were females. Helmets were worn by only 32% of drivers and 12% of passengers. There were 4 (8%; 95% CI, 3%-20%) fatal animal collisions; 9% of the collisions with large animals were fatal compared with 3% of nonanimal collisions (P = .0411). CONCLUSIONS: Animal-motorcycle collisions are a small subgroup of all motorcycle collisions, but with a high mortality rate. Efforts should be made to increase helmet usage, mitigate these collisions, and increase awareness of this problem among motorcycle riders.

CXCR4 physically associates with the T cell receptor to signal in T cells.

SDF-1alpha (CXCL12) signaling via its receptor, CXCR4, stimulates T cell chemotaxis and gene expression. The ZAP-70 tyrosine kinase critically mediates SDF-1alpha-dependent migration and prolonged ERK mitogen-activated protein (MAP) kinase activation in T cells. However, the molecular mechanism by which CXCR4 or other G protein-coupled receptors activate ZAP-70 has not been characterized. Here we show that SDF-1alpha stimulates the physical association of CXCR4 and the T cell receptor (TCR) and utilizes the ZAP-70 binding ITAM domains of the TCR for signal transduction. This pathway is responsible for several of the effects of SDF-1alpha on T cells, including prolonged ERK MAP kinase activity, increased intracellular calcium ion concentrations, robust AP-1 transcriptional activity, and SDF-1alpha costimulation of cytokine secretion. These results suggest new paradigms for understanding the effects of SDF-1alpha and other chemokines on immunity.

Characterization of the CXCR4 signaling in pancreatic cancer cells.

CXCL12 and its receptor, CXCR4, are emerging as promising targets for modulating growth, angiogenesis, and metastasis in several human cancers. Indeed, blocking the receptor is sufficient to prevent metastasis and angiogenesis in experimental breast cancer xenografts. Recently, the biological effect of the CXCR4 in pancreatic cancer, one of the most deadly neoplastic diseases, has been reported. However, the molecular mechanism by which CXCR4 contributes to these properties is not completely understood. In this paper, we characterize the signaling pathways activated by CXCR4 in pancreatic cancer. We show that after CXCR4 activation, EGFR becomes tyrosine phosphorylated, and the kinase activity of this receptor, together with the activation of MMPs, Src, and PI3-Kinase, is required for CXCR4-mediated ERK activation. Analysis of this cascade in pancreatic cancer cells revealed that the ERK-mediated pathway regulates genes involved in angiogenesis, such as VEGF, CD44, HIF1alpha, and IL-8. Furthermore, ERK blockage inhibits the migration and tube formation of endothelial cells induced by CXCL12. Considering that inhibitors for several components of this pathway, including CXCR4 itself, are at different stages of clinical trials, this study provides theoretical justification for the clinical testing of these drugs in pancreatic cancer, thus extending the list of potential targets for treating this dismal disease.

Fundamentals of transcription factors and their impact on pancreatic development and cancer.

Transcription factors are proteins that regulate gene expression by modulating the synthesis of messenger RNA. Since this process, known as gene transcription, is often the dominant control point in the production of many proteins, transcription factors are key regulators of numerous cellular functions, including secretion, proliferation, differentiation, and apoptosis. Most transcription factors are also the final effectors of signaling pathways that transduce signals from the cell membrane to the nucleus. Therefore alterations in the activity or expression of some transcription factors have a significant impact on the biology of human cells and may lead to the development of diseases. In this article we review this field of research with a particular emphasis on the role of transcription factors in pancreatic development and cancer.