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.

Reliability of urine drug testing among patients on buprenorphine transdermal patch.

BACKGROUND: Urine drug testing (UDT) plays a significant role in monitoring patients on chronic opioid therapy (COT) for non-medical opioid use (NMOU). UDT, at times, can be inconsistent and misleading. We present a case where a patient on a buprenorphine patch had false negative results. CASE DESCRIPTION: A female in her 70s with metastatic breast cancer presented with uncontrolled pain from a T6 compression fracture. She had no relief with tramadol 50 mg every 6 hours as needed. Due to an allergic reaction to hydromorphone, our team prescribed a buprenorphine patch of 5 µg/h. Subsequently, she expressed excellent pain control, and the clinician confirmed the patch placement on examination. She underwent a UDT during the visit. The UDT was negative for both buprenorphine and its metabolites. The literature review showed that false negative UDT results are relatively common among patients with low-dose buprenorphine patches. The combination of a thorough physical examination, a review of the Prescription Drug Monitoring Program, and reassuring scores on screening tools placed her at low risk for NMOU. DISCUSSION: Buprenorphine has a ceiling effect on respiratory depression and a lower risk for addiction. However, when used in low doses, the drug might not have enough metabolites in the urine, leading to a false negative UDT. Such results might affect patient-physician relationships. CONCLUSION: In addition to the UDT, a thorough history, screening for NMOU, physical exam, a review of PDMP, and a good understanding of opioid metabolism are necessary to help guide pain management.

Benefits and risks of off-label olanzapine use for symptom management in cancer patients-a case report.

BACKGROUND: Cancer patients often experience symptoms such as anorexia, anxiety and insomnia, which can impact their quality of life. Randomized placebo-controlled trials support prophylactic use of olanzapine for the prevention of nausea and vomiting due to moderate and high-emetic risk chemotherapy. In the setting of palliative care, olanzapine is increasingly utilized as an off-label treatment of symptoms including anorexia-cachexia, anxiety, and insomnia. The following case reports will highlight the potential benefits and risks of off-label olanzapine use for symptom management in cancer patients. CASE DESCRIPTION: Patient 1 is a female in her 70s with stage IV infiltrating ductal carcinoma of the right breast was having trouble tolerating treatment with letrozole, palbociclib, and denosumab due to uncontrolled nausea resulting in weight loss. Her nausea was refractory to multiple anti-emetics. Low dose olanzapine (2.5 mg) prevented nausea and allowed her to tolerate treatment. Patient 2 is a male in his 50s with renal cell carcinoma, who was receiving treatment with cabozantinib, presented with uncontrolled pain improved with opioid rotation from oxycodone to morphine. He was also experiencing uncontrolled anxiety despite treatment with alprazolam. Alprazolam was weaned and replaced with olanzapine resulting in improvement of his symptoms. Patient 3 is a male in his 60s with pancreatic adenocarcinoma who presented with muscle weakness and fatigue resulting in discontinuation of gemcitabine plus cisplatin. He also had symptoms of depression, poor appetite, and sleep problems. He was prescribed short course of dexamethasone 4 mg by mouth twice daily and olanzapine 5 mg by mouth nightly to improve symptoms. One week after, he presented with confusion and workup revealed hyperammonia which was treated with lactulose, which led to the return of baseline mentation. CONCLUSIONS: Olanzapine antagonizes multiple receptors and has potential to treat a host of symptoms including nausea, anorexia, anxiety, and insomnia, but healthcare providers should be mindful of potential risks and unclear benefits for off-label indications. More research and funding are needed evaluating off-label use of olanzapine for palliation of symptoms in cancer patients who are often frail and susceptible to adverse events.

Efforts to Improve Naloxone Co-Prescription for Patients With Cancer Pain at Risk of Opioid Overdose.

Importance: Naloxone can be lifesaving in an opioid-related overdose (OD). However, the co-prescription of take-home naloxone (THN) is not widely adopted in routine clinical practice. We implemented a pilot program focused on increasing clinicians' awareness of THN and observed if this impacts THN prescriptions for our patients with cancer pain receiving opioids. Intervention: In January 2020, we initiated an educational program by twice-weekly video presentations and installed pamphlets in all clinic workstations highlighting the risk factors for ODs. We retrospectively reviewed electronic health records (EHR) of randomly selected patient visits, 200 each from eight weeks before intervention (BI) and eight weeks after the intervention (AI). Data on patient characteristics, risk factors for ODs, and THN prescriptions were collected. Results: In all, 380 unique patients were eligible for analysis. The median age was 60, 53% female, and 70% Caucasian. Eighty-two percent (152) BI and 73% (142) AI carried risk factors for ODs (p = 0.13). THN was prescribed to 21% (32/152) BI and 26% (37/142) AI (p = 0.53). Morphine-equivalent daily dose (MEDD) ≥100 mg (30%) and pulmonary disease (25%) were the most prevalent risk factors. The patient's likelihood of receiving a THN prescription increased by 0.9% for every 1-milligram increase in MEDD (p < 0.001, 95% confidence interval: 1.006-1.011). Conclusion: The educational intervention did not significantly increase the frequency of THN prescriptions. More direct interventions, including automatic EHR triggers, may need to be tested in future trials.

Levorphanol as a Second Line Opioid in Cancer Patients Presenting to an Outpatient Supportive Care Center: An Open-label Study.

CONTEXT: Levorphanol is a potent opioid agonist and NMDA receptor blocker with minimal drug interactions, and there are few reports of its use in cancer patients. OBJECTIVES: We aimed to determine the frequency of successful opioid rotation (OR) to levorphanol and the median opioid rotation ratio (ORR) from Morphine Equivalent Daily Dose (MEDD). METHODS: This is a prospective, single-group, interventional study. Cancer outpatients requiring an OR and receiving a MEDD of 60-300 mg were rotated to levorphanol using a ratio of 10:1 and assessed daily for 10-day. Successful OR was defined as a 2-point improvement in the Edmonton Symptom Assessment System (ESAS) pain score on day 10 or achieving the personalized pain goal between days 3-10 in patients with uncontrolled pain or resolution of opioid side effects (OSE) in those undergoing OR for OSE alone. The ORR to levorphanol was calculated using net-MEDD (MEDD before OR minus the MEDD of the breakthrough opioid used along with levorphanol after OR). RESULTS: Forty patients underwent OR to levorphanol, and uncontrolled pain 35/40 (87.5%) was the most common indication. The median net-MEDD and levorphanol doses were 95 and 10 mg, respectively, and 33/40 (82.5%) had a successful OR with a median (IQR) ORR of 8.56 (7.5-10). Successful OR was associated with significant improvement in ESAS and OSE scale scores. There was a strong association between MEDD and levorphanol dose. CONCLUSION: This study provided preliminary data that cancer patients could be successfully rotated to levorphanol using an ORR of 8.5. Levorphanol was associated with improved pain and symptom control and was well- tolerated.

Health Care Provider Attitudes and Beliefs Toward Nonmedical Opioid Use in Patients with Cancer Pain.

Background: Data on health care providers' (HCPs') perceptions about patients with cancer pain and nonmedical opioid use (NMOU) are lacking. We examined the perceptions and attitudes of HCPs and assessed the usefulness of an interdisciplinary opioid stewardship program (OSP) while caring for these patients. Methods: An anonymous cross-sectional survey was conducted among the supportive care HCPs between September and November 2021. Results: Of 85 HCPs, 64 responded (75%) to the survey. Participants perceived that NMOU is underdiagnosed (42/64; 67%), and caring for such patients is difficult (58/64, 91%) and time consuming (54/64, 87%). A majority (50/51, 98%) were aware of the OSP, and (48/51; 94%) found it helpful. Conclusion: HCPs reported that NMOU is underdiagnosed and is challenging to manage. They endorsed the utility of an OSP in managing patients with concurrent cancer pain and NMOU. Future research should identify ways to standardize care and integrate OSP in routine supportive oncology practice.

Opioid Rotation and Conversion Ratios Used by Palliative Care Professionals: An International Survey.

Background: The opioid rotation ratios (ORRs) and conversion ratios (CRs) used worldwide among palliative care (PC) professionals to perform opioid rotations (ORs) and route conversions may have a wide variation. Methods: We surveyed PC professionals on opioid ratios used through email to the Multinational Association of Supportive Care in Cancer's PC study group and Twitter and Facebook posts between September and November 2020. Results: We received 370 responses from respondents from 53 countries: 276 (76%) were physicians, 46 (13%) advanced practice providers, 39 (11%) pharmacists, and 9 respondents did not report their profession. There were statistically significant variations in median CR from intravenous (IV) to oral morphine (2-3), IV to oral hydromorphone (2-4.5), ORR from IV hydromorphone to oral morphine (10-20), and ORR from transdermal fentanyl mcg/hour to oral morphine (2-3.5) across various groups. Conclusion: This survey highlights the wide variation in ORRs and CRs among PC clinicians worldwide and the need for further research to standardize practice.

Interdisciplinary intervention for the management of nonmedical opioid use among patients with cancer pain.

BACKGROUND: Few studies have assessed interventions aimed at managing nonmedical opioid use (NMOU) behavior among patients with cancer. The authors developed the Compassionate High-Alert Team (CHAT) intervention to manage patients receiving opioids for cancer pain who demonstrate NMOU behavior. The objective of this study was to determine the change in frequency of NMOU behaviors, pain intensity, and opioid requirements among those who received the intervention. METHODS: A total of 130 patients receiving opioids for cancer pain that had documented evidence of NMOU and received the CHAT intervention were reviewed. Demographic and clinical information such as NMOU behaviors, pain scores, and morphine equivalent daily dose at baseline, 3, and 6 months post-intervention was obtained. RESULTS: NMOU behaviors significantly decreased from a median (interquartile range) of 2 (1-3) at baseline to 0 (0-1) at both 3 and 6 months post-intervention (p < .001). A total of 45 of 75 (60%) and 31 of 50 (62%) of CHAT recipients achieved complete response to the intervention at 3 and 6 months, respectively. Higher baseline number of NMOU behaviors was independently associated with patient response to the intervention (odds ratio [OR], 1.97; 95% confidence interval [CI],1.09-4.28, p = .049 at 3 months; OR, 2.5; 95% CI, 1.20-6.47, p = .03 at 6 months). The median pain score decreased from 7 at baseline to 6 at both 3 and 6 months (p = .01). Morphine equivalent daily dose did not significantly change during that same period (143 mg/day vs. 139 mg/day, p = .13). CONCLUSIONS: Most patients who received the CHAT intervention improved in their NMOU behaviors and pain intensity scores 3 and 6 months post-intervention. These preliminary findings support the efficacy of CHAT in managing patients receiving opioids for cancer pain who demonstrate NMOU behavior.

Opioids and Cancer Mortality.

OPINION STATEMENT: Opioids are the gold standard for the treatment of cancer-related pain. Preclinical studies have associated opioids with cancer progression and overall survival. In mice models, opioids have been shown to possess pro-tumor activity secondary to immunosuppression, migration of tumor cells, increased activity of vascular endothelial growth factor receptors, and angiogenesis leading to tumor progression. In contrast, opioids have also been associated with having antitumor activity by activation of apoptosis and phagocytosis. However, high-quality randomized controlled trials in humans that are focused on the association between opioids and survival in cancer patients are lacking, which underscores the importance of being cautious when interpreting the results of the preclinical studies. Cancer-related pain is complex and multifactorial and may worsen as the disease progresses leading to higher opioid utilization. Moreover, cancer pain by itself has been associated with poor survival. The survival in these advanced cancer patients taking opioids may be more likely to be associated with cancer progression and not the opioid use. Adequate treatment of cancer pain has the potential to improve quality of life and performance status, highlighting the importance of continuing to use opioids to manage pain efficiently. More research is clearly needed.

Renal Replacement Therapy in Patients With Stage IV Cancer Admitted to the Intensive Care Unit With Acute Kidney Injury at a Comprehensive Cancer Center Was Not Associated With Survival.

INTRODUCTION: In patients with advanced cancer, prolongation of life with treatment often incurs substantial emotional and financial expense. Among hospitalized patients with cancer since acute kidney injury (AKI) is known to be associated with much higher odds for hospital mortality, we investigated whether renal replacement therapy (RRT) use in the intensive care unit (ICU) was a significant independent predictor of worse outcomes. METHODS: We retrospectively reviewed patients admitted in 2005 to 2014 who were diagnosed with stage IV solid tumors, had AKI, and a nephrology consult. The main outcomes were survival times from the landmark time points, inpatient mortality, and longer term survival after hospital discharge. Logistic regression and Cox proportional regression were used to compare inpatient mortality and longer term survival between RRT and non-RRT groups. Propensity score-matched landmark survival analyses were performed with 2 landmark time points chosen at day 2 and at day 7 from ICU admission. RESULTS: Of the 465 patients with stage IV cancer admitted to the ICU with AKI, 176 needed RRT. In the multivariate logistic regression model after adjusting for baseline serum albumin and baseline maximum Sequential Organ Failure Assessment (SOFA), the patients who received RRT were not significantly different from non-RRT patients in inpatient mortality (odds ratio: 1.004 [95% confidence interval: 0.598-1.684], P = .9892). In total, 189 patients were evaluated for the impact of RRT on long-term survival and concluded that RRT was not significantly associated with long-term survival after discharge for patients who discharged alive. Landmark analyses at day 2 and day 7 confirmed the same findings. CONCLUSIONS: Our study found that receiving RRT in the ICU was not significantly associated with inpatient mortality, survival times from the landmark time points, and long-term survival after discharge for patients with stage IV cancer with AKI.