Effect of Drug Disposal Kits and Fact Sheets on Elimination of Leftover Prescription Opioids: The DISPOSE Multi-Arm Randomized Controlled Trial.

OBJECTIVE: To determine how passively providing informational handouts and/or drug disposal kits affects rates of leftover prescription opioid disposal. DESIGN: A multi-arm parallel-group randomized controlled trial with masked outcome assessment and computer-guided randomization. SETTING: Johns Hopkins Health System outpatient pharmacies. SUBJECTS: Individuals who filled ≥1 short-term prescription for an immediate-release opioid for themselves or a family member. METHODS: In June 2019, 499 individuals were randomized to receive an informational handout detailing U.S. Food and Drug Administration-recommended ways to properly dispose of leftover opioids (n = 188), the informational handout and a drug disposal kit with instructions on its use (n = 170), or no intervention (n = 141) at prescription pickup. Subjects were subsequently contacted by telephone, and outcomes were assessed by a standardized survey. The primary outcome was the use of a safe opioid disposal method. RESULTS: By 6 weeks after prescription pickup, 227 eligible individuals reported they had stopped taking prescription opioids to treat pain and had leftover medication. No difference in safe disposal was observed between the non-intervention group (10% [6/63]) and the group that received disposal kits (14% [10/73]) (risk ratio = 1.44; 95% confidence interval: 0.55 to 3.74) or the group that received a fact sheet (11% [10/91]) (risk ratio = 1.15; 95% confidence interval: 0.44 to 3.01). CONCLUSIONS: These findings suggest that passive provision of a drug disposal kit at prescription pickup did not increase rates of leftover opioid disposal when compared with provision of a fact sheet alone or no intervention. Active interventions may deserve further investigation.

Association of goals of care meetings for hospitalized cancer patients at risk for critical care with patient outcomes.

BACKGROUND: Caring for cancer patients with advanced and refractory disease requires communication about care preferences, particularly when patients become ill enough to be at risk for critical care interventions potentially inconsistent with their preferences. AIM: To describe the use of goals of care discussions in patients with advanced/refractory cancer at risk for critical care interventions and evaluate associations between these discussions and outcomes. DESIGN: Cohort study describing patients/families' perceptions of goals of care meetings and comparing health care utilization outcomes of patients who did and did not have discussions. SETTING/PARTICIPANTS: Inpatient units of an academic cancer center. Included patients had metastatic solid tumors or relapsed/refractory lymphoma or leukemia and were at risk for critical care, defined as requiring supplemental oxygen and/or cardiac monitor. RESULTS: Of 86 patients enrolled, 34 (39%) had a reported goals of care discussion (study group). Patients/families reported their needs and goals were addressed moderately to quite a bit during the meetings. Patients in the study group were less likely to receive critical care (0% vs 22%, p = 0.003) and more likely to be discharged to hospice (48% vs 30%, p = 0.04) than the control group. Only one patient in the study group died during the index hospitalization (on comfort care) (3%) compared with 9(17%) in the control group (p = 0.08). CONCLUSION: Goals of care meetings for advanced/refractory cancer inpatients at risk for critical care interventions can address patient and family goals and needs and improve health care utilization. These meetings should be part of routine care for these patients.

Evaluation of opioid use disorder treatment outcomes in patients receiving split daily versus once daily dosing of buprenorphine-naloxone.

INTRODUCTION: In clinical practice, sublingual (SL) buprenorphine-naloxone is prescribed as once daily or split daily dosing for the management of opioid use disorder (OUD). Evidence is lacking that assesses how split daily buprenorphine-naloxone affects OUD outcomes. This study aims to evaluate how the dosing frequency of SL buprenorphine-naloxone impacts therapy effectiveness when treating patients with OUD. METHODS: This retrospective analysis included adult outpatients prescribed treatment with SL buprenorphine-naloxone for OUD between July 1, 2016, and March 1, 2020. The study excluded patients with sickle cell disease, recent methadone treatment, or pregnancy. We characterized study groups by dosing frequency, either once daily or split dosing. The study compared retention in treatment, medication adherence, adherence to treatment program, and hospital encounters between groups. RESULTS: The study screened eight-hundred and seven patients, and included 250 patients newly prescribed SL buprenorphine-naloxone. Fifty-seven patients (22.8 %) were prescribed once daily dosing and 193 patients (77.2 %) were prescribed split daily dosing. The study found no significant differences noted in 12-month rates of treatment retention (52.6 % vs. 45.6 %, p = .35). These outcomes remained similar when assessed at three and six months. Within a year of buprenorphine-naloxone initiation, the study found no differences in the percentage of patients with hospitalizations (26.3 % vs. 38.3 %, p = .10), median number of hospitalizations (2 vs. 2), or proportion of days covered by a prescription ≥80 % (93.3 % vs. 92.0 %, p = .82). CONCLUSIONS: In this study, patients receiving once daily buprenorphine-naloxone had similar treatment outcomes to patients receiving split dosing. Further controlled studies are necessary to evaluate which patients are more likely to benefit from split dosing.

Adult cancer pain.

Pain is a common symptom associated with cancer and its treatment. Pain management is an important aspect of oncologic care, and unrelieved pain significantly comprises overall quality of life. These NCCN Guidelines list the principles of management and acknowledge the range of complex decisions faced in the management oncologic pain. In addition to pain assessment techniques, these guidelines provide principles of use, dosing, management of adverse effects, and safe handling procedures of pharmacologic therapies and discuss a multidisciplinary approach for the management of cancer pain.

Perioperative methadone prescribing and association with respiratory depression.

OBJECTIVE: Over 80 percent of surgery patients experience acute post-operative pain and less than half feel their pain is adequately controlled. Patients receiving chronic opioids, including methadone, are at the highest risk of inadequate pain control. Guidelines do not provide specific recommendations for analgesia management in this population. The purpose of this study was to evaluate the association between post-operative methadone use and respiratory depression. DESIGN: This study was a single center, retrospective, cohort study of adult patients. SETTING: Patients included were admitted to a single academic medical center from July 2016 to September 2018. PARTICIPANTS: Medical records of adult inpatients with an operative procedure who received perioperative methadone were reviewed. MAIN OUTCOME MEASURES: Preoperative methadone use was evaluated for all patients. Post-operative methadone dosing was compared to preoperative methadone dosing. Post-operative respiratory depression was evaluated. Logistic regression was performed to identify risk factors for respiratory depression. RESULTS: Two hundred ninety-eight patients were included in the study. Patients were divided into groups based on pre-operative methadone use. Over 90 percent of patients were on preoperative methadone. There were no significant differences in baseline characteristics between groups. In the initial seven post-operative days, 14.8 percent of patients had documented respiratory depression. Respiratory depression was more common among patients who were newly initiated on methadone post-operatively. Factors associated with respiratory depression included male sex, increased age, and new post-operative methadone initiation. CONCLUSIONS: Most patients who were administered post-operative methadone were on preoperative methadone. New post-operative methadone initiation was a risk factor for respiratory depression.

Current state of opioid stewardship.

PURPOSE: The opioid epidemic continues to result in significant morbidity and mortality even within hospitals where opioids are the second most common cause of adverse events. Opioid stewardship represents one model for hospitals to promote safe and rational prescribing of opioids to mitigate preventable adverse events in alliance with new Joint Commission standards. The purpose of this study was to identify the prevalence of current hospital practices to improve opioid use. METHODS: A cross-sectional survey of hospital best practices for opioid use was electronically distributed via electronic listservs in March 2018 to examine the presence of an opioid stewardship program and related practices, including formulary restrictions, specialist involvement for high-risk patients, types of risk factors screened, and educational activities. RESULTS: Among 133 included hospitals, 23% reported a stewardship program and 14% reported a prospective screening process to identify patients at high risk of opioid-related adverse events (ORAEs). Among those with a prospective screening process, there was variability in ORAE risk factor screening. Formulary restrictions were dependent on specific opioids and formulations. Patient-controlled analgesia was restricted at 45% of hospitals. Most hospitals reported having a pain management service (90%) and a palliative care service providing pain management (67%). CONCLUSION: The absence of opioid stewardship and prospectively screening ORAEs represents a gap in current practice at surveyed hospitals. Hospitals have an opportunity to implement and refine best practices such as access to pain management specialists, use of formulary restrictions, and retrospective and prospective monitoring of adverse events to improve opioid use.

Optimizing opioid prescribing and pain treatment for surgery: Review and conceptual framework.

PURPOSE: Millions of Americans who undergo surgical procedures receive opioid prescriptions as they return home. While some derive great benefit from these medicines, others experience adverse events, convert to chronic opioid use, or have unused medicines that serve as a reservoir for potential nonmedical use. Our aim was to investigate concepts and methods relevant to optimal opioid prescribing and pain treatment in the perioperative period. METHODS: We reviewed existing literature for trials on factors that influence opioid prescribing and optimization of pain treatment for surgical procedures and generated a conceptual framework to guide future quality, safety, and research efforts. RESULTS: Opioid prescribing and pain treatment after discharge from surgery broadly consist of 3 key interacting perspectives, including those of the patient, the perioperative team, and, serving in an essential role for all patients, the pharmacist. Systems-based factors, ranging from the organizational environment's ability to provide multimodal analgesia and participation in enhanced recovery after surgery programs to other healthcare system and macro-level trends, shape these interactions and influence opioid-related safety outcomes. CONCLUSIONS: The severity and persistence of the opioid crisis underscore the urgent need for interventions to improve postoperative prescription opioid use in the United States. Such interventions are likely to be most effective, with the fewest unintended consequences, if based on sound evidence and built on multidisciplinary efforts that include pharmacists, nurses, surgeons, anesthesiologists, and the patient. Future studies have the potential to identify the optimal amount to prescribe, improve patient-focused safety and quality outcomes, and help curb the oversupply of opioids that contributes to the most pressing public health crisis of our time.

Cancer pain management in the 21st century.

Cancer causes pain as it invades bone, compresses nerves, produces obstructive symptoms in the pulmonary, gastrointestinal, and genitourinary systems, and distends involved visceral organs. This manuscript reviews progress in cancer pain management during the past 2 decades. Since the 1980s, we have seen (1) genuine advances in research on the biology of pain, (2) new approaches to the treatment of cancer pain, and (3) important changes in the health-care system to ensure that pain is appropriately assessed and managed. Currently, clinicians have the appropriate diagnostic and therapeutic tools to ensure that the vast majority of patients with cancer pain can be comfortable during their illness. Nevertheless, too many patients with terminal malignancies continue to die in pain in nations around the globe. An effective strategy to make alleviating pain a major health-care priority remains the primary challenge to effectively palliating patients with cancer pain.

Equianalgesic dosing of opioids.

The concept of opioid equianalgesia, limitations in current dose conversion systems, equianalgesic dose tables, and computer assisted dose conversions are discussed. Conversions for methadone, fentanyl and hydromorphone are described.

Team Leadership and Cancer End-of-Life Decision Making.

End-of-life decision making in cancer can be a complicated process. Patients and families encounter multiple providers throughout their cancer care. When the efforts of these providers are not well coordinated in teams, opportunities for high-quality, longitudinal goals of care discussions can be missed. This article reviews the case of a 55-year-old man with lung cancer, illustrating the barriers and missed opportunities for end-of-life decision making in his care through the lens of team leadership, a key principle in the science of teams. The challenges demonstrated in this case reflect the importance of the four functions of team leadership: information search and structuring, information use in problem solving, managing personnel resources, and managing material resources. Engaging in shared leadership of these four functions can help care providers improve their interactions with patients and families concerning end-of-life care decision making. This shared leadership can also produce a cohesive care plan that benefits from the expertise of the range of available providers while reflecting patient needs and preferences. Clinicians and researchers should consider the roles of team leadership functions and shared leadership in improving patient care when developing and studying models of cancer care delivery.

Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant aprepitant.

PURPOSE: Ifosfamide is metabolized by the cytochrome P450 system to its active form, ifosforamide mustard. A potential side effect is neurotoxicity, often manifesting as confusion, hallucination, or seizure. Aprepitant, a neurokinin-1 inhibitor, is recommended for highly and moderately emetogenic chemotherapy regimens and may interfere with the metabolism of ifosfamide as it inhibits CYP3A4. The objective of the study is to identify if an increase in the incidence of neurotoxicity may be associated with the use of aprepitant with concomitant ifosfamide. METHODS: A retrospective study of inpatients with sarcoma who received a two or four-day regimen of MAI (mesna, doxorubicin, and ifosfamide) between January 1, 2004 and December 31, 2006 was conducted. Data collection focused on characterizing neurotoxicity of patients receiving ifosfamide with or without aprepitant. Correlation between serum creatinine, albumin, liver function tests, age, gender, and total doses of ifosfamide was examined. RESULTS: A total of 45 patients received ifosfamide of which 23 (51%) were male and 24 (53%) received aprepitant. All baseline characteristics were similar for those who received aprepitant versus those who did not. No significant differences were noted between patients with or without neurotoxicity for age, gender, or liver enzymes. Eight patients (18%) of 45 developed neurotoxicity of which six (75%) of those patients also received aprepitant. A trend of increased occurrence of neurotoxicity was noted with aprepitant administration (6 vs. 2 patients respectively, p = 0.176), although a statistical difference was not observed. A relative risk of 2.6 (95% CI, 0.47-26.6) was associated with the addition of aprepitant. CONCLUSIONS: An increased risk was identified for ifosfamide-induced neurotoxicity associated with aprepitant use; however, the observed difference was not statistically significant. The necessity of aprepitant given in association with ifosfamide may need to be reconsidered due to this risk.