Optimizing the use of ketamine to reduce chronic postsurgical pain in women undergoing mastectomy for oncologic indication: study protocol for the KALPAS multicenter randomized controlled trial.

BACKGROUND: Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25-60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. METHODS: Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. DISCUSSION: This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Addressing opioid medication misuse at point of service in community pharmacy: A study protocol for an interdisciplinary behavioral health trial.

BACKGROUND: >1 in 3 of the 9 million individuals engaged in opioid medication misuse obtain legitimate opioid prescriptions and fill these in community pharmacies, which are subsequently misused. This study is testing the efficacy of a pharmacist-led intervention-Brief Intervention-Medication Therapy Management (BI-MTM)-compared to standard medication counseling (SMC) to address opioid medication misuse. METHODS: Design. This study is a single-blinded 2-group parallel randomized trial within 13 community pharmacies that will enroll 350 individuals. Participant Recruitment. Pharmacy staff approach patients and ask about interest in completing a brief confidential screening tool, which includes opioid medication misuse assessment. Interested patients who report misuse are asked to provide informed consent. Enrolled patients are assessed for behavioral and physical health at enrollment, 2-months post-enrollment, and 6-months post-enrollment. INTERVENTIONS: Following baseline assessment, participants are randomized (1:1 ratio) to: SMC, a medication information/counseling intervention or BI-MTM, an intervention comprised by 4 evidence-based components: medication therapy management, brief intervention, naloxone dispensing, and patient navigation. ANALYSES: Primary analyses involve estimating 3-level generalized linear mixed models to relate repeated assessments across time of opioid medication misuse (i.e., the Prescription Opioid Misuse Index) to the intervention. CONCLUSION: Study results will provide the first critical step towards integrating a highly accessible, low-cost approach to managing risks related to opioid use. Community pharmacies provide an incredibly important setting in which patients can receive high quality care to support health behavior change. Successfully completing this project sets the stage for a large-scale effectiveness study. (NCT#: NCT05141266).

Prospective Association of Serum Opioid Levels and Clinical Outcomes in Patients With Cancer Pain Treated With Intrathecal Opioid Therapy.

BACKGROUND: Opioids remain the mainstay of cancer pain management but are associated with systemic toxicity. In refractory cancer pain, intrathecal therapy (ITT) is associated with improved pain control, reduced systemic side effects, and improved survival. It has been assumed that ITT decreases systemic serum opioid levels and their associated toxicity, but there are limited data to support this assumption. This study hypothesizes that serum opioid levels decrease with ITT. Secondary objectives include comparative measures of pain, bowel function, and other cancer-related symptoms. METHODS: Fifty-one cancer patients undergoing ITT for cancer pain were recruited in a prospective observational study. Daily oral morphine equivalency (OME) dose, serum opioid levels, Brief Pain Inventory (BPI), MD Anderson Symptom Inventory (MDASI), and a constipation questionnaire were obtained at the time of implant, and 4 and 8 weeks postoperatively. RESULTS: Average baseline daily OME was 375 mg (median, 240; interquartile range, 150-405; range, 0-3160), mean serum morphine concentration was 53.7 ng/mL (n = 17), and mean oxycodone concentration was 73.7 ng/mL (n = 20). At 4 weeks, 87.5% of patients had discontinued non-IT opioids, and 53% had undetectable (<2 ng/mL) serum opioid concentrations. At 8 weeks, 92% remained off all non-IT opioids and 59% had undetectable serum opioid levels. IT morphine doses >4.2 mg/d were invariably associated with detectable serum levels; with doses <4.2 mg, morphine was undetectable in 80% of subjects. IT hydromorphone doses >6.8 mg/d were detectable in the serum. Using linear mixed model analyses, there were statistically significant decreases in the mean "worst pain," "average pain," and MD Anderson symptom severity and interference scores at 4 and 8 weeks. This change was independent of serum opioid levels; when analyzed separately, there was no difference in the pain scores of subjects with detectable serum opioid levels compared to those with undetectable levels at 4 and 8 weeks. Constipation ranked as "quite a bit" or "very much" decreased from 58.7% to 19.2% of subjects at week 4 (P < .001) and to 37.5% at 8 weeks (P = .23). A very low complication rate was observed. CONCLUSIONS: ITT for cancer pain was associated with a marked reduction in serum opioid concentrations, with the majority of patients having undetectable serum levels. Reducing serum opioid concentrations in cancer patients may have implications with respect to restoring bowel function, improving fatigue, and promoting the integrity of antitumor immune function and warrants further study.

Perioperative Pain Management for the Chronic Pain Patient With Long-Term Opioid Use.

In the United States nearly one in four patients presenting for surgery reports current opioid use. Many of these patients suffer from chronic pain disorders and opioid tolerance or dependence. Opioid tolerance and preexisting chronic pain disorders present unique challenges in regard to postoperative pain management. These patients benefit from providers who are not only familiar with multimodal pain management and skilled in the assessment of acute pain, but also empathetic to their specific struggles. Chronic pain patients often face stigmas surrounding their opioid use, and this may lead to underestimation and undertreatment of their pain. This article aims to review the challenges presented by these complex patients and provide strategies for treating acute postoperative pain in opioid-tolerant patients.

Medical student-developed obesity education program uses modified team-based learning to motivate adolescents.

BACKGROUND: Childhood obesity is reaching epidemic proportions and requires intervention. AIMS: To educate high school (HS) students on the effects of obesity and implement small healthy changes. Train medical students to educate and motivate adolescents and utilize a modified team-based learning format. METHODS: A medical student-created HS-based module was developed to educate adolescents on obesity's effects on health. Over 2 years, 25 medical students from each semester were trained and presented to 1590 freshmen and sophomores at suburban HSs in Milwaukee, Wisconsin. The program included an interactive power point and a 30-day challenge to make small measurable changes in their current health behaviors. A modified team-based learning format was included to engage students and increase classroom interaction. RESULTS: Medical students reported the program improved their ability to communicate with adolescents and enhanced their training as future physicians. Teachers felt students had sustained retention of knowledge at the end of 30 days and the majority of students fulfilled their self-imposed challenge. CONCLUSION: A student-run HS obesity education module using a portion of team-based learning was successfully implemented into HS health science curriculums, exposed medical students to community advocacy while educating and motivating adolescents to improve health behaviors.