Faculty Bibliography

We estimated the extent to which different pain management practices, considered together as well as individually, mediated the relationship between chronic pain or physical disability and new-onset opioid use disorder (OUD) in a large cohort of adult Medicaid patients. Considering the plausibility of the assumptions required to identify different mediational estimands, we estimated natural indirect effects when considering mediation through the group of mediators together and estimated interventional indirect effects when considering mediation through each pain management practice individually. We estimated each effect using a nonparametric one-step estimator. The pain management variables we examined mediated all of the total effect of chronic pain on OUD risk and nearly half of the total effect of physical disability on OUD risk. High-dose, long-duration opioid prescribing and co-prescription of opioids with benzodiazepines, gabapentinoids, and muscle relaxants each contributed substantially to the increased risk of OUD due to chronic pain (contributing to 10-37% of the overall effect) and more moderately to the increased risk of OUD due to physical disability (contributing to 3-19% of the overall effect). Antidepressant or anti-inflammatory prescribing and physical therapy generally did not contribute to increased OUD risk, and, in some cases, even contributed to small reductions in risk.

BACKGROUND/UNASSIGNED:The informed consent process has traditionally taken place in person. The introduction of electronic consent (eConsent) has made remote consenting processes possible. Use of eConsent has increased since the COVID-19 pandemic. It has streamlined the process of consenting patients and has been shown to benefit the research study team and participants. ECONSENT IN THE KETAMINE ANALGESIA FOR LONG-LASTING PAIN RELIEF AFTER SURGERY KALPAS STUDY/UNASSIGNED:The KALPAS study is a multicenter, double-blind, randomized controlled study investigating the effectiveness of ketamine in reducing chronic post-mastectomy pain in women undergoing mastectomy for oncologic indication. The study uses a two-part consent form consisting of a master consent with information applicable to all sites and site-specific information. All potential participants receive the full two-part consent form for review. When signing the eConsent, however, all potential participants are provided with a concise summary of the informed consent document, an approach not widely used by multicenter studies. eConsent has been noted to be beneficial to research staff when trying to gather informed consent from participants who live far away from the hospital, want to include their family and friends, and for researchers who can approach patients outside of their clinical appointments. CONCLUSION/UNASSIGNED:The ability to consent patients remotely has allowed for a flexible workflow within sites and a more patient-centric process that focuses on including loved ones in the discussion and scheduling time to speak to a principal investigator. Demand for eConsent will likely continue in the post-COVID era, and use of a concise summary can allow for a more efficient consenting process.

INTRODUCTION/BACKGROUND:People with chronic pain are at increased risk of opioid misuse. Less is known about the unique risk conferred by each pain management treatment, as treatments are typically implemented together, confounding their independent effects. This study estimated the extent to which pain management treatments were associated with risk of opioid use disorder (OUD) for those with chronic pain, controlling for baseline demographic and clinical confounding variables and holding other pain management treatments at their observed levels. METHODS:Data were analyzed in 2024 from 2 chronic pain subgroups within a cohort of non-pregnant Medicaid patients aged 35-64 years, 2016-2019, from 25 states: those with (1) chronic pain and physical disability (CPPD) (N=6,133) or (2) chronic pain without disability (CP) (N=67,438). Nine pain management treatments were considered: prescription opioid (1) dose and (2) duration; (3) number of opioid prescribers; opioid co-prescription with (4) benzo- diazepines, (5) muscle relaxants, and (6) gabapentinoids; (7) nonopioid pain prescription, (8) physical therapy, and (9) other pain treatment modality. The outcome was OUD risk. RESULTS:Having opioids co-prescribed with gabapentin or benzodiazepine was statistically significantly associated with a 37-45% increased OUD risk for the CP subgroup. Opioid dose and duration also were significantly associated with increased OUD risk in this subgroup. Physical therapy was significantly associated with an 18% decreased risk of OUD in the CP subgroup. DISCUSSION/CONCLUSIONS:Coprescription of opioids with either gabapentin or benzodiazepines may substantially increase OUD risk. More positively, physical therapy may be a relatively accessible and safe pain management strategy.

Significant knowledge gaps exist in the perioperative pain management of patients with a history of chronic pain, substance use disorder, and/or opioid tolerance as highlighted in the US Health and Human Services Pain Management Best Practices Inter-Agency Task Force 2019 report. The report emphasized the challenges of caring for these populations and the need for multidisciplinary care and a comprehensive approach. Such care requires stakeholder alignment across multiple specialties and care settings. With the intention of codifying this alignment into a reliable and efficient processes, a consortium of 15 professional healthcare societies was convened in a year-long modified Delphi consensus process and summit. This process produced seven guiding principles for the perioperative care of patients with chronic pain, substance use disorder, and/or preoperative opioid tolerance. These principles provide a framework and direction for future improvement in the optimization and care of 'complex' patients as they undergo surgical procedures.

Chronic pain affects one in five adults. It is not only a major cause of disability for individual patients but also a driver of costs for entire healthcare systems. Treatment of pain remains a challenge, and the use of opioids has further led to a concurrent opioid epidemic. In this review, we discuss current standard treatment options for chronic pain, including pharmacological, behavioral, and interventional treatments. In addition, we review ongoing research in different areas that will potentially unlock new therapies.

PURPOSE OF REVIEW/OBJECTIVE:Up to 60% of breast cancer patients continue to experience pain three months or more after surgery, with 15 to 25% reporting moderate to severe pain. Post-mastectomy pain syndrome (PMPS) places a high burden on patients. We reviewed recent studies on perioperative interventions to prevent PMPS incidence and severity. RECENT FINDINGS/RESULTS:Recent studies on pharmacologic and regional anesthetic interventions were reviewed. Only nine of the twenty-three studies included reported a significant improvement in PMPS incidence and/or severity, sometimes with mixed results for similar interventions. Evidence for prevention of PMPS is mixed. Further investigation of impact of variations in dosing is warranted. In addition, promising newer interventions for prevention of PMPS such as cryoneurolysis of intercostal nerves and stellate ganglion block need confirmatory studies.

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/CONCLUSIONS: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/BACKGROUND:ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Cannabidiol (CBD) is one of the most interesting constituents of cannabis, garnering significant attention in the medical community in recent years due to its proven benefit for reducing refractory seizures in pediatric patients. Recent legislative changes in the United States have made CBD readily available to the general public, with up to 14% of adults in the United States having tried it in 2019. CBD is used to manage a myriad of symptoms, including anxiety, pain, and sleep disturbances, although rigorous evidence for these indications is lacking. A significant advantage of CBD over the other more well-known cannabinoid delta-9-tetrahydroncannabinol (THC) is that CBD does not produce a "high." As patients increasingly self-report its use to manage their medical conditions, and as the opioid epidemic continues to drive the quest for alternative pain management approaches, the aims of this narrative review are to provide a broad overview of the discovery, pharmacology, and molecular targets of CBD, its purported and approved neurologic indications, evidence for its analgesic potential, regulatory implications for patients and providers, and future research needs.