Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

Targeted Program in an Academic Rheumatology Practice to Improve Compliance With Opioid Prescribing Guidelines for the Treatment of Chronic Pain.

OBJECTIVE: The Centers for Disease Control and Prevention (CDC) and many state governments have issued guidelines for opioid prescribing for the treatment of chronic noncancer-associated pain. We sought to decrease practice variation and increase compliance with these guidelines in a tertiary academic rheumatology practice by developing an interdisciplinary opioid working group and using electronic health record (EHR)-integrated data feedback. METHODS: Division leadership and providers established shared goals at interdisciplinary meetings involving rheumatology, pain medicine, nursing, and pharmacy. Interventions included educational sessions on opioid prescribing guidelines and the sharing of individual de-identified prescribing patterns. An opioid dashboard page within the EHR allowed every provider to see individualized and division-wide data that tracked process measures based on CDC and state-specific guidelines. Baseline data from June to August 2017 were compared with monthly data through December 2018. RESULTS: At baseline, 40% of patients had an active opioid agreement (a Pennsylvania guideline and a New Jersey law), 25% had a urine drug screen result within 12 months of their most recent opioid prescription, and 24% had a concurrent benzodiazepine prescription. After 16 months, these percentages improved to 88%, 66%, and 16%, respectively. The average number of opioid tablets prescribed per month decreased from 59,733 to 48,966 (-18%; P = 0.02). CONCLUSION: Shared goals developed through interdisciplinary input and readily accessible data feedback can markedly increase provider compliance with national and state-specific guidelines for opioid prescribing for the treatment of chronic noncancer-associated pain in rheumatology.

Reduction of Postoperative Opioid Use After Elective Spine and Peripheral Nerve Surgery Using an Enhanced Recovery After Surgery Program.

OBJECTIVE: Enhanced recovery after surgery (ERAS) pathways have previously been shown to be feasible and safe in elective spinal procedures. As publications on ERAS pathways have recently emerged in elective neurosurgery, long-term outcomes are limited. We report on our 18-month experience with an ERAS pathway in elective spinal surgery. METHODS: A historical cohort of 149 consecutive patients was identified as the control group, and 1,141 patients were prospectively enrolled in an ERAS protocol. The primary outcome was the need for opioid use one month postoperation. Secondary outcomes were opioid and nonopioid consumption on postoperative day (POD) 1, opioid use at three and six months postoperation, inpatient pain scores, patient satisfaction scores, postoperative Foley catheter use, mobilization/ambulation on POD0-1, length of stay, complications, and intensive care unit admissions. RESULTS: There was significant reduction in use of opioids at one, three, and six months postoperation (38.6% vs 70.5%, P < 0.001, 36.5% vs 70.9%, P < 0.001, and 23.6% vs 51.9%, P = 0.008) respectively. Both groups had similar surgical procedures and demographics. PCA use was nearly eliminated in the ERAS group (1.4% vs 61.6%, P < 0.001). ERAS patients mobilized faster on POD0 compared with control (63.5% vs 20.7%, P < 0.001). Fewer patients in the ERAS group required postoperative catheterization (40.7% vs 32.7%, P < 0.001). The ERAS group also had decreased length of stay (3.4 vs 3.9 days, P = 0.020). CONCLUSIONS: ERAS protocols for all elective spine and peripheral nerve procedures are both possible and effective. This standardized approach to patient care decreases opioid usage, eliminates the use of PCAs, mobilizes patients faster, and reduces length of stay.

Closing the gaps in opioid use disorder research, policy and practice: conference proceedings.

Drug overdose deaths involving opioids have surged in recent years and the economic cost of the opioid epidemic is estimated to be over $500 billion annually. In the midst of calls for declaring a national emergency, health policy decision makers are considering the best ways to allocate resources to curb the epidemic. On June 9, 2017, 116 invited health researchers, clinicians, policymakers, health system leaders, and other stakeholders met at the University of Pennsylvania to discuss approaches to address the gaps in evidence-based substance use disorder policy and practice, with an emphasis on the opioid epidemic. The conference was sponsored by the Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV (CHERISH), a NIDA-funded National Center of Excellence, and hosted by the Leonard Davis Institute of Health Economics of the University of Pennsylvania. The conference aims were to: (1) foster new relationships between researchers and policymakers through a collaborative work process and (2) generate evidence-based policy recommendations to address the opioid epidemic. The conference concluded with an interactive work session during which attendees self-identified as researchers or policymakers and were divided equally among 13 tables. These groups met to develop and present policy recommendations based on an opioid use disorder case study. Thirteen policy recommendations emerged across four themes: (1) quality of treatment, (2) continuity of care, (3) opioid prescribing and pain management, and (4) consumer engagement. This conference serves as a proposed model to develop equitable, working relationships among researchers, clinicians, and policymakers.

Pennsylvania State Core Competencies for Education on Opioids and Addiction.

OBJECTIVE: The objective of this project was to develop core competencies for education on opioids and addiction to be used in all Pennsylvania medical schools. METHODS: The Pennsylvania Physician General created a task force that was responsible for the creation of the core competencies. A literature review was completed, and a survey of graduating medical students was conducted. The task force then developed, reviewed, and approved the core competencies. RESULTS: The competencies were grouped into nine domains: understanding core aspects of addiction; patient screening for substance use disorder; proper referral for specialty evaluation and treatment of substance use disorder; proper patient assessment when treating pain; proper use of multimodal treatment options when treating acute pain; proper use of opioids for the treatment of acute pain (after consideration of alternatives); the role of opioids in the treatment of chronic noncancer pain; patient risk assessment related to the use of opioids to treat chronic noncancer pain, including the assessment for substance use disorder or increased risk for aberrant drug-related behavior; and the process for patient education, initiation of treatment, careful patient monitoring, and discontinuation of therapy when using opioids to treat chronic noncancer pain. Specific competencies were developed for each domain. CONCLUSIONS: These competencies will be incorporated into the educational process at all Pennsylvania medical schools. It is hoped that these curriculum changes will improve student knowledge and attitudes in these areas, thus improving patient outcomes.

The Initiation of Chronic Opioids: A Survey of Chronic Pain Patients.

This study reports the results of a researcher-administered survey with 115 patients receiving chronic opioid therapy (>90 days) to obtain information regarding how chronic opioid therapy was started. Chronic opioids were started after surgery (27.0%, 95% confidence interval [CI], 18.5-35.5) or for the treatment of acute injury-related pain (27.0%, 95% CI, 18.5-35.5). Many who initiated opioid therapy after surgery reported postoperative complications (61.3%, 95% CI, 50.8-71.8) and many with injury-related pain reported follow-up corrective surgery (58.1%, 95% CI, 47.5-68.7), which led to the continuation of opioids. A large percentage of patients had concurrent depression (43.5%, 95% CI, 34.0-53.0) and anxiety (23.5%, 95% CI, 15.3-31.7). Many participants had a medical history of aberrant drug-related behavior (32.5%, 95% CI, 23.5-41.5) and self-reported history of addiction (21.7%, 95% CI, 13.7-29.7). Almost one-quarter reported taking opioids for a different indication than that for which opioids were started (95% CI, 26.6-45.0). Patients receiving long-term opioid therapy often transitioned to chronic use after starting opioids for the short-term treatment of postoperative or injury-related pain. It is not evident if a clear decision to continue opioids on a chronic basis was made. This survey provides insight as to how chronic opioid therapy is started, and may suggest opportunities for improved patient selection for opioid therapy. PERSPECTIVE: This article explores the reasons why patients using chronic opioid therapy (>90 days) initiated opioid medications. The results of this study may help clinicians better select patients for chronic opioid therapy.

The Pain Medical Home: A Patient-Centered Medical Home Model of Care for Patients with Chronic Pain.

Chronic pain affects an estimated 100 million people a year in the United States and costs society anywhere from $560 to $635 billion annually. The patient-centered medical home and the patient-centered medical home-neighbor models of care have been advocated to improve patient outcomes. These models of care advocate improved coordination of care within the primary care and specialty care setting. The authors present the patient-centered medical home model of care and suggest how this model of care might be used to improve patient outcomes for patients with chronic pain.

Cardiac Effects of Opioid Therapy.

OBJECTIVE: The use of opioids to treat chronic pain has come under increased scrutiny, as such use has been associated with significant risk of death, with limited data regarding the long-term effectiveness, especially when used to treat noncancer pain. The purpose of this manuscript is to discuss the cardiac effects associated with long-term opioid therapy. DESIGN: A literature search was performed using OVID. RESULTS: Most opioids have little direct negative effect on cardiac contractility. However, opioid administration can be associated with decreased cardiac function when administered in combination with other medications, including benzodiazepines. Opioids can lead to bradycardia and vasodilation, and as a result can rarely lead to edema, hypotension, orthostatic hypotension, and syncope when used at analgesic doses. While most opioids have no effect on cardiac conductivity, methadone, and buprenorphine can prolong QTc, especially when used in patients at increased risk for QTc prolongation. Electrocardiogram (ECG) monitoring of QTc at baseline and following dose increases is appropriate in patients receiving these medications. CONCLUSIONS: There are limited data to suggest that chronic opioid administration may be associated with an increased risk for cardiac-related adverse effects. However, this observation has not yet been confirmed. Regardless, while opioids are an important medication for the treatment of a multitude of chronic pain conditions, careful patient selection, and diligent monitoring is likely to decrease the risk of harm and improve patient outcomes.

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

The QTc effect of low-dose methadone for chronic pain: a prospective pilot study.

OBJECTIVE: Methadone is associated with QT prolongation and serious cardiac complications, but this has been primarily demonstrated in opioid dependent patients receiving moderate to high doses. This study investigates the effect of low-dose methadone on the QTc interval in a chronic pain population. DESIGN AND SUBJECTS: We conducted a prospective cohort study in a chronic pain clinic including 82 patients receiving methadone and 102 patients receiving non-methadone opioid therapy. METHODS: We analyzed automated QTc calculations from 12-lead electrocardiograms at baseline and during the subsequent 6 months. The primary outcome of interest was the incidence of QTc greater than 470 milliseconds or an increase from baseline of greater than 60 milliseconds. RESULTS: The methadone group did not manifest an overall higher frequency of QTc > 470 milliseconds (6% for the methadone group vs 5% for controls, P = 0.722) or an increase in the QTc of > 60 milliseconds (4% for the methadone group vs 4% for controls, P = 0.94). In the first month after initiating methadone, patients demonstrated an increase in QTc compared to controls (5% for the methadone group vs 0% for the controls, P = 0.073) but the difference disappeared in the third and sixth months. CONCLUSION: Data from our chronic pain clinic support a potential association of QTc prolongation during the initiation of methadone, but this effect is small and short lived. We believe larger scale studies to further characterize the safety profile of low-dose methadone are warranted.