Prescription opioid treatment for non-cancer pain and initiation of injection drug use: large retrospective cohort study

Objective To assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of substance use. Design Retrospective cohort study. Setting Large administrative data source (containing information for about 1.7 million individuals tested for hepatitis C virus or HIV in British Columbia, Canada) with linkage to administrative health databases, including dispensations from community pharmacies. Participants Individuals age 11-65 years and without a history of substance use (except alcohol) at baseline. Main outcome measures Episodes of prescription opioid use for non-cancer pain were identified based on drugs dispensed between 2000 and 2015. Episodes were classified by the increasing length and intensity of opioid use (acute (lasting <90 episode days), episodic (lasting ≥90 episode days; with <90 days’ drug supply and/or <50% episode intensity), and chronic (lasting ≥90 episode days; with ≥90 days’ drug supply and ≥50% episode intensity)). People with a chronic episode were matched 1:1:1:1 on socioeconomic variables to those with episodic or acute episodes and to those who were opioid naive. IDU initiation was identified by a validated administrative algorithm with high specificity. Cox models weighted by inverse probability of treatment weights assessed the association between opioid use category (chronic, episodic, acute, opioid naive) and IDU initiation. Results 59 804 participants (14 951 people from each opioid use category) were included in the matched cohort, and followed for a median of 5.8 years. 1149 participants initiated IDU. Cumulative probability of IDU initiation at five years was highest for participants with chronic opioid use (4.0%), followed by those with episodic use (1.3%) and acute use (0.7%), and those who were opioid naive (0.4%). In the inverse probability of treatment weighted Cox model, risk of IDU initiation was 8.4 times higher for those with chronic opioid use versus those who were opioid naive (95% confidence interval 6.4 to 10.9). In a sensitivity analysis limited to individuals with a history of chronic pain, cumulative risk for those with chronic use (3.4% within five years) was lower than the primary results, but the relative risk was not (hazard ratio 9.7 (95% confidence interval 6.5 to 14.5)). IDU initiation was more frequent at higher opioid doses and younger ages. Conclusions The rate of IDU initiation among individuals who received chronic prescription opioid treatment for non-cancer pain was infrequent overall (3-4% within five years) but about eight times higher than among opioid naive individuals. These findings could have implications for strategies to prevent IDU initiation, but should not be used as a reason to support involuntary tapering or discontinuation of long term prescription opioid treatment.

Chronic Opioid Use Is Highly Prevalent in Patients Undergoing Allogeneic Transplant and Impacts Long Term Outcomes

Opioid analgesics are used to treat cancer-related pain and improve quality of life, however overuse of these high-risk drugs has been associated with significant public health implications as exhibited by the national attention received during the opioid pandemic. In addition, pain associated with hematologic malignancies is frequent yet not well understood. There is no data examining opioid use and outcomes in patients with hematologic malignancies and recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we sought to describe chronic opioid use (COU) and its impact on long-term outcomes in patients undergoing allo-HSCT. We analyzed outcomes of adult patients ≥ 18 years (n=159) diagnosed with hematologic malignancies (n=151) or benign hematologic disorders (n=8) (excluding sickle cell disease) who received allo-HSCT between 2012 and 2019 at a single urban medical center. COU was defined as having a documented active prescription for 3 consecutive months. Daily opioid doses were converted to morphine milligram milliequivalents (MME) using standard conversion factors. Among the entire cohort, the median age was 55.4 (19.4-74.3) years, 94 (59.1%) were male, 70 (44%) were White, 42 (26.4%) were Hispanic, and 26 (16.4%) were Black. The majority of patients were diagnosed with acute leukemia, with 89 (56%) having AML and 16 (10%) having ALL patients. Of the remaining patients, 14 (8.8%) were CML-BP or CML-AP, 16 (10%) NHL/HD, and 15 (9.4%) MPDs. 33.5% of patients were found to have high or very high DRI prior to allo-HSCT. Most patients received either a myeloablative (n=102, 64.2%) or reduced-intensity (n=55, 34.6%) conditioning regimen. At baseline (immediately prior to allo-SCT), COU was observed in 38 (23.9%) patients, 20 (52.6%) of which were diagnosed with AML. Only 23 (60.5%) patients with COU had a documented indication for opioid analgesia. The baseline median MME per day was 23.5mg (range: 2-150). In logistic regression analysis including demographic and social factors such as insurance type (i.e. Medicare, Medicaid, private payer), education level, smoking, alcohol, illicit drug and/or benzodiazepine use, and employment status, only older age (RR 0.97, 95% CI 0.94-0.99; p=0.026) was associated with a lower likelihood of baseline COU. In total, 149 (93.7%) patients received opioids during the allo-HSCT admission, while 45 (28.3%) were discharged on opioids. The reason for being discharged on opioids was related to musculoskeletal pain (n=19), residual mucositis-related pain (n=7), and headache (n=3). This was found to persist over time, with 35 (92.1%) of the 45 patients discharged on opioids remaining on opioids at 180 days after allo-HSCT thus meeting the definition for COU. The only factor found to predict for COU at 6 months was discharge from initial transplant hospitalization with an opioid (RR 2.24, 95% CI 1.16-4.32, p=0.016). Not only did a significant number of post-transplant survivors meet the definition for COU, but the MME was found to be relatively high with a median of 50mg (range: 10-540) at discharge and 30mg (range: 4.5-202) on days +30, 90, 180 as well as at 1 and 5 years after allo-HSCT. In a multivariable modified Poisson regression with robust standard errors for binary outcomes, when adjusted for established prognostic characteristics (i.e., disease, DRI, HCT-CI), we found that COU prior to admission strongly predicted for worse overall survival (HR 2.99, 95% CI 1.59-5.64; p=0.001), progression free survival (HR 2.72, 95% CI 1.48-4.99), and GVHD free, relapse-free survival (HR 1.78, 95% CI 1.05-3.03; p=0.033). This study is the first to describe patterns of COU, an important public health problem, among patients undergoing allo-HSCT, and in particular in long term survivors. We demonstrate high rates of baseline COU in patients undergoing allo-HSCT as well as persistent long term COU, which is linked to prescribing patterns after the initial transplant hospitalization. In addition, we show the negative impact of baseline COU on overall survival, even when adjusted for disease- and transplant-related factors. These data highlight the need to improve understanding and management of pain in hematologic malignancies as well as to reinforce the need for continuous reassessment of the use of opioids prior to and after allo-HSCT. Disclosures Calip: Flatiron Health: Current Employment; Roche: Current equity holder in publicly-traded company; Pfizer: Research Funding. Rondelli: Vertex: Membership on an entity's Board of Directors or advisory committees. Patel: Celgene: Consultancy.

Mindfulness-Oriented Recovery Enhancement remediates anhedonia in chronic opioid use by enhancing neurophysiological responses during savoring of natural rewards

Background Neuropsychopharmacologic effects of long-term opioid therapy (LTOT) in the context of chronic pain may result in subjective anhedonia coupled with decreased attention to natural rewards. Yet, there are no known efficacious treatments for anhedonia and reward deficits associated with chronic opioid use. Mindfulness-Oriented Recovery Enhancement (MORE), a novel behavioral intervention combining training in mindfulness with savoring of natural rewards, may hold promise for treating anhedonia in LTOT. Methods Veterans receiving LTOT (N = 63) for chronic pain were randomized to 8 weeks of MORE or a supportive group (SG) psychotherapy control. Before and after the 8-week treatment groups, we assessed the effects of MORE on the late positive potential (LPP) of the electroencephalogram and skin conductance level (SCL) during viewing and up-regulating responses (i.e. savoring) to natural reward cues. We then examined whether these neurophysiological effects were associated with reductions in subjective anhedonia by 4-month follow-up. Results Patients treated with MORE demonstrated significantly increased LPP and SCL to natural reward cues and greater decreases in subjective anhedonia relative to those in the SG. The effect of MORE on reducing anhedonia was statistically mediated by increases in LPP response during savoring. Conclusions MORE enhances motivated attention to natural reward cues among chronic pain patients on LTOT, as evidenced by increased electrocortical and sympathetic nervous system responses. Given neurophysiological evidence of clinical target engagement, MORE may be an efficacious treatment for anhedonia among chronic opioid users, people with chronic pain, and those at risk for opioid use disorder.

Perioperative Factors Associated With Chronic Opioid Use After Spine Surgery

Study Design: Retrospective case control. Objectives: The purpose of the current study is to determine risk factors associated with chronic opioid use after spine surgery. Methods: In our single institution retrospective study, 1,299 patients undergoing elective spine surgery at a tertiary academic medical center between January 2010 and August 2017 were enrolled into a prospectively collected registry. Patients were dichotomized based on renewal of, or active opioid prescription at 3-mo and 12-mo postoperatively. The primary outcome measures were risk factors for opioid renewal 3-months and 12-months postoperatively. These primarily included demographic characteristics, operative variables, and in-hospital opioid consumption via morphine milligram equivalence (MME). At the 3-month and 12-month periods, we analyzed the aforementioned covariates with multivariate followed by bivariate regression analyses. Results: Multivariate and bivariate analyses revealed that script renewal at 3 months was associated with black race ( P = 0.001), preoperative narcotic ( P < 0.001) or anxiety/depression medication use ( P = 0.002), and intraoperative long lumbar ( P < 0.001) or thoracic spine surgery ( P < 0.001). Lower patient income was also a risk factor for script renewal ( P = 0.01). Script renewal at 12 months was associated with younger age ( P = 0.006), preoperative narcotics use ( P = 0.001), and ≥4 levels of lumbar fusion ( P < 0.001). Renewals at 3-mo and 12-mo had no association with MME given during the hospital stay or with the usage of PCA ( P > 0.05). Conclusion: The current study describes multiple patient-level factors associated with chronic opioid use. Notably, no metric of perioperative opioid utilization was directly associated with chronic opioid use after multivariate analysis.

Approaching trauma analgesia using prolonged and novel continuous peripheral nerve blocks - A case report -

Background A supraclavicular brachial plexus nerve block provides analgesia for the shoulder, arm, and hand; however, the maximum safe duration for a continuous infusion remains controversial. A novel continuous peripheral nerve block (CPNB) technique combining the Lateral, Intermediate, and Medial femoral cutaneous nerves (termed the ‘LIM’ block) to provide analgesia to the lateral, anterior, and medial cutaneous areas of the thigh while preserving quadriceps strength will also be described in detail here. CaseWe present a complex case in which simultaneous utilization of an unilateral supraclavicular CPNB (5 weeks) and bilateral LIM CPNB (5 days) are successfully performed to provide analgesia for a traumatic degloving injury resulting in multiple surgeries.Conclusions The analgesic plan in this case study eliminated previous episodes of opioid-induced delirium, facilitated participation in recovery, and removed concerns for respiratory depression and chronic opioid use in a patient at particular risk for both issues.