High-dose Opioid Use Research Articles

Increased risk of adverse events in non-cancer patients with chronic and high-dose opioid use-A health insurance claims analysis.

Chronic and high dose opioid use may result in adverse events. We analyzed the risk associated with chronic and high dose opioid prescription in a Swiss population. Using insurance claims data covering one-sixth of the Swiss population, we analyzed recurrent opioid prescriptions (≥2 opioid claims with at least 1 strong opioid claim) between 2006 and 2014. We calculated the cumulative dose in milligrams morphine equivalents (MED) and treatment duration. Excluded were single opioid claims, opioid use that was cancer treatment related, and opioid use in substitution programs. We assessed the association between the duration of opioid use, prescribed opioid dose, and benzodiazepine use with emergency department (ED) visits, urogenital and pulmonary infections, acute care hospitalization, and death at the end of the episode. In 63,642 recurrent opioid prescription episodes (acute 38%, subacute 7%, chronic 25.8%, very chronic (>360 days) episodes 29%) 18,336 ED visits, 30,209 infections, 19,375 hospitalizations, and 9,662 deaths occurred. The maximum daily MED dose was <20 mg in 15.8%, 20-<50 mg in 16.6%, 50-<100 mg in 21.6%, and ≥100 mg in 46%. Compared to acute episodes (<90 days), episode duration was an independent predictor of ED visits (chronic OR 1.09 (95% CI 1.03-1.15), very chronic (>360 days) OR 1.76 (1.67-1.86)) for adverse effects; infections (chronic OR 1.74 (1.66-1.82), very chronic 4.16 (3.95-4.37)), and hospitalization (chronic: OR 1.22 (1.16-1.29), very chronic OR 1.82 (1.73-1.93)). The risk of death decreased over time (very chronic OR 0.46 (0.43-0.50)). A dose dependent increased risk was observed for ED visits, hospitalization, and death (≥100mg daily MED OR 1.21 (1.13-1.29), OR 1.29 (1.21-1.38), and OR 1.67, 1.50-1.85, respectively). A concomitant use of benzodiazepines increased the odds for ED visits by 46% (OR 1.46, 1.41-1.52), infections by 44% (OR 1.44, 1.41-1.52), hospitalization by 12% (OR 1.12, 1.07-1.1), and death by 45% (OR 1.45, 1.37-1.53). The length of opioid use and higher prescribed morphine equivalent dose were independently associated with an increased risk for ED visits and hospitalizations. The risk for infections, ED visits, hospitalizations, and death also increased with concomitant benzodiazepine use.

Prevalence of Prescribed Opioid Claims Among Persons With Traumatic Spinal Cord Injury in Ontario, Canada: A Population-Based Retrospective Cohort Study

ObjectivesTo examine prescription opioid claims among individuals with traumatic spinal cord injury (SCI) and to identify factors associated with both chronic opioid and chronic high-dose opioid use. DesignRetrospective cohort study using population-level administrative data. SettingOntario, Canada. ParticipantsIndividuals (N=1842) with traumatic SCI between April 1, 2004 and March 31, 2015. InterventionsNot applicable. Main Outcome MeasuresProportion of cohort with chronic opioid use (≥90d supply) and proportion with chronic high-dose opioid use (≥90d supply exceeding 90 mg morphine equivalent) between April 1, 2016 and March 31, 2017 (observation period). ResultsA total of 1842 individuals with traumatic SCI were identified (74% men), with a median age of 51 years (interquartile range [IQR], 34-64y) and median duration of injury of 6 years (IQR, 4-9y). During the observation period, 35% were dispensed at least 1 opioid and 19.8% received chronic opioids, 39% of whom received more than 90 mg daily (chronic high dose). The median daily morphine equivalent dose was 212 mg morphine equivalent (IQR, 135.5-345.3 mg) for chronic high-dose users. Significant risk factors for chronic opioid use were male sex; age between 40 and 60 years; lower income; multimorbidity; thoracic, lumbar, or sacral level of injury; and having a previous diagnosis of osteoarthritis. Risk factors for chronic high-dose opioid use were an extended time since injury, age between 40 and 50 years, and increasing comorbidity. ConclusionsA large proportion of individuals with traumatic SCI were dispensed an opioid in a recent 1-year period. A substantial proportion were dispensed more than 90 mg of morphine equivalents, which is the maximum recommended by the Canadian opioid guideline. Further research is needed to understand the risk factors associated with chronic, high-dose opioid use in this population.

Opioid use after adult spinal deformity surgery: patterns of cessation and associations with preoperative use.

The objectives of the study were to determine, among patients with adult spinal deformity (ASD), the following: 1) how preoperative opioid use, dose, and duration of use are associated with long-term opioid use and dose; 2) how preoperative opioid use is associated with rates of postoperative use from 6 weeks to 2 years; and 3) how postoperative opioid use at 6 months and 1 year is associated with use at 2 years. Using a single-center, longitudinally maintained registry, the authors identified 87 patients who underwent ASD surgery from 2013 to 2017. Fifty-nine patients reported preoperative opioid use (37 high-dose [≥ 90 morphine milligram equivalents daily] and 22 low-dose use). The duration of preoperative use was long-term (≥ 6 months) for 44 patients and short-term for 15. The authors evaluated postoperative opioid use at 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery. Multivariate logistic regression was used to determine associations of preoperative opioid use, dose, and duration with use at each time point (alpha = 0.05). The following preoperative factors were associated with opioid use 2 years postoperatively: any opioid use (adjusted odds ratio [aOR] 14, 95% CI 2.5-82), high-dose use (aOR 7.3, 95% CI 1.1-48), and long-term use (aOR 17, 95% CI 2.2-123). All patients who reported high-dose opioid use at the 2-year follow-up examination had also reported preoperative opioid use. Preoperative high-dose use (aOR 247, 95% CI 5.8-10,546) but not long-term use (aOR 4.0, 95% CI 0.18-91) was associated with high-dose use at the 2-year follow-up visit. Compared with patients who reported no preoperative use, those who reported preoperative opioid use had higher rates of use at each postoperative time point (from 94% vs 62% at 6 weeks to 54% vs 7.1% at 2 years) (all p < 0.001). Opioid use at 2 years was independently associated with use at 1 year (aOR 33, 95% CI 6.8-261) but not at 6 months (aOR 4.3, 95% CI 0.95-24). Patients' preoperative opioid use, dose, and duration of use are associated with long-term use after ASD surgery, and a high preoperative dose is also associated with high-dose opioid use at the 2-year follow-up visit. Patients using opioids 1 year after ASD surgery may be at risk for long-term use.

PIH47 DEMENTIA SEVERITY AND OPIOID USE IN LONG-TERM CARE NURSING HOME RESIDENTS

National information on opioid use in long-term care nursing homes is unknown. We examined the temporal trends in opioid use and the association of dementia severity with opioid use in long-term care nursing home residents. This retrospective study used 20% national Minimum Data Set and Medicare claims from 2011-2017. For primary analysis, we selected long-term care residents with moderate to severe pain (n=16,855). In a secondary analysis, we included nursing home residents who had an emergency room visit for a fracture (n=12,860). Among nursing home residents with moderate to severe pain, association of dementia severity with any, prolonged (>90 days) and high-dose (≥90 morphine milligram equivalent [MME] dose/day) opioid use was evaluated using logistic regression. Among nursing home residents with a fracture, we determined if they received at least one prescription of an opioid within 7 days after emergency room discharge. We controlled for patient's sociodemographic and clinical characteristics, and nursing home characteristics. Opioid use declined from 47.8% in 2012 to 40.3% in 2017 (p=0.0007) in residents with severe dementia with a fracture. Among nursing home residents with moderate to severe pain (n=16,855), 72.7% used at least one opioid, 37.3% used for over 90 days and 4.1% used high-dose opioids. Severe dementia reduced the odds of any (66.6% vs. 76.4%; OR=0.85, 95%CI=0.79-0.91), prolonged (30.5% vs. 41.9%; OR=0.91, 95%CI=0.82-0.99) and high-dose (2.1% vs. 5.7%; OR=0.55, 95%CI=0.44-0.70) opioid use. After fracture, moderate (40.7% vs. 48.9%; OR=0.70, 95% CI=0.63-0.78) and severe (43.5 vs. 48.9%; OR=0.80, 95% CI=0.73-0.88) reduced opioid use. Severe dementia reduces opioid use and may reflect under-recognition and under-treatment of pain in this population. To improve quality of care, systemic efforts from healthcare professionals, nursing home administrators and policymakers are needed to evaluate opioid use in nursing home residents with dementia.

Outcomes in Long-term Opioid Tapering and Buprenorphine Transition: A Retrospective Clinical Data Analysis.

There are significant medical risks of long-term opioid therapy (LTOT) for chronic pain. Consequently, there is a need to identify effective interventions for the reduction of high-dose full-agonist opioid medication use. The current study details a retrospective review of 240 patients with chronic pain and LTOT presenting for treatment at a specialty opioid refill clinic. Patients first were initiated on an outpatient taper or, if taper was not tolerated, transitioned to buprenorphine. This study analyzes potential predictors of successful tapering, successful buprenorphine transition, or failure to complete either intervention and the effects of this clinical approach on pain intensity scores. One hundred seven patients (44.6%) successfully tapered their opioid medications under the Centers for Disease Control and Prevention guideline target dose (90 mg morphine-equianalgesic dosage), 45 patients (18.8%) were successfully transitioned to buprenorphine, and 88 patients (36.6%) dropped out of treatment: 11 patients during taper, eight during buprenorphine transition, and 69 before initiating either treatment. Conclusions. Higher initial doses of opioids predicted a higher likelihood of requiring buprenorphine transition, and a co-occurring benzodiazepine or z-drug prescription predicted a greater likelihood of dropout from both interventions. Patterns of change in pain intensity according to treatment were mixed: among successfully tapered patients, 52.8% reported greater pain and 23.6% reported reduced pain, whereas 41.8% reported increased pain intensity and 48.8% reported decreased pain after buprenorphine transition. Further research is needed on predictors of treatment retention and dropout, as well as factors that may mitigate elevated pain scores after reduction of opioid dosing.

521 Developing and Validating a Prediction Model to Identify Patients at High Risk for Failing Standard Sedation for Routine GI Endoscopy

INTRODUCTION: In recent years, use of anesthesia-assisted (AA) sedation for routine GI endoscopy has increased markedly. One factor contributing to this increased use is clinical uncertainty about which patients are most likely to benefit from AA. We aimed to develop a prediction model to help providers identify patients who require AA due to high-risk of failing standard sedation (SS). METHODS: This was an IRB-approved retrospective longitudinal study of national Veterans Affairs (VA) data of all patients who underwent an EGD and/or colonoscopy in 2009-13 (during which AA was used for 4.1% of routine GI endoscopy in VA). Using step-wise logistic regression, we developed a model to predict the primary outcome of failed sedation using potentially predictive patient and procedure-level variables (Table 1). Failed sedation cases were identified electronically as patients who had a routine procedure (without polypectomy, dilation, or injection) with AA within 3-months of a prior similar SS procedure. All cases were manually validated by chart review (index endoscopy report or other records) documenting patient discomfort/agitation and/or medical instability resulting in either an incomplete procedure or specific mention of need for AA for future procedures. 10-fold cross validation was used to validate the final model. RESULTS: Of 710,252 SS procedures, there were 398 cases of failed sedation (173 EGD, 225 colonoscopy; prevalence = 0.06%). None of the factors found to be significant predictors of failed sedation (e.g., high-dose opioid use, younger age) had an odds ratio &gt; 3; factors NOT associated with failed sedation included body mass index, obstructive sleep apnea, functional GI disorders, and others (Table 1). 10-fold cross-validation yielded a mean area under the curve (AUC) of 0.67 (range 0.63-0.71). The model was well-calibrated, but patients in the top decile of risk had a failed sedation prevalence of only 0.16% (Table 2). CONCLUSION: Failed sedation among patients undergoing routine outpatient GI endoscopy with SS is very rare, even among patients in the highest decile of risk. This suggests that concerns regarding failed sedation due to commonly cited factors such as chronic opioid use, obesity, or increased comorbidity do not justify forgoing SS in favor of AA in most patients. It also suggests that use of AA is generally unnecessary, since failed sedation is very uncommon even in VA where overall use of AA is much lower than in the private sector.

Disability Benefits and Change in Prescription Opioid Dose.

Among chronic low back pain (CLBP) patients, workers' compensation is associated with longer term prescription opioid analgesic use (OAU). The aim was to study the association between receiving Social Security Disability Insurance (SSDI) benefits and course of OAU. This prospective cohort study utilized data from primary care patients diagnosed with non-cancer CLBP. The outcomes were morphine equivalent dose (MED) - categorized as no OAU, 1-50mg MED, or >50mg MED - and change in MED over time using mixed multinomial logistic regression models. Covariates included sociodemographics, pain severity, pain management characteristics, continuity of care with their physician, health-related quality of life, number of comorbid health conditions, obesity, depression, and anxiety. In adjusted analysis, SSDI vs. non-SSDI patients were more likely to be receiving >50mg MED vs. no OAU at baseline (OR = 10.19; 95% CI:1.51-68.83). Differences in OAU trajectory between SSDI groups were nonsignificant (P = 0.204). Collection of SSDI benefits was an independent predictor of higher MED at baseline and persistently higher MED during 2 years of follow-up. Providers should consider the risk of persistent, high-dose opioid use in patients receiving SSDI benefits.

Trends in Opioid Use Among Older Survivors of Colorectal, Lung, and Breast Cancers.

Cancer survivors may be at increased risk for opioid-related harms. Trends in opioid use over time since diagnosis are unknown. Using data from SEER and Medicare, we conducted multilevel logistic regression analyses to compare chronic opioid use (≥ 90 consecutive days) among opioid-naïve survivors of colorectal, lung, and breast cancers diagnosed from 2008 to 2013 and matched with noncancer controls. Among cases and controls with chronic use, we compared rates of high-dose opioid use (average ≥ 90 morphine milligram equivalents daily). We included 46,789 survivors and 138,136 noncancer controls. In the first year after the index date (survivor's diagnosis date), chronic use among colorectal and lung cancer survivors exceeded chronic use among controls (colorectal cancer: odds ratio, 1.34; 95% CI, 1.22 to 1.47; lung cancer: odds ratio, 2.55; 95% CI, 2.34 to 2.77). Differences in chronic use between survivors and controls declined each year after the index date. Chronic use among breast cancer survivors was less than that of controls each year after the index date. Survivors with chronic use were more likely to have a high daily dose than controls with chronic use in the first 3 to 5 years. Among three large populations of older cancer survivors, chronic opioid use varied by cancer. However, by 6 years after diagnosis, survivors were no longer more likely to be chronic users than controls. Strategies for appropriate pain management during and after cancer treatment should take into account the risks associated with chronic high-dose opioid use.

Magnesium for the Management of Chronic Noncancer Pain in Adults: Protocol for a Systematic Review.

BackgroundChronic pain is a highly prevalent and complex health problem that is associated with a severe symptom burden, as well as substantial economic and social impact. Many patients with chronic pain still suffer from unrelieved or undertreated pain due to the incomplete efficacy and dose-limiting adverse effects of current therapies. Long-term and high-dose opioid use has considerably increased in the past 20 years despite limited evidence supporting its effectiveness in several chronic pain conditions, and serious concerns have emerged regarding adverse effects and potential misuse. Until recently, the steady increase in opioid prescribing rates has been associated with rising opioid-related mortality and other serious problems, emphasizing the need for better nonopioid therapies. Emerging evidence supports the safe use of magnesium in controlling chronic pain, but its overall efficacy and safety is still unclear.ObjectiveThis paper aims to assess the efficacy and safety of magnesium compared with a placebo for the treatment of chronic noncancer pain.MethodsWe will conduct a detailed search on Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from their inception until the date the searches are run to identify relevant randomized controlled trials. The reference lists of retrieved studies as well as Web-based trial registries will also be searched. We will include randomized double-blind trials comparing magnesium (at any dose, frequency, or route of administration) with placebo using participant-reported pain assessment. Two reviewers will independently evaluate studies for eligibility, extract data, and assess trial quality and potential bias. Risk of bias will be assessed using criteria outlined in the Cochrane Handbook for Systematic Review of Interventions. Primary outcomes for this review will include any validated measure of pain intensity or pain relief. Dichotomous data will be used to calculate the risk ratio and number needed to treat or harm. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.ResultsThis protocol is grant-funded and has undergone a peer-review process through the Queen’s University Department of Anesthesiology and Perioperative Medicine Vandewater Endowed Studentship. This project is also supported, in part, by the Chronic Pain Network of the Canadian Institutes of Health Research Strategy for Patient-Oriented Research. The electronic database search strategies are currently being developed and modified. The entire review is expected to be completed by January 1, 2019.ConclusionsThe completion of this review is expected to identify available high-quality evidence describing the efficacy and safety of magnesium for the treatment of chronic noncancer pain.International Registered Report Identifier (IRRID)PRR1-10.2196/11654

A complete national cohort study of prescriptions of analgesics and benzodiazepines to cancer survivors in Norway 10 years after diagnosis.

Chronic pain due to surgery, radiotherapy, or chemotherapy is prevalent in long-term cancer survivors. Chronic pain due to successful cancer treatment should be treated as chronic nonmalignant pain, primarily with nonpharmacological strategies. Based on complete national data from the Cancer Registry of Norway and the Norwegian prescription database, the aim of this study was to compare the use of nonopioid analgesics, opioids, and benzodiazepines 10 years after cancer diagnosis in long-term cancer survivors and the age- and sex-adjusted general population. The 1-year periodic prevalence of use was higher in long-term cancer survivors in all the studied drug classes: opioids (143.5 vs 129.6/1000), paracetamol (88.3 vs 80.7/1000), nonsteroidal anti-inflammatory drugs (229.1 vs 221.7), gabapentinoids (13.4 vs 10.0/1000), benzodiazepines (88.3 vs 77.9/1000), and benzodiazepine-like hypnotics (118.1 vs 97.4/1000). The prevalence of persistent and high-dose opioid use (>365 defined daily doses [DDDs] and >730 DDDs, respectively, during 365 days, and prescriptions all quarters of the year) was also higher in the cancer survivors than in the general population (6.5 vs 4.8/1000 for persistent use and 2.7 vs 1.3/1000 for high-dose use). Less than 10% of persistent and high-dose users received only long-acting opioid formulations. Furthermore, most long-term cancer survivors with persistent or high-dose opioid use were also high-dose users (>100 DDDs/year) of either benzodiazepines or benzodiazepine-like hypnotics. It is an issue of concern that most of those using opioids did not adhere to guidelines regarding opioid formulation and comedication with other drugs with addictive properties.

An observational study assessing high dose opioid prescribing and associated adrenal insufficiency

BackgroundLong-term opioid use is known to affect endocrine function, with case reports indicating an association with adrenal insufficiency.AimThis study aims to investigate long-term, high-dose opioid use (≥80mg morphine or equivalent per day) at a Suffolk (UK) General Practice and its effect on adrenal function.MethodFrom a practice list of 18,300, retrospective data was collected for patients prescribed high-dose opioids for non-cancer pain for at least three months on current repeat prescription. Patient demographics and prescribing information were collected using SystmOne. Cortisol levels in the high-dose opioid patients, and short synacthen testing if indicated, were performed.ResultsThe 35 identified patients (0.2% of practice list) were predominantly female (77%) ≥70 years old (37%), and taking opioids prescribed for osteoarthritis or back pain (77%). 6% were prescribed &gt;280mg morphine or equivalent per day, with one patient prescribed 705 mg. Routine evaluation for development of adrenal suppression and subsequent management was poor. 31% (11 of 35) had developed symptoms potentially indicative of adrenal insufficiency. One of these patients was among the 21% (7 of 35) with suppressed serum cortisol. Adrenal insufficiency secondary to opioids was confirmed in one patient using short synacthen testing. There was no statistical difference in either opioid dose or months of use for those with or without early morning cortisol suppression.ConclusionThe investigation highlights both the considerable use of high-dose opioids for non-malignant pain and their apparent association with adrenal suppression, demonstrating the need for formal guidelines to aid recognition and diagnosis.

Healthcare costs and utilization associated with high-risk prescription opioid use: a retrospective cohort study

BackgroundPrevious studies on high-risk opioid use have only focused on patients diagnosed with an opioid disorder. This study evaluates the impact of various high-risk prescription opioid use groups on healthcare costs and utilization.MethodsThis is a retrospective cohort study using QuintilesIMS health plan claims with independent variables from 2012 and outcomes from 2013. We included a population-based sample of 191,405 non-elderly adults with known sex, one or more opioid prescriptions, and continuous enrollment in 2012 and 2013. Three high-risk opioid use groups were identified in 2012 as (1) persons with 100+ morphine milligram equivalents per day for 90+ consecutive days (chronic users); (2) persons with 30+ days of concomitant opioid and benzodiazepine use (concomitant users); and (3) individuals diagnosed with an opioid use disorder. The length of time that a person had been characterized as a high-risk user was measured. Three healthcare costs (total, medical, and pharmacy costs) and four binary utilization indicators (the top 5% total cost users, the top 5% pharmacy cost users, any hospitalization, and any emergency department visit) derived from 2013 were outcomes. We applied a generalized linear model (GLM) with a log-link function and gamma distribution for costs while logistic regression was employed for utilization indicators. We also adopted propensity score weighting to control for the baseline differences between high-risk and non-high-risk opioid users.ResultsOf individuals with one or more opioid prescription, 1.45% were chronic users, 4.81% were concomitant users, and 0.94% were diagnosed as having an opioid use disorder. After adjustment and propensity score weighting, chronic users had statistically significant higher prospective total (40%), medical (3%), and pharmacy (172%) costs. The increases in total, medical, and pharmacy costs associated with concomitant users were 13%, 7%, and 41%, and 28%, 21% and 63% for users with a diagnosed opioid use disorder. Both total and pharmacy costs increased with the length of time characterized as high-risk users, with the increase being statistically significant. Only concomitant users were associated with a higher odds of hospitalization or emergency department use.ConclusionsIndividuals with high-risk prescription opioid use have significantly higher healthcare costs and utilization than their counterparts, especially those with chronic high-dose opioid use.

Interventions for the reduction of prescribed opioid use in chronic non-cancer pain.

This is the first update of the original Cochrane Review published in 2013. The conclusions of this review have not changed from the 2013 publication. People with chronic non-cancer pain who are prescribed and are taking opioids can have a history of long-term, high-dose opioid use without effective pain relief. In those without good pain relief, reduction of prescribed opioid dose may be the desired and shared goal of both patient and clinician. Simple, unsupervised reduction of opioid use is clinically challenging, and very difficult to achieve and maintain. To investigate the effectiveness of different methods designed to achieve reduction or cessation of prescribed opioid use for the management of chronic non-cancer pain in adults compared to controls. For this update we searched CENTRAL, MEDLINE, and Embase in January 2017, as well as bibliographies and citation searches of included studies. We also searched one trial registry for ongoing trials. Included studies had to be randomised controlled trials comparing opioid users receiving an intervention with a control group receiving treatment as usual, active control, or placebo. The aim of the study had to include a treatment goal of dose reduction or cessation of opioid medication. Two review authors independently extracted data and assessed risk of bias. We sought data relating to prescribed opioid use, adverse events of opioid reduction, pain, and psychological and physical function. We planned to assess the certainty of the evidence using the GRADE approach, however, due to the heterogeneity of studies, we were unable to combine outcomes in a meta-analysis and therefore we did not assess the evidence with GRADE. Three studies are new to this update, resulting in five included studies in total (278 participants). Participants were primarily women (mean age 49.63 years, SD = 11.74) with different chronic pain conditions. We judged the studies too heterogeneous to pool data in a meta-analysis, so we have summarised the results from each study qualitatively. The studies included acupuncture, mindfulness, and cognitive behavioral therapy interventions aimed at reducing opioid consumption, misuse of opioids, or maintenance of chronic pain management treatments. We found mixed results from the studies. Three of the five studies reported opioid consumption at post-treatment and follow-up. Two studies that delivered 'Mindfulness-Oriented Recovery Enhancement' or 'Therapeutic Interactive Voice Response' found a significant difference between groups at post-treatment and follow-up in opioid consumption. The remaining study found reduction in opioid consumption in both treatment and control groups, and between-group differences were not significant. Three studies reported adverse events related to the study and two studies did not have study-related adverse events. We also found mixed findings for pain intensity and physical functioning. The interventions did not show between-group differences for psychological functioning across all studies. Overall, the risk of bias was mixed across studies. All studies included sample sizes of fewer than 100 and so we judged all studies as high risk of bias for that category. There is no evidence for the efficacy or safety of methods for reducing prescribed opioid use in chronic pain. There is a small number of randomised controlled trials investigating opioid reduction, which means our conclusions are limited regarding the benefit of psychological, pharmacological, or other types of interventions for people with chronic pain trying to reduce their opioid consumption. The findings to date are mixed: there were reductions in opioid consumption after intervention, and often in control groups too.

Characterization of opioid use in sickle cell disease.

Opioid analgesics are commonly used to treat vaso-occlusive pain episodes in sickle cell disease (SCD), but comprehensive evidence characterizing opioid use in this patient population is limited. Our objective was to characterize opioid use patterns among SCD patients using a large nationwide database. A large, US medical claims database was utilized to identify a cohort of 3882 SCD patients, and characteristics of opioid use were analyzed. Clinical variables including age, gender, medication use, health care utilization, and medical history were evaluated for correlations with opioid use. Forty percent of patients took opioid medications during a 12-month span, and the prevalence of any opioid use was highest for 20 to 29-year-old patients (58%). The median daily opioid dose was 1.85mg (interquartile range: 0.62-10.68mg) oral morphine equivalents (OME). While most opioid users took between 0 and 5mg OME daily, 3% of pediatric patients and 23% of adult patients used more than 30-mg OME daily. High-dose opioid use was associated with older age, hydroxyurea therapy, nonsteroidal anti-inflammatory drug (NSAID) use, and frequent inpatient hospitalizations. In multivariable-adjusted analyses, patients with vaso-occlusive complications such as pain crisis (OR=3.8, 95% CI 2.7-5.3) and avascular necrosis (AVN) (OR=3.7, 95% CI 2.7-5.1) were associated with high-dose opioid use. Our study showed that only 40% SCD patients were on opioid analgesics during a 12-month span. However, a non-trivial number of patients used a much higher dose of opioids despite a relatively low average daily opioid dose among SCD patients, particularly with vaso-occlusive complications.

Association of high-dose postoperative opioids with recurrence risk in esophageal squamous cell carcinoma: reinterpreting ERAS protocols for long-term oncologic surgery outcomes.

Esophageal squamous cell carcinoma (ESCC) is associated with a poor prognosis and high postoperative recurrence rate. Although postoperative opioid use has been associated with cancer recurrence, its relevance in ESCC has not been determined. Therefore, this study investigated whether high-dose postoperative opioid use was associated with recurrence risk in patients with ESCC. For this retrospective analysis, the medical records of patients who were diagnosed with ESCC and who underwent surgery between January 2006 and December 2010 in the National Cancer Center, Korea were evaluated. Total opioid administration over a 10-day period, from during surgery to postoperative day 9, was calculated. A cutoff value was determined using receiver operating characteristic curve analysis, and patients were classified into the high-use and low-use groups. The primary and secondary outcomes of the study were freedom from recurrence and overall survival, respectively. After propensity score matching, the effect of opioid use on freedom from recurrence and overall survival was evaluated using the Kaplan-Meier method. The final analysis set included 258 patients. The cumulative opioid dose cutoff point was 1783.5 mg of oral morphine. High-dose postoperative opioid use was a significant factor affecting recurrence (Hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.583-2.954; P<0.0001). In contrast, postoperative opioid use was not associated with death (HR, 1.274; 95% CI, 0.922-1.761; P=0.1422). In patients with ESCC, compared with low-dose opioid use, high-dose intraoperative and postoperative opioid use was significantly associated with an increased risk of recurrence. However, opioid dosage did not affect overall survival.

OPRM1 Methylation Contributes to Opioid Tolerance in Cancer Patients.

We demonstrate that epigenetic regulation of OPRM1 contributes to opioid tolerance in cancer patients, and that targeted gene therapy could treat cancer-induced nociception and opioid tolerance in a mouse cancer model.

Deficits in autonomic indices of emotion regulation and reward processing associated with prescription opioid use and misuse.

Prescription opioid misuse and high-dose opioid use may result in allostatic dysregulation of hedonic brain circuitry, leading to reduced emotion regulation capacity. In particular, opioid misuse may blunt the ability to experience and upregulate positive affect from natural rewards. The purpose of this study was to examine associations between opioid use/misuse and autonomic indices of emotion regulation capability in a sample of chronic pain patients receiving prescription opioid pharmacotherapy. Chronic pain patients taking long-term opioid analgesics (N=40) completed an emotion regulation task while heart rate variability (HRV) was recorded, and also completed self-report measures of opioid misuse, craving, pain severity, and emotional distress. Based on a validated cut-point on the Current Opioid Misuse Measure, participants were grouped as opioid misusers or non-misusers. Opioid misuse status and morphine equivalent daily dose (MEDD) were examined as predictors of HRV and self-reports of emotion regulation. Opioid misusers exhibited significantly less HRV during positive and negative emotion regulation, and significantly less positive effect, than non-misusers, after controlling for confounders including pain severity and emotional distress. MEDD was inversely associated with positive emotion regulation efficacy. Findings implicate the presence of reward processing deficits among chronic pain patients with opioid-misusing behaviors, and opioid dosage was associated with deficient emotion regulation, suggesting the presence of compromised top-down cognitive control over bottom-up hedonic processes. Emotion regulation among opioid misusers may represent an important treatment target.

Same-day use of opioids and other central nervous system depressants amongst people who tamper with pharmaceutical opioids: A retrospective 7-day diary study

ObjectiveThe aims were to determine: (i) quantity and frequency of same-day use of opioids with benzodiazepines and/or alcohol amongst people who regularly tamper with pharmaceutical opioids; and (ii) socio-demographic, mental health, harms and treatment profile associated with same-day use of high doses. MethodThe cohort (n=437) completed a retrospective 7-day diary detailing opioid, benzodiazepine, and alcohol intake. Oral morphine equivalent (OME) units and diazepam equivalent units (DEU) were calculated, with >200mg OME, >40mg DEU and >4 standard alcoholic drinks (each 10g alcohol) considered a “high dose”. ResultsOne-half (47%) exclusively consumed opioids without benzodiazepines/alcohol; 26% had days of opioid use with and without benzodiazepines/alcohol; and 26% always used opioids and benzodiazepines/alcohol. Same-day use of opioids with benzodiazepines/alcohol typically occurred on 1–3days in the past week. Six in ten (61%) participants reported high dose opioid use on at least one day; one in five (20%) reported high dose opioid and high dose benzodiazepine/alcohol use on at least one day. The latter group were more likely to use prescribed opioid substitution therapy, often alongside diverted pharmaceutical opioids. Socio-demographic and clinical profiles did not vary according to high dose opioid, alcohol and benzodiazepine use, and there was no association with harms. ConclusionsSame-day use of opioids with benzodiazepines/alcohol, and high dose combinations, are common amongst people who tamper with pharmaceutical opioids. Assessment of concomitant benzodiazepine/alcohol use during opioid therapy, implementation of real-time prescription monitoring systems, and research to clarify upper safe limits for polydrug depressant use, are potential implications.

Trends in Opioid Dosing Among Washington State Medicaid Patients Before and After Opioid Dosing Guideline Implementation.

By 2007, opioid-related mortality in Washington state (WA) was 50% higher than the national average, with Medicaid patients showing nearly 6 times the mortality of commercially-insured patients. In 2007, the WA Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain was released, which recommended caution in prescribing >120mg morphine-equivalent dose per day for patients not showing clinically meaningful improvement in pain and function. We report on opioid dosing in the WA Medicaid fee-for-service population for 273,200 adults with a paid claim for an opioid prescription between April 1, 2006 and December 31, 2010. Linear regression was used to test for trends in dosing over that time period, with quarter-year as the independent variable and median daily dose as the dependent variable. Prescription opioid use among WA Medicaid adults peaked in 2009, as evidenced by the unique number of opioid users (105,232), the total number of prescriptions (556,712), and the total person-years of prescription opioid use (29,442). Median opioid dose was unchanged from 2006 to 2010 at 37.5mg morphine-equivalent dose, but doses at the 75th, 90th, 95th, and 99th percentiles declined significantly (P<.001). These results suggest that opioid treatment guidelines with dosing guidance may be able to reduce high-dose opioid use without affecting the median dose used. Some fear that opioid dosing guidelines might restrict access to opioid therapy for patients who could benefit. However, there is evidence that high-dose opioid therapy entails significant risks without demonstrated benefit. These findings indicate that high-dose opioid therapy can be reduced without altering median opioid dose in a Medicaid population.

Changes in Opioid Prescribing for Washington Workers' Compensation Claimants After Implementation of an Opioid Dosing Guideline for Chronic Noncancer Pain: 2004 to 2010

An opioid overdose epidemic emerged in the United States following increased opioid prescribing for chronic noncancer pain. In 2007, Washington State agencies implemented an opioid dosing guideline on safe prescribing for chronic noncancer pain. The objective of this population-based observational study was to evaluate opioid use and dosing before and after guideline implementation. We identified 161,283 workers aged 18 to 64 years with ≥1 opioid prescriptions in Washington Workers' Compensation, April 1, 2004, to December 31, 2010. Prevalence and incidence rates of opioid use were assessed. We compared pre- and postguideline chronic and high-dose use (≥120 mg/d) among incident users. The mean monthly prevalence of opioid use declined by 25.6% between 2004 (14.4%) and 2010 (10.7%). Fewer incident users went on to chronic opioid therapy in the postguideline period (4.7%; 95% confidence interval [CI], 4.5–5.0%) than in the preguideline period (6.3%; 95% CI, 6.1–6.6%). Compared with preguideline incident users, postguideline incident users were 35% less likely to receive high doses (adjusted odds ratio = .65; 95% CI, .59–.71). Although the extent to which decreases were due to the guidelines is uncertain, to our knowledge, this is the first report of significant decreases in chronic and high-dose prescription opioid use among incident users. PerspectiveEvidence-based strategies for opioid risk management are needed to help abate the epidemic of opioid-related morbidity and mortality. The study findings suggest that opioid dosing guidelines that specify a “yellow flag” dosing threshold may be a useful tool in preventing escalation of doses into ranges associated with increased mortality risk.