Long-acting Opioid Analgesics Research Articles

Comparison of Enhanced Recovery After Surgery (ERAS) Pathway Versus Standard Care in Patients Undergoing Elective Stoma Reversal Surgery- A Randomized Controlled Trial

BackgroundPractices such as prolonged preoperative fasting, bowel preparation, delayed ambulation and resumption of orals result in morbidity in 15-20% of stoma reversal cases which can be improved by Enhanced Recovery After Surgery (ERAS) pathways. AimTo evaluate the safety, feasibility and efficacy of ERAS pathway in patients undergoing elective loop ileostomy or colostomy reversal surgery MethodsThis was an open-labeled, superiority randomized controlled trial in which patients undergoing loop ileostomy or colostomy reversal were randomized to standard or ERAS care. Patients with ASA class ≥3, needing laparotomy for stoma reversal, cardiac, renal and neurological illnesses were excluded. Components of ERAS protocol included pre-operative carbohydrate loading, avoidance of mechanical bowel preparation, goal directed fluid therapy, avoidance of long-acting opioid anesthetics or analgesics, avoidance of drains, urinary catheter or nasogastric tube, early mobilization and early enteral feeding. The primary outcome was length of stay (LOS) while the secondary outcomes were postoperative recovery and morbidity parameters. ResultsForty patients each were randomized to standard care and ERAS. Demographic and laboratory parameters between the two groups were comparable. ERAS group patients had significantly reduced LOS (5.3±0.3 vs 7 ± 2.6; mean difference: 1.73 ± 0.98; p=0.0008). Functional recovery was earlier in the ERAS group compared to the standard care group, such as early resolution of ileus (median-2 days; p<0.001), time to first stool (median-3 days; p=0.0002), time to the resumption of liquid diet (median-3 days; p<0.001) and solid diet (median-4 days; p<0.001). Surgical site infections (SSI) were significantly lesser in ERAS group (12.5% vs 32.5%; p=0.03) while postoperative nausea/vomiting (p=0.08), pulmonary complications (p=0.17) and urinary tract infections (p=0.56) were comparable in both groups. ConclusionERAS pathways are feasible, safe and significantly reduces LOS in patients undergoing elective loop ileostomy or colostomy reversal surgery.

Long-Acting Opioid Analgesics for Acute Pain: Pharmacokinetic Evidence Reviewed.

Long-acting injectable (LAI) opioid formulations mitigate the harm profiles and management challenges associated with providing effective analgesia for animals. A single dose of a long-acting opioid analgesic can provide up to 72 h of clinically relevant pain management. Yet, few of these new drugs have been translated to products for veterinary clinics. Regulatory pathways allow accelerated drug approvals for generic and biosimilar drugs. These pathways depend on rigorous evidence for drug safety and pharmacokinetic evidence demonstrating bioequivalence between the new and the legacy drug. This report reviews the animal PK data associated with lipid and polymer-bound buprenorphine LAI formulations. Buprenorphine is a widely used veterinary opioid analgesic. Because of its safety profile and regulatory status, buprenorphine is more accessible than morphine, methadone, and fentanyl. This review of PK studies coupled with the well-established safety profile of buprenorphine suggests that the accelerated approval pathways may be available for this new family of LAI veterinary pharmaceuticals.

COMET – effectiveness and tolerability of methocarbamol versus oral opioid-analgesics as add-on measure in patients with non-specific low back pain refractory to recommended 1st line treatments. A retrospective analysis of depersonalized propensity score matched open-label real-world 4-week data from the German Pain e-Registry

Background To compare the 4-week effectiveness and tolerability of an add-on treatment with oral high dose methocarbamol (MET) vs long-acting oral opioid analgesics (LAO) in patients with non-specific low back pain (nsLBP) poorly responsive to recommended 1st line treatments. Methods Analysis of anonymized, propensity score-matched real-world data from the German Pain e-Registry, using a sequential non-inferiority superiority approach, for adult outpatients with nsLBP who had initiated treatment with MET or LAO between 1st January 2018 and 31st December 2019 (EUPAS identifier: 38484). The primary effectiveness variable was the absolute change of the average 24-h. pain intensity index (PIX). Safety was assessed by incidence of physician-confirmed drug-related adverse events (DRAEs), and DRAEs leading to discontinuation. Results Propensity score-matched data were analyzed for 374 patients treated with MET and 374 patients treated with LAO. Mean ± SD (median) MET dose over the 4-week evaluation period was 2390.4 ± 1980 (3000) mg and 69.6 ± 25.9 (60) mg morphine equivalent for LAO. With 25.8 ± 11.4 (median 26, 95%CI: 24.5–27.1) vs. 11.4 ± 6.8 (median 11; 95%CI: 10.6–12.2) mm VAS, absolute 4-week improvement vs. baseline was superior for MET vs. LAO [p < .001; effect size 1.6; least square mean difference 14.4 (95%CI: 13.4–15.3)]. Percentages of patients with a PIX improvement ≥ MCID was 81.8 vs. 24.6% [p < .001; OR: 13.8 (9.7–19.6), RR: 4.0 (3.2–5.0), NNT: 1.7]. A significantly lower number of patients treated with MET vs. LAO reported DRAEs in response to study medication: 36 (9.6%) vs. 139 (37.2%; p < .001; NNT 4), and 9 patients treated with MET (2.4%) vs. 86 (23.0%) treated with LAO discontinued treatment in response to these DRAEs (p < .001; NNT: 5). Conclusion 4-week add-on treatment with MET in patients with nsLBP who showed an inadequate response to recommended 1st line treatments is superior effective to LAO and significantly better tolerated. KEY MESSAGES Low back pain is the most common musculoskeletal problem worldwide. In the majority of patients, LBP does not have a specific cause and the most prevalently coded form is mechanical, non-specific (ns) LBP associated with muscular tension, restrictions in mobility, and static malposition. Current treatment recommendations for nsLBP are largely “non-specific” as well, limited to symptomatic pain-relieving measures. In our propensity score-matched two cohort analyses of depersonalized real-world data from the German Pain e-Registry, a 4-week treatment with the muscle relaxant methocarbamol proved superior effective and significantly better tolerated than treatment with oral long-acting opioid analgesics in patients who poorly responded to recommended 1st line treatments.

Effectiveness, Safety, and Tolerability of Nabiximols Oromucosal Spray vs Typical Oral Long-Acting Opioid Analgesics in Patients with Severe Neuropathic Back Pain: Analysis of 6-Month Real-World Data from the German Pain e-Registry.

ObjectiveTo compare the effectiveness, safety, and tolerability of add-on nabiximols (NBX) oromucosal spray vs typical oral long-acting opioid (LAO) analgesics in patients with severe (± chronic) peripheral neuropathic back pain poorly responsive to other treatments.MethodsRetrospective analysis of anonymized, propensity score–matched data from the German Pain e-Registry of adult outpatients who initiated NBX or LAO between March 2017 and March 2020.ResultsData were analyzed from propensity score–matched patients treated with NBX (n = 655) or LAO (n = 655): mean age ≈51 years; 57% female; mean pain duration ≈2.6 years; chronic pain 61%; severe dysfunctional pain 93%. At 6 months, NBX was noninferior to LAO for overall symptom relief, based on the least-squares mean difference between cohorts in change from baseline in patient-reported, pain-related aggregated nine-item scale scores (−27.84%; 95% confidence interval [CI] −29.71 to −25.96; P < 0.001) and individual pain-related scale scores. Subsequent prespecified superiority analysis of the primary endpoint showed that NBX was superior to LAO: all secondary endpoints measuring symptoms of pain and physical function improved significantly with NBX and LAO, with between-group differences favoring NBX (all P < 0.001). Fewer patients treated with NBX than LAO experienced treatment-related adverse events (25.5% vs 76.0%; P < 0.001) or discontinued treatment because of treatment-related adverse events (7.9% vs 29.3%; P < 0.001).ConclusionWithin study limitations (e.g., observational design, all potential biases), add-on NBX was superior to and better tolerated than add-on treatment with typical oral LAO analgesics in patients with neuropathic back pain inadequately controlled by recommended/established systemic therapies.

An international multidisciplinary consensus statement on the prevention of opioid-related harm in adult surgical patients.

This international multidisciplinary consensus statement was developed to provide balanced guidance on the safe peri-operative use of opioids in adults. An international panel of healthcare professionals evaluated the literature relating to postoperative opioid-related harm, including persistent postoperative opioid use; opioid-induced ventilatory impairment; non-medical opioid use; opioid diversion and dependence; and driving under the influence of prescription opioids. Recommended strategies to reduce harm include pre-operative assessment of the risk of persistent postoperative opioid use; use of an assessment of patient function rather than unidimensional pain scores alone to guide adequacy of analgesia; avoidance of long-acting (modified-release and transdermal patches) opioid formulations and combination analgesics; limiting the number of tablets prescribed at discharge; providing deprescribing advice; avoidance of automatic prescription refills; safe disposal of unused medicines; reducing the risk of opioid diversion; and better education of healthcare professionals, patients and carers. This consensus statement provides a framework for better prescribing practices that could help reduce the risk of postoperative opioid-related harm in adults.

MOP-dependent enhancement of methadone on the effectiveness of ALA-PDT for A172 cells by upregulating phosphorylated JNK and BCL2.

Methadone, as a long-acting opioid analgesic, shows an ability to sensitize the treatment of ALA-PDT for glioblastoma cells (A172) in vitro by promoting apoptosis. However, the mechanisms how methadone enhances the effectiveness of ALA-PDT for tumor cells remains to be clarified. The expression of mu opioid receptor (MOP), apoptosis, phosphorylated c-Jun N-terminal kinase (JNK) and phosphorylated apoptosis regulator B cell lymphoma 2 (BCL2) were measured by flow cytometry. Cytotoxicity was determined using Cell Counting Kit-8 (CCK-8). A MOP antagonist, naloxone, was used to evaluate the role of MOP in the above process. It was found that A172 cells show the expression of MOP and that naloxone inhibits the enhancement of the methadone effect on apoptosis following ALA-PDT (p < 0.05). Phosphorylated JNK and BCL2 induced by ALA-PDT were promoted in the presence of methadone (p < 0.05). These methadone effects were also inhibited by naloxone (p < 0.05). The results suggest that apoptosis induced by ALA-PDT is enhanced by methadone, mostly MOP-mediated, through the upregulation of accumulation of phosphorylated JNK and BCL2, leading to a promotion of cytotoxicity of ALA-PDT for A172 cells.

Incidence of Opioid Overdose Among Patients Using ER/LA Opioid Analgesics Before and After Implementation of the Class-Wide Opioid Risk Evaluation and Mitigation Strategy.

IntroductionThe United States (US) Food and Drug Administration (FDA) required a Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting (ER/LA) opioid analgesics on 09 July 2012.MethodsThis study compared the incidence of opioid overdose before (July 2010-June 2012) and after (July 2013-September 2016) the initiation of the Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting (ER/LA) opioid analgesics. We identified patients with ≥1 ER/LA opioid dispensing in either time period in national data from the HealthCore Integrated Research DatabaseSM (HIRD) and in United States (US) Medicaid claims data from four states. We described each population, calculated the incidence rate (IR) of opioid overdose, and assessed crude and propensity score adjusted incidence rate ratios (IRR) comparing the overdose rate after vs before implementation of the REMS.ResultsA total of 121,229 commercially insured and 11,488 Medicaid patients were included in the analysis. Rates of overdose were substantially higher in Medicaid patients than in the commercially insured patients (IR 192.0, 95% confidence interval [CI] 162.60–225.18 versus 102.60, 95% CI 93.0–112.93 in the active period). The IRRs for opioid overdose were 1.01 (95% CI 0.87–1.17) in the commercially insured population and 0.70 (95% CI 0.52–0.93) in Medicaid.ConclusionThis leveling off of overdose rates among commercially insured patients and decline among Medicaid patients is encouraging, but it is difficult to disentangle the specific impact of the REMS from many other ongoing initiatives with similar goals.

Treating postoperative pain? Avoid tramadol, long-acting opioid analgesics and long-term use

A recent cohort study investigated ‘the risk of transitioning from acute to prolonged use’ of opioid analgesics in patients undergoing elective surgery. Patients given tramadol or long-acting opioids after discharge...

Changes in Mortality Involving Extended-Release and Long-Acting Opioids After Implementation of a Risk Evaluation and Mitigation Strategy.

ObjectiveTo assess changes in mortality rates in extended-release and long-acting (ER/LA) opioid analgesics after the implementation of the Risk Evaluation and Mitigation Strategy (REMS).SettingAll drug poisoning deaths in three states: Florida, Oregon, and Washington. Data were obtained through state vital records offices and the Researched Abuse, Diversion and Addiction-Related Surveillance System Medical Examiner Program.MethodsUsing cause-of-death literal text from death certificates, individual opioid active pharmaceutical ingredients (APIs) involved in each death were identified using rules-based natural language processing. Population-adjusted and prescriptions dispensed–adjusted mortality rates were calculated for all ER/LA opioid analgesic and individual opioid APIs. Rates before and after implementation of the REMS were compared. Rate changes were compared with rates from two APIs with little or no inclusion in the REMS: benzodiazepines and hydrocodone.ResultsThe mean ER/LA opioid analgesic population-adjusted mortality rate significantly decreased in all three states (FL: P = 0.003; OR: P = 0.003; WA: P < 0.001). Mortality rates for benzodiazepines and hydrocodone also decreased and were not statistically different. Significant heterogeneity in mortality rates of individual opioids was observed between the three states. When adjusted for prescription volume, the ER/LA opioid analgesic mortality rate decreased in all three states, but was significant only for Washington (P < 0.001).ConclusionsThe population-adjusted mortality rate of ER/LA opioid analgesics has decreased in three states. Notably, the contributions to mortality rates by individual opioid analgesics were not uniform across the three states in this study. However, these changes were not generally distinct from changes in mortality rates where comparator substances were involved.

Long-acting Opioid Use and the Risk of Serious Infections: A Retrospective Cohort Study.

Although evidence from animal and human studies indicates opioid analgesics increase susceptibility to infections, it is unclear whether the risk varies by specific opioid. We compared the risk of serious infection among patients initiating long-acting opioid analgesics with and without previously reported immunosuppressive properties. We conducted a retrospective cohort study of Tennessee Medicaid enrollees age ≥18 years initiating long-acting opioids (1995-2015). Hospitalizations for serious infection were identified using validated coding algorithms. We used multivariable Poisson regression models to calculate adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) to compare the infection risk among patients using long-acting opioids with known immunosuppressive properties (morphine, fentanyl, methadone) to the infection risk among patients using long-acting opioids without known immunosuppressive properties (oxycodone, oxymorphone, tramadol) accounting for demographics, opioid dose, comorbidities and pain conditions, medication use, frailty indicators, and healthcare encounter history using exposure propensity scores. We further compared users of individual long-acting opioids to long-acting morphine users (considered the prototypical immunosuppressive opioid). Among the 61 240 patients initiating opioids with immunosuppressive properties and 22 811 patients initiating opioids without immunosuppressive properties, we identified 1906 serious infections. Nonimmunosuppressive opioid users had a lower rate of infections than immunosuppressive opioid users (aIRR:0.78 [CI: 0.66-0.91]). Among individual opioids, oxycodone users had a lower rate of infection than morphine users (aIRR:0.73 [CI: 0.60-0.89]). There were no significant differences in the infection risk between other opioids and morphine. The risk of serious infections among long-acting opioid users varies by opioid type. Providers should carefully consider the risk of serious infections when making pain management decisions.

Identifying Levorphanol Ingestion Using Urine Biomarkers in Health Care Patients

Background: Levorphanol is a long-acting opioid analgesic that is an optical isomer of dextrorphan, a metabolite of the over-the-counter cough suppressant dextromethorphan. Providers prescribing levorphanol for pain management may need to assess compliance through urine drug testing, as this agent is subject to abuse. Therefore, it is important to differentiate between dextromethorphan and levorphanol ingestion. Objectives: This article is the first to report urine concentrations of levorphanol/dextrorphan and 3-hydroxymorphinan in human urine and assesses the need for an enantiomeric analysis to distinguish between dextromethorphan and levorphanol ingestion. Study Design: Retrospective data review. Methods: Medication compliance test results were reviewed for 521 urine samples submitted to Aegis Sciences Corporation between July 2014 and July 2016. Samples were included in this analysis if dextromethorphan or levorphanol testing was requested by the ordering provider. Urine samples were hydrolyzed with β-glucuronidase and analyzed using liquid chromatographytandem mass spectrometry (LC-MS/MS). An enantiomeric analysis to distinguish levorphanol from dextrorphan and (-)-3-hydroxymorphinan (norlevorphanol) from (+)-3-hydroxymorphinan was not performed. Results: Nineteen urine samples with levorphanol listed as prescribed had median levorphanol/ dextrorphan and 3-hydroxymorphinan concentrations of 1,881 ng/mL and 141 ng/mL, respectively. One-quarter of the urine samples with dextromethorphan listed as prescribed did not have any detectable dextromethorphan or 3-methoxymorphinan. Limitations: An enantiomeric analysis was not utilized with the LC-MS/MS testing method; therefore, levorphanol could not be differentiated from dextrorphan, and (-)-3-hydroxymorphinan could not be differentiated from (+)-3-hydroxymorphinan. The hepatic and renal function for these patients was unknown; however, both could impact the metabolism, distribution, and excretion of levorphanol biomarkers in urine. The dextromethorphan and/or levorphanol dose and timing of last ingestion was also not assessed. Conclusions: It may be impossible to distinguish between levorphanol and dextromethorphan ingestion based on urine biomarkers, unless dextromethorphan or 3-methoxymorphinan is present or an enantiomeric analysis is performed. Therefore, the potential exists for patients prescribed levorphanol to ingest dextromethorphan and appear compliant with levorphanol therapy. This should prompt clinicians to consider the parameters of their laboratory’s testing method when interpreting levorphanol drug test results. Key words: Levorphanol, dextrorphan, dextromethorphan, 3-hydroxymorphinan, urine testing, urine concentration, drug testing, medication compliance testing

Is Fentanyl Patch End-Of-Dose Failure Associated with Body Mass Index? (FR441A)

•Explain to all patients the nature and possibility of end-of-dose failure to patients when initiating therapy with fentanyl transdermal preparations.•Increase screening of patients on using transdermal fentanyl preparations for end-of-dose failure, with particular attention to patients with cancer cachexia. Transdermal fentanyl is widely used for patients with cancer pain requiring a long-acting opioid analgesic. The delivery of fentanyl in this form relies on a drug reservoir forming in subcutaneous fat. The manufacturer-recommended initial dosing frequency is every 72 hours. However, some patients experience “end-of-dose failure” (EDF) with worsening pain after a shorter interval. No studies have examined whether EDF correlates with body mass index (BMI). To assess whether low BMI is associated with prescription of transdermal fentanyl at q48h dosing frequency. All outpatient fentanyl patch prescriptions dispensed between January 1, 2014 and December 31, 2015 at our academic cancer center were extracted using an institutional database. For each prescription patient age, sex, race, patch dose, dosing frequency, and cancer type, as well as height and weight (used to calculate BMI) were collected. A generalized estimating equations (GEE) model was fit to account for correlation within patient and determine association between BMI and patch frequency. A total of 2,750 patients filled 6,569 fentanyl patch prescriptions over the study period. Patients were a median of 60 years old, 56.1% female, and 73.3% white (11.2% African American, 7.2% Asian). The median number of prescriptions per patient was 1 at a median dose of 37. Among 287 underweight patients (BMI<18.5), 34 (11.8%) received at least one q48h fentanyl patch prescription compared with 62 (10.2%) of obese (BMI>30) patients. Patients who received q48h patch had lower BMI (.58 unit decrease; p<0.01) than patients who received the q72h patch. Lower BMI is associated with q48h fentanyl patch dosing, suggesting that it may also be associated with end-of-dose failure in cancer patients. These patients should be closely monitored and alerted to this possibility.

Extended-Release and Long-Acting Opioid Analgesics Risk Evaluation and Mitigation Strategy (REMS):

In response to the proliferation and abuse of opioids in the United States, the U.S. Food and Drug Administration (FDA) recently required manufacturers of extended-release and long-acting (ER/LA) opioid analgesics to provide education for prescribers of these medications through an FDA-approved risk management program. As a part of its Risk Evaluation and Mitigation Strategy (REMS), the FDA provided a blueprint for content to help accredited continuing medical education (CME) providers develop educational modules for prescribers. The University of Nebraska Medical Center (UNMC), the Federation of State Medical Boards (FSMB), the FSMB Foundation, The France Foundation, and CECity worked collaboratively to create “Extended-Release and Long-Acting Opioid Analgesics,” a prescriber education program aligned with the FDA blueprint, comprised of live meetings and web-based enduring activities that spanned April 2014 to February 2016. A total of 4,535 health care providers participated in the live and enduring REMS CME activities and completed evaluations of these activities. The evaluations were analyzed to learn more about the impact of the content on prescribers' knowledge and clinical decision-making. Results were similar for live and enduring activities. Participant-knowledge increased by 22 percentage points. Several competence measures suggest that learners returned to practice with more confidence, and 83% declared specific practice changes they planned to make to improve patient assessment and care. More than one-third of the evaluation respondents felt there were no barriers to making intended practice changes. More than 95% of the respondents said the activity increased their ability to apply knowledge, skills, and judgment in practice. Analysis suggests that live and enduring educational activities, following the FDA REMS blueprint, can impact prescriber attitudes and future care-decisions related to ER/LA opioid analgesics. These results justify additional efforts to involve more participants in these REM activities.

Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System

Objective: A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics.Design: Retrospective cohort study.Setting: Sentinel, a distributed database with electronic healthcare data on &gt;190 million predominantly commercially insured members.Patients, participants: Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013.Main outcome measure(s): We examined the proportion of opioid-tolerantonly ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing.Results: We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opioid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation.Conclusions: These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

A Guide for Pain Management in Developing Nations: The Diagnosis and Assessment of Pain in Cancer Patients

The fundamental approach to cancer patients with pain is to identify the pain sites, and describe, quantify, and categorize the pain by type at each site. There are many validated tools to serve the clinician in these efforts, particularly for pain assessment. Multimechanistic pain syndromes are common in cancer patients. Cancer patients may experience nociceptive pain. They may also experience neuropathic pain due to chemotherapy-induced or cancer-related nerve damage. Analgesic choices must be guided by the pain mechanisms, nature, and severity of the pain, comorbid conditions, and patient characteristics. Long-acting opioid analgesics or fixed-clock dosing can eliminate end-of-dose analgesic gaps. The potential for opioid abuse is an important public health challenge but one that should not undermine the appropriate treatment of moderate to severe cancer pain. Abuse-deterrent opioid formulations can be useful. Care is needed for special populations of cancer patients dealing with pain, such as geriatric, pediatric, or obese patients. While morphine has long been the gold standard of oral opioid products, recent clinical trials suggest that oral hydrocodone and oral oxycodone may offer advantages over oral morphine. Patient adherence is crucial for adequate analgesia and patient education can promote adherence and manage expectations.

Integrated Palliative Care for Management of Elderly Patients with Advanced Chronic Kidney Disease (FR433)

Accreditation System (NAS), the ACGME is increasingly emphasizing the teaching of patient safety and QI in training programs. It is critical that palliative care practitioners of all disciplines have an understanding of QI processes and the ability to implement these processes in the clinical setting. Using a multiinstitutional, interdisciplinary team of quality experts and education leaders in palliative care, we aim to demonstrate how audience members can incorporate novel teaching methods into QI for their own learners. We will introduce a tool for reporting and assessing QI projects. Then, using this tool, we will review three examples of QI projects from several institutions in a small-group format, inviting open conversation regarding their strengths, weaknesses, and applicability. This will spur lively discussions on the challenges and barriers of QI initiatives within our field or those that integrate with other disciplines. Lastly, we will review successful methods from our own experience of integrating QI into the longitudinal curriculum of our palliative care fellowships and interdisciplinary teams, such as risk evaluation and mitigation strategies (REMS) for buprenorphine, extendedrelease and long-acting opioid analgesics, and transmucosal immediate-release fentanyl products; institutional risk reporting systems; and patient safety committees. Overall, we aim to provide audience members with an implementable action plan to take home that inspires lifelong QI.

A prospective multicentre study to evaluate the efficacy and tolerability of osmotic release oral system (OROS) hydromorphone in opioid-naive cancer patients: Results of the Korean South West Oncology Group study.

Osmotic release oral system (OROS) hydromorphone is a potent, long-acting opioid analgesic, effective and safe for controlling cancer pain in patients who have received other strong opioids. To date, few studies have examined the efficacy of hydromorphone for pain relief in opioid-naive cancer patients. A prospective, open-label, multicentre trial was conducted to determine the efficacy and tolerability of OROS hydromorphone as a single and front-line opioid therapy for patients experiencing moderate to severe cancer pain. OROS hydromorphone was administered to patients who had not previously received strong, long-acting opioids. The baseline evaluation (visit 1) was followed by two evaluations (visits 2 and 3) performed two and 14 weeks later, respectively. The starting dose of OROS hydromorphone was 4 mg⁄day and was increased every two days when pain control was insufficient. Immediate-release hydromorphone was the only accepted alternative strong opioid for relief of breakthrough pain. The efficacy, safety and tolerability of OROS hydromorphone, including the effects on quality of life, and patients' and investigators' global impressions on pain relief were evaluated. The primary end point was pain intensity difference (PID) at visit 2 relative to visit 1 (expressed as %PID). A total of 107 patients were enrolled in the present study. An improvement in pain intensity of >50% (≥50% PID) was observed in 51.0% of the full analysis set and 58.6% of the per-protocol set. The mean pain score, measured using a numerical rating scale, was significantly reduced after two weeks of treatment, and most adverse events were manageable. Quality of life also improved, and >70% of patients and investigators were satisfied with the treatment. OROS hydromorphone provided effective pain relief and improved quality of life in opioid-naive cancer patients. As a single and front-line treatment, OROS hydromorphone delivered rapid pain control.

Implementation of an opioid management initiative by a state Medicaid program.

The utilization of prescription opioids has increased over the last 2 decades. Associated with this is the misuse of prescription opioids for nonmedical purposes. Medicaid programs have struggled with developing strategies that balance best practice models, appropriate utilization, and reduction in costs associated with the opioid medication class. To examine the impact of a 2-year stepwise initiative to reduce utilization and therapy costs of long-acting opioid analgesics (LAOA) by addressing issues of high dose, daily dose, and preferred therapeutic alternatives. Utilization data from the Massachusetts Medicaid pharmacy program for LAOAs were reviewed and compared for 2 time periods. The calendar year prior to the initiative, 2002, was used as a base year and represents a time period when there were no restrictions in place for members to obtain long-acting opioids. The calendar year 2005 was the comparison year representing a time period after the multiple steps of the initiative had been implemented. A retrospective claims-based analysis was performed to determine the impact of restrictions on LAOAs, defined as brand and generic versions of oxycodone ER, morphine ER, methadone, and fentanyl transdermal system. The primary measure was the percentage of change of unique utilizers, paid claims, and average daily dose for each LAOA following the implementation of the opioid management initiative. Secondary measures included a cost analysis. Compared with 2002, the overall number of LAOA unique utilizers declined 17.8% (P < 0.0001), and the overall number of claims declined by 4.1% (P < 0.0001), while Medicaid pharmacy benefit member enrollment remained relatively stable. Average daily dose declined in methadone and morphine ER and increased in oxycodone ER and fentanyl transdermal system. The 2005 overall cost of LAOAs decreased 8.0% compared with the overall cost in 2002. The per-member-per-month (PMPM) cost for opioid users in 2002 was $110.57 ($120.04 when adjusted to 2005 dollars) compared with $123.75 in 2005. In comparison, the overall PMPM for all members in 2002 was $3.52 ($3.82 when adjusted to 2005 dollars) compared with $3.59 in 2005. Our study successfully demonstrated that a state Medicaid program initiative can result in a significant overall decrease in opioid class utilization specifically for the targeted, more costly agents. This was achieved via the implementation of a Therapeutic Class Management multidisciplinary workgroup that established a prior authorization process implementing limits on dose, as well as identified preferred less costly agents. It further facilitated the direct opportunity for pharmacy-prescriber collaboration for LAOA medication management.

Changes in Prevalence of Prescription Opioid Abuse after Introduction of an Abuse-Deterrent Opioid Formulation

The reformulation of oxycodone hydrochloride controlled-release (CR) tablets in August 2010 created a natural experiment at a national scale, providing an opportunity to evaluate patterns of abuse of prescription opioids and other drugs before and after introduction of this abuse-deterrent formulation (ADF). Observational, cross-sectional study Sentinel sample of adults assessed for substance abuse treatment within the NAVIPPRO® surveillance system Two hundred thirty-two thousand and eight hundred seventy-four adults at 437 facilities during January 1, 2008 through December 31, 2011. Time-series analysis using logistic regression to estimate quarterly prevalence of past 30-day abuse (adjusted for covariates and prescription volume) and changes in abuse pre-and post-ADF introduction. Increases in abuse prevalence occurred for all prescription opioids as a class and for extended-release (ER) opioids. Significantly greater abuse of ER oxymorphone and buprenorphine occurred in the post-ADF period (relative risk [RR] = 2.91, 95% confidence interval [CI] = 2.59-3.27 and RR = 1.85, 95% CI = 1.74-1.96). Increases in abuse for these two compounds were significant among groups who reported abuse via preferential routes of administration (oral only, snorting only, injection only) post-ADF introduction. Replacement of a widely prescribed opioid formulation known for its abuse potential alone may have had little impact on overall rates of prescription opioids as a class. However, changes in abuse levels of certain opioids coinciding with ADF introduction suggest possible switching of abuse among this study sample to specific long-acting opioid analgesics. Additional follow-up studies will be important to monitor changing abuse patterns and their public health impact as new opioid formulations are developed and introduced to market.

Labeling Changes Promoting Safe Use of Long-Acting Opioids

* The labeling of extended-release and long-acting opioid analgesics has been revised to warn practitioners that the drugs have been associated with misuse, abuse, life-threatening respiratory depression, accidental exposure, neonatal opioid withdrawal syndrome, and (with some drugs) serious drug interactions with alcohol. * The labeling will also state that long-acting opioids should only be used if other pain relief methods aren't effective.