Impact of opioid-induced constipation on healthcare resource utilization and costs for cancer pain patients receiving continuous opioid therapy.

PURPOSE: Opioid therapy is often associated with adverse effects, including opioid-induced constipation (OIC), in patients receiving opioids for cancer pain. This retrospective observational cohort study evaluated healthcare utilization and costs during the first year after initiating opioid therapy among cancer patients with (cohort 1) and without (cohort 2) constipation. METHODS: This study used administrative claims data from the HealthCore Integrated Research Environment between January 1, 2006, and April 30, 2014. Eligible patients included adults ≥ 18 years with a diagnosis of cancer who initiated continuous opioid therapy (≥ 30 days). Propensity scores were used to match patients with constipation in a 1:1 ratio to those without constipation. Generalized linear models were used to evaluate healthcare utilization and costs during the 12 months after initiating opioid therapy. RESULTS: After matching, 1369 patients were included in each cohort. Patients with constipation were more than twice as likely as those without constipation to have an all-cause inpatient hospitalization (odds ratio [95% confidence interval (CI)], 2.47 [2.11-2.90]), or pain-related hospitalization (2.15 [1.82-2.54]) during the 12 months after initiating therapy. Mean unadjusted overall healthcare costs during the first 12 months post-index were $21,629 (95% CI, $14,850-$29,018) higher for patients with constipation than for those without constipation. For patients with constipation, total mean (SD) constipation-related costs were $9196 ($26,896). CONCLUSIONS: These results suggest that OIC is associated with significantly increased healthcare and economic burden in cancer pain patients and that early and ongoing recognition and management of OIC are unmet needs in this population.

Alternative routes to oral opioid administration in palliative care: a review and clinical summary.

OBJECTIVE: A major goal of palliative care is to provide comfort, and pain is one of the most common causes of treatable suffering in patients with advanced disease. Opioids are indispensable for pain management in palliative care and can usually be provided by the oral route, which is safe, effective, and of lowest cost in most cases. As patients near the end of life, however, the need for alternate routes of medication increases with up to 70% of patients requiring a nonoral route for opioid administration. In order to optimize patient care, it is imperative that clinicians understand existing available options of opioid administration and their respective advantages and disadvantages. METHODS: We performed a literature review to describe the most commonly used and available routes that can substitute for oral opioid therapy and to provide a summary of factors affecting choice of opioid for use in palliative care in terms of benefits, indications, cautions, and general considerations. RESULTS: Clinical circumstances will largely dictate appropriateness of the route selected. When the oral route is unavailable, subcutaneous, intravenous, and enteral routes are preferred in the palliative care population. The evidence supporting sublingual, buccal, rectal, and transdermal gel routes is mixed. CONCLUSIONS: This review is not designed to be a critical appraisal of the quality of current evidence; rather, it is a summation of that evidence and of current clinical practices regarding alternate routes of opioid administration. In doing so, the overarching goal of this review is to support more informed clinical decision making.

Evaluation of the performance improvement CME paradigm for pain management in the long-term care setting.

OBJECTIVE: A performance improvement continuing medical education (PI CME) activity was designed to assist clinicians with accurately identifying and appropriately managing persistent pain in long-term care facility (LTCF) residents. DESIGN: Volunteer LTCFs participated in a three-stage PI CME model consisting of: 1) baseline assessment, 2) implementation of practice improvement interventions, and 3) reassessment. Expert faculty chose performance measures and interventions for the activity. A champion was designated ateach LTCF to collect resident charts and enter data into an online database. SETTING: Eight LTCFs located across the United States participated in the activity. PATIENTS: Fifty resident charts were randomly selected by each LTCF champion (25 for stage 1 and 25 for stage 3); a total of 350 charts were reviewed. INTERVENTIONS: In addition to a toolkit containing numerous performance improvement resources, an in-service meeting led by an expert faculty member was conducted at each LTCF. OUTCOME MEASURES: Stage 3 data were collected 6 weeks after implementation of interventions and compared with stage 1 baseline data to measure change in performance. RESULTS: Aggregate data collected from seven LTCFs completing the PI CME activity through stage 3 revealed improvements from baseline in four of five performance measures. CONCLUSIONS: This CME activity allowed for collection of data demonstrating performance improvement in persistent pain management. The tools used as part of the intervention (available at http://www.achlpicme.org/LTC/toolkit) may help other clinicians enhance their management of LTCF residents with persistent pain.

Cannabinoids for neuropathic pain.

Treatment options for neuropathic pain have limited efficacy and use is fraught with dose-limiting adverse effects. The endocannabinoid system has been elucidated over the last several years, demonstrating a significant interface with pain homeostasis. Exogenous cannabinoids have been demonstrated to be effective in a range of experimental neuropathic pain models, and there is mounting evidence for therapeutic use in human neuropathic pain conditions. This article reviews the history, pharmacologic development, clinical trials results, and the future potential of nonsmoked, orally bioavailable, nonpsychoactive cannabinoids in the management of neuropathic pain.

Transformation of acute cancer pain to chronic cancer pain syndromes.

For many cancer survivors, disease-related long-term morbidities and the application of advanced cancer treatments have resulted in the development of a chronic pain state. This brief review explores the relationship between what is known about the treatment of active cancer pain syndromes-both continuous pain and breakthrough pain-and persisting pain syndromes in cancer survivors. We also posit that because there is evidence to suggest that poorly treated acute pain can lead to protracted pain conditions, acute pain should be recognized and treated promptly, both for short- and long-term gain. In the short term, better acute pain treatment can improve functionality and psychological well-being, whereas in the long term, mounting evidence suggests that it could prevent of future chronic pain.

Treatment guidelines for the pharmacological management of pain in older persons.

BACKGROUND: Chronic or persistent pain is a common problem in older adults and is often associated with significant physical disability and psychosocial problems. The potential benefits, risks, and costs of pharmacotherapy as a mainstay in the treatment of moderate to severe pain in this population must be well-understood and weighed accordingly. Recent treatment guidelines have been introduced that can guide decision making to optimize pain-related treatment outcomes in older individuals OBJECTIVES AND RESULTS: This review article describes and summarizes key evidence-based recommendations that were derived by a committee convened by the American Geriatrics Society in order to provide guidance to optimize pharmacotherapy in the management of persistent pain in older individuals. CONCLUSIONS: It is postulated that ongoing education of clinicians who treat older patients with persistent moderate to severe pain will lead to improved outcomes in this vulnerable population.

Overdose deaths demand a new paradigm for opioid rotation.

OBJECTIVE: An increasing number of deaths have been inferred to be associated with current opioid rotation practices and evidence is mounting that the use of widely accepted protocols for opioid rotation is an important contributing factor. Based on the findings of a literature review published in conjunction with this article, we propose a new paradigm for a potentially safer method of opioid rotation and present a case study illustrating the paradigm. This new paradigm suggests three easy-to-remember steps in opioid rotation and obviates the need to use a conversion table. DESIGN: Report of a clinical case of a patient undergoing opioid rotation using this new paradigm. SUMMARY: The patient was successfully rotated from extended-release oxycodone to extended-release hydromorphone. The dose of oxycodone was slowly decreased, while the hydromorphone dose was slowly titrated. A critical element to this approach involved providing sufficient immediate-release opioid to treat breakthrough pain and to reverse acute abstinence signs and symptoms if the dosing changes prove insufficient. CONCLUSION: A safer new paradigm for opioid rotation may provide an important incremental step forward in reducing adverse public health consequences of inappropriate opioid dosing.

Review and critique of opioid rotation practices and associated risks of toxicity.

OBJECTIVES: A dramatic increase in unintentional deaths from opioids has occurred over the past decade with strong inference that many of these deaths may be resulting from prescriber's error. Recent evidence suggests that the use of dose conversion ratios published in equianalgesic tables may lead to fatal or near-fatal opioid overdoses. The objective of this review was to determine whether the current practice of opioid rotation may be contributing to high rate of unintentional deaths. METHODS: We performed a focused literature review to identify reports of fatal or near-fatal outcomes that have occurred in conjunction with opioid rotation, to evaluate clinician competence in opioid rotation, and to identify inconsistencies in published protocols for opioid rotation. Further information was obtained by reviewing dosing instructions contained in product labels for extended-release formulations of several opioids. RESULTS: An increasing body of literature suggests that widely used opioid rotation practices, including the use of dose conversion ratios found in equianalgesic tables, may be an important contributor to the increasing incidence of opioid-related fatalities. These errors may be due, in part, not only to inadequate prescriber's competence but also to proliferation of inconsistent guidelines for opioid rotation, conflation of equianalgesic tables as conversion tables, and limitations inherent in the equianalgesic dose tables. CONCLUSIONS: Most of the fatal outcomes occurring during opioid rotation are preventable. The current process being used for opioid rotation has important flaws that must be corrected.

The effect of a translating research into practice (TRIP)--cancer intervention on cancer pain management in older adults in hospice.

BACKGROUND: Pain is a major concern for individuals with cancer, particularly older adults who make up the largest segment of individuals with cancer and who have some of the most unique pain challenges. One of the priorities of hospice is to provide a pain-free death, and while outcomes are better in hospice, patients still die with poorly controlled pain. OBJECTIVE: This article reports on the results of a Translating Research into Practice intervention designed to promote the adoption of evidence-based pain practices for older adults with cancer in community-based hospices. SETTING: This Institutional Human Subjects Review Board-approved study was a cluster randomized controlled trial implemented in 16 Midwestern hospices. METHODS: Retrospective medical records from newly admitted patients were used to determine the intervention effect. Additionally, survey and focus group data gathered from hospice staff at the completion of the intervention phase were analyzed. RESULTS: Improvement on the Cancer Pain Practice Index, an overall composite outcome measure of evidence-based practices for the experimental sites, was not significantly greater than control sites. Decrease in patient pain severity from baseline to post-intervention in the experimental group was greater; however, the result was not statistically significant (P = 0.1032). CONCLUSIONS: Findings indicate a number of factors that may impact implementation of multicomponent interventions, including unique characteristics and culture of the setting, the level of involvement with the change processes, competing priorities and confounding factors, and complexity of the innovation (practice change). Our results suggest that future study is needed on specific factors to target when implementing a community-based hospice intervention, including determining and measuring intervention fidelity prospectively.

Recommendations for urine drug monitoring as a component of opioid therapy in the treatment of chronic pain.

OBJECTIVE: Several prominent guidelines recommend that patients on long-term opioid therapy have periodic urine drug monitoring (UDM) for appropriate use; however, none address the specific questions of which patients to test, which substances to test for, how often to test, and how to act on the results. DESIGN: In the absence of adequate scientific evidence in the literature, a panel of experts in the field of pain and addiction medicine was convened to develop consensus UDM recommendations. The panel met three times between March 2010 and April 2011, and reviewed several drafts of the recommendations document between meetings. RESULTS: The group was able to achieve consensus on a set of UDM recommendations addressing test selection, test frequency, interpretation of results, and how to handle discrepancies based on specific results. CONCLUSION: While the participating panel members recognize that there currently is a limited evidence base to support the expert panel's recommendations, primary care providers and pain specialists are largely acting today based on anecdote, intuition, and individual experience. The recommendations are meant to begin to provide a framework for standardizing practices for UDM in the treatment of chronic pain, and to serve as a catalyst to advance research that quantifies the effects of UDM on opioid therapy management and patient outcomes.

Long-term consequences of chronic pain: mounting evidence for pain as a neurological disease and parallels with other chronic disease states.

OBJECTIVE: This article reviews the potential physical and psychological consequences of chronic pain and the importance of implementing effective therapeutic strategies to mitigate the harms associated with inadequate treatment. RESULTS: A review of recent literature examining the neurobiology and pathophysiology of chronic pain reveals that this highly prevalent condition negatively impacts multiple aspects of patient health, including sleep, cognitive processes and brain function, mood/mental health, cardiovascular health, sexual function, and overall quality of life. Furthermore, chronic pain has the capacity to become increasingly complex in its pathophysiology, and thus potentially more difficult to treat over time. The various health complications related to chronic pain can also incur significant economic consequences for patients. CONCLUSIONS: Like other chronic conditions, it is important that chronic pain is managed with the objective of minimizing or avoiding its associated long-term sequelae. In line with this approach, early and effective multimodal treatment strategies, including analgesic therapy that controls pain intensity, are essential to improving outcomes and returning patients to normal levels of function.

An analysis of the root causes for opioid-related overdose deaths in the United States.

OBJECTIVE: A panel of experts in pain medicine and public policy convened to examine root causes and risk factors for opioid-related poisoning deaths and to propose recommendations to reduce death rates. METHODS: Panelists reviewed results from a search of PubMed and state and federal government sources to assess frequency, demographics, and risk factors for opioid-related overdose deaths over the past decade. They also reviewed results from a Utah Department of Health study and a summary of malpractice lawsuits involving opioid-related deaths. RESULTS: National data demonstrate a pattern of increasing opioid-related overdose deaths beginning in the early 2000s. A high proportion of methadone-related deaths was noted. Although methadone represented less than 5% of opioid prescriptions dispensed, one third of opioid-related deaths nationwide implicated methadone. Root causes identified by the panel were physician error due to knowledge deficits, patient non-adherence to the prescribed medication regimen, unanticipated medical and mental health comorbidities, including substance use disorders, and payer policies that mandate methadone as first-line therapy. Other likely contributors to all opioid-related deaths were the presence of additional central nervous system-depressant drugs (e.g., alcohol, benzodiazepines, and antidepressants) and sleep-disordered breathing. CONCLUSIONS: Causes of opioid-related deaths are multifactorial, so solutions must address prescriber behaviors, patient contributory factors, nonmedical use patterns, and systemic failures. Clinical strategies to reduce opioid-related mortality should be empirically tested, should not reduce access to needed therapies, should address risk from methadone as well as other opioids, and should be incorporated into any risk evaluation and mitigation strategies enacted by regulators.

Treatment of breakthrough pain with fentanyl buccal tablet in opioid-tolerant patients with chronic pain: appropriate patient selection and management.

BACKGROUND: Opioids can be a safe and effective option for carefully selected patients with a structured treatment program that includes consistent monitoring. However, the benefits and risks of opioid therapy for patients with chronic pain, and society as a whole, have been sharply debated. A key component of this debate has involved the administration of rapid-onset opioids for the management of breakthrough pain. OBJECTIVE: Review key aspects of breakthrough pain management with fentanyl buccal tablet, with a focus on minimizing risk to optimize therapeutic outcomes. Recommendations that apply broadly to all rapid-onset opioids are also discussed. DESIGN: Available fentanyl buccal tablet clinical and post-marketing data were reviewed. RESULTS: Like other schedule II controlled substances, and because fentanyl buccal tablet is a highly potent opioid, its use is associated with risk of overdose, misuse, and diversion. As with all rapid-onset opioids, particular attention to patient selection and risk assessment is warranted. The inclusion and exclusion criteria in fentanyl buccal tablet clinical studies represent patient selection standards that should be translated to clinical practice, most importantly, that patients are opioid-tolerant before fentanyl buccal tablet initiation. Titration of fentanyl buccal tablet from a low starting dose to a successful dose allows the safe identification of a dose that provides the greatest pain relief without unacceptable adverse events. After initiating fentanyl buccal tablet therapy, all patients should continue to be regularly monitored for response, including analgesia, functioning, tolerability, and aberrant behavior. CONCLUSIONS: Fentanyl buccal tablet can be an effective and generally safe treatment for breakthrough pain when appropriate patient selection, administration, dosing, and monitoring are applied.

Long-acting opioids and short-acting opioids: appropriate use in chronic pain management.

In recent years, opioid therapy for the management of chronic noncancer pain has become more widely accepted following the publication of data demonstrating the efficacy of this class of drugs in a variety of pain conditions, including osteoarthritis, neuropathic pain, and low back pain. An array of short-acting and long-acting opioids has been formulated to help prescribers more effectively tailor the management of chronic pain based on the quality and temporal profile of the pain as well as the functional goals of the individual patient. Evidence suggests that both of these groups of medications offer unique benefits to individual patients and that neither is more efficacious than the other. Rather, both short-acting and long-acting opioids should be considered in the overall pharmacotherapeutic treatment of patients with chronic noncancer pain.

Transforming long-term care pain management in north america: the policy-clinical interface.

BACKGROUND: The undertreatment of pain in older adults who reside in long-term care (LTC) facilities has been well documented, leading to clinical guideline development and professional educational programs designed to foster better pain assessment and management in this population. Despite these efforts, little improvement has occurred, and we postulate that focused attention to public policy and cost implications of systemic change is required to create positive pain-related outcomes. OBJECTIVE: Our goal was to outline feasible and cost-effective clinical and public policy recommendations designed to address the undermanagement of pain in LTC facilities. METHODS: We arranged a 2-day consensus meeting of prominent United States and Canadian pain and public policy experts. An initial document describing the problem of pain undermanagement in LTC was developed and circulated prior to the meeting. Participants were also asked to respond to a list of relevant questions before arriving. Following formal presentations of a variety of proposals and extensive discussion among clinicians and policy experts, a set of recommendations was developed. RESULTS AND CONCLUSIONS: We outline key elements of a transformational model of pain management in LTC for the United States and Canada. Consistent with previously formulated clinical guidelines but with attention to readily implementable public policy change in both countries, this transformational model of LTC has important implications for LTC managers and policy makers as well as major quality of life implications for LTC residents.

Opioid utilization patterns among patients with cancer and non-cancer pain.

OBJECTIVE: Opioid pain medication continues to be an important treatment option for patients with moderate to severe cancer and non-cancer pain; however, limited evidence is available regarding differences in opioid use between these two populations. The objective of this analysis was to compare real-world opioid use patterns over time in these two populations. DESIGN: Retrospective analysis of administrative claims data. SETTING: HealthCore Integrated Research Environment database. PATIENTS: Adults with ≥1 opioid pharmacy claim (and a confirmed cancer diagnosis for the cancer pain cohort). MAIN OUTCOME MEASURES: Opioid doses and dose changes following the initial prescribed (index) dose were determined. RESULTS: In the cancer pain (n = 9,209) and non-cancer pain (n = 409,703) cohorts, median index opioid doses were 51.7 and 45.0 morphine-equivalent units (MEU), respectively, and median post-index opioid doses were 55.8 and 45.1 MEU for the cancer pain and non-cancer pain cohorts, respectively. The most common dose escalation in both groups was up to a dose doubling (cancer pain, 31.8 percent; non-cancer pain, 28.3 percent). The proportions of patients with dose increases exceeding two times the index dose were low and clinically comparable between cohorts (cancer pain, 9.9 percent; non-cancer pain, 7.4 percent). CONCLUSIONS: Opioid use was consistent between patients with cancer pain and non-cancer pain, including clinically comparable total daily opioid doses and consistent rates of dose escalations and chronic utilization. Opioid medications are an important element of cancer and non-cancer pain management; thus, access to appropriate therapies, use patterns, and risk assessment and management are important for both patient populations.