Healthcare utilization and cost burden among women with endometriosis by opioid prescription status in the first year after diagnosis: a retrospective claims database analysis.

Aims: Opioids do not represent standard therapy for endometriosis; however, women with endometriosis are frequently prescribed an opioid to manage related abdominal or pelvic pain. The aim of this study was to evaluate the impact of opioid use on endometriosis-related economic and healthcare burden in the United States.Materials and methods: We performed a retrospective, propensity-matched cohort analysis of the Truven MarketScan Commercial database from 1 January 2011 to 31 December 2016. Eligible women had at least 1 inpatient or 2 outpatient codes for endometriosis and 12 months of continuous enrollment before and after the index date (i.e. first recorded endometriosis diagnosis). The primary analysis examined healthcare costs and utilization for 12 months after the index date in women who filled at least 1 opioid prescription versus those who did not. The secondary analysis examined healthcare costs and utilization by the pattern of opioid use.Results: The primary analysis matched 43,516 women across 2 groups and the secondary analysis matched 13,230 women across 5 groups. In the primary analysis, total 12-month healthcare costs were significantly higher in the opioid group compared to the non-opioid group ($29,236.00 vs. $18,466.00, respectively; p < .001); the same pattern was observed for all healthcare utilization parameters. In the secondary analysis, higher morphine equivalent daily dose and proportion of days covered were associated with the highest healthcare costs and utilization compared to the non-opioid group.Limitations: Retrospective design and inability to confirm whether filled opioid prescriptions were actually taken.Conclusions: Filling an opioid prescription within 1 year after an endometriosis diagnosis was associated with significant excess healthcare burden. Patients prescribed an opioid may experience inadequate symptom management and benefit from the use of disease-specific, non-opioid therapies.

Outcome measures in placebo-controlled trials of osteoarthritis: responsiveness to treatment effects in the REPORT database.

INTRODUCTION: Treatment response in randomized clinical trials (RCT) of osteoarthritis (OA) has been assessed by multiple primary and secondary outcomes, including pain, function, patient and clinician global measures of status and response to treatment, and various composite and responder measures. Identifying outcome measures with greater responsiveness to treatment is important to increase the assay sensitivity of RCTs. OBJECTIVE: To assess and compare the responsiveness of different outcome measures used in placebo-controlled RCTs of OA. SEARCH STRATEGY: The Resource for Evaluating Procedures and Outcomes of Randomized Trials database includes placebo-controlled clinical trials of pharmacologic treatments (oral, topical, or transdermal) for OA identified from a systematic literature search of RCTs published or publicly available before August 5, 2009, which was conducted using PubMed, the Cochrane collaboration, publicly-available websites, and reference lists of retrieved publications. DATA COLLECTION AND ANALYSIS: Data collected included: (1) pain assessed with single-item ratings and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale; (2) patient and clinician global measures of status, improvement, and treatment response; (3) function assessed by the WOMAC function subscale; (4) stiffness assessed by the WOMAC stiffness subscale; and (5) the WOMAC and Lequesne Algofunctional Index composite outcomes. Measures were grouped according to the total number of response categories (i.e., <10 categories or ≥10 categories). The treatment effect (difference in mean change from baseline between the placebo and active therapy arms) and standardized effect size (SES) were estimated for each measure in a meta-analysis using a random effects model. RESULTS: There were 125 RCTs with data to compute the treatment effect for at least one measure; the majority evaluated non-steroidal anti-inflammatory drugs (NSAIDs), followed by opioids, glucosamine and/or chondroitin, and acetaminophen. In general, the patient-reported pain outcome measures had comparable responsiveness to treatment as shown by the estimates of treatment effects and SES. Treatment effects and SESs were generally higher for patient-reported global measures compared with clinician-rated global measures but generally similar for the WOMAC and Lequesne composite measures. CONCLUSIONS: Comparing different outcome measures using meta-analysis and selecting those that have the greatest ability to identify efficacious treatments may increase the efficiency of clinical trials of treatments for OA. Improvements in the quality of the reporting of clinical trial results are needed to facilitate meta-analyses to evaluate the responsiveness of outcome measures and to also address other issues related to assay sensitivity.

Development and preliminary experience with an ease of extractability rating system for prescription opioids.

One important factor in the abuse potential of an opioid product is the ease with which active drug can be extracted. There are currently no standards for testing or reporting extractability. This article describes the development of an Extractability Rating System for use by the pharmaceutical industry and regulators. Despite several limitations, this effort serves as a call for standardized testing and reporting so that products can be accurately rated, and should help establish goals for drug developers who wish to develop "abuse-resistant" opioid products.

A randomized, double-blind, placebo-controlled trial of a glycine antagonist in neuropathic pain.

BACKGROUND: Nerve injury results in increases in spinal glutamate, which opens the NMDA ionophore channel, causing an influx of calcium. A glycine-binding site must be occupied for the channel to open. GV196771 is a selective antagonist of the glycine-binding site of the NMDA ionophore. OBJECTIVE: To determine the efficacy of GV196771 in subjects with chronic neuropathic pain in a proof-of-concept study. METHODS: With informed consent, 63 subjects (31 placebo, 32 GV196771) with neuropathic pain (diabetic neuropathy, postherpetic neuralgia, complex regional pain syndrome, or peripheral nerve injury), a visual analogue score averaging > or =30 mm during the screening period, and a well-defined primary area of mechanical allodynia were recruited for the study. A multicenter, randomized, double-blind, placebo-controlled, parallel-group study design was utilized. Subjects came to the research center for a total of five visits over a 21-day period, which consisted of a 14-day treatment period followed by a 7-day washout period. Spontaneous and evoked pain scores, mechanical sensory testing, quantitative sensory testing, Short Form McGill Pain Questionnaire, patient global satisfaction, and safety assessments were made during the study. RESULTS: There was no significant effect of GV196771 on spontaneous or evoked pain, quantitative sensory testing, or patient global satisfaction. There was a significant effect of GV196771 on the area of dynamic and static allodynia on days 7 and 14. The overall incidence of adverse events during treatment was similar for GV196771 (56%) and placebo (71%). The incidence of drug-related adverse events during treatment was higher for placebo (42%) than GV196771 (28%). CONCLUSIONS: Although the glycine antagonists show anti-hyperalgesic action in animal models of neuropathic pain, GV196771 does not appear to be an effective treatment in subjects with chronic neuropathic pain. This may be due to insufficient penetration of GV196771 to central sites of action, differences between the human and animal glycine receptors, or differences between neuropathic pain in animal models and humans.

Characteristics of methadone maintenance patients with chronic pain.

Chronic pain patients who have limited access to opioids may be redirected to methadone maintenance centers for management of their pain. Unfortunately, little information exists on the incidence and characteristics of methadone maintenance patients with chronic pain. The aim of this study was to survey individuals at methadone maintenance centers in order to determine the prevalence of chronic pain and to explore differences between patients with and without pain in this treatment setting. Of 248 participants interviewed at three centers, 152 (61.3%) reported chronic pain. Compared with patients without pain, those with pain reported significantly more health problems (P < 0.001), more psychiatric disturbance (P < 0.05), more prescription and nonprescription medication use (P < 0.001), and greater belief that they were undertreated (P < 0.001); 44% of those with pain believed that opioids prescribed for their pain had led to an addiction problem. Most of the methadone maintenance patients stated that they had always required some substance (alcohol or opioids) to feel normal. These results raise many questions about chronic-pain treatment policies and resources for persons with a history of substance abuse. Further investigations are needed to define the needs of this population and to improve their access to effective pain management.

MorphiDex (MS:DM) double-blind, multiple-dose studies in chronic pain patients.

Preclinical and double-blind single-dose placebo-controlled studies demonstrated that MorphiDex (MS:DM), a 1:1 ratio of morphine sulfate (MS) to dextromethorphan hydrobromide (DM), provides significantly greater analgesia than an equal dose of immediate release MS, with a faster onset, and a duration of > or = 8 h. The analgesic effect of MS:DM compared to MS was evaluated in 2 double-blind, multiple-dose studies in 321 patients with cancer and other chronic pain: a crossover study that consisted of two 2-wk periods and a 4-wk parallel study. As specified in the study protocols, patients took sufficient MS or MS:DM to achieve satisfactory pain control. In the crossover study, the MS:DM group required half as much morphine as the MS group to achieve satisfactory pain control (80 mg and 162 mg, respectively). The interval between doses and the time from the last dose of the day to the first dose of the next day were significantly longer for MS:DM compared to MS. In the parallel study, MS:DM also provided pain control at a significantly lower dose. After four weeks of treatment, the mean daily dose of MS increased, while there was little change in the MS:DM mean daily dose (P = 0.025) to maintain satisfactory pain control. More patients preferred MS:DM to run-in MS than preferred MS to run-in MS (P = 0.026). The addition of DM to MS did not increase the incidence of adverse events, which were those commonly associated with opioid use. These studies confirm that MS:DM provides satisfactory pain relief but at a significantly lower morphine daily dose.

Opioid therapy for chronic noncancer back pain. A randomized prospective study.

STUDY DESIGN: A randomized, open, long-term, repeated-dose comparison of an anti-inflammatory drug and two opioid regimens in 36 patients with back pain. OBJECTIVES: To examine the long-term safety and efficacy of chronic opioid therapy in a randomized trial of patients with back pain. METHODS: All participants underwent a 4-week washout period of no opioid medication before being randomly assigned to one of three treatment regimens for 16 weeks: 1) naproxen only, 2) set-dose oxycodone, or 3) titrated-dose oxycodone and sustained-release morphine sulfate. All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks. Finally, all participants were monitored for a 1-month posttreatment washout period. Each patient was called once a week for a report on pain, activity, mood, medication, hours awake, and adverse effects and was monitored carefully for signs of abuse and noncompliance. RESULTS: Weekly reports during the experimental phase showed the titrated-dose group to have less pain (P < 0.001) and less emotional distress (P < 0.001) than the other two groups. Both opioid groups were significantly different from the naproxen-only group. During the titration phase, patients also reported significantly less pain and improved mood. Few differences were found in activity or hours asleep, or between average pretreatment and posttreatment phone-interview and questionnaire variables. No adverse events occurred, and only one participant showed signs of abuse behavior. CONCLUSIONS: The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep. Opioid therapy for chronic back pain was used without significant risk of abuse. However, tapered-off opioid treatment is palliative and without long-term benefit.

Labour pain management in a parturient with an implanted intrathecal pump.

PURPOSE: We report the peripartum anaesthetic management for vaginal delivery of a chronic pain patient with an implanted intrathecal pump. This is the first report describing labour analgesia in a patient with such a device. As intrathecal systems become more popular for the management of nonmalignant pain, this situation is likely to be encountered with increasing frequency in the future. CLINICAL FEATURES: The patient was a nulliparous 23-yr-old with a history of chronic hereditary pancreatitis whose intractable pain had been managed with intrathecal morphine 3 mg.day-1 via an implantable pump for four years. Inadequate time between presentation and onset of labour prevented us from using this system. Intravenous patient controlled analgesia with fentanyl using a bolus of 25 micrograms and a lockout of five minutes was ineffective and epidural analgesia using bupivacaine was initiated and resulted in satisfactory analgesia. CONCLUSION: The presence of an existing intrathecal delivery system does not preclude the use of supplemental epidural analgesia during labour.

Chronic opioid therapy for nonmalignant pain in patients with a history of substance abuse: report of 20 cases.

A history of substance abuse is considered by many to be a contraindication to chronic opioid therapy for nonmalignant pain. Twenty patients with a history of chronic nonmalignant pain and substance abuse treated with chronic opioid therapy for a period of more than 1 year were retrospectively evaluated to determine the factors associated with prescription abuse. The prevalence of six aberrant behavioral patterns was assessed to see if these correlated with a history of prescription abuse, as reported by the patient's pain clinic physician. Those who did not abuse opioid therapy were more likely to have a history of alcohol abuse alone or a remote history of polysubstance abuse. They were also more likely to be active members of Alcoholics Anonymous and to have a stable family or other similar support system. In contrast, those who abused opioid therapy showed characteristic aberrant patterns of behavior in their management, which indicated a clear pattern of prescription abuse early in the course of therapy. Those patients were more likely to be recent polysubstance abusers, or have a prior history of oxycodone abuse. None of them were active members of Alcoholics Anonymous. Signing an "opioids contract" was not in and of itself a predictor of successful outcome.

Degenerative lumbar spinal stenosis. Diagnostic value of the history and physical examination.

OBJECTIVE: To assess the value of the history and physical examination findings in the diagnosis of symptomatic degenerative lumbar spinal stenosis (LSS). METHODS: The study was performed in 3 specialty clinics, and included patients with low back pain who were at least age 40. Findings from a standardized history and physical examination were compared with the diagnostic impression of expert attending clinicians. Imaging studies were available in 88% of those with LSS, and the findings further supported the diagnosis of LSS in each case. The sensitivity, specificity, and likelihood ratio associated with each history and physical examination finding were calculated in bivariate analyses, and independent correlates of LSS were identified with multivariate analyses. RESULTS: Ninety-three patients were evaluated. History findings most strongly associated with the diagnosis of LSS (likelihood ratio > or = 2) were greater age, severe lower-extremity pain, and absence of pain when seated. Physical examination findings most strongly associated with the diagnosis were wide-based gait, abnormal Romberg test result, thigh pain following 30 seconds of lumbar extension, and neuromuscular deficits. Independent correlates of LSS included advanced age (P = 0.0001), absence of pain when seated (P = 0.006), wide-based gait (P = 0.013), and thigh pain following 30 seconds of lumbar extension (P = 0.002). CONCLUSION: Specific history and physical examination findings are useful in the diagnosis of LSS and should be ascertained routinely in older patients with low back pain.

Post-dural puncture thoracic pain without headache: relief with epidural blood patch.

We report two unusual cases of postural, post-dural puncture upper thoracic interscapular backache, without headache, that were relieved by epidural blood patching. There is controversy concerning the aetiology of headache associated with the post-dural puncture syndrome. Mechanisms previously proposed have included traction on pain-sensitive intracranial structures such as the dura or blood vessels, or a vascular mechanism which may be adenosine-receptor mediated. These two cases suggest that traction on cervical or upper thoracic nerve roots should be considered as a possible mechanism of pain in the post-dural puncture syndrome.

The discrimination of similarly colored objects in computer images of the ocular fundus.

The STARE (STructured Analysis of the REtina) project uses object-identification and artificial intelligence techniques to provide automated diagnoses from color pictures and fluorescein angiograms of the ocular fundus, or automated change detection from sequential images. As part of the object-identification process, we apply expert judgment and experimentation to define features--such as size, shape, color, and texture--of objects (disk, blood vessels, lesions) in digitized images. In our initial investigations, we explored color alone, because it yields a great deal of information in the classification process. We verified that even similarly colored lesions (exudates, cotton-wool spots, and drusen) could be classified by color with moderate success by a quadratic discriminant function. When color alone is not sufficient, refinement in the classification of objects may be achieved by using more features in statistical pattern recognition. Ultimately, we build a description of the fundus image which can be used either to identify one or more diagnoses that can cause the pattern of lesions in the ocular fundus or to recognize change in sequential images.