Srdjan S. Nedeljkovic

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.

Electronic diaries for monitoring chronic pain : 1-year validation study

&NA; Electronic data collection for monitoring pain has become increasingly popular in clinical research. However, no direct comparison has been made between electronic diaries and self‐report paper diaries or phone interviews. We asked 36 patients with chronic low back pain to monitor their pain for 1 year; 20 of them used both a palmtop computer and paper diaries, and 16 used paper diaries alone. All patients were called once a week and asked to rate their pain. Regression analyses with a measurement error model were run on hourly pain scores recorded by both palmtop computer and paper diaries. Ratings of pain intensity were highly reliable between data recorded with a palmtop computer and with data from paper diaries. Patients who monitored their pain with the palmtop computer entered data on average 6.75 times a week and were 89.9% compliant with daily monitoring throughout the year. Two‐way messaging available through the palmtop computer seemed to encourage continued use of the device. Internal consistency of reporting and correlations with phone reports and standardized measures were highly significant, suggesting that data from electronic diaries are both reliable and valid. Patients using electronic diaries preferred them to paper diaries and showed much higher rates of compliance and satisfaction over the 1‐year trial.

Urine toxicology screening among chronic pain patients on opioid therapy: frequency and predictability of abnormal findings.

ObjectiveTo examine the incidence of abnormal urine toxicology screening among chronic pain patients prescribed opioids for their pain and to relate these results to patient descriptors and type, number, and dose of prescribed opioids. MethodsA retrospective analysis of data from 470 patients who had urine screening at a pain management program in an urban teaching hospital was performed. Urine samples were analyzed using gas chromatography-mass spectrometry. Patients were categorized as having urine screens that were “normal” (expected findings based on their prescribed drugs) or abnormal. Abnormal findings were those of (1) absence of a prescribed opioid, (2) presence of an additional nonprescribed controlled substance, (3) detection of an illicit substance, and (4) an adulterated urine sample. ResultsForty-five percent of the patients were found to have abnormal urine screens. Twenty percent were categorized as having an illicit substance in their urine. Illicit substances and additional drugs were found more frequently in younger patients than in older patients (P<0.001). No other variables were found to predict abnormal urine screen results. DiscussionThese results confirm past findings that random urine toxicology screens among patients prescribed opioids for pain reveal a high incidence of abnormal findings. Common patient descriptors, and number, type, and dose of prescribed opioids were found to be poor predictors of abnormal results.

Assessment of efficacy of long-term opioid therapy in pain patients with substance abuse potential.

Clinical experience supports the notion that opioids can be used successfully to treat many chronic pain conditions. Unfortunately, few controlled trials have assessed which individuals benefit from long-term opioid therapy, and there is concern about the use of long-term opioid therapy in individuals with a substance-abuse history. This article contains three sections relevant to the assessment of individuals with chronic pain and a substance-abuse history who are receiving long-term opioid therapy. The first reviews the literature on opioid therapy, with a critique of biologic and environmental susceptibility factors for addiction. The second briefly reviews uncontrolled and controlled trials of opioid therapy for pain. The third reviews areas critical in assessing treatment efficacy and substance abuse in patients with chronic pain, both in terms of documentation of past behaviors and as a measure of outcome of opioid therapy. Potential guidelines for use of opioids in patients with chronic noncancer pain are outlined. Finally, questions are posed for future investigations of the efficacy of opioid therapy for patients with chronic pain and a substance-abuse history.

Association of Early Imaging for Back Pain With Clinical Outcomes in Older Adults

IMPORTANCE In contrast to the recommendations for younger adults, many guidelines allow for older adults with back pain to undergo imaging without waiting 4 to 6 weeks. However, early imaging may precipitate interventions that do not improve outcomes. OBJECTIVE To compare function and pain at the 12-month follow-up visit among older adults who received early imaging with those who did not receive early imaging after a new primary care visit for back pain without radiculopathy. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort of 5239 patients 65 years or older with a new primary care visit for back pain (2011-2013) in 3 US health care systems. We matched controls 1:1 using propensity score matching of demographic and clinical characteristics, including diagnosis, pain severity, pain duration, functional status, and prior resource use. EXPOSURES Diagnostic imaging (plain films, computed tomography [CT], magnetic resonance imaging [MRI]) of the lumbar or thoracic spine within 6 weeks of the index visit. MAIN OUTCOME AND MEASURES PRIMARY OUTCOME back or leg pain-related disability measured by the modified Roland-Morris Disability Questionnaire (score range, 0-24; higher scores indicate greater disability) 12 months after enrollment. RESULTS Among the 5239 patients, 1174 had early radiographs and 349 had early MRI/CT. At 12 months, neither the early radiograph group nor the early MRI/CT group differed significantly from controls on the disability questionnaire. The mean score for patients who underwent early radiography was 8.54 vs 8.74 among the control group (difference, -0.10 [95% CI, -0.71 to 0.50]; mixed model, P = .36). The mean score for the early MRI/CT group was 9.81 vs 10.50 for the control group (difference,-0.51 [-1.62 to 0.60]; mixed model, P = .18). CONCLUSIONS AND RELEVANCE Among older adults with a new primary care visit for back pain, early imaging was not associated with better 1-year outcomes. The value of early diagnostic imaging in older adults for back pain without radiculopathy is uncertain.

Psychiatric Comorbidity Is Associated Prospectively with Diminished Opioid Analgesia and Increased Opioid Misuse in Patients with Chronic Low Back Pain.

Background:Opioids are frequently prescribed for chronic low back pain (CLBP), but there are little prospective data on which patient subgroups may benefit. Psychiatric comorbidity, such as high levels of depression and anxiety symptoms (termed comorbid negative affect [NA]), is a common presentation and may predict diminished opioid analgesia and/or increased opioid misuse. Methods:The authors conducted a 6½-month prospective cohort study of oral opioid therapy, with an active drug/placebo run-in period, in 81 CLBP patients with low, moderate, and high levels of NA. Treatment included an opioid titration phase with a prescribing physician blinded to NA group assignment and a 4-month continuation phase, during which subjects recorded daily pain levels using an electronic diary. The primary outcome was the percent improvement in average daily pain, summarized weekly. Results:There was an overall 25% dropout rate. Despite the high NA group being prescribed a higher average daily dose of morphine equivalents, linear mixed model analysis revealed that the 24 study completers in each of the high NA and low NA groups had an average 21 versus 39% improvement in pain, respectively (P < 0.01). The high NA group also had a significantly greater rate of opioid misuse (39 vs. 8%, P < 0.05) and significantly more and intense opioid side effects (P < 0.01). Conclusions:These results indicate that the benefit and risk considerations in CLBP patients with high NA versus low NA are distinctly different. Thus, NA is an important phenotypic variable to characterize at baseline, before deciding whether to prescribe opioids for CLBP.

Psychopathology predicts the outcome of medial branch blocks with corticosteroid for chronic axial low back or cervical pain: a prospective cohort study

BackgroundComorbid psychopathology is an important predictor of poor outcome for many types of treatments for back or neck pain. But it is unknown if this applies to the results of medial branch blocks (MBBs) for chronic low back or neck pain, which involves injecting the medial branch of the dorsal ramus nerves that innervate the facet joints. The objective of this study was to determine whether high levels of psychopathology are predictive of pain relief after MBB injections in the lumbar or cervical spine.MethodsThis was a prospective cohort study. Consecutive patients in a pain medicine practice undergoing MBBs of the lumbar or cervical facets with corticosteroids were recruited to participate. Subjects were selected for a MBB based on operationalized selection criteria and the procedure was performed in a standardized manner. Subjects completed the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) just prior to the procedure and at one-month follow up. Scores on the HADS classified the subjects into three groups based on psychiatric symptoms, which formed the primary predictor variable: Low, Moderate, or High levels of psychopathology. The primary outcome measure was the percent improvement in average daily pain rating one-month following an injection. Analysis of variance and chi-square were used to analyze the analgesia and functional rating differences between groups, and to perform a responder analysis.ResultsEighty six (86) subjects completed the study. The Low psychopathology group (n = 37) reported a mean of 23% improvement in pain at one-month while the High psychopathology group (n = 29) reported a mean worsening of -5.8% in pain (p < .001). Forty five percent (45%) of the Low group had at least 30% improvement in pain versus 10% in the High group (p < .001). Using an analysis of covariance, no baseline demographic, social, or medical variables were significant predictors of pain improvement, nor did they mitigate the effect of psychopathology on the outcome.ConclusionPsychiatric comorbidity is associated with diminished pain relief after a MBB injection performed with steroid at one-month follow-up. These findings illustrate the importance of assessing comorbid psychopathology as part of a spine care evaluation.

Study protocol: The back pain outcomes using longitudinal data (BOLD) registry

BackgroundBack pain is one of the most important causes of functional limitation, disability, and utilization of health care resources for adults of all ages, but especially among older adults. Despite the high prevalence of back pain in this population, important questions remain unanswered regarding the comparative effectiveness of commonly used diagnostic tests and treatments in the elderly. The overall goal of the Back pain Outcomes using Longitudinal Data (BOLD) project is to establish a rich, sustainable registry to describe the natural history and evaluate prospectively the effectiveness, safety, and cost-effectiveness of interventions for patients 65 and older with back pain.Methods/designBOLD is enrolling 5,000 patients ≥ 65 years old who present to a primary care physician with a new episode of back pain. We are recruiting study participants from three integrated health systems (Kaiser-Permanente Northern California, Henry Ford Health System in Detroit and Harvard Vanguard Medical Associates/ Harvard Pilgrim Health Care in Boston). Registry patients complete validated, standardized measures of pain, back pain-related disability, and health-related quality of life at enrollment and 3, 6 and 12 months later. We also have available for analysis the clinical and administrative data in the participating health systems’ electronic medical records. Using registry data, we will conduct an observational cohort study of early imaging compared to no early imaging among patients with new episodes of back pain. The aims are to: 1) identify predictors of early imaging and; 2) compare pain, functional outcomes, diagnostic testing and treatment utilization of patients who receive early imaging versus patients who do not receive early imaging. In terms of predictors, we will examine patient factors as well as physician factors.DiscussionBy establishing the BOLD registry, we are creating a resource that contains patient-reported outcome measures as well as electronic medical record data for elderly patients with back pain. The richness of our data will allow better matching for comparative effectiveness studies than is currently possible with existing datasets. BOLD will enrich the existing knowledge base regarding back pain in the elderly to help clinicians and patients make informed, evidence-based decisions regarding their care.

Study Protocol- Lumbar Epidural Steroid Injections for Spinal Stenosis (LESS): a double-blind randomized controlled trial of epidural steroid injections for lumbar spinal stenosis among older adults

BackgroundLumbar spinal stenosis is one of the most common causes of low back pain among older adults and can cause significant disability. Despite its prevalence, treatment of spinal stenosis symptoms remains controversial. Epidural steroid injections are used with increasing frequency as a less invasive, potentially safer, and more cost-effective treatment than surgery. However, there is a lack of data to judge the effectiveness and safety of epidural steroid injections for spinal stenosis. We describe our prospective, double-blind, randomized controlled trial that tests the hypothesis that epidural injections with steroids plus local anesthetic are more effective than epidural injections of local anesthetic alone in improving pain and function among older adults with lumbar spinal stenosis.MethodsWe will recruit up to 400 patients with lumbar central canal spinal stenosis from at least 9 clinical sites over 2 years. Patients with spinal instability who require surgical fusion, a history of prior lumbar surgery, or prior epidural steroid injection within the past 6 months are excluded. Participants are randomly assigned to receive either ESI with local anesthetic or the control intervention (epidural injections with local anesthetic alone). Subjects receive up to 2 injections prior to the primary endpoint at 6 weeks, at which time they may choose to crossover to the other intervention.Participants complete validated, standardized measures of pain, functional disability, and health-related quality of life at baseline and at 3 weeks, 6 weeks, and 3, 6, and 12 months after randomization. The primary outcomes are Roland-Morris Disability Questionnaire and a numerical rating scale measure of pain intensity at 6 weeks. In order to better understand their safety, we also measure cortisol, HbA1c, fasting blood glucose, weight, and blood pressure at baseline, and at 3 and 6 weeks post-injection. We also obtain data on resource utilization and costs to assess cost-effectiveness of epidural steroid injection.DiscussionThis study is the first multi-center, double-blind RCT to evaluate the effectiveness of epidural steroid injections in improving pain and function among older adults with lumbar spinal stenosis. The study will also yield data on the safety and cost-effectiveness of this procedure for older adults.Trial RegistrationClinicaltrials.gov NCT01238536

Trajectories of symptoms and function in older adults with low back disorders.

Study Design. Prospective cohort study. Objective. To determine whether there are distinct trajectories of back pain and function among older adults and to identify characteristics that distinguish among patients with substantially different prognoses. Summary of Background Data. Although the differential diagnosis and course of low back pain among older adults may differ from middle-aged adults, there is little evidence. Better understanding variability in recovery among older adults may help target patients for more intensive clinical interventions, plan resource use, and design clinical studies of more homogeneous patient groups. Methods. Patients aged 65 years or older with a new episode of care for back pain were recruited at 3 geographically diverse sites. Patients completed pain intensity and Roland-Morris Disability measures at baseline and 3, 6, and 12 months later. We used latent class analysis to identify distinct trajectories of pain and function and then logistic regression to identify predictors of membership in the improving trajectories. Results. There were 3929 participants who completed outcome measures at every follow-up interval. Latent class analysis identified subgroups with low, intermediate, or high pain or disability scores who remained relatively stable over time. However, small subgroups showed dramatic improvement from baseline to 1 year (17% with major improvement in Roland score, pain intensity, or both). Shorter pain duration, higher patient confidence in improvement, and fewer comorbid conditions at baseline were each associated independently with favorable prognosis. Conclusion. Although most patients remained relatively stable over a year, latent class analysis identified small groups with major improvement in pain, function, or both. This technique may, therefore, be useful for studying back pain prognosis. Our results should help assemble more prognostically homogeneous groups for research, and the technique may help identify subgroups of patients with uniquely successful responses to investigational interventions. Level of Evidence: 3