Scott R. Griffith

Randomized, Double-blind, Placebo-controlled, Dose- response, and Preclinical Safety Study of Transforaminal Epidural Etanercept for the Treatment of Sciatica

Background:Recent evidence implicates the inflammatory cytokine tumor necrosis factor as a major cause of radiculopathy. Yet, whereas open-label studies with systemically delivered tumor necrosis factor inhibitors have yielded positive results, a placebo-controlled study failed to demonstrate efficacy. One variable that may have contributed to poor outcomes is low drug levels at the site of nerve inflammation. To date, no studies have evaluated the efficacy or safety of epidurally administered anti-tumor necrosis factor agents. Methods:A double-blind, placebo-controlled, dose-response study was conducted to evaluate an epidural tumor necrosis factor inhibitor. Twenty-four patients with subacute lumbosacral radiculopathy were randomly assigned to receive two transforaminal epidural injections of 2, 4, or 6 mg of entanercept 2 weeks apart in successive groups of eight. In each group, two patients received epidural saline. A parallel epidural canine safety study was conducted using the same injection doses and paradigm as in the clinical study. Results:The animal and human safety studies revealed no behavioral, neurologic, or histologic evidence of drug-related toxicity. In the clinical arm, significant improvements in leg and back pain were collectively noted for the etanercept-treated patients, but not for the saline group, one month after treatment. One patient in the saline group (17%), six patients in the 2-mg group (100%), and four patients each in the 4-mg and 6-mg groups (67%) reported at least 50% reduction in leg pain and a positive global perceived effect one month after treatment. Six months after treatment, the beneficial effects persisted in all but one patient. Conclusion:Epidural entanercept holds promise as a treatment for lumbosacral radiculopathy.

Multicenter, Randomized, Comparative Cost-effectiveness Study Comparing 0, 1, and 2 Diagnostic Medial Branch (Facet Joint Nerve) Block Treatment Paradigms before Lumbar Facet Radiofrequency Denervation

Background:Among patients presenting with axial low back pain, facet arthropathy accounts for approximately 10–15% of cases. Facet interventions are the second most frequently performed procedures in pain clinics across the United States. Currently, there are no uniformly accepted criteria regarding how best to select patients for radiofrequency denervation. Methods:A randomized, multicenter study was performed in 151 subjects with suspected lumbar facetogenic pain comparing three treatment paradigms. Group 0 received radiofrequency denervation based solely on clinical findings; group 1 underwent denervation contingent on a positive response to a single diagnostic block; and group 2 proceeded to denervation only if they obtained a positive response to comparative blocks done with lidocaine and bupivacaine. A positive outcome was predesignated as ≥50% pain relief coupled with a positive global perceived effect persisting for 3 months. Results:In group 0, 17 patients (33%) obtained a successful outcome at 3 months versus eight patients (16%) in group 1 and 11 (22%) patients in group 2. Denervation success rates in groups 0, 1, and 2 were 33, 39, and 64%, respectively. Pain scores and functional capacity were significantly lower at 3 months but not at 1 month in group 2 subjects who proceeded to denervation compared with patients in groups 0 and 1. The costs per successful treatment in groups 0, 1, and 2 were

Epidural Steroids, Etanercept, or Saline in Subacute Sciatica: A Multicenter, Randomized Trial

6,286,

A double-blind, placebo-controlled, dose-response pilot study evaluating intradiscal etanercept in patients with chronic discogenic low back pain or lumbosacral radiculopathy.

17,142, and

Presentation, diagnoses, mechanisms of injury, and treatment of soldiers injured in operation Iraqi freedom : An epidemiological study conducted at two military pain management centers

15,241, respectively. Conclusions:Using current reimbursement scales, these findings suggest that proceeding to radiofrequency denervation without a diagnostic block is the most cost-effective treatment paradigm.

Nucleoplasty with or without intradiscal electrothermal therapy (IDET) as a treatment for lumbar herniated disc

BACKGROUND Active surveillance (AS) and watchful waiting (WW) have been proposed as management strategies for low-risk, localized prostate cancer. PURPOSE To systematically review strategies for observational management of prostate cancer (AS or WW), factors affecting their utilization, and comparative effectiveness of observational management versus immediate treatment with curative intent. DATA SOURCES MEDLINE and Cochrane databases (from inception to August 2011). STUDY SELECTION Screened abstracts and reviewed full-text publications to identify eligible studies. DATA EXTRACTION One reviewer extracted data, and another verified quantitative data. Two independent reviewers rated study quality and strength of evidence for comparative effectiveness. DATA SYNTHESIS Sixteen independent cohorts defined AS, 42 studies evaluated factors that affect the use of observational strategies, and 2 evidence reports and 22 recent studies reported comparisons of WW versus treatment with curative intent. The most common eligibility criteria for AS were tumor stage (all cohorts), Gleason score (12 cohorts), prostate-specific antigen (PSA) concentration (10 cohorts), and number of biopsy cores positive for cancer (8 cohorts). For monitoring, studies used combinations of periodic PSA testing (all cohorts), digital rectal examination (14 cohorts), and rebiopsy (14 cohorts). Predictors of receiving no active treatment included older age, comorbid conditions, lower Gleason score, tumor stage, PSA concentration, and favorable risk group. No published studies compared AS with immediate treatment with curative intent. Watchful waiting was generally less effective than treatment with curative intent; however, applicability to contemporary patients may be limited. LIMITATIONS Active surveillance and WW often could not be differentiated in the reviewed studies. Published randomized trials have assessed only WW and did not enroll patients diagnosed by PSA screening. CONCLUSION Evidence is insufficient to assess whether AS is an appropriate option for men with localized prostate cancer. A standard definition of AS that clearly distinguishes it from WW is needed to clarify scientific discourse. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Epidural steroid injections, conservative treatment, or combination treatment for cervical radicular pain: a multicenter, randomized, comparative-effectiveness study.

Background:In recent years, convincing evidence has emerged implicating tumor necrosis factor α as a causative factor in radiculopathy and discogenic back pain. But although preliminary open-label studies demonstrated promising results for the treatment of low back pain with tumor necrosis factor-α inhibitors, early optimism has been tainted by a controlled study showing no significant benefit in sciatica. To determine whether outcomes might be improved by a more direct route of administration, the authors evaluated escalating doses of intradiscal etanercept in 36 patients with chronic lumbosacral radiculopathy or discogenic low back pain. Methods:A double-blind, placebo-controlled pilot study was conducted whereby six patients received 0.1, 0.25, 0.5, 0.75, 1.0, or 1.5 mg etanercept intradiscally in each pain-generating disc. In each escalating dose group of six patients, one received placebo. A neurologic examination and postprocedure leukocyte counts were performed in all patients at 1-month follow-up visits. In patients who experienced significant improvement in pain scores and function, follow-up visits were conducted 3 and 6 months after the procedure. Results:At 1-month follow-up, no differences were found for pain scores or disability scores between or within groups for any dose range or subgroup of patients. Only eight patients remained in the study after 1 month and elected to forego further treatment. No complications were reported, and no differences were noted between preprocedure and postprocedure leukocyte counts. Conclusions:Although no serious side effects were observed in this small study, a single low dose of intradiscal etanercept does not seem to be an effective treatment for chronic radicular or discogenic low back pain.

Epidural steroid injections compared with gabapentin for lumbosacral radicular pain: multicenter randomized double blind comparative efficacy study

In recent military conflicts the major source of soldier attrition has not been battle injuries but more mundane causes similar to those encountered in civilian life. In an effort to determine the pain conditions affecting soldiers during wartime, we conducted an observational study among 162 soldiers medically evacuated from Operation Iraqi Freedom who were referred to 2 large pain treatment centers located outside the theaters of combat. Fifty-three percent of soldiers presented with either radicular (n = 49) or axial (n = 37) low back pain, with lumbar herniated disk being the most frequently diagnosed condition (24%). The two most implicated etiologies were exacerbation of a previous pain condition treated with surgery (15%) and motor vehicle accidents(12%). Only 17% of patients were injured during battle. Seventy-two percent of soldiers received at least one nerve block/injection, the most common of which was lumbar epidural steroid administration (22%). Nonsteroidal antiinflammatory drugs were prescribed to 56% of patients, opioids to 49%, and some form of alternative therapy to 17%. Among the 49 patients in whom data were available, only 2% returned to combat duty in Iraq. With the exception of battle-related injuries, the pain conditions suffered during modern warfare seem to be similar to those encountered in civilian pain clinics. To improve the return-to-duty rate, better preventive measures and more aggressive treatment conducted in forward-deployed medical units are recommended.

A Multi-Center Analysis Evaluating Factors Associated with Spinal Cord Stimulation Outcome in Chronic Pain Patients

Background and Objective: In industrialized societies, the prevalence of radicular low back pain has exploded in recent years. The growing economic and personal costs of this challenging entity have led to the development of a wide array of new treatments, ranging from pharmacotherapy with neuropathic medications to open surgical treatment. Among the therapeutic options to emerge are a plethora of minimally invasive treatments aimed at removing nuclear material and lowering intradiscal pressure through devices inserted percutaneously into intervertebral discs. Yet there is a compelling lack of clinical evidence to support the use of these procedures. This study was undertaken to determine the treatment outcomes of 16 consecutive patients with lumbar radicular pain secondary to a herniated disc who underwent nucleoplasty as their primary therapy. Methods: Included in this series were nine patients with significant axial back pain, sitting intolerance, and positive discography who also underwent intradiscal electrothermal therapy (IDET). Among the 7 patients who only had nucleoplasty, 4 had 2 discs treated and 3 had 1 disc. In the 9 patients who also had IDET, 6 had 1 disc treated and 3 had 2 discs treated. Of the 32 total disc treatments, 20 were at L5-S1, 10 were at L4-5 and 2, one each for IDET and nucleoplasty, were at L3-4. Results: In the overall cohort, the average Visual Analogue Scale (VAS) pain score decreased from 6.7 to 5.6 at a mean follow-up of 9 months. In the seven patients who underwent only nucleoplasty, the mean VAS score decreased from 6.0 to 4.8. Only one patient reported a ≥50% reduction in pain score. Conclusions: We conclude that with use of the present selection criteria, nucleoplasty is not an effective long-term treatment for lumbar radiculopathy, either alone or with IDET. Before conducting future clinical trials, we recommend modifying these criteria to include only those patients with small (<6-mm) contained disc herniations whose annular integrity is documented by computed tomography discography and corresponding radicular symptoms confirmed by either selective nerve root blocks or electromyography and nerve conduction studies.

Incidence and root cause analysis of wrong-site pain management procedures: a multicenter study.

Background:Cervical radicular pain is a major cause of disability. No studies have been published comparing different types of nonsurgical therapy. Methods:A comparative-effectiveness study was performed in 169 patients with cervical radicular pain less than 4 yr in duration. Participants received nortriptyline and/or gabapentin plus physical therapies, up to three cervical epidural steroid injections (ESI) or combination treatment over 6 months. The primary outcome measure was average arm pain on a 0 to 10 scale at 1 month. Results:One-month arm pain scores were 3.5 (95% CI, 2.8 to 4.2) in the combination group, 4.2 (CI, 2.8 to 4.2) in ESI patients, and 4.3 (CI, 2.8 to 4.2) in individuals treated conservatively (P = 0.26). Combination group patients experienced a mean reduction of −3.1 (95% CI, −3.8 to −2.3) in average arm pain at 1 month versus −1.8 (CI, −2.5 to −1.2) in the conservative group and −2.0 (CI, −2.7 to −1.3) in ESI patients (P = 0.035). For neck pain, a mean reduction of −2.2 (95% CI, −3.0 to −1.5) was noted in combination patients versus −1.2 (CI, −1.9 to −0.5) in conservative group patients and −1.1 (CI, −1.8 to −0.4) in those who received ESI; P = 0.064). Three-month posttreatment, 56.9% of patients treated with combination therapy experienced a positive outcome versus 26.8% in the conservative group and 36.7% in ESI patients (P = 0.006). Conclusions:For the primary outcome measure, no significant differences were found between treatments, although combination therapy provided better improvement than stand-alone treatment on some measures. Whereas these results suggest an interdisciplinary approach to neck pain may improve outcomes, confirmatory studies are needed.