A multi-center analysis evaluating factors associated with spinal cord stimulation outcome in chronic pain patients.

BACKGROUND: In addition to its conventional use as a treatment for refractory neuropathic extremity pain, spinal cord stimulation (SCS) has recently emerged as a possible treatment for visceral and arthritic pain. But concurrent with the expansion of possible conditions amenable to SCS, other studies have questioned the long-term efficacy of SCS for traditional indications. These disparate findings argue strongly for the refinement of selection criteria. The purpose of this study is to identify correlates of outcome for SCS. METHODS: Data were retrospectively collected on 244 patients who underwent a SCS trial at two academic medical centers. Success was predefined as ≥50% pain relief sustained for ≥6 months. Variables analyzed for their association with outcome included demographics, location of pain, diagnosis, presence of coexisting diseases, pain descriptors, opioid and adjuvant medication use, duration and pain relief during trial, and complications. RESULTS: The presence of allodynia and/or hyperalgesia correlated with both a positive SCS trial (P = 0.01) and long-term implantation outcome (P = 0.05). History of substance abuse was associated with a negative permanent SCS outcome (P = 0.05) but bore no relationship to trial results. The variable most strongly associated with an SCS outcome was experiencing <50% pain relief during the trial, which strongly presaged a negative result (P < 0.001). CONCLUSIONS: Although weak associations with outcome were noted for several clinical variables, none was strongly associated with trial and permanent implantation results. The strongest predictor of a negative SCS outcome was obtaining <50% pain relief during the trial period.

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 > or =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 $6,286, $17,142, and $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.

Outcome predictors for sacroiliac joint (lateral branch) radiofrequency denervation.

BACKGROUND AND OBJECTIVE: Sacroiliac (SI) joint pain is a challenging condition characterized by limited treatment options. Recently, numerous studies have reported excellent intermediate-term outcomes after lateral-branch radiofrequency (RF) denervation, but these studies are characterized by wide variability in technique, selection criteria, and patient characteristics. The purpose of this study was to determine whether any demographic or clinical variables can be used to predict SI joint RF denervation outcome. METHODS: Seventy-seven patients with refractory, injection-confirmed SI joint pain underwent SI joint denervation at 2 academic institutions. A composite binary variable "successful" outcome was predefined as greater than 50% reduction in pain lasting at least 6 months coupled with a positive global perceived effect. Secondary outcome measures included Oswestry Disability Index scores, medication reduction, and retention on active duty for soldiers. Factors retrospectively evaluated for their association with outcome included demographic variables, duration of pain, opioid usage, pain referral pattern, physical examination signs, number of blocks and percentage of pain relief after SI joint injection, prognostic lateral-branch blocks, previous surgery, levels lesioned, RF technique, disability status, and coexisting medical conditions. RESULTS: Forty patients (52%) obtained a positive outcome. In multivariate analysis, preprocedure pain intensity, age older than 65 years, and pain radiating below the knee were significant predictors of failure. A trend was noted whereby patients receiving regular opioid therapy were more likely to experience a negative outcome. The use of cooled, rather than conventional RF, was associated with a higher percentage of positive outcomes. CONCLUSIONS: Whereas several factors were found to influence outcome, no single clinical variable reliably predicted treatment results. The use of more stringent selection criteria was not associated with better outcomes.

Comparison of fluoroscopically guided and blind corticosteroid injections for greater trochanteric pain syndrome: multicentre randomised controlled trial.

OBJECTIVE: To determine whether fluoroscopic guidance improves outcomes of injections for greater trochanteric pain syndrome. DESIGN: Multicentre double blind randomised controlled study. SETTING: Three academic and military treatment facilities in the United States and Germany. PARTICIPANTS: 65 patients with a clinical diagnosis of greater trochanteric pain syndrome. INTERVENTIONS: Injections of corticosteroid and local anaesthetic into the trochanteric bursa, using fluoroscopy (n=32) or landmarks (that is, "blind" injections; n=33) for guidance. PRIMARY OUTCOME MEASURES: 0-10 numerical rating scale pain scores at rest and with activity at one month (positive categorical outcome predefined as >or=50% pain reduction either at rest or with activity, coupled with positive global perceived effect). Secondary outcome measures included Oswestry disability scores, SF-36 scores, reduction in drug use, and patients' satisfaction. RESULTS: No differences in outcomes occurred favouring either the fluoroscopy or blind treatment groups. One month after injection the average pain scores were 2.7 at rest and 5.0 with activity in the fluoroscopy group compared with 2.2 and 4.0 in the blind injection group. Three months after the injection, 15 (47%) patients in the blind group and 13 (41%) in the fluoroscopy group continued to have a positive outcome. CONCLUSION: Although using fluoroscopic guidance dramatically increases treatment costs for greater trochanteric pain syndrome, it does not necessarily improve outcomes. TRIAL REGISTRATION: Clinical trials NCT00480675.

Lumbar zygapophysial (facet) joint radiofrequency denervation success as a function of pain relief during diagnostic medial branch blocks: a multicenter analysis.

BACKGROUND CONTEXT: The publication of several recent studies showing minimal benefit for radiofrequency (RF) lumbar zygapophysial (l-z) joint denervation have led many investigators to reevaluate selection criteria. One controversial explanation for these findings is that the most commonly used cutoff value for selecting patients for l-z (facet) joint RF denervation, greater than 50% pain relief after diagnostic blocks, is too low and hence responsible for the high failure rate. PURPOSE: To compare l-z joint RF denervation success rates between the conventional greater than or equal to 50% pain relief threshold and the more stringently proposed greater than or equal to 80% cutoff for diagnostic medial branch blocks (MBB). STUDY DESIGN/SETTING: Multicenter, retrospective clinical data analysis. PATIENT SAMPLE: Two hundred and sixty-two patients with chronic low back pain who underwent l-z RF denervation at three pain clinics. OUTCOME MEASURES: Outcome measures were greater than 50% pain relief based on visual analog scale or numerical pain rating score after RF denervation persisting at least 6 months postprocedure, and global perceived effect (GPE), which considered pain relief, satisfaction and functional improvement. METHODS: Data were garnered at three centers on 262 patients who underwent l-z RF denervation after obtaining greater than or equal to 50% pain relief after diagnostic MBB. Subjects were separated into those who received partial (greater than or equal to 50% but less than 80%) and near-complete (greater than or equal to 80%) pain relief from the MBB. Outcomes between groups were compared with multivariate analysis after controlling for 14 demographic and clinical variables. RESULTS: One hundred and forty-five patients obtained greater than or equal to 50% but less than 80% pain relief after diagnostic MBB, and 117 patients obtained greater than or equal to 80% relief. In the greater than or equal to 50% group, success rates were 52% and 67% based on pain relief and GPE, respectively. Among patients who experienced greater than 80% relief from diagnostic blocks, 56% obtained greater than or equal to 50% relief from RF denervation and 66% had a positive GPE. CONCLUSIONS: Using more stringent pain relief criteria when selecting patients for l-z joint RF denervation is unlikely to improve success rates, and may lead to misdiagnosis and withholding a potentially valuable treatment from good candidates.

Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice.

Epitope vaccines have shown promise for inducing cellular immune responses in animal models of infectious disease. In cases where cellular immunity was augmented, peptide vaccines composed of covalently linked minimal cytotoxic T-lymphocyte (CTL) and T-helper (T(H)) epitopes generally showed the most efficacy. To address a clinical vaccine strategy for cytomegalovirus (CMV) in the context of HCT (hematopoietic cell transplantation), we observed that linking the synthetically derived pan-DR epitope peptide (PADRE) or one of several tetanus T(H) epitopes to the immunodominant human leukocyte antigen (HLA) A*0201-restricted CTL epitope from CMV-pp65 to create a fusion peptide caused robust cytotoxic cellular immune responses in HLA A*0201/K(b) transgenic mice. Significantly, the fusion peptides are immunogenic when administered in saline solution by either subcutaneous or intranasal routes. CpG-containing single-stranded DNA (ss-oligodeoxynucleotide [ODN]) added to the fusion peptides dramatically up-regulated immune recognition by either route. Notably, target cells that either expressed full-length pp65 protein from vaccinia viruses or were sensitized with the CTL epitope encoded in the vaccine were recognized by splenic effectors from immunized animals. Visualization of murine peptide-specific CTL by flow cytometry was accomplished using an HLA A*0201 tetramer complexed with the pp65(495-503) CTL epitope. T(H)-CTL epitope fusion peptides in combination with CpG ss-ODN represent a new strategy for parenteral or mucosal delivery of vaccines in a safe and effective manner that has applicability for control or prophylaxis of infectious disease, especially in situations such as vaccination of donors or recipients of HCT, where highly inflammatory adjuvants are not desired.

Characterization of cytotoxic function of CMV-pp65-specific CD8+ T-lymphocytes identified by HLA tetramers in recipients and donors of stem-cell transplants.

BACKGROUND: Human cytomegalovirus (CMV) is a ubiquitous herpesvirus that is an important complication of bone marrow and allogeneic stem-cell transplant (HSCT). CD8 T-lymphocytes have an important role in immunity against CMV, but correlation between antigen-specific subpopulations of these cells and protection are still unclear. METHODS: Flow analysis with fluorescently-conjugated human leukocyte antigen (HLA) class I tetramers (Tet) was used to investigate levels of CMV-specific CD8 T-lymphocytes in peripheral blood monocyte cells (PBMC) samples from HSCT donors and recipients and their ability to produce interferon (IFN)-gamma on stimulation with either CMV antigenic peptide or nonspecific mitogenic stimulation. Chromium release assays were used to evaluate ex vivo CMV-specific cytotoxicity associated with the PBMC samples. RESULTS: Use of Tet in conjunction with fluorescently conjugated anti-T-cell receptor (TCR) beta-chain variable (Vbeta) monoclonal antibodies indicated that the Vbeta repertoires associated with Tet cells seen in two HSCT recipients were similar to the Vbeta repertoires of the Tet cells in their HSCT donors. Significant ex vivo cytotoxicity against peptide-loaded targets was measured from several recipient samples after transplant. However, PBMC from the HSCT donors, even when containing populations of CMV-specific Tet cells capable of secreting IFN-gamma in response to peptide stimulation, possessed no ex vivo CMV-specific cytotoxicity. CONCLUSIONS: We hypothesize that in the setting of the reconstituting immune system of HSCT recipients, CMV reactivation may stimulate a functional change in CMV-specific CD8 T-lymphocytes, rendering them able to directly lyse target cells presenting CMV antigens without in vitro stimulation. These findings have important implications for development of vaccines designed to induce protective cellular immunity to CMV in transplant recipients.