Durable responses at 24 months with high-frequency spinal cord stimulation for nonsurgical refractory back pain.

OBJECTIVE: The objective of this study was to evaluate the 24-month durability of pain relief, function, quality of life, and safety outcomes for patients with nonsurgical refractory back pain (NSRBP) treated with high-frequency spinal cord stimulation (SCS) within a large, national, multicenter randomized controlled trial (RCT). METHODS: Following the completion of an RCT comparing high-frequency SCS plus CMM with CMM alone for the treatment of NSRBP, patients gave additional consent for a follow-up extension to 24 months. Presented is the cohort analysis of all patients treated with high-frequency SCS following the optional crossover at 6 months. The outcomes assessed to 24 months included responder rate of ≥ 50% pain relief measured according to the visual analog scale [VAS]), disability (Oswestry Disability Index [ODI]), quality of life (EQ-5D 5-level [EQ-5D-5L]), opioid reduction. RESULTS: Of the 125 patients who received a permanent implant, 121 completed the 12-month follow-up, 101 gave additional consent for extended follow-up, and 98 completed the 24-month follow-up. At 24 months after implantation, the mean back pain VAS score was reduced by 73% and the responder rate was 82%. ODI and EQ-5D-5L both improved by at least double the minimal clinically important difference for each measure. No unexpected adverse events were observed, and the rates of serious adverse events (3.4%) and device explantations (4.8%) were low. CONCLUSIONS: The addition of high-frequency SCS to CMM in patients with NSRBP offers profound improvements at 24 months in pain, function, quality of life, and reduced opioid use. This study provides much-needed evidence to inform current clinical practice for managing patients with NSRBP.

Cost-effectiveness of 10-kHz spinal cord stimulation therapy compared with conventional medical management over the first 12 months of therapy for patients with nonsurgical back pain: randomized controlled trial.

OBJECTIVE: This analysis evaluated if spinal cord stimulation (SCS) at 10 kHz plus conventional medical management (CMM) is cost-effective compared with CMM alone for the treatment of nonsurgical refractory back pain (NSRBP). METHODS: NSRBP subjects were randomized 1:1 into the 10-kHz SCS (n = 83) or CMM (n = 76) group. Outcomes assessed at 6 months included EQ-5D 5-level (EQ-5D-5L), medication usage, and healthcare utilization (HCU). There was an optional crossover at 6 months and follow-up to 12 months. The incremental cost-effectiveness ratio (ICER) was calculated with cost including all HCU and medications except for the initial device and implant procedure, and cost-effectiveness was analyzed based on a willingness-to-pay threshold of < $50,000 per quality-adjusted life-year. RESULTS: Treatment with 10-kHz SCS resulted in a significant improvement in quality of life (QOL) over CMM (EQ-5D-5L index score change of 0.201 vs -0.042, p < 0.001) at a lower cost, based on reduced frequency of HCU resulting in an ICER of -$4964 at 12 months. The ICER was -$8620 comparing the 6 months on CMM with postcrossover on 10-kHz SCS. CONCLUSIONS: Treatment with 10-kHz SCS provides higher QOL at a lower average cost per patient compared with CMM. Assuming an average reimbursement for device and procedure, 10-kHz SCS therapy is predicted to be cost-effective for the treatment of NSRBP compared with CMM within 2.1 years.

Treatment of nonsurgical refractory back pain with high-frequency spinal cord stimulation at 10 kHz: 12-month results of a pragmatic, multicenter, randomized controlled trial.

OBJECTIVE: Spinal cord stimulation (SCS) at 10 kHz (10-kHz SCS) is a safe and effective therapy for treatment of chronic low-back pain. However, it is unclear from existing evidence whether these findings can be generalized to patients with chronic back pain that is refractory to conventional medical management (CMM) and who have no history of spine surgery and are not acceptable candidates for spine surgery. The authors have termed this condition "nonsurgical refractory back pain" (NSRBP) and conducted a multicenter, randomized controlled trial to compare CMM with and without 10-kHz SCS in this population. METHODS: Patients with NSRBP, as defined above and with a spine surgeon consultation required for confirmation, were randomized 1:1 to patients undergoing CMM with and without 10-kHz SCS. CMM included nonsurgical treatment for back pain, according to physicians' best practices and clinical guidelines. Primary and secondary endpoints included the responder rate (≥ 50% pain relief), disability (Oswestry Disability Index [ODI]), global impression of change, quality of life (EQ-5D-5L), and change in daily opioid use and were analyzed 3 and 6 months after randomization. The protocol allowed for an optional crossover at 6 months for both arms, with observational follow-up over 12 months. RESULTS: In total, 159 patients were randomized; 76 received CMM, and 69 (83.1%) of the 83 patients who were assigned to the 10-kHz SCS group received a permanent implant. At the 3-month follow-up, 80.9% of patients who received stimulation and 1.3% of those who received CMM were found to be study responders (primary outcome, ≥ 50% pain relief; p < 0.001). There was also a significant difference between the treatment groups in all secondary outcomes at 6 months (p < 0.001). In the 10-kHz SCS arm, outcomes were sustained, including a mean 10-cm visual analog scale score of 2.1 ± 2.3 and 2.1 ± 2.2 and mean ODI score of 24.1 ± 16.1 and 24.0 ± 17.0 at 6 and 12 months, respectively (p = 0.9). In the CMM arm, 74.7% (56/75) of patients met the criteria for crossover and received an implant. The crossover arm obtained a 78.2% responder rate 6 months postimplantation. Five serious adverse events occurred (procedure-related, of 125 total permanent implants), all of which resolved without sequelae. CONCLUSIONS: The study results, which included follow-up over 12 months, provide important insights into the durability of 10-kHz SCS therapy with respect to chronic refractory back pain, physical function, quality of life, and opioid use, informing the current clinical practice for pain management in patients with NSRBP.

Pain relief and opioid usage in upper limb and neck pain patients after 10-kHz spinal cord stimulation treatment: subanalysis of USA studies.

Aim: It is argued that chronic pain patients who reduce/eliminate their opioids may have compromised pain relief. This study therefore aimed to analyze if reduced opioid consumption associated with 10-kHz spinal cord stimulation adversely affected pain relief. Methods: Post hoc analysis was performed on data from two prospective studies in subjects with upper limbs and neck pain conducted in USA. Results & conclusion: A 10-kHz spinal cord stimulation treatment was associated with reduction in mean visual analog scale scores for upper limbs and neck pain and mean daily opioid consumption. Pain scores decreased in subjects who decreased opioid use and in those who maintained/increased use. Opioid reduction and pain relief was also achieved in subjects taking >90 mg morphine equivalents of opioids at baseline.

Ten kilohertz SCS for Treatment of Chronic Upper Extremity Pain (UEP): Results from Prospective Observational Study.

BACKGROUND: Chronic upper extremity pain (UEP) has complex etiologies and is often disabling. It has been shown that 10 kHz SCS can provide paresthesia-free and durable pain relief in multiple pain types and improve the quality of life of patients. OBJECTIVE: To gain additional evidence on the safety and effectiveness of 10 kHz SCS for the treatment of chronic UEP. STUDY DESIGN: It was a prospective, multicenter, and observational study. The study was registered on ClinicalTrials.gov prospectively (clinical trial identifier: NCT02703818). SETTING: Multicenter. PATIENTS INTERVENTION AND MAIN OUTCOMES: A total of 43 subjects with chronic UEP of ≥5 cm (on a 0-10 cm visual analog scale; VAS) underwent a trial of 10 kHz SCS, and subjects with ≥40% pain relief received a permanent implant. All subjects had upper limb pain at baseline, while some had concomitant shoulder or neck pain. Subject outcomes were assessed for 12 months, and the primary outcome was the responder rate (percentage of subjects experiencing ≥50% pain relief from baseline) at three months. RESULTS: Thirty-eight subjects successfully completed the trial (88.3% success rate), 33 received permanent implants (five withdrew consent), and 32 had device activation (per protocol population). There were no paresthesias or uncomfortable changes in stimulation related to changes in posture during the study and there were no neurological deficits. Responder rates at 12 months for upper limb, shoulder, and neck pain in per protocol population (N=32) were 78.1%, 85.2%, and 75.0%, respectively. At 12 months, 84.4% of subjects were satisfied or very satisfied with 10 kHz SCS, and 38.7% either reduced or eliminated opioid usage. CONCLUSION: This study further supports the effectiveness of 10 kHz SCS for chronic UEP treatment and documents the safety profile of the therapy. CLINICAL TRIAL IDENTIFIER: NCT02703818.

Effects of improved water, sanitation, and hygiene and improved complementary feeding on environmental enteric dysfunction in children in rural Zimbabwe: A cluster-randomized controlled trial.

BACKGROUND: Environmental enteric dysfunction (EED) may be an important modifiable cause of child stunting. We described the evolution of EED biomarkers from birth to 18 months in rural Zimbabwe and tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF), on EED. METHODOLOGY AND FINDINGS: The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial was a 2x2 factorial cluster-randomised trial of improved IYCF and improved WASH on child stunting and anaemia at 18 months of age. 1169 infants born to HIV-negative mothers provided plasma and faecal specimens at 1, 3, 6, 12, and 18 months of age. We measured EED biomarkers that reflect all domains of the hypothesized pathological pathway. Markers of intestinal permeability and intestinal inflammation declined over time, while markers of microbial translocation and systemic inflammation increased between 1-18 months. Markers of intestinal damage (I-FABP) and repair (REG-1ß) mirrored each other, and citrulline (a marker of intestinal epithelial mass) increased from 6 months of age, suggesting dynamic epithelial turnover and regeneration in response to enteric insults. We observed few effects of IYCF and WASH on EED after adjustment for multiple comparisons. The WASH intervention decreased plasma IGF-1 at 3 months (ß:0.89, 95%CI:0.81,0.98) and plasma kynurenine at 12 months (ß: 0.92, 95%CI:0.87,0.97), and increased plasma IGF-1 at 18 months (ß:1.15, 95%CI:1.05,1.25), but these small WASH effects did not translate into improved growth. CONCLUSIONS: Overall, we observed dynamic trends in EED but few effects of IYCF or WASH on biomarkers during the first 18 months after birth, suggesting that these interventions did not impact EED. Transformative WASH interventions are required to prevent or ameliorate EED in low-income settings.

Penalized regression models to select biomarkers of environmental enteric dysfunction associated with linear growth acquisition in a Peruvian birth cohort.

Environmental enteric dysfunction (EED) is associated with chronic undernutrition. Efforts to identify minimally invasive biomarkers of EED reveal an expanding number of candidate analytes. An analytic strategy is reported to select among candidate biomarkers and systematically express the strength of each marker's association with linear growth in infancy and early childhood. 180 analytes were quantified in fecal, urine and plasma samples taken at 7, 15 and 24 months of age from 258 subjects in a birth cohort in Peru. Treating the subjects' length-for-age Z-score (LAZ-score) over a 2-month lag as the outcome, penalized linear regression models with different shrinkage methods were fitted to determine the best-fitting subset. These were then included with covariates in linear regression models to obtain estimates of each biomarker's adjusted effect on growth. Transferrin had the largest and most statistically significant adjusted effect on short-term linear growth as measured by LAZ-score-a coefficient value of 0.50 (0.24, 0.75) for each log2 increase in plasma transferrin concentration. Other biomarkers with large effect size estimates included adiponectin, arginine, growth hormone, proline and serum amyloid P-component. The selected subset explained up to 23.0% of the variability in LAZ-score. Penalized regression modeling approaches can be used to select subsets from large panels of candidate biomarkers of EED. There is a need to systematically express the strength of association of biomarkers with linear growth or other outcomes to compare results across studies.

Force perception at the shoulder after a unilateral suprascapular nerve block.

There are two key sources of information that can be used to match forces-the centrally generated sense of effort and afferent signals from mechanical receptors located in peripheral tissues. There is currently no consensus on which source of information is more important for matching forces. The corollary discharge hypothesis argues that subjects match forces using the centrally generated sense of effort. The purpose of this study was to investigate force matching at the shoulder before and after a suprascapular nerve block. The nerve block creates a sensory and muscle force mismatch between sides when matching loads. The torque matching accuracy did not change after the nerve block was administered. Directionally, the torque error was in the direction proposed by the corollary discharge hypothesis. However, the mismatch between deltoid EMG was substantially greater compared to the changes in the torque matching error after the block. The results support that sensory information is used during force matching tasks. However, since the nerve block also created a sensory disruption between sides, it is not clear how sensory information is reweighted following the nerve block and a role for sense of effort is still implicated.

Enhancement of Meditation Analgesia by Opioid Antagonist in Experienced Meditators.

OBJECTIVE: Studies have consistently shown that long-term meditation practice is associated with reduced pain, but the neural mechanisms by which long-term meditation practice reduces pain remain unclear. This study tested endogenous opioid involvement in meditation analgesia associated with long-term meditation practice. METHODS: Electrical pain was induced with randomized, double-blind, cross-over administration of the opioid antagonist naloxone (0.15-mg/kg bolus dose, then 0.2-mg/kg per hour infusion dose) with 32 healthy, experienced meditation practitioners and a standardized open monitoring meditation. RESULTS: Under saline, pain ratings were significantly lower during meditation (pain intensity: 6.41 ± 1.32; pain unpleasantness: 3.98 ± 2.17) than at baseline (pain intensity: 6.86 ±1.04, t(31) = 2.476, p = .019, Cohen's d = 0.46; pain unpleasantness: 4.96 ±1.75, t(31) = 3.746, p = .001, Cohen's d = 0.68), confirming the presence of meditation analgesia. Comparing saline and naloxone revealed significantly lower pain intensity (t(31) = 3.12, p = .004, d = 0.56), and pain unpleasantness (t(31) = 3.47, p = .002, d = 0.62), during meditation under naloxone (pain intensity: 5.53 ± 1.54; pain unpleasantness: 2.95 ± 1.88) than under saline (pain intensity: 6.41 ± 1.32; pain unpleasantness: 3.98 ± 2.17). Naloxone not only failed to eliminate meditation analgesia but also made meditation analgesia stronger. CONCLUSIONS: Long-term meditation practice does not rely on endogenous opioids to reduce pain. Naloxone's blockade of opioid receptors enhanced meditation analgesia; pain ratings during meditation were significantly lower under naloxone than under saline. Possible biological mechanisms by which naloxone-induced opioid receptor blockade enhances meditation analgesia are discussed.

The contribution of the supraspinatus muscle at sub-maximal contractions.

During maximum effort, the supraspinatus muscle contributes approximately 50% of the torque need to elevate the arm, but this has not been examined at sub-maximal levels. The purpose of this study was to determine the contribution of the supraspinatus muscle to shoulder elevation at sub-maximal levels. Seven healthy subjects (four males, three females) performed isometric ramp contractions at the shoulder. Middle deltoid electromyography (EMG) and force applied at the wrist were collected before and after a suprascapular nerve block. For the same level of deltoid EMG, less external force will be measured after the nerve block as the supraspinatus muscle no longer contributes. The difference between the EMG/force curve was the contribution of the supraspinatus muscle. The supraspinatus contributed 40%, 95% CI [32%-48%], to shoulder elevation. The effect of angle (p = .67) and % maximal voluntary contraction (p = .13) on supraspinatus contribution were not significant. The maximum is slightly less than reported in a previous suprascapular nerve block study using maximal contractions. The results from this study can be used to assess supraspinatus contribution in rotator cuff tears, after rehabilitation interventions, and as a restraint in computation modelling.

Age and Sex Normalization of Intestinal Permeability Measures for the Improved Assessment of Enteropathy in Infancy and Early Childhood: Results From the MAL-ED Study.

OBJECTIVES: The aim of the study was to describe changes in intestinal permeability in early childhood in diverse epidemiologic settings. METHODS: In a birth cohort study, the lactulose:mannitol (L:M) test was administered to 1980 children at 4 time points in the first 24 months of life in 8 countries. Data from the Brazil site with an incidence of diarrhea similar to that seen in the United States and no growth faltering was used as an internal study reference to derive age- and sex-specific z scores for mannitol and lactulose recoveries and the L:M ratio. RESULTS: A total of 6602 tests demonstrated mannitol recovery, lactulose recovery, and the L:M ratio were associated with country, sex, and age. There was heterogeneity in the recovery of both probes between sites with mean mannitol recovery ranging for 1.34% to 5.88%, lactulose recovery of 0.19% to 0.58%, and L:M ratios 0.10 to 0.17 in boys of 3 months of age across different sites. We observed strong sex-specific differences in both mannitol and lactulose recovery, with boys having higher recovery of both probes. Alterations in intestinal barrier function increased in most sites from 3 to 9 months of age and plateaued or diminished from 9 to 15 months of age. CONCLUSIONS: Alterations in recovery of the probes differ markedly in different epidemiologic contexts in children living in the developing world. The rate of change in the L:M-z ratio was most rapid and consistently disparate from the reference standard in the period between 6 and 9 months of age, suggesting that this is a critical period of physiologic impact of enteropathy in these populations.

Plasma Tryptophan and the Kynurenine-Tryptophan Ratio are Associated with the Acquisition of Statural Growth Deficits and Oral Vaccine Underperformance in Populations with Environmental Enteropathy.

Early childhood enteric infections have adverse impacts on child growth and can inhibit normal mucosal responses to oral vaccines, two critical components of environmental enteropathy. To evaluate the role of indoleamine 2,3-dioxygenase 1 (IDO1) activity and its relationship with these outcomes, we measured tryptophan and the kynurenine-tryptophan ratio (KTR) in two longitudinal birth cohorts with a high prevalence of stunting. Children in rural Peru and Tanzania (N = 494) contributed 1,251 plasma samples at 3, 7, 15, and 24 months of age and monthly anthropometrics from 0 to 36 months of age. Tryptophan concentrations were directly associated with linear growth from 1 to 8 months after biomarker assessment. A 1-SD increase in tryptophan concentration was associated with a gain in length-for-age Z-score (LAZ) of 0.17 over the next 6 months in Peru (95% confidence interval [CI] = 0.11-0.23, P < 0.001) and a gain in LAZ of 0.13 Z-scores in Tanzania (95% CI = 0.03-0.22, P = 0.009). Vaccine responsiveness data were available for Peru only. An increase in kynurenine by 1 µM was associated with a 1.63 (95% CI = 1.13-2.34) increase in the odds of failure to poliovirus type 1, but there was no association with tetanus vaccine response. A KTR of 52 was 76% sensitive and 50% specific in predicting failure of response to serotype 1 of the oral polio vaccine. KTR was associated with systemic markers of inflammation, but also interleukin-10, supporting the association between IDO1 activity and immunotolerance. These results strongly suggest that the activity of IDO1 is implicated in the pathophysiology of environmental enteropathy, and demonstrates the utility of tryptophan and kynurenine as biomarkers for this syndrome, particularly in identifying those at risk for hyporesponsivity to oral vaccines.

Lactulose: mannitol diagnostic test by HPLC and LC-MSMS platforms: considerations for field studies of intestinal barrier function and environmental enteropathy.

OBJECTIVES: The lactulose:mannitol (L:M) diagnostic test is frequently used in field studies of environmental enteropathy (EE); however, heterogeneity in test administration and disaccharide measurement has limited the comparison of results between studies and populations. We aim to assess the agreement between L:M measurement between high-performance liquid chromatography with pulsed amperometric detection (HPLC-PAD) and liquid chromatography-tandem mass spectrometry (LC-MSMS) platforms. METHODS: The L:M test was administered in a cohort of Peruvian infants considered at risk for EE. A total of 100 samples were tested for lactulose and mannitol at 3 independent laboratories: 1 running an HPLC-PAD platform and 2 running LC-MSMS platforms. Agreement between the platforms was estimated. RESULTS: The Spearman correlation between the 2 LC-MSMS platforms was high (ρ ≥ 0.89) for mannitol, lactulose, and the L:M ratio. The correlation between the HPLC-PAD platform and LC-MSMS platform was ρ = 0.95 for mannitol, ρ = 0.70 for lactulose, and ρ = 0.43 for the L:M ratio. In addition, the HPLC-PAD platform overestimated the lowest disaccharide concentrations to the greatest degree. CONCLUSIONS: Given the large analyte concentration range, the improved accuracy of LC-MSMS has important consequences for the assessment of lactulose and mannitol following oral administration in populations at risk for EE. We recommend that researchers wishing to implement a dual-sugar test as part of a study of EE use an LC-MSMS platform to optimize the accuracy of results and increase comparability between studies.

Humeral head translation after a suprascapular nerve block.

Subacromial impingement syndrome is the most common shoulder disorder. Abnormal superior translation of the humeral head is believed to be a major cause of this pathology. The first purpose of the study was to examine the effects of suprascapular nerve block on superior translation of the humeral head and scapular upward rotation during dynamic shoulder elevation. The secondary purpose was to assess muscle activation patterns during these motions. Twenty healthy subjects participated in the study. Using fluoroscopy and electromyography, humeral head translation and muscle activation were measured before and after a suprascapular nerve block. The humeral head was superiorly located at 60 degrees of humeral elevation, and the scapula was more upwardly rotated from 30 to 90 degrees of humeral elevation after the block. The differences were observed during midrange of motion. In addition, the deltoid muscle group demonstrated increased muscle activation after the nerve block. The study's results showed a compensatory increase in humeral head translation, scapular upward rotation, and deltoid muscle activation due to the nerve block. These outcomes suggest that increasing muscular strength and endurance of the supraspinatus and infraspinatus muscles could prevent any increased superior humeral head translation. This may be beneficial in reducing shoulder impingement or rotator cuff tears over time.

Sensor-driven position-adaptive spinal cord stimulation for chronic pain.

BACKGROUND: Variation in the intensity of neurostimulation due to body position is a practical problem for many patients implanted with spinal cord stimulation (SCS) systems because positional changes may result in overstimulation or understimulation that leads to frequent need for compensatory manual programming adjustments. OBJECTIVES: The purpose of this study was to assess the safety and effectiveness of a novel type of SCS therapy designed to automatically adapt stimulation amplitude in response to changes in a patient's position or activity.The primary objective of the study was to demonstrate that automatic position adaptive SCS benefited patients in terms of pain relief and/or convenience compared with neurostimulation adjusted with conventional manual programming. Secondary objectives included assessment of worsened pain relief with automatic adjustment; change in pain score; and the number of manual programming adjustments with position-adaptive neurostimulation compared with manual programming. STUDY DESIGN: Prospective, multicenter, open-label, randomized crossover study. SETTING: Ten interventional pain management centers in the US. METHODS: Patients were enrolled a minimum of one week after a successful SCS screening trial. They were then implanted with the RestoreSensor neurostimulation device (Medtronic, Inc., Minneapolis, MN) that could be programmed to either automatic position-adaptive stimulation (AdaptiveStim) or manual adjustment of stimulation parameters. After implant, all devices were programmed to conventional manual adjustment for a 4-week postoperative period. The patients were then randomized to either conventional manual programming adjustment or position-adaptive stimulation with crossover to the opposite treatment arm occurring at 6 weeks after randomization. The patients were followed for another 6 weeks after crossover. This study was conducted under an FDA-approved Investigational Device Exemption (IDE) and approval of the responsible Institutional Review Boards (IRBs) of the study centers. RESULTS: Seventy-nine patients were enrolled in the study. In an intent-to-treat analysis, 86.5% of patients achieved the primary objective of improved pain relief with no loss of convenience or improved convenience with no loss of pain relief using automatic position-adaptive stimulation compared with using conventional manual programming adjustment alone. This was statistically significantly greater than the predefined minimum success rate of 25%, p < 0.001 (exact one-sided 97.5% lower confidence limit was 76.5%). Only 2.8% of patients reported worsened pain relief during position-adaptive stimulation compared with manual programming. There was a statistically significant reduction in the mean numeric pain rating scale score compared with baseline scores in both treatment arms. Additionally, position-adaptive stimulation demonstrated a statistically significant 41% reduction in the daily average number of programming button presses for amplitude adjustment compared with manual programming (18.2 per day versus 30.7 per day, P = 0.002). Functional improvements reported with position-adaptive stimulation included: improved comfort during position changes (80.3%); improved activity (69%); and improved sleep (47.9%). Adverse events associated with uncomfortable sensations from stimulation did not differ significantly between treatment arms. The incidence of device-related serious adverse events was 3.9%. LIMITATIONS: Patients and physicians were not blinded to whether devices were programmed to automatic position-adaptive stimulation or manual adjustment. Responses to assessment questionnaires were based on patient recall. CONCLUSIONS: The study demonstrated that automatic position-adaptive stimulation is safe and effective in providing benefits in terms of patient-reported improved pain relief and convenience compared with using manual programming adjustment alone. CLINICAL TRIAL: NCT01106404.

Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain.

OBJECTIVE: To assess the safety and efficacy of adding intrathecal ziconotide to intrathecal morphine in patients being treated with a stable intrathecal morphine dose. DESIGN: Phase II, multicenter, open-label study with a 5-week titration phase and an extension phase. SETTING: Outpatient clinics. PATIENTS: Patients with suboptimal pain relief receiving stable intrathecal morphine doses (2-20 mg/day). INTERVENTIONS: Intrathecal morphine dosing remained constant during the titration phase. Ziconotide therapy began at 0.60 microg/day and was titrated to a maximum of 7.2 microg/day. During the extension phase, ziconotide and intrathecal morphine dosing were adjusted at the investigator's discretion. OUTCOME MEASURES: Safety was assessed primarily via adverse event reports. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. RESULTS: Twenty-six patients were enrolled. Treatment-emergent adverse events were generally mild or moderate; the most common (> or = 15% of patients in either study phase) study drug-related (i.e., ziconotide/morphine combination [or ziconotide monotherapy in the extension phase only]) events were confusion, dizziness, abnormal gait, hallucinations, and anxiety. The mean percentage improvement in visual analog scale of pain intensity scores was 14.5% (95% confidence interval: -9.4% to 38.5%) from baseline to week 5 and varied during the extension phase (range: -0.4% to 42.8%). Mean percentage change from baseline in systemic opioid consumption was -14.3% at week 5 and varied considerably during the extension phase. CONCLUSIONS: Ziconotide, combined with stable intrathecal morphine, may reduce pain and decrease systemic opioid use in patients with pain inadequately controlled by intrathecal morphine alone.

Suprascapular nerve block results in a compensatory increase in deltoid muscle activity.

A balance exists between the deltoid and rotator cuff contribution to arm elevation. Both cadaver and computer models have predicted an increase in deltoid muscle force with dysfunction of the rotator cuff. The goal of the present study was to verify this phenomenon in vivo by examining the effects of paralysis of the supraspinatus and infraspinatus muscles with a suprascapular nerve block on the electrical activity of seven shoulder muscles. Electromyographic data were collected before and after the administration of the block. The block resulted in a significant increase in muscle activity for all heads of the deltoid, with a higher percentage increase noted at lower elevation angles. Although the deltoid activity was reduced as the subjects recovered from the block, even low levels of cuff dysfunction were found to result in increased deltoid activity. These results suggest that even small disruptions in the normal function of some rotator cuff muscles (e.g., due to fatigue or impingement syndrome), may result in an increase in deltoid activity. It is possible that such compensation may result in higher superior loads at the glenohumeral joint, possibly increasing the risk of tendon damage.

Suprascapular nerve block disrupts the normal pattern of scapular kinematics.

BACKGROUND: Patients with full thickness rotator cuff tears typically demonstrate an increase in scapular motion, both in the clinic and under controlled laboratory conditions. To better understand the mechanisms behind this pattern of motion, we propose a suprascapular nerve block as an appropriate model of dysfunction of the supraspinatus and infraspinatus, which are the two tendons most commonly affected in cuff tear patients. METHODS: Healthy subjects underwent testing for 3D scapular kinematics with a Polhemus magnetic tracking device and isometric force measurements during external rotation. A suprascapular nerve block was then performed with the injection of lidocaine into the suprascapular notch of each subject. Scapular kinematics and isometric force measurements were repeated after confirmation of the block. FINDINGS: The nerve block resulted in no significant changes in clavicular rotations and scapular posterior tilting. However, there was a significant increase in scapular external rotation and upward rotation. While kinematic changes returned to baseline within 25 min of the block, force measurements did not return to baseline until 75 min post-block. Interpretation. The results of this study, especially those for upward rotation, are in general agreement with what has been found for patients with rotator cuff tears. While the supraspinatus and infraspinatus do not directly control the movement of the scapula, they appear to result in a compensatory change in scapular motion. Although more work needs to be done, it appears that abnormal scapular motion patterns observed in patients with cuff tears may therefore be compensatory in nature.

Long-term intrathecal opioid therapy with a patient-activated, implanted delivery system for the treatment of refractory cancer pain.

The present study evaluated the safety and efficacy of patient-activated delivery of intrathecal morphine sulfate boluses delivered by way of a novel internalized intrathecal delivery system. Patients with refractory cancer pain or uncontrollable side effects were enrolled at 17 US and international sites in this prospective, open-label study. Pain relief, reduction in systemic opioid use, and reduction in opioid-related complications were analyzed both individually and together as a measure of overall success. One hundred forty-nine patients were enrolled and 119 were implanted. Average numeric analog scale pain decreased from 6.1 to 4.2 at 1 month and was maintained through month 7 (P <.01) and through month 13 (P <.05). Systemic opioid use was significantly decreased throughout the study (P <.01). Significant reduction in the opioid complication severity index was demonstrated at all 4 follow-up visits (P <.01). Overall success (>/=50% reduction in numeric analog scale pain, use of systemic opioids, or opioid complication severity index) was reported in 83%, 90%, 85%, and 91% of patients at months 1, 2, 3, and 4, respectively. This study demonstrated that patients with refractory cancer pain or intolerable side effects achieved better analgesia when managed with patient-activated intrathecal delivery of morphine sulfate via an implanted delivery system.