Spinal Cord Stimulation (SCS)-The Implantable Systems Performance Registry (ISPR).

OBJECTIVES: The Implantable Systems Performance Registry (ISPR) was created to monitor the product performance of Medtronic Spinal Cord Stimulation (SCS) and implanted intrathecal drug infusion systems available in the United States. MATERIALS AND METHODS: Data were collected on 2605 patients from 44 centers from various geographic regions across the United States implanting and following patients with SCS systems between June 25, 2004 and January 31, 2014. Actuarial life table methods are used to estimate device performance over time. Of the 2605 patients, 1490 (57.2%) were female, 1098 (42.1%) were male and 17 (0.7%) did not provide gender data. The average age at enrollment was 56.3 years (range: 4-97, SD = 14.3) and average follow-up time was 20.1 months (SD = 22.5). RESULTS: Currently the estimates of device survival from neurostimulator-related events exceed 97% for all neurostimulator models across the applicable follow-up time points and all applicable extension models had greater than 95% survival from extension events. The majority of product performance events were lead-related. At 5 years of follow-up, all applicable lead families, with the exception of the Pisces-Quad LZ family, had greater than 75% survival from lead events. CONCLUSIONS: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.

Assessment of patient preference for constant voltage and constant current spinal cord stimulation.

OBJECTIVES: Spinal cord stimulation devices control energy by generating either constant voltage (CV) pulses or constant current (CC) pulses. This study aimed to investigate: 1) whether patients feel differences between CV and CC stimulation; 2) if patients prefer CV or CC stimulation. METHODS: Fourteen patients blinded to the type of pulse generation received 20 randomized pairs of 15-sec pulse trains (CC-CV, CV-CC, CV-CV, or CC-CC). Patients identified whether the pairs were the same or different, and if they preferred the first or second train. RESULTS: There was no difference in charge-per-pulse input between CV and CC modes. Patients performed at chance level in identifying identical pairs (55.7 ± 24.1% correct, 10 trials), and slightly better in identifying different pairs (67.1 ± 25.2% correct, 10 trials). No patients correctly identified all pairs. Patients were categorized based on their performance in this task. Only three patients fell into a category where preference could be established with some confidence with respect to the group averages. Two of these patients preferred CV, while one patient preferred CC. CONCLUSION: The lack of patient ability to discriminate in this preliminary investigation suggests that patient preference for a stimulation type should not be the key determining factor in choosing a spinal cord stimulation system.

Factors affecting dosing regimens of morphine sulfate extended-release (KADIAN) capsules.

Although most extended-release morphine formulations are indicated for use once-daily (q24h) or twice-daily (q12h), KADIAN (morphine sulfate extended-release) capsules, which contain polymer-coated, extended-release morphine sulfate pellets, are indicated for q24h and q12h dosing. This analysis identified factors that might impact decisions to choose q24h or q12h regimens for patients with chronic, nonmalignant pain. Data were obtained from a supplemental analysis of the KRONUS-MSP trial, a community-based, open-label, 4-week study in which patients with chronic, nonmalignant pain (N = 1,428) were randomized to KADIAN q24h dosed either AM or PM. At week 2, investigators could switch to q12h dosing if indicated. For this analysis, demographics, baseline pain features, efficacy outcomes (changes in pain intensity, sleep interference, quality of life [SF-36v2 Health Survey], and Patient and Clinician Global Assessments of Therapy) were compared between patients who remained on q24h regimens and those who switched to q12h. By week 4 (n = 1,042), 56.8 percent of patients reporting were on q24h dosing, and 43.2 percent were dosing q12h. Older patients remained on q24h regimens more frequently than did younger patients. There were no differences in dosing regimen based on sex or race. Mean daily KADIAN doses and baseline pain scores were lower in patients who remained on q24h compared with those who switched to q12h. Patients who switched to q12h had higher pain scores at baseline and week 2 compared with patients who remained on q24h dosing. They demonstrated a smaller degree of change on the other efficacy outcomes than those who remained on q24h dosing at the week 2 visit. However, once switched to q12h, improvements in efficacy measures at week 4 were comparable between the two schedules; Patient and Clinician Global Assessments of Therapy scores also increased compared with previous therapy. Results were significant versus baseline for all outcomes. Adverse event rates were similar for the two groups; the most common adverse events were constipation and nausea. Results demonstrate that KADIAN was effective in relieving pain and improving sleep and quality-of-life scores, regardless of whether patients dosed q24h or q12h, and that dosing decisions can be made, based on individual factors, within the first few weeks of therapy.

Effectiveness of polymer-coated extended-release morphine sulfate capsules in older patients with persistent moderate-to-severe pain: A subgroup analysis of a large, open-label, community-based trial.

UNLABELLED: Abstract. BACKGROUND: Opioid analgesics may offer benefits over nonopioids in some older patients, especially those with moderate-to-severe pain. Polymer-coated extended-release morphine sulfate (P-ERMS) has been found to be efficacious and well tolerated in patients with chronic, moderate-to-severe, nonmalignant pain when used QD or BID. OBJECTIVE: The purpose of this analysis was to determine the effectiveness of P-ERMS in older patients (aged >65 years) with persistent, moderate-to-severe, inadequately controlled, nonmalignant pain. METHODS: This was a subgroup analysis of the older population from an openlabel trial in community-based pain clinics in which patients underwent treatment with P-ERMS for persistent, moderate-to-severe, inadequately controlled, nonmalignant pain (≥4 on a scale of 0-10). Patients received P-ERMS at a dose determined by the investigator based on their previous analgesic regimen, QD (morning or evening) for a 4-week treatment period. Dose increases were permitted after weeks 1 and 2; switching to BID was allowed after week 2, if needed. Measurements included changes in pain and sleep scores (0-10 scale), quality of life (QOL) scores (physical and mental component summaries [PCS and MCS, respectively] of the 36-Item Short-Form Health Survey instrument), and patient and clinician assessments of current treatment based on a 9-point scale ranging from -4 to +4. RESULTS: One hundred forty-eight older patients (mean [SD]age, 73.4 [5.5] years) began treatment with P-ERMS; 86 (58.1%) of those patients completed the study. Pain and sleep scores significantly improved (decreased) from baseline to week 4 (7.4 vs 5.0 and 5.0 vs 3.2, respectively; both, P < 0.001). PCS and MCS scores significantly improved (increased) from baseline (27.7 vs 31.6 and 37.6 vs 40.8, respectively; both, P < 0.05), as did patient and clinician global assessments (-1.2 vs 1.1 and -1.5 vs 1.4; both, P < 0.001). Results found in these older patients were similar to those observed in the younger patients (aged ≤65 years). A majority (71.4%) of the older patients remained on QD administration and took significantly lower mean daily doses than younger patients (77.0 vs 105.2 mg/d, respectively; P = 0.001). The dropout rate for the subgroup was 41.1%, which was similar to that reported in previous studies in mixed-age populations taking other extended-release morphine formulations. Of the patients who discontinued (n = 60), adverse events (AEs) were the most prevalent reason (n = 29). The most common treatment-related AEs were constipation (19.6%) and nausea (9.5%). CONCLUSIONS: This subgroup analysis of a previously published study revealed that the older patients in that study who were receiving P-ERMS for persistent, moderate-to-severe, inadequately controlled, nonmalignant pain who completed the study attained significant improvements in pain, sleep, and QOL scores compared with baseline. Patient and clinician satisfaction with treatment increased significantly from baseline to study end. Older patients utilized significantly lower mean daily doses than younger patients (P < 0.001), and >70% remained on a QD administration regimen for the duration of the study.

Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain.

OBJECTIVE: To assess the long-term efficacy, tolerability and safety of polymer-coated extended-release morphine sulfate (P-ERMS) (KADIAN) compared with controlled-release oxycodone HCl (CRO) (OxyContin) in treating chronic, nonmalignant, moderate to severe pain in a community-based outpatient population. DESIGN: Phase IV, prospective, randomized, open-label. PARTICIPANTS: Adults (N = 112) with chronic, nonmalignant, moderate to severe pain with visual numeric scale (VNS) scores > or = 4 (0 = no pain; 10 = worst pain). INTERVENTIONS: Patients were randomized to receive either P-ERMS once-daily (QD) dosing or CRO twice-daily (BID) dosing for a 24-week treatment period. Upward titration of dose and switching P-ERMS to BID or CRO to thrice-daily (TID) dosing was allowed Weeks 2-24. MAIN OUTCOME MEASURES: Quality of life (Physical [PCS] and Mental [MCS] Component Summary scores of the SF-36v2 Health Survey), pain and sleep scores (0-10), and patient and clinician assessments of current therapy (-4 to +4). RESULTS: Patients in both treatment groups experienced significant improvements in PCS scores (P-ERMS, +2.6; CRO, +3.1; p < 0.05 vs. baseline); patients taking CRO also demonstrated improvements in MCS scores (+4.7, p < 0.05 vs. baseline). Both groups attained significant reductions from baseline to 24 weeks in pain (P-ERMS, -2.0; CRO, -1.4; p < or = 0.001 vs. baseline); the reduction with P-ERMS was clinically meaningful (as defined by at least a 2-point reduction in VNS score). Patients attained significant improvement in sleep scores (P-ERMS, -2.6; CRO, -1.6; p < 0.001 vs. baseline; p < 0.05, P-ERMS vs. CRO). At Week 24, both groups indicated significantly increased patient (P-ERMS, +2.6; CRO, +1.7; p < 0.001 vs. baseline) and clinician (P-ERMS, +4.0; CRO, +3.1; p < 0.001 vs. baseline) global assessments of therapy. After 24 weeks, all patients on P-ERMS were dosing within the FDA-approved frequencies (65% QD, 35% BID); 56% of patients on CRO dosed BID, but 38% dosed TID and 6% dosed four times daily (QID). Most common adverse events were constipation, nausea, and somnolence, with no significant difference between treatment groups. CONCLUSIONS: P-ERMS and CRO both relieved chronic nonmalignant pain in this community-based population; however, patients taking P-ERMS dosed in accordance with FDA-approved frequencies (QD/BID); 44% of those taking CRO dosed more frequently (TID/QID).

Treatment of chronic moderate-to-severe non-malignant pain with polymer-coated extended-release morphine sulfate capsules.

OBJECTIVE: To demonstrate the efficacy and tolerability of polymer-coated extended-release morphine sulfate (P-ERMS)(KADIAN) for the treatment of chronic, moderate-to-severe, non-malignant pain in a community-based outpatient population not satisfactorily relieved with their current therapies. DESIGN: Phase IV, prospective, randomized, open-label, blinded endpoint. PARTICIPANTS: Adults (N = 1428) with chronic, moderate-to-severe, non-malignant pain with visual numeric scale scores >or= 4 (0 = no pain; 10 = worst pain). INTERVENTIONS: Patients were randomized to P-ERMS once daily in AM or PM for a 4-week treatment period. Dose increases were allowed; however, switching to twice-daily dosing was reserved until week 2. MAIN OUTCOME MEASURES: Improvement from baseline in pain and sleep scales (0-10) (after weeks 2 and 4), quality of life (physical and mental component summary scores of the SF-36v2 Health Survey) (week 4), and patient (weeks 2 and 4) and clinician (week 4) assessments of current therapy (-4 to +4). Patient satisfaction was assessed again 1 month after the study. RESULTS: Approximately 70% of patients completed the study, with 2.4% (n = 34) discontinuing due to lack of efficacy, and 9.6% (n = 136) discontinuing due to an adverse event. Improvements were seen in pain and sleep scores, physical and mental component scores of the SF-36v2, and patient and clinician global assessment scores (p < 0.0001, all assessments). Patients attained similar results regardless of AM vs. PM dosing. More than half (55.4%) of patients were maintained on once-daily therapy, with the remainder on a twice-daily regimen, in accordance with the prescribing information. Most adverse events (71.6%) were mild to moderate in severity, the most common being constipation (11.6%) and nausea (9.2%). One-month follow-up indicated continued satisfaction with P-ERMS vs. previous medication (p < 0.0001). CONCLUSIONS: P-ERMS was efficacious and well tolerated in patients with chronic, moderate-to-severe, non-malignant pain when used once or twice daily.

Prevention of mechanical failures in implanted spinal cord stimulation systems.

Introduction. Spinal cord stimulation (SCS) is an effective procedure for the treatment of neuropathic extremity pain, with success rates approaching 70%. However, mechanical failures, including breakage and migration, can significantly limit the long-term effectiveness of SCS. A systematic analysis of surgical techniques was undertaken by a consensus group, coupled with extensive in vivo and in vitro biomechanical testing of system components. Methods. A computer model based on morphometric data was used to predict movement in a standard SCS system between an anchored lead and pulse generator placed in various locations. These displacements were then used to determine a realistic range of forces exerted on components of the SCS system. Laboratory fixtures were constructed to subject leads and anchors to repetitive stresses until failure occurred. An in vivo sheep model also was used to determine system compliances and failure thresholds in a biologically realistic setting. A panel of experienced implanters then interpreted the results and related them to clinical observations. Results. Use of a soft silastic anchor pushed through the fascia to provide a larger bend radius for the lead was associated with a time to failure 65 times longer than an anchored but unsupported lead. In addition, failures of surgical paddle leads occurred when used with an anchor, whereas without an anchor, no failures occurred to 1 million cycles. Based on these findings, the panel recommended a paramedian approach, abdominal pulse generator placement, maximizing bend radius by pushing the anchor through the fascia, and anchoring of the extension connector near the lead anchor. Discussion. Several factors are important in longevity of SCS systems. We discovered that technical factors can make a large difference in SCS reliability and that strict attention to these "best practices" will provide the best chance for maintaining the integrity of SCS systems over the long term.