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Aim: The Combining Mechanisms for Better Outcomes randomized controlled trial assessed the effectiveness of various spinal cord stimulation (SCS) modalities for chronic pain. Specifically, combination therapy (simultaneous use of customized sub-perception field and paresthesia-based SCS) versus monotherapy (paresthesia-based SCS) was evaluated. Methods: Participants were prospectively enrolled (key inclusion criterion: chronic pain for ≥6 months). Primary end point was the proportion with ≥50% pain reduction without increased opioids at the 3 month follow-up. Patients were followed for 2 years. Results: The primary end point was met (n = 89; p Clinical Trial Registration: NCT03689920 ( ClinicalTrials.gov ), Combining Mechanisms for Better Outcomes (COMBO)

Objectives Subperception spinal cord stimulation (SCS) is described mostly utilizing waveforms that require high energy. However, the necessity of these waveforms for effective subperception has not been established. We aimed to explore whether effective subperception pain relief can be achieved using frequencies below 1 kHz. Materials and methods Thirty chronic pain patients implanted with SCS were enrolled as part of a multicenter, real-world, consecutive, observational case series. An effective stimulation location was determined using a novel electric field shape designed to preferentially modulate dorsal horn elements. Subsequently, programs at lower frequencies (600, 400, 200, 100, 50, and 10 Hz) were provided with pulse-width and amplitude adjusted to optimize response. Results All tested frequencies (1 kHz down to 10 Hz) provided effective subperception relief, yielding a mean of 66-72% reduction in back, leg, and overall pain. It was found that to maintain analgesia, as frequency was decreased, the electrical or "neural" dose had to be adjusted according to parameter relationships described herein. With the reduction of frequency, we observed a net reduction of charge-per-second, which enabled energy savings of 74% (200 Hz) and 97% (10 Hz) relative to 1 kHz. Furthermore, pain reduction was sustained out to one year, with 85% of patients reporting a preference for frequencies of 400 Hz or below. Conclusions We have derived an electric field configuration and, along with previous learnings in the kHz range, a set of neural dosing parameter relationships (10-10,000 Hz), which enable the expansion of effective subperception SCS to low frequency and achieve major energy savings.

Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease.This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396.Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation.This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes.Boston Scientific.

Objective The WHISPER randomized controlled trial (RCT) evaluates safety and clinical effectiveness of subperception spinal cord stimulation (SCS) at ≤1.2 kHz in subjects previously implanted with an SCS system for treatment of chronic, neuropathic pain. Methods WHISPER is a prospective, multicenter RCT with a crossover design sponsored by Boston Scientific, Marlborough, MA (ClinicalTrials.gov: NCT02314000). Eligible subjects were randomized (N = 140) to receive subperception or supraperception for three months and then crossed over to receive the alternative. Upon completion of crossover period, subjects who preferred subperception were followed up to one year. Overall pain, quality-of-life, and other outcomes were collected in the study. The primary endpoint was the overall pain responder rate (≥50% improvement from baseline) with no increase in medications. Secondary endpoints consisted of pain scores, physical disability, quality of life, and treatment preference. Results The study met its primary endpoint and demonstrated noninferiority between supraperception and subperception in a prespecified cohort of 70 randomized subjects (Interim Analysis). Thirty-nine percent of subjects with subperception settings and 29% with supraperception settings had a greater than or equal to 50% reduction in their overall pain scores with no increase in average daily medication at three-months post-activation as compared with baseline. Further assessment of all participating study subjects (N = 140) revealed similar results. Subjects were previously implanted 3.8 ± 2 years and had a disability score (Oswestry Disability Index) of 70.2 ± 11.4 at study start. Of the randomized subjects that completed the End of Period 2 Visit, 93 (66%) preferred subperception SCS and their mean overall pain reduced from 7.3 ± 1.1 (N = 89) at baseline to 4.0 ± 2.1 (N = 80) at 12-months post-activation. Post hoc analysis also demonstrated that multiple options provide superior outcomes, as supported by a 74% increase in the responder rate when subjects could choose their most effective option (47%) compared with supraperception alone (27%). Discussion Subperception SCS at ≤1.2 kHz is safe and effective in subjects with extreme physical disability and previously implanted for chronic pain. Further, by providing study participants with different waveform options, increased pain relief was achieved.

Background The aim of this study was to determine whether spinal cord stimulation (SCS) using 3D neural targeting provided sustained overall and low back pain relief in a broad routine clinical practice population. Study Design and Methods This was a multicenter, open-label observational study with an observational arm and retrospective analysis of a matched cohort. After IPG implantation, programming was done using a patient-specific, model-based algorithm to adjust for lead position (3D neural targeting) or previous generation software (traditional). Demographics, medical histories, SCS parameters, pain locations, pain intensities, disabilities, and safety data were collected for all patients. Results A total of 213 patients using 3D neural targeting were included, with a trial-to-implant ratio of 86%. Patients used seven different lead configurations, with 62% receiving 24 to 32 contacts, and a broad range of stimulation parameters utilizing a mean of 14.3 (±6.1) contacts. At 24 months postimplant, pain intensity decreased significantly from baseline (ΔNRS = 4.2, N = 169, P

Women with long-acting, reversible contraceptive devices inserted may choose to remove them prior to their planned expiry dates.The objective of this study was to explore Australian women's experiences with the etonogestrel subdermal contraceptive implant (Implanon NXT) and why they had it removed early.Semi-structured interviews were conducted with 18 women between June 2013 and January 2014. Transcriptions of the audio-taped interviews were analysed using a constant comparative analysis framework.Two core themes of participants' responses that were identified in this study were influences on choice of contraception, which included convenience and information sources; and influences on removal of contraception, which included side effects and their negative impacts on relationships and financial costs.This study highlights that women's experiences with side effects contribute to the early removal of long-acting contraceptive devices such as Implanon NXT. This study emphasises the importance of general practitioners (GPs) in providing comprehensive information about the benefits and potential side effects associated with using these implants.

International audience; INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the management of motor symptoms of Parkinson disease (PD) is typically performed under conscious sedation with awake evaluation during intraoperative physiologic testing. However, developments in surgical techniques now allow for subjects to be asleep during the procedure using general anesthesia. Previously reported long-term outcomes of subjects who underwent STN-DBS under general anesthesia demonstrated postoperative safety and efficacy out to 1 year. In this study, we examine outcomes between subjects undergoing the STN-DBS procedure who used general anesthesia vs those using conscious sedation with awake evaluation as part of the ongoing VANTAGE clinical trial. METHODS: VANTAGE is a prospective, multicenter, nonrandomized, open-label interventional trial, sponsored by Boston Scientific Corporation. The trial assesses motor improvement in subjects with moderate-to-severe PD following bilateral STN-DBS. Assessments include motor scores such as Unified Parkinson's Disease Rating Scale (UPDRS) and quality-of-life measurements such as PDQ-39. Forty subjects were implanted bilaterally with the Vercise DBS System (Boston Scientific Corporation) at 6 European centers. Of these, 19 (47%) underwent the DBS procedure under general anesthesia. RESULTS: Analysis of both study groups did not indicate a statistically significant difference in motor function outcomes. However, subjects utilizing general anesthesia were found not to display motor function outcomes that were necessarily clinically inferior to those consciously sedated with awake evaluation. Sample size and variation in baseline differences in selected subjects may have contributed to these final results, because a tendency for subjects undergoing general anesthesia to report an improvement in motor function similar to or better than those consciously sedated (vs baseline) was observed. CONCLUSION: No inferiority in clinical outcomes was observed in subjects that underwent general anesthesia vs those that were consciously sedated with awake evaluation.

International audience; INTRODUCTION: Deep brain stimulation (DBS) has been demonstrated to be effective for Parkinson disease (PD) symptom relief. We sought to characterize the benefit of subthalamic nucleus (STN) DBS for PD patients using a recently CE-marked multiple-source, constant-current system that permits a well-defined distribution of applied current. We report the 3-year results of the first clinical trial using multiple independent current control (MICC) DBS in the management of symptoms of PD. METHODS: VANTAGE is a monitored, prospective, multicenter, nonrandomized, open-label interventional trial sponsored by Boston Scientific Corporation. Forty subjects with idiopathic PD were implanted bilaterally with a DBS system (Vercise) targeting the STN and followed up to 3 years after lead placement. Motor improvement was evaluated using Unified Parkinson's Disease Rating Scale (UPDRS) III scores in stim ON/meds OFF in comparison with preoperative scores. Other assessments such as CAPSIT motor tests, Tremor Rating Scale, Dyskinesia Rating Scale, PDQ-39, SF-36, Schwab and England, and resource utilization were administered. Patient motor diaries were collected over 3 days. Adverse events were also recorded. RESULTS: This study will report the safety and effectiveness outcomes of VANTAGE subjects at 3 years postimplantation as compared with baseline. CONCLUSION: The VANTAGE trial is the first reported trial of a multiple-source, constant-current rechargeable system for use in the management of PD symptoms. Study outcomes will inform clinicians on the use of this system and its flexibility to manage the symptoms of idiopathic PD.

International audience; Background High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinson's disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinson's disease. Methods We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21–75 years, had been diagnosed with bilateral idiopathic Parkinson's disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinson's disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. Findings Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3–15·7) compared with baseline (37·4 [8·9], 34·5–40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3–27·3; p

The purpose of this study is to re-examine the probable directive effect of the distal stump of a severed peripheral nerve on regenerating axons. Forssman postulated the existence of such a directive influence and Cajal interpreted it as chemotactic in nature. This view was subsequently refuted by Weiss and Taylor. In our study the proximal stumps of transected rodent sciatic nerve were inserted into the single inlet end of a Y-shaped autogenous inferior vena cava graft. Into one limb of the double outlet end, namely the common iliac nerve bifurcation, the distal stump of the same sciatic nerve was inserted, while the counter limb was ligated in one group, left open in the second group, inserted with a segment of autogenous tendon in the third, and grafted with a segment of autogenous nerve in the fourth group. Both outlets were left unoccupied in yet another group as the control. The vena cava conduit was prepared so that a 1.5 cm gap existed between the proximal stumps of the sciatic nerve and the distal sciatic nerve stumps and the tendon grafts respectively. The grafted sciatic nerves were explored and biopsied after 12 weeks. The direction of nerve tissue regeneration in each group was analyzed histologically. Predilection of the regenerating nerve fibers toward the distal stumps was observed in each of the test groups. These results indicate the existence of a guiding influence at the distal stump toward the regeneration nerve fibers.