Maximal Analgesic Effect Attained by the Use of Objective Neurophysiological Measurements With Closed-Loop Spinal Cord Stimulation.

Objectives: Spinal cord stimulation (SCS) has been challenged by the lack of neurophysiologic data to guide therapy optimization. Current SCS programming by trial-and-error results in suboptimal and variable therapeutic effects. A novel system with a physiologic closed-loop feedback mechanism using evoked-compound action potentials enables the optimization of physiologic neural dose by consistently and accurately activating spinal cord fibers.

Identifying SCS Trial Responders Immediately After Postoperative Programming with ECAP Dose-Controlled Closed-Loop Therapy.

Introduction: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction.

Neurophysiological outcomes that sustained clinically significant improvements over 3 years of physiologic ECAP-controlled closed-loop spinal cord stimulation for the treatment of chronic pain.

Introduction: A novel, spinal cord stimulation (SCS) system with a physiologic closed-loop (CL) feedback mechanism controlled by evoked compound action potentials (ECAPs) enables the optimization of physiologic neural dose and the accuracy of the stimulation, not possible with any other commercially available SCS systems. The report of objective spinal cord measurements is essential to increase the transparency and reproducibility of SCS therapy. Here, we report a cohort of the EVOKE double-blind randomized controlled trial treated with CL-SCS for 36 months to evaluate the ECAP dose and accuracy that sustained the durability of clinical improvements.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

Introduction: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant.

Methods: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS.

Durability of Clinical and Quality-of-Life Outcomes of Closed-Loop Spinal Cord Stimulation for Chronic Back and Leg Pain: A Secondary Analysis of the Evoke Randomized Clinical Trial.

Importance: Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system.

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.

Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial.

Background: Spinal cord stimulation has been an established treatment for chronic back and leg pain for more than 50 years; however, outcomes are variable and unpredictable, and objective evidence of the mechanism of action is needed. A novel spinal cord stimulation system provides the first in vivo, real-time, continuous objective measure of spinal cord activation in response to therapy via recorded evoked compound action potentials (ECAPs) in patients during daily use. These ECAPs are also used to optimise programming and deliver closed-loop spinal cord stimulation by adjusting the stimulation current to maintain activation within patients' therapeutic window.

Multicenter, Randomized, Double-Blind Study Protocol Using Human Spinal Cord Recording Comparing Safety, Efficacy, and Neurophysiological Responses Between Patients Being Treated With Evoked Compound Action Potential-Controlled Closed-Loop Spinal Cord Stimulation or Open-Loop Spinal Cord Stimulation (the Evoke Study).

Background: The spinal cord (SC) response to stimulation has yet to be studied in a pivotal clinical study. We report the study design of an ongoing multicenter, randomized, double-blind, controlled, parallel-arm study of an evoked compound action potential (ECAP) controlled closed-loop spinal cord stimulation (SCS) system, which aims to gain U.S.

Quantum gravity and taoist cosmology: Exploring the ancient origins of phenomenological string theory.

This paper carries forward the author's contribution to PBMP's previous special issue on Integral Biomathics (Rosen 2015). In the earlier paper, the crisis in contemporary theoretical physics was described and it was demonstrated that the problem can be addressed effectively only by shifting the foundations of physics from objectivist Cartesian philosophy to phenomenological philosophy. To that end, a phenomenological string theory was proposed based on qualitative topology and hypercomplex numbers.

The Polyanalgesic Consensus Conference (PACC): Recommendations for Intrathecal Drug Delivery: Guidance for Improving Safety and Mitigating Risks.

Introduction: Intrathecal therapy is an important part of the pain treatment algorithm for chronic disease states. The use of this option is a viable treatment strategy, but it is inherent for pain physicians to understand risk assessment and mitigation. In this manuscript, we explore evidence and mitigating strategies to improve safety with intrathecal therapy.

The Polyanalgesic Consensus Conference (PACC): Recommendations for Trialing of Intrathecal Drug Delivery Infusion Therapy.

Introduction: Intrathecal (IT) drug infusion is an appropriate and necessary tool in the algorithm to treat refractory cancer and noncancer pain. The decision-making steps/methodology for selecting appropriate patients for implanted targeted drug delivery systems is controversial and complicated. Therefore, a consensus on best practices for determining appropriate use of IT drug infusion may involve testing/trialing this therapy before implantation.

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines.

Introduction: Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice.

Methods: The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012.

Editorial.

Preparing this ambitious Special Issue has challenged everyone involved: authors, reviewers, and guest editors. The editors solicited contributions from many leading figures in a broad array of scientific and philosophical disciplines, with emphasis on phenomenological approaches to philosophy (see Section I). The motivating force was the conviction that if we could find a viable bridge for the gap between the "two cultures"(1) of science and philosophy, fundamental problems in each camp could be addressed more fruitfully than ever before and a new kind of science be born.

Why natural science needs phenomenological philosophy.

Through an exploration of theoretical physics, this paper suggests the need for regrounding natural science in phenomenological philosophy. To begin, the philosophical roots of the prevailing scientific paradigm are traced to the thinking of Plato, Descartes, and Newton. The crisis in modern science is then investigated, tracking developments in physics, science's premier discipline.

Increased pain catastrophizing associated with lower pain relief during spinal cord stimulation: results from a large post-market study.

Background: Pain catastrophizing is a negative cognitive distortion to actual or anticipated pain. Our aim was to determine if greater catastrophizing has a deleterious relationship with pain intensity and efficacy outcomes in patients receiving SCS.

Methods: As part of an ongoing Institutional Review Board-approved, multi-site, single arm post-market study, 386 patients were implanted with an Eon Mini™ SCS system and had follow-up visits at 3, 6, and 12 months post-implant.

Intrathecal administration of Infumorph® vs compounded morphine for treatment of intractable pain using the Prometra® programmable pump.

Objectives: The intrathecal administration of morphine sulfate has become an established alternative to oral opiate therapy for the treatment of chronic pain. Currently, Infumorph(®) is the only morphine sulfate approved by the US Food and Drug Administration for continuous intraspinal administration with an infusion pump. However, in order to achieve and maintain adequate pain relief, patients may require concentrations outside of those commercially available products resulting in the use of compounded morphine.

Development of a microparticle-based on-site immunoassay for the detection of atrazine in soil and water samples.

Atrazine is widely used as a herbicide in agriculture and has been identified as a major groundwater contaminant in the US. Because of the possible hazard associated with its usage, there is a need for an efficient and economic screening method for on-site field testing of atrazine and other s-triazine herbicides in soil and water. We have developed a rapid, on-site test for the detection of atrazine based on the principle of microparticle agglutination inhibition immunoassay.