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Complex systems can exhibit sudden transitions or regime shifts from one stable state to another, typically referred to as critical transitions. It becomes a great challenge to identify a robust warning sufficiently early that action can be taken to avert a regime shift. We employ landscape-flux theory from nonequilibrium statistical mechanics as a general framework to quantify the global stability of ecological systems and provide warning signals for critical transitions. We quantify the average flux as the nonequilibrium driving force and the dynamical origin of the nonequilibrium transition while the entropy production rate as the nonequilibrium thermodynamic cost and thermodynamic origin of the nonequilibrium transition. Average flux, entropy production, nonequilibrium free energy, and time irreversibility quantified by the difference in cross-correlation functions forward and backward in time can serve as early warning signals for critical transitions much earlier than other conventional predictors. We utilize a classical shallow lake model as an exemplar for our early warning prediction. Our proposed method is general and can be readily applied to assess the resilience of many other ecological systems. The early warning signals proposed here can potentially predict critical transitions earlier than established methods and perhaps even sufficiently early to avert catastrophic shifts.
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Ecosistema , Física , Termodinámica , EntropíaRESUMEN
The frequency distributions can characterize the population-potential landscape related to the stability of ecological states. We illustrate the practical utility of this approach by analyzing a forest-savanna model. Savanna and forest states coexist under certain conditions, consistent with past theoretical work and empirical observations. However, a grassland state, unseen in the corresponding deterministic model, emerges as an alternative quasi-stable state under fluctuations, providing a theoretical basis for the appearance of widespread grasslands in some empirical analyses. The ecological dynamics are determined by both the population-potential landscape gradient and the steady-state probability flux. The flux quantifies the net input/output to the ecological system and therefore the degree of nonequilibriumness. Landscape and flux together determine the transitions between stable states characterized by dominant paths and switching rates. The intrinsic potential landscape admits a Lyapunov function, which provides a quantitative measure of global stability. We find that the average flux, entropy production rate, and free energy have significant changes near bifurcations under both finite and zero fluctuation. These may provide both dynamical and thermodynamic origins of the bifurcations. We identified the variances in observed frequency time traces, fluctuations, and time irreversibility as kinematic measures for bifurcations. This framework opens the way to characterize ecological systems globally, to uncover how they change among states, and to quantify the emergence of quasi-stable states under stochastic fluctuations.
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Fenómenos Ecológicos y Ambientales , Procesos Estocásticos , Ecosistema , Entropía , Cinética , Poaceae , Termodinámica , ÁrbolesRESUMEN
BACKGROUND: Neurostimulation is a highly effective therapy for the treatment of chronic Intractable pain, however, due to the complexity of pain, measuring a subject's long-term response to the therapy remains difficult. Frequent measurement of patient-reported outcomes (PROs) to reflect multiple aspects of subjects' pain is a crucial step in determining therapy outcomes. However, collecting full-length PROs is burdensome for both patients and clinicians. The objective of this work is to identify the reduced set of questions from multiple validated PROs that can accurately characterize chronic pain patients' responses to neurostimulation therapies. METHODS: Validated PROs were used to capture pain, physical function and disability, as well as psychometric, satisfaction, and global health metrics. PROs were collected from 509 patients implanted with Spinal Cord Stimulation (SCS) or Dorsal Root Ganglia (DRG) neurostimulators enrolled in the prospective, international, post-market REALITY study (NCT03876054, Registration Date: March 15, 2019). A combination of linear regression, Pearson's correlation, and factor analysis were used to eliminate highly correlated questions and find the minimal meaningful set of questions within the predefined domains of each scale. RESULTS: The shortened versions of the questionnaires presented almost identical accuracy for classifying the therapy outcomes as compared to the validated full-length versions. In addition, principal component analysis was performed on all the PROs and showed a robust clustering of pain intensity, psychological factors, physical function, and sleep across multiple PROs. A selected set of questions captured from multiple PROs can provide adequate information for measuring neurostimulation therapy outcomes. CONCLUSIONS: PROs are important subjective measures to evaluate the physiological and psychological aspects of pain. However, these measures are cumbersome to collect. These shorter and more targeted PROs could result in better patient engagement, and enhanced and more frequent data collection processes for digital health platforms that minimize patient burden while increasing therapeutic benefits for chronic pain patients.
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Dolor Crónico , Estimulación de la Médula Espinal , Humanos , Dolor Crónico/terapia , Dolor Crónico/psicología , Ganglios Espinales/fisiología , Manejo del Dolor , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Estudios Clínicos como AsuntoRESUMEN
We analyze a spatially extended version of a well-known model of forest-savanna dynamics, which presents as a system of nonlinear partial integro-differential equations, and study necessary conditions for pattern-forming bifurcations. Homogeneous solutions dominate the dynamics of the standard forest-savanna model, regardless of the length scales of the various spatial processes considered. However, several different pattern-forming scenarios are possible upon including spatial resource limitation, such as competition for water, soil nutrients, or herbivory effects. Using numerical simulations and continuation, we study the nature of the resulting patterns as a function of system parameters and length scales, uncovering subcritical pattern-forming bifurcations and observing significant regions of multistability for realistic parameter regimes. Finally, we discuss our results in the context of extant savanna-forest modeling efforts and highlight ongoing challenges in building a unifying mathematical model for savannas across different rainfall levels.
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Ecosistema , Pradera , Modelos Biológicos , Conceptos Matemáticos , ÁrbolesRESUMEN
OBJECTIVE: This study aimed to assess the safety and effectiveness of a new charge-distributed multiphase stimulation paradigm during an extended spinal cord stimulation (SCS) trial. MATERIALS AND METHODS: This prospective, multicenter, randomized, single-blind, feasibility study included participants with chronic low back and/or leg pain and baseline numerical rating scale (NRS) for overall pain intensity ≥6. After a successful commercial SCS trial, participants were randomized to multiphase SCS therapy A (approximately 600-1500 Hz) or B (approximately 300-600 Hz), delivered via an investigational external pulse generator and existing leads during an 11-to-12-day testing period. Primary end points were mean NRS change from baseline to final in-office visit for each multiphase therapy and between therapies. Secondary end points included mean NRS change from end of commercial trial to final study visit and incidence of device-related adverse events (AEs). Additional measures included patient-reported outcomes collected at home through electronic watches and written diaries. Power usage was compared between multiphase and commercial therapies. RESULTS: A total of 122 participants initiated a commercial trial; 77 were randomized to a multiphase arm, and 65 completed the study. Reductions in mean NRS scores from baseline to final study visit were significant for multiphase therapy A and B (-4.3 and -4.7, respectively; both p < 0.0001). There was no statistically significant difference in mean NRS reduction or percent pain relief between multiphase therapies. In an additional analysis, 63.9% of participants reported greater pain relief with multiphase than with commercial SCS therapy in the at-home setting. On average, multiphase required less power than did commercial devices. One non-serious device-related AE was reported, and no infections occurred during the extended trial. CONCLUSIONS: Multiphase SCS effectively reduced pain in participants with chronic low back and/or leg pain during a trial, with no unanticipated device-related AEs reported. Future studies should evaluate long-term effectiveness of multiphase stimulation. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03594266.
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Dolor Crónico , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/efectos adversos , Estimulación de la Médula Espinal/métodos , Dolor Crónico/diagnóstico , Dolor Crónico/terapia , Pierna , Estudios Prospectivos , Método Simple Ciego , Resultado del Tratamiento , Médula EspinalRESUMEN
OBJECTIVE: Spinal cord stimulation (SCS) is effective for relieving chronic intractable pain conditions. The Dorsal spInal cord STImulatioN vs mediCal management for the Treatment of low back pain study evaluates the effectiveness of SCS compared with conventional medical management (CMM) in the treatment of chronic low back pain in patients who had not undergone and were not candidates for lumbar spine surgery. METHODS AND MATERIALS: Patients were randomized to passive recharge burst therapy (n = 162) or CMM (n = 107). They reported severe pain and disability for more than a decade and had failed a multitude of therapies. Common diagnoses included degenerative disc disease, spondylosis, stenosis, and scoliosis-yet not to a degree amenable to surgery. The six-month primary end point compared responder rates, defined by a 50% reduction in pain. Hierarchical analyses of seven secondary end points were performed in the following order: composite responder rate (numerical rating scale [NRS] or Oswestry Disability Index [ODI]), NRS, ODI, Pain Catastrophizing Scale responder rate, Patient Global Impression of Change (PGIC) responder rate, and Patient-Reported Outcome Measure Information System-29 in pain interference and physical function. RESULTS: Intention-to-treat analysis showed a significant difference in pain responders on NRS between SCS (72.6%) and CMM (7.1%) arms (p < 0.0001). Of note, 85.2% of those who received six months of therapy responded on NRS compared with 6.2% of those with CMM (p < 0.0001). All secondary end points indicated the superiority of burst therapy over CMM. A composite measure on function or pain relief showed 91% of subjects with SCS improved, compared with 16% of subjects with CMM. A substantial improvement of 30 points was observed on ODI compared with a Asunto(s)
Dolor Crónico
, Dolor de la Región Lumbar
, Estimulación de la Médula Espinal
, Humanos
, Dolor de la Región Lumbar/terapia
, Dolor de la Región Lumbar/psicología
, Resultado del Tratamiento
, Estudios Prospectivos
, Dolor de Espalda
, Estimulación de la Médula Espinal/métodos
, Dolor Crónico/diagnóstico
, Dolor Crónico/terapia
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INTRODUCTION: DeRidder's burst stimulation design has become a key spinal cord stimulation (SCS) waveform because it reduces the intensity of pain as well as its associated emotional distress. The brain pathways underlying these outcomes may also allow for the effects of stimulation to carry over after stimulation is turned off, making it amenable to intermittent application. Here, the utility of intermittently cycled burst was evaluated using data from two large real-world prospective studies (TRIUMPH, REALITY). MATERIALS AND METHODS: Subjects used intermittent dosing in a 1:3 ratio (30 sec on, 90 sec off; N = 100) in TRIUMPH and 1:12 ratio in REALITY (30-sec on, 360-sec off; N = 95) for six months. Pain intensity (0-10 numeric rating scale), pain-related emotions on the pain catastrophizing scale (PCS), and physical function on PROMIS questionnaires were compared with preimplant baseline ratings and by group. RESULTS: In both groups, mean pain intensity decreased by nearly 50% relative to baseline, PCS scores significantly decreased, and physical function improved. Importantly, no differences between the 1:3 and 1:12 groups were identified. A high proportion, 80% and 77% of the 1:3 and 1:12 groups, respectively, were considered responders on a multiple measures. No adverse events were associated with intermittent stimulation. DISCUSSION: Intermittent cycling of burst SCS lowers the overall electric charge delivered to the spinal cord and preserves battery consumption, without compromising pain relief and associated symptoms.
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Dolor Crónico , Estimulación de la Médula Espinal , Humanos , Dolor , Manejo del Dolor , Estudios Prospectivos , Médula Espinal , Resultado del TratamientoRESUMEN
INTRODUCTION: The field of neurostimulation for the treatment of chronic pain is a rapidly developing area of medicine. Although neurostimulation therapies have advanced significantly as a result of technologic improvements, surgical planning, device placement, and postoperative care are of equal importance to optimize outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for these often-overlooked areas of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based on their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from the last NACC publication in 2017 to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on evidence strength and consensus when evidence was scant. RESULTS: This NACC project provides guidance on preoperative assessment, intraoperative techniques, and postoperative management in the form of consensus points with supportive evidence. These results are based on grade of evidence, strength of consensus, and expert opinion. CONCLUSIONS: The NACC has given guidance for a surgical plan that encompasses the patient journey from the planning stage through the surgical experience and postoperative care. The overall recommendations are designed to improve efficacy and the safety of patients undergoing these neuromodulation procedures and are intended to apply throughout the international community.
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Dolor Crónico , Estimulación de la Médula Espinal , Dolor Crónico/terapia , Consenso , HumanosRESUMEN
INTRODUCTION: Intermittent dosing (ID), in which periods of stimulation-on are alternated with periods of stimulation-off, is generally employed using 30 sec ON and 90 sec OFF intervals with burst spinal cord stimulation (SCS). The goal of this study was to evaluate the feasibility of using extended stimulation-off periods in patients with chronic intractable pain. MATERIALS AND METHODS: This prospective, multicenter, feasibility trial evaluated the clinical efficacy of the following ID stimulation-off times: 90, 120, 150, and 360 sec with burst waveform parameters. After a successful trial (≥50% pain relief) using ID stimulation, subjects were titrated with OFF times beginning with 360 sec. Pain, quality of life, disability, and pain catastrophizing were evaluated at one, three, and six months after permanent implant. RESULTS: Fifty subjects completed an SCS trial using ID stimulation settings of 30 sec ON and 90 sec OFF, with 38 (76%) receiving ≥50% pain relief. Pain scores were significantly reduced from baseline at all time points (p < 0.001). Improvements in quality of life, disability, and pain catastrophizing were aligned with pain relief outcomes; 45.8% of the subjects that completed the six-month follow-up visit used an OFF period of 360 seconds. CONCLUSIONS: ID burst SCS effectively relieved pain for six months. The largest group of subjects used IDB settings of 30 sec ON and 360 sec OFF. These findings present intriguing implications for the optimal "dose" of electricity in SCS and may offer many advantages such as optimizing the therapeutic window, extending battery life, reducing recharge burden and, potentially, mitigating therapy habituation or tolerance.
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Dolor Crónico , Estimulación de la Médula Espinal , Dolor Crónico/terapia , Humanos , Manejo del Dolor , Estudios Prospectivos , Calidad de Vida , Médula Espinal , Resultado del TratamientoRESUMEN
INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) is dedicated to improving the safety and efficacy of neuromodulation and thus improving the lives of patients undergoing neuromodulation therapies. With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion (DRG) stimulation has significantly improved the treatment of complex regional pain syndrome (CRPS), among other conditions. Through funding and organizational leadership by the International Neuromodulation Society (INS), the NACC reconvened to develop the best practices consensus document for the selection, implantation and use of DRG stimulation for the treatment of chronic pain syndromes. METHODS: The NACC performed a comprehensive literature search of articles about DRG published from 1995 through June, 2017. A total of 2538 article abstracts were then reviewed, and selected articles graded for strength of evidence based on scoring criteria established by the US Preventive Services Task Force. Graded evidence was considered along with clinical experience to create the best practices consensus and recommendations. RESULTS: The NACC achieved consensus based on peer-reviewed literature and experience to create consensus points to improve patient selection, guide surgical methods, improve post-operative care, and make recommendations for management of patients treated with DRG stimulation. CONCLUSION: The NACC recommendations are intended to improve patient care in the use of this evolving therapy for chronic pain. Clinicians who choose to follow these recommendations may improve outcomes.
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Terapia por Estimulación Eléctrica/métodos , Ganglios Espinales , HumanosRESUMEN
Aim: Low Back Pain (LBP) is a prevalent condition. Spinal cord stimulation (SCS) has emerged as a more effective, long-term treatment compared to conventional medical management (CMM). The DISTINCT study enrolled and randomized chronic LBP patients with no indication of traditional spine surgery. This analysis focuses comparing study outcomes on patients initially randomized to receive CMM treatment and subsequently crossed over to SCS after 6 months. Purpose: To compare the therapeutic effectiveness and cost-efficiency of passive recharge burst SCS to CMM. Patients and Methods: A total of 269 patients were enrolled with 162 randomly assigned to SCS and 107 to CMM. The DISTINCT study design allowed a crossover to the alternative treatment arm after 6 months. Patients underwent a trial and received a permanent implant if they reported ≥50% pain reduction. Outcome analysis included pain (NRS), disability (ODI), catastrophizing (PCS), quality of life (PROMIS-29) and health care utilization. Results: Seventy out of eighty-one patients opted to cross over to trial SCS at 6M with 94% (66/70) undergoing a trial. Among those, 88% (58/66) reported a ≥50% or more pain relief and 55 received a permanent implant. At 12M visit, 71.4% reported a ≥50% pain improvement sustained at the 18M visit, with 24.5% (12/49) indicating a ≥80% improvement. Disability reductions (79% meeting the minimally important difference of a 13-point decrease), decreased catastrophizing, and significant improvements in all PROMIS-29 domains were noted. Furthermore, 42% of the patients reported decreased or discontinued opioid usage. Clinical benefits at the 12M visit were sustained through the 18M visit accompanied by a significant reduction in healthcare utilization and a $1214 cost savings. Conclusion: SCS demonstrates superior, long-term performance and safety outcomes compared to CMM therapy in LBP patients who received both CMM and SCS therapy. Additionally, SCS patients experienced reduced healthcare resource utilization and lower costs compared to those receiving CMM.
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Background: Low back pain (LBP) is a highly prevalent, disabling condition affecting millions of people. Patients with an identifiable anatomic pain generator and resulting neuropathic lower extremity symptoms often undergo spine surgery, but many patients lack identifiable and/or surgically corrective pathology. Nonoperative treatment options often fail to provide sustained relief. Spinal cord stimulation (SCS) is sometimes used to treat these patients, but the lack of level 1 evidence limits its widespread use and insurance coverage. The DISTINCT RCT study evaluates the efficacy of passive recharge burst SCS compared to conventional medical treatment (CMM) in alleviating chronic, refractory axial low back pain. Methods: This prospective, multicenter, randomized, study with an optional 6-month crossover involved patients who were not candidates for lumbar spine surgery. The primary and secondary endpoints evaluated improvements in low back pain intensity (NRS), back pain-related disability (ODI), pain catastrophizing (PCS), and healthcare utilization. Patients were randomized to SCS therapy or CMM at 30 US study sites. Results: The SCS arm reported an 85.3% NRS responder rate (≥ 50% reduction) compared to 6.2% (5/81) in the CMM arm. After the 6M primary endpoint, SCS patients elected to remain on assigned therapy and 66.2% (49/74) of CMM patients chose to trial SCS (crossover). At the 12M follow-up, SCS and crossover patients reported 78.6% and 71.4% NRS responder rates. Secondary outcomes indicated significant improvements in ODI, PCS, and reduced healthcare utilization. Six serious adverse events were reported and resolved without sequelae. Conclusion: DISTINCT chronic low back pain patients with no indication for corrective surgery experienced a significant and sustained response to burst SCS therapy for up to 12 months. CMM patients who crossed over to the SCS arm reported profound improvements after 6 months. This data advocates for a timely consideration of SCS therapy in patients unresponsive to conservative therapy.
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Spinal Cord Stimulation (SCS) is a well-established therapy for treating chronic pain. However, perceived treatment response to SCS therapy may vary among people with chronic pain due to diverse needs and backgrounds. Patient Reported Outcomes (PROs) from standard survey questions do not provide the full picture of what has happened to a patient since their last visit, and digital PROs require patients to visit an app or otherwise regularly engage with software. This study aims to assess the feasibility of using digital biomarkers collected from wearables during SCS treatment to predict pain and PRO outcomes. Twenty participants with chronic pain were recruited and implanted with SCS. During the six months of the study, activity and physiological metrics were collected and data from 15 participants was used to develop a machine learning pipeline to objectively predict pain levels and categories of PRO measures. The model reached an accuracy of 0.768 ± 0.012 in predicting the pain intensity of mild, moderate, and severe. Feature importance analysis showed that digital biomarkers from the smartwatch such as heart rate, heart rate variability, step count, and stand time can contribute to modeling different aspects of pain. The results of the study suggest that wearable biomarkers can be used to predict therapy outcomes in people with chronic pain, enabling continuous, real-time monitoring of patients during the use of implanted therapies.
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BACKGROUND: Neurostimulation is an effective therapy for treating and management of refractory chronic pain. However, the complex nature of pain and infrequent in-clinic visits, determining subject's long-term response to the therapy remains difficult. Frequent measurement of pain in this population can help with early diagnosis, disease progression monitoring, and evaluating long-term therapeutic efficacy. This paper compares the utilization of the common subjective patient-reported outcomes with objective measures captured through a wearable device for predicting the response to neurostimulation therapy. METHOD: Data is from the ongoing international prospective post-market REALITY clinical study, which collects long-term patient-reported outcomes from 557 subjects implanted by Spinal Cord Stimulator (SCS) or Dorsal Root Ganglia (DRG) neurostimulators. The REALITY sub-study was designed for collecting additional wearables data on a subset of 20 participants implanted with SCS devices for up to six months post implantation. We first implemented a combination of dimensionality reduction algorithms and correlation analyses to explore the mathematical relationships between objective wearable data and subjective patient-reported outcomes. We then developed machine learning models to predict therapy outcome based on the subject's response to the numerical rating scale (NRS) or patient global impression of change (PGIC). RESULTS: Principal component analysis showed that psychological aspects of pain were associated with heart rate variability, while movement-related measures were strongly associated with patient-reported outcomes related to physical function and social role participation. Our machine learning models using objective wearable data predicted PGIC and NRS outcomes with high accuracy without subjective data. The prediction accuracy was higher for PGIC compared with the NRS using subjective-only measures primarily driven by the patient satisfaction feature. Similarly, the PGIC questions reflect an overall change since the study onset and could be a better predictor of long-term neurostimulation therapy outcome. CONCLUSIONS: The significance of this study is to introduce a novel use of wearable data collected from a subset of patients to capture multi-dimensional aspects of pain and compare the prediction power with the subjective data from a larger data set. The discovery of pain digital biomarkers could result in a better understanding of the patient's response to therapy and their general well-being.
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INTRODUCTION: Lumbar degenerative disease and the accompanying pain and dysfunction affect a significant number of patients in the USA and around the world. As surgery and innovation are moving towards minimally invasive treatments, this study looks to explore interspinous fixation as a standalone posterior approach to treat lumbar degenerative disc disease in the presence of neurogenic claudication and spinal stenosis. METHODS: This study was approved by an institutional review board (IRB) and is actively enrolling in a single-arm, multicenter, prospective, open-label fashion. Patients are followed with reporting at 3 months, and 12 months for primary endpoint analysis of efficacy and safety based on improved composite endpoints relative to baseline, with success defined as greater than 20 mm back pain reduction in Visual Analog Scale 100 mm (VAS) while standing or walking, greater than 20 mm leg pain reduction in VAS while standing or walking, Zurich Claudication Questionnaire (ZCQ) improvement of 0.5 or greater in two or three domains, Oswestry Disability Index (ODI) improvement of a least 10 points and no reoperations or revisions at the index level(s). Secondary endpoints included a multidimensional assessment in the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v2.1 and Patient Global Impression of Change (PGIC). RESULTS: In this interim 3-month analysis, 82% of patients reported they were improved from the procedure, while 65% of patients demonstrated clinical meaningful improvement in their pain and function, as defined by the VAS, ODI, and ZCQ. There was only one adverse event and no complications were identified at last clinic research follow-up visit. CONCLUSIONS: This interim analysis of the first 20% of the enrolled patients out to 3 months was to determine safety of the procedure and report on adverse events, acknowledging the heterogeneity of surgical specialty. Further follow-up and greater numbers are needed as the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05504499.
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Purpose: Lumbar interlaminar decompression with interspinous fixation is an established safe and effective treatment for spinal stenosis. Early maintenance of improvements in pain intensity and function are critical for durability of symptom relief. The purpose of this study was to investigate the efficacy of minimally invasive treatments for low back pain during the early period after treatment and their utility in setting the course for longer term success. Patients and Methods: This study utilized patient evaluations at 3- and 6-months following treatment and is part of an actively enrolling, institutional review board (IRB) approved, single-arm, multicenter, prospective, open-label 12-month study. Clinical efficacy was assessed primarily using the change from baseline in Oswestry Disability Index (ODI), Visual Analog Scale (VAS) of the back and leg pain during walking and standing, and Zurich Claudication Questionnaire (ZCQ), and secondarily using the Patient Global Impression of Change (PGIC) and Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v2.1. The safety endpoints were the adverse events and reoperations or revisions at the index level(s). Results: At 6-month post-op, 76%, 62%-64%, and 64% of patients demonstrated clinical meaningful, and statistically significant improvement in their pain as defined by ZCQ, VAS (back and leg), and ODI, respectively. In addition, 78% of patients noted improvement in PGIC. Two procedure-related adverse events were noted which fully resolved without surgical intervention. Conclusion: This 6-month interim analysis at 42% enrollment of patients was conducted to determine prolonged safety and efficacy of the interspinous fusion device. Our analysis showed a sustained improvement in clinical efficacy, and safety endpoints, when compared to the 3-months evaluations, across both interventional pain and neurosurgery specialties.
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AIMS: To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN). METHODS: The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment. In total, 142 patients with a 10 kHz SCS system were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. Assessments included pain intensity, health-related quality of life (HRQoL), sleep, and neurological function. Investigators assessed neurological function via sensory, reflex, and motor tests. They identified a clinically meaningful improvement relative to the baseline assessment if there was a significant persistent improvement in neurological function that impacted the participant's well-being and was attributable to a neurological finding. RESULTS: At 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing ≥50% pain relief. Participants had significantly improved HRQoL and sleep, and 65.7% demonstrated clinically meaningful neurological improvement. Five (3.2%) SCS systems were explanted due to infection. CONCLUSIONS: Over 24 months, 10 kHz SCS provided durable pain relief and significant improvements in HRQoL and sleep. Furthermore, the majority of participants demonstrated neurological improvement. These long-term data support 10 kHz SCS as a safe and highly effective therapy for PDN. TRIAL REGISTRATION: ClincalTrials.gov Identifier, NCT03228420.
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Diabetes Mellitus , Neuropatías Diabéticas , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/métodos , Neuropatías Diabéticas/terapia , Calidad de Vida , Estudios Prospectivos , Dolor , Resultado del TratamientoRESUMEN
INTRODUCTION: Intrathecal therapy has been limited by non-randomized prospective studies, particularly for those suffering from non-cancer. Further, no prospective, randomized studies investigating the efficacy, safety, and utilization of intrathecal polyanalgesic consensus guidelines exist. METHODS: After IRB approval, patients were enrolled in a 1:1 fashion for intrathecal drug delivery (IDD) or conventional management (CMM), employing standard of care, excluding intrathecal drug delivery, based on the principal investigator's discretion. They were followed 3, 6, 9, and 12 months. Assessments included PROMIS 29, NPRS, and PriceMonkey. RESULTS: Seventy-nine patients were screened, 54 patients were enrolled: 26 to IDD and 28 to CMM. At 3 months, there was no measurable difference in pain improvement in either subgroups within the CMM for chronic pain-related syndromes (CPRS) or failed back and related spine disorders (FBRS). For the IDD, early and maintained benefit from the baseline was statistically achieved. Cost analysis of pump to CMM breakeven was 4.5 months. There were no adverse events related to compounded intrathecal medications. CONCLUSION: This is the first randomized prospective, multicenter study investigating the safety, cost, and efficacy of off-label medications for intrathecal therapy, as compared to conventional management, and suggests early detection of improvement, cost savings, safety of intrathecal compounded medication use, and safety and efficacy of employing the PACC guidance.
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Dolor Crónico , Humanos , Dolor Crónico/tratamiento farmacológico , Estudios Prospectivos , Sistemas de Liberación de Medicamentos , Manejo del DolorRESUMEN
Objective: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy. Patients and Methods: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months. Results: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were "satisfied" or "very satisfied" with the 10-kHz SCS treatment. Conclusion: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy. Trial registration: clincaltrials.gov Identifier: NCT03228420.
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The sacroiliac joint (SIJ) is a large, irregularly shaped, serpentine joint structure bordered anteriorly and posteriorly by the sacroiliac ligaments. With increased recognition of the SIJ as a pain source, treatments have been historically nonsurgical in nature. Common treatments include bracing, medications, activity modification, manual therapy, chiropractic manipulation, physical therapy, and intra-articular SIJ injections. Surgical stabilization and/or fusion of the SIJ may be considered when a patient has persistent moderate to severe pain, functional impairment, and failed conservative management. Surgical stabilization and fusion has traditionally been by way of the transiliac approach. More recent SIJ fusion systems have proposed not only a posterior approach but one that stabilizes the joint space by placing an allograft within the SIJ. Anatomically, a posterior approach is able to avoid neurovascular structures that otherwise are encountered with the transiliac approach and may be performed percutaneously. Preliminary evidence reports consistent pain reduction with minimal complications. This paper is purposed to detail the present evidence of minimally invasive posterior SIJ fusion, as well as highlight the need for further research moving forward.