Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial.

INTRODUCTION: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. METHODS: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. RESULTS: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p<0.001 at all time points). CONCLUSION: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. TRIAL REGISTRATION NUMBER: NCT02924129.

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. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group. CONCLUSION: This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS. TRIAL REGISTRATION NUMBER: NCT02924129.

Holistic Treatment Response: An International Expert Panel Definition and Criteria for a New Paradigm in the Assessment of Clinical Outcomes of Spinal Cord Stimulation.

BACKGROUND: Treatment response to spinal cord stimulation (SCS) is focused on the magnitude of effects on pain intensity. However, chronic pain is a multidimensional condition that may affect individuals in different ways and as such it seems reductionist to evaluate treatment response based solely on a unidimensional measure such as pain intensity. AIM: The aim of this article is to add to a framework started by IMMPACT for assessing the wider health impact of treatment with SCS for people with chronic pain, a "holistic treatment response". DISCUSSION: Several aspects need consideration in the assessment of a holistic treatment response. SCS device data and how it relates to patient outcomes, is essential to improve the understanding of the different types of SCS, improve patient selection, long-term clinical outcomes, and reproducibility of findings. The outcomes to include in the evaluation of a holistic treatment response need to consider clinical relevance for patients and clinicians. Assessment of the holistic response combines two key concepts of patient assessment: (1) patients level of baseline (pre-treatment) unmet need across a range of health domains; (2) demonstration of patient-relevant improvements in these health domains with treatment. The minimal clinical important difference (MCID) is an established approach to reflect changes after a clinical intervention that are meaningful for the patient and can be used to identify treatment response to each individual domain. A holistic treatment response needs to account for MCIDs in all domains of importance for which the patient presents dysfunctional scores pre-treatment. The number of domains included in a holistic treatment response may vary and should be considered on an individual basis. Physiologic confirmation of therapy delivery and utilisation should be included as part of the evaluation of a holistic treatment response and is essential to advance the field of SCS and increase transparency and reproducibility of the findings.

Gradation of Clinical Holistic Response as New Composite Outcome to Evaluate Success in Spinal Cord Stimulation Studies for Pain.

INTRODUCTION: The most prominent outcome measurement in the field of neuromodulation is pain relief. Nevertheless, the number of studies that rely on composite outcomes has increased. The aims of this study are twofold: (1) to evaluate which measures are important to include in a composite outcome and (2) to develop this new composite outcome to evaluate the degree of being a clinical holistic responder with a corresponding minimal clinical important difference (MCID). MATERIALS AND METHODS: Data from patients with persistent spinal pain syndrome type 2 treated with High-Dose Spinal Cord Stimulation (HD-SCS) were used. Pain intensity for low back and leg pain, disability, health-related quality of life, medication use, and patient satisfaction were measured at baseline and after 12 months of HD-SCS. Exploratory and Confirmatory Factor Analyses were used to evaluate which measures should be included in the composite outcome. Anchor-based and distribution-based methods were applied to determine the MCID of the newly developed outcome measurement. RESULTS: A three-factor model was the most appropriate for this data set, in which leg pain intensity, EQ5D VAS, and disability had the largest loading on these factors. A clinical holistic outcome was created with a total score ranging from 0 (=better [no pain, no disability, and perfect health status]) to 300 (=worse [maximal pain, maximal disability, and worst health status]). The MCID value based on an absolute change score from baseline up to 12 months of HD-SCS was 87.97. When calculating with percentage changes, a MCID value of 48.4% was revealed. CONCLUSIONS: This new composite outcome evaluating the degree of deviation from being a holistic responder is a step toward a meaningful, overall outcome assessment for patients who are treated with SCS. Further studies to evaluate the psychometric properties and the generalizability toward other patient populations still need to be performed.

Mindfulness-Based Interventions During Pregnancy: a Systematic Review and Meta-analysis.

This systematic review aims to assess the effect of mindfulness-based interventions carried out during pregnancy exploring mindfulness and mental health outcomes. A systematic review was conducted to appraise the current literature on the subject area. Inclusion and exclusion criteria were agreed and after reviewing titles, abstracts and full papers, 14 articles met the inclusion criteria and were included in the review. The quality of included articles was checked using the Quality Assessment Tool for Quantitative Studies. Pooled results of the randomised controlled trials (RCTs) reporting outcomes on anxiety, depression and perceived stress indicated no differences between the mindfulness intervention group and the control group. Pooled results of the non-RCTs reporting anxiety, depression and perceived stress showed a significant benefit for the mindfulness group. Mindfulness as an outcome was assessed in four RCTs for which the pooled results show a significant difference in favour of the mindfulness intervention when compared to a control group. The pooled results of the four non-RCTs also indicate a significant difference following mindfulness intervention. Results suggest that mindfulness-based interventions can be beneficial for outcomes such as anxiety, depression, perceived stress and levels of mindfulness during the perinatal period. Further research would be useful to explore if such benefits are sustained during the post-natal period.

An overview of treatment approaches for chronic pain management.

Pain which persists after healing is expected to have taken place, or which exists in the absence of tissue damage, is termed chronic pain. By definition chronic pain cannot be treated and cured in the conventional biomedical sense; rather, the patient who is suffering from the pain must be given the tools with which their long-term pain can be managed to an acceptable level. This article will provide an overview of treatment approaches available for the management of persistent non-malignant pain. As well as attempting to provide relief from the physical aspects of pain through the judicious use of analgesics, interventions, stimulations, and irritations, it is important to pay equal attention to the psychosocial complaints which almost always accompany long-term pain. The pain clinic offers a biopsychosocial approach to treatment with the multidisciplinary pain management programme; encouraging patients to take control of their pain problem and lead a fulfilling life in spite of the pain.

Complications of Spinal Cord Stimulation and Peripheral Nerve Stimulation Techniques: A Review of the Literature.

OBJECTIVE: Spinal cord and peripheral neurostimulation techniques have been practiced since 1967 for the relief of pain, and some techniques are also used for improvement in organ function. Neuromodulation has recognized complications, although very rarely do these cause long-term morbidity. The aim of this article is to present a review of complications observed in patients treated with neurostimulation techniques. METHODS: A review of the major recent publications in the literature on the subjects of spinal cord, occipital, sacral, and peripheral nerve field stimulation was conducted. RESULTS: The incidence of complications reported varies from 30% to 40% of patients affected by one or more complications. Adverse events can be subdivided into hardware-related complications and biological complications. The commonest hardware-related complication is lead migration. Other lead related complications such as failure or fracture have also been reported. Common biological complications include infection and pain over the implant. Serious biological complications such as dural puncture headache and neurological damage are rarely observed. CONCLUSIONS: Spinal cord and peripheral neurostimulation techniques are safe and reversible therapies. Hardware-related complications are more commonly observed than biological complications. Serious adverse events such as neurological damage are rare.

A systematic literature review of psychological characteristics as determinants of outcome for spinal cord stimulation therapy.

Psychological factors are deemed important when considering patients for suitability for Spinal Cord Stimulation (SCS). However, there is to date no consensus on which psychological characteristics or tests to undertake. This review analyses the literature to determine findings concerning the psychological characteristics observed and their impact on SCS efficacy for chronic pain. A search in the databases Cochrane, EBSCOhost (CINAHL, MEDLINE, PsycINFO and PsycARTICLES) and a hand search of reference lists from selected articles were performed, resulting in nine relevant articles. The Minnesota Multiphasic Personality Inventory was the most commonly used tool for assessing psychological factors. Only one study used a semi-structured interview instead of questionnaires. Studies lacked long term followup. Depression was identified in six studies as a factor that reduces efficacy, also as a characteristic that can improve after successful SCS by two studies. One study did not include patients with depression, due to previous research indicating depression as a contra-indication. Hypochondriasis and hysteria had conflicting results for prediction of efficacy. Mania was predicted by only two studies as a positive indicator for success. Further long term studies of psychological factors on outcome from SCS are needed.