Background: Paresthesia-based spinal cord stimulation (PB-SCS) is used for the treatment of complex regional pain syndrome (CRPS), but many patients are refractory to PB-SCS or experience attenuation of analgesic effect over time due to tolerance. Novel SCS modes including high-frequency, BurstTM, and high-density (HDTM) stimulation were introduced recently and this systematic review was conducted to summarize the evidence on their role for CRPS.Materials and Methods: We searched MEDLINE and other databases  for studies including adults with refractory CRPS treated by paresthesia-free SCS (PF-SCS) modes compared to placebo, conventional medical treatment, or PB-SCS. We determined the posttreatment intensity of pain (up to 24 months after intervention), changes in CRPS-associated symptoms, and associated domains. Sustainability and adverse effects were also assessed.Results: We identified 13 studies  including 62 patients with upper or lower limb CRPS. Eleven papers reported on outcomes of high-frequency stimulation at 10 kHz (HF-10) and other high frequencies, two papers were on Burst, and one paper was on HD. In 59 patients, pain intensity with novel SCS modes was reduced by 30% to 100% with a corresponding reduction in analgesic medications. Novel SCS modes also attenuated CRPS-associated symptoms and six papers reported significant improvement of quality of life.Conclusions: Novel SCS modes have the potential to provide analgesia in patients with CRPS. However, the low quality of available evidence necessitates definitive and prospective comparative effectiveness studies to establish the role of these modes in CRPS. The incidence of this syndrome is 5.46–26.2 per 100 000 person-years with a prevalence of 20.57 cases per 100 000 person-years.2 More women than men seem to be affected and the upper extremity is the most commonly involved body part.3 Though identifying this syndrome accurately can be a challenge, the criteria to diagnose CRPS were refined in 2007 to improve the specificity and reduce sensitivity.4 Several mechanisms seem to play a role in the development of CRPS, including inflammation, vasomotor dysfunction, central sensitization, neuroplasticity, and autoimmune involvement.5Complex regional pain syndrome (CRPS) is characterized by spontaneous and or evoked regional pain that is seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion. The pain is regional but may not (CRPS type I) or may be (CRPS type II) in the distribution of a specific nerve territory or dermatome. CRPS usually has a predominance of abnormal sensory, motor, sudomotor, vasomotor, and trophic findings and it shows variable progression over time.7 Physical therapies should be the mainstay of treatment and these include desensitization, restoration of range of motion, and strength of muscles in the affected extremity. Interventional approaches include neural plexus and sympathetic chain blocks. However, failure to relieve pain and resolve associated symptoms of CRPS is common with these pharmacological and physical therapies.Though a variety of treatment modalities have been proposed for treatment of CRPS, a significant number of patients experience unsatisfactory pain relief and/or have adverse effects from existing pharmacological or neuromodulatory interventions. Pharmacological therapies include nonsteroidal anti-inflammatory drugs, corticosteroids, anticonvulsants, antidepressants, dimethylsulfoxide, N-acetylcysteine, transdermal patches , intravenous infusions of ketamine, and vasodilators.9 Paresthesia-based spinal cord stimulation (PB-SCS), with stimulating frequencies between 30 and 60 Hz that confer a tingling sensation, has been extensively used to treat CRPS over the last 2 decades but it suffers from limitations including attenuation of benefit with time and painful or unwanted paresthesias. The recent increase in availability and use of novel SCS modes promises to address these shortcomings.Neuromodulation approaches including spinal cord, dorsal root ganglia, and peripheral nerve stimulation have been used for chronic pain syndromes with traditionally neuropathic but more recently nociceptive pathologies, including failed back surgery syndrome, CRPS, and other neuropathic pain syndromes.TM), and BurstTM stimulation. It has been proposed these modes share the property of delivering higher amounts of electric charge to the spinal cord, or perhaps the same amount of charge with a higher efficacy, with frequencies in the range of 500 Hz to 10 kHz and stimulation amplitudes that are below the perception threshold.10 These “higher” stimulation frequencies potentially modulate  action potentials that contribute to painful sensations or sympathetic dysregulation but come with the advantage of being paresthesia free.11 It has been suggested that in patients with failure of conventional low-frequency PB-SCS to achieve analgesia, at the time of either SCS trial or loss of benefit with passage of time despite initial success, increasing the stimulation frequency or changing the stimulation pattern to deliver one of the novel SCS modes could confer analgesic benefit despite the absence of paresthesias.12There are three new stimulation modes currently in use: high-frequency stimulation at 10 kHz (HF-10), high-density .13Though the three novel SCS modes share the feature of not having paresthesias, there are some differences among these three modes due to unique combinations of frequency, subperception threshold amplitude, and pulse width. Clinically used high-frequency SCS is usually at a stimulation frequency of 10 kHz applied via bipolar stimulation but any stimulating frequency above 1 kHz has been considered as high.It is not surprising that there has been an increasing interest in the use of PF-SCS in patients with CRPS, a cohort that lacks access to effective analgesic options. There are now a number of recent publications and conference presentations on this topic. The objectives of this scoping review were to evaluate the analgesic impact and adverse effects of PF-SCS on patients with CRPS who had received these modes either as a primary neuromodulation treatment or when it was introduced following failure of PB-SCS.15 This review was registered with PROSPERO .This scoping review was conducted according to the recommendations of the Cochrane Collaboration and it is reported as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (Appendix 1).www.clinicaltrials.gov). Papers in all languages were included when it was possible to translate them into English. Examples of specific search terms used include “spinal cord stimulation,” “neuromodulation,” “burst stimulation or neuromodulation,” “paresthesia-free stimulation,” “high frequency stimulation or neuromodulation,” “high density stimulation or neuromodulation,” “stimulation frequency above 500 kHz,” “complex regional pain syndrome (CRPS),” “algodystrophy,” “Südeck’s atrophy,” and “reflex sympathetic dystrophy.” Boolean operators  were used to combine search terms. The scope of studies included randomized controlled trials, systematic reviews, observational or cohort studies, case–control studies, case series/reports, and conference abstracts.We conducted comprehensive, serial searches of the literature from inception to September 21, 2017, with the assistance of a medical information specialist. The following databases were searched: EMBASE, 1947 onward; MEDLINE, 1946 onward; MEDLINE In-Process and Other Non-Indexed Citations ; and Cochrane Database of Systematic Reviews. PROSPERO and Cochrane Central Register of Controlled Trials were included to identify reviews or trials that may have been published but missed during the initial search on MEDLINE and EMBASE. We also searched Google Scholar (first 200 search results were reviewed) to complement search results from the aforementioned databases with the objective of accessing all content relevant to the topic. Proceedings of the major annual meetings of anesthesiology and pain societies  in the last 2 years were also searched. We also searched for trials in the metaregister of controlled trials , refractive to conventional medical management and or conventional PB-SCS.Intervention: The interventions of interest were the novel SCS modes, including Burst, high-frequency (HF-10), and HD stimulation.Comparator: Comparators included placebo treatment or conventional medical management or conventional PB-SCS.Outcome: Our primary outcome was change in intensity of pain assessed on a numeric rating scale (NRS) or visual analogue scale (VAS) at 1 to 12 months after initiation of the intervention. Secondary outcomes of interest included change in CRPS-associated vasomotor, sudomotor, and trophic symptoms and impact of SCS on pain-associated domains . Sustainability of analgesic benefit and adverse effects were also noted.We prespecified eligibility criteria using the population, intervention, comparator, and outcomes model as follows:Titles, abstracts, and, when required, full text of the papers identified from the initial search were examined for relevance as per the inclusion criteria for this review. Only studies that met the abovementioned criteria were included for data extraction. We completed the search by reviewing the bibliographies of every selected article to look for possible additional articles that were not identified by the initial search.The reference data, populations, and outcomes were extracted from the articles into prespecified tables using a standardized data extraction form. The data collection form was pilot-tested before its use. We extracted information on studies’ source (study ID and reviewer ID), number of patients, type of study, patient characteristics, details of intervention, comparator group where reported, previous treatments, follow-up time points, outcomes, and adverse effects of the intervention. Dichotomous outcomes were extracted where indicated. For continuous data, extraction of means (or medians) and standard deviations (or interquartile ranges or ranges) was performed. We also contacted authors of studies included in our scoping review when we needed more information about their analysis or reported results.Data were independently extracted by two reviewers (Y.H. and M.C.) and any conflicts were resolved by consensus and inputs from the senior author (A.B.).High: Any trial with a high risk of bias listed on three or more domains.Unclear: Any trial with a high risk of bias listed on more than one domain but less than three domains.Low: Any trial with a high risk of bias on no domain or one domain and with no significant methodologic concerns that may have affected the study results.Two review authors (Y.H. and A.B.) independently assessed the risk of bias for randomized controlled trials using the Cochrane Collaboration’s instrument for assessing the risk of bias. Any disagreement was resolved through discussion or, if necessary, arbitration by the senior author (A.B.). The risk of bias instrument assesses the following domains: generation of the allocation sequence, allocation concealment, blinding of investigators and participants, blinding of outcome assessors, incomplete outcome data, selective outcome reporting, and other sources of bias that have less empirical evidence of bias but together may be considered important . Each item was classified as low, unclear, or high risk of bias. A decision to classify “overall bias” as low, unclear, or high was made by the reviewers using the following method:16 This tool has 18 items with three response choices to each question: Yes, unclear/partially reported, or no.The quality of the case series was assessed using the quality appraisal tool developed by Moga et al.Our synthesis of clinical studies was anticipated to focus on results from randomized controlled trials followed by prospective trials or case series or reports. Limited scope for meta-analysis was anticipated due to the limited number, clinical heterogeneity, methodological diversity, and paucity of clinical trials.Our initial search revealed a total of 2099 records. We found another three articles while perusing references from articles that were short-listed and 15 records were found in the clinical trial registries. Details of the search strategy for high-frequency SCS for treatment of CRPS are provided in Appendix 2. Similar methodology was followed for searches for role of Burst and HD SCS in CRPS.21 five conference abstracts,26 and one randomized controlled trial (RCT27)   and 2.1027The results for assessment of the quality of case series included in this review are listed in Appendix 3. Overall, the quality of the case series was moderate with the number of “yes” responses suggesting adherence to quality metrics (maximum possible score is 18) varying from 10 to 13 in the three studies. The overall risk of bias was deemed to be low for the single RCT in this review.13 Use of the IASP Budapest criteria to diagnose CRPS4 was stated only in two papers.23 Twenty-three patients had CRPS in the upper limbs and 39 patients had CRPS in the lower limbs. One publication did not provide details about the location of CRPS but positioning of the SCS leads suggested that patients had CRPS in the lower limbs.13 The duration of CRPS prior to interventions ranged from 5 months to 16 years but this information was not provided in four papers.26The selected papers included a total of 62 patients with CRPS, of whom the majority were females. The age range of patients was between 30 to 75 years and pain intensity in all patients was severe with NRS of 6/10 (or VAS of 60/100) or higher. A diagnosis of CRPS with details of the affected anatomy was provided in all papers except one.27 two described use of Burst SCS mode,27 one described use of HD SCS mode,13 and three studies described use of high-frequency stimulation in the 500 to 10 000 Hz range.27 The pulse width of HF-10 SCS waves was provided in only one study22 (30 ms) and another study on SCS at 1.15 kHz reported the pulse width as 120 ms.20 Of the only two studies on high-frequency SCS up to 10 kHz that reported on the stimulation amplitude, the amplitude range was 0.5–3.5 mA12 and 0.5–10 V19 and the study with SCS at 1.15 kHz reported the amplitude as 5.0 V.20 The two studies on Burst SCS described use of similar parameters: pulse frequency of 500 Hz with a burst frequency of 40 Hz, amplitude of 0.225 mA, and pulse width of 1000 ms.27 The solitary paper on use of HD SCS in patients with CRPS reported use of a frequency range between 130 and 1000 Hz (median 409 Hz), amplitude of 2.4 V, and pulse width ranging from 150 to 1000 ms.13A majority (ten) of these studies involved use of HF-10 SCS therapy,26CRPS is a challenging condition to treat and it is not unusual for a variety of therapeutic modalities to be trialed before an effective option is found. Out of the 62 patients in this review, 15 patients had failed treatment with a multitude of approaches prior to use of PF-SCS. These previous therapies included conventional medical management , peripheral nerve and lumbar sympathetic blocks or radiofrequency lesioning, topical treatments, physiotherapy, transcutaneous electrical nerve stimulation (TENS), cognitive behavioral therapy (CBT), and PB-SCS.26 Though details were not provided, gradual development of tolerance to PB-SCS with increase in intensity of pain after several years of pain relief and/or patients’ dislike of paresthesias (or paresthesias in nonpainful body regions) associated with PB-SCS were the common themes that instigated trials of PF-SCS. Two studies reported failure of PB-SCS during the trial phase.24 Only one RCT conducted a direct comparison of multiple SCS modes: 500 Hz, 1200 Hz, Burst, conventional, and placebo.27 All five modes were programmed in random order during the 10-week crossover period with 2 weeks per setting in this study.A total of eight patients in four reports were previously treated with conventional PB-SCS with analgesic benefit for up to 4 years.26 Burst,27 and other high-frequency SCS modes.27 In the 39 patients with CRPS of the lower limb, stimulating contacts were placed at the eighth to twelfth thoracic vertebral (T8–T12) levels for HF-10,27 HD,13 other high frequencies,27 and Burst SCS modes.27 Only two papers described checking for paresthesias in the region of pain by stimulation to aid radiological guidance for positioning the lead for HF-1012 or Burst and other high-frequency SCS therapies.27 In one study, the authors did not specify the level of SCS lead contacts but stated that “optimal positioning with overlapping paresthesia in painful area” were achieved for Burst SCS (p. 3).18In the 23 patients with documented CRPS of the upper limb, the stimulating contacts of SCS leads were at the second to seventh cervical vertebral (C2–C7) levels for HF-10,25 and another study that used 1.15 kHz for SCS mentioned that the patient had a pre-existing implanted paddle lead.20Details of the type of SCS trial (percutaneous versus tunneled) were not provided in majority of the studies included in this review. Only two papers mentioned that a trial with HF-10 mode was done percutaneously26 or Burst and other high frequencies.27 However, three of the papers in this review did not provide any details about the type or number of leads.19The majority of studies included in this review described the type and number of leads used for delivering PF-SCS. Octopolar cylindrical leads (one or two) were used in 55 patients for HF-1021 high-frequency SCS at 1.15 kHz,20 and Burst and other high-frequency SCS27 and the duration of follow-up was up to 12 months in four publications involving HD13 or HF-10.26 In one study on two patients, HF-10 SCS was delivered for only half a day as part of a trial process.19 Eight patients in three papers included in this review were followed beyond 12 months with Burst18 and HF-10 SCS.25The extent of follow-up had a wide variation in papers included in this review, with a range of less than a day to 24 months. Six of the 13 papers including 41 patients published results of follow-up up to 6 months after initiation of HF-10 SCS,17 used the NRS or VAS to measure intensity of pain and the reduction in intensity of pain ranged from 30% to 100%. Of the 62 patients treated with the novel SCS modes, three failed to get analgesic benefit from the 10-kHz HF-SCS. Of note, these three patients had CRPS involving the feet and they also failed an additional week of conventional PB-SCS despite adequate paresthesia coverage of the affected area.12 None of the 13 papers reported worsening of intensity or symptoms of CRPS with the novel SCS modes.All of the papers included in this review except one27 Al-Kaisy and colleagues used the painDETECT12 as a screening tool to establish whether pain was neuropathic in nature. All six patients with CRPS in this study had high painDETECT scores but the authors did not attempt to correlate these scores with success or failure of HF-SCS. A study by Kriek and colleagues described use of the McGill Pain Questionnaire (MPQ).27 The authors described significant reduction in scores on the sensory scale of the MPQ following therapy with all stimulation modes in the trial  but not with placebo.Characteristics of pain prior to initiation of SCS was assessed in only two studies with the aid of validated tools.26 or Burst SCS18 with reversal to normal or a halt in progression of these features. None of the studies included in this review mentioned the effect of the novel SCS modes on trophic symptoms and signs of CRPS. The impact of these modes on range of motion ranged from “no worsening” in one report18 to an overall improvement26 and one case report in which the patient was able to resume pre-injury activities.25The impact of PF-SCS on vasomotor and sudomotor symptoms was described in five papers involving use of HF-1025 Santarelli and colleagues used the Short Form 36 (SF-36) for this domain with use of HF-10 SCS and they reported significant improvement.23 Two other publications commented on improvement in quality of life with high frequency (1.15 kHz) and HF-10 SCS without specifying which tool was used.21 The severity of pain and the impact on patient’s daily functioning was also investigated with the use of the Brief Pain Inventory (BPI) in one paper with an improvement (reduction) of 45% in the BPI score in all three patients who responded to HF-10 SCS.12The impact of the novel SCS modes on quality of life, measured with the EuroQol–five dimensions (EQ-5D) score in two reports that had four patients in total, ranged from an improvement of 101% at 6 months to 341% improvement at 18 months with HF-10 mode.26 Burst,18 or high-frequency (1.15 kHz) SCS.20Nine of the 13 studies included in this review commented on impact of PF-SCS on analgesic medications. All patients with analgesic benefit from HF-10 SCS were able to lower their daily use of anticonvulsants and opioids, with some patients reporting complete discontinuation of all analgesics with HF-10,23 and one study assessed anxiety subjectively.21 All three papers involved use of HF-10 SCS and reported significant reduction in PCS and CES-D scores and anxiety. Furthermore, only one study commented on improvement of sleep quality with high-frequency (1.15 kHz) SCS but the authors did not use a validated tool to evaluate this domain.20Only two studies reported use of validated tools to measure pain-related catastrophization and depression 27We found only one RCT that compared patients’ preferences about the type of stimulation for CRPS. Four types of stimulation  were compared with placebo in this trial. Fifty-two percent of the study patients preferred nonparesthesia SCS . Though VAS pain scores were lower with preferred stimulation type in responders, all nonparesthesia SCS settings had higher global perceived effect (GPE) scores than placebo.27 Inability to feel paresthesias was identified as a limitation of the novel SCS modes by some patients in this trial. High-frequency SCS (but not Burst) consumes large amounts of energy and it often requires a rechargeable battery with frequent charging and longer duration of charging times compared to conventional PB-SCS. This lack of “recharge burden” with conventional PB-SCS was another reason for some patients preferring this mode in this trial.27The adverse effects profile of the novel SCS modes appeared to be similar to conventional PB-SCS and no adverse effects on the central or peripheral nervous system were reported in the publications included in this review. However, Kriek and colleagues identified factors that played a role in patients choosing the type of SCS when they were given an option to trial SCS at 40 Hz, 500 Hz, or 1200 Hz or using Burst stimulation.13 Burst,18 high frequency at 1.15 kHz,20 and HF-1026 settings, with the authors reporting some degree of restoration of analgesic benefit to the patients. We also found one publication in which it was reported that a patient was reprogrammed to HF-10 SCS after a negative conventional SCS-based trial. This patient responded with complete relief of pain, improved range of motion, and resolution of vasomotor and sudomotor changes with a reduction in analgesic requirement after initiation of HF-10 SCS.21Loss of analgesic effect in patients who previously responded to conventional PB-SCS can have several reasons, including dislocation or malfunction of hardware or development of tolerance. In this review, we came across reports of six patients in four publications who stopped having analgesic benefit with conventional SCS after initial success and despite no lead migration. These patients were reprogrammed with novel SCS modes including HD,This scoping review of the literature on the role of the novel modes of SCS for patients with CRPS is the first of its kind to evaluate evidence for high-frequency, HF-10, Burst, and HD stimulation for this syndrome. Twelve case series or reports and one RCT reported on the use of the novel SCS modes, with failure of conventional PB-SCS being the most common indication for use of these modes. Outcomes were monitored for variable periods of time following initiation of the novel modes.8 Conventional SCS is tonic or paresthesia based and its frequency of stimulation ranges between 30 and 80 Hz with patients perceiving nonpainful paresthesias in lieu of otherwise painful sensations. PB-SCS has been shown to deliver good outcomes for some patients with CRPS but many patients have no or unsatisfactory pain relief with this type of SCS or they cannot tolerate the paresthesias. Another therapeutic challenge with conventional SCS is the development of tolerance, leading to diminishing analgesic effect.28 These limitations have spurred the search for innovations in neuromodulation for treating CRPS. Though not a novel stimulation mode, an excellent example of these efforts is the recently published RCT on stimulation of the dorsal root ganglia  to treat CRPS.29 However, this modality relies on a specific anatomic target while using conventional frequencies and subthreshold amplitudes for stimulation.Though a variety of therapeutic modalities are used to treat CRPS, SCS is one of the few modalities with a high rate of analgesic success for this syndrome.11 Evidence for this SCS mode suggests suppression of mechanical hypersensitivity similar to PB-SCS, while requiring significantly lower intensity of stimulation intensity.32 The mechanism of action of Burst is also unclear, but proposed explanations include modulation of the medial pain pathway directly by actions on C-fibers synapsing onto lamina I neurons and disruption of synchronous burst firing of the high-threshold fibers that results in inhibition of activation directly related to pain perception.10 This is an interesting theory because conventional SCS exerts its effect at the level of the spinal cord and it predominantly modulates the lateral pain pathways.33 HD SCS is delivered by increasing the frequency while retaining pulse width of 300–500 ms and keeping the amplitude below the perception threshold. This mode is postulated to transmit higher amounts of electric charge from the SCS electrodes to the neural tissue, thereby increasing analgesic efficacy, without discomfort or damage to the nervous system.13None of the novel SCS modes are associated with paresthesias, but the postulated mechanisms of action vary for each mode. A majority of papers (11 out of 13) included in our review described the use of high-frequency SCS, an entity that lacks a consensus definition, but any mode with a frequency above 1 kHz is generally accepted in this classification.34 Thus, eliminating reliance on paresthesias can save time and reduce patient discomfort while avoiding the need to adjust stimulation intensity with change in position of the patient.35 Use of novel SCS modes also avoids problems due to paresthesias in the painful region or unwanted paresthesias in the nonpainful body locations. These advantages can shorten SCS trial and implantation procedure times. However, this approach requires definitive knowledge of epidural levels of SCS lead placement for pain in specific body regions that provide relief in CRPS. Though the space between the ninth and tenth thoracic vertebra is accepted as the appropriate level for HF-SCS to relieve low back pain, there is a lack of information regarding appropriate levels to relieve pain in the limbs (as is often the presentation in CRPS), especially in the lower limbs.36 This may explain the finding that all three patients with CRPS of the feet failed to get any benefit from HF-10 SCS in one of the studies included in our review.12 Pending availability of more information regarding “sweet spots” for placing SCS leads to treat CRPS in the limbs, it may be reasonable to check for paresthesias in the region of pain when placing SCS leads with the goal of delivering SCS with one of the novel modes , an approach that was utilized in the RCT by Kriek and colleagues included in this review.27 The recently published Effects of Pulse Rate on Clinical Outcomes (PROCO) study has contributed to knowledge regarding optimal lead placement and stimulation frequency for high-frequency modes. This study recruited patients with low back pain (with or without lower limb pain) who were implanted with SCS systems and underwent an 8-week search to identify the best location (sweet spot) of stimulation at 10 kHz within the searched region (T8–T11). Patients who responded to 10-kHz SCS proceeded to double-blind rate randomization to 1-, 4-, 7-, and 10-kHz SCS at the same sweet spot found for 10 kHz in randomized order (4 weeks at each frequency). The authors found that all four frequencies provided equivalent pain and the mean charge per second differed across frequencies, with 1-kHz SCS requiring 60%–70% less charge than higher frequencies.37 However, the authors did not specify whether patients with CRPS were enrolled in this study. In another study by Al-Kaisy and colleagues, 24 subjects with predominantly axial low back pain undergoing SCS therapy for failed back surgery syndrome were randomized to sham, 1200 Hz, 3030 Hz, and 5882 Hz with a four-phase crossover design over 12 weeks.38 The authors found that SCS at 5882 Hz stimulation produced significant pain relief for axial low back pain compared with lower frequencies and sham stimulation.38 Results from these studies suggest the need for more research into optimal “high” frequency for analgesia, especially in patients with CRPS.Relying on paresthesias to decide on optimal lead positioning in the epidural space and maintaining paresthesias at the location of pain can be challenging and frustrating for patients and health care providers. It requires time and cooperation from a patient who may be quasisedated during the SCS lead placement procedure.24 However, in the RCT included in this review,27 patients were sequentially transitioned from one stimulation mode to another. Though a short washout period (2 days) was provided between application of different SCS modes in this study, a therapeutic bias is possible because the analgesic effects of novel SCS modes could be influenced by previous effects of conventional SCS due to a carryover effect. The same bias could have affected results of two case reports in this review in which HF-10 SCS modes were introduced after failure of conventional SCS, although the follow-up periods exceeded 4 months with preservation of the good results, thereby minimizing the influence of carryover effects.24 Finally, lack of blinding of patients in these papers to the introduction of novel SCS modes after failure of conventional SCS may have influenced reporting of outcomes by patients.This review shows that patients who are unresponsive to conventional PB-SCS, or those who develop tolerance to it over time, can attain therapeutic benefit by switching to the novel SCS modes.23 Further, though CRPS type II is a neuropathic pain syndrome, CRPS type I does not meet the most recent IASP definition of neuropathic pain due to the absence of an identifiable nerve injury.39 However, both types of CRPS have a phenotype that is similar to the presentation of neuropathic pain syndromes. Using validated tools to establish that the pain is neuropathic  and then serial follow-ups with appropriate tools  to establish whether there is resolution of neuropathic character of the pain with use of novel SCS modes can help build confidence in the ability of these modes to relieve pain in patients with CRPS. Finally, though CRPS has abnormal sensory, sudomotor, vasomotor, trophic, and motor features, the majority of papers in our systematic review only focused on the effect of stimulation on pain and sensory changes. Because all components of CRPS contribute to morbidity, effects of therapies on all domains should be evaluated. Only five papers in this review mentioned the effect of novel SCS modes on nonsensory domains of CRPS.26Though the Budapest diagnostic criteria for CRPS were accepted by the IASP over 5 years ago, these criteria were used in only two of the papers in this review.40 SCS is a resource-intensive intervention and comprehensive evaluation of outcomes to establish its impact in CRPS is essential. Recently published studies have also cast doubts on the assumption that benefit from high-frequency SCS is enhanced proportional to the frequency of stimulation.37 Thus, multidomain monitoring of features of CRPS and estimation of cost–benefit ratios are essential for establishing efficacy and effectiveness of novel SCS modes.A majority of the papers included in this review did not describe use of validated tools to evaluate psychological  and physical function. This is surprising because the importance of evaluating pain-related domains in clinical and research settings is established and validated tools to evaluate these domains are also widely available.11 However, HF-10 and HD potentially deliver electrical charge of a higher magnitude or with a higher efficacy to the spinal cord10 and require frequent recharging of the implanted pulse generator. These modes are also fairly new to clinical practice and their long-term adverse effects, if any, are unknown.None of the papers included in this review reported any serious adverse effects or safety issues when novel SCS modes were used in patients with CRPS. Animal and clinical studies have been published on the possible adverse effects of HF-10 on the spinal cord and these studies report a safety profile similar to that of conventional SCS.We have provided recommendations for data elements to be included in studies on novel SCS modes for patients with CRPS in 21 and five conference abstracts.26 Case series or reports occupies a low rung in the hierarchy for evidence-based medicine because observational data are prone to various types of biases, including expectation, measurement, and reporting biases.41 Further, abstracts are often not considered to be peer reviewed. A case in point is the absence of papers in the literature that report failure of novel SCS modes in CRPS. The wide range of follow-up periods in papers included in this review also makes it difficult to gauge the longevity of benefit from these modes. One of the case series included in this review had an observation period of only half a day following initiation of the novel SCS modes but the authors acknowledged that their study was not designed to test the long-term effect of such therapy. We agree with the authors reasoning about the observation that patients experienced benefit with high-frequency stimulation suggests a strong effect of high-frequency SCS therapy. Only 30% of patients included in this review were followed beyond 6 months following initiation of novel SCS modes and a few papers reported outcomes at 12 months or beyond following initiation of these modes.25 Follow-up for a year and beyond is usually required to assess longevity of analgesic effects, as well as the effect of novel SCS modes on other CRPS symptoms and the possible long-term adverse effects and failure resulting in explantation of the system.There are some limitations of our review. Although we conducted a comprehensive search of literature, only 13 papers on novel SCS modes for CRPS with a total of 62 patients were identified. The quality of evidence supporting use of these modes was modest and the papers included in this review were seven case reports or seriesIn our scoping review, we found papers that reported benefit from HF-10, Burst, and HD SCS modes in patients with CRPS. However, the low quality of this evidence precludes any definitive conclusions as to whether these novel SCS modes provide better therapeutic efficacy over the long term compared to conventional paresthesia-based modes in patients with CRPS. Rigorous head-to-head comparisons of the novel SCS modes against each other and against conventional paresthesia-based modes in patients with a diagnosis of CRPS established as per IASP criteria are required. Evaluation of all pain-related domains over a period of time (at least one year) in these trials is essential to build a high-quality pool of evidence for the role of novel SCS modes in SCS.Click here for additional data file.


Is provision of pictorial information on asymptomatic atherosclerosis to physicians and patients associated with prescribing of lipid-lowering or antihypertensive drugs during the following 465 days?In this randomized clinical trial including 3532 participants with low to moderate cardiovascular disease risk, use of pictorial information on carotid intima-media thickness and carotid plaques based on ultrasonographic examination was evaluated. Physician prescription increased for lipid-lowering medications but not for antihypertensive drugs.The findings of this randomized clinical trial demonstrate that information on carotid intima-media thickness and the presence of carotid plaques can improve prescription of lipid-lowering drugs. Preventive drugs are often underused. Carotid intima-media thickness and carotid plaques are associated with cardiovascular disease (CVD), and their detection could possibly improve estimation of the likelihood of CVD and prescription of preventive drugs.To evaluate whether pictorial information on participants’ asymptomatic atherosclerosis based on carotid ultrasonographic examinations to participants and their physicians had an effect on prescribing of lipid-lowering or antihypertensive drugs during the following 465 days.Visualization of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention is a pragmatic randomized clinical trial nested within the Västerbotten Intervention Program, a CVD screening and prevention program in Sweden with 60% to 70% participation rates and small social selection bias. A total of 4177 individuals aged 40, 50, or 60 years participating in the Västerbotten Intervention Program who had low to moderate risk of CVD were invited to enroll in this trial from April 29, 2013, to June 7, 2016. Prescriptions for all participants were monitored for 465 days after the intervention. Data analysis was conducted from December 6, 2019, to April 2, 2020.Participants and their family physicians were randomly assigned 1:1 to receive or not receive pictorial information from carotid ultrasonographic determination of vascular age, assessed as carotid intima-media thickness and the presence of carotid plaques, combined with a follow-up call to participants by nurses.Two outcome measures of prescriptions of antihypertensive and lipid-lowering drugs within 465 days after ultrasonography was performed. Data obtained through intention-to-treat analysis are presented as proportions of individuals with a prescription among those who had no baseline prescription for agents from these drug classes.P < .001) and women . There were no significant differences in the proportion with prescription of antihypertensive drugs in the intervention vs control groups after ultrasonography among men  and women .Of the 4177 individuals invited to enroll, 3532 participants were randomized and included in the analysis; 1870 (52.9%) were women, 2278 (64.5%) were aged 60 years, 978 (27.7%) were 50 years, and 276 (7.8%) were 40 years. First prescriptions of lipid-lowering drugs were higher in the intervention group vs the control group among men (118 of 639 [18.5%] vs 38 of 692 [5.5%]; The findings of this trial demonstrate that provision of pictorial information on vascular age and carotid plaques based on the results of ultrasonographic examination increased physician prescription of lipid-lowering drugs but not antihypertensive drugs within the following 465 days.NCT01849575ClinicalTrials.gov Identifier:  This randomized clinical trial examines the effect of the use of pictorial information including carotid ultrasonographic images with explanation on prescribing of lipid-lowering and antihypertensive drugs. The results of the VIPVIZA primary outcome at 1 year follow-up showed significant differences in the Framingham risk score and European Systematic Coronary Risk Evaluation between the intervention and control participants.In this secondary analysis of VIPVIZA, we aimed to assess whether the proportion of participants with a first prescription of lipid-lowering or antihypertensive drugs differed between intervention and control groups during 465 days following the carotid ultrasonographic examination and whether first prescriptions were related to the information about carotid plaques. Furthermore, we investigated whether factors other than vascular age and plaques were associated with prescription of lipid-lowering or antihypertensive drugs.CONSORT) reporting guideline for randomized clinical trials.VIPVIZA has been approved by the Regional Ethical Review Board, Umeå University. All participants have given informed written consent; no financial compensation was provided. The trial protocol and statistical analysis plan are available in 13 The VIP invites all individuals in the county the year they turn 40, 50 and 60 years old to risk factor screening and individual health promotion at their primary health care center. Follow-up and pharmacologic treatment are provided according to clinical guidelines. From April 29, 2013, to June 7, 2016, participants who went through the VIP program were thereafter invited to enroll in VIPVIZA if they fulfilled the inclusion criteria. Data analysis was conducted from December 6, 2019, to April 2, 2020.The pragmatic randomized controlled study VIPVIZA was set up within the VIP. The VIP is a population-based program for CVD prevention in Västerbotten County, Sweden. The VIP has been running for over 25 years and the participation rates during 2013-2016 were 60%-70% with only small social selection bias.Inclusion criteria for VIPVIZA were (1) age 40 years and first-degree relative with a history of CVD at age less than 60 years, (2) age 50 years and at least 1 designated risk factor , or (3) age 60 years.12 A list with a computer-generated random allocation sequence  was prepared in advance, and participants were allocated consecutively before examination. The allocation was concealed from both participants and examiners. Participants who were found to have stenosis greater than or equal to 50% of the carotid lumen (n = 22) were excluded from the study and referred to specialized care for evaluation and treatment.All individuals who agreed to participate in VIPVIZA underwent a carotid ultrasonographic examination but did not receive any information on the results during the examination. Examinations were performed by trained sonographers from the Heart Centre, Umeå University Hospital, according to a standardized protocol  or antihypertensive drug  at baseline if they had received at least 1 prescription within 465 days before the date of the ultrasonographic examination or at follow-up if they had received at least 1 prescription within 465 days after the ultrasonographic examination. Data from the follow-up are presented as the proportion of individuals with a first prescription among those without a baseline prescription.12 and the diagram with further information specific to the present trial is shown in eFigure 2 in A period of 465 days was chosen because prescriptions in Sweden often cover 400 days’ supply. Operational definitions of variables are reported in eTable 1 in 12P values <.05 were used to signify statistical significance on 2-sided hypotheses testing. Baseline data were analyzed separately for men and women. Using intention-to-treat analysis, we compared the proportion of participants with prescriptions in the intervention and control groups using the χ2 test. We performed subgroup analysis based on the presence of plaques. Multivariable logistic regression models were used to compare the odds of prescriptions among participants in the intervention compared with the control group and to investigate which factors, other than plaque and cIMT, were associated with prescription. Independent variables in the logistic regression models included age, sex, educational level, diabetes, blood pressure greater than or equal to 140/90 mm Hg, serum cholesterol levels, prescription of antihypertensive or lipid-lowering drugs at baseline, and year of baseline data collection. Information about plaque and cIMT were included in separate analyses for the intervention group only, because this information was concealed from participants and physicians in the control group. Data were analyzed using SPSS Statistics, version 26 (IBM Corp).A sample size of 1500 individuals per group would allow identification of minimum detectable change of 0.02 mm in cIMT from baseline to 3-year follow-up with a power of 80% and precision of 5%. Estimation of the effects of our primary and secondary outcomes would maintain the same level of power and precision in our study with even smaller sample sizes.P < .001), but only 12.8% of women had been prescribed a lipid-lowering drug compared with 19.9% of men (P < .001). A larger proportion of men had blood pressure levels greater than or equal to 140/90 mm Hg  and had a prescription for an antihypertensive drug at baseline . Other baseline characteristics are presented in From April 29, 2013, to June 7, 2016, 3532 participants were recruited to enroll in VIPVIZA, of whom 1870 (52.9%) were women, 2278 (64.5%) were aged 60 years, 978 (27.7%) were 50 years, and 276 (7.8%) were 40 years. Higher levels of baseline total cholesterol levels were observed in women , and 15.5% (126 of 814) of women in the intervention group compared with 4.7% (38 of 817) in the control group (P < .001) were prescribed lipid-lowering drugs. Only 2 of all prescriptions for a lipid-lowering drug were not a statin. There were no significant differences in the proportion of participants with a first prescription for antihypertensive drugs between the intervention and control group among either men or women: 12.0% (58 of 482) of men in the intervention group compared with 10.6% (56 of 528) in the control group (P = .47), and 9.8% (60 of 612) of women in the intervention group compared with 10.4% (64 of 615) in the control group (P = .73) were prescribed antihypertensive drugs. In the logistic regression models, we observed an association between the intervention and prescription of lipid-lowering drugs but not with antihypertensive drugs (Prescription of lipid-lowering drugs after ultrasonography to participants without a baseline prescription for lipid-lowering drugs was more common in the intervention group among both men and women: 18.5% (118 of 639) of men in the intervention group compared with 5.5% (38 of 692) in the control group  and those without plaques . However, the proportion was more than 3 times higher in participants with plaques , an antihypertensive drug at baseline , or a higher level of total serum cholesterol  increased the odds of a first prescription . In the P = .18) or antihypertensive drugs  to participants with a baseline prescription for these agents.Prescriptions were renewed within 465 days after the ultrasonographic examination in 523 (91.8%) of the 570 participants with a baseline prescription for a lipid-lowering drug and 1233 (95.2%) of the 1295 participants with a baseline prescription for an antihypertensive drug. There were no significant differences between the intervention and control groups in prescription of either lipid-lowering drugs , the power to find a difference between the groups in the rate of new prescriptions of antihypertensive drugs was lower than for lipid-lowering drugs.Pictorial information about the presence of subclinical carotid atherosclerosis had a different effect on physician prescription of lipid-lowering drugs compared with antihypertensive drugs. Prescription of lipid-lowering but not antihypertensive drugs increased if participants and their physicians received pictorial information about the presence of carotid plaques and vascular age based on carotid ultrasonography findings (the intervention group) compared with those who did not receive any information (the control group). Prescription of lipid-lowering drugs was also more common among those with an increased risk of CVD . Prescription of antihypertensive drugs was associated with blood pressure level, diabetes, and age. The presence of plaque was also associated with prescription of antihypertensive drugs, although the provision of pictorial information had no influence on the total prescription of antihypertensive drugs in the intervention group. Information about vascular age was associated with higher levels of prescription for lipid-lowering agents but not antihypertensive drugs  was objectively measured in all participants. A lipid-lowering or antihypertensive drug is available by prescription only in Sweden. Our study included all prescriptions for lipid-lowering and antihypertensive drugs in the Region Västerbotten database.15 All study participants (intervention and control groups) were also VIP participants and hence had previously received risk factor information and a health dialogue aiming at health promotion. When needed according to guidelines, they also received a follow-up and physician evaluation regarding pharmacologic treatment. Thus, the only difference between the intervention and control groups was the pictorial presentation of carotid ultrasonography results.After receiving the results, participants in the intervention group were contacted by telephone from a research nurse for support and clarification, but the participants or primary care physicians had to initiate another appointment or prescription if this action was considered important. The outcome of this study was physician prescribing behavior, but prescribing also depends on the participants´ inclination to seek health care and interest in using drugs.16 Individuals with plaques were, according to the current clinical guidelines,5 classified as having a very high risk for CVD and should, in most cases, be prescribed lipid-lowering drugs and, if their blood pressure is high, antihypertensive drugs. Information about whether participants had been offered treatment but declined was not available. Among participants not using drugs, there could have been an intention to try lifestyle changes instead of or before initiating drug treatment. The use of evidence-based drug treatments for prevention of CVD has also been low in other studies.17The presence of plaque is an anatomical marker of atherosclerosis and estimates the probability of cardiovascular events in asymptomatic individuals.20 In an observational study from the US on the outcomes of carotid ultrasonographic screening, physicians were more likely to prescribe lipid-lowering drugs but not antihypertensive drugs to participants with carotid plaques or cIMT greater than the 75th percentile.18 In a nonrandomized study from the UK, there was a significant increase in the use of antihypertensive but not lipid-lowering drugs in participants with plaque or cIMT greater than or equal to 1 mm.19 Furthermore, a meta-analysis suggested that identifying calcified coronary plaques increased the initiation of both lipid-lowering and antihypertensive drug treatment.20 None of these studies used pictorial images to inform participants about the ultrasonographic examination results.Previous studies on the association between atherosclerosis detection and the prescription of drugs are mainly nonrandomized.This trial had limitations. Drugs prescribed outside health services funded by the Region were not included in our analysis; however, because the Region funds almost all health care in Västerbotten, this factor was not likely to have any significant influence on the results. We did not use information on the quantities prescribed, prescription duration, whether a prescription was withdrawn due, for example, to adverse drug reactions, or whether the prescribed drugs were actually used.To our knowledge, this is the first randomized clinical trial on the effect of pictorial information from carotid ultrasonographic screening on the prescription of lipid-lowering and antihypertensive drugs in individuals with subclinical atherosclerosis. The first prescription of lipid-lowering but not antihypertensive drugs was higher in the 465 days after the prescription if participants and their physicians were provided with pictorial information based on the ultrasonographic findings combined with a nurse-led follow-up call to the participants compared with no information about ultrasonography results.


All participants completed a graded exercise test and performed two exercise sessions (HIIE and MICE) in random order. Affective responses were assessed during and after each exercise session, using the rating of perceived exertion (RPE), Self-Assessment-Manikin (SAM), and Subjective Exercise Experience Scale (SEES). The results showed that the RPE scores were significantly higher in HIIE than in MICE. HIIE resulted in significantly lower pleasure scores using the SAM while arousal and dominance scores were significantly higher with HIIE compared to MICE. Positive well-being scores using the SEES were significantly lower with HIIE and both psychological distress and fatigue scores were significantly higher with HIIE. The results showed that affective responses with MICE were more positive than with HIIE, but no differences were found between normal and overweight/obese women. Based on these results, MICE may be a more acceptable exercise program for inactive women regardless of their weight status.This study aimed to investigate the effects of an acute bout of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on affective responses in inactive women. Thirty women with normal body mass index (BMI) and 30 women with BMI ≥ 24 kg/m Affective responses can be viewed as an umbrella term that encompasses related concepts, including core affect  and arousal), emotions , and moods  ,2. AffecThe same research group expanded the study by recruiting participants who are normal weight, overweight and obese women. Obese women gave lower pleasure ratings to a one-bout exercise test, compared to normal- and over-weight women. The authors reported that the lower levels of pleasure experienced by obese women, compared to the non-obese women, could be due to their dramatically low levels of physical activity participation  . MoreoveAffective responses to exercise represent an important opportunity to predict the future physical activity level . MattssoWhile lack of time has been reported to be the most common barrier to physical activity in Taiwan , high-in2) and 30 participants whose BMI indicated overweight/obese (24–34.9 kg/m2). All participants were informed about the purpose, procedures, and precautions of the study before they signed the Informed Consent Form approved by the Kaohsiung Medical University Institutional Review Board (KMUH-IRB-20140034).A total of 60 female participants were recruited through word of mouth or webpage from Kaohsiung Medical University, Taiwan, including 30 participants whose body mass index (BMI) indicated normal body weight (18.5–23.9 kg/m2. Participants were excluded if they: (1) engaged in regular physical activity  [2) or had other physical contraindications to exercise  [To enroll in this study, participants had to be: (1) female between 20 and 40 years of age, which is the population with the lowest exercise participation rate in Taiwan  and (2)  months) ; (2) werdisease) ; or (3) 2max test during the first visit. Each participant then was scheduled for two additional visits for exercise sessions: high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE). The order of the exercise sessions was randomized and counterbalanced, and the two exercise sessions were at least one day apart. Exercise sessions were scheduled between the 5th and 10th day post-menstruation for each participant, during the same time of a day and conducted by the same examiner. The temperature of the laboratory remained at 25 °C for all sessions. All participants were also instructed to: (1) have enough sleep the night before the test, (2) avoid caffeine consumption during the day of exercise session, and (3) abstain from food for at least 1 h prior to the exercise session.All participants were asked to complete body composition measurement and the VODuring each exercise session, participants were asked to complete the SAM and their rated perceived exertion (RPE) assessments before each session, during the first 5 min, half-way through the exercise session, in the last 5 min, at the end of the exercise session, as well as at 5, 15 and 30 min post exercise session. The SEES was completed by the participants before and after the exercise session as well as at 5, 15 and 30 min post exercise session. Participants shared their preference for exercise mode when prompted after the completion of both exercise sessions. Since the SEES was difficult to measure during exercise, it was measured half-way through the exercise session.2max was measured using the Åstrand cycle test protocol [2max test. The test was terminated and the VO2max was determined when one of the following criteria was reached: (1) participants were unable to remain cycling at 50 rpm; (2) the heart rate failed to increase with increase in exercise intensity; or (3) the participant was fatigued and could not continue the testing.The participants’ VOprotocol . The parprotocol  at the eParticipants’ body weight, BMI, fat mass and body fat percentage were obtained by using a multifrequency bioelectrical impedance analyzer .Self-Assessment Manikin (SAM) is a non-verbal pictorial assessment technique that directly measures the pleasure, arousal, and dominance associated with a person’s affective reaction to an object or event . SAM ranThe 3-factor SEES is a measure of global psychological responses to the exercise. The 3 factors comprise 4 items each: (1) positive well-being ; (2) psychological distress ; (3) fatigue . Participants were asked to score each item on a 7-point Likert scale with verbal anchors of “not at all” (1), “very much so” (7), and a midpoint anchor of “moderately so” (4).The exercise protocol used in the present study was adapted from previous published studies ,15, and 2 reserve for all participants [Exercise intensity was 50% VOicipants . The exe2max and maximal heart rate, were generated and compared between normal-weight and overweight/obese groups using the Student T-test. The differences in exercise modes between groups and at each time point were assessed using the three-way repeated measures analysis of variance (ANOVA). Significant F-tests were followed by post-hoc comparisons using the Bonferroni correction method. Estimates of effect size using the partial eta squared (η2) and Cohen’s d were reported to present the magnitude of the effect. The significance level (α level) was set at 0.05.Data were analyzed using SPSS 19.0  for Windows. Descriptive statistics (mean ± SD) for continuous variables, such as age, BMI, percentage of body fat, heart rate, VO2max was lower    The averp < 0.03). Similar findings were found in the normal weight group, where the RPE was greater for HIIE than MICE during the exercise session, at the end of the exercise session, and at 5 and 15 min post exercise session . There was no significant difference between the groups in RPE pre-exercise or changes in the RPE during/post exercise session.In the overweight/obese group, the RPE was greater for HIIE, compared to MICE, during the exercise session, at the end of the exercise session, and at 5, 15, and 30 min post exercise session . Similar results were found in the normal weight group, where the score of pleasure was lower for HIIE than that for MICE during the exercise session, at the end of the exercise session, and at 5 and 15 min post exercise session . When measured at the pre-exercise session timepoint, the score of pleasure for HIIE was greater in the overweight/obese group than that in the normal weight group (p = 0.005). There was no significant difference between the groups in changes in the pleasure score during/post exercise session . Similar results were found in the normal weight group, where the score of arousal was greater for HIIE than MICE during the exercise session, at the end of the exercise session, and at 5 and 15 min post exercise session . There was no significant difference between the groups in the score of arousal pre-exercise or changes in the arousal score during/post exercise session . Similar results were found in the normal weight group, where the score of dominance was greater for HIIE than MICE during the exercise session, at the end of the exercise session, and at 30 min post exercise session . There was no significant difference between the groups in the score of dominance pre-exercise or changes in the dominance score during/post exercise session . Similar results were found in the normal weight group, where the score of positive well-being was lower for HIIE than MICE at the end of the exercise session and at 5, 15 and 30 min post exercise session . There was no significant difference between the groups in the score of positive well-being pre-exercise or the change in positive well-being score during/post exercise session . Similar results were found in the normal weight group, where the score of psychological distress was greater for HIIE than MICE at the end of the exercise session and at 5, 15 and 30 min post exercise session . There was no significant difference between the groups in the score of psychological distress pre-exercise or the change in psychological distress score during/post exercise session . Similar results were found in the normal weight group, where the score of fatigue was greater for HIIE than MICE at the end of the exercise session and at 5, 15, and 30 min post exercise session . When compared between the groups, there was a significant difference in the change in fatigue score through the entire exercise course (p = 0.032); however, when separated by exercise modes, no significant difference was observed between the groups in either the HIIE or the MICE session. There was no significant difference between the groups in the score of fatigue pre-exercise  [2peak) than at lower intensity (40% VO2peak) [When affective responses were assessed using the SAM, pleasure was rated lower for HIIE than that for MICE, and remained lower even 15 min after the exercise session was terminated. Previous studies have found that the pleasure level was rated lower when participants performed higher intensity exercise (70% VOVO2peak) ,21,22. SVO2peak) , it may max cycling session while no change was found during a 40% HRmax cycling session. These studies imply that the perception and affective responses to exercise training modes vary between men and women and between active and inactive individuals [The score for positive well-being, measured by SEES, was lower after the HIIE session than that after the MICE session. Previous research found that the score of positive well-being was rated higher during a cycling session at 50% HRR, compared to that at 85% HRR in young women . On the ividuals ; thus, i2peak exercise session than that during a 60% VO2peak exercise session [Psychological distress was greater post HIIE session than that after the MICE session. These findings indicated that inactive women perceived a higher level of psychological distress after HIIE. Previous studies related to psychological distress showed mixed findings. One study showed that women reported greater psychological distress during a 80% VO session . On the  session . The disSimilar to the findings for psychological distress and RPE, the score of fatigue was higher post HIIE session than that after MICE. This finding complied with a previous study, where a higher level of fatigue presented during a 85% HRR cycling session than that during a 50% HRR cycling session in young women .All of the participants chose MICE as their preferred mode of exercise compared to HIIE and rated higher positive affective responses to MICE than HIIE. Given the growing research evidence indicating that affective response to a single exercise session can affect the physical activity level and exercise compliance in the future , our resThese findings were found in women aged between 20 and 28 years; thus, the results may not be generalized to men and other age groups. In addition, the affective responses to exercise sessions, assessed by subjective questionnaires, could have been influenced by participants’ physical and psychological status during the day or by the interaction between the participant and the examiner. The exercise sessions in the present study were all scheduled between the 5th and 10th day post-menstruation for all the participants, at the same time in a day, and conducted by the same examiner to avoid the fluctuation of physical and psychological status. We only used one HIIE protocol in the present study; therefore, in the future, comparison of affective responses to multiple HIIE protocols  is warranted. The conventional MICE seemed to be favored by all the participants in the present study; however, participants’ long-term compliance to a MICE program requires further examination.Both normal-weight and overweight/obese inactive women reported higher levels of pleasure and positive affective responses to MICE, compared to HIIE. All participants chose MICE as their preferred mode of exercise for future training, suggesting that the affective response during a single bout of exercise session may be associated with the choice of future exercise sessions. Although HIIE is a time-efficient training strategy which provides health benefits similar to MICE, MICE appears to be a preferred approach producing more positive affective responses and possibly better adherence to exercise in the future for inactive women.