A nonhomogenous QTT profile appears to be predictive of response to capsaicin. We hypothesize patients with a partial loss of cutaneous nerve fibers or receptors are more likely to respond. By contrast, when severe nerve damage or normal cutaneous sensations are present, the pain is likely due to central sensitization and thus not responsive to capsaicin. Prospective studies with larger patient samples are needed to confirm this hypothesis.There are no reliable predictors of response to treatment with capsaicin. Given that capsaicin application causes heat sensation, differences in quantitative thermal testing (QTT) profiles may predict treatment response. The aim of this study was to determine whether different QTT profiles could predict treatment outcomes in patients with localized peripheral neuropathic pain (PeLNP). We obtained from medical records QTT results and treatment outcomes of 55 patients treated between 2010 and 2013. Warm sensation threshold (WST) and heat pain threshold (HPT) values were assessed at baseline at the treatment site and in the asymptomatic, contralateral area. Responders were defined as those who achieved a > 30% decrease in pain lasting > 30 days. Two distinct groups were identified based on differences in QTT profiles. Most patients  with a homogenous profile were nonresponders. By contrast, more than half of the patients  with a nonhomogenous profile were responders ( Neuropathic pain is a chronic condition that is very difficult to treat , and onlδ-fibers. High-concentration capsaicin activates TRPV1 channels by overstimulating the nociceptors, resulting in the defunctionalization of the nociceptor nerve fibers and thereby reducing spontaneous nerve activity, leading to a loss of responsiveness. After defunctionalization, patients perceive a decrease in PeNP [Capsaicin works by directly targeting, with a highly selective agonism, the transient receptor potential vanilloid 1 (TRPV1) receptor, which is primarily present in C-fibers and in some A in PeNP –7, whichThe European Medical Agency (EMA) has recommended that CP8% be applied by a doctor or other healthcare professionals under the supervision of a doctor . As a reGiven that capsaicin affects unmyelinated or slightly myelinated fibers and studies have shown that the CP8% patch involves heat sensation , we hypoThis was a retrospective analysis of all patients treated with the CP8% patch for PeNP at our pain clinic between 2010 and 2013. From patient medical records, we obtained QTT results and treatment outcomes (response versus nonresponse) for all patients. All procedures were performed according to clinical protocols in place at our institution during the study period. Douleur Neuropathique 4 Scale (DN4), followed by consultations with a pain physician and a neurophysiologist for complete neurological assessment. Based on this evaluation, patients are classified into one of the following pain categories: (1) postherpetic neuralgia (PHN) and (2) chronic postsurgical pain (CPSP), or type I or II complex regional pain syndrome (CRPS). PeNP is considered possible when the patient meets the criteria given in the International Association for the Study of Pain (IASP) recommendations [Since late 2010, all patients presenting at our pain clinic with a high suspicion for PeNP have been asked to complete thendations . In casendations . PatientPrior to treatment, a discontinuous line is drawn with a permanent-ink marker on the skin to mark the boundaries between the painful area  and the area with normal skin sensation. Transparent paper is used to copy this area and save for further patch applications.A numerical pain rating scale (NPRS), ranging from 0 to 10 points, is used to assess the pain level, with 0 indicating no pain and 10 indicating the worst imaginable pain. Patients are asked to rate their pain scores at the following times: at first visit, before patch application, throughout the treatment procedure see , at one 2 thermode  [A QTT profile is routinely obtained in all patients at the following time points: pretreatment, one to two weeks after the first consultation and at PeNP diagnosis. The QTT test is always performed in the same room under the same environmental conditions. We determine warm sensation threshold (WST) and heat pain threshold (HPT) values, first in the normal contralateral skin area and then in the affected skin area, using the limits method . The QTT Israel) , 18. TheOn the day of treatment, the patients are told to eat a small meal  before presenting at the outpatient clinic. Topical local anaesthetic is applied for 75–90 minutes before procedure. The anaesthetic cream is then removed and the skin washed and dried. Afterwards, the patch is cut to fit using the previously created transparent sheet and applied to the patient's skin for 30 to 60 minutes, depending on the location. Health professionals and patients are required to wear the recommended protection at all times . Once thAs part of the treatment protocol, patients are asked to rate their actual discomfort level using the NPRS. This is reevaluated every 20 minutes for one-hour procedures and every 15 minutes for 30-minute procedures. Blood pressure is also taken after every pain rating. After the CP8% treatment has finished, patients are discharged and given two sheets of malleable frozen gel for home use. Instructions are also provided for extra treatment with nonsteroidal oral analgesics.Treatment response  was defined as a > 30% decrease in the NPRS from baseline to the posttreatment assessment at weeks 4–6. In cases in which the difference is exactly 30% or when the patient is unable to rate pain relief with the NPRS, then treatment efficacy is determined by asking the patient to estimate overall improvement and willingness to repeat treatment.t-test for independent samples for parametric values. χ2 was calculated for responders. Given that the total sample size was barely enough to perform the chi-squared test for some groups, the Fisher exact test was also calculated in these cases.The statistical analysis was performed with the VassarStats online software . To chechttps://doi.org/10.1155/2017/7425907); different pain localizations involving one or several nerve territories. For these reasons, we were unable to compare out sample to normalized data reported elsewhere [The patient sample was highly heterogenous due to variability in the following factors/conditions: time elapsed from injury to treatment; the use of multiple different concomitant medications; use of drugs acting on central nervous system (CNS)   area and at the asymptomatic contralateral site. Differences between the WST and HPT values in the target and control areas were considered not significant when there was a crossover between mean results (±1.96 SD) for the measurement on both areas; when this occurred, the painful area was considered to present normal thermal sensations. By contrast, if there was no crossover, we considered the WST (or HPT) for the treatment site to be significantly different (higher or lower) from the contralateral site.We initially identified a total of 65 patients diagnosed with PeLNP who had been treated with CP8% during the 2010–2013 period. Of these, 10 were excluded from the study for varying reasons: five were excluded because the contralateral area was not asymptomatic . Three other patients were excluded for the following reasons: one had an interventional pain procedure between treatment and assessment, another developed a recurrence requiring radiotherapy before the follow-up visit; and QTT data was not available in the third case. As a result, the final sample consisted of 55 patients. Pattern 1. There were no significant differences in WST or HPT between the painful area and the control areal.Pattern 2. WST is not significantly different between the control and target areas while the HPT value showed significant abnormal thermal sensations (either high or low) at the painful area.Pattern 3. HPT presents no significant differences while the WST value shows significant abnormal thermal sensations (either high or low) in the painful area.Pattern 4. Both WST and HPT values present significant differences between the two areas (both high or both low). Both WST and HPT show abnormal thermal sensations at the pain site.Two distinct groups were identified based on differences in QTT profiles for responders and nonresponders . One group presented nonhomogenous WST and HPT results while the second group had homogenous WST and HPT results .(i) Homogenous Profile Group. The first group presented homogenous WST and HPT profiles, defined as either the presence of significant differences in the same direction (both high or both low) in WST and HPT values between the PeLNP region and the asymptomatic contralateral area or no significant difference in these measures .(ii) Nonhomogenous Group. The second group consisted of patients with nonhomogenous WST and HPT profiles, defined as the presence of significant differences between the PeLNP area and the contralateral site in only one (either WST or HPT) measure but not the other.There were no baseline differences between responders and nonresponders in terms of gender, age, DN4 scores, etiological diagnosis, or NPRS. There was a slightly larger number of females in the nonresponse group, but this was not statistically significant.χ2 was 8.94 (p = 0.0028) and Fisher exact test (two tailed) was p = 0.0014 for patients who responded to treatment and had nonhomogenous WST and HPT values.p = 0.0028). Although the reasons for this difference are not clear, we hypothesize patients with a partial loss of cutaneous nerve fibers or receptors are more likely to respond to treatment. By contrast, when severe nerve damage or normal cutaneous sensations are present, the pain is likely due to central sensitization and thus not responsive to capsaicin.At present, there are no reliable predictors of response to treatment with capsaicin for analgesia. Given that the application of capsaicin causes heat sensation, the aim of this study was to assess quantitative thermal testing (QTT) profiles in a group of patients with localized peripheral neuropathic pain (PeLNP) treated with topic capsaicin, to determine whether different QTT profiles could predict treatment outcomes. We did a retrospective analysis of 55 patients treated between 2010 and 2013 for PeLNP, where, as part of the routine treatment procedures, both warm sensation threshold (WST) and heat pain threshold (HPT) values were assessed at baseline in the treatment (PeLNP site) area and the asymptomatic contralateral site. From the analysis, two different groups were identified based on their QTT profile. The first group presented homogenous WST and HPT profiles, defined as either the presence of significant differences in the same direction (both high or both low) in WST and HPT values between the PeLNP region and the asymptomatic contralateral area or no significant difference in these measures . The second group consisted of patients with nonhomogenous WST and HPT profiles, defined as the presence of significant differences between the PeLNP area and the contralateral site in only one (either WST or HPT) measure but not the other. Most patients  with a homogenous profile were nonresponders. By contrast, more than half of the patients  with a nonhomogenous profile were responders , endocannabinoids anandamide and N-arachidonyl-dopamine, or chemicals such as capsaicin (8-methyl-N-vanillyl-6-nonenamide) , 28, ally fibers , 28, 31.y fibers . Transduy fibers , 33. Many fibers .In primary afferents, the nociceptors, upon activation, trigger the release of various peptides, including glutamate, neurokinin A, substance P, and the peptide related to the calcitonin gene in the dorsal horn (DH) of the spinal cord –38. ThesMultiple inflammatory stimuli increase the expression of TRPV1 and even increase the density of axons positive for TRPV1 –46. A prCapsaicin is a well-known exogenous activator of TRPV1. Its pain relief effect is believed to be due to the activation of small diameter afferent nerve fibers and specialized DRG neurons that respond to many different noxious stimuli . CapsaicCutaneous injection of capsaicin activates the TRPV1 receptors, causing an influx of sodium and calcium ions into the cytoplasm of nociceptive neurons expressing that receptor . At the R2 = 0.17) in healthy volunteers. Yarnitsky et al. [R2 = 0.39).Previous studies  have fouy et al.  showed iThe present study involves a cohort of patients treated as part of routine clinical practice at a single center. We retrospectively identified patients who had been treated with CP8% and who also had a pretreatment QTT profile test available. The main aim was to determine the existence (or not) of a QTT pattern that could help identify those patients likely to respond to CP8% treatment. The main limitation to this study is its retrospective design. Other limitations include the relatively small number of patients, which precluded the use of subgroup analysis. We found no differences in demographics  between responders and nonresponders. We assume that the demographic data represent a normal distribution although this cannot be verified. Another limitation is that the number of responders in our study was larger than expected in the context of the high NNT reported in other studies . There aWe found that the clinical effects of CP8% were better in patients with nonhomogenous QTT profiles. These patients showed a significantly higher response rate than patients with homogenous QTT profiles. This difference may be due to incomplete nerve damage in these patients, leading to an imbalance in the sensitive inputs to second-order neurons from peripheral receptors and to the presence of ectopic discharges on nerve endings. If so, pain in these patients may be purely peripheral, with no additional CS mechanisms. Capsaicin application in these patients could eliminate the factor resulting in dysaesthesia when they activate the remaining TRPV1 receptors, desensitizing the nerve terminals of nociceptors by destroying the remaining axons and nociceptors.By contrast, the group of patients with homogeneous QTT profiles had little or no clinical improvement. These patients either had no peripheral damage  or may have had complete peripheral nerve damage . When no peripheral nerve damage is present, there should not be any receptor loss and thus there should be no differences in WST/HPT values between the painful area and the asymptomatic contralateral area. The opposite should also be true: in the case of complete peripheral nerve damage, nearly complete loss of receptors is to be expected, meaning that both warmth and heat sensations are likely to significantly differ between the painful and control areas. Thus, in both of these cases , the QTT tests should be homogenous, with capsaicin therapy unlikely to be efficacious in either of these two groups. Indeed, our results point in this direction. Pain in these patients could be due to CS mechanisms, with inputs multiplied at the DH as explained above; that is, the origin of the pain in these patients is probably less peripheral and more central. For this reason, the capsaicin is less effective in providing pain relief.In the 3rd pattern identified  the hypoesthesia (high WST only) subgroup presented a better response rate (8 responders versus only 1 nonresponder). Although we were unable to perform a subgroup analysis due to the small sample size, these findings support the hypothesis developed by Malmberg et al. , who argOverall, and within the aforementioned study limitations, our results seem to confirm previous reports. Höper et al.  evaluateDespite the findings described above, it is possible that unilateral PeLNP may be associated with bilateral changes in PNS . ThreshoTables S1, S2 and S3 represent the distribution of quantitative thermal tests for patients for different etiologies. Table S1 represent patients who suffered from Post-Herpetic Neuralgia. Table S2 represent patients who had chronic post-surgical pain. Table S3 represent other etiologies. All tables, patients are grouped for Responders and Non-Responders (see righthand column). Secondly to it, patients were grouped for homogeneity  between results for warm sensation threshold and heat pain threshold for the painful area compared to the control asymptomatic area. From the tables it can be appreciated that non-responders are mostly present within the non-homogeneous results, being the non-homogeneous the ones with more responders in it.


Background. Capsaicin, one of several capsaicinoid compounds, is a potent TRPV1 agonist. Topical application at high concentration  induces a reversible disappearance of epidermal free nerve endings and is used to treat peripheral neuropathic pain (PNP). While the benefit of low-concentration capsaicin remains controversial, the 8%-capsaicin patch  has shown its effectiveness. This patch is, however, costly and natural high-concentration capsaicinoid solutions may represent a cheaper alternative to pure capsaicin. Methods. In this retrospective study, 149 patients were screened, 132 were included with a diagnosis of neuropathic pain, and eighty-four were retained in the final analyses  with PNP who were treated with topical applications of natural high-concentration capsaicinoid solutions . Indications were postsurgical PNP (85.7%) and nonsurgical PNP (14.3%) . Objectives. To assess the feasibility of topical applications of natural high-concentration capsaicinoid solutions for the treatment of PNP. Results. The median treated area was 250 cm2 [IQR25–75: 144–531]. The median amount of capsaicinoids was 55.1 mg [IQR25–75: 28.7–76.5] per plaster and the median concentration was 172.3 μg/cm2 [IQR25–75: 127.6–255.2]. Most patients had local adverse effects on the day of treatment, such as mild to moderate burning pain and erythema. 13.6–19.4% of the patients experienced severe pain or erythema. Following treatment, 62.5% of patients reported a lower pain intensity or a smaller pain surface, and 35% reported a sustained pain relief lasting for at least 4 weeks. Conclusion. Analgesic topical treatment with natural high-concentration capsaicinoid is feasible and may represent a low cost alternative to alleviate PNP in clinical practice.  Peripheral neuropathic pain (PNP) results from disease, damage, or dysfunction of the somatosensory system . Its mul Capsicum includes species commonly called “pepper” plants and “chilli” peppers. The first recorded use dates back to 3000 BC  and the median amounts of solution per application were 100 drops [IQR25–75: 50–155], or 2.8 mL [IQR25–75: 1.4–4.4]. The skin region to be treated was always intact and dried before the plaster was applied by an anaesthesiologist. An intravenous catheter was placed before treatment for safety and pain management. Patients were premedicated with 5% lidocaine gel on the target skin, lidocaine-infiltration, or tramadol 100 mg, performed 60 minutes before plaster application. After application, the plaster remained on the target skin for 60 minutes. Elastic bandages were used to improve adhesion between the skin and plaster. After removal, the skin was cleaned with a cleaning gel and cooled with a cold pack. The duration of cooling depended on the patient's needs and patients were recommended to continue its use at home for several days, if necessary. Where the cold pack proved to be insufficient, treatment-related discomfort was alleviated before going home with paracetamol 1 g, tramadol 50 mg, or titrated IV morphine. Any adverse events were reported and followed up until they were resolved and explained. After the initial visit, follow-up visits were offered to the patients for several weeks. A second capsaicinoid plaster was applied at the next visit to the hospital if the pain threshold had risen again after the initial relief, even if it was not as intense as the first. A majority of the study subjects had concomitant chronic medications. Some patients had painkillers which were classified based on the analgesic ladder which has three steps: paracetamol and nonsteroidal anti-inflammatory drugs belong to the first step, tramadol and tilidine-naloxone belong to the second, and morphine belongs to the third. Other patients had current systemic treatments like tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, or anticonvulsants. Those chronic medications were kept and reevaluated throughout the follow-up.Patients were treated with a plaster gauze, adjusted to the painful area previously drawn on the skin. Before applying the gauze onto the skin, it was impregnated with capsaicinoid solution. Ten patients were treated with the first solution and 53 with the second one. The median area per application was 250 cmPain levels were assessed before the treatment using a 0–10 Visual Analog Scale (VAS). Presence of neuropathic symptoms was assessed clinically by an anaesthesiologist (French version of the DN4 questionnaire) . Pain waμg/cm2 or ≥200 μg/cm2).To assess the potential of the treatment, data from subgroups of patients were analysed for differences in terms of global impression of pain change, lower pain intensity, and surface area after the first high-concentration capsaicinoid plaster application. The cohorts of patients compared were based on (i) the DN4 (DN4 < 4 versus DN4 ≥ 4); (ii) the pain origins ; (iii) the premedication given (tramadol versus other premedications); (iv) the pain intensity and erythema reaction after application (none or mild pain versus medium or strong pain); and (v) the concentration of capsaicinoids given (<200  t-test (paired t-test) for independent-sample comparisons. Statistical analysis was performed using R language (version 3.2.0). The threshold for statistical significance level was set at p < 0.05.Biometrical analysis followed statistical analysis rules. Data were described as mean ± SD and median [IQR25–75] when appropriate. Proportion, in percentage, was expressed with 95% confidence interval (95% CI). Subgroup differences, in terms of pre- and posttreatment pain scores per patient, were analysed using Student's qualitativeOne hundred and forty-nine patients were considered for inclusion in this study. Seventeen were excluded for not meeting the inclusion criteria regarding the diagnosis of neuropathic pain. One hundred and thirty-two patients received a total number of 291 applications of the natural high-concentration capsaicinoid. Of these patients, evaluation files were completed for 137 applications from 84 patients, 30 of whom were males (35.7%) and 54 were females (64.3%). The median age was 57.5 years [IQR25–75: 44.7–67.1]. The median baseline VAS pain score was 6 [IQR25–75: 5–7]. In seventy-three patients, the DN4 questionnaire was complete, with a median baseline DN4 score of 4 [IQR25–75: 3–6]. Fifty-one patients scored ≥4, and twenty-four scored <4 (in which 4 patients scored 2). Of these patients, 14.3% had nonsurgical PNP while 85.7% had postsurgical PNP. 52.4% of the previous group received a knee surgery. The population is further described in μg/cm2 [IQR25–75: 127.6–255.2], with a median of 55.1 mg [IQR25–75: 28.7–76.5] of capsaicinoids per plaster. Before the high-concentration capsaicinoid application, 85.4% of patients received tramadol 100 mg (n = 41) while 8.3% had another premedication such as topical-lidocaine (n = 1) and local anaesthetic infiltration (n = 2). 6,3% (n = 3) did not receive any premedication. Immediately after the application, evaluation showed that most of the 132 patients had local adverse effects with 83.3% of patients reporting mild or medium burning pain (n = 66), 70.8% having mild or medium erythema (n = 72), and only 13.6% having strong burning pain and 19.4% having strong erythema , tingling (73.2%), and pins and needles (62.5%). Clinical examination indicated a tactile hyperesthesia, hyperalgesia, or allodynia in 91.0% of patients . Severalerythema . Treatmen = 80). Within this group, 75.0% reported a decrease in their pain intensity (n = 44) and 86.1% reported a decrease in their pain surface area (n = 36) .The follow-up visits, several weeks after the application, showed that 62.5% of the 132 patients had a positive global impression of pain change ((n = 36) . We did This analysis confirms the feasibility of natural high-concentration capsaicinoid applications as a treatment of PNP in clinical practice. As a retrospective study, this analysis is limited by the lack of a control group and can therefore not be used for the assessment of treatment effectiveness.The population sample was relatively homogeneous with 85.7% of patients suffering from postsurgical PNP. This homogeneity is due to the fact that most of our patients were being sent by orthopaedic and cardiovascular surgeons. However, even if all the patients met the IASP criteria for definite neuropathic pain, a recent consensus of the NeuPSIG group report that, without additional investigations, the presence of neuropathic pain can only be seen as “probable” to “definite” . Of note2). In comparison to our median amounts of capsaicinoids per application of 55.1 mg [IQR25–75: 28.7–76.5], the high-concentration Qutenza has a concentration of 640 μg/cm2 and 179 mg of capsaicin per plaster [Despite some clear variability in our results, the quantity of capsaicinoids per application was relatively high because of the large amounts of solution used to impregnate the plasters (about 2.8 mL per application). We believe this variability may be easily reduced by establishing a standardised table of number of drops per standard-sized plaster (drop/cm plaster , and theThe application of high-concentration capsaicinoids was generally well-tolerated, with 6.9% of patients needing a treatment-related-discomfort medication to alleviate the side effects in comparison to the 15–44% often reported in clinical trials –19. OnlyAlthough the aim of our study was not to assess the efficacy of high-concentration capsaicinoids and the results did not have enough power to allow a statistical assessment of clinical efficacy, the emerging trends for pain reduction in global impression of change observed in this study seem to be comparable to that found in previous RCTs on high-concentration capsaicin , 16–19. In conclusion, this retrospective study showed that topical treatment of PNP using natural high-concentration capsaicinoid applications is feasible, with generally mild to moderate and short-lasting side effects. This low cost alternative may constitute a new opportunity to widen the topical treatments available for patients suffering from PNP.


Benign spinal cysts are relatively common, but can cause significant pain. However, consensus regarding the best method for treating these cysts has not been established. We aimed to examine the usefulness of epiduroscopic neural laser decompression (ENLD), a novel percutaneous treatment, for treating lumbo-sacral cysts.Ten patients  with benign lumbo-sacral cysts underwent ENLD. The lumbo-sacral cysts were caused by multiple pathophysiologies and displayed different characteristics. Cysts were evaluated using a recorded epiduroscopic procedure video, magnetic resonance imaging (MRI), and electronic medical records. In all patients, MRI identified cysts with well-defined margins that were compressing the nerves in the lumbo-sacral region and were associated with the pain symptoms of the patients. Retrospectively, we reviewed a series of consecutive patients who underwent surgery . Low back/leg pain was evaluated using a 1–10 visual analog scale. Functional improvement was evaluated using Oswestry Disability Index scores. Outcomes were evaluated pre- and post-operatively and 1 year post-surgery.p < .001) and from 5.8 pre-surgery to 1.6 post-surgery . Disability scores decreased from 27.2% pre-surgery to 14.6% post-surgery.Patients were examined between May 2016 and August 2017. Average pain scores improved from 4.7 pre-surgery to 1.8 post-surgery (low back; Currently, no standard treatment strategy for symptomatic spinal cysts exists. These results show that ENLD using a Holmium: YAG laser can be useful in treating symptomatic benign spinal cysts.Not applicable as this is a retrospective chart review. Benign spinal cysts are a relatively common type of expanding lesion that form in the spinal canal. Benign cysts can be the cause of both chronic back pain and lower extremity radiculopathy . The negTill date, there are only been seven options for treating benign cysts—four open invasive options and three percutaneous non-invasive procedures. Open procedures for treating benign cysts include (1) laminectomy for cyst decompression and nerve root resection –4, (2) lSince Choy et al. first introduced epiduroscopic neural laser decompression (ENLD), the technique and instrumentation of ENLD has significantly improved . Due to Ten adult patients participated in this prospective study between May 2016 and August 2017. We received approval from the Institutional Review Board of Himchan Hospital Health System (No. 112294-01-201801-01), and all participants provided written informed consent.Participants were eligible to participate in the study if they exhibited single-lesion, low back and/or radicular pain, with clear evidence of cystic lesions on magnetic resonance imaging (MRI), and correlated back and/or leg radiating pain which had not responded to conservative treatment (medication and physiotherapy) within 6 weeks. Participant age (in years), sex , and estimated duration of pain (in months) were collected during epiduroscopic video recording. Exclusion criteria for the study included (1) evidence of intradural mass lesion or suggestive malignant lesions, (2) presence of multiple cystic lesions or metastatic lesions on cross-sectional MR images, and (3) pain due to infection, instability, herniated lumbar disc, and spondylolisthesis.All surgical procedures were performed in the prone position on a radiolucent spine table. After aseptic draping in the usual manner, local anesthesia , intravenous analgesia , and intermittent sedation  were used for pain control and sedation. The arrangement of the surgical room is depicted in Fig. The principles of the procedures, according to the type of cyst, are illustrated in Fig. Changes in back and leg pain following surgical decompression of cysts using ENLD were evaluated using a 1–10 visual analog scale (VAS). Improvement in function following surgery was evaluated using the Oswentry Disability Index (ODI) .p values were less than 0.05.All parameters were analyzed statistically. Data are presented as mean and standard deviation (mean ± SD). Differences between pre- and post-operative VAS pain scores and ODI scores were compared non-parametrically using separate Wilcoxon signed-rank tests. Differences were considered statistically significant if All ten patients underwent minimally invasive cyst rupture using ENLD technique with Holmium: YAG laser. The average duration of follow-up for participants in the study was 12.6 ± 1.0 months. The average duration of cyst surgery was 21.3 ± 3.0 min. The average length of participants’ hospital stay was 1.5 ± 0.5 days (Table p < .001). Mean VAS scores for leg pain decreased from 5.8 ± 1.2 to 1.6 ± 0.7 (p < .001). Mean ODI scores (%) decreased from 27.2 ± 10.7% to 14.6 ± 7.7% post-surgery (p < .001). There were no significant complications, such as post-operative infection or hematoma, or a need for a repeat surgery. During the follow-up period, there was no symptom recurrence that warranted a repeat surgery.Analysis of VAS scores revealed significant improvement in both back and leg pain from pre- to post-surgery Table . Mean VAA 26-year-old man visited the hospital on August 21, 2016, with a 6-month history of pain in his right leg. The pain had a radiating quality and had not been relieved by medication. On examination, the patient exhibited monoparesis of the sacral (S) 1-innervated gastrocnemius muscle, with difficulty in pushing the foot, revealing a lower right limb power of 4/5. Other neurological parameters were within normal limits. There was no related familial or past history. Results of MRI performed on August 23 showed a single fluid-containing lesion at the lumbar (L) 4–5 level measuring 8 × 6 mm Fig. ; the nerA 52-year-old woman presented at the hospital on October 21, 2017, with a 12-month history of low back pain and right leg numbness. Her back pain had increased progressively, and she had developed radiating pain in her right leg along with hypoesthesia. Physical examination showed normal motor strength and deep tendon reflexes. There was no related past or familial history. She was initially prescribed non-steroidal anti-inflammatories (NSAIDs) for more than 6 months, but her symptoms did not improve, at which point she was transferred to our clinic.The MR images showed a single fluid-containing lesion at the L5–S level measuring 12 × 8 mm and originating from the right interarticular facet of the lesion Fig. . The L5 A 44-year-old man visited the hospital on November 27, 2016, with a history of buttock and leg pain. The buttock pain had persisted for more than 8 months, while the leg pain had presented 4 weeks ago. Physical examination showed normal motor strength, reflexes, and sensory capability. There was no related past or familial history. He was initially managed with pain medication (NSAIDs) and physiotherapy symptomatically. Subsequent MRI of the spine revealed a large cystic lesion at the S1–2 level with T2 high signal intensity. The size of cystic mass was 50 × 45 mm; due to the mass effect of the cyst, the S1 and S2 nerve roots on the left had been moved to the right side, and the right S1 root could not be identified on imaging. When the epiduroscope was advanced merely 50 mm from the sacral hiatus, we identified a well-defined cystic mass at the S2 level. Cyst rupture was performed at a low voltage  to protect surrounding neural structures Fig. . After ePatients with degenerative changes in the lumbo-sacral region often present with pain and neurological deficits. However, benign cysts, such as discal, juxtafacet, and perineural cysts also commonly present with radiating pain because of their anatomical location, which can interfere with the traversing and exiting nerve roots , 16.The cysts in the first case presented here originated in the intervertebral space. Gas-filled cysts in the intervertebral space which share space with the posterior longitudinal ligaments have been previously described as a cause of radiculopathy , 17, 18.The second case was that of a synovial cyst. It is one of the most common benign extradural masses found in the spine. Synovial cysts within the facet joints have been reported to cause nerve compression , 20. TheAlthough radiologically, benign lumbo-sacral cysts are typically asymptomatic , some caCurrently, there is no consensus regarding the best treatment for symptomatic cystic lesions. Surgical procedures have shown favorable outcomes, but neurological deterioration and sequelae of laminectomy have also been reported . FluorosEpiduroscopic management using the Holmium: YAG laser is an emerging minimally invasive procedure without the risk of bone and ligament injury, compared with other surgical procedures, that may be applied for many spinal conditions. It has undergone trials for the treatment of herniated lumbar discs, spinal stenosis, failed-back-syndrome, and facet cysts ; ENLD yiThere are some limitations of this study which must be acknowledged. Firstly, the data in this study was acquired from a small trial with no control group. Therefore, it is possible that the potential benefit of undergoing ENLD for patients was overestimated. It is also possible that patient selection for the study, which included patients with symptomatic cysts, influenced the outcomes. Secondly, remnant cysts can recur due to the characteristics of the fenestration procedure, and the short follow-up duration underestimates this possible complication. Despite these limitations, we believe that this study is clinically important and demonstrates a novel minimally invasive treatment approach for benign cystic mass.The results of this study suggest that ENLD with HD visualization and Holmium: YAG laser can be used to treat benign spinal cysts safely, precisely, and effectively; ENLD renders cyst fenestration via epiduroscopy possible without incision and bony destruction. Although this is a preliminary report for a novel technique, ENLD for symptomatic cysts may be a valuable alternative to surgery. Although ENLD was not associated with post-surgical complications for any of the participants, careful follow-up is necessary. Large, randomized, multicenter trials are needed to further explore the potential of ENLD.


The management of breakthrough pain in cancer patients is always a challenge for medical professions. Occurring in 80% of cancer patients with advanced disease, breakthrough pain significantly decreases both patient’s and caregiver’s quality of life. The aim of this study is to assess the analgesic efficacy of a fixed inhaled nitrous oxide/oxygen mixture for adult cancer patients with breakthrough pain.This is a randomized, placebo-controlled, double-blind study; it will be conducted in the General Hospital of Ningxia Medical University. The target study subjects are at least 18 years old, and are hospitalized cancer patients who are receiving routine opioids to control cancer-related pain but still experience breakthrough pain. A total of 240 patients will be recruited and randomly allocated between three treatment groups  and a control group (group D) in a ratio of 3:1. All treatment groups  will receive standard pain treatment  plus a pre-prepared nitrous oxide/oxygen mixture, and the control group (D) will receive the standard pain treatment plus oxygen. Patients, doctors, nurses, and data collectors are all blind to the experiment. Assessments will be taken before treatment (T0), at 5 min (T1) and 15 min (T2) during treatment, and at 5 min after treatment (T3). The primary endpoint measures will be the percentage of patients whose pain is relieved at T1, T2, and T3. Secondary outcome measures will include the safety of treatment, adverse events, and satisfaction from both health professionals and patients.This study aims to provide an effective and practical intervention for a fast breakthrough pain relief and to improve cancer patients’ quality of life significantly. The Evidence-Based Medicine Working Group claim that a randomized, double-blind, placebo-controlled experimental intervention is the most appropriate design to demonstrate its efficacy, so this study could give a new approach to controlling breakthrough pain episodes.ChiCTR-INC-16008075. Registered on 8 March 2016.The online version of this article (doi:10.1186/s13063-016-1739-9) contains supplementary material, which is available to authorized users. In 2015, there were approximately 15 million newly diagnosed cancer cases in the world and about 4.3 million new cases in China alone . According to anesthetists, oral immediate-release opioid is the first choice in controlling breakthrough pain in China. However, with its slow onset of action  , it delaThis study is a randomized, double-blind, placebo-controlled, parallel clinical trial to test the analgesic efficacy of a fixed inhaled nitrous oxide/oxygen mixture on adult cancer patients with breakthrough pain. This article has been drafted following SPIRIT guidelines  see Add. PatientAll cancer patients from the oncology ward who have breakthrough pain will be invited to participate. Davies’ Adapted Diagnostic Algorithm will be used to screen patients for the presence of breakthrough pain . The maiEligible patients will receive oral immediate-release morphine with a proportion of 10–20% daily total doses of oral morphine as the standard breakthrough pain treatment . Patientn = 180, and one control group (D), n = 60. The allocation sequence of each patient is decided by a computer-generated schedule, which is numbered by a statistician. The randomization schedule will be kept and sealed in an independent research room. Apart from the project manager, who is responsible for gas distribution, no other nurses or data collectors will have access to the data allocation. The nurse is blind to the double-blind randomized controlled trial lists , Patient’s demographic data , cancer diagnosis, baseline breakthrough pain intensity, current background pain opioid medication dosage, duration of nitrous oxide/oxygen mixture use, dosage of oral rescue morphine medication, and any side or adverse effects of nitrous oxide/oxygen mixture treatment will be recorded by researchers . A numerThe primary endpoint measures will be the percentage of patients receiving pain relief at T1, T2, and T3. Repeated-measures analysis of variance will be used for data analysis.Secondary outcome measures will include treatment safety, adverse events, and satisfaction from both health professionals and patients. The total time of nitrous oxide/oxygen mixture administration will be also recorded.According to our previous study on burn-dressing pain , 37, we t test  or a nonparametric two-sample Mann–Whitney test . Statistical significance will be considered for P < 0.05.Before the study, all data collectors will be trained in the data collection procedure. Data from withdrawn patients will not be used in the final analysis. SPSS version 22.0  will be used to conduct quantitative analysis following the intention-to-treat principle for a case-control randomized trial. Descriptive statistics will be analyzed by medians (inter-quartile ranges), means (standard deviations), and proportions , as appropriate. Proportions will be compared by using the chi squared test or the Fisher’s exact test. Means will be compared using Student’s Many studies on transmucosal fentanyl showed excellent breakthrough pain reduction after 15 min administration , 30, 48.The study of Li et al. on burns-dressing procedure pain showed faster pain reduction, within 15–20 s, for the pre-prepared nitrous oxide/oxygen mixture group , 37. HowTo our knowledge, this study is the first randomized controlled trial to evaluate the effectiveness of the pre-prepared nitrous oxide/oxygen mixture to treat breakthrough pain in cancer patients with advanced disease. If this treatment appears beneficial, this study can help to generate preliminary guidelines on breakthrough pain management in cancer patients with advanced disease. We intend to disseminate the results of this study to international journals and conferences.Patient recruitment will start on 24 July 2016.


Patients are free to choose conventional or Korean medicine treatment under the dual medical system in Korea, and the prevalence of patients who choose Korean medicine treatment for whiplash-associated disorders (WADs) is high. This study analyzed the sociodemographic characteristics and medical service use in this population to provide healthcare providers with basic usage information of complementary and alternative medicine for WAD.A total of 8291 outpatients who registered under automobile insurance coverage and visited the main branch of Jaseng Hospital of Korean Medicine from April 1, 2014 to August 10, 2016 were included. Data on sociodemographic characteristics, symptoms, and accident and treatment-related details were collected from electronic medical records. Univariate and multivariate regression analyses were performed to identify baseline factors predictive of total treatment duration.The most prevalent demographic of patients who chose Korean medicine for WAD treatment was males in their thirties whose initial visit to the hospital was 16.1 ± 94.1 days from the accident. Neck pain accompanied by low back pain (57.0%) was the most common complaint, and for singular pain, neck pain (13.5%) was the most prevalent. Baseline numeric rating scale (NRS) pain levels were generally moderate (4–6) regardless of area. Patients received 7.2 ± 10.2 sessions of treatment for 32.6 ± 55.3 days. The most commonly prescribed treatment modalities in order of highest frequency were acupuncture, cupping, pharmacopuncture, and herbal medicine, which collectively accounted for > 90% of treatments. Acupuncture was administered 29.0 ± 40.8 times, and cupping 14.0 ± 18.7 times as the two highest frequency treatments. In multivariate regression analysis, longer treatment periods were found to be associated with higher NRS, older age, and delayed initial visits at baseline.This study highlights the characteristics and Korean medicine use of WAD patients. These results are particularly relevant and informative for consideration of personal preferences and effective prioritization in further insurance coverage. Traffic accidents (TAs) are among the primary causes of mortality and injury , and varWhiplash can be defined as a transfer of energy to the neck via an acceleration–deceleration mechanism. It usually occurs as a result of rear-end or side-impact automobile collisions. The impact may result in bony or soft-tissue injuries (whiplash-injury), which may in turn lead to a range of clinical manifestations commonly referred to as whiplash-associated disorders (WADs) . GeneralTraining of Korean medicine physicians in Korea employs a dual education system where students are required to complete (a) a 6-year undergraduate course consisting of 2 years of pre-medicine and 4 years of medical school adopted by 11 private universities; or (b) a specialized 4-year postgraduate course comprising of 4 years of undergraduate and 4 years of postgraduate courses operated by a national university to graduate and qualify for the national licensing examination for Korean medicine doctors. In the two years of pre-medicine, an introduction to Korean medicine, and courses in liberal arts, medical Chinese, and basic conventional medicine are provided, and in the four years of medical school, various basic and clinical courses are conducted along with clinical training sessions .Many countries have policies addressing WAD-related medical problems, and various research into the occurrence and medical service use of WAD is in progress. In Australia, TA insurance data studies on the status of hospitalization  and physHowever, considering that the insurance company of the assailant bears the medical expenses of the injured party depending on the degree of culpability, WAD treatment follows not only the level of evidence but also TA coverage guidelines set by the Korean Ministry of Land, Infrastructure and Transport and the policy of the Auto Insurance Medical Fee Review Council under the Health Insurance Review and Assessment Service. The current correlation level between clinical practice and insurance and policies is high, and Korean medicine clinical practice guidelines for traffic injuries was initiated in 2016 for standardization of clinical practice, and the guidelines which were published in 2017 are expected to provide a standard for Korean medicine practice in traffic injuries. This current report on Korean medicine treatment of TA injuries was conducted as part of establishing these clinical practice guidelines in an effort to bridge the gap between policy, evidence-based medicine and personal preferences and incorporate them systematically in clinical practice.Analysis of WAD patients is expected to reflect Korean medicine services preferred by physicians and patients for musculoskeletal disorder treatment and provide valuable data for identifying and understanding patient groups with preference for insurance-supported Korean medicine treatment. This descriptive study examined the sociodemographic characteristics, pain patterns, status of frequency of Korean medicine treatments, and treatment details of WAD patients visiting an integrative medicine hospital for Korean medicine treatment to the aim of providing basic knowledge on this condition to related healthcare providers, researchers, and legislators in Korea, and other countries where complementary and alternative medicine use for WAD is not as prevalent.A total of 8291 outpatients who visited the main branch of Jaseng Hospital of Korean Medicine  and registered under automobile insurance during the index period from April 1, 2014 to August 10, 2016 were retrospectively analyzed for characteristics and treatment details using electronic medical records. Jaseng Hospital of Korean Medicine is a spine-specializing Korean medicine hospital designated as such by the Korean Ministry of Health and Welfare. Each year, over 900,000 spine and joint patients receive treatment at Jaseng using acupuncture, herbal medicine, and Chuna manual therapy for non-surgical treatment of musculoskeletal disorders. Conventional medicine is utilized for diagnostic assistance and complementary treatment means , 18.Various Korean medicine treatments, such as acupuncture, pharmacopuncture, herbal medicine, cupping, manipulation ), and traction, are used to treat TA injuries according to the patient’s symptoms under automobile insurance coverage. Pharmacopuncture  is a relatively new acupuncture technique that combines acupuncture and herbal medicine, where herbal extracts are injected into acupoints . In ChunUpon their first visit to the hospital, patients provided basic sociodemographic information, including their name, sex, date of birth, type of insurance, and mode of hospital entrance using tablet PCs that interwork with the electronic record database. Occupation was categorized into nine types according to the Korean Standard Classification of Occupations (KSCO) . Data onHospital entrance method was categorized into three types: self-walking when the patient walked in unassisted; assisted walking when walking frames, wheelchairs or outside help was necessitated; and stretcher-dependent when carried in by stretcher-car.Current pain severity was measured using the numeric rating scale (NRS) (0 representing no pain and 10 the worst pain imaginable) as assessed by the patient and categorized into three stages, 1–3, 4–6, and 7–10, for analysis. Pain regions were divided into three areas: neck pain; LBP; and joint pain (knee or shoulder), and the areas were analyzed both independent of and in combination with comorbid pains. Regarding prior treatment of the current episode, whether the patient had received other treatments, and details of oral analgesic prescription and administration and steroid injections received at other hospitals were recorded.For radiographic examination, X-rays were referred to the department of radiology, and additional magnetic resonance imaging (MRI), computed tomography (CT), or ultrasonography was taken if deemed necessary. If the patient had prior radiographic imaging results relevant to the current accident, then additional radiographic examinations may have been forgone at the Korean medicine doctor’s discretion.Treatments are automatically recorded when the Korean medicine doctor responsible for treatment enters prescription codes into the electronic patient records for treatment means. Treatment details were thus determined based on the prescription codes entered into the electronic medical records which were extracted from the electronic database and comprehensively reviewed by the researchers, and the treatment administration details were analyzed by a designated statistician.The basic characteristics, initial treatment timepoint, total treatment duration, radiological diagnosis, and Korean medicine treatment details of WAD patients who visited a Korean medicine hospital were analyzed. The treatment period was set from the first hospital visit to the last treatment date recorded in the hospital electronic system. When the patient had suffered two or more TAs within the index period and had been required to register again, the two events were analyzed separately. Demographic characteristics, past medical history, pain, and treatment service use are presented as descriptive statistics. Continuous variables were calculated by mean and standard deviation, and nominal variables by frequency and percentage (%). For analysis of predictive factors at baseline that affected total treatment period, univariate/multivariate regression analyses were performed. Statistical testing was performed with a significance level of 0.05. All statistics were analyzed using SAS 9.4  and STATA 14.0 .This study was approved by the Institutional Review Board of Jaseng Hospital of Korean Medicine  and adhered to all relevant research ethics. Written informed consent was obtained from patients to access and use medical records for academic means.The total number of TA patients who visited the hospital for WAD treatment within the index period was 8291. The average age was 36.0 ± 10.9 years, and 55.7% were male. First hospital visits were made an average 16.1 ± 94.1 days after the accident. Of these patients, 32.9% visited the hospital within a day, 38.7% within 2–7 days, 11.9% within 8–14 days, and 16.5% after more than 14 days, which shows that most of the patients visited the hospital within a week of sustaining their injury.In prior treatments for WAD-related neck pain and LBP episodes, 552 patients with neck pain and 428 patients with LBP took analgesics an average of 7.4 ± 6.5 and 7.9 ± 6.8 times, respectively. Fifty patients with neck pain and 71 patients with LBP took steroids, which displays a relatively higher use by LBP patients, but the average number of times of steroids taken was comparable for neck pain and LBP at 2.2 ± 1.8 and 2.1 ± 2.1 times, respectively. In comparisons of previous interventions and operations, only non-surgical interventions were analyzed, as no neck pain patients or LBP patients had received surgery for their current pain . Each appeared independently in 13.5%, 7.0%, and 1.5% of patients, respectively, and neck pain combined with LBP was reported by 57.0% of patients, which indicates a high prevalence of accompanying spinal pain. With regard to concurrent spinal and joint pain, 1.6% of patients had LBP and joint pain, 1.8% neck pain and joint pain, and 5.0% all three  together. The severity of pain was analyzed in four groups  by baseline NRS, which were reported on average as 5.1 ± 1.4 for LBP, 5.1 ± 1.4 for neck pain, 5.4 ± 1.4 for shoulder pain, and 5.0 ± 1.5 for knee pain. These results show that baseline NRS scores were all in the 4–6 category, regardless of the pain area Table .Table 2DThe total treatment period was less than a week for 3304 patients (33.9%), 2–4 weeks for 2436 patients (29.4%), 5–12 weeks for 1678 patients (20.3%), 13–26 weeks for 625 patients (7.5%), and more than 26 weeks for 244 patients (2.9%). Patients received 7.2 ± 10.2 sessions of treatment over an average of 32.6 ± 55.3 days. In order of decreasing frequency, the types of Korean medicine treatment administered were acupuncture, cupping, pharmacopuncture, and herbal medicine, which collectively accounted for more than 90% of treatment prescriptions. On average, patients treated using acupuncture or cupping, the two most commonly used treatments, received acupuncture 29.0 ± 40.8 times, and cupping 14.0 ± 18.7 times.Of the patients subjected to conventional diagnostic imaging, 7470 received X-rays, and an average of 2.4 ± 1.1 exams were performed on these patients. CT examinations were performed an average of 1.0 ± 0.1 times in 162 patients, and MRI was performed 1.1 ± 0.3 times in 1070 patients. X-rays, CTs, and MRIs were conducted at 0.2 ± 4.5, 2.8 ± 7.8, and 20.0 ± 27.5 days after the patient’s first visit to the hospital, respectively , manipulation (28%), acupuncture 18%), cupping (11%), pharmacopuncture (9%), and traction (1%) , and the fact that the main hospital branch is located in a highly populated urban district with high work traffic intensity. This could also be related to the overall occupational and population distribution of Korea and/or Seoul [Most TA patients who visited the hospital were in their 30s, so considering the fact that most patients who use Korean medicine are in their 40s, the population of traffic accident patients using Korean medicine is relatively young . While Aor Seoul .Patients first visited the hospital an average of 16.1 ± 94.1 days after the accident, and this average seems high when compared to the median . In some cases, patients visited the hospital for the first time after considerable time had lapsed, which subsequently increased the mean period between the onset of injury and their first visit to the hospital. Meanwhile, most patients visited the hospital within ten days, which appears to be associated with the acute manifestation of WAD symptoms following the accident. Complaints of single area symptoms appeared as neck pain, LBP, and joint pain, which indicates that neck pain was the main symptom among WAD patients. Furthermore, over half reported neck pain combined with LBP, and this combination was also the most prevalent complaint reported. An additional 10.2% of patients reported joint pain, such as shoulder or knee pain.The reason X-ray examinations were conducted most frequently and in the shortest time was to verify the magnitude of the injury (i.e. to rule out fractures). Comparing MRI and CT, CT was performed in addition to X-ray examinations within a relatively short period - as early as 2.8 ± 7.8 days after the first hospital visit - which may be attributed to the need to further diagnose fractures and potential causes of bleeding in higher resolution. MRI was conducted within 20.0 ± 27.5 days to diagnose residual neurological symptoms and damage to soft tissue. To rate WADs, X-ray examination is required for differentiation of fractures, and previous studies report the evaluation of muscle and tendon injuries using MRI , 25. HowGenerally, treatment lasted for less than a month (69.3%) or for 3 months (cumulative percentage 89.6%), but cases that required longer periods of treatment also reached 10.4%. Investigation of the association between baseline risk factors and long-term treatment revealed that current smoking, higher baseline NRS of LBP, older age, and a longer period between the first hospital visit and pain onset were correlated with longer treatment periods. The individual appearances of LBP and radiating pain were not as common as neck pain, but the baseline NRS of LBP exerted a large influence on prognosis. To shorten the treatment period and increase treatment effectiveness, patient education on the importance of early visits to the hospital after TA and lifestyle management appears necessary.The analysis of the total cost of Korean medicine treatment shows that while acupuncture and cupping are the most frequently used , their cost percentages compared to the total cost are only 18% and 11%, and herbal medicine and Do-in (conduction exercise) costs are high. The differences among these cost ratios can be attributed to the high per session costs of herbal medicine and manipulation sessions. In prescription of herbal medicine, preparation expenses including the price of herbal ingredients, and decocting and shipping charges are included in the total cost, and prescription orders are usually filled in 7 to 10 day units. Further, the legal definition of manipulation requires Korean medicine doctors to conduct manipulation treatment for 10 min or longer, which results in higher per session costs compared to other more prevalent procedures such as acupuncture.Some strengths of this study include that it covers the greatest number of patients compared to previous studies of Korean medicine treatment in TA patients, to the best of our knowledge. This study also uses hospital medical records as opposed to insurance databases or physician surveys to capture patient sociodemographic and pain characteristics, as well as the utilization status of high frequency Korean medicine treatments and treatment details of patients visiting an integrative medicine hospital to receive Korean medicine treatment. With the exception of a few interventions such as acupuncture and cupping, many commonly used Korean medicine treatments are not covered by Korean national health insurance. Therefore, the previous literature on the use of Korean medicine for general musculoskeletal diseases reflects the substantial out-of-pocket costs of Korean medicine treatment and its limited insurance coverage availability. However, in TA patients the distribution of the use of various treatments in analysis of Korean medicine is less influenced by cost because most Korean medicine treatment modalities for TA patients are covered by automobile insurance. Rather, the distribution is more reflective of physician and patient preferences, which holds significance in prioritizing treatment options in Korean medicine and/or CAM to improve and strengthen national health insurance coverage. For example, pharmacopuncture and herbal medicine were used to similar extents as acupuncture, which supports their clinical relevance in treating musculoskeletal diseases. Reduction of medical expenses through shorter treatment duration is also an important issue in treatment of TA patients, and this study provides basic data on various patient characteristics and their implications.This study also has several limitations. This is a retrospective study of electronic medical records, and some data may have been erroneously entered or omitted owing to computer or human error. Missing data were subsequently excluded from analysis. In addition, as recorded hospital visits were used to calculate patient treatment periods, patient visit information as recorded in the electronic system may differ from the actual date of treatment initiation and conclusion. Moreover, clinical improvement scales such as pain intensity, functional scale and quality of life (QoL), satisfaction, and other treatment effect measures were not included as this study mainly pertained to administrative records. Lastly, although automobile insurance covers a wider range of treatment than national health insurance, treatment administration is still partially limited, and the results should therefore be interpreted with caution. For example, Do-in (conduction exercise) and Chuna manual therapy are required to be prescribed separately to qualify for automobile insurance reimbursement and cannot be prescribed simultaneously, and coverage of herbal medicine is curtailed beyond 20 days.Through the analysis of medical records of WAD patients who visited an integrative medicine hospital for Korean medicine treatment, this study comprehensively examined patient characteristics and distribution, pain patterns, and treatment period and details of WAD patients receiving Korean medicine treatment. The results of this study are expected to contribute basic knowledge for related healthcare service providers, researchers, and legislators to effectively prioritize items for insurance coverage and in establishing clinical practice guidelines for traffic injuries.


Heterogeneity in patients with low back pain is well recognised and different approaches to subgrouping have been proposed. One statistical technique that is increasingly being used is Latent Class Analysis as it performs subgrouping based on pattern recognition with high accuracy. Previously, we developed two novel suggestions for subgrouping patients with low back pain based on Latent Class Analysis of patient baseline characteristics , which resulted in 7 subgroups when using a single-stage analysis, and 9 subgroups when using a two-stage approach. However, their prognostic capacity was unexplored. This study (i) determined whether the subgrouping approaches were associated with the future outcomes of pain intensity, pain frequency and disability, (ii) assessed whether one of these two approaches was more strongly or more consistently associated with these outcomes, and (iii) assessed the performance of the novel subgroupings as compared to the following variables: two existing subgrouping tools (STarT Back Tool and Quebec Task Force classification), four baseline characteristics and a group of previously identified domain-specific patient categorisations .This was a longitudinal cohort study of 928 patients consulting for low back pain in primary care. The associations between each subgroup approach and outcomes at 2 weeks, 3 and 12 months, and with weekly SMS responses were tested in linear regression models, and their prognostic capacity (variance explained) was compared to that of the comparator variables listed above.The two previously identified subgroupings were similarly associated with all outcomes. The prognostic capacity of both subgroupings was better than that of the comparator variables, except for participants’ recovery beliefs and the domain-specific categorisations, but was still limited. The explained variance ranged from 4.3%–6.9% for pain intensity and from 6.8%–20.3% for disability, and highest at the 2 weeks follow-up.Latent Class-derived subgroups provided additional prognostic information when compared to a range of variables, but the improvements were not substantial enough to warrant further development into a new prognostic tool. Further research could investigate if these novel subgrouping approaches may help to improve existing tools that subgroup low back pain patients.The online version of this article (doi:10.1186/s12891-017-1708-9) contains supplementary material, which is available to authorized users. Low back pain (LBP) is highly prevalent and has several negative consequences for society and individual patients , 2. In oMany of the existing subgrouping approaches for use in primary care have been developed using a quite narrow spectrum of patient characteristics –16, for These and other subgrouping approaches have increased our understanding of LBP but their prognostic capacity is still limited –26, and One aspect to consider is that most previous subgrouping approaches have used traditional regression modelling techniques in which the multivariable relationships between the included variables are assumed to be the same for all people in the sample. However, one of the theories underlying subgrouping is that these multivariable relationships might vary, with one subgroup having one set of relationships between these variables and another subgroup having a different set of multivariable relationships. For example, hypothetically there may be a strong relationship in one subgroup between fear of movement and activity limitation, whereas this relationship may be weak or absent in another subgroup with different patient characteristics. It is likely that the essential information about prognosis and response to treatment does not lie in single variables but in certain scoring patterns across several variables, and also possible that these scoring patterns may differ across subgroups of patients. The identification of such subgroups may be a key to a better understanding and management of LBP patients. Classifying the population of LBP patients into such subgroups may also address the issue that the relationship between the outcome and some baseline variables may differ dependent on other baseline variables and that subgroup membership may be one of those variables .A recent study  attempteSo, this study explored whether these two novel subgrouping approaches have any clinical significant difference in their capacity for improving prognostic estimates, as a mechanism to determine whether this aspect of external validity differed between the two subgrouping approaches. Therefore, the aim of this paper was to (i) determine whether membership in these previously identified subgroups was associated with outcomes of pain intensity, pain frequency and disability over the 12 months after the baseline consultation, (ii) assess whether one of these two subgroup models was more strongly and/or consistently associated with these outcomes, and (iii) assess the prognostic performance of these novel models compared to two existing subgrouping tools, four baseline characteristics that are known to have some prognostic capacity and to previously identified domain-specific patient categorisations.This study used data from a prospective observational cohort study which included adult patients with LBP who had consulted one of 17 chiropractic clinics in the research network of the Nordic Institute for Chiropractic and Clinical Biomechanics in Denmark between September 2010 to January 2012. The patients were followed for 1 year during which interventions were not influenced by participation in the study. Further information about the cohort study has been reported previously –37. ConsIncluded patients had a main complaint of LBP with or without leg pain, were between 18 and 65 years old, could adequately read and write Danish, had a mobile phone and were able to send a text message. The patients were included regardless of the duration of their LBP episode as our pragmatic interest was in subgroups that could be found within the broad spectrum of cases that present in primary care and because episode duration was one of the inputs to the LCA it could influence subgroup formation. Prospective participants were excluded if they were pregnant, had serious pathology including pathology of the back that necessitated referral for acute surgical assessment or had attended more than one consultation for LBP in the preceding 3 months. The latter was to establish a cohort of patients who were included at the time point when first seeking care for an episode of LBP.In total, 947 patients fulfilled the inclusion criteria and provided written consent. For 928 of those, both the patient- and clinician-reported questionnaires were completed at baseline, and therefore they were included in the current study. The available sample size was not based on the requirements of the current study, but was nonetheless adequate for applying regression models to test the statistical association between an outcome and many independent variables simultaneously, using the typical rule-of-thumb that a minimum of ten participants per independent variable is required or other related rules .Participation in this study did not affect treatment and accordingly under Danish law, no ethical approval was needed . ApprovaThe main focus in this study was the subgroup membership in the two subgroupings previously identified by way of two separately conducted LCAs , one usiIn this paper, the six independent domain-specific patient categorisations (from the first stage of the two-stage approach) were also used , which has three subgroups that are based on patients’ risk of persistent LBP disability  calculated from a patient self-reported questionnaire , 22, 40.Four simple and commonly used baseline variables known to have some prognostic capacity were also used for the comparisons of prognostic capacity. These were: typical LBP and typical leg pain intensity during the preceding week measured by 0 to 10 Numeric Rating Scales , 42, theTwo outcomes at 2 weeks, 3 and 12 months were collected by post using patient self-completed questionnaires: LBP intensity  and pain-related disability . Three other outcome measures were collected via weekly responses over 12 months using automated SMS, with participants replying with a number to each of the following questions 1) days with LBP the last week (0–7), 2) typical pain intensity the last week (0–10) and, 3) days with activity limitation the last week (0–7) , 47. The2 test for nominal variables, and Kruskal-Wallis equality-of-populations rank test and Wilcoxon rank-sum test (Mann–Whitney U test) for ordinal and continuous variables in relation to subgroups and responders, respectively.In the descriptive analysis, nominal scale variables were presented as proportions and continuous scale variables as medians and their interquartile range. Baseline comparisons between the single-stage and two-stage LCA subgroups, between responders and non-responders at the three follow-up time points, as well as comparisons between compliant SMS responders (less than 10 missing weeks of SMS replies ) and nonThe distribution of scores from each subgroup at every follow-up time point were visualised and graphically compared using stacked bar charts (pain intensity) and box plots (disability). Linear regression modelling with robust variance estimations was used to analyse if the subgroups were significantly associated with the outcome measures at 2 weeks, 3 months and 12 months follow-ups. In addition, illustrations of course trajectories that showed the mean score per week over 12 months for each subgroup were visually compared between the subgroups for each of the three SMS outcome measures.p-values. No pairwise comparison were performed. The visually observed differences between the mean trajectories were summarized across the three outcomes verbally.The significance of the differences between subgroups were assessed by a longitudinal linear regression model with the time in weeks as well as the subgroups as categorical covariates, taking the within-patient clustering (due to 52 weekly SMS responses being modelled for each patient) into account by using robust variance estimation to compute 2 obtained in linear regression models, which was used for comparisons between the LCA-derived subgroupings and the previously described baseline characteristics. In addition, we considered the adjusted R2 from a regression model that included the six domain-specific patient categorisations as categorical covariates: this way we could assess whether we lost prognostic information in the second stage of the two-stage approach.Prognostic capacity was measured by the amount of variance explained in outcomes and quantified by the adjusted R2 obtained from models including only these baseline variables, and models in which the subgrouping variable was added. Although the inclusion of the baseline values is conceptually the same as analysing change scores, we chose to include the baseline values as these are available for the clinician when considering the prognosis of the individual patients, and change scores are unknown. Lastly, we calculated the additional prognostic capacity after taking into account both the baseline value of the respective outcome variables and the participants’ recovery beliefs. Again, for each of the investigated models, the added prognostic capacity of the LCA-derived subgroupings was compared to that of the two other subgrouping tools, the remaining baseline variables and the domain-specific patient categorisations.To explore if the LCA-derived subgroupings added prognostic capacity to that of the baseline values of the outcome measures of pain intensity and disability, or to that of participants’ recovery beliefs, we used linear regression models to calculate the difference in adjusted RP value <.05 was considered significant.All subgroup types  were entered as categorical variables in the regression analysis. The four simple baseline variables were entered as continuous variables. In all tests of associations, a All analyses were performed using STATA/IC 14.1 .Females were 45% of the participants, the mean age was 43 and the most common duration of LBP before consulting the chiropractor was 2 weeks or less (62%) , SS6 (persistent) and SS7 (severe), and two-stage subgroups: TS6 (work-related), TS7 (nerve root), TS8 (very recent) and TS9 (severe).The response rates to the follow-up questionnaires varied across outcomes and follow-up time points with the lowest rates on any outcome being 67% at 2 weeks, 79% at 3 months and 73% at 12 months. Baseline differences between responders and non-responders were similar across outcomes and time points with non-responders being younger, more often males and having slightly lower recovery beliefs , had a slightly higher baseline leg pain intensity  and slightly lower recovery beliefs . Only the single-stage subgroups differed statistically in their response rates with non-compliant responders being slightly underrepresented in the SS2 (recent disability) and SS4 (nerve root) subgroups.There was a high response rate across the whole year to the SMS questions with 80% of individuals having less than 10 weeks with missing SMSs (compliant responders), and 76% of the participants responded to the SMS questions in all of the last 3 weeks (week 50 to week 52). The baseline differences between the compliant and non-compliant SMS responders were similar across the three SMS questions . The patients in subgroups SS1 (mild), SS2 (recent disability) and SS5 (very recent) had the mildest trajectories across these SMS outcomes and the SS3 (work-related) patients differed from them by having had a higher intensity and frequency of LBP. The patients in subgroups SS4 (nerve root), SS6 (persistent) and SS7 (severe) had the most severe trajectories although SS4 (nerve root) patients reported slightly less intense LBP than the other two subgroups  we found statistically significant differences between the single-stage subgroups and the outcome , SS2 (recent disability), SS5 (very recent), SS3 (work-related), SS4 (nerve root), SS6 (persistent) and SS7 (severe).There was a statistically significant association between the two-stage subgroups and pain intensity at all three outcome time points Table . Overallp < 0.001). Generally, TS1 (mild) patients had the mildest trajectory across SMS outcomes and TS2 , TS3 , TS5 (sleep issues), TS6 (work-related) and TS8 (very recent) patients differed from those in TS1 (mild) by having a slightly higher pain intensity and frequency. The TS7 (nerve root) and TS9 (severe) patients had the most severe pain intensity trajectories but differed from each other as TS7 (nerve root) patients had a higher frequency of days with activity limitation and pain. The TS4 (mild persistent) patients differed from TS9 (severe) patients by having slightly lower pain intensity and fewer days with activity limitation  we found statistically significant differences between the two-stage subgroups and the outcome , TS2 , TS3 , TS8 (very recent), TS5 (sleep issues), TS6 (work-related), TS4 (mild persistent), TS9 (severe) and TS7 (nerve root).An overview of the prognostic capacity of the subgroupings compared to the prognostic variables used in this study is presented in Table At each follow-up, the prognostic capacity of the single-stage and the two-stage subgroupings was similar on both the outcomes of pain intensity and disability Table . OverallAs expected, the prognostic capacity ascribed to the subgroups decreased when including the baseline values of the outcomes, and still there was no difference between the two LCA approaches to subgrouping Table . Again, Once again, the prognostic capacity of the new subgroupings was very similar for both outcomes when added to that of participants’ recovery beliefs Table . Also, tHere also, there was no difference in prognostic capacity of the new subgroupings for the outcomes of pain intensity and disability when taking into account both the baseline values of these outcomes and participants’ recovery beliefs Table . Again, An overview of the process and final results are shown in Fig. 2 ranging from 4.3% to 6.9%), but more substantial for the outcome of disability (6.8% to 20.3%), and highest at the first follow-up time point. The subgroupings did not provide substantial additional prognostic information when added to regression models that included the baseline values of participants’ recovery beliefs and either pain or disability.This study investigated the prognostic capacity of two novel LCA-derived subgroupings of patients with LBP. Neither of these LCA approaches were judged to have a better prognostic capacity then the other, as the single-stage and the two-stage subgroupings were similarly associated with the questionnaire-based outcomes of pain intensity and disability at 2 weeks, 3 and 12 months, and were similarly associated with the weekly SMS-collected outcomes of pain intensity, pain frequency and disability over 12 months. Their prognostic capacity was similar to, or somewhat better, than the two existing subgrouping tools that were included for comparison in this study for the outcome measures of pain intensity and disability. Their prognostic capacity was also similar to, or somewhat better than, the prognostic capacity of baseline LBP intensity and disability. These two novel subgroupings generally had a higher prognostic capacity than that of the baseline leg pain intensity for the outcome of disability, but not consistently so for the outcome of pain intensity. Compared to participants’ recovery beliefs, the subgroupings had a lower prognostic capacity for the outcome of pain intensity at 3 months and for the outcome of disability at 12 months, and similar prognostic capacity for the outcome pain intensity at 2 weeks and 12 months and for the outcome of disability at 3 months. These novel subgroupings also had a lower prognostic capacity than that of the domain-specific patient categorisations formed in the first stage of the two-stage LCA approach. The prognostic capacity of these two novel subgroupings was limited in size for the outcome of pain intensity  whose members were also mildly affected at baseline, but differed from the others as they had a high severity level over time. Patients in this subgroup, and the subgroups that were severely affected at baseline, differed qualitatively on the degree of nerve root involvement, psychological issues and persistence of their LBP. This aligns with previous evidence for markers of a poor prognosis , 40, 48.The prognostic capacity of the two new subgroupings were similar across time points and outcome measures, and therefore neither of these subgroupings was more strongly or consistently associated with outcomes than the other. However, the prognostic capacity of the new subgroupings was somewhat better than that of the two existing subgrouping tools used for comparison and therefore, there seems to be potentially important information within these new subgroups. This may be predictable, given that the new subgroupings were based on the same baseline characteristics covered by the existing subgrouping tools, plus additional baseline information. However, this indicates that additional prognostic information may be derived from clusters of the variables that are traditionally measured at an initial consultation for LBP.Still, it remains unclear how we can best extract and use this information. In particular, the domain-specific patient categorisations from the first stage of the two-stage approach showed a quite large prognostic capacity when entered directly into regression models. This indicates that the approach to aggregate information into a simple subgrouping – as done by the two-stage approach – is suboptimal with respect to the use of the available information. However, the prediction rule based on using the domain-specific categorisations as input would not currently be directly applicable in practice. It would require a determination of each patient’s assignment to a subgroup within each domain and then to build a summary score model involving overall 37 weights. Hence, there remains a task to find better and simpler ways to aggregate these domain specific categorisations.One strength of this study was the use of multiple and frequently used LBP outcome measures to test novel LCA-derived subgroupings. Another strength was that the LCA-derived subgroupings were formed in a large sample of LBP patients and these subgroups were selected not only on statistical criteria but also on their qualitative differences. This allowed identification of otherwise unrecognised relationships between baseline characteristics and was used to incorporate more of the clinical complexity of LBP into this prognostic study. The extent to which the results of such complex subgroupings can be generalised to other patient populations is unknown and this should be investigated.Comparing the prognostic capacity of our novel subgrouping approaches to two other subgrouping tools , and other known predictors, also strengthened our study. However, as there is evidence that the predictive ability of the SBT is stronger in populations with LBP of more than 2 weeks duration , which wIn addition, we recognise that neither the Quebec classification nor the SBT are primarily designed to be prognostic tools. However, the Quebec classifications, especially the characteristics of pain localisation and neurological signs have been shown to influence prognosis and therefore, the use of the Quebec classification as a comparator was considered reasonable , 51. TheIn evaluating the subgroupings derived from the LCA approaches, we ignored that there may have been potential misclassification of some subjects, as we relied purely on the highest posterior probability. Alternatively, we may have used the posterior probabilities themselves as input to the regression models (i.e. considered their prognostic capacity) or may have used approaches to correct for bias due to misclassification BCH, , 53). Ho. Ho53]).In this paper, we did not address the clinically feasibility of the subgroupings, e.g. whether they can be identified in practice based only on the verbal description or whether they can be implemented by using algorithmic support. Taking the rather low prognostic capacity into account, there is currently no merit for investigating this aspect. However, the promising results when using the domain specific categorisations and the role of single variables like the patient’s recovery beliefs may pave a way to obtain clinically feasible subgroupings or scoring rules in the future based on our data.Subgroups can have clinical significance if they predict better response to more targeted treatment and/or if they allow more precise estimates of prognosis. In this study, we only investigated the prognostic implications of these novel subgroups and found a relatively small amount of added prognostic capacity compared to simpler subgrouping tools. Consequently, we do not currently see direct implications of these LCA-derived subgroupings for clinical practice, in particular as their complexity suggests that direct clinical application would require software support. However, if these novel subgroups were further investigated and found to respond better to treatment that targets subgroup-specific modifiable factors, then a clinical implication of these subgroups may appear. Our current prognostic findings do not justify developing these new subgroupings into clinical prediction rules, especially when taking into account the comprehensive and time-consuming baseline questionnaires that formed the subgroupings. However, further research could aim at identifying the distinct characteristics that carried additional prognostic capacity in order to improve existing subgrouping tools and also investigate if distinctive aspects of these subgroups might be suitable for targeted treatment. Furthermore, the characteristics that differentiated these subgroups could be investigated in a causal model framework to determine whether they suggest the existence of different casual pathways.In addition, the lower prognostic capacity of the two-stage subgrouping, compared to using domain-specific patient categorisations, indicates that there is an information loss going from the first to the second stage of the two-stage LCA approach. This warrants further methodological investigation from both a statistical and a conceptual perspective.