The diagnosis of rare diseases poses a particular challenge to clinicians. This study analyzes whether patients’ pain drawings (PDs) help in the differentiation of two pain-associated rare diseases, Ehlers-Danlos Syndrome (EDS) and Guillain-Barré Syndrome (GBS).The study was designed as a prospective, observational, single-center study. The sample comprised 60 patients with EDS  and 32 patients with GBS . Patients marked areas afflicted by pain on a sketch of a human body with anterior, posterior, and lateral views. PDs were electronically scanned and processed. Each PD was classified based on the Ružička similarity to the EDS and the GBS averaged image (pain profile) in a leave-one-out cross validation approach. A receiver operating characteristic (ROC) curve was plotted.60–80% of EDS patients marked the vertebral column with the neck and the tailbone and the knee joints as pain areas, 40–50% the shoulder-region, the elbows and the thumb saddle joint. 60–70% of GBS patients marked the dorsal and plantar side of the feet as pain areas, 40–50% the palmar side of the fingertips, the dorsal side of the left palm and the tailbone. 86% of the EDS patients and 96% of the GBS patients were correctly identified by computing the Ružička similarity. The ROC curve yielded an excellent area under the curve value of 0.95.PDs are a useful and economic tool to differentiate between GBS and EDS. Further studies should investigate its usefulness in the diagnosis of other pain-associated rare diseases. This study was registered in the German Clinical Trials Register, No. DRKS00014777 , on 01.06.2018. Rare diseases present a great challenge for patients and physicians. The long way of suffering most patients must go through before they receive the correct diagnosis and treatment not only leads to enormous mental, physical, and social distress, but also places high economic burdens on our health care system , 2.The rareness and diversity of orphan diseases corresponds to a lack of knowledge among health care professionals, and both factors impede diagnosis and therapy , 4. OfteAgainst this backdrop the current study aims to explore the utility of patients’ pain drawings as a novel diagnostic tool in the differentiation and diagnosis of two rare diseases, Ehlers-Danlos Syndrome (EDS) and Guillain-Barré Syndrome (GBS). This methodological approach is based on the idea that repeating patterns in pain drawings (PDs) could help to accelerate diagnostic proceedings and sensitize physicians for rare diseases. The concept of pain drawing was implemented in 1949 by Palmer  and sincFor practical reasons regarding availability of patients, we chose EDS and GBS as two different disorders representing rare diseases associated with pain as primary symptom. EDS includes a heterogeneous group of inherited disorders, which are caused by different mutations in genes encoding fibrillar collagen or collagen-modifying enzymes , 9. The While PDs are valuable tools to communicate which part of the body is affected, they however do not contain information about quality and intensity of pain. Therefore, patients also filled in a pain questionnaire based on the “painDETECT questionnaire” and the “German pain questionnaire” in order to obtain information with regards to the quality of the pain experienced. This information was gathered in order to complement the regional information obtained from the PDs, and to have a data basis for future endeavors to combine PDs and questionnaire results into a single tool. The results are summarized in Table The study included 60 patients diagnosed with EDS. Within the EDS group, most of the patients (86.7%) indicated to suffer from pain for more than 5 years. None of the patients experienced pain for less than a year. Almost half of the patients (45%) reported pain attacks with pain in between. One third (28.3%) reported persistent pain with severe fluctuations. More than one-tenth each indicated to experience persistent pain with light fluctuations or pain attacks with pain-free episodes. In patients with pain attacks, the average attack lasted hours and occurred weekly to daily.The study comprised 32 patients diagnosed with GBS. Within the GBS group, 75% of the patients reported to suffer from pain for more than 1 year. One quarter of the patients who completed the questionnaire reported suffering from pain for more than 5 years. The majority (34.4%) experienced pain attacks with pain-free episodes. While one quarter of the patients reported persistent pain with light fluctuations, 6.3% reported persistent pain with severe fluctuations. In 21.9% of the patients, pain attacks occurred with pain in between. In patients with pain attacks, the average attack lasted hours and occurred several times a day.PDs were filled in by marking the painful areas in black in the body outline sheet shown in Fig. As depicted in Fig. Within the GBS group some regions of the body, like parts of the ventral side of the thorax and the lower side of the head, were marked by none of the participants  and Guillain-Barré syndrome (GBS) are two rare diseases associated with pain, but with dissimilar clinical presentation and etiology. EDS is a heritable connective tissue disorder with a number of subtypes, and has an estimated prevalence of 1 in 5000. EDS is characterized by joint hypermobility, skin hyperextensibility and tissue fragility with bruising, and definitive diagnosis is verified by genetic testing, with exception of the hypermobile EDS subtype, for which the genetic basis is unknown . GBS is By collecting PDs from patients with the previously verified diagnosis EDS or GBS, and averaging all PDs from each disease, we obtained a specific disease pattern for EDS and GBS, the pain profile (PP). Using the Ružička similarity coefficient, the binary classifier from Pain2D  was ableAs chronic pain occurs in one of five patients with rare diseases, and is frequently the first symptom that leads to medical consultation , pain asTo our knowledge, Pain2D  is the fComparison of our results with other computer aided diagnostic tools is difficult due to the differences in approaches, as is pointed out by the authors of a recent scoping review summarizing current developments in the field of rare disease diagnosis support . They idOf note, the main goal of the present study was not a new diagnostic approach to EDS and GBS, since their differential diagnoses would not normally overlap due to the clear differences in clinical presentation and etiology . Instead, it represents the first step towards a general rare disease classifier based on pain drawings. The excellent performance of our binary classifier for EDS.GBS classification suggests that PDs are indeed a valid tool to distinguish between rare diseases and shows that Pain2D  has the From a practical perspective in a clinical setting, Pain2D  in its fWhile we plan to include most rare diseases presenting with pain into future iterations of the tool, it will not be able to diagnose everything, since some diseases might have pain profiles that are more randomly distributed over the body, and it is of course unable to diagnose diseases that don’t present with pain. In addition, a limitation inherent to rare diseases is the relatively small sample size due to the small number of patients suffering from rare diseases. Furthermore, like all self-report instruments, the binary classifier has to deal with subjective interpretation of pain perception. The procedure for PD evaluation also has its limitations, since painful regions were marked using only one color. Thus, it is not possible to distinguish different qualities or intensities of pain, nor between e.g. pain of the skin at the joints, vs. joint pain. This is a limitation of the method, that for now, for the two examples used, is however not interfering with correct classification, as shown by the excellent results of the binary classifier Table . A combiRecently, Grigull et al. developed a questionnaire-based diagnostic support tool for several rare neuromuscular diseases by combining patient-oriented questions and data mining algorithms , a studyPDs are a useful and valid tool to distinguish between Ehlers-Danlos-Syndrome and Guillain-Barré-Syndrome. Future studies should analyze their potential in the detection of pain-associated rare diseases, as they could contribute to the optimization of diagnostic procedures in rare diseases.The trial was designed as a prospective, observational, non-interventional study in patients with Ehlers-Danlos-Syndrome and Guillain-Barré-Syndrome. The study design and protocol were reviewed and approved by the local ethics committee, registered in the German Clinical Trials Register No. DRKS00014777 , and performed in accordance with the Declaration of Helsinki and in compliance with Good Clinical Practice. Written informed consent was obtained from each patient.Between 2017 and 2018, a total of 60 patients with EDS  and 32 patients with GBS  participated in this study. To recruit patients, we contacted support groups for the diseases and attended their meetings. In addition, we used different social media platforms organized by support groups to draw attention to the study.After informed consent patients received a questionnaire and a PD by mail or via personal contact. To be sure that the patients filled out the questionnaire and the PD properly, we added a brief explanation see Fig. . PDs werOnly patients without any other chronic disease besides the ones investigated in this study were included. Inclusion criteria were as follows: patients with GBS or EDS with a minimum age of 18 years, and written consent obtained after a detailed explanation of the investigation.To evaluate different aspects of pain symptomatology, patients filled in a questionnaire based on the “painDETECT questionnaire” and the “German pain questionnaire”. Besides personal information , the questionnaire asked for the chronicity of pain , pain course pattern , frequency of pain attacks , duration of the pain attacks (from a few seconds to more than 3 days), and dependency on time of the day. In addition, a list of eight adjectives describing the sensory, and four adjectives describing the emotional aspect of pain perception was used. Furthermore, seven questions concerning specific characteristics of neuropathic pain were included.In addition to the questionnaire the patients received a sketch of a human body (PD) with anterior, posterior and lateral views. Additionally, head, mouth, as well as anterior and posterior views of hands and feet were magnified to receive more detailed information of these regions see Fig. . PatientThe patients marked the afflicted areas of pain on the drawings. If the PDs for different reasons  lacked electronic readability, the template PD was transferred into a new PD with thicker lines or an uncreased questionnaire. This problem occurred in 10% of the PDs in the EDS group and 16% of the PDs in the GBS group.We used the software Pain2D, which was previously developed by our group , to geneIn a leave-one-out cross-validation approach, each PD was classified by the binary classifier of Pain2D  as eitheNS developed a software Pain2D  with the


Background and Objectives: Lumbar traction is widely used as a non-operative treatment for lumbar intervertebral disc disease. The effect of traditional traction (TT) using linear-type traction devices remains controversial for various reasons, including technical limitations. Thus, the purpose of this study was to compare the effects of the newly developed lumbar lordotic curve-controlled traction (L-LCCT) and TT on functional changes in patients and morphological changes in the vertebral disc. Materials and Methods: A total of 40 patients with lumbar intervertebral disc disease at the L4/5 or L5/S1 level as confirmed by magnetic resonance imaging were recruited and divided into two groups (L-LCCT or TT). The comprehensive health status changes of the patients were recorded using pain and functional scores  and morphological changes  before and after traction treatment. Results: Pain scores were significantly decreased after traction in both groups (p < 0.05). However, functional scores and morphological changes improved significantly after treatment in the L-LCCT group only (p < 0.05). Conclusions: We suggest that L-LCCT is a viable option for resolving the technical limitations of TT by maintaining the lumbar lordotic curve in patients with lumbar intervertebral disc disease. Lumbar traction is widely used on patients with intervertebral disc disease, as a way to reduce pressure on the vertebral foramen by releasing tension between adjacent spinal vertebrae ,2,3. ThuSince individual physical conditions vary, standard therapeutic guidelines need to be customized, which requires time and effort. As there are no standard protocols or previous well-designed studies for traction treatment, it may be difficult to evaluate the efficacy of traction treatment compared to a control. As suggested by Clarke et al. , it is dIn addition to the reasons mentioned above, there can be technical limitations to applying traction in patients with intervertebral disc disease. One possible reason for a technical limitation in applying traction is the change in the lordotic curve. First, the lordotic curve may be decreased during lumbar traditional traction (TT). When traction force is applied to the spine in the TT method, the main effect is to straighten spinal structures, rather than decompress intervertebral discs. This also decreases the natural lordotic curve, and may be the cause of discomfort and poor treatment outcomes after spinal traction ,15,16. WConsequently, we wondered if applying a traction force to vertebrae while maintaining the lordotic curve would result in equal force distribution to the anterior and posterior parts of the spinal structure. In this sense, the lumbar lordotic curve-controlled traction device (L-LCCT), which targets the L3–5 intervertebral disc space, has been invented. In our previous study , we measTo date, no study has measured functional outcomes and morphological changes of vertebral discs in lumbar intervertebral disc disease patients using L-LCCT. Therefore, the purpose of our study was to investigate the clinical efficacy of L-LCCT compared to TT in patients with lumbar intervertebral disc disease.This study was a double-blinded randomized controlled trial comparing L-LCCT and TT. After acquiring informed consent, all patients with intervertebral disc disease were selected from the outpatient clinic. This study was conducted in accordance with the Declaration of Helsinki. All patients received sufficient explanation regarding the objectives and methods of the study before participating. Patients were randomly assigned into the two groups (L-LCCT or TT) by a research physician, with the help of a computer-generated table of random numbers. No patients knew which group they belonged to. Evaluations were carried out by a physician who was blinded to the treatment. This study was approved on 20 April 2016 by the institutional review board (IRB 04-2016-029).A total of 40 patients  with lumbar intervertebral disc disease at the L4/5 or L5/S1 level, as confirmed by MRI (Magnetic Resonance Imaging), were recruited between June 2016 and February 2017. The inclusion criterion was a diagnosis of herniated intervertebral disc disease (HIVD) in the lumbar spine, with unrelenting low back pain and/or sciatica symptoms lasting more than 3 months. Exclusion criteria were as follows: patients with acute inflammation, unstable lumbar vertebrae, joint hypermobility, inhibited flexion or extension of the lumbar vertebrae, or a released disc fragment . Each paThe L-LCCT  was used to maintain the natural lordotic curve of the spine by supporting the lumbar curve at the L3–5 intervertebral disc space. After the patient assumed a supine position, the chest and pelvis were belted. Initially, a magnetic marker was attached to the skin at the L4 intervertebral disc space by physical palpation and an automated tracking system . The autThe TT method was applied to patients without supporting the lumbar lordotic curve. We followed the same protocol as for L-LCCT, except without the lordotic curve modification, and with the patient lying in a supine position. According to previous reports and patient clinical compliance, all patients received traction three days per week for five weeks . TractioPain and functional outcomes were measured before the first intervention and after the last treatment session.Pain in the trunk and lower extremities that was exacerbated during daily living activities was measured using the mean pain score from the VAS, which ranges from 0 to 10. The patients were asked to place a mark along the line to denote their pain level, where 0 reflected “no pain” and 10 reflected the “worst pain”.The ODI and RM were used to assess patients’ functional status. The ODI consists of 10 items that refer to daily living activities that might be disrupted by pain. These items are as follows: pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, and traveling. Each item is rated on a six-point Likert scale. The total score is then translated to a scale ranging from 0 to 100, where 0 indicates no disability and 100 indicates the worst possible disability . The RM We assessed the changes in the lumbar central canal area before and after lumbar traction. All MRI examinations were performed using a 3 Tesla MRI . Using T2-weighted images (field of view (FOV): 150 × 150 mm; echo time (TE): 108 ms; repetition time (TR): 4500 ms), the axial image of the disc level associated with the greatest neurological compression was selected for measurement. In this study, the L4/5 or L5/S1 intervertebral disc level was selected. Digital measurement of the central canal area outline was performed by tracing the dural cross-sectional area boundaries on the axial MRI at the disc level . MeasureThe evaluations of pain (VAS), function (ODI and RM), and morphology (lumbar spine MRI) were conducted within two days of the first and last treatment sessions.t-tests. The significance level was set at p < 0.05. All analyses were performed using SPSS software v.22.0 .Sample size analysis showed that at least 40 participants were required for a two-sided significance level of 0.05 and an inter-class correlation coefficient of 0.8. Thus, 40 patients were enrolled, considering potential loss to follow-up. Data were analyzed using paired and independent p > 0.05). All patients completed the full five-week study period .Patient demographic data are presented in p < 0.05), while there were no significant changes in the central canal area in the TT group after treatment (p > 0.05).Patients’ pain, functional status, and morphological changes are presented in Both groups showed significant decreases in pain scores. However, changes in functional scores and central canal area improvements were significantly greater in the L-LCCT group than the TT group .Prolonged periods of pain due to intervertebral disc disease have abnormal neurological mechanisms . Such neDespite its theoretically favorable effects as a spinal traction device, the clinical usefulness of the TT method in treating lumbar disc disease has been low in clinical settings ,25,26,27In this study, we also obtained favorable results for the group with L-LCCT compared to TT in terms of pain, function, and morphological outcomes . Both grIn addition to pain and functional scores, which could be considered subjective measurements, we also compared morphological changes using lumbar spine MRI. After treatment, the L-LCCT group showed significant widening in the central canal area. However, the TT group did not show any significant differences in the central canal area after treatment. This may be related to the L-LCCT’s ability to maintain or restore the lumbar lordotic curve during spinal traction, thereby reducing the unnecessary muscle guarding to load a sufficient traction force. However, this study has several limitations. First, although we recruited a sufficient sample size, more subjects of different ages will be necessary to generalize our results. As disease status can vary from individual to individual, our results need to be carefully re-evaluated before they can be applied clinically. Age, sex, race, and individual physical factors should also be considered in future studies. Second, vertebral discs can differ in several characteristics including resilience, softness, or severity. In this study, disc disease patients with relatively mild disabilities and low ODI scores were recruited. Regarding geometric status, pain threshold and functional outcome differences could also lead to different outcomes.Third, although this study recruited patients with more than 3 months of unrelenting intervertebral disc disease, there was no control group without disc disease in this study. As it is possible that disc disease could have resolved spontaneously, a control group with stricter requirements should be included in future studies.In this study, we obtained immediate responses from patients after traction sessions, and the final outcome measurement was done after completing 15 sessions of traction (approximately 1.5 months). Although this does not reflect the long-term efficacy of traction treatment, we were able to compare the therapeutic effects of the different treatments in a given time. The long-lasting effects of the treatment should be determined in future studies.Despite these limitations, the newly invented L-LCCT is recommended as an effective treatment method for lumbar intervertebral disc disease. Future studies should be conducted to re-establish traction guidelines such as intensity, interval, and treatment frequency, with the goal of obtaining the best results.This study showed that a newly invented traction device that maintained the lumbar lordotic curve was more effective than a traditional traction device in improving pain, functional status, and morphological changes. Thus, this could be an ideal treatment option for patients with lumbar intervertebral disc disease.


The Michigan Hand Questionnaire (MHQ) is widely used to assess the hand/wrist conditions. We translated the original version into Thai (Thai MHQ) and evaluated its psychometric properties.After receiving permission, the original MHQ was translated and cross-culturally adapted to Thai following standard guidelines. Two hundred and seventeen patients who had hand/wrist injuries or disorders were included in the study. Internal consistency was evaluated using Cronbach’s alpha. Test-retest reliability was analyzed using the intraclass correlation coefficient (ICC). Spearman’s rank correlation among the subscales of Thai MHQ, Thai DASH and Thai EQ-5D-5L and also confirmatory factor analysis (CFA) were used to explore construct validity. The standardized response mean (SRM) was used to evaluate the responsiveness of the Thai MHQ.r = 0.77, P < 0.0001). For unrelated dimensions, a weak correlation was found between the Aesthetics subscale in the Thai MHQ and the Mobility subscale in the Thai EQ-5D-5L . The Thai MHQ had strong correlation with Thai DASH  and Thai EQ-5D-5L . CFA showed that the 6-factor model demonstrated an acceptable fit to the data. The SRM of the Thai MHQ was 0.78, indicating relatively large responsiveness. The MIC of Thai MHQ using distribution methods (SEM) was 5.2.All subscales showed an acceptable Cronbach’s alpha (0.79–0.98). The test-retest reliability of each subscale was good (ICC = 0.83–0.95). In related dimensions, strong correlation was demonstrated between the Activities of daily living subscale of the Thai MHQ and the Common activities subscale in the Thai DASH (The Thai MHQ provides adequate internal consistency in all subscales as well as good construct validity and reliability for Thai patients and a relatively large standardized response mean at 2 months after treatment. Hand and wrist are common areas for upper extremity injuries –6. To evThe Michigan Hand Outcomes Questionnaire (MHQ) is one of the widely used patient-rated outcome measurement instruments for patients with hand disorders. This questionnaire is the subjective assessment for musculoskeletal, neurological or nonspecific pathology which providing the ordinal data type according to The World Health Organization International Classification on Functioning Disability and Health (WHO ICF) summary . The oriEvaluations of psychometric properties of the MHQ have documented high internal consistency and test-retest reliability , 17–19. Presently, what is lacking is a hand/wrist outcome measurement which is reliable, valid and responsive specifically for Thai patients who have hand/wrist injuries or disorders. Although a Thai version of MHQ has recently been reported by Dhippayom et al., that version has some limitations. The study was conducted with a small sample size (30 patients) and demonstrated a relatively low statistical power (0.51). Additionally, factor analysis and responsiveness evaluations have not been reported .The aims of this study were to create a Thai version of the original MHQ, including translation and cross-cultural adaptation, and to investigate the psychometric properties of the Thai version including reliability, validity and responsiveness.The first of two stages in this study was the translation and cross-cultural adaptation of the original MHQ to create a Thai version. The second step was to explore the psychometric properties of the Thai MHQ, including reliability, validity and responsiveness. We hypothesized that the Thai version could maintain the reliability, validity and responsiveness of other versions of MHQ. This observational study was approved by the local institutional research ethics committee.The Michigan Hand Outcomes Questionnaire (MHQ) consists of specific questions in 6 subscales including overall hand function (5 items each for left and right hand), activities of daily living ; work performance (5 items); pain (5 items each for left and right hand); aesthetics (4 items each for left and right hand); and satisfaction with hand function (6 duplicate items each for left and right hand) . The relStage 1. Forward translation. Two bilingual translators  independently translated the original MHQ into Thai versions (T1 and T2) .Stage 2. Synthesis. The two translators discussed differences point by point and created a synthesis of the T1 and T2 versions (T-12). The differences were also discussed with an Orthopaedic hand specialist to arrive at a consensus.Stage 3. Back translation. The T-12 version was back translated into English (BT1 and BT2 versions) by two bilingual English/Thai speakers (English language lecturers) to ensure that the concept of the original version was maintained.Stage 4. Review by an expert committee on hand surgery and measurement development. An expert committee, composed of one hand surgeon, one rehabilitation specialist, one psychiatrist and two linguistics experts, reviewed and consolidated the pre-final version of Thai MHQ from all the translated versions .Stage 5. Field testing of the pre-final version. Field testing was conducted with 15 healthy volunteers and 15 patients who had hand/wrist injuries. All were native Thai speakers who were fluent in reading, writing and understanding the Thai language. They were requested to examine all instructions and items for item-objective congruence (IOC) and to provide suggestions. If any item demonstrated an IOC value less than 0.5, that item was reconstructed and reevaluated until the IOC value reached at least 0.5. Finally, the pre-final version of the Thai MHQ was translated back into English and sent to Chung et al. for approval.The authors requested permission from Chung et al. to translate the original version into Thai. Translation and cross-cultural adaptation was performed following the recommendations of Beaton et al. which consist of 5 stages as described below .Stage 1Internal consistency, construct validity, factor analysis, test-retest reliability and responsiveness of Thai MHQ were evaluated in Thai patients who were enrolled prospectively at the Hand Outpatient Clinic of Academic University Hospital from December 2018 to December 2019. Inclusion criteria were patients who had hand/wrist musculoskeletal disorders, used Thai as their first language and had the ability to read and understand Thai, age between 15 and 70 years and had the ability to complete the questionnaire without major assistance. Patients who had a musculoskeletal disorder above wrist level, an active cerebral disorder or communication problems were excluded. Since there were many types of hand and wrist injuries or disorders, the treatments might include both conservative and operative treatments. The follow-up schedule to evaluate responsiveness was at least 4 weeks after treatment depending on the diagnosis of each patient. This study adhered to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist .After giving informed consent, patients were enrolled in study. Patient demographic data recorded include age, sex, dominant hand, injured hand, diagnosis and time taken to complete the questionnaire.Internal consistency is the degree of correlation between items measuring the same outcome. Cronbach’s alpha was used to measure the internal consistency of each subscale and the total score of Thai MHQ. Values can range from 0 to 1, with higher scores indicating greater interrelatedness between items. Values of 0.70 or higher are considered to be adequate .Test-retest reliability is the ability of successive measurements to obtain similar results in a stable individual. The recommended time between the initial and the repeat administration of the measurement is 1 week to avoid recall and to ensure that clinically significant change has not occurred. The Thai MHQ was administered twice with a 7-day interval before treatment . The intr < 0.3), moderate (0.3 ≤ r ≤ 0.6), or strong (r > 0.6) [Construct validity is a measure of the association between an instrument and theoretically hypotheses concerning the concepts being measured , 37. Ther > 0.6) .The Thai DASH questionnaire consists of 30 self-reported items to assess symptoms and disability status. It also contains 2 optional modules, a Work and sports subscale and a Performing arts subscale . The Thahttps://euroqol.org/eq-5d-instruments/eq-5d-5l-about/valuation-standard-value-sets/crosswalk-index-value-calculator/). We used the Thai index which ranged from − 0.452 to 1.000 [The EQ-5D-5L is a two-part outcome measurement extensively used to evaluate health status , 45. Theto 1.000 .2/df < 3 [Construct validity of the Thai MHQ was also investigated using confirmatory factor analysis (CFA) to evaluate the nature of and relations between latent constructs. Maximum likelihood estimation was used to evaluate the parameters. Both unidimensional construct and 6-factor-model of the Thai MHQ were analyzed. Indexes used for evaluating goodness of fit included a comparative fit index (CFI) of ≥0.95, a non-normed fit index (NFI) or Tucker-Lewis Index (TLI) ≥0.9. A root-mean-square error of approximation (RMSEA) ≤0.6 (0.08) was considered an acceptable fit , 48 and 2/df < 3 , 48. Mod2/df < 3 .Responsiveness is the ability of a measurement to detect clinically significant changes over time . Responsability) . The sma.96×2×SEM.Floor or ceiling effects were considered to be present if more than 15% of patients reported the lowest or highest possible scores . If flooP < 0.05. In multiple comparisons, the P-value was adjusted using Bonferroni’s method. Following on Mundfrom et al. regarding levels of communality the ratio of the number of variables to the number of factors indicated, a minimum sample size of 200 patients was sufficient for factor analysis in this study with 37 variables and 5 factors [For demographic data, categorical variables are reported as frequencies and percentages. Continuous variables are reported as means and standard deviations. Statistical significance was set at  factors . The preMinor cross-cultural adaptations were modified in the activities of daily living subscale. The item “Eat with a knife/fork” was changed to “Eat with spoon and fork”. Other adaptations were made in the patient characteristics (information) section. The items “What is your ethnic background?”, “What is your racial background?” and “How long after your surgery did you return to the job you were doing before your injury” were removed. The range of family income was changed in the item “What is your approximate family income”. During field testing, 30 volunteers  completed the pre-final version. All items had an IOC >0.5, an acceptable level. The final Thai version was approved by Michigan Center for Hand Outcomes and Innovation Research.Demographic data are shown in Table The internal consistency of the Thai MHQ was assessed with 217 patients Table .Table 2r = 0.58, P < 0.0001) as well as between the Thai MHQ and the Thai EQ-5D-5L . A strong correlation  was demonstrated between the Activities of daily living in the Thai MHQ and the Common activities in the Thai DASH, indicating convergent validity. Among unrelated dimensions, there were the weak negative correlations between the Aesthetics subscale in the Thai MHQ and the Pain subscale in the Thai DASH  and also between the Aesthetics subscale in the Thai MHQ and the Mobility subscale in the Thai EQ-5D-5L  indicating discriminant validity. There were the strong correlations between Thai MHQ and Thai DASH  and between Thai MHQ and Thai EQ-5D-5L .Evaluation of the construct validity of the Thai MHQ was conducted with 217 patients. The correlation of subscales for the Thai MHQ, the Thai DASH and the Thai EQ-5D-5L was compared Table . In relaCFA2 = 891.834, df = 374 (p < 0.001). However, the 6-factor solution fitted the data best with the following statistics: CFI was 0.995, TLI was 0.994, RMSEA was 0.047 , SRMR was 0.041, and a χ2 = 570.062, df = 385 (p < 0.001). The fit statistics for all models were based on the fact that the error terms of the indicators within the same subscale were correlated.The unidimensional model showed an acceptable fit to the data with a CFI of 0.985, TLI of 0.983, RMSEA of 0.080 , SRMR of 0.067, and a χFifty patients continued with followed-up after receiving initial treatment and completed all items in the Thai MHQ questionnaire both before treatment and at follow-up. The mean time to follow-up was 52 days. The three most common treatments were steroid injection (32%), surgical fixation 26%) and surgical release (20%). The SRM and ES of the Thai MHQ were 0.78 and 0.69 respectively indicating relatively large responsiveness , although the Aesthetics subscale was slightly lower (0.79 for right and 0.80 for left). The internal consistency of this subscale is comparable to the Korean , Turkish , Canadian French  and previous Thai versions (0.48) , 32, 58.Exploration of the test-retest reliability of the Thai MHQ showed good to excellent reliability in all subscales (ICC = 0.83–0.95), results comparable to the original MHQ and other versions (ICC range 0.73 to 0.99) , 57, 58.r = − 0.77). This correlation could be due to the similarity of questions in both subscales. Among unrelated subscales, a weak correlation was revealed when comparing each subscale of the Thai MHQ and the Mobility subscale of the Thai EQ-5D-5L (r < 0.3)  and exploratory factor analysis (EFA). In comparing subscales between the Thai MHQ and other instruments, a strong correlation was found between the Activities of daily living subscale in the Thai MHQ and the Common activities subscale in the Thai DASH (3) Table . These r3) Table .Our CFA findings were consistent with the original version, supporting the 6 hypothesized model . HoweverThe responsiveness of the Thai MHQ demonstrated a relatively large standardized response mean (SRM = 0.78) which was slightly lower than the SRM of the Thai DASH for the same cohort 0.85) (Table  Table 5. As a reThere are some limitations in the present study. First, responsiveness to treatment for each diagnosis was not included because our aim was to focus on generalized hand/wrist injuries or disorders. Further studies could be conducted to evaluate the responsiveness with specific diagnoses, treatments and follow-up periods. Second, in the test-retest reliability and responsiveness assessments, patients who were not followed up or who did not complete the entire questionnaire were excluded, although the number of patients remaining was still comparable to previous studies , 57, 58.The Thai MHQ provides adequate internal consistency in all subscales as well as good construct validity and reliability for assessing Thai patients with wrist/hand injuries or disorders and provides a relatively large standardized response mean at 2 months after treatment. The Thai MHQ is one of the standard patient-rated outcome measurements available for clinicians and researchers to use in evaluating symptoms and functions of the hand/wrist in both clinical healthcare and in medical research.


In the recovery unit, there was less need for pain medication in patients with UKA (p = 0.004 for non-opioids). The opiate consumption was similarly lower for the UKA group, but not statistically significant (p = 0.15). In the ward, the UKA group needed less opioids (p < 0.001). Patient subjective parameters were significantly better for UKA. After implantation of unicompartmental knee arthroplasty, patients showed lower pain scores, a reduced need for pain medication and better patient subjective parameters in the early postoperative course in this study.Unicompartmental knee arthroplasty and total knee arthroplasty are well established treatment options for end-stage osteoarthritis, UKA still remains infrequently used if you take all knee arthroplasties into account. An important factor following knee arthroplasty is pain control in the perioperative experience, as high postoperative pain level is associated with persistent postsurgical pain. There is little literature which describes pain values and the need for pain medication following UKA and/or TKA. So far, no significant difference in pain has been found between UKA and TKA. The aim of the study was to evaluate differences in the postoperative course in unicompartmental knee arthroplasty vs. total knee arthroplasty regarding the need for pain medication and patient-reported outcomes including pain scores and side effects. We hypothesized that unicompartmental knee arthroplasty is superior to total knee arthroplasty in terms of postoperative pain values and the need of pain medication. In this project, we evaluated 2117 patients who had unicompartmental knee arthroplasty and 3798 who had total knee arthroplasty performed, from 2015 to 2018. A total of 4144 patients could be compared after performing the matched pair analysis. A professional team was used for data collection and short patient interviews to achieve high data quality on the first postoperative day. Parameters were compared after performing a 1:1 matched pair analysis, multicenter-wide in 14 orthopedic departments. Pain scores were significantly lower for the UKA group than those of the TKA group ( The medial compartment is associated with a higher incidence of arthritis compared to the lateral compartment, therefore medial UKA is performed more often than lateral UKA. Because of the anatomic and kinematic differences between the medial and lateral compartment, lateral UKA is technically more challenging than medial UKA5.There are controversial discussions, whether a retro-patellar replacement should be performed primarily for prosthesis implantation. A uniform recommendation has not yet been issued10. Unicompartmental knee arthroplasty allows patients a faster return to a more functional level than TKA, but postoperative pain management still remains a challenge, since there is no significant difference in pain16. Pain negatively affects the functional outcome, patient satisfaction and their psychological well-being19. Postoperative pain management strategies include oral or intravenous analgesics, patient-controlled analgesia (PCA), single shot or continuous peripheral nerve blocks or local infiltration analgesia (LIA). The aim of postoperative pain management is to improve the patients’ comfort, satisfaction and functional outcome after UKA and TKA. Insufficient pain management can be revealed by Continuous Quality Improvement (CQI) strategies. The “Quality Improvement in Postoperative Pain Management (QUIPS)” project is an outstanding tool20 to compare and then improve pain management. Despite the fact that the successful use of a knee arthroplasty increases the quality of the patient’s life, 20–30% of all patients remain permanently dissatisfied with the results of their operation21. Kehlet et al. reported, that 10–34% of the patients may develop chronic pain after implantation of TKA. A high postoperative pain level is associated with persistent postsurgical pain23. Previous studies have mainly used PROM scores (WOMAC/KSS) to assess postoperative pain in the follow-up after surgery. An investigation of early postoperative pain, the need of pain medication, side effects and functional impairments after UKA and/or TKA has not been considered extensively so far.UKA has been shown to have several advantages over TKA, including reduced blood loss, shorter length of hospitalization, improved postoperative patient-reported functional outcomes and less postoperative morbidity25.The purpose of this study was to evaluate differences in the short-term perioperative course after unicompartmental knee arthroplasty vs. total knee arthroplasty. We also looked at the need for pain medication and patient-reported outcomes as well as pain intensity and side effects, since total knee arthroplasty still is, by far, the more frequently used technique. In a relevant amount of cases, UKA could have been used considering indication criteriaThis large-scale multicenter study evaluated the need for pain medication, subjective functional score, as well as pain intensity scores in the immediate postoperative course of unicompartmental or total knee arthroplasty. We assumed that unicompartmental knee arthroplasty is superior to total knee arthroplasty, in terms of postoperative pain and the need of pain medication.26. The study was approved by the Ethics Committee, as well as, the Data Security Board of the Jena University Hospital, Jena, Germany, and by the Ethics Committee of the University of Regensburg. Furthermore, the project was registered in the German Register of Clinical Studies (DRKS) with the approval number DRKS00006153 (WHO register). The study was applied in accordance with the ethical standards of the Declaration of Helsinki 1975.The QUIPS  project is an initiative to compare patient-reported outcomes related to perioperative pain management. With over 450,000 data records, QUIPS is one of the largest acute pain databases in the world. In participating hospitals of the QUIPS project, data was obtained on the first postoperative day. The QUIPS project is supported by the German Society of Surgeons and the German Society of AnesthesiologistsAll primary unicompartmental and total knee arthroplasties included in the QUIPS data base (see below) regardless of the anesthetic technique used, meeting the inclusion and exclusion criteria were evaluated. Inclusion criteria were as follows: (1) patients older than 18 years of age, (2) able to communicate and (3) who had primary unicompartmental or total knee replacement surgery performed. Information about QUIPS was supplied to all potential patients. Participation was voluntary. Informed consent was obtained from all participants. Exclusion criteria were: (1) absence of the patient in the ward, (2) patients who refused to participate and (3) patients who were asleep or sedated at the time of data collection and interviews 24 h postoperative.27. For those patients, who needed an opioid postoperatively, the opioid equivalent was calculated in mg by using morphine as a basis for comparing the different opioid agonists.The QUIPS questionnaire is divided into sections dealing with pain intensity, functional impairment, side effects of pain treatment and global assessment by the patient  and the TKA group (n = 3798) were matched according to age, sex and ASA score. If there was more than one matching partner for one patient, one patient was randomly chosen. A total of 4144 patients were finally analyzed and compared  and TKA (n = 3798). The following statistical evaluation was performed according to Greimel et al.p-values are two-sided and a p value < 0.05 was considered statistically significant. All analyses were performed using SPSS 25.0 .Continuous variables were indicated by mean (standard deviation) or median (interquartile range) depending on the underlying distribution. Categorical data was presented as absolute numbers and/or relative frequencies. The opioid equivalent was calculated using the Mann–Whitney-U-test. To compare the use of pain medication, side effects or functional parameters between the UKA group and the TKA group, a Pearson’s chi-squared test was used for each pairwise comparison. The differences in the NRS values between the two study groups were analyzed by using t-tests. Normality was assessed visually by Q-Q-Plots and by the parameters median, mean, skewness and kurtosis. Normal distributed data were compared using students t-Test. Non-Normal data were compared using the Mann–Whitney-U Test. All reported A total of 4144 patients  were finally statistically analyzed and compared after performing a matching of age, sex and ASA score because of demographic inhomogeneity and to reduce confounding variable bias   advantage for the UKA group  and in the TKA group 4.4 (± 2.4). Mean activity pain was significantly lower for the UKA group (.3 and inp = 0.004). The opioid consumption was similarly lower for the UKA group, but not statistically significant (p = 0.15) (Table In the recovery unit for UKA patients the need for non-opioids was significantly lower than for the TKA patients p = 0.00. The opip < 0.001). The use for non-opioids was statistically higher for UKA than for TKA (p < 0.001). The calculation of the opioid equivalent (mg) in relation to morphine showed no statistically significant difference between the two groups . All other items did not differ significantly after comparing the two groups in question.Functional outcome parameters and side effects are shown in Table 30, but no difference in pain, comparing UKA to TKA16. These studies in general used PROM scores (KSS/WOMAC) for evaluation of pain intensity in the follow-up after UKA and/or TKA. Literature evaluating early postoperative pain and pain management after UKA and TKA is emerging. In addition, possible side effects of pain therapy and functional impairments were rarely investigated. The aim of this study was to compare the use of pain medication, pain control and patient’s subjective parameters after having had UKA or TKA performed as early pain control can have an impact on postoperative outcome and length of hospitalization.In recent years many studies have been carried out on the comparison of the clinical outcomes of patients after UKA and TKA. Among these studies, the consensus conclusion, is that patients who underwent UKA have better function PROM scores, better range of movement, quicker recovery period and shorter hospitalization31 in which 71 patients with UKA and 37 patients with PFA  were matched by sex and age to 108 patients with TKA. Opioid consumption in the first postoperative ward round was significantly lower for the UKA group than for the TKA group or PFA. A consistent result was found in the Kalbian et al. study32. Patients required a significantly lower rate of opioid prescription after UKA-implantation compared to TKA-implantation. We considered that the reduced consumption of opioids after UKA implantation was due to lesser surgical trauma caused by a smaller incision and a greater perseveration of native structures.Similar results to our study can be seen in the study of Melnic et al.We did not expect anesthesia procedures to represent a potential confounder, as anesthesia procedures did not differ in percentage between the two groups of UKA and TKA Table .For those patients who needed an opioid, the calculation of the opioid equivalent in the recovery unit and in the ward showed no significant difference between the two groups. One possible explanation could be an increased individual need for opioids. In total, patients after UKA had a lower opioid consumption compared to patients after TKA, but those who had taken an opioid may have needed a comparatively higher dose, since significantly fewer patients required an opioid after UKA than after TKA by an equivalent opioid dose Table . On the Another important parameter was the patient’s subjective pain level. A lower postoperative pain level means increased comfort and satisfaction for the patient and consequently an improved postoperative function. Postoperatively, there was a significant difference in pain under mobilization, measured according to the NRS-scale, with less pain in the UKA group in comparison to the TKA group. The pain maximum and pain minimum (NRS) were also significantly lower for the UKA group. Fig. , Table 315 pain specific PROM scores were found to be equivocal after UKA compared with TKA with no significant difference between the two groups. The matched pair analysis of Lombardi et al. 13 showed no significant difference in pain after UKA and TKA in the KS pain score after a follow up of 6 weeks and an average of 30 months. The study by Noticewala et al. reported a significant difference in the WOMAC pain score and the WOMAC physical function score in the follow-up 3 years after UKA or TKA with better result for UKA33. A recently published study by Lakra et al.34 has shown that an improved management of early postoperative pain was associated with a better functional outcome in the follow-up 2-years after TKA. Our results showed lower pain under mobilization and lower minimum and maximum pain for the UKA group. Higher postoperative patient-reported functional outcomes were described in several studies with advantages for UKA26.To date, there are hardly any studies that have investigated early postoperative pain differences between UKA and TKA implantation. In general, pain was investigated using PROM scores, e.g. the KS pain score or the WOMAC score. In the systematic review and meta-analysis of Wilson et al. 35. A correlation between the postoperative pain level and the development of chronic pain has been shown23. An improvement in pain management in the early postoperative course could be a contributing factor in reducing chronic pain. This could lead to faster recovery and mobilization, psychological well-being and to a general improvement of the outcome.The risk of developing chronic pain after knee surgery is reported to be even higher than in e.g. hip replacement surgeryFurthermore, the group of UKA had significantly better results for side effects “very tired”, “vertiginous”, “nausea” and functional outcome parameters: “woke up because of pain” and “pain affecting mood” Table . The patThis study shows several limitations such as the assessment of postoperative pain and pain management. Because of organizational reasons these values have been collected on the first postoperative day and differences in the continuing postoperative period could not be evaluated. Within the QUIPS study protocol, factors such as indication criteria for UKA or TKA, intraoperative surgical details such as the use of tourniquets or drains could not be investigated.Big data studies have a general restriction in explanatory power. A huge data quantity could provide significant results despite small differences in value. Nevertheless, in daily clinical routine big data studies are of great interest to evaluate the efficacy of interventions.Furthermore, selection bias cannot be barred, but the matching tries to reduce the influence of confounding variables. One possible selection bias could have been preoperative pain intensity and anesthetic technique used, but after matching both groups showed similar pain intensity preoperatively. We have demonstrated statistically significant results for pain level between the both groups of UKA and TKA, but possibly they are below clinical relevance. This big data study represents daily clinical routine and is therefore, of great interest in the clinical decision-making process in choosing treatment options. A high percentage of patients, who are eligible for primary joint replacement with isolated unicompartmental osteoarthritis still have TKA performed.In contrast to previous studies, our study has shown that patients undergoing UKA have had lower pain scores postoperatively and less need for opioids in the ward, in a multicenter matched pair analysis in 4144 cases. Furthermore, patient subjective parameters were significantly better for UKA. Although opiate consumption was less likely for patients with UKA than for patients with TKA, there was no significant difference in opiate equivalent.


Ehlers–Danlos syndrome (EDS) is a connective tissue disorder characterized by joint hypermobility and skin extensibility and is often accompanied by chronic pain. Rhythmic sensory stimulation (RSS) can be defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain. In this current study, we conducted an open-label pilot study of 15 patients with hypermobile EDS using RSS as the intervention. Posttreatment improvements were seen in 11 of the 15 patients (73%), whereas 3 of the 15 patients (20%) experienced worse outcomes. Of the 14 patients that completed the experiment, 6 participants (43%) were classified as “responders” to the device while 8 participants (57%) were classified as “nonresponders.” Responders demonstrated significant improvements in pain interference (51.5 ± 16 preintervention vs. 43.5 ± 16.4 postintervention BPI score) and depression symptoms (34.0 ± 15.9 preintervention vs. 26.8 ± 12.1 postintervention CESD score). Poststudy interviews confirm the improvements of pain interference, mood, and bowel symptoms. Furthermore, analysis of medical conditions within the responder group indicates that the presence of depression, anxiety, irritable bowel syndrome, and fibromyalgia may indicate a greater likelihood for patients to benefit with vibroacoustic applications. These results indicate a possible potential for RSS, delivered using a vibroacoustic device, in managing pain-related symptoms. Further research is necessary to elucidate the exact mechanism behind the physiological benefits of RSS. Ehlers–Danlos syndrome (hEDS) is a congenital, heterogeneous group of connective tissue disorders characterized by joint hypermobility and skin extensibility . Many foSeveral theories have been proposed to explain the mechanism(s) of chronic pain. Melzack and Wall's gate control theory (GCT) involves a bottom-up approach which posits that stimulation of peripheral nerves by nonnoxious stimuli can impede the transmission of painful stimuli . MelzackRhythmic sensory stimulation (RSS) is defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus low-frequency sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain , 17. ThiAlthough research using RSS has been conducted within an array of conditions, little research has focused on chronic pain in hEDS. In a previous single-case study of a patient with hEDS , we founA total of 15 participants entered the study, and 14 completed the study. The inclusion criteria comprised the following: (1) a clinical diagnosis of hEDS by the clinical staff at Mount Sinai Hospital's Wasser Pain Management Centre and Medical Genetics Department or a completed and signed referral form by health care practitioners indicating diagnosis; (2) joint hypermobility; (3) confirmed joint dislocations; (4) a Beighton score of 5 or more out of 9; (5) ongoing chronic pain of at least 6 months; (6) the ability to read and write English adequately; (7) self-reported satisfactory bilateral hearing; (8) the ability to operate the supplied RSS device, the Sound Oasis VTS1000, and to pick up and return the device at the Wasser Pain Management Centre.The exclusion criteria were as follows: (1) serious concomitant illnesses, such as malignancy and vertebral fracture; (2) active inflammatory conditions, such as spinal infection and ankylosing spondylitis; (3) history of pathological fracture; (4) pregnancy; (5) coccydynia; (6) metabolic bone disease; (7) bleeding or clotting disorder; (8) hypotension; (9) active psychiatric disorders, such as bipolar disorder, schizophrenia, severe/psychotic depression, or anxiety disorder ; (10) the use of pacemakers, implanted defibrillators, or neurostimulators.BPI-SF: the brief pain inventory assesses the severity of pain and the impact of pain on daily functions. Although first made for cancer patients, it is reliable and valid for assessing noncancer-related pain . Scores POMS-SF: the profile of mood states is used to measure psychological distress. A five-point scale ranging from “not al all” to “extremely” is administered, and a number from 0 to 4 is associated with this scale in a direction depending on the type of questions. Greater scores are associated with worse conditions. Reliability and validity for the POMS have been conducted .SF-36: the short form healthy survey measures the quality of health and is commonly used in health economics to calculate cost-effectiveness of a health treatment. The SF-26 consists of eight scaled scores that are weighted sums of a section of questions. Each scale is converted into a 0–100 point value in which a lower score indicates more disability and a higher score indicates less disability. Reliability and validity for the SF-36 have been conducted .CES-D: this is a brief self-report to measure depressive symptoms. The questionnaire consists of 20 questions, scores from 0 to 3, totaling 0–60 points. Higher scores indicate greater depressive symptoms. Reliability and validity for the CES-D have been conducted .PGI-C: PGI-C consists of one item that measures the change in patient health. The range is 0–7 with a score of 1–3 indicating improvement, 4 being no improvement, and 5–7 being worse after the treatment. Reliability and validity for the PGI-C have been conducted .A one-group pre-post treatment design was implemented. There were three assessments. The first assessment served as a baseline before study initiation and utilized four self-reported measures, including the Brief Pain Inventory, Short Form (BPI-SF) ; the ProCan you please tell me about your experience with using the RSS system?Have you started any new treatments to help manage your pain since you began this study 4 weeks ago? Have you changed your medication regime since you began this study 4 weeks ago? If you have changed your medication regime, why did you do so? Did you experience any negative side effects using the RSS stimulation system? Did you notice any positive effects/changes that you feel are a result of using the RSS system? What did you dislike about using the RSS stimulation system, if anything? Would you choose to use the RSS system in the future? On a scale of 0–10 with 0 representing not helpful at all and 10 representing extremely helpful, how helpful do you feel the RSS system was in helping you manage the severity of your pain?On a scale of 0–10 with 0 representing not helpful at all and 10 representing extremely helpful, how helpful do you feel the RSS system was in improving your mood?On a scale of 0–10 with 0 representing not helpful at all and 10 representing extremely helpful, how helpful do you feel the RSS system was in helping you manage daily activity levels?Secondary endpoints included changes in scores from time of treatment termination to the final assessment following the washout period. Qualitative analysis was conducted on the responses from the semistructured interviews to explore patients' experience and perceived effectiveness of the RSS system for managing pain and mood. Open-ended questions from semistructured interviews included the following questions:To analyze and present this qualitative data, all answers were compiled and categorized into common phrases represented by 1-E2 words, counted, and then presented in bar graphs as a percentage of the total number of participant responses for each question of interest.During this 4-week study, patients were given an RSS device (Sound Oasis VTS1000) which they self-administered daily for 30 minutes, five days per week. The patients were instructed to select a time of day to use the RSS device; however, it was recommended that participants use the RSS device in the morning and use it consistently at the same time. The patients were given a diary in order to record their usage and the presence or absence of side effects.Participants were instructed to place the device on a bed or chair, turn the device on, and choose the “Energize therapy session” program that is supplied on this commercially available device. “Energize” comprises of three tracks . The music uses the bass, guitar, piano, and digital keyboard and features mono and binaural high alpha and beta entrainment. A somatosensory vibration generated by an audible low-frequency sound wave can be felt from the shoulders to the low-back, and relaxing but not “ambient” instrumental music can be heard prompting the participant to begin timing their 30-minute session. Patients were instructed to turn the low-frequency sound driven vibration intensity to 15 and the volume level of the music to 1 or 2. However, participants were informed that if discomfort was experienced due to these settings, they were to adjust the vibration and volume level to alleviate the discomfort. Participants were asked to note any deviations to the recommended procedure in the diary.All patients consented to the study after being provided a clear description of the study and their rights of participation, withdrawal, and confidentiality. The study was conducted in accordance with the principles set out in the Declaration of Helsinki  and apprDescriptive statistics including percentages, means, and standard deviations were used to report demographic data such as age, gender, pain location, and pain duration. Data were analyzed by comparing baseline, posttreatment, and washout measurements using repeated measures ANOVA analysis. Interview answers were compiled, and common keywords or phrases were derived from each answer, counted, and then presented as a percentage of total participants. Outcomes were analyzed using SPSS for Windows, version 22, with 5% as the significance threshold.A total of 15 patients with hEDS were recruited for participation, of which 14 completed the intervention and poststudy interviews. The average age was 35.8 years (SD = 13.2 years), ranging from 23 to 59 years. All patients were female and reported the presence of a concomitant condition such as depression, anxiety, or chronic pain conditions. More than half of the patients were either married or in a relationship. The demographic and clinical characteristics have been described in p < 0.05, Posttreatment improvements in both pain interference and depression were seen in 11 of the 15 patients (73%) Figures . During Qualitative analysis of poststudy interviews indicated that 57% of patients reported the device to have a positive effect on their quality of life, with 21% reporting a neutral effect and 21% reporting a negative effect . Open-enp < 0.05). Data analysis on responders indicated a significant improvement in pain interference and depression symptoms but not pain severity from pretreatment to posttreatment, with p < 0.05  to report how many patients experienced a meaningful change after treatment. Following the procedure outlined in a review on MCID, the PGI-C scale was used to determine the MCID (a score of “3” or better) . Of the p < 0.05 . Analysip < 0.05 , whereasp < 0.05 .To study the difference between responders and nonresponders in more detail, an analysis of the prevalence of concurrent medical conditions was conducted and this yielded a potentially important observation . MedicalThe present study investigated the effects of rhythmic sensory stimulation on pain and mood symptoms of hEDS patients. Our findings revealed that 43% of hEDS reported benefit from using RSS in their symptoms. The proportion of hEDS responders to this RSS treatment is similar to the proportion of fibromyalgia responders (40%) in a previous study that used a similar protocol . The meaConsistent with the initial case report, we found that pain interference is significantly improved  in responders without significant changes in pain severity. Furthermore, poststudy interviews reveal that one of the common positive benefits of the device was muscle relaxation. This suggests that the vibrotactile sensation produced by the RSS device could have improved mobility-related pain and functionality, which has been demonstrated in previous studies using low-frequency stimulation –41. MechWe also found significant improvements in depression symptoms in responders after using the intervention. Improvements seen in mood symptoms may be due to improvements seen in pain interference, as this increases the types of activities that patients can engage in and thus improves quality of life. However, the cognitive and affective effects of music also play a major role, increasing dopamine and serotonin levels in the brain and improving mood symptoms more directly , 19. A pAn additional consideration is the evidence for aberrant neural oscillations that have been associated with the sensation of chronic pain , 49, depAuditory and vibrotactile RSS can be an additional tool to reduce hEDS symptoms including pain, mood, sleep, and potentially bowel movements. hEDS patients that report these particular symptoms may be more likely to benefit from 40 Hz of auditory and vibrotactile, while a small percentage of patients may find it discomforting. Further research is necessary to elucidate the mechanisms underpinning the physical and psychological effects of RSS.


Objective: To explore the clinical and imaging characteristics of subacute combined degeneration of the spinal cord (SCD) related to recreational nitrous oxide (N2O) use.Methods: Clinical and imaging data were retrospectively collected from patients with SCD related to recreational N2O use who were diagnosed and treated at Shengjing Hospital of China Medical University from January 2016 to June 2020. The clinical and imaging features of patients with recreational N2O-related SCD were compared with those of patients with N2O-unrelated SCD, who were diagnosed and treated during the same period of time.Results: The study enrolled 50 patients  with N2O-related SCD and 48 patients  with SCD unrelated to N2O use. The most common signs/symptoms of the patients in both groups were limb numbness and weakness and unsteady gait, but the incidence of limb weakness, unsteady gait, disorders of urination and defecation, anorexia, reduced deep sensation in lower limbs, ataxia, and positive Babinski sign were lower in the N2O-related SCD group than those in the N2O-unrelated SCD group (P < 0.05). The functional disability rating score of patients in the N2O-related SCD group  was also significantly lower than the score in the N2O-unrelated SCD group  (P < 0.05). The serum vitamin B12 level was significantly lower in the N2O-unrelated SCD group  than the level in the N2O-related SCD group  (P < 0.05), while both groups had similarly increased levels of homocysteine (P > 0.05). Compared with the N2O-unrelated SCD patients, more patients with N2O-related SCD had abnormal spinal magnetic resonance imaging (MRI) scans (80.0 vs. 64.2%). The patients with N2O-related SCD also had wider spinal lesions on sagittal MRI (5.3 ± 0.8 mm vs. 4.2 ± 1.0 mm), fewer spinal segments with lesions , and a higher incidence of the inverted V sign on axial MRI (72.0 vs. 31.2%) .Conclusion: The recreational use of N2O has become an important cause of SCD in young patients. Compared with the N2O-unrelated SCD patients, the N2O-related SCD patients had less severe clinical presentations, less obvious decrease in serum VB12 levels, and more obvious MRI changes. Although early diagnosis and treatment are key to good outcomes, many young patients who use N2O are reluctant to divulge their exposure history. Thus, it is important for clinicians to be aware of the clinical and imaging features of SCD induced by N2O use to avoid missing patients suspected of its use. In this retrospective study, we aimed to identify the clinical and imaging characteristics of patients with N2O-related SCD. We analyzed and compared the clinical and magnetic resonance imaging (MRI) data of patients with N2O-related SCD with the data of patients who were diagnosed and treated during the same period of time with classical SCD that was unrelated to N2O use at our center.The recreational use of nitrous oxide  history of N2O inhalation without the concomitant use of other addictive agents and narcotics; (2) subacute or acute onset with signs/symptoms of impaired posterior and/or lateral funiculus of the spinal cord after N2O use; (3) decreased serum Vitamin B12 (VB12) level or positive response to VB12 treatment; (4) no other causes of VB12 deficiency  or past history of macrocytic anemia or VB12 deficiency before exposure to N2O; (5) no other types of spinal cord conditions. The inclusion criteria for N2O-unrelated SCD patients were as follows: (1) relevant causes for VB12 deficiency ; (2) subacute or acute onset with the signs/symptoms of impaired posterior and/or lateral funiculus of the spinal cord; (3) decreased serum Vitamin B12 level or positive response to VB12 treatment; (4) no exposure history to N2O; (5) no other spinal cord problems.The inclusion criteria for the patients with NDetailed clinical data were collected, such as demographic data, clinical manifestations, functional disability rating scores (FDRS), laboratory test results, and spinal MRI findings.In the laboratory tests, serum homocysteine was detected by colorimetry and serum VB12 and folic acid were determined by chemiluminescence immunoassay. Blood routine was detected by Sysmex XN9000 automatic hematocyte analyzer. This study was approved by the Ethics Committee of Shengjing Hospital, according to the Helsinki Declaration (2013).We evaluated the clinical signs/symptoms of the 2 groups of the patients based on the FDRS. The specific items that were assessed and the assessment scores are described here. Gait was rated as normal (0), unable to maintain the Romberg position (1), impaired, but able to walk unsupported (2), substantial support required for ambulation (3), or wheelchair- or bed-bound (4). Sensory disturbance  was rated as absent (0), impairment only in toes and fingers (1), impairment in ankles and wrists (2), or impairment in upper arms and legs (3). Mental function was rated as normal (0), intellectual or behavioral impairment requiring no social support (1), partial dependence for activities of daily living (2), or complete dependence for all activities of daily living (3). Neuropathy (assessment of reflexes) was rated as absent (0), loss or reduction of deep tendon reflexes of the ankle (1), loss or reduction of deep tendon reflexes of the patella (2), or loss or reduction of deep tendon reflexes of the arms (3). Pyramidal tract functioning was rated as normal (0), positive Babinski sign (1), spastic paraparesis (2), or spastic tetraparesis (3). The minimum overall score was 0 and the maximum was 16. Higher scores represented increased severity of neurological impairment .Spinal MRI was performed by a Trio 3.0 T MRI scanner . The scanning sequences included sagittal and axial T1 weighted imaging (T1WI), T2WI, and fluid attenuated inversion recovery (FLAIR) sequences. The extent of spinal lesions was measured in the T2WI sagittal images , and was assessed according to the number of affected spinal segments, lesion widths  and analyzed by the Mann-Whitney U-test. P < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS 24.0 .Quantitative data were presented as means and standard deviation (SD) (x ± s). Intergroup comparisons were performed by the 2O-related SCD group and the N2O-unrelated SCD group, respectively . At admission, the most common clinical manifestations in both groups were limb numbness and weakness, and unsteady gait. Other neurologic manifestations included urination and defecation disorders, impaired memory, abnormal limb movements, anorexia, and abnormal skin pigmentation. The incidence rates of limb weakness, unsteady gait, urination and defecation disorders and anorexia in the N2O-related SCD group were significantly lower than those in the N2O-unrelated SCD group. Patients in the N2O-related SCD group also showed fewer positive signs such as impaired deep sensation and a positive Babinski sign on neurological examination than patients in N2O-unrelated SCD group (P < 0.05). Accordingly, the difference between the FDRS of the 2 groups was significant , indicating that on admission, the patients with N2O-related SCD had milder disease than the patients with N2O-unrelated SCD.The study enrolled 50  and 48  patients in the Nectively . The dif2O-related SCD had a higher VB12 level than the patients with N2O-unrelated SCD . A lower proportion of patients with N2O-related SCD than patients with N2O-unrelated SCD had VB12 deficiency  and megaloblastic anemia .Approximately 80% of the patients in each group had an elevated homocysteine level, which was the most common laboratory abnormality. The patients with N2O-related SCD patients compared with the N2O-unrelated SCD patients had a higher positivity rate on spinal magnetic resonance imaging (MRI) (80.0 vs. 64.2%), wider spinal lesions on sagittal MRI (5.3 ± 0.8 mm vs. 4.2 ± 1.0 mm), fewer spinal segments with lesions , and higher rate of the inverted V sign on axial MRI (72.0 vs. 31.2%)  . The most common type of peripheral neuropathy was mixed axonal and demyelinating neuropathy.N < 0.05) . The rat2O use who were admitted to our hospital over the last 5 years was comparable to the number of patients with classical SCD, which indicates that recreational N2O use has become one of the main causes of SCD in China, especially in young patients. Although the definitive pathophysiological mechanisms involved in the development of SCD induced by N2O use are not entirely clear, the main mechanism is believed to be the irreversible oxidation of the cobalt atom of VB12 by N2O, which interferes with the methylation of the myelin protein, finally leading to myelinoclasis  of the patients in this group had hyperhomocysteinemia. Therefore, the serum VB12 level is of limited value for the diagnosis of SCD induced by N2O inhalation, while an increase in homocysteine due to inactivated VB12 may be a more effective index. The percentage of N2O-unrelated SCD patients with megaloblastic anemia was significantly higher than the percentage of N2O-related SCD patients. This finding might be attributed to the longer duration of VB12 deficiency in the N2O-unrelated SCD patients, which exerted more severe effects on the hematological systems of these patients.Many studies have shown that patients with SCD related to Nteinemia , 16. Hyp2O-unrelated SCD patients, the spinal lesions of N2O-related SCD patients shared the following characteristics: (1) lesions were usually localized to the cervical spinal cord and rarely extended to the thoracic spinal cord; (2) lesions were wider, which is a manifestation of swelling; and (3) the inverted V sign was more common. These findings might be related to the relatively acute process of spinal cord demyelination, which was due to the inhalation of a large amount of N2O over a short time and which was accompanied by an inflammation stage manifested by swelling of the spinal cord. Spinal demyelination induced by other factors such as a vegetarian diet is a chronic process with limited inflammatory changes. Thus, spinal MRI positivity rate of N2O-related SCD patients was significantly higher than the rate of N2O-unrelated SCD patients. Additionally, the age difference between the 2 patient groups also contributed to the difference between the MRI positivity rate. A study by Lan et al. showed that while only half of adult N2O-related SCD patients had abnormal MRI findings, almost all the adolescent N2O-related SCD patients had abnormal MRI changes . DZ: writing (review and editing). All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Spinal cord stimulation (SCS) has been used over decades for pain management, but migration of percutaneous leads has been the most common complication. Better surgical techniques and newer SCS technologies likely reduced the incidence of lead migration requiring surgical revision, although data are sparse. This study aimed to retrospectively evaluate the incidence of clinically significant percutaneous lead migration in patients permanently implanted with a 10 kHz SCS system.  Consecutive patients with chronic trunk and/or limb pain, permanently implanted between January 2016 and June 2019, were included in the analysis. Data were collected from the hospital's electronic medical records and the manufacturer's database. Clinically significant lead migration, defined as diminished pain relief followed by surgery to correct lead location, was assessed at the 6-month follow-up.  At the 6-month follow-up, there were no cases of clinically significant lead migration, average pain relief was 65.2%, 82% of patients had response (≥50% pain relief), improvement of function was noted in 72% of patients, and decrease of medication was observed in 42% of patients. Therapy efficacy was sustained in patients with >12 months follow-up; the average pain relief was 58.5%, and the response rate was 82%.  The surgical techniques in use today are designed to minimise the risk of percutaneous lead migration and may have reduced its incidence. In addition, new SCS systems may give greater opportunity to mitigate cases of minor lead movement using alternative stimulation programs. It is well-established that pain is the leading cause of lost workdays globally . PatientIn 1967, Shealy and colleagues reported the first case of spinal cord stimulation (SCS), providing successful pain relief in a patient with metastatic cancer . AccordiThe efficacy of SCS is well-established, as is its associated complications: risk of infection, surgery-related pain, and device malfunction , 7. HoweAs the issue of lead migration unfolded, surgical (paddle) leads emerged as possibly providing reduced migration rates compared with percutaneously placed leads –12. HoweFurthermore, novel waveforms have been developed over the last decade. One such waveform is 10 kHz SCS, which delivers low-amplitude (1.0–5.0 mA) electrical pulses to the spinal cord at 10 kHz frequency and 30 µs pulse width via leads placed in the epidural space of the spinal canal. Unlike during traditional (low-frequency) SCS, whose success is dependent on paraesthesia masking pain in the affected area , patientHowever, evidence of reduced clinically significant lead migration rates with modern implant procedures and novel SCS hardware is sparse . TherefoInstitutional review board (IRB) approval was obtained for the study from Western Institute Review Board. Informed consent was not required and was waived by the IRB due to the retrospective nature of the study and the use of anonymous data.TM, Nevro Corp., Redwood City, CA, USA) between January 2016 and June 2019 at the University of Wisconsin Hospital, USA. A single surgeon carried out all procedures. All patients who had failed more conservative treatments were considered appropriate candidates for 10 kHz SCS as part of their standard of care and had undergone a successful therapy trial prior to permanent implantation. Data were gathered from the hospital's electronic medical records (EMRs) and the manufacturer's anonymised commercial database (NevroCloudTM).This study is a retrospective case series of all patients with chronic trunk and/or limb pain who underwent permanent implantation of percutaneous leads and a 10 kHz SCS device , patients proceeded to permanent implantation.Under general anaesthesia, a small incision of 1.5–2.0 cm was made approximately 1½–2 vertebral body levels below the intended site of needle entry in the interlaminar space. The incision was dissected down to the level of the lumbodorsal fascia . The neeTwo 8-contact stimulation leads were introduced through the Touhy needles under fluoroscopic guidance into the midline dorsal epidural space and navigated to the desired vertebral level, usually spanning T8–T12, and placed in a staggered fashion. The Tuohy needles were removed, and the leads were anchored to the lumbodorsal fascia Figures  using neTM). The primary measure was the incidence of clinically significant lead migration at 6 ± 1-month follow-up physician assessment and the occurrence of any surgical procedure to revise lead location after permanent implantation. Baseline data collected included demographics, the reason for implantation, and preoperative pain intensity score measured using an 11-point numerical rating scale . Patient-reported pain relief obtained from the therapy (0% = no pain relief to 100% = complete pain relief) was recorded at the end of the trial and at the 6-month physician follow-up. Additional information in patients with >12 months follow-up assessment was collected from the manufacturer's database, which included patient-reported pain relief, improvement in function (yes or no), and medication intake .Data were gathered from the hospital's EMRs and the manufacturer's database  was evaluated from the patient-reported percentage pain relief documented during the trial, at the 6-month follow-up visit, and at the last visit before data analysis.TM.Continuous variables such as the pain intensity score and patient-reported percentage pain relief are reported as mean ± standard deviation (SD). Patients with ≥50% pain relief were considered responders. All data were analysed as observed. Data were collected and analysed using ExcelBetween January 2016 and June 2019, 101 chronic trunk and/or limb patients underwent permanent implantation of percutaneous leads and a 10 kHz SCS device. The demographics and baseline characteristics of the implanted participants are detailed in N = 51). Median follow-up in the patients was 24.4 months, and within the subset, the last follow-up was >24 months in 24 patients  of the cohort , and 41.Spinal cord stimulation has been used since 1967 to treat intractable pain, and since that time, it has become an established tool for the treatment of various pain syndromes –35. The As SCS has emerged as front line therapy for patients with chronic neuropathic pain syndromes, one of its greatest issues has been lead migration. Original studies quoted lead migration rates as high as 23% . This teIn our retrospective review of all patients in our centre implanted with percutaneous leads and a 10 kHz SCS device by a single physician over two and a half years, there were no cases of lead migration requiring corrective surgery. Importantly, the responder rate found in our study was similar to rates previously reported for 10 kHz SCS , and theThe absence of clinically relevant lead migration among our cohort is important for several reasons. First, it provides additional evidence that the rate of clinically significant percutaneous lead migration has decreased with the development of surgical techniques. It also suggests that device reprogramming can mitigate minor cases of lead movement in 10 kHz SCS systems, potentially reducing the necessity of further interventions to verify electrode position and relocate leads. The absence of paraesthesia in 10 kHz SCS may be beneficial in cases of lead migration that might otherwise produce uncomfortable paraesthesia during postural changes, which is a common occurrence during traditional low-frequency SCS , 47. FurThe nil rate of clinically significant lead migration in our cohort is also less than that of the recently published rates for SCS (2%–9%) –17. Overth rib, ipsilateral to the incision site, ensured that the IPG was in the same anatomical plane as the anchor and entry point regardless of body position, thus reducing lead flexion and mobility [The consistent use of surgical techniques designed to reduce the risk of lead migration in our centre may also account for our results. Dissecting all the way through to the lumbodorsal fascia and securing the lead with a modern anchor at this deep fascia level rather than to subcutaneous tissue or muscle may have helped the leads stay in situ , 55, 56.mobility . Bench tmobility . Hence, mobility . In addimobility , 60 and The main limitation of our study is its retrospective design, which does not take into account all confounders and prevented the collection of X-rays from our cohort that would confirm the presence or absence of lead migration at the follow-up visit after 6-month assessment. As such, our evaluation of clinically significant lead migration was indirect, which limits the interpretation of our results and comparisons with other published literature. Another limitation of our study is the use of patient-reported percentage pain relief instead of a visual analogue scale- (VAS-) based calculation of pain relief, which is a widely used measure. However, VAS scores are not routinely collected during the clinic follow-up, and these data were not retrospectively available for our patients. Finally, all included patients were treated by the same physician; the outcomes are dependent, to some degree, on the expertise and experience of the physician.The surgical techniques in use today may have reduced the incidence of clinically significant percutaneous lead migration. In 10 kHz SCS patients, minor cases of lead movement presenting as diminished pain relief may be mitigated with alternative stimulation programs. Since percutaneous lead implantation is less invasive compared with paddle leads, patient recovery can be faster, and the approach could be preferred for permanent implants. Current findings encourage additional studies on cost savings and healthcare utilisation with percutaneous leads versus paddle leads.