EFTA00305864.pdf

I Study Protocol Clinical Trial Medicine OPEN The effectiveness and safety of nonsurgical integrative interventions for symptomatic lumbar spinal spondylolisthesis A randomized controlled multinational, multicenter trial protocol Kiok Kim, KMD, PhDs, Yousuk Youn, KMD, PhD', Sang Ho Lee, KMD, PhDa, Jung Chul Choi, MD', Jae Eun Jung, MD°, Jaehong Km, MBAa, Wenchun Qu, MD, PhD", Jason Eldrige, MDd, Tae-Hun Kim, KMD, PhDa Abstract Background: Surgery is generally accepted as the main therapeutic option for symptomatic Unbar spondylolisthesis. However, new nonsurgical therapeutic options need to be explored for this population. Objectives: The objective of this study is to assess the effectiveness and safety of a 5-week Mokhuri treatment program compared with conventional nonsurgical treatments for symptomatic lumbar spondylobsthesis. Methods: This is a study protocol for a multinational, multicenter clinical randomized controlled trial comparing the effectiveness and safety of 5 weeks of nonsurgical integrative treatments (a Mokhuri treatment program consisting of Chuna, acupuncture, and patient education) with nonsurgical conventional treatments (drugs for pain relief, epidural steroid injections, and physical therapy). Clinical outcomes including visual analogue scale (VAS) scores ranging from 0 to 100 for low back pain and leg pain, EQ-5D scores. Oswestry disabikty index (ODI) scores. Roland-Morris Disability Questionnaire (RMDO) scores. Zurich Claudication Questionnaire RCO) scores. walking duration and distance without leg pain, and a 5-minute treadmill test, and the ratio between the actual duration of participation and the originally scheduled duration in each group, the presence of any additional spondylolisthesis treatments. the types of concomitant treatments during the follow-up period, and adverse events (AEs) will be assessed at 7 weeks, 18 weeks. 30 weeks. 54 weeks. and 102 weeks after the end of the treatments. Conclusion and discussion: The results of this study will provide clinical evidence on nonsurgical integrative interventions for patients with symptomatic lumbar spondylolisthesis. Clinical trial registry: clinicaltrials.gov (NCT03107468) Abbreviations: AE = adverse event, ODI = Osweshy disability index, RMDQ = Roland-Morris Disability Questionnaire, SD = standard deviation. SOP = standard operating procedure, VAS = visual analogue grate., ZOO = Zurich Claudication Questionnaire. Keywords: acupuncture, Chuna, clinical trial, conventional therapy, epidural steroid injection, non-surgical treatment, protocol, Spondylolisthesis Fundng/sup . 771s reseafcti was supported by a grant of the Koran Heath 1. Introduction Technology= Praed through the Korea Heath industry Degdoprent &Istituto Degenerative lumbar spondylolisthesis is a chronic spinal (KHO). funded by the Ministry of Heath & Welfare. Ropt.tk of Korea (grant number H(16C1626). condition that causes instability of the segmental spinal bones The mews have no Luillias of interest to dscbse. due to degenerative changes in the spinal joints. According to a cross-sectional study released in 2009, the prevalence rate of •Department of Spine Center, Mokhun Neck and Beck Hospital, Seoul, bHong& Neurosurgery Hospitd, Seongnsm. Repubbc of Korea. `Department of Physical degenerative lumbar spondylolisdiesis was estimated to be as Modoine and Rehabatation. ° Department of Anesthesdogy. airision of Pan high as 13.6% in an adult community-based population, which Afflit,ine. Mayo ant. Rochester. MN. USA. "Kaman Meotne Clara, Thai suggests that a considerable proportion of general population Center. Korean Modern's Hosatd. Kyung Hee Unryerstty. Seoul. Repubk of have this conditionil l Most people with lumbar spondylolisthesis Korea. do not have any symptoms, and only approximately 10% of this 'Correspondence: Tae-Hun Kim. Korean Medicine Ctital Trial Center, Korean population have clinical symptoms that require treatment. Medkine Hosplat Kywg Hee University. Scout Repubk of Korea (e-mail: tsehunaimfekhu.ac.kr). However, once symptoms occur, more than 50% of the patients Copyright an 2018 the Author(s). Pubrehed by Wolters KMve• Health. Inc. complain of considerable pain and dysfunction and in severe This is an open access article distributed trader the Creabire Commons cases, cauda equina syndrome?' AtffibUtiOn License 4.0 (CCSY), which permits unresbicted use. dstnbutian, and Nonsurgical conservative treatments are recommended for reproduction in any medum. provided the original worn is properly cited. patients with symptomatic spondylolisthesis as a first-line Medoine (2018)97:19(00667) therapy, but surgical treatments are considered in cases of failure %wired: 7? Apr' 2018/Accepted: 16 Apd 2018 of conservative treatments?' Surgical interventions are per- tittp://dx.dolarg/10.1097/MD.0000000000010667 formed to achieve decompression of nervous tissue, to relieve 1 EFTA00305864 Kim at S. Medicine (2018) 97:19 Medicine joint instability, and to lead to a comparatively good prognosis141 alert campaigns, and public advertisement. Any included patients However, considerable complication rates related to surgical will undergo 5 weeks of treatments in the outpatient unit and up interventions and considerable reoperation rates after spinal to 96 weeks of follow-up evaluations. surgery have been reported.l5.61 In addition, surgical treatment should be avoided if the patient has severe chronic conditions, 2.3. Inclusion and exclusion criteria multilevel stenosis, osteoporosis, or poor complianceil l Consid- ering this, nonsurgical interventions are recognized as an Individuals who meet all the following criteria will be included as important option for the management of lumbar spinal appropriate participants in the clinical trial: spondylolisthesis. (1) Those aged from 19 to 78 years; According to the results of our previous observational study (2) Those with a diagnosis of degenerative lumbar spinal involving Mokhuri nonsurgical integrative treatments performed spondylolisthesis or who have low back pain, lower limb on patients diagnosed with Meyerding grade 2 lumbar spinal radiating pain, or leg discomfort when standing or walking spondylolisthesis, considerable clinical improvement was ob- with a severity of at least 5 on a visual analogue scale (VAS) served after nonsurgical integrative treatments; the average of 0 to 100 for each symptom; walking distance without pain increased from 55 to 165m, while (3) Those suffering from neurologic claudication or radicular the intensity of pain experienced when walking was reduced by pain for at least 1 year; 80% compared with the baseline assesstnent.ri In another (4) Those with neurogenic claudication within 5 minutes of previous retrospective audit study, on a numeric rating scale from walking on a treadmill at a speed of 1.5 miles per hour; 0 to 10, 44 spondylolisthesis patients reported a reduction in (5) Those who have not received an epidural injection within numeric rating scale scores from 7.1 to 3.1, and walking distance the past month; without pain increased from 193 to 568 m after treattnent.isl (6) Those who have not undergone lumbar surgery; These observational studies provide clues for the potential benefit (7) Those who have confirmed spondylolisthesis on lumbar of nonsurgical integrative treatments and suggest that these spine AP, lateral, nd both oblique views; treatments might be effective for pain relief and functional (8) Those who weigh 250 lbs (113.398 kg) or less; restoration in patients with symptomatic lumbar spinal spondy- (9) Those whose height is 2.1m (6.890 ft) or shorter; and lolisthesis. However, observation studies cannot provide clinical (10) Those who agreeing to participate in this clinical trial after evidence, so these new therapeutic options should be evaluated receiving a thorough explanation of the purposes and through rigorous, high-powered clinical trials. characteristics of the trial and who are willing to sign the The objective of this study is to assess the effectiveness and the written informed consent form. safety of a 5-week Mokhuri treatment program compared with conventional nonsurgical treatments for symptomatic lumbar Participants who have any of following conditions will be spondylolisthesis. excluded: (1) Those with a past or current history of diseases that cause 2. Methods ambulatory functional disability; (2) Those with knee joint and hip joint disorders that severely 2.1. Study design limit walking (i.e., moderate or severe osteoarthritis of the This is a study protocol for a multinational, multicenter clinical knee or hip joints); randomized controlled trial that is designed to evaluate the (3) Those who have been previously diagnosed with peripheral effectiveness and safety of nonsurgical integrative treatment in blood vessel diseases or vascular diseases, those who show patients with symptomatic lumbar spinal spondylolisthesis who an ankle-brachial index below 0.9 or those who have been continue to have symptoms after a sufficient duration of diagnosed with peripheral arterial disease by Doppler conservative treatment. Patients with symptomatic lumbar spinal ultrasonography of lower limbs, if necessary; spondylolisthesis will be randomly allocated to one of the (4) Those with severe diseases (cardiac disorders or renal interventions: a 5-week Mokhuri treatment program (Chuna, insufficiency) to such a degree that an ambulatory acupuncture, and patient education) or nonsurgical conventional evaluation cannot be performed; standard treatment (drugs for pain relief, epidural steroid (5) Those with other specific spinal diseases (ankylosing injections, and physical therapy). The trial participants who spondylitis, spinal osteomyelitis, metabolic diseases, severe agree to participate in the clinical trial after written informed osteoporosis, etc.); consent will undergo the required examinations and tests (6) Those with severe neurological defects including foot drop according to the plan for the clinical trial. After 5 weeks of or cauda equine syndrome; treatment, the clinical outcomes of both groups will be evaluated (7) Those with spinal instability confirmed by lumbar spine X- during follow-up, which will take place at 7, 18, 30, 54, and ray flexion and extension views, where spinal instability will 102 weeks after the end of the treatments. be defined as observing one or more of the following: 4.5 mm sagittal plane translation, 20 degrees of sagittal plane rotation at 14.5, or 25 degrees of sagittal plane rotation at 2.2. Study setting 15.51; The trial will be conducted at the Mayo Clinic in the United States (8) Those with malignancies; and the Mokhuri Oriental Medicine Hospital in Korea. (9) Those with past or current psychiatric conditions, such as Participants will be recruited at the division of Pain Medicine major depressive disorder, anxiety disorders, panic disor- at the Mayo Clinic in Minnesota, US and at the Mokhuri Oriental ders, or episodes of mania, delusion, and schizophrenia; Medicine Hospital in Seoul, South Korea. Participants will he (10) Those using narcotic analgesics including external dosage recruited through flyer advertisement within the hospital, e-mail forms or patches; 2 EFTA00305865 Km et al. Medicine (2018) 97:19 (11) Those women who are pregnant, lactating, or planning to trial, such as medicines the participants have been taking for 4 become pregnant; weeks prior to participating, will be allowed. In addition, in both (12) those who appear to be likely to encounter difficulties in the Mokhuri treatment group and the conventional treatment adhering to this protocol; and group, participants will be allowed to continue using the same (13) Those subjects whom the clinical investigators judge to be types of pain medications at the same doses and frequencies that inappropriate. they have been taking them before participating in this study. 2.4. Interventions 2.8. Research personnel training All the participants in each group will undergo 5 weeks of One month of training for practitioners participating in the treatments. In the Mokhuri treatment group, participants will treatments will be planned at 5 days a week for 8 hours a day for undergo 10 sessions of acupuncture therapy, Chuna therapy, and 160 hours in total. The training program will include the theory consultation with physicians. In the control group, participants of the treatments, the practice of Chuna, and patient education. A will be administered drugs every day, have 1 or 2 epidural steroid contmon standard operating procedure (SOP) for treatments will injections, and participate in 10 sessions of physical therapy for be provided, and practitioners will follow this SOP. At the end of 5 weeks. every week, trainees will be evaluated for competence. 2.5. Interventions in the Mokhuri treatment group 2.9. Sequence generation and allocation concealment All the treatments in this group will be conducted by Korean Two sets of random sequences will be generated for the 2 research Medical doctors in Korea and an acupuncture practitioner in the institutions using the statistical program SAS (SAS institute Inc, US, both with at least 5 years of clinical practice experience. All Cary, NC) by an independent statistician. The block size will not the treatments in this group will be offered twice a week for be known to the investigators so as not to predict the random 5 weeks (a total of 10 sessions). For acupuncture treatment, sequence. All participants will have equal chances of being points including both L14, ST36, LV3, BL22, 8123, 11124, and selected for either the Mokhuri treatment group or the control BL25 will be selected for stimulation. Disposable sterile group. Sealed opaque envelopes with the assigned results for acupuncture needles (0.25 x 40 mm, Dong-bang Acupuncture, each participant will be used for allocation concealment. The Seong-Nam, Korea) will be used. Chuna treatment, which is a investigators at each of the study institutions will open a random kind of manual therapy consisting of relaxation and mobilization assignment envelope and assign the participant to an intervention of the lumbar joint sand back muscles using an Ergo Style TM group in the consecutive order of the patients' serial numbers. FX-5820 Table (Chattanooga Group, TN), will be conducted during every treatment visit. Participants will lie on the table in 2.10. Outcomes the prone position, and a practitioner will relax the back muscles of the patient, while the table causes the patient's spine to flex and The validated English version for the Mayo Clinic and the Korean extend automatically?) Along with the acupuncture and Chuna version for the Mokhuri hospital will be used for all the outcome treatment, patient consultation regarding advice for everyday life assessments. Outcome assessors will be blinded to the allocation activities, walking, and particular movements and exercises will results. be offered to participants during every visit. The primary outcome will be VAS scores from 0 to'100 for low back pain. The degree of pain will be evaluated on a 100 mm straight line, where the left edge of the straight line will indicate 2.6. Interventions in the control group "0: no symptoms," and the right edge will indicate "100: the Participants in the control group will undergo 5 weeks of most severe pain." The participant will indicate the average level nonsurgical conventional standard treatments including drug of lumbar pain experienced for the past week. therapy, epidural injections, and physical therapy. Through The secondary outcomes will include VAS scores from 0 to'100 consultation with neurosurgeons or anesthesiologists or rehabili- for leg pain, EQ-5D scores, Oswestry disability index (OD1) tation medicine specialists, drugs including muscle relaxants, scores, Roland—Morris Disability Questionnaire (RMDQ) NSA!Ds, gabapentin, pregabalin or tricyclic antidepressants will scores, Zurich Claudication Questionnaire (ZCQ) scores, be prescribed based on each patient's condition. Epidural steroid walking duration and distance without leg pain, a 5-minute injections will be performed once or twice during the 5-week treadmill test, the ratio between the actual duration of participation period. Physicians will assess the participants' pain participation and the originally scheduled duration in each condition and decide whether they might need an epidural steroid group, the presence of any additional spondylolisthesis treat- injection at each visit. Physicians will re-evaluate the pain severity ments, the types of concomitant treatments during the follow-up of the participant and perform epidural injections after a 2-week period, and adverse events (AEs). interval if necessary. Epidural injections will be performed at the For assessing leg pain, a VAS score from 0 to 100 for leg affected spinal level. Physiotherapists will conduct physical pain will be assessed. The participant will indicate the average therapies, including heating pad application for'10 to 20 minutes level of leg pain experienced for the past week. The EQ-5D is and transcutaneous electrical nerve stimulation for 5 to 10 a common assessment tool for measuring health-related minutes, twice a week during the 5 weeks of participation. quality of life. It contains 5 dimensions including mobility, self-care, usual activities, pain (discomfort), and anxiety (depression). In this study, we will use the EQ-5D-3L, which 2.7. Allowed cotreatments has 3 levels of severity for each dimension.ltgttl The ODI According to the investigators' decisions, medications that do not consists of 10 topics concerning pain, lifting, ability of self- appear to influence the interpretation of the results of this clinical care, ability to walk, sit, stand and travel, sexual function, 3 EFTA00305866 Kim at at. Medicine (2018) 97:19 FAedleine social life, and sleep quality and is intended to assess disability After that, participants will undergo 10 treatments over 5 and quality of life related to low back pain. ODI scores range weeks. After treatment, evaluations will be performed from 0 (no disability) to 100 (maximum disability possi- immediately (7 weeks) and at 18 weeks, 30 weeks, 54 weeks ble)P2•13) The RMDQ is a tool that is widely used for (1-year follow-up), and 102 weeks (2-year follow-up). AEs evaluating the functional conditions of patients with low back will be assessed at each visit (Table I). pain. It contains 24 statements regarding the patient's perceptions about pain and disability, such as physical 2.12. Sample size activity, sleep, psychosocial, and pain frequency. RMDQ scores range from 0 (no disability) to 24 (maximal disability To calculate the sample size, a retrospective study performed on possible)! t4•tsi The ZCQ is an instrument for assessing pain 44 patients with lumbar spinal spondylolisthesisisi and the and symptoms related to spinal stenosis. It consists of 3 previous clinical trial data that assessed physical therapy for domains with 18 questions assessing the symptom severity hospitalized patients in a similar study setting118t were used. To over the last month, physical functioning over the last month determine a meaningful difference between groups, a minimal on a specific day, and the patient's satisfaction with current clinically important difference of 2.5 points on the numeric rating treatment. The results are recorded as a percentage of the scale of 0 to 10 was used.R9I The standard deviation (SD) was possible maximum score, and higher scores represent worse 4.65 from the abovementioned previous studies. For the sample conditions.I"I The walking duration and distance without leg size calculation, the significance level (a) was 0.05, and the power pain and a treadmill test will be used to assess the physical (1—(3) was 0.80. The following formula was used for the function of the patients. Patients will be asked to walk a calculation. Assuming a drop-out rate of 10%, 61 participants distance of 25 m on a round track at their preferred speed, and will be needed in each study group, yielding a total of 122 the distance will be measured when they are no longer able to participants needed for this study. walk due to pain in the lower limb or lumbar region. For the treadmill test, the participants will walk on the level treadmill 2(42 + 24 202 n— at a speed of 1.5 miles per hour, and the time until they start Itr)2 to feel pain in their legs will be measured.' "I The presence of any additional treatments for spondylolisthesis and the types In terms of the total 122 participants in the study, 108 of treatments will be assessed during the follow-up period. participants will be recruited at the Mokhuri Oriental Medicine Because the treatments in each of the groups will end, patients Hospital and 14 participants at the Mayo Clinic. will be allowed to use additional treatments for spondylolis- thesis if they wish to. During this period, participants will be 2.13. Statistical analysis asked whether they used other additional treatments for symptoms related to spinal spondylolisthesis and what types Statistical analysis will be performed based on an intention-to- of treatments they used. The ratio between the actual duration treat analysis for the assessment of effectiveness outcomes and of participation and the originally scheduled duration in each a per-protocol analysis for the assessment of safety. The group will be assessed as well. Participants whose VAS scores missing values will be substituted with the most recently from 0 to 100 for back pain and leg pain decrease below 1 at observed value (the last observation carried forward method). every weekly evaluation will stop the treatment immediately, For the demographic information, continuous data will be according to the early termination rule of this study. The presented as the mean and SD, and categorical data will be number of patients who stop the scheduled treatments early reported with a frequency table. The 2-sample t test (or and the number of those who finish all the scheduled Wilcoxon rank-sum test) will be used for the analysis of treatments will be assessed in each group, and the differences continuous variables after evaluating the data distribution. For in the ratio between groups will be assessed. AEs will be categorical data, the chi-square test (or Fisher exact test) will be assessed during each visit. Participants will be asked to report used. Outcome variables including VAS scores for lumbar pain AEs voluntarily, and researchers will observe participants' and leg pain, EQ-5D scores, ODI scores, RMDQ scores, ZCQ conditions on a regular basis. For each reported AE, the scores, walking duration and distance without leg pain, and the symptoms, signs, starting date, duration, severity, and causal treadmill test will be summarized with means and SDs. For relationship will be assessed by researchers. statistical analysis of continuous outcomes, changes in the scores before and after treatments will be regarded as dependent variables, with the baseline scores and research 2.11. Participant time schedule institutions as covariates and the groups as fixed factors, to At the screening visit, participants will be given detailed perform the analysis of covariance. To verify the trends for explanations of the objectives and contents of this clinical trial each visit in the 2 groups, repeated measures analysis of and will receive the written agreement form. During this visit, variance will be performed. For categorical outcome data, the a 5-minute treadmill test, lumbar physical and radiological chi-square test (or Fisher exact test) will be used. examinations, ankle-brachial index assessment (or Doppler ultrasonography of lower limbs if necessary), bone mineral 2.14. Ethics densitometer assessment, and inclusion criteria assessment will be conducted. If the participant can be enrolled in the Approval from each institutional review board has been obtained study, random assignment of the participant will take place at for the protocols before the start of this study (institutional review the following visit. Before the treatments begin, the VAS board application number: MI-DOH-16031 at the Mokhuri scores for low back pain and for leg pain, EQ-5D scores, ODI hospital and 15.008457 at the Mayo Clinic). Prior to the clinical scores, RMDQ scores, ZCQ scores, walking duration and trial, the participants will provide written informed consent for distance free of leg pain, and a treadmill test will be assessed. participation in the study. 4 EFTA00305867 Km et al. Medicine (2016) 97:19 Table 1 Participant schedule. Clinical trial phase Screening Treatment and observation Evaluation after completion Week. 1 2 3 4 5 6 7 18 30 50 102 Visit 0 1-2 3-0 5-6 7-8 9-10 11 12 13 14 15 Informal cement Demographic and sodobgcal data Medical Way OOOOO ••••• lumbar phyacal examination lumbar spire lARI and X-ray (flexion and anemia) ABI assessment. Doppler Lltrascnography of the lover limbs Chest PA. 8MD Treadmill test A A A A A Assessment for inclusion aid occlusion criteda Meastrement d Kral signs Meastrement c4 treatment excematiorstrarklon assignment A China. acupuncture Swam and patient consultation 8 B B B B Admnistrabon of ccreentional medcaterts 8 B B B B Physical therapy 8 B B B B Epidural Injections C C. VAS fa kW back pain and leg pan • A A A A A E0-50 A A A A A oswestry disability index A A A A A CIMDO A A ZCO A A Waking duration and distance free of leg pain A A A A A Clinical laboratory testing • • Evaluation of are additional treatments n relation to sporityldisthesis upon beatment completion • • • • Adverse events Changes In combined modcattons and therapy Both br tlu ramrod, pup and tbecortrot group; k the lest 'Asa heath vie*. & trace aweek. tor a total& 10 sesso-s al ointment C. on.va week. A8l=arlde.brachaiindex.81,1D=tcnemrira isannometa MRI=nerinc rescrence imagig. RAIDO=Ftdand—Morris Disahilty Otesticrnare. V/S=Usual analogue wale. 2C0=2urch Clulcation 0ueslxrxwire. One addixcial in,ccbon d the plyiecian decides to pertain an injecan again hand cri the patients condor,. 3. Discussion Hopefully, this study will provide clinical evidence on nonsurgical This is a multinational, multicenter study protocol for a clinical integrative interventions for symptomatic spondylolisthesis. trial assessing the effectiveness and safety of nonsurgical integrative interventions for symptomatic lumbar spondylolis- Acknowledgment thesis. Conservative interventions are regarded as effective in The authors thank a grant of the Korea Health Technology most lumbar spinal spondylolisthesis patients, but there are no Project through the Korea Health Industry Development Institute appropriate options other than spinal surgery for patients who (KHIDI), funded by the Ministry of Health Sc Welfare, Republic have continuing symptoms after conservative treatment.1201 As of Korea (grant number: H116C162.5). surgery is not always promising for all patients, new nonsurgical therapeutic options need to be explored for this population. Author contributions This multinational study will ensure generalizability of the study results. This is the most important strong point of this Conceptualization: Kiok Kim, Yousuk Youn, Sang Ho Lee, Jung study. Generalizability is an important issue when implementing Chul Choi, Jae Eun Jung, Jaehong Kim, Wenchun Qu, Jason the results of studies into clinical practice. An randomized Eldrige, Tae-Hun Kim. controlled trial, which can reduce the risk of bias in study Data curation: Kiok Kim. participant selection, may not be able to ensure external validity if Funding acquisition: Kiok Kim, Jaehong Kim. the study population is limited to homogeneous group under Investigation: Kiok Kim, Sang Ho Lee, Jaehong Kim, Tae-Hun strict eligibility criteria.121IFrom this perspective, a multinational, Kim. multicenter clinical trial has benefits of ensuring generalizability Methodology: Kiok Kim, Yousuk Youn,Jung Chul Choi,Jae Eun because patients with diverse regional and ethnic characteristics Jung, Jaehong Kim, Wenchun Qu, Jason Eldrige, Tae-Hun are recruited. Kim. One important limitation of this study is its lack of internal Project administration: Kiok Kim. validity. Researchers with different levels of clinical experience Writing - original draft: Tae-Hun Kim. and educational backgrounds will participate in this study, so Writing - review & editing: Tae-Hun Kim. internal validity between the 2 research institutions may be a potential problem. To protect against potential bias from this References aspect, we generated a common SOP for treatments and Kalithinan L, Kim DH, Li L, et al. Spondylolysis and spondylolisthesis: conducted 1 month of an integrated education program for prevalence and association with low back pain in the adult community- researcher proficiency. based population. Spine (Phila Pa 1976) 2009;34:199. 5 EFTA00305868 Kim et S. Medicine (2018) 97:19 MedICIne 121 Matz PG, Meagher RJ, Lamer T, et al. Guideline summary review: an [12] Fairbank JC, Pynsent PB. The Oswestry disability index. Spine 2000; evidence-based clinical guideline for the diagnosis and treatment of 25:2940-53. degenerative lumbar spondylolisthesis. 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