Pain is a common complication in patients with cystic fibrosis (CF) and is associated with shorter survival. We evaluated the impact of osteopathic manipulative treatment (OMT) on pain in adults with CF.A pilot multicenter randomized controlled trial was conducted with three parallel arms: OMT , sham OMT  and no treatment . Medical investigators and patients were double-blind to treatment for groups A and B, who received OMT or sham OMT monthly for 6 months. Pain was rated as a composite of its intensity and duration over the previous month. The evolution of chest/back pain after 6 months was compared between group A and groups B+C combined (control group). The evolution of cervical pain, headache and quality of life (QOL) were similarly evaluated.There was no statistically significant difference between the treatment and control groups in the decrease of chest/back pain ; also, group A did not differ from group B. However, chest/back pain decreased more in groups A (p = 0.002) and B (p = 0.006) than in group C. Cervical pain, headache and QOL scores did not differ between the treatment and control groups.This pilot study demonstrated the feasibility of evaluating the efficacy of OMT to treat the pain of patients with CF. The lack of difference between the group treated with OMT and the control group may be due to the small number of patients included in this trial, which also precludes any definitive conclusion about the greater decrease of pain in patients receiving OMT or sham OMT than in those with no intervention.NCT01293019ClinicalTrials.gov  Cystic Fibrosis (CF) is an inherited multi systemic autosomal recessive disease with high morbidity and mortality, involving primarily the lungs and gastrointestinal tract The aim of this pilot study was to demonstrate the feasibility of evaluating the efficacy of OMT to treat the pain of adult patients with CF.The protocol for this trial and supporting CONSORT checklist are available as supporting information; see http://clinicaltrials.gov/ct2/show/NCT01293019). The delay in registering the study was due to a change in the statistician responsible for the study. The authors confirm that all ongoing and related trials for this intervention are registered.The study was approved by our Institutional Review Committee (Comité de Protection des Personnes “Ile de France II” # 2009-A00359-48) and all subjects provided written informed consent. The study was registered at ClinicalTrials.gov #NCT01293019 on February 9, 2011  and cervical, back or chest pain, rated 2 or higher on a 10-point visual analog scale (VAS) The patients were randomly assigned to one of the three groups: OMT  for 16 patients (group A), sham OMT (sham treatment) for 8 patients (group B) and no additional treatment  for 8 patients (group C). Randomization was performed according to a computer-generated list with blocks of fixed size, stratified by center. In each block of four, there were two arms A, one arm B and one arm C. The list was prepared and maintained by an independent statistician at an independent clinical trial unit. The investigators did not have access to the randomization list, and allocation was concealed through an internet-based system.For cases receiving experimental treatment or sham OMT, medical investigators, patients and outcome assessors were blinded, and only the osteopathic practitioner knew the allocation to the treatment arm. However, blinding was not feasible for cases receiving usual care without OMT.The experimental treatment was OMT. The intervention consisted of six monthly sessions of OMT. All OMT was provided by a single osteopathic practitioner (LS) trained according to international standards Table S1), (3) intervention consisting of either OMT or light touch sham OMT according to the randomization arm (Table S4). (See the supplementary Methods section for more details).A standardized treatment plan for diagnosed somatic dysfunction was used The control group was divided into two groups. One group was treated according to usual care and received no OMT. Patients in the sham OMT group received light touch at the skull and at the sacrum, a sham osteopathic procedure used in previous trials The primary efficacy endpoint was a composite outcome reflecting the intensity of pain and the number of painful days over the previous month evaluated after 6 months. For each patient, we calculated the mean value of the two following variables: (1) chest and back pain over the previous month (VAS from 0 to 10) Secondary endpoints included:Pain involving the neck and trapezius at 6 months evaluated as the mean value of: neck and trapezius pain over the previous month (VAS from 0 to 10) and [the number of days with neck and trapezius pain in the previous month/number of days in the previous month]×10 (score from 0 to 10).Headache at 6 months evaluated as the mean value of: headache over the previous month (VAS from 0 to 10) and [the number of days with headache in the previous month/number of days in the previous month]×10 (score from 0 to 10).QOL scores at 6 months with validated French-language versions of the questionnaire (Cystic Fibrosis Questionnaire (CFQ) 14+) The need for analgesics.At the end of the study, all patients completed a questionnaire to collect data about their interest in the study and their satisfaction with the treatment received.At the base-line visit, we collected demographic data and information about the characteristics of the patient’s CF, including respiratory function evaluated by measuring forced expiratory volume in one second (FEV1), and nutritional status evaluated with the body mass index (BMI). All patients were evaluated at the base-line visit (M0), after 3 months (M3) and after 6 months (M6) at the end of the study. Upon entry into the study, the participants were given a diary in which they recorded their pain symptoms(location and intensity) daily at baseline and during the trial; this diary was kept at home and brought for each study visit, and returned to the investigators at the end of the study. The CF physicians (DH or DG) checked the patient’s diary and recorded the patient’s pain after the patient had self-reported his pain on a VAS , collected the CFQ 14+, listed concomitant treatment including analgesics, and adverse events. The osteopathic practitioner (LS) performed osteopathic tests for all patients.We planned to include 32 subjects . Because this study was a pilot study in a rare disease, there was no formal calculation of sample size; nevertheless, this sample was expected to be sufficient to identify a difference of one standard deviation between the mean VAS for pain in the OMT group versus the two other groups with 1−β = 80% and α = 5%.All randomized patients were analyzed in their allocated group whatever the treatment received.Baseline data are described using means and standard deviations (SD) for quantitative variables, and medians and interquartile ranges (IQR) for variables with asymmetric distributions. For qualitative variables, frequencies and percentages were computed.Primary comparisons were between the OMT group (group A) and the sham OMT group+no additional treatment group pooled (group B+C).t-test at a 5% level in order to test the non nullity of the coefficient of interest in the model.The difference for the primary outcome between the two groups was evaluated at 6 months using a linear mixed longitudinal model estimating the difference in change from baseline between the 2 groups (coefficient for time × group interaction) and taking into account the correlation for data of a same patient (random effect). This difference was tested using the Student’s Pairwise comparisons between all three groups were also performed at a 1.67% level to take into account the multiplicity induced by these three comparisons. To check consistency with the parametric analysis, Wilcoxon’s tests with significance set at 5% were used for a non-parametric comparison of the difference between the two groups in the distribution of changes from baseline to month 6.Final composite outcomes (M6) for neck and trapezius pain, headache and QOL scores were analyzed with the same strategy as the primary outcome.The need for analgesics was analyzed using a mixed logistic regression model with a random intercept at the individual patient level.The nlme package Thirty-two patients were included between November 2009 and October 2010; 16 patients were randomized to osteopathic manipulative treatment (group A), eight patients to sham OMT (group B) and eight patients to usual care (group C). No patient dropped out of the study after randomization, and all 32 patients attended all the visits planned in the study until month 6. The last study visit took place on April 2011. Results for all 32 patients were included in the analysis Figure 1Demographic and clinical factors are reported in We performed prespecified ancillary analyses for the primary outcome (composite chest/back pain) in the three groups, differentiating between the sham OMT (group B) and no treatment (group C) groups Table 2.No differences between the treatment group and the control group (group B+C) were found for the secondary outcome measures cervical pain, headache Table 3,Table S5). The difference of change from baseline for chest/back pain between the experimental group treated with OMT and the control group was −1.96  for mean VAS [CI 95%]), p = 0.076.When taking into account the mean VAS score and the mean number of days in pain in all arms of the study, the results were similar .The need for analgesics did not differ significantly between groups Table 4.No harm or unintended effect was reported due to treatment.Twenty-six patients (81%) indicated that they had been interested in the study and six (19%) that they had been slightly interested. Fifteen of the 16 patients in the treatment arm were very satisfied (94%) and one was reasonably satisfied (6%); five of the eight patients in the sham group were very satisfied (62%), two were reasonably satisfied (25%) and one patient (12%) was not satisfied.Our pilot study is the first to demonstrate that it is feasible to evaluate OMT against the pain affecting CF patients. However, it did not show any difference in the decrease of pain between the group treated with OMT and the control group, though chest/back pain decreased more in patients receiving OMT and sham OMT than in those with no intervention. Our study was therefore not powered to be able to draw firm conclusions on the efficacy of OMT against the pain of patients with CF.A sufficient number of patients were rapidly recruited  and none of the 32 patients dropped out of the study. This reflects the significant expectations that CF patients have for complementary medicine for pain relief. In a survey in French CF patients, 326 of 714 respondents (46%) had used CAM and 38% had experience of OMT In our study, it is noteworthy that the majority of our patients were women. Indeed, in CF there is a female disadvantage in terms of survival and morbidity, called the “CF gender gap” As complementary medical techniques become more mainstream, we anticipate that more adults with CF will attempt alternative therapies for pain relief. Our study is the first to assess a treatment of this type in CF patients. We chose to evaluate the effects of OMT on chest/back pain because pain at these sites is prevalent among adults with CF, affecting 15–72% of CF patients We found no statistically significant difference in the decrease of chest/back pain between patients treated with OMT and the control group. There was no statistically significant difference between patients receiving the OMT intervention treatment and those receiving the OMT sham treatment. However, chest/back pain decreased significantly more in patients receiving the OMT intervention treatment and in those receiving the osteopathic sham treatment than in patients only receiving usual routine care. There was also no difference between the intervention group and the control group with respect to neck/trapezius pain, headache, QOL scores or the need for analgesics. It has been reported that alternative medicine may be an especially successful placebo-generating health care system A systematic review and meta-analysis of randomized, controlled trials assessed the effect of OMT on chronic low back pain: it concluded that OMT reduced low back pain significantly more than expected from placebo effects, and that the beneficial effects persisted for at least three months In conclusion, our pilot study shows that the assessment of the effects of OMT on chest and back pain in adults with CF is feasible. Patients have substantial expectations and hopes for such studies. The lack of any significant difference between the intervention OMT group and the control group might be related to the small number of patients, which also precludes any definitive conclusion about the greater decrease of pain in patients receiving OMT or sham OMT than in those with no intervention. This may raise the question of a placebo effect and highlights the importance of psychological factors and human relationships in the treatment of pain. Nevertheless, the results need to be interpreted with caution, due to the small number of patients in our pilot study and the multiplicity of the tests. Larger and more powerful studies are needed to determine whether OMT could be beneficial for CF patients who suffer chest and back pain.Table S1Criteria for clinical decision about the severity of somatic dysfunction according to the three categories of tests.(DOCX)Click here for additional data file.Table S2Different techniques of the Osteopathic Manipulative Treatment.(DOCX)Click here for additional data file.Table S3Intervention used in the twoOMT groups.(DOCX)Click here for additional data file.Table S4Position of the patient and of the practitioner during the different techniques.(DOCX)Click here for additional data file.Table S5Change in pain intensity and days in pain between the experimental OMT group (A) and the control group (B+C).(DOCX)Click here for additional data file.Checklist S1CONSORT checklist.(DOC)Click here for additional data file.Protocol S1Trial protocol.(DOCX)Click here for additional data file.Methods S1Supplementary methods.(DOCX)Click here for additional data file.


Among the multiple conservative modalities, physiotherapy is a commonly utilized treatment modality in managing chronic non-specific spinal pain. Despite the scientific progresses with regard to pain and motor control neuroscience, treatment of chronic spinal pain (CSP) often tends to stick to a peripheral biomechanical model, without targeting brain mechanisms. With a view to enhance clinical efficacy of existing physiotherapeutic treatments for CSP, the development of clinical strategies targeted at ‘training the brain’ is to be pursued. Promising proof-of-principle results have been reported for the effectiveness of a modern neuroscience approach to CSP when compared to usual care, but confirmation is required in a larger, multi-center trial with appropriate evidence-based control intervention and long-term follow-up.The aim of this study is to assess the effectiveness of a modern neuroscience approach, compared to usual care evidence-based physiotherapy, for reducing pain and improving functioning in patients with CSP. A secondary objective entails examining the effectiveness of the modern neuroscience approach versus usual care physiotherapy for normalizing brain gray matter in patients with CSP.The study is a multi-center, triple-blind, two-arm (1:1) randomized clinical trial with 1-year follow-up. 120 CSP patients will be randomly allocated to either the experimental (receiving pain neuroscience education followed by cognition-targeted motor control training) or the control group , each comprising of 3 months treatment. The main outcome measures are pain  and self-reported disability. Secondary outcome measures include brain gray matter structure, motor control, muscle properties, and psychosocial correlates. Clinical assessment and brain imaging will be performed at baseline, post-treatment and at 1-year follow-up. Web-based questionnaires will be completed at baseline, after the first 3 treatment sessions, post-treatment, and at 6 and 12-months follow-up.Findings may provide empirical evidence on: (1) the effectiveness of a modern neuroscience approach to CSP for reducing pain and improving functioning, (2) the effectiveness of a modern neuroscience approach for normalizing brain gray matter in CSP patients, and (3) factors associated with therapy success. Hence, this trial might contribute towards refining guidelines for good clinical practice and might be used as a basis for health authorities’ recommendations.NCT02098005.ClinicalTrials.gov Identifier:  Chronic spinal pain (CSP) is a major public health problem worldwide as it is a common disorder and a major cause of disability and health care utilization -4. TakinManagement of CSP should aim at achieving and maintaining a clinically important reduction in pain and disability with a minimum amount of costs and inconveniences related to the intervention ,9. For CIn non-specific CSP, there is increasing evidence for supraspinal abnormalities  in addition to the compelling evidence for impaired motor control of spinal muscles (reviewed elsewhere -24). As Addressing the proof-of-concept, 1 single case study  and 2 smPrevious work from our research group has shown that therapeutic pain neuroscience education alone is able to improve brain-orchestrated endogenous analgesia in patients with chronic widespread pain . Until nBased on this background, this 12-month prospective study has been designed in order to estimate the effectiveness of a modern neuroscience approach in CSP patients, its determinants and its changes during a 1-year follow-up.Table The present study is a 12-month multi-center, triple-blind, randomized, controlled, parallel group trial that will be carried out between February 2014 and April 2017. Patients with CSP  will be enrolled in a structured 3-month rehabilitation program organized in 2 university hospitals in Belgium . More specifically, therapeutic pain neuroscience education combined with cognition-targeted motor control training will be compared to back/neck school and general exercises. Treatment outcomes will be assessed at baseline, after 3 treatment sessions, post-treatment (at 3 months), at 6 months and 1 year follow-up  from the hospital, from primary care practices  and via adverts. Dutch speaking male and female adult (aged 18 – 65 years) patients with non-specific CSP (at least 3 days/week) for at least 3 months, currently seeking care for low back or neck pain, not starting new treatments or medication and continuing usual care 6 weeks prior to and during study participation (to obtain a steady state), will be eligible for study participation after signing the informed consent. Patients with neuropathic  or chronAfter eligibility has been confirmed, patients will be informed about the study comparing two physiotherapeutic treatment options. After obtaining written informed consent, baseline measurements will be performed (see next paragraph). Participants will then be randomized to either control or experimental group (1:1 ratio) using a stratified permuted block allocation with stratification factors being treatment center (Ghent or Brussels), dominant pain location (low back or neck) and gender  and with a block size of four ,35. RandPain and restrictions in functioning will be the primary outcome measures. Secondary outcome measures will include brain gray matter structure, motor control, muscle properties, and psychosocial factors that may interfere with pain. Methods for assessment will include web-based questionnaires (Dutch version), clinical testing and brain imaging using magnetic resonance imaging (MRI).self-administered online tools will be used for pain assessment at baseline, post-treatment, and at 6 and 12-months follow-up:Pain, including symptoms and indices of central sensitization, will be assessed through a self-reported web-based questionnaire and a clinical assessment. The following A Numerical Rating Scale (NRS) for pain ranging from 0 = “no pain” to 10 = “the worst pain imaginable”  and an additional enquiry about the number of health visits for spinal pain over the course of the follow-up period: “Since your assessment on [date of final assessment], how many times have you consulted a health care professional for your spinal pain?” ,the Central Sensitization Inventory (CSI) , compristhe SF-36 , see below.Clinical assessment of pain will comprise pressure pain threshold (PPT) measurements and the cold pressor test (CPT). Measurements will be taken at baseline, post-treatment, and at 1-year follow-up.2/s   will be Low back pain patients will perform a lumbopelvic control test in the sitting and standing position. A clinical rating scale (article submitted for publication) comprising the quality of the lumbopelvic motion, control of the adjacent areas, preference of motion direction, breathing, and repetitions will be used for evaluation, with higher scores indicating better performance.As the observers’ level of experience is important for good test reliability, all tests will be rated by the same experienced observer -69.The assessment of intrinsic muscle properties  will take place at baseline, post-treatment and at 1-year follow-up.muscle strength will be measured with a hand-held dynamometer  with a sensitivity of 0.4 N. In neck pain patients, the testing procedure will consist of seated isometric strength measures for neck flexion, extension and side bending (left and right). For each movement, the dynamometer will be placed on specific marker points: the imaginary line through the supra-orbital notch for flexion, the protuberance of the occiput for extension and the temporal bone for side bending. In patients with dominant low back pain, trunk flexor and extensor muscle strength will be evaluated. Trunk flexor muscle strength will be measured with the patient in a semi-upright sitting position (45 degrees), knees extended, arms flexed alongside the trunk, hands placed on the homolateral shoulder, and head mid-line. The end piece of the dynamometer will be applied on the sternum at the centre of the chest. Trunk extensor muscle strength will be measured with the subject in prone, hands underneath the forehead and head mid-line. The dynamometer will be applied at the inferior angle of the scapulae at the centre of the back. For muscle strength tests, patients will be allowed 1 warm-up trial, followed by 3 successive maximal effort trials separated by 10-s rest periods. Patients will be asked to take 1 or 2 s to come to maximum effort and then, 5 s as forcefully as possible. The mean of 3 consecutive measurements per movement will be taken.Isometric Muscle endurance will be assessed using isometric tests, i.e. patients will be instructed to maintain an imposed posture as long as possible. In neck pain patients, endurance of the neck flexors will be evaluated with the deep neck flexor endurance test [nce test ,71: patince test . Isometrnce test ,72,73. FPatients will complete a web-based online battery of questionnaires at baseline, after 3 treatment sessions, post-treatment, and at 6- and 12-month follow-ups. The following standardized and reliable questionnaires (Dutch version) will be used to measure psychological factors that may interfere with pain:The Pain Catastrophizing Scale (PCS) will be included to assess catastrophic thinking about pain. It consists of 13 items describing different thoughts and feelings that individuals may have when experiencing pain. Items are scored on a 5-point scale. A general score and scores on 3 subscales  will be obtained; higher scores indicate more severe catastrophic thoughts about pain ,75. The The Pain Vigilance and Awareness Questionnaire (PVAQ) will be used to investigate patients’ attention to pain. It is a 16-item measure of attention to pain that assesses awareness, consciousness, vigilance, and observation of pain. Scores range from 0 to 80 and high scores correspond to hypervigilance for pain. The items have demonstrated good internal consistency  in a population of chronic low back pain patients .The Tampa Scale for Kinesiophobia (TSK) is a 17-item questionnaire that will be used to measure the fear of (re) injury due to movement ,80. ScorThe Illness Perception Questionnaire-Revised (IPQ-R), consisting of 3 domains, will be used to measure patients’ illness perceptions . In the Before starting the study, physiotherapists involved in the treatment will be trained extensively by expert therapists in the domain. They will also receive a manual containing descriptions of procedures and checklists. Using a therapists’ treatment diary, therapy will be monitored and evaluated.Within a 12-week period, patients in each group will receive 18 treatment sessions from their trained physiotherapist. In both groups, the first 3 sessions (spread over 2 weeks) will consist of education, whereas the next 15 sessions (spread over the next 10 weeks) will be exercise according to the protocol. All sessions are one-on-one sessions lasting about 30 minutes, except for session 1  and session 2 (online module performed at home).The educational information will be presented verbally (explanation by the therapist) and visually . After the first session, patients will also receive an information leaflet about the education according to the protocol and will be asked to read it carefully. Although initiated during the first 3 sessions, education will be ongoing throughout exercise therapy. In addition to the individually tailored exercises performed in physiotherapy, a home exercise program will be established for each patient. For home exercises, modalities and clear verbal, written and visual instructions will be given. Patients will be strongly encouraged to continue these exercises during the follow-up year.The modern neuroscience approach will entail therapeutic pain neuroscience education followed by cognition-targeted motor control training. Pain neuroscience education will be applied to reconceptualize pain and to convince the patients that all pain is in the brain, and that hypersensitivity of the central nervous system rather than local tissue damage may be the cause of their symptoms. The education will cover the physiology of the nervous system in general and of the pain system in particular. The content and pictures of the educational sessions are based on the book “Explain Pain”  and haveIn the present study, the Dutch Neurophysiology of Pain Test (patient version)  will be As such, therapeutic pain neuroscience education (or rather “communication”) will prepare the patients for a time-contingent, cognition-targeted approach to daily  activity and exercise therapy. Once adaptive beliefs are acquired regarding CSP, the exercise therapy with specific emphasis on spinal motor control training will be initiated (session 4). This training will consist of sensorimotor control training by facilitating the proprioceptive system and optimizing the coordinative muscle recruitment patterns ,91-93. HA time-contingent progression will be used to integrate exercises with increasing complexity. In order to maximize transfer to daily situations, late-stage progression will not only involve exercising during physically demanding tasks, but also exposure to the feared movements or activities, and exercising during cognitively and psychosocially stressful conditions ,30. ThroFurther details of the modern neuroscience approach to CSP, including practice guidelines, were presented previously ,94,95.Those in the control group will receive traditional back/neck school, including back care education and general exercises. Back care education will cover anatomy and biomechanics of the spine, common causes of spinal pain, the load-tolerance model, nociceptive pain processing, and ergonomic counseling based on the inherent postural strain associated with various postures and daily activities . As such, the education sessions will prepare the patients for a symptom-contingent, biomedical approach to daily  activity and exercise therapy. In session 4, the general exercise therapy will be started with specific emphasis on treating dysfunctional muscles and joints. Different therapeutic goals will be pursued  depending on what emerges from the clinical reasoning as the most dominant peripheral dysfunction. Importantly, abdominal and paraspinal muscles will be targeted without involvement of deep muscle activation. The program will also involve aerobic fitness improving exercises. The progressive exercise program will mainly entail an increase in exercise intensity, and an evolution towards functional activities and more physically demanding tasks while keeping the spine in physiological neutral positions to minimize strain imposed upon the spinal structures. All exercises will be performed in a symptom-contingent way.The main difference between the 2 groups is the treatment of cognitive aspects of pain in the modern neuroscience group , which will not be applied in the control group .Sample size calculations were performed with G*Power 3.1.3  based on the therapy effects on pain in the pilot study of Moseley , and acct test. Associations between baseline parameters will be examined. Possible changes in the outcome measures in response to the intervention will be examined between the two groups by using repeated measures analysis of variance with intervention serving as the between-subjects factor and time as the within-subjects factor. In these analyses, treatment center, dominant pain location and gender will be entered as covariates. Regression analyses will be used to determine predictors for therapy success and reasons for poor therapy outcome. For all statistical tests, the significance level will be set at 0.05. Risk ratios and their 95% confidence intervals will be calculated as are effect sizes [Data analysis will be performed using SPSS for Windows , or the newest available version, under the intention-to-treat-principle. Baseline data will be analyzed in order to determine descriptive statistics for the different outcome measures for the complete CSP group. Comparability of the groups before the intervention will be studied with the Fisher exact test and independent samples ct sizes . The numThe present study is a triple-blind randomized controlled trial. The patient, assessor and outcomes assessor will be blind to the treatment groups. To keep patients unaware of any expected treatment group benefit, patients will be informed that the effect of 2 well-established therapies is to be evaluated. An independent and blinded assessor will perform the baseline and follow-up assessments. Statistical analysis will be blinded regarding treatment group code. The researcher who will perform the statistical analyses will not be involved in taking the measurements. The treating physiotherapists will be blinded to the results of the measurements and questionnaires.This trial will be conducted in compliance with the Declaration of Helsinki (1964 and amendments) and Good Clinical Practices. Patients will give their written informed consent prior to the start of any study-related procedure. Approval to conduct this study was granted by the Ethics Committee of the Ghent University Hospital and the University Hospital Brussels.Inclusion of patients began in February 2014 and is expected to last until March 2016. Results are expected in 2017.The aim of this study is to compare usual care physiotherapy and a modern neuroscience approach in CSP patients. The main study question is which of the 2 treatment strategies is more effective in reducing pain and disability associated with CSP, both in the short and long term (1-year follow-up). Further objectives are: to evaluate the effect on brain gray matter structure, the factors associated with therapy success, the relationships between (changes in) outcome parameters being pain, disability, brain structure, motor control, muscle properties and psychosocial correlates.With the inclusion of 120 patients with CSP, this will be the largest study to investigate the effectiveness of 2 well-founded physiotherapy treatment strategies for patients with CSP. Furthermore, the multi-center design of the study increases the external validity of the study findings as it implies treatment by different physiotherapists in different settings and a large geographical area for patient recruitment. Importantly, the treating physiotherapists, blinded to the results of the measurements and questionnaires, are equally instructed and experienced in applying the respective treatments. Randomization is organized centrally by the Biostatistics Unit and the randomization schedule is only known to 1 investigator who is not involved in recruiting patients. The patients, assessors performing the baseline and follow-up evaluations and the researcher performing statistical analyses are blinded to group allocation. Hence, the study is designed in a way that minimizes potential biases.It is expected that this randomized controlled trial will provide novel data on the effectiveness of a modern neuroscience approach when compared to usual care physiotherapy on key patient-centered outcome measures . These results will also contribute to understanding the associations between (changes in) pain, disability, psychosocial correlates and physical factors, including brain structure. Moreover, the study will provide insights into major factors associated with (sub) optimal treatment success. As such, this 12-month prospective trial may contribute towards refining guidelines for good clinical practice and may be used as a basis for health authorities’ recommendations.COP: Centre of pressure; CSP: Chronic spinal pain; CPT: Cold pressor test; CSI: Central Sensitization Inventory; IPQ-R: Illness Perception Questionnaire-Revised; MR: Magnetic resonance; MRI: Magnetic resonance imaging; NRS: Numerical Rating Scale; PCS: Pain Catastrophizing Scale; PDI: Pain Disability Index; PPT: Pressure pain threshold; PVAQ: Pain Vigilance and Awareness Questionnaire; SF-36: Medical outcomes Short Form 36 Health Service Survey; TSK: Tampa Scale for Kinesiophobia.The authors declare that they have no competing interests.All authors contributed to the design of the study and have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/15/149/prepub


Multiple rib fractures and unstable thoracic cage injuries are common in blunt trauma. Surgical management of rib fractures has received increasing attention in recent years and the aim of this 1-year, prospective study was to assess the long-term effects of surgery.Fifty-four trauma patients with median Injury Severity Score 20 (9–66) and median New Injury Severity Score 34 (16–66) who presented with multiple rib fractures and flail chest, and underwent surgical stabilization with plate fixation were recruited. Patients responded to a standardized questionnaire concerning pain, local discomfort, breathlessness and use of analgesics and health-related quality of life (EQ-5D-3 L) questionnaire at 6 weeks, 3 months, 6 months and 1 year. Lung function, breathing movements, range of motion and physical function were measured at 3 months, 6 months and 1 year.p < 0.0001) after 6 weeks to 1 year. Lung function improved significantly with predicted Forced vital capacity and Peak expiratory flow increasing from 86 to 106 % (p = 0.0002) and 81 to 110 % (p < 0.0001), respectively, from 3 months to 1 year after surgery. Breathing movements and range of motion tended to improve over time. Physical function improved significantly over time and the median Disability rating index was 0 after 1 year.Symptoms associated with pain, breathlessness and use of analgesics significantly decreased from 6 weeks to 1 year following surgery. After 1 year, 13 % of patients complained of pain at rest, 47 % had local discomfort and 9 % used analgesics. The EQ-5D-3 L index increased from 0.78 to 0.93 and perceived overall health state increased from 60 to 90 % (Patients with multiple rib fractures and flail chest show a gradual improvement in symptoms associated with pain, quality of life, mobility, disability and lung function over 1 year post surgery. Therefore, the final outcome of surgery cannot be assessed before 1 year post-operatively. The inc® (DePuy Synthes) Fixation System consisting of pre-shaped angular locked plates in titanium and intra-medullary splints was used to stabilize rib fractures. Post-operative pain was managed using either an intra-pleural or epidural catheter with adjunct, oral pain medication. Intravenous broad-spectrum antibiotic therapy was given prophylactically until the chest tubes had been removed. Low-molecular weight heparin was given subcutaneously as thrombotic prophylaxis. A surgeon assessed patients at 6 weeks, 3 months, 6 months and 1 year post-operatively using a standardized questionnaire concerning pain, local discomfort, breathlessness and analgesics and QoL according to EQ-5D-3 L [n = 16) at 3 months, 6 months and 1 year post-operatively. The selected patients all had flail chest, no co-morbidities and spoke Swedish. Standardized lung function tests [® Spirometer . Breathing movements were measured at rest and during maximal breathing by using a Respiratory Movement Measuring Instrument, RMMI®  [th costae and the xiphoid process), flexion and lateral flexion in a standardized manner [Pre-operative Three-Dimensional (3D) reconstructions of Computer Tomography (CT) images of the thorax were used for planning the surgical procedure. The 3D reconstructions were based on images with 0.625 mm slice thickness and produced in the program AW Volume Share™ 5 . Patients were intubated with a double lumen endotracheal tube. A non-muscle sparing thoracotomy was performed to clean out hematoma and debris, identify and, if necessary, manage intra-thoracic injuries. The reason for a non-muscle sparing approach was to gain good access to the chest wall and the multiple fractured ribs. The MatrixRIBQ-5D-3 L . Pain waQ-5D-3 L . A cheston tests  were perIceland) . The rand manner . Physicad manner  where 10p < 0.05.The SAS® statistical software package  was used for all statistical analyses. Results are presented as median with range or mean with standard deviation (SD) for continuous variables and n and % for categorical variables. For comparison over time, the Wilcoxon Signed Rank test was used for continuous variables and Sign test was used for categorical variables. The significance level was considered Of the 60 patients operated six were excluded from this follow-up. Two patients died during the immediate post-operative period due to multiple organ system failure and respiratory insufficiency. Four patients were excluded due to concomitant injuries resulting in tetraplegia in one case and severe head injury in three patients. Of the 54 patients included in the study 49 patients participated while 5 patients were lost to follow-up Fig. . Nineteep = 0.039) between 6 weeks and 3 months after surgery. Problems associated with pain on breathing and breathlessness decreased progressively by 21 % (p = 0.039) and 27 % (p = 0.022), respectively, during the first post-operative year. After 1 year, 13 % of patients complained of pain at rest, 9 % experienced pain on breathing and 16 % experienced breathlessness. Local discomfort did not decrease with time, but remained constant and affected approximately 47 % of patients. Despite enduring pain, there was a significant, 49 % (p < 0.0001) decrease in the proportion of patients using analgesia, with 9 % on pain medication after 1 year (Table The proportion of patients seen at follow-up with pain at rest decreased with 26 % (p = 0.022), self-care , performance of usual activities , and pain or discomfort  from 6 weeks to 1 year after surgery. There was no significant improvement in symptoms of anxiety or depression over time. The QoL measured by Visual Analogue Scale (VAS) improved significantly over time: median VAS was 60 % (20–96) at 6 weeks, 76 % (40–97) at 3 months, 80 % (20–100) at 6 months and 90 % (30–100) after 1 year. Quality of life significantly increased  between 6 weeks to 1 year following surgery.Patients’ QoL measured with EQ-5D-3 L showed median index values that progressively increased from 0.78 at 6 weeks to 0.93 after 1 year, with the greatest improvement occurring between 6 weeks and 3 months after surgery Fig. . There wp = 0.0002) from 3 to 6 months and by 19.8 %  from 3 months to 1 year after surgery. There was no significant improvement in FEV1 over time. There was no significant improvement in mean predicted PEF between 3 and 6 months, but PEF significantly increased by 28.5 %  from 3 months to 1 year. After 1 year the mean FVC was 106 %, PEF was 110 % and FEV1 was 80 % compared to predicted values  decrease in median DRI and between 3 months and 1 year, there was an 18.4 mm (p = 0.013) decrease with a median DRI of 0. Of the subset of 16 patients, the number who experienced no disability was three at 3 months, six at 6 months and 10 after 1 year  died within 1 year after surgery; one patient died after 65 days due to cardiac arrest, one patient died after 137 days due to complications of Chronic Obstructive Lung Disease (COPD) and the third patient died after 277 days due to osteomyelitis in the tenth thoracic vertebra.In this prospective study of 54 trauma patients who underwent stabilizing surgery of rib fractures, we found progressive improvement in pain, mobility, activity, QoL, lung function and disability during the first, post-operative year.per se is associated with morbidity, however, and 47 % of our patients experienced some form of local discomfort, although it was unclear whether this was due to the trauma or surgery. Despite enduring pain and discomfort, only 9 % of patients used analgesics, suggesting mild and not particularly disabling symptoms. Patient QoL improved gradually after surgery; the median EQ-5D-3 L VAS was 90 % after 1 year, which is higher than that of a Swedish population study, which showed a mean VAS of 77.4 and 75.8 % for men and women, respectively [The primary end-point in previous studies of surgical treatment of flail chest has mainly focused on aspects associated with respiratory insufficiency. Although acute pain can contribute to respiratory problems, chronic pain can be debilitating and lead to decreased QoL. We found that 13 % of our patients experienced enduring chest pain at rest after 1 year. In contrast, a previous observational study of conservatively-managed patients with flail chest showed that 49 % experienced enduring pain after a mean follow-up of 5 years . Surgeryectively . The medectively , where mectively , but it . [. [. used biodegradable inion plates and found no difference in lung function after 3 months [® (DePuy Synthes) Fixation System is superior since the plates mimic the biodynamic characteristics of the ribs and are fixed with angular locked screws creating stability in movement without losing strength over time.Lung function in a subgroup of patients improved significantly over time and patients reached FVC and PEF values of greater than 100 % of predicted values after 1 year. The FEV did not improve over time and was approximately 80 % of the predicted value, which indicates a remaining obstructive component. Tanaka et al.  found pr. [.  used Kir3 months , 10, we . found that 71 % of conservatively managed patients experienced daily limitations and disabilities after 3 months compared to 48 % of operated patients, suggesting that surgical management of flail chest decreases prolonged disability, although this may be particularly evident in cases of isolated thoracic injuries.None of the RCTs have studied breathing movements and range of motion at follow-up. We found that breathing movements were decreased on the operated side, but tended to improve gradually over time, and whilst a statistically significant improvement was found in movements of the upper thorax at rest, these changes were not clinically significant and there was no major difference between operated and non-operated side. The range of motion was statistically improved as regards the lower level thoracic excursion, flexion and extension but the changes were small and of little clinical relevance. Physical function, assessed by DRI, improved gradually and significantly with time; the median was 0 after 1 year, indicating no loss of function. However, the range of 0–67 suggests a spread, with some patients experiencing some difficulty (≥25) or difficulty (≥50) in function. The results may also reflect long-term outcome of concomitant injuries; however, we found that at least 50 % of trauma patients who have undergone surgical fixation of flail chest have no remaining disability after 1 year. Previous studies of conservatively-managed patients with flail chest have shown that 66 and 38 % of them experienced persistent disability after 2 months , respectLate complications were seen in four out of 60 patients with two undergoing re-operations due to deep wound infection and subjective symptoms from a protruding plate. We consider this a low rate of complications considering these were among the first patients operated at our centre.The results of this study are limited as this was an uncontrolled study. The patients included were mostly subjected to poly-trauma, as demonstrated by a median ISS of 20. Poly-trauma patients are an inherent, heterogeneous group with associated injuries in addition to their thoracic trauma, which serve as confounding factors influencing the perception of pain, function, activity and QoL. Results from patients with isolated thoracic injury are likely to have been more homogenous and easier to interpret, but such a group would not have been representative of the population at large. Even in isolated thoracic injury, however, there are confounding factors due to commonly associated clavicle and scapular fractures that influence the mobility, function and pain of the thoracic cage. Moreover, the pre-existing pain, function and disability were unknown for patients in this study. Between 63–83 % of patients in our study attended each follow-up but only 22 patients attended all dates, which poses a weakness and a potential bias in the results. However, the age, sex, ISS and NISS values compared between included patients and those at each follow-up were similar.Surgical treatment of rib fractures has received increasing attention in recent years. While previous studies have largely focused on the treatment of flail chest, it is not clearly defined if patients with multiple rib fractures or dislocated ribs also benefit from surgery. We chose to study the long-term results of patients with flail chest as this group has been the main focus of previous studies. However, patients with multiple rib fractures that required surgery for other reasons, such as air leakage or bleeding, were also stabilized and therefore included in this study. With the development of minimally invasive approaches to rib fixation more will be gained from surgery and the indications may well include multiple rib fractures in the future. A muscle-sparing approach to the ribs and a selective usage of thoracotomy would presumably decrease post-operative pain. However, muscle-sparing techniques minimize access to the injured chest wall making it difficult to fixate multiple rib fractures. Video-assisted thoracoscopic surgery (VATS) could be used to clear out hematoma and resect leaking lung tissue. However, the technique does require lung deflation to some extent, which may not be possible in all trauma patients with severe lung contusions.The method used for stabilizing ribs varies between different studies, making comparison difficult as the biomechanical properties of the implants differ. There is a need for larger prospective RCTs that compare not only the outcome of surgery concerning ventilator support and Intensive Care Unit (ICU) care, but also the long-term outcomes associated with pain, function, activity and QoL, as well as cost-benefit of such surgical management.Patients who underwent surgical plate fixation of multiple rib fractures and flail chest showed a gradual improvement in symptoms associated with pain, physical function, lung function and QoL, which continued throughout the first post-operative year. Breathing movements, range of motion, symptoms of anxiety or depression, and local discomfort did not improve significantly over time. We conclude that the final outcome after plate fixation of rib fractures cannot be assessed before 1 year post-operatively.3D, Three-Dimensional; COPD, Chronic Obstructive Lung Disease; CT, Computer Tomography; DRI, Disability Rating Index; FEV1, Forced Expiratory Volume in One second; FVC, Forced Vital Capacity; ICU, Intensive Care Unit; ISS, Injury Severity Score; NISS, New Injury Severity Score; PEF, Peak Expiratory Flow; QoL, Quality of Life; RCT, Randomized Controlled Trial; RMMI, Respiratory Movement Measuring Instrument; SD, Standard Deviation; TTO, Time Trade-Off; VAS, Visual Analogue Scale.


Aim of the study was to verify the efficacy of an individualized physiotherapy treatment based on a protocol assessment of cervical spine disorders in patients with chronic tension-type headache (cTTH).We enrolled patients with cTTH (ICHD3-beta criteria) attending the Headache Centre of Trieste who preferred not to take pharmacological treatment. Patients were prophylaxis free in the last 3 months and were asked to fill in an ad hoc diary in a three-month baseline period. The physiotherapy group (PhG) underwent a three-month combined protocol of postural advice, exercises and manual therapy. Intensity (NRS), frequency and duration of pain were analysed with GraphPad InStat 3.06. Cervical range of motion (CROM) was evaluated with a headgear provided with goniometer and spirit level. Neck pain was studied with the Neck Pain and Disability Scale I (NPDS) Questionnaire. A control group (CG) treated with amitriptyline for three months was compared with PhG.We enrolled 8 PhG patients  and 8 CG patients . Six of the 8 PhG patients improved, in 2 patients headache was eliminated, none worsened. All headache patterns were statistically reduced . The patients who were headache-free had the most significant clinical improvement in the NPDS-I Questionnaire, while the 2 patients without improvement had null score. The NPDS score improved statistically after the treatment (p = 0.03). Most CROM improvement were Flexion 44% and Rotations . In the CG, duration (from 24 to 1 hour per crisis [p = 0.0001]) and frequency (from 23±3 to 7±6 days per month [p = 0.0005]) were significantly reduced, but no reduction in intensity (NRS from 3.25±0.7 to 2.5±0.9 [p = NS]) was noted.An individualized physiotherapy treatment based on combined exercises, manual therapy and postural advice, is efficient in improving headache, cervical motion and disability in cTTH. Individualized physiotherapy may represent an effective alternative option in treating patients with cTTH who prefer not to take prophylactic drugs.Written informed consent to publish was obtained from the patient(s).


Because of less systemic side effects of topical medications in pain relief of the painful form of diabetic peripheral neuropathy, this study aimed to compare the effect of amitriptyline and capsaicin cream in relieving pain in this condition.In this randomized, double-blind and non -inferiority trial, 102 patients received amitriptyline 2% and capsaicin 0.75% creams 3 times a day for 12 weeks on the feet. Pain relief was measured by the visual analog scale (0–10). Treatment responding was considered as cure rate greater than 50% from baseline. Evaluations of the pain severity, compliance and drugs adverse effects were performed at each of the 4-week follow -up visits.P < 0.001 for both). Treatment responders were similar in both groups (P = 0.545). Intention-To-Treat analysis showed no significant difference in the efficacy between the two treatments (P = 0.703). Adverse events were more common in capsaicin group (P = 0.001). Dermatologic complications were the most common: itching, blister formation and erythema in the capsaicin group and skin dryness and itching in the amitriptyline group.Both drugs significantly relieved pain in 12 weeks compared with baseline values (This study demonstrates the similar efficacy of amitriptyline cream with capsaicin cream in managing diabetic neuropathic pain with fewer side effects. Diabetic peripheral neuropathy (DPN) is one of the most common, expensive, and disabling complications of diabetes . PreviouStudy participantsPatients with type 2 diabetes, aged between 30 and 70 years, who had DPN were considered for the study. Patients with chronic daily pain for more than three months, who had a pain score of at least 4 as assessed by visual analog scale (VAS), were enrolled in the study. Patients with less than one year duration of diabetes, opium or alcohol use, other causes of neuropathy, hepatic or renal failure (serum creatinine > 1.5 mg/dl), clinically significant cardiovascular disease, HA1C ≥ 9%, pregnancy or lactation, ulcer or infection of foot and hypersensitivity to pepper were excluded from the study. Use of any medication for neuropathic pain was discontinued two weeks before enrolling in the study and throughout it, but required therapies including insulin and oral hypoglycemic agents were maintained throughout the study.Study design and treatmentThis study was approved by Hamedan University of Medical Sciences Research Ethics Committee (D/P/16/35/9/1282) and had been registered in IRCT (Registration ID: IRCT201209238308N2). This 12-week, randomized, double-blind, parallel-group and non-inferiority trial was conducted to compare the efficacy and safety of amitriptyline and capsaicin for pain associated with DPN. Laboratory tests, physical examinations, body weight, height, blood pressure and general characteristics including age, duration of diabetes, history of hypertension, pain duration and medications were recorded at the base of the study. PDN was confirmed by NSS (Neuropathy Symptom Score) and NDS (Neuropathy Disability Score) criteria , 16. Pat. Physicochemical and microbial tests of amitriptyline cream were assessed by ICH methods and USP guidelines. Formulation was kept at 45ºC and 75% humidity for 6 months (accelerated conditions) and during this period, stability data were getting at month 1, 3 and 6. No changing in pH, viscosity, density, formulation color, odor and etc was seen. Also total bacterial count (CFU/g) and total fungi and yeast count (CFU/g) were determined. The study drugs were amitriptyline 2% cream and capsaicin 0.75% cream in no label laminated tubes containing 100 gram of material. In order to fabricate amitriptyline oil/water cream, both Lipid phase  and aqueous phase  were separately heated to 75ºC. After that, the hot water phase was added to the lipid phase under stirring (600 rpm) and cooled down to 25ºC. We used 2% concentration of the amitriptyline cream because a few controlled clinical trials examined previously this concentration and had demonstrated its efficacy and safety , 14, 17.Amitriptyline or capsaicin was dispensed to patient according to randomized group assignment. Patients applied either of drugs topically below the ankles on the feet 3 times a day.The end point of the study was the reduction in the median pain score from baseline, as assessed by the VAS (0-10 points). Evaluations of the patients including assessment of the pain severity, vital signs and examination and questioning regarding the adverse effects were performed at each of the 4-week follow-up visits. Compliance was assessed by direct questioning. The investigator was accessible by telephone to all patients throughout the study.Statistical analysisThe efficacy analyses were performed on both per protocol analysis and the intention-to-treat (ITT) analysis. ITT population was defined as randomized patients who took at least one dose of medication and provided at least one baseline and one post-baseline efficacy assessment. The efficacy endpoint was the change in mean monthly pain score on the Visual Analogue Scale (VAS). Values are expressed as means ± SD and numbers and percentages. The patient VAS was compared using the Student t test. Cure rates between treatment groups and incidence of adverse events were compared by Chi-Square Test. Repeated measure analysis was performed on VAS change scores (from baseline to week 12). Baseline parameters were compared by the Student t test, Mann-Whitney or Chi-Square tests. Missing data for subjects who terminated early were imputed using multiple imputations by regression method. A P value < 0.05 was considered significant. SPSS (version 20.0) was used to perform analysis.The study was conducted between February 2013 and January 2014. Patients’ demographic and baseline characteristics were comparable between two groups of treatments as presented in P = 0.219).patients of 354 screened patients were enrolled in the study. The ITT population for the efficacy analysis consists of 51 patients receiving amitriptyline and 51 patients receiving capsaicin. 64 patients of a total of 102 completed the study with 62.7% compliance. A total of 38 (37.2%) patients discontinued therapy during the treatment period: 16 (31.3%) taking amitriptyline and 22 (43.1%) taking capsaicin (P = 0.545).Treatment responders (≥ 50% reduction from baseline on the VAS assessment)  in the IPain in the intention to treat population decreased with time as shown in Adverse events were more common in capsaicin group: 13 (25.5%) patients in amitriptyline group and 29 (56.9%) patients in capsaicin group (P = 0.001). Dermatologic complications were the most common reported adverse events. In the amitriptyline group skin dryness and then itching were the most common dermatologic adverse effects . The most common local side effects of capsaicin were itching, blister formation and erythema respectively .This randomized, double-blind and non-inferiority, 12-week trial demonstrates the comparable efficacy of amitriptyline cream in comparison with capsaicin cream in the management of pain due to peripheral neuropathy in type 2 diabetic patients. In addition to relieving pain, treatment with amitriptyline cream was also associated with less adverse events.A few studies evaluated the effect of topical amitriptyline in this field. A study by Kopsky described two cases of neuropathic pain of those treated effectively with topical amitriptyline 5% and 10% . In a raIn sum, this study demonstrates that amitriptyline is effective in managing diabetic neuropathic pain similar to capsaicin cream with less side effects and better patient compliance. Treatment with topical amitriptyline was safe and without significant side effects associated with systemic therapies. Further studies are required to confirm the efficacy and safety of topical amitriptyline as a treatment of PDN.


Data were collected at baseline and once a month. Outcome measures were pain intensity  and quality of life (the Roland-Morris Disability Questionnaire [RDQ] and Short Form SF-36 questionnaire [SF-36]).At baseline, the VAS, RDQ, and SF-36 scores showed similar levels between the groups. After 6 months, the AKA-H group had more improvement in the VAS (42.8% improvement) and RDQ score (31.1% improvement) than the sham group . The respective scores for the SF-36 subscales  were also significantly more improved in the AKA-H group than in the sham group . The scores for the physical, psychological, and social aspects of the SF-36 subscales showed similar improvement in the AKA-H group.The AKA-H method can be effective in managing chronic low back pain.UMIN000006250.UMIN Clinical Trials Registry (UMIN-CTR)  Chronic low back pain is one of the major causes of health problems. Of all people, 60–85% have low back pain at some time in their lives –4. One sVarious conservative treatments for low back pain have been developed worldwide, and there are several guidelines for treating low back pain in different countries and regions. The use of diagnostic triage for low back pain has been recommended to assess whether there is a specific spinal pathology or nerve root pain and to assess the prognostic factors in combination with the pathophysiology and psychosocial variables , 10. In The Arthrokinematic Approach-Hakata (AKA-H) method is a manual procedure for treating abnormalities of intra-articular movement of the synovial joint , and it guides movement on the joint surface . The AKAThe present study was performed to verify the effects of manual medicine for low back pain. The AKA-H method is not indicated for a specific disease but is indicated for joint dysfunction, arthrogenic pain, joint contractures, and neuromuscular retraining. Hakata et al. demonstrated the efficacy of the AKA-H method in the treatment of acute low back pain . HoweverThis clinical trial is registered in UMIN-CTR as R000007397, ID: UMIN000006250, and written informed consent . Patients were informed that they may receive the sham technique. Thus, it was promised that those who were randomized to the sham technique would subsequently receive the AKA-H method after completing the 6-month study. Patients who understood the aforementioned explanation, met the inclusion criteria, and agreed to participate in this randomized, controlled trial were consecutively enrolled. We recruited participants from August 30, 2011 and followed them until July 31, 2012.Low back pain was defined as pain localized from the twelfth rib to the inferior gluteal fold . NonspecThe inclusion criteria were as follows: 1) nonspecific low back pain lasting for at least the previous 6 months; 2) the patient received conservative orthopedic treatment from an orthopedic physician or another physician but had no improvement; and 3) the patient’s age was between 18 and 79 years. Patients who underwent surgery of the lumbar spine within the previous 6 months were excluded. In addition, it was assumed that oral medications were continued during the study.http://www.r-project.org), patients were randomly assigned to the AKA-H method (AKA-H group) or the sham technique (S group). The eligible patients were relatively uniform, and special consideration was not made for age, sex, or severity. Tasks were performed and confirmed by outpatient nurses who were independent of those who performed the treatment. Authors were not involved in the patient randomization. In addition, treatments were scheduled by appointment only to prevent information from being exchanged among patients. Also, all treatment was performed at the Saitama Prefectural Rehabilitation Center’s outpatient office.The protocol and CONSORT checklist for this trial are available as supporting information . Using aThe sham technique was chosen as the control to prove that the effectiveness of the AKA-H method was not just a placebo effect. Similarly, a comparison between acupuncture and the sham technique was conducted to prove its efficacy by Vickers et al. .This study was a parallel group comparison in which the AKA-H group and S group were compared for 6 months. The study was randomized at the level of the individual patient, and it was a single-blind test in which only patients were blinded to the details. The advantage of this single-blind study is that by blinding participants, researchers are more likely to avoid potentially biased responses. The disadvantage of this single-blind study is that an experimenter risks consciously or subconsciously affecting subjects’ responses. The study flow chart is depicted in Interventions were only conducted by the first author, a physician certified as a qualified preceptor by the Japan Medical Society of the Arthrokinematic Approach. Patients were randomized to receive the AKA-H method or sham technique. The AKA-H method was applied once a month for 6 months to the sacroiliac joint for treatment of low back pain using the following techniques: 1) upward gliding, 2) downward gliding, 3) superior distraction, and 4) inferior distraction .Patients were asked to lie on his/her side with the upside being treated, and the therapist stood in front of the patient. In upward gliding, the left index finger was placed on the S1 spinous tubercle, and the proximal phalanx of the right thumb was placed on the highest position of the iliac crest with palmar abduction of the right thumb. The right ring finger glided from the caudal side with the radial side of the ring finger pressed hard on the posterior superior iliac spine, pushing into the cranial direction, and when movement of the sacroiliac joint was felt, the S1 spinous tubercle was pushed in the cranial ventral direction using the left index finger. In downward gliding, the same procedure for upward gliding was performed until movement of the sacroiliac joint was felt. Then the S3 spinous tubercle was pushed in the caudal direction using the left index finger. In superior distraction, the left thumb was lightly placed on the S1 spinous tubercle, and the proximal phalanx of the right thumb was placed on the highest position of the iliac crest with palmar abduction of the right thumb. Next, the distal phalanx of the right ring finger was placed on the posterior superior iliac spine, the position was shifted about 1 cm to the cranial side, and from there, the hand slid in the caudal direction. When the proximal phalanx of the thumb hit the iliac crest and the ulnar side of the ring finger hit the posterior superior iliac spine, the fingertips were pressed down hard to stop the sliding. Then the force was applied to either the right ring finger or the thumb to pull the ilium in the longitudinal direction of the therapist’s right forearm. In inferior distraction, the right thumb was lightly placed on the S3 spinous tubercle, the left thumb was placed on the anterior superior iliac spine with palmar abduction, and the left ring finger was placed on the posterior superior iliac spine. The position of the left hand was shifted about 1 cm to the caudal side, and from there, the left hand slid in the cranial direction. When the radial side of the distal phalanx of the left thumb hit the anterior superior iliac spine and the ulnar side of the distal phalanx of the left ring finger hit the posterior superior iliac spine, the fingertips were pressed down hard to stop the sliding. Then the force was applied to either the left thumb or the ring finger to pull the ilium in the longitudinal direction of the therapist’s left forearm.During the sham technique, the patient was in the side-lying position with both hips and knees extended (each joint was close-packed), and the therapist stood on the ventral side of the patient. The therapist’s thumb, on the cephalic side of the patient, was placed on the S1 spinous tubercle, giving a light downward force while the index finger of the therapist’s other hand was placed underneath the S1 spinous tubercle to counteract the downward force; thus, the sacroiliac joint did not actually move. The same procedure was performed in which the therapist’s thumb, on the caudal side of the patient, was placed on the S3 spinous tubercle with the index finger of the therapist’s other hand underneath it. This procedure was slowly repeated twice with the procedure on S1 first, followed by S3, alternately. Because AKA-H is manual therapy for gently and slightly moving the sacroiliac joint, a warm-up is not necessary. Both techniques took about 15–20 minutes to complete.Outcomes were assessed using the visual analogue scale (VAS) , JapanesPatients were also asked to complete the RDQ and SF-36 in the waiting room prior to each treatment. The nurse checked for any omissions, and if descriptions were missing, patients were required to complete their answers.The RDQ is a scale that allows patients to assess their degree of disability experienced during daily activities due to low back pain. Since it is generally difficult to compare the RDQ by using raw scores, a comparison was made using the deviation score method with reference to the mean values by age and sex in Japanese individuals –44. The In the deviation score method, the mean score was set at 50 points, and the standard deviation was set at 10. Therefore, it was easy to determine where the RDQ score of a patient was in the distribution of the RDQ scores for the entire patient population. This was the advantage of this method –31.The SF-36 questionnaire is frequently used to evaluate one’s general quality of life (QOL) –36. Thisα of 5% and power of 80%. Assuming a dropout of <10%, we set the total sample size to 186 participants.Considering changes in the VAS score (as a main outcome) in the AKA-H  and S groups (the independent control arm), differences in the VAS score between groups was 10 (mean level) with a standard deviation of 23 (based on our preliminary experience). Therefore, we needed to recruit 84 participants in each group with an Data are presented as mean ± standard deviation. Differences between data at baseline between groups were analyzed using the unpaired t and chi-square tests. Since rare dropout cases (3 in AKA-H group and 4 in Sham group) existed and most cases did not dropout easily, missing data were analyzed by applying the list-wise case deletion method. Additionally, last observation carried forward was performed . A two-wAmong 246 eligible patients with low back pain, 210 attended the admission interview between August 30, 2011 and July 31, 2012. Of 210 patients, 24 did not consent to randomization and declined to participate in the study after the first visit to our outpatient office. Therefore, 186 patients agreed to participate in this study.There were 3 dropouts in the AKA-H group . In the sham group, there were 4 dropouts . Therefore, the analysis was done with 90 research participants from the AKA-H group and 89 from the sham group, totaling 179 patients.Mean age of 179 subjects was 59.8 ± 13.1 years. The majority were women (62.0%), and we used Asian BMI classification to represent patients’ degree of obesity . Mean duRegarding outcomes every month after starting treatment, there were no significant differences in the VAS score between groups for the first 2 months. However, from the third month, the VAS score was significantly reduced in the AKA-H group compared to the sham group , Fig 3.Two questionnaires also provided evidence for the efficiency of the AKA-H method in the treatment of low back pain. The RDQ (deviation score) scores were significantly higher in the AKA-H group than in the sham group from the fourth month . The SF-Side effects such as low back pain and muscle weakness were reported by 8 patients in the AKA-H group and by 10 in the S group. However, symptoms were mild in all patients. These side effects improved within 2–3 days post-treatment, and patients continued participation .The present study found that the AKA-H method improved pain intensity and the QOL in patients with chronic nonspecific low back pain to a greater degree than the sham technique during a 6-month period. Until recently, there has been little evidence on the efficacy of this treatment, although the AKA-H method has been used for treating low back pain in Japan and the Japanese Medical Society of Arthrokinematic Approach is acknowledged as a member of the International Federation for Manual/Musculoskeletal Medicine . Since mThere are many conservative treatments for chronic nonspecific low back pain such as pharmacological treatments –49, cognAlternatively, an additional study reported that a significant improvement was seen in the group of patients who practiced an exercise program such as increasing muscle strength and stretching as instructed by medical staff at an outpatient clinic, compared to the group treated with non-steroidal anti-inflammatory drugs (NSAIDs) . This stAccording to the European guidelines for the management of chronic nonspecific low back pain, cognitive-behavioral treatment, multidisciplinary interventions, noradrenergic or noradrenergic-serotonergic antidepressants, muscle relaxants, NSAIDs, and weak opioids are recommended as treatments . GuideliThere are at least 11 international guidelines for low back pain, and most have similar statements regarding the recommended treatments, although there are some differences regarding exercise therapy, spinal manipulation, and the use of muscle relaxants ,73. ThisFrom the results of the present study, the AKA-H method can be a useful tool for treating chronic low back pain. In addition, there were no specific side effects associated with the AKA-H method. The occurrence rates of the side effects were at least similar to that of the sham technique. Our findings further indicate the usefulness of administration of the AKA-H method in the clinical setting.The underlying mechanism of the efficacy of the AKA-H method for low back pain remains unclear in our study. We know that the possibility of impairment to the intra-articular movements, which is referred to as joint dysfunction , has somAs for the effectiveness of a labor-intensive (1:1) approach such as the AKA-H method for chronic low back pain, an asymmetrical relationship can occur, in which the doctor is the provider and the patient is the dependent, and this may result in a sick-role dependency. This seems to be similar to the condition of acute low back pain. Even when using the RCT methodology, it is necessary to be aware of drawbacks such as this. However, although there is a lack of detailed description in the methods, the effectiveness of AKA-H for patients with acute low back pain is suggested in this same way as in the present research. The same type of treatment may be effective for patients with acute and chronic pain, and this can be considered an advantage of this approach.Our study has limitations. First, the doctor was not blinded to the treatment, which was impossible to accomplish in this study. Second, this study was performed at only one hospital in Japan, and we did not invite the public to participate. Generalization of the results is limited; therefore, collaborative research at multiple centers should be conducted in the future. With regard to the statistical analyses, there is a possibility that better results could have been obtained if a third group  was added for comparison between groups. However, participants of this study were patients who had already suffered from chronic low back pain for a long period with no effect from common treatment methods. Additionally, randomizing individuals to a group that would receive no treatment or only the common treatment would discourage participation. Third, most patients (62%) were women, but in this study, the results were not assessed according to sex differences. Women have been reported to note pain more emphatically than men , and a pAlthough there are many limitations, the present study found that the AKA-H method significantly improved pain intensity and the QOL in patients with chronic nonspecific low back pain during a 6-month period. This suggests that the AKA-H method can be effective in managing chronic low back pain.S1 CONSORT Checklist(PDF)Click here for additional data file.S1 Consent Form(PDF)Click here for additional data file.S2 Consent Form(PDF)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.S1 Protocol(DOCX)Click here for additional data file.S2 Protocol(DOCX)Click here for additional data file.S1 TableData are shown as mean ± standard deviation. VAS, visual analogue scale; RDQ, Roland-Morris Disability Questionnaire; SF-36, 36-Item Short-Form Health Survey; AKA-H, Arthrokinematic approach Hakata method. Significant difference : * P < 0.05, ** P < 0.01. The AKA-H vs. sham group using Bonferroni multicomparison tests, † P < 0.008, †† P < 0.0016.(DOCX)Click here for additional data file.


The control of postoperative pain is important in children, and poor pain control leads to organ dysfunction and behavioral problems.We compared the analgesic effects of suppository acetaminophen, bupivacaine wound infiltration, and caudal block with bupivacaine on postoperative pain in pediatric inguinal herniorrhaphy.P < 0.05 was considered significant.In this double-blinded, randomized controlled clinical trial, 90 children of American Society of Anesthesiologists (ASA) grade I-II, aged between 3 months and 7 years, and scheduled for elective unilateral inguinal herniorrhaphy under general anesthesia were assigned to three equal groups. Patients in the first group received 20 mg/kg of suppository acetaminophen. In the second group, 2 mg/kg of 0.5% bupivacaine was infiltrated in the incisional site, and in the third group, a caudal block was performed with 0.75 mL/kg of 0.25% bupivacaine. The Face, Legs, Activity, Cry, Consolability (FLACC) pain scale was applied 30 minutes after operation. Thereafter, the FLACC score was obtained every hour during the next 6 hours. If the FLACC score was 4 or over, we administered 0.5 mg/kg of intravenous meperidine. The data was transferred to SPSS-10 software and analyzed statistically with chi-square and analysis of variance tests. P = 0.9), but the differences between the bupivacaine infiltration and acetaminophen groups (P = 0.034) and the caudal block and acetaminophen groups (P = 0.039) were significant. With regard to meperidine administration, significant differences were not observed between the bupivacaine infiltration and caudal block groups (P = 0.848), but significant differences were observed between these two groups and the acetaminophen group (P < 0.05).The mean analgesic duration in the acetaminophen, bupivacaine infiltration, and caudal block groups was 4.07, 5.40, and 5.37 hours, respectively. Significant differences were not observed between the bupivacaine infiltration and caudal block groups (Patients in the bupivacaine infiltration and caudal block groups had less postoperative pain than those in the acetaminophen group and received lower amount of meperidine. We concluded that in children, bupivacaine infiltration and caudal block with bupivacaine produce better analgesia than suppository acetaminophen. It seems that bupivacaine infiltration is better than caudal block because of its simplicity, lower incidence of complications, and failure rate. Individual variations in the response to pain are influenced by the genetic makeup, cultural background, age, and gender. Certain patient populations are at risk of inadequate pain control and require special attention, including pediatric patients, geriatric patients, and patients with difficulty in communication .Pain may trigger biochemical and physiologic stress responses and leads to impairments in pulmonary, cardiovascular, neuroendocrinal, gastrointestinal, immunological, and metabolic function even in children and newborns , 3. EffeIn pediatrics, acute postoperative pain is commonly treated with simple analgesics that often are not very effective and frequently are used at doses lower than would be optimal .Several routes of drug administration are available for pediatric patients. Oral and rectal routes are the most commonly used. Additionally, epidural and peripheral nerve blocks, wound infiltration of local anesthetics, and sublingual or transmucosal drug administration can be used for pediatric postoperative pain management. Intramuscular administration should be avoided, not only because of pain and the psychological impact but because of unpredictable drug absorption and the timing of the clinical effect –9.The benefits of regional analgesia for children include safety and efficacy with a lack of increased risk when compared with general anesthesia alone. For use in children, local anesthetics should have a low risk of systemic toxicity. Motor block is a frightening experience for young children who do not understand the reason for this event, and it is therefore better to separate the sensory and motor block as much as possible –9.We compared three different methods for pediatric postoperative pain management including suppository acetaminophen, caudal block with bupivacaine, and bupivacaine wound infiltration.This study was performed after receiving permission from the institution’s human subjects committee as well as informed consent from the participants’ parents. In this randomized, double-blinded, controlled clinical trial, 90 children between the ages of 3 months and 7 years, ASA I–II, who were scheduled for elective unilateral inguinal herniorrhaphy were assigned to three equal groups (by using colored cards). Patients with a positive history of anticonvulsive, opioid, analgesic, sedative, corticosteroid, and nonsteroidal anti-inflammatory drug consumption were excluded from this study. For premedication, 0.02 mg/kg midazolam, 1 μg/kg fentanyl, and 0.02 mg/kg atropine were administered intravenously to all patients. The patients also received 5 mg/kg sodium thiopental and 0.5 mg/kg atracurium intravenously for induction of anesthesia and isoflurane (1%) with O2 and N2O (50%–50%) during the maintenance of anesthesia.For postoperative analgesia, one group received suppository acetaminophen (20 mg/kg). Because of the average time of operation (30–45 minutes) and the delayed onset of the action of suppository acetaminophen (30–60 minutes), the acetaminophen was administered before premedication. In the second group, bupivacaine 0.5% (2 mg/kg) was infiltrated in the wound by the surgeon, and in the third group, a single-shot caudal block with bupivacaine 0.25% (0.75 mL/kg) was performed by the anesthesia provider at the end of surgery. Because the caudal blocks in children were performed while the child was anesthetized, it was not possible to assess the effectiveness of the block by testing for sensory analgesia levels. Thus, we predicted the success of caudal block from the laxity of the anal sphincter secondary to the reduction in sphincter tone from the local anesthetic block.Initially, 30 minutes after operation in the recovery room and then every hour during the next 6 hours of postoperative period, the FLACC pain scale was applied by one trained researcher who was not aware of the methods of analgesia.Table 1).The FLACC pain scaling system is a behavioral pain assessment scale that is used to assess pain for children between the ages of 2–7 years or individuals that are unable to communicate their pain. The scale has five criteria, and each is assigned a score of 0, 1, or 2. The FLACC is scored in a range of 0–10, with 0 representing no pain, relaxed and comfortable; 1–3: mild discomfort; 4–6: moderate pain; 7–10: severe discomfort or pain or both .The study groups were comparable with respect to age, sex and weight (Table 3).Significant differences between the bupivacaine infiltration group and caudal block group were not observed with regard to the duration of postoperative analgesia (FLACC < 4), but there were significant statistical differences between these two groups and the acetaminophen group (Eleven patients in the acetaminophen group (36.7%), four patients in the bupivacaine infiltration group (13.3%), and four patients in the caudal block group (13.3%) had a FLACC score ≥ 4, and they received 0.5 mg/kg intravenous meperidine for postoperative pain treatment. The mean and standard deviation of the amount of meperidine administered in the acetaminophen group, the bupivacaine infiltration group, and the caudal block group was 2.5 ± 0.97 mg, 0.66 ± 0.11 mg, and 0.83 ± 0.13 mg, respectively.P = 0.848), but significant statistical differences were observed between these two groups and the acetaminophen (P < 0.05).With regard to meperidine administration, significant differences were not observed between the bupivacaine infiltration and caudal block groups .During most of the study, patients in the acetaminophen group had higher FLACC scores than those in the bupivacaine infiltration and caudal block groups. The mean FLACC score of these two groups was approximately 2 or less in the first five hours of the study. The mean FLACC score in the acetaminophen group increased significantly during the first 2 hours of the postoperative period and decreased after meperidine administration in some patients. During the last hour of the study, the FLACC score increased again in this group  were noted in the three study groups.Pain is a subjective symptom that can be difficult to evaluate with regard to intensity, duration, tolerance, and threshold in pediatrics. Postoperative pain is a subjective symptom that has been extensively studied in adults but only minimally in children. The use of low analgesic doses and failure to document the pain and its management are common concerns in pediatric patients .There is an incorrect assumption that young children do not have well-developed pain pathways and therefore do not require as much analgesia as older patients. In young children who are unable to express pain verbally, crying is sometimes attributed to the mothers’ absence, hunger, or the unfamiliar hospital environment rather than pain , 11, 12.Thus, it is now widely accepted that infants and children require appropriate pain relief in the post-operative period. Postoperative pain management not only minimizes patient suffering but also can reduce morbidity and facilitate rapid recovery and early discharge from hospital, which can reduce hospital costs .et al. demonstrated that the addition of clonidine did not enhance the postoperative analgesia of a caudal block using 0.125% bupivacaine and epinephrine and did not significantly decrease the overall need for rescue analgesics in children aged 2–8 years and undergoing surgical procedures below the umbilicus (Some studies have evaluated which analgesic technique is ideal to use during the postoperative period for pediatric surgeries. Wheeler mbilicus .In another study in Australia, caudal analgesia, landmark-based penile block and penile block under ultrasonography were compared for circumcision in children, and it was demonstrated that caudal block and penile block under ultrasonography resulted in a longer duration of postoperative analgesia .In the other study, the postoperative analgesic effect of suppository paracetamol was compared with the combination of suppository paracetamol and bupivacaine wound infiltration for inguinal herniorrhaphy. The combination of these two methods produced better analgesia than suppository paracetamol alone .Razavi and colleagues compared suppository acetaminophen and caudal anesthesia in relieving pain after pediatric surgery and concluded that caudal block was more effective than suppository acetaminophen .The purpose of our study was to compare the effects of suppository acetaminophen, bupivacaine wound infiltration, and caudal block with bupivacaine on postoperative pain in pediatric inguinal herniorrhaphy. In this study, there was no significant statistical difference among the three groups with regard to age, sex, and weight. From this study, we can infer that bupivacaine wound infiltration and caudal block with bupivacaine provide a similar postoperative analgesic effect. They are also more effective than suppository acetaminophen for controlling pediatric postoperative pain.In conclusion, the performance of caudal block requires experience and may lead to complications, and block failure is not unusual. In contrast, wound infiltration is simple without significant side effects or failure. Thus, bupivacaine wound infiltration may be a preferred technique for producing postoperative analgesia in pediatric inguinal herniorrhaphy.