Repeated pain during haemodialysis access cannulations is a serious problem for haemodialysis patients even when prescribed oral or topical analgesics. Although some studies have observed the efficacy of music therapy for improving pain and anxiety, its effectiveness during haemodialysis access cannulations during dialysis is uncertain. The purpose of this study is to investigate the effects of music therapy for pain when cannulating haemodialysis access for haemodialysis patients.A prospective, multi-facility, single-blind, crossover, randomised controlled trial will be implemented. The intervention includes listening to Mozart, along with a white noise control condition. One hundred twenty haemodialysis patients will be enrolled across five facilities. Patients will be randomly allocated to either an Early-sequence group or a Later-sequence group. The Early-sequence group will receive cannulation while listening to Mozart’s Sonata for two pianos in D major (K.448) during the second week (Music period) and white noise during the fourth week (White noise period). The Later-sequence group will receive cannulation along with white noise first, followed by Mozart. All patients will also undergo cannulation during a no-sound period (wearing only headphones) during the first and third week (No-sound period). The music or no-music protocol will begin 8 min prior to the cannulating procedure, and participants will finish listening after starting haemodialysis during each period. The primary outcomes that will be assessed include the Visual Analogue Scale (VAS) score for pain during cannulation, and secondary outcomes are blood pressure, heart rate, VAS anxiety score, State-Trait Anxiety Inventory score, and salivary amylase activity. The operators who are in charge of haemodialysis access cannulation will be blind to the listening condition and VAS report.The proposed study has several methodological benefits. First, using white noise is a suitable control condition for addressing the role of sound in pain management. Additionally, using a crossover design with repeated measurements can help control individual differences between participants, which should better distinguish between- and within-participant variability. Overall, music therapy is a safe and inexpensive intervention that does not have the problematic side effects typically associated with pharmacological treatment. If effective, music therapy can be easily implemented for reducing pain and anxiety during cannulation.000032850).This trial was prospectively registered to UMIN Clinical Trials Registry on 1 July 2018 (UMIN  When kidney disease reaches its end stage, most patients undergo haemodialysis at least three times per week for life support. At the beginning of each session, two cannulations are required to be made. One is for removing blood from patients’ haemodialysis access, and the other is for returning blood to it. As such, patients often experience a significant amount of pain. This pain can be particularly problematic, especially given that many haemodialysis patients often undergo this procedure at least 150 times in a year . AlthougGiven the aforementioned limitations of pharmacological treatment, the present study advocates the use of music therapy for pain management. Music therapy is safe and inexpensive and has been shown to improve pain and anxiety associated with several diseases –29. In tThe proposed study is a crossover, randomised controlled trial investigating the effectiveness of music therapy on pain during haemodialysis access cannulations administered to haemodialysis patients. Many previous studies assessing the effectiveness of music used only a no-sound control group , which cOur main purpose for this trial is to clarify whether music therapy can truly alleviate pain, measured using a VAS metric, during cannulation into a haemodialysis access point, as compared with white noise. This protocol has been reported according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines 2013  during the first (run-in) week (No-sound period), listen to music during the second week (music period), listen to no-sound during the third (washout) week (No-sound period), and listen to white noise during the fourth week (White noise period). For the Later-sequence group, the no-sound period commences in the first (run-in) week, white noise during the second week, no-sound during the third (washout) week, and music during the fourth week.This trial will be performed at five outpatient maintenance haemodialysis facilities: Jisyukai Ueda Kidney Clinic , Nagasaki Renal Center , Fujiidera Keijinkai Clinic , Mihama Narita Clinic , and Hakuyu Chiyoda Clinic . The staff in all facilities will receive training on the trial method and protocol.Across the five facilities, patients over the age of 20 years who are undergoing outpatient haemodialysis three times a week, who have received dialysis for more than 6 months, and who indicated experiencing pain during cannulation based on a prior questionnaire will be enrolled. To evaluate the patients’ pain status, we will not adopt the VAS but rather a simple categorical scale questionnaire that will enable us to exclude patients who do not experience any pain (with a VAS of 0 mm) throughout the week of the intervention. The questionnaire is as follows:Q-1) Do you feel pain when your haemodialysis access is cannulated?Answer) A. Always; B. Sometimes; C. Never.Q-2) Please answer Q-2 if you answered B on Q-1. About how often do you feel pain?Answer) A. Once a week or more; B. Less than once a week.Patients who answer A on Q-1, B on Q-1, and A on Q-2 are considered to have experienced pain and are eligible to participate. The use of analgesics is allowed throughout this trial.The exclusion criteria are as follows: not willing to participate; having a hearing, writing, or visual impairment; being paralysed; facing a difficulty communicating; having a psychiatric disorder or dementia; undergoing haemodialysis therapy fewer than three times per week; and receiving dialysis through an indwelling catheter.The intervention for this protocol is referred to as ‘listening to sound’. The protocol will be performed while the patient is on a bed. The patient wears headphones  connected to a tablet PC . The sound will be provided by the Research Electronic Data Capture (REDCap) system  on a tablet PC. When the intervention is started, the participant will adjust the volume on the tablet PC screen. To reduce noise other than the sound from the headphones, we will use a noise-cancelling function. The specific intervention is outlined below Fig. .Fig. 2SFor this condition, patients will listen to music during cannulation. Mozart’s Sonata for two pianos in D major (K.448), which has been verified as the ‘Mozart effect’ in several studies –46, willhttps://www.youtube.com/watch?v=_CMzWGteDCY.) White noise has no orderly arrangement regarding melody, harmony, rhythm, tone or pitch, which is required for a sound to be considered musical [During the white-noise period, the patient will listen to white noise during cannulation . White n musical , 51. WhiThe no-sound period includes attaching headphones with no sound present. Outer noise is still cancelled out by the headphones . This inFigure Figure Baseline information—including age, gender, height, weight, duration of haemodialysis, history of smoking, medication, type and location of blood access, cause of kidney dysfunction, history of diseases  and musThe STAI is a commonly used measure to assess trait and state anxiety –56. The Conditional information regarding the cannulation will also be collected. This includes planned removal of water volume, weather , usThe primary outcome is the VAS pain score during the cannulation. The VAS comprises a 100-mm line. The leftmost value is 0, which indicates no pain. The rightmost value is 100, which indicates maximum pain. Patients mark a point with their finger on the screen . AlthougThe secondary outcomes include BP, HR, VAS anxiety score , STAI  and S-AMY .BP and HR will be measured immediately after putting on the headphones and after the puncture procedure (once each time) via an electronic sphygmomanometer attached to the dialysis console. Each patient will be measured in the same posture (sitting up or supine) throughout the procedure.Anxiety will be assessed via VAS on a tablet PC just after starting haemodialysis. The anxiety scale is in the same format as the pain scale and will be completed in the same manner .Patients’ state anxiety via the STAI (Y-1) will be assessed immediately after the puncture during the No-sound period, Music period, and White noise period, respectively.S-AMY fluctuates on the basis of autonomic nervous system activity, thus making it a reliable and objective marker of mental and physical stress –64. WithS-AMY levels will be evaluated prior to and after the cannulation at the end of the No-sound period, Music period, and White noise period, respectively. After each intervention period, adverse events will be assessed.As cannulations are a regular procedure in a haemodialysis session and listening to sounds is not a major invasive procedure, there is no expected harm for patients to participate in this intervention, as no negative effects of music therapy have been reported in prior studies. The saliva collection method is also harmless. Nevertheless, participant safety will be ensured during the protocol.We conducted a pilot two-arm randomised controlled trial at four facilities, whereby eight haemodialysis patients were assigned randomly into either of the two groups: Group 1 listened to Mozart, and Group 2 listened to the news on the radio. The primary outcome was cannulation pain evaluated via a VAS. A previous review suggested that patients who record a baseline VAS score of more than 30 mm might indicate at least moderate pain . Moura aHaemodialysis patients who meet all inclusion criteria and do not meet any of the exclusion criteria will be randomly assigned to the Early-sequence group or the Later-sequence group during the enrolment period (HD1). The permuted block randomisation will be performed by using REDCap , 54. OnlWe will explain to the patients that the first period and third period are no-sound periods and that the second period and the fourth period are sound-listening periods (music or white noise) when we are obtaining informed consent. Operators will also receive these explanations in advance; moreover, during the no-sound period, they will be informed that it is a no-sound period on the tablet’s screen. The reason for such an explanation is to prevent patients from mistakenly believing it is a no-sound period if equipment malfunctions or if the volume of the sound is too low in the initial setting. Of course, patients and operators will not know in advance the results of allocation  to maintain study blindness.Blinding participants to the allocation and evaluation of the VAS and STAI scores is not possible, as patients will be aware of what they will be hearing and the specific evaluations conducted. However, if participants are told that the purpose of this study is to assess the effectiveness of the music therapy, a demand characteristic, which refers to participants playing the role of a ‘good participant’ by altering their behaviour in order to obtain the researchers’ expected outcome, could emerge, resulting in information bias , 69. ThuAs the patients will not be blinded to the treatment allocation, it is important that the person evaluating the outcome measure of VAS be blinded to the study. Although the outcome evaluator needs to also perform the randomisation, we created an automated process in REDCap to randomly choose and play either the music or the white noise without letting the study personnel know which sound is being played. Along with randomisation, they will be blinded to the music operation and evaluation procedures to measure the VAS as follows. The operator will dispense the sounds from REDCap; however, the REDCap screen will not indicate whether music or white noise is being played. Participants will wear a headset while the music or white noise is being played, and they will be instructed not to tell the study personnel what sound is being played. The patients will provide VAS and STAI scores via an online questionnaire via REDCap. Therefore, the operator will not see these results. Each haemodialysis facility will have designated staff with access to the REDCap and enter the data.A software toolset and workflow methodology for electronic data collection and management (REDCap) will be used. REDCap servers are managed by Osaka City University using cloud servers. All web-based information transmission will be encrypted. All protocols, consent forms, and data will be stored in the REDCap system. Data monitoring will be performed by an independent data coordinating centre. Two independent statisticians will be able to access the trial dataset.A set of outcome variables, which includes the VAS pain score as the primary outcome and the VAS anxiety score, STAI score, and S-AMY as the secondary outcomes, will be assessed during a single dialysis session. Each study period will last for a week including three dialyses. Patients will undergo two study periods; thus, each patient will be assessed for six sets of the outcome variables (three in the music period and other three in the white noise period).t test to compare the two means of three pain scores between the two periods. Paired Linear mixed model to compare the two means of the three pain scores between the groups. (The unit of observation is the same as 1.)Linear mixed model to compare the six pain scores between the two periods. A linear mixed model will be applied to compare the means of the three repeated outcome measures between the music and the white noise periods. For the outcome that accompanies the baseline measures, the mixed model will compare the mean of three repeated change scores between the two periods. Compound symmetry was used for variance-covariance to estimate dependency among the repeated measures. Two-sided significance level will be set at 0.05. The normality of the residuals will be confirmed via Q-Q plots, and the mathematical transformation of the outcome variable will be performed if necessary. The mixed-model approach was chosen on the basis of a Monte Carlo simulation study in order to compare the statistical power of three different analytical strategies, which include the following  will be used. FAS is obtained when participants are allocated to the Early-sequence or Later-sequence after eligibility, and VAS pain scores are available at one or more cannulations during the music or white noise conditions. Furthermore, a target group conforming to the implementation plan is defined as per protocol set (PPS). For PPS, when an observation is discontinued by stopping the protocol, the subsequent data are not used in the analysis. Analysis of primary and secondary outcomes is the main focus of FAS. We also will perform analyses targeting PPS so as to confirm the stability of the analytic outcomes.An independent data coordinating centre will monitor the input data by using the data log on REDCap, which records the input time and listening time.When a participant withdraws consent, we will discard all data gathered from the study initiation to the withdrawal date.Data collection for a participant will be discontinued, and data collected from the study initiation to the dropout are used in the analyses.* When the shunt is occluded and a vascular anastomosis is re-created surgically.* When the participant dies or is transferred to another hospital.* When the participant wishes to terminate his or her participation. If some patients drop out, no new patients will be enrolled, and the data will be analysed according to the intention-to-treat principle with use of the FAS cohort.Data collection will be interrupted. When the study resumption becomes possible, data collection will be resumed.* When a participant is hospitalised.* When the haemodialysis access is narrowed and a percutaneous transluminal angioplasty (PTA) is performed.* When the haemodialysis access is occluded and blood flow restarts via non-surgical treatment such as massage or PTA.* When study continuation is difficult because of unavoidable circumstances to participants.* When study continuation is difficult because of unavoidable circumstances to medical staff.As a mixed effect model allows for a robust analysis of missing data , we willRepeated pain during haemodialysis access cannulations is a common symptom reported by haemodialysis patients. Music therapy is a safe and inexpensive means for addressing these painful experiences. Music therapy has been effective at alleviating pain and anxiety in a variety of disease contexts –30, 33. The most important characteristic of this trial is the use of a white noise condition as a control comparison. Since several previous studies used a ‘no-sound’ condition as a control but did not address potential placebo effects of the music intervention , the effThe planned protocol comprises a crossover randomised controlled trial. VAS pain scores will serve as the primary outcome. Feelings regarding cannulation and the effect of music therapy are likely to differ greatly between individuals. If we were to use a parallel-group trial, there would be concerns that individual differences could mask the treatment effect. Hence, there is quite a bit of variability in past studies concerning the effect of music therapy on cannulation pain. With a crossover randomised controlled trial, it is possible to exclude the influence of individual differences –75; thusWe will also evaluate, as secondary outcomes, whether music therapy improves anxiety prior to cannulation and whether BP and HR change at the start of dialysis , 76–78. We will be using Mozart’s Sonata for two pianos in D major (K.448). This piece has been used in various studies assessing the effects of music therapy , 82–84. A few study limitations should be noted. First, participants cannot be made blind to their intervention allocation and some of the outcome measures. To address this issue, we will tell participants that both music and white noise are known to facilitate relaxation. Furthermore, all VAS assessments will be conducted without operator assistance. Therefore, all reports will be kept confidential. Second, this is a crossover randomised controlled trial and carry-over effects could occur. To minimise this possibility, we will implement a washout period (1 week) between the white noise and music periods. If carry-over effects emerge, we will use only data from the second week (HD5–7) for the analysis, as it is a randomised parallel-group design. The current sample size was computed on the basis of the single period data alone; thus, the estimated sample size would be sufficient for the period-specific analysis. Third, the proposed study will be somewhat protracted (no fewer than 4 weeks for each patient). Therefore, there is a risk of participant dropout, which could create a selection bias. We will try to alleviate dropout through monetary incentives for participation .The proposed protocol will include a multi-facility, operator-blind, crossover randomised controlled trial to examine whether music therapy successfully reduces cannulation pain for dialysis patients. If predicted results manifest, we should have evidence that patients’ cannulation phobia and pain experiences can be reduced through a safe and cost-effective treatment strategy.https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000037447). The first patient was enrolled on 22 August 2018. At the original submission of the protocol, we have completed our pilot study (UMIN000024754). So far, 102 participants have been randomly assigned. Patients are being recruited now and the recruitment was scheduled to be completed at the end of September 2019.This study received ethical approval from the chief ethics committee at Nagasaki University Hospital on 19 June 2018. This study was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR): UMIN 000032850 on 1 July 2018  2013 Checklist: recommended items to address in a clinical trial protocol and related documents.Additional file 2. Monte Carlo simulation study for selecting an optimal statistical test.


Background and objectives: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established.Method: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients.Result: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality . However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients .Conclusion: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain. The incidence of chronic kidney disease (CKD) is still increasing worldwide despite integrative care and timely referral . CKD patPatients with CKD often suffer from chronic pain ,4. For ePain was considered as an important symptom in CKD patients ,9. In ad2 [determined by the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation] in 2 separate measurements within an interval of 3 months [Pre-dialysis CKD patients who visited an outpatient clinic at the Nephrology Department of Chang Gung Memorial Hospital at Keelung from March 2006 to July 2007 were recruited for the study. Patients satisfying the following criteria were included in this study consecutively: age >18–<80 years and with stable CKD in the 3 months before the start of the study. CKD was defined as the presence of persistent proteinuria or a decreased estimated glomerular filtration rate (eGFR) of <90 mL/min per 1.73 m3 months . A totalThe study evaluated the association between chronic MS pain and renal prognosis in CKD patients. All eligible patients were carefully interviewed to identify primary disease and current medications. Chronic MS pain was evaluated by using the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) questionnaire . All eliFor patients with MS pain, pain was assessed using a visual analog scale (VAS), on a range of 0 mm (no pain) to 100 mm (very painful), after which the patients were examined by a rheumatologist to confirm the information and characterize MS pain symptoms. For the calculation of prevalence and for all other analyses, chronic MS pain was defined as non-traumatic MS pain for over 3 months with a VAS score of >1 .Basic demographic data were collected, including information on age, gender, nutrition status – body mass index (BMI), history of smoking, current use of NSAIDs or Chinese herbal medicines, and the presence of diabetes, hypertension, coronary artery disease (CAD), and hyperuricemia. Baseline hematological and biochemical data of these patients were also collected. Current use of NSAIDs was defined by self-reported use of ibuprofen, naproxen, sulindac, piroxicam, indomethacin, tolmetin, or diclofenac, COX (cyclooxygenase)-2 inhibitor (with brand names and combination formulas identified) daily or nearly every day for the last 30 days. Current use of Chinese herb was defined by self-reported use of any Chinese herb daily or nearly every day for the last 30 days. Full laboratory profiles were obtained. The laboratory parameters included levels of blood urea nitrogen, serum creatinine (Scr), hemoglobin, albumin, high-sensitivity C-reactive protein (hs-CRP), calcium (Ca) and phosphate (P). Serum creatinine levels were assessed by spectrophotometric analysis using a modified kinetic Jaffe reaction.t-test or the Mann–Whitney U-test was used to compare the means of continuous variables and the Chi-square test was used to compare categorical data. Kaplan–Meier curves were used to assess renal survival in patients. Adjusted risk estimates for progression to the endpoint were calculated using univariate regression, followed by multivariate Cox proportional hazard regression. Co-variants selection based on univariate analysis with variables with p < .05 was selected. All statistical tests were two-tailed, and a p value less than .05 was considered statistically significant. Data were analyzed using the SPSS 23.0 for Windows .Descriptive statistics are expressed as means ± standard deviations or as medians and ranges or percentages, as appropriate. Student’s 2. A total of 243 patients (53.3%) had chronic MS pain. At baseline, 36 patients (7.8%) reported the use of an NSAID and 44 patients (9.6%) reported the use of a Chinese herbal medicine. Those patients with male, higher BMI, co-morbidity of hyperuricemia, higher levels of systolic blood pressure, lower levels of proteinuria, higher serum levels of hemoglobin and product of serum calcium and phosphate levels, and less co-morbidity of diabetes-prone to associated with chronic MS pain. In our study patients, the prevalence of mild pain, moderate pain and severe pain are 15.6% (n = 38/243), 28.4% (n = 69/243) and 58% (n = 141/243), respectively. About the CKD stage and chronic MS pain severity, severe chronic MS pain was found in 54.2% (n = 64/118) of CKD patients with stage 1–2 disease, 54.9% (n = 62/113) of CKD patients with stage 3–4 disease and 83.3% (n = 10/12) of CKD patients with stage 5 disease (p < .001). About the cause of chronic MS pain, we found 71% of those chronic MS pain had co-morbidity of gout, 0.4% had co-morbidity of rheumatoid arthritis, 1.2% had co-morbidity of spine osteoarthritis, 19.8% had co-morbidity of back pain. In our study with follow-up of about 6 years, there were 13 patients drop out, 31 patients died, 36 patients initiated hemodialysis, 10 patients initiated peritoneal dialysis at the end of the study.The mean age was 63.3 ± 14.1 years and 194 patients (42.5%) were male . The meap = .857), use of NSAID , and use of a Chinese herbal medicine .A total of 82 patients (17.9%) experienced renal progression with a mean follow-up time of 44.6 ± 12.8 months. Among these 82 patients, 36 patients had eGFR less than 50% of baseline and 46 patients progressed to ESRD . Patientp < .001), hypertension , lower eGFR , low serum levels of hemoglobin , low serum levels of albumin , low serum levels of calcium , high serum levels of phosphate , high product of serum levels of calcium and phosphate , higher serum levels of uric acid , higher systolic blood pressure , higher levels of proteinuria  were significantly associated with renal progression (p = .984) (p = .446) (p < .001), low BMI , low levels of eGFR , high levels of hs-CRP , high levels of uric acid , low levels of diastolic blood pressure , higher levels of proteinuria  were significantly associated with all-cause mortality. But those CKD patients with chronic MS pain were not significantly associated with higher all-cause mortality  (p < .001), low eGFR , low serum levels of hemoglobin , low serum levels of albumin , high serum levels of hs-CRP , low serum levels of calcium , high serum levels of phosphate , high serum levels of uric acid , high levels of systolic blood pressure , low levels of diastolic blood pressure , and higher levels of proteinuria  were significantly associated with composite endpoints. Furthermore, those CKD patients with chronic MS pain were not significantly associated with composite endpoints   . The eGF = .446) . About a = .903) . In addi = .774) . In addip = .233) and composite endpoints  (p = .049) after adjustment of age, gender, co-morbidity of diabetes, hypertension, baseline eGFR, serum hemoglobin, albumin, hs-CRP, calcium, phosphate, Ca × P, and proteinuria. Besides, co-morbidity of diabetes mellitus  and proteinuria  were also significantly independently associated with renal progression. And proteinuria was independently significantly associated with composite endpoints . However, baseline NSAID or Chinese herbal medicine use was also not independently significantly associated with primary and composite endpoints. The study also showed increased uric acid level is significantly associated with renal progression, all-cause mortality, and composite endpoints . But the association between uric acid level and renal progression, all-cause mortality and composite endpoints  loss significance after adjustment in the multivariate cox-regression analysis.The analysis of multivariate Cox regression was also performed to evaluate the exact association between chronic MS pain and other factors, and primary and composite endpoints. The results indicated that the presence of chronic MS pain was not independently significantly associated with renal progression  . But theNumerous factors underlie the progression of CKD. The present study enrolled pre-dialysis CKD patients and evaluated the effect of chronic MS pain on CKD progression. The present study was a prospective follow-up study of patients and considered numerous measurable risk factors for CKD progression, including the presence of chronic MS pain, use of an NSAID, and use of a Chinese herbal medicine. The main results found that those patients with and without chronic MS pain had similar risk for CKD progression. But patients with chronic MS pain had independently significantly higher all-cause mortality than those patients without chronic MS pain. However, the inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.Our predialysis CKD patients had a high prevalence of chronic MS pain (53.3%) and our results indicate that male patients, high BMI, and co-morbidity of hyperuricemia, and a Ca × P imbalance were significantly associated with this symptom. However, we were surprised to find that patients with and without chronic MS pain used NSAIDs and Chinese herbal medicines at similar levels, had similar levels of inflammatory markers (hs-CRP), and had similar levels of serum albumin. Our long-term follow-up of about 6 years indicated that patients with chronic MS pain had similar risk of CKD progression as those without chronic MS pain. Pain and inflammation are nearly always associated with each other. Hyper-inflammation was associated with CKD progression ,18. The p values=.074). One study showed that chronic MS pain was prevalence in advanced CKD patients  [p values=.377). So, the result suggested that CKD stages and also advanced CKD were not associated with chronic MS pain. Caravaca et al. enrolled advanced CKD patients and found chronic MS pain was associated with higher inflammation and poor prognosis, but the association was not significant after adjustment of the demographic factor. In our study patients, we found chronic MS pain was significantly associated with all-cause mortality after adjustment. But we cannot find the association between chronic MS pain and inflammation. It may be due to chronic MS pain in some patients may not link to inflammation. Chronic MS pain caused by inflammation is more likely to be associated with advanced CKD patients. Due to the recruited patients, CKD with different stages and the number of our advanced CKD patients was not enough, we cannot find this association in our study patients.In this study, we found that CKD stages were not significantly different between chronic MS pain and no chronic MS pain  . BecauseThe focus of this study was to examine CKD patients with chronic MS pain and CKD progression. We found that those with chronic MS pain and baseline use of a NSAID or Chinese herbal medicine had similar risk of CKD progression as those without chronic MS pain and use of a NSAID or Chinese herbal medicine. Besides, the inflammatory marker-hs-CRP serum levels were similar between those CKD patients with and without chronic MS pain. Our study has some limitation. The use of NSAID and Chinese herb agents was based on a self-reported questionnaire and the prevalence of NSAID and Chinese herb use was not recorded during the follow-up period. Besides, we did not collect acute kidney injury outcome data. Also, we did not collect the information on opioid use. Opioid is related to proteinuria. Those patients with chronic MS pain may use opioid instead of NSAID or CHM for pain relief. Due to lacking information about opioid use, the study cannot conclude NSAIDs or Chinese herb agents do not associate with CKD progression. In addition, a sample size of NSAIDs or CHM user is too low to detect this association. However, our results found the presence of chronic MS pain was independently significantly associated with increased all-cause mortality.In summary, our study demonstrated that CKD patients with chronic MS pain were independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.


Background: Postoperative pain is defined as pain of any degree after initiation of endodontic treatment either intra-appointment or post-obturation and is considered an undesirable occurrence for both patient and dentist. It was suggested that bacterial injury is probably the major cause of pain. Intra-canal medicaments are widely used to kill any bacteria surviving after instrumentation and irrigation. The aim of this study was to assess the ability of double antibiotic paste versus calcium hydroxide used as intra-canal medication in reducing postoperative pain.Methods: 36 patients with single rooted necrotic premolars with apical periodontitis were randomly assigned into two groups according to the intra-canal medication used: calcium hydroxide group (CH) and double antibiotic paste group (DAP). Preoperative pain was recorded using numerical rating scale. After isolation, access cavity was performed followed by chemico-mechanical preparation using rotary Race files with 2.5% sodium hypochlorite irrigation. Subsequently, intra-canal medication was placed and postoperative pain was recorded at 6, 12, 24 and 48 hours postoperatively.Results: There was no statistically significant difference between both groups. Both groups resulted in an increase in median pain value from preoperative to 6 hours postoperative, followed by gradual decrease from 6 hours to 12, 24, 48 hours postoperatively with statistically significant difference. When comparing both groups, DAP group showed lower postoperative pain values than CH group at 12 and 24 hours, but this was not statistically significant.Conclusion: The use of intra-canal medication in necrotic teeth with apical periodontitis was efficient in reducing postoperative pain regardless of type of intra-canal medication used.Trial registration: PACTR201605001482394 (Date: 22nd February 2016). Post-endodontic pain remains a serious problem facing the dental profession. It may occur as a result of several factors, including chemical, mechanical or bacterial irritation to the periapical tissues2. It has been suggested that the presence of bacteria as a result of failure to properly disinfect the root canal is the major cause of pain3. Many studies have found a direct relationship between root canal infection and the level of pain after endodontic treatment4. Thus, endodontic treatment is primarily focused on utmost elimination of these bacteria. Antibacterial intra-canal medicaments have been advocated in efforts to kill any bacteria surviving after chemico-mechanical preparation.Pain is the main symptom in many medical and dental conditions that can significantly alter the person’s general functioning5. It has been suggested that calcium hydroxide has pain preventive characteristics due to its antibacterial action or tissue altering effects. Moreover, it controls inflammation and has repair potential6. However, there is no clear evidence of its effect on post-endodontic pain7. Other studies found that calcium hydroxide was not very effective in decreasing post-treatment pain when used alone9.Several intra-canal medications have been used, including calcium hydroxide which is the most widely used intra-canal medication. It is characterized by its initial bactericidal, bacteriostatic effect and its high pH10. When commonly used medicaments fail in eliminating the symptoms, then antibiotic paste can be used for treatment of teeth with large periapical lesions11.Double antibiotic paste is a mixture of metronidazole and ciprofloxacin, which is used as intra-canal medication for disinfection of necrotic teeth. It has been reported to be effective at reducing bacterial counts in the infected root canalsThe objectives of the present study were to test the null hypothesis of whether the use of double antibiotic paste will be more effective in reduction of pain than calcium hydroxide, or if this paste will have disadvantages and complaints more than the traditional method used.The article has been written in concordance with CONSORT guidelines .The study design is a parallel randomized controlled trial with allocation ratio 1:1 and a Superiority Framework. The study was conducted in the duration between March 2016 and March 2017. The protocol of this study was approved by the Ethics Committee of the Faculty of Oral and Dental Medicine, Cairo University, Egypt . The nature of this study, and associated risks were fully explained to the patients and informed consent forms were signed before initial treatment.et al. (2003), a medium effect size of approximately 0.25 is expected. A total sample size of 24 patients will be sufficient to detect an effect size of 0.25, a power of 80%, and a significance level of 5%. This number has been increased to a total sample size of 28, to adjust for using nonparametric tests. The number is again increased to a total sample size of 36 (18 in each of the two groups) to allow for losses of around 25%. Sample size was calculated using G*Power program . Minimal clinical difference 3.5 and 4.5 at 24 hrs and 48 hrs respectively.Based on a previous study by EhrmannIn total, 36 participants were included in the study with maxillary or mandibular non-vital single rooted premolar teeth showing tenderness to percussion.Exclusion criteria: pregnant women, patients who had received antibiotic treatment during the last 3 months, patients having more than one tooth requiring root canal treatment, teeth with periodontal probing depth >4mm, teeth that couldn't be isolated with a rubber dam, teeth with previous root canal treatment, or teeth with fluctuant facial swelling where emergency management should include incision and drainage.Patients were randomly assigned into two groups (n=18/group) according to the intra-canal medication used, using a computer generated random number table at the Center of Evidence-based Dentistry (EBD), Cairo University. The assistant supervisor generated the random sequence and assigned the participants to the intervention or control groups.Experimental group: double antibiotic paste (DAP); control group: calcium hydroxide paste (CH). All clinical procedures were performed by a single endodontist.All patients accepted two-visit root canal treatment. Preoperative pain was recorded before any intervention.First visit: Teeth were anaesthetized using nerve block or infiltration technique by local anesthesia  and properly isolated with rubber dam. After access cavity preparation, the working length was checked using apex locator and confirmed by a radiograph. The root canals were prepared using rotary Race files  along with 2.5% sodium hypochlorite irrigation. The canals were dried and filled with intra-canal medication plugged into the canal by using Lentulo spiral according to the randomly selected group . The access cavities were properly filled with glass ionomer to ensure proper sealing with no leakage of any oral fluids inside the root canal, which might disturb the action of the intra-canal medication.Patients were instructed to record their postoperative pain level (see below) after 6, 12, 24 and 48 hours.Second visit: After 7 days, all the patients returned the pain charts and the root canals were obturated using lateral condensation technique and resin-based root canal sealer.Primary outcome measure is postoperative pain.A pain chart using numerical rating scale (NRS) was used to record the patients’ pain level. The NRS  consists of a line anchored by two extremes “No pain” and “the worst pain”. Patients were asked to choose the mark that represented their level of pain from 0 to 10. Pain level was assigned as follow: 0, “no pain”; 1–3, “mild pain”; 4–6, “moderate pain”; 7-10, “severe pain”.The study was double-blinded (the participants and the assessor). Participants did not know which group they were treated with; they chose a folded paper inside an opaque envelope which contained the numbers of each random sequence for both groups. The assessor, who assessed all outcome data, did not know which group the participants were related to.Data was analyzed using IBM SPSS 21 . The level of pain was described as median and range. Pain score was compared between the two groups using Mann-Whitney U test. Friedman test was performed to test the significance between the 4-time periods within each group. Chi square test was used to compare qualitative pain score. The level of significance was set at P < 0.05. All tests were two tailed.In total, 36 patients were included in this study;The overall highest incidence of pain values in both groups was at 6 hours postoperatively, whereas the lowest incidence of pain values was at 48 hours postoperatively with no statistically significant difference between them. The DAP group showed lower postoperative pain values at 12 and 24 hours compared with the CH group, but with no statistical significance difference .Datasheet containing patients age, gender, and pain score for all time points for both the CH and DAP groupsClick here for additional data file.Copyright: © 2018 Samir Abouelenien S et al.2018Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).12. Necrotic pulp with periapical periodontitis was selected for assessment of postoperative pain, as the highest frequency of postoperative pain occurred in patients with necrotic pulp and apical periodontitis13 that harbored large number of bacteria due to its polymicobial nature as reported in previous studies18. In the present study, pain was recorded using a numerical rating scale (NRS), which is considered a consensus-based, standardized assessment method and reports better compliance compared to other scales19. The literature shows that the NRS provides sufficient distinctive power for chronic pain patients for describing their pain intensity20. As well, it was preferred by the majority of patients in different regions22. In the present study, the Rotary Race system was chosen for root canal preparation, owing to the fact that rotary NiTi instruments result in minimal debris extrusion compared to hand instrumentation23, which in turn would result in less postoperative pain. This was attributed to their rotary action, as well as copious irrigation associated with these instruments24.Effective control over the intra-canal microbial load before root canal obturation is a key element that increases the success rate of endodontic treatmentet al.25 reported no statistically significant difference in postoperative pain between calcium hydroxide and triple antibiotic paste (TAP), although TAP was more effective that calcium hydroxide but this was not statistically insignificant. As reported in other studies27, there was no statistically significant difference in postoperative pain between calcium hydroxide paste and no intra-canal medication. In contrast, some studies counteracted our findings29, suggesting that CH had pain-preventive properties because of its antimicrobial as well as its tissue-altering effects. These properties could be referred to the chemical, physical, and antimicrobial effects of calcium hydroxide due to the diffusion of its hydroxyl (OH−) ions produced from ionization in aqueous solution, which leads to a highly alkaline environment. This is not conducive for the survival of microorganisms inside root canals30, and most of the microorganisms cannot sustain that high a pH (15.5).In the present study, in patients with necrotic teeth with apical periodontitis, the use of double antibiotic paste showed no difference regarding postoperative pain compared to CH. DAP showed lesser postoperative pain at 12 and 24 hours than the CH group but this didn’t reach a level of statistical significance. This might be attributed to the combined spectrum of antimicrobial activity and synergetic or additive action of antibiotics found in DAP. In accordance with the results of this study, PaiThe use of intra-canal medication for 7 days in necrotic teeth with apical periodontitis was efficient in reducing postoperative pain regardless of the type of intra-canal medication used.The data referenced by this article are under copyright with the following copyright statement: Copyright: © 2018 Samir Abouelenien S et al.Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).https://doi.org/10.5256/f1000research.16820.d22435931F1000Research: Dataset 1. Datasheet containing patients age, gender, and pain score for all time points for both the CH and DAP groups., The objective of this study was to assess the ability of double antibiotic paste versus calcium hydroxide used as intra-canal medication in reducing postoperative pain. Post-operative pain is currently a relevant subject in the dental practice. Overall, the study was well written and designed. Additionally, it fits in a Randomized Control Trial, which increases the significance of the research. The results are well described, and no differences were observed between the groups; however, clinically, the antibiotic pastes present some disadvantages compared to calcium hydroxide. The sample size is adequate for this kind of research. I recommend the manuscript for indexing.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Approved: No changes are required.  The experimental design, including controls and methods, is adequate; results are presented accurately and the conclusions are justified and supported by the data.The research is clear and cites the current literature in the topic of post-operative pain after intra-canal medication.The data published and the supplemental data provided is sufficient and clear to allow replication The conclusion is sufficiently supported by the results but could omit the (7 days) to prevent confusion.This article addresses the links between intra-canal medication used and the post operative pain after endodontic treatment, as mentioned in the article, post operative pain is multifactorial, however the design of the experiment is adequate including experimental and control groups, the primary outcome was measured preoperatively and after 6, 12, 24 and 48 hours only, however in the conclusion its mentioned that the 7 days was sufficient for reducing the post-operative pain. . I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Chronic idiopathic axonal polyneuropathy (CIAP) is a term describing axonal neuropathies of insidious onset, with slow or no progression of the disease over at least 6 months and with no etiology being identified despite appropriate investigations. We aimed to establish the prevalence of pain in patients with CIAP and investigate the impact of pain on quality of life (QoL).All consecutive patients with CIAP attending a specialist neuropathy clinic were invited to participate. Pain was assessed via the DN4 questionnaire and the visual analogue scale (VAS). Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The SF‐36 questionnaire was used to measure participants’ quality of life.β = −0.259, p = 0.049), with the emotional well‐being domain  and the general health perception domain .Fifty‐five patients with CIAP were recruited . Based on the DN4 questionnaire, peripheral neuropathic pain was present in 33 patients (60.0%). After having adjusted for age, gender and disease severity pain showed significant negative correlations with the energy/fatigue domain of QoL (Pain is very prevalent in CIAP and is associated with poorer emotional well‐being, worse general health perception, and increased fatigue. For all studies, temperature was above 32°C for the upper extremity and above 31°C for the lower extremity. The temperature was measured before and after each study on the dorsum of the hand and the foot. Frequency filters were 2 Hz (low) and 2 kHz (high) for the sensory studies and 3 Hz (low) to 10 kHz (high) for the motor studies. SNAPs were measured as peak‐to‐peak, whereas CMAPs were measured as onset‐to‐peak.F‐wave latency above the upper limit of normal values; or (d) abnormal temporal dispersion (>30% negative‐peak CMAP duration increase) in two or more nerves.Based on the published normal values . The electrophysiological diagnosis of symmetrical sensorimotor axonal polyneuropathy was based on finding reduced distal sensory and/or motor amplitudes on nerve conduction studies and a distal to proximal gradient of re‐innervation or denervation on EMG Albers, . SensoryThe severity of neuropathy was assessed by the overall limitations neuropathy scale (ONLS), which is a validated scale that measures limitations in the everyday activities of the upper and lower limbs  ranging from 0  to 10 (worst pain you can imagine). Pain intensity was assessed for two time points: pain at recruitment and maximum peripheral pain experienced during the disease course. Only patients reporting pain intensity of equal to or greater than 4 at any point were considered to suffer from a painful neuropathy.The 36‐Item Short Form Survey (SF‐36), a self‐reported measure of health status and quality of life . Frequencies and descriptive statistics were examined for each variable. Comparisons between patients with painful CIAP and patients with painless CIAP were made using Student's p value of lower than 0.10 were found, these variables were entered into linear regression models, with the QoL domain score being the dependent variable. All accuracy and generalization assumptions for the model were checked.Where differences with a The level of statistical significance was set at the 0.05 level.33.1Fifty‐five patients with CIAP were recruited . Forty‐seven patients (85.5%) had a symmetrical length‐dependent sensorimotor axonal PN, and eight (14.5%) had a sensory ganglionopathy. Mean age at neuropathic symptoms’ onset was 63.1 ± 110.5 years (ranging from 25 to 85 years). Overall ONLS scores ranged from 1 to 7 (mean 3.3 ± 1.6).Eleven patients (20%) reported pain to be the first symptoms of the PN .Based on the DN4 questionnaire, and a VAS score of at least 4/10, neuropathic pain at any point was present in 33 patients (60.0%). Based on a VAS score of at least 4/10, pain was present on examination in 20 patients (36.4%), whereas the other 13 patients reported spontaneous neuropathic pain, occurring randomly during the day. The pain intensity on examination ranged from 0 to 10 (mean 4.1 ± 2.9), when the maximum pain experienced ranged from 5 to 10 (mean 8.6 ± 1.6).None of the 22 patients reporting no pain were on anti‐neuralgic treatment.3.2p = 0.024).Table p = 0.002), role limitations due to physical health (p = 0.009), energy/fatigue (p = 0.007), emotional well‐being (p = 0.001), general health (p = 0.002), and health change (p = 0.019), whereas there was a trend of statistically significant difference in the domain of social functioning (p = 0.056).As shown in Table 3.3β = −0.259, p = 0.049), emotional well‐being , and general health perception .Table 4This cross‐sectional study demonstrates that three out of five patients with CIAP suffer from peripheral neuropathic pain secondary to their neuropathy. Very importantly, presence of pain is correlated with worse quality of life in the energy/fatigue domain, the emotional well‐being domain, and the general health perception domain.Contrary to the common misperception that painful neuropathies are related to diabetes, our study strengthens the evidence that neuropathies of etiologies other than diabetes can be equally painful. The reported prevalence of pain in patients with diabetic PN, confirmed with NCS, is estimated to be 40%–50% Ware, . PreviouIn 2010, Erdmann et al. described a case series of ninety‐one patients with CIAP and they reported that the overall prevalence of pain in CIAP is 69%  had a sensory ganglionopathy, rather than a symmetrical length‐dependent neuropathy, whereas in Edmann's cohort all patients had a symmetrical sensorimotor neuropathy. The univariate analysis showed that presence of pain does not depend on the neurophysiological type of CIAP.In this study, we also described the QoL of patients with CIAP. In the univariate analysis, we found that patients with pain have significantly worse scores on all QoL domains apart from the domain of role limitations due to emotional problems  and the domain of social functioning . This observation differs to what has been reported by Erdmann et al. who found only significant correlations between pain and the physical functioning domain  is a PCORI initiative, through the University of Kansas, aiming to address this particular question; the results of this study (registration NCT02260388) are expected to be available in late 2018. Therefore, until then, the management of pain in CIAP should be based on the published guidelines for the management of neuropathic pain (Vadalouca et al., Our results should be interpreted with some caution, however, given the limitations of our design. This is a cross‐sectional observational study comparing CIAP patients with and without peripheral neuropathic pain based on patients attending a specialized clinic, and the results may not be generalizable to other settings. For example, in our study, we used the ONLS to determine the clinical severity of the neuropathy, whereas other departments use other scales. The independent role of pain in the overall QoL might differ if other tools are used, something that could be investigated in a future study. Furthermore, our cohort included patients with large fiber axonal peripheral neuropathies only. Idiopathic small fiber neuropathy is another area that merits further consideration, as it is a particularly painful condition. Finally, we were able to demonstrate that the presence of pain is an independent determinant of QoL after having adjusted for age, gender, and neuropathy clinical severity as this was assessed via the ONLS. The latter evaluates fine movements of the upper limbs and gait. Thus, primarily, it depends on the motor involvement secondary to neuropathy or can be abnormal in cases of severe sensory ataxia leading to gait impairment. Therefore, we have not adjusted for the presence of other sensory symptoms such as itchiness and tingling, though in our clinical practice patients rarely complain about how other sensory symptoms than pain affect their lives.In conclusion, pain is very prevalent in CIAP and significantly impacts on QoL. Optimum management of pain in such patients might prove beneficial in improving QoL. Future prospective studies are needed to explore further the relationship between pain and QoL.None.


Pain intensity was measured using VAS. After supplementation with vitamin D serum, the concentration of 25(OH)D3 significantly increased in the SUPL group (∗p < 0.005) and was significantly higher as compared to the PL group (∗p < 0.001). A significant reduction in pain intensity was observed 4 weeks after surgery and after rehabilitation in both groups. In the SUPL group, serum CRP and IL-6 concentration significantly decreased after rehabilitation, compared with the postsurgical level (ap < 0.04). The level of TNF-α was significantly lower after rehabilitation only in the supplemented group (∗p < 0.02). There were no significant changes in the IL-10 level in both groups during the study. Our data indicate that supplementation with vitamin D may reduce systemic inflammation and when combined with surgery and early postsurgical rehabilitation, it may decrease the intensity of pain in LBP patients undergoing PLIF. Data indicate that LBP patients undergoing spine surgery should use vitamin D perioperatively as a supplement.The aim of this experimental study was to assess whether 5 weeks of preoperative supplementation with vitamin D affects the intensity of pain and the level of inflammatory markers in patients undergoing posterior lumbar interbody fusion (PLIF) followed by rehabilitation. 42 patients were divided, by double-blind randomization, into two groups: supplemented (SUPL) vitamin D (3200 IU dose of vitamin D/day for 5 weeks) and placebo group (PL) treated with vegetable oil. The 10-week program of early rehabilitation (3 times a week) was initiated 4 weeks following PLIF. Measurements of serum 25(OH)D Musculoskeletal pain including low back pain (LBP) is very common, affecting from 10%  to 33%  of the g3 from 21 to 29 ng/mL (52.5–72.5 nmol/L) is insufficient and a level lower than 20 ng/mL (50 nmol/L) is considered as deficient Deficient . Sufficieficient . Vitamineficient  predomineficient . Moreoveeficient .The vitamin D receptor (VDR) has been identified in muscle tissue and could explain the association with muscle weakness and regional pain disorders such as low back pain . The pre2D3 effectively up-regulates the synthesis of the anti-inflammatory cytokine, interleukin 10 (IL-10) and induces IL-10 receptor expression in vitro , conformed with the Declaration of Helsinki, and was registered as a Clinical Trial NCT03417700. Written informed consent was obtained from the participants of this study. The study included patients aged 33–65 year qualified by a neurosurgeon for lumbar spine surgery utilizing static or dynamic implants . Qualification criteria for PLIF surgery included: classification procedures segmental instability, secondary to segmental spinal pathology, discopathy, permanent back pain in patients after non-surgical treatments without improving back pain, resulting in functional disability for at least 6 months, and no history of previous spinal surgery. The exclusion criteria were the following: patients beyond the age range, a previous lumbar spinal operation, spinal tumors, new fractures, an inability to follow the rehabilitation protocol, and a failure to perform daily activities due to comorbidities , and a missed follow-up visit. All the patients used perioperative antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), perfalgan, and tramadol for the same time duration. 39 out of 42 enrolled patients were included in the study, based on the qualification and exclusion criteria. 3 patients who resigned at the beginning of the study were excluded from further analyses. Three patients smoked and none of the qualified patients drank alcohol while the project was running. Fifteen patients were noted to have hypertension after being examined by a medical doctor. The patients were randomly divided into two groups: the placebo group (PL) was supplemented with vegetable oil, whereas the supplemented group (SUPL) obtained 3200 IU of vitamin D/day for 5 weeks . The characteristics of patients are presented in g for 10 min at 4°C, the serum was collected and stored in aliquots at -80°C until analysis.Blood samples were taken from the antecubital vein into the vacutainer tubes with silica clot activator. After centrifugation at 2000 × 3 level was determined using the 25-OH Vitamin D total ELISA kit  according to the manufacturer’s instructions. The intra-assay coefficients of variability (CVs) and inter-assay CVs reported by the manufacturer were 2–8% and 4–9%, respectively. Serum CRP, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-10 (IL-10) concentration were measured using the ELISA kit  according to the manufacturer’s instructions. The intra-assay coefficients of variability (CVs) and inter-assay CVs reported by the manufacturer were 2–8% and 4–9%, respectively.Serum 25(OH)DVisual Analogue Scale (VAS) was used to determine the intensity of pain in both groups. At each time point the patients were asked to rate their pain intensity on a 10 cm VAS (from 0 to 10), with 0 indicating no pain and 10 “worst possible pain.”post hoc test. The results were statistically significant at p < 0.05.Statistical analyses were performed using a software package . The results are expressed as the mean ± standard error (SEM). The differences between the means (time points and between-group term) were tested using repeated measurements (RM) ANOVA. If a difference was detected in the ANOVA model, the significant differences were determined using Bonferroni’s 3 concentration in LBP patients was insufficient in both study groups. There was a significant increase in serum 25(OH)D3 in the SUPL group after 5 weeks of supplementation with vitamin D . The level of vitamin D in serum was also significantly higher in the SUPL group as compared to the PL group after supplementation Dap < 0.006, bp < 0.0001, ap < 0.02, bp < 0.0001; We did not observe a significant change in pain intensity after 5 weeks of the vitamin D or placebo supplementation. However, there was a significant reduction in the VAS score after surgery and after rehabilitation of LBP patients in both groups D surgery .3 levels are related to heightened central sensitivity (particularly augmented pain processing) upon mechanical stimulation in chronic pain patients  and conformed to the Declaration of Helsinki and was registered as a Clinical Trial NCT03 417700 KK and JK: conceptualization and writing – original draft. JK: data curation and project administration. KK, WS, PS, KD, and DF: formal analysis. KK, WS, EL PS, DF, WL, and JK: investigation. WS, WK, and JK: methodology. WS and JK: supervision. WS, EL, PS, KD, DF, WK, and WL: writing – review and editing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: Opiate-based pain medications may incur adverse effects following bariatric surgery. The aim of this study was to evaluate the efficacy of intravenous Acetaminophen (IVAPAP) on length of stay (LOS) after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery.Methods: This was a prospective, double-blind, randomized controlled trial conducted from October 2011 to March 2014 at a 416-bed teaching hospital. Eighty-nine total patients were included . Patients were administered either 1000 mg of IVAPAP or placebo every 6 h beginning preoperatively and continuing for four doses. LOS, total narcotic consumption, pain and nausea scores, time to return of flatus (ROF), and postoperative rescue pain medication used were measured during the first 24 h after surgery.Results: LOS was significantly decreased in the treatment group compared with control . There was significant reduction in time to ROF . Pain was significantly decreased in the first 2 postoperative hours in the treatment group (p = 0.02). Total opioid consumption, postoperative nausea scores, and use of rescue pain medications were not affected.Conclusions: The use of IVAPAP significantly decreases LOS following LRYGB, improves acute postoperative pain control, and mediates quicker return of bowel function. The most frequently cited narcotic-related adverse effects include nausea and vomiting, urinary retention, fatigue, pruritus, dizziness, headaches, ileus, and respiratory failure.2–4 Previous studies have identified associations between opioid consumption and increased length of stay (LOS) following laparoscopic Roux-en-Y gastric bypass (LRYGB).5 As a result, nonnarcotic analgesics have garnered interest as potential useful adjuncts in the postoperative setting.P5–17 These studies have shown that the use of IVAPAP decreases the overall need for opioids, minimizes adverse effects, and decreases LOS.7–9 In the bariatric patient population, there are limited retrospective data on the benefits of IVAPAP in combined multimodal therapy. Therefore, the purpose of this prospective study was to evaluate the effect of IVAPAP in bariatric patients who undergo LRYBGP with respect to overall hospital LOS as well as opiate-induced adverse events. The primary hypothesis was that by administering IVAPAP to our LRYGB patients, we would see an overall shorter LOS in the hospital as well as decreased use of postoperative opioid medications.In many countries, intravenous Acetaminophen (IVPAP) is a commonly used pain medication and serves as an adjunct to the use of opioid pain medications. In the US, it has only recently been studied in a variety of surgical patients and deemed an appropriate adjunct to standard postoperative opioid agents in multimodal analgesic models.ClinicalTrials.gov (NCT01460667). All patients provided written preoperative consent to participate in the study before enrollment. All patients underwent surgery by a single supervising surgeon.This study was a single-institution, prospective, randomized, double-blinded placebo controlled trial conducted at a community teaching hospital between October 2011 to March 2014. The study was approved by the hospital's Institutional Review Board and was registered at 2 and American Society of Anesthesiologists (ASA) score 1, 2, or 3. Exclusion criteria consisted of hypersensitivity to acetaminophen, use of opiate medications before the study for greater than 7 days, or hepatic insufficiency that would preclude the use of acetaminophen. Discharge criteria included tolerance of bariatric diet, oral medication pain control, and return of bowel function.A total of 110 patients were enrolled in the study. Patients were then randomized after being scheduled for LRYGB. This study included male and female adults between the ages of 18 and 65 years, with a body mass index (BMI) greater than 35 kg/mPharmacy personnel were instructed and trained before the start of the study and responsible for the randomization process on the day of surgery. One-hundred milliliters of normal saline (NS) placebo or IVAPAP* (Ofirmev™) was prepared and blinded by pharmacy. All active drug and placebo solutions, containers, and labels were identical in appearance, avoiding any recognizable symbols. Funding from Mallinckrodt Pharmaceuticals  was used to cover the cost of the IVAPAP provided in this study.The control group received standard postoperative analgesia supplemented with four scheduled doses of NS as placebo. The treatment group received four scheduled doses of 1000 mg IVAPAP. All study medications were prepared by a designated pharmacist allocated to the study in identical unlabeled bottles on the day of surgery. Each group received the first dose of the placebo or the study medication preoperatively and continued for a total of four doses at 6 h intervals.All patients were allotted hydromorphone via patient-controlled analgesia (PCA) (0.1 mg with an 8-min lock-out). Each patient had an OnQ**  pain system placed at the conclusion of surgery that stayed in place until discharge or for a total of 5 days, if the patient remained in the hospital. The OnQ Pain Relief System* is a nonnarcotic elastomeric pump  that delivers (4 mL/h) a flow of local anesthetic (0.5% Bupivacaine) to the patient's surgical site through two copper catheters placed in the operating room. Narcotic consumption per patient was recorded by nursing staff over the initial 24 postoperative hours with time “zero” and PCA initiation starting upon arrival to the floor from postanesthesia care unit (PACU).A visual analog pain scale  and nausea scoring (0–100) was measured at 2 h intervals postoperatively once the patients were admitted to the floor (time “zero”) from the PACU. Pain levels were assessed using the VAS system from 0 to 100 with 0 representing no pain and 100 representing the most severe pain. Pain and nausea levels were assessed by nursing staff and entered into the electronic medical record. The assessment of pain scores during a subject's sleep was evaluated using the last-observation-carried-forward method.18 All study medications were stopped after 24 h, which comprised the data collection period of the study.Patients experiencing breakthrough pain received IV Hydromorphone or Fentanyl depending upon the level of pain. Study personnel were instructed to offer rescue medication to patients who reported pain intensities at 80 or greater on the VAS. Rescue medications were IV Hydromorphone unless the patient had an adverse reaction to this medication at which time alternative IV opioid medication (Fentanyl) was administered. After the initial 24 h, the choice of rescue medications was expanded to include Ketorolac. Consumption of rescue medications was converted to an oral morphine-equivalent dose for analysis using a prespecified conversion factor .18 All sClinical characteristics , surgical procedure, narcotic consumption (mg), postoperative pain and nausea score, return of bowel function by means of passing flatus, date of discharge, LOS, and the number of pain rescue medications were assessed and analyzed.Study primary endpoint was LOS, while secondary endpoints were postoperative PCA opioid usage (mg), return of flatus (ROF), pain (VAS) scores, nausea scores, and rescue pain medication usage (number of times needed) in the initial 24-h postoperative time period. Adverse events were defined as any complication or unwanted event experienced by the patient in association with the study medication. All patients underwent preoperative screening, including complete blood count and liver function tests . Women of reproductive age (18–55) completed a urine pregnancy test preoperatively.t-Test. The Wilcoxon Rank-sum test was used for comparison in LOS and time to ROF. The postoperative pain scores were analyzed using a repeated measures analysis of variance. Rates and comparison of rescue pain medications given were analyzed using the chi-square test. This study was powered to detect differences between the two groups in LOS and narcotic use of 20% or greater at a beta power level of 0.85 and a significance of p-value <0.05. At least 110 subjects (55 each group) was required to achieve this calculated power. Statistical analysis was carried out using MINITAB 17 Statistical Software (2010). Statistical significance was denoted by p-value <0.05.LOS, time to ROF, opioid consumption and postoperative pain scores were compared for the control and treatment groups using a two-sample A total of 110 patients who met criteria for our study were selected and randomized into either the treatment group or the control group. Of the initial 110 participants, 54 were in the control group and 56 in the treatment group. Eighty-nine were included in the final data analysis . Among tp = 0.8). The mean age was 45.3 years in the control group compared with 43.6 years in the treatment group (p = 0.48). The mean BMI of the 89 patients was 49.1 kg/m2 in the control group and 50.9 kg/m2 in the treatment group. There were no significant differences between the groups in regard to demographic variables .Among the 89 patients included in the final analysis, 68 (76%) were female and 21 (24%) were male (p = 0.035) with the distribution of the treatment group being significantly fewer days than control. The addition of IVAPAP to the postoperative pain regimen led to an overall reduction in LOS of nearly half of a day (0.46 days) (p = 0.03). The control group did have three patients with a LOS of 6 and 7 days, while the treatment group had all LOS between 2 and 4 days.The LOS was recorded from the time of admission on the day of the operation, considered day 0 until the time of discharge. The LOS ranged from 2 to 7 days with a median of 3 (variance = 1.5) days in the control group and a median LOS of 3 days (variance = 0.39) in the treatment group with a range of 2–4 days. The Median Test for two Independent Samples showed a significant difference (p = 0.04). Every patient in our study had a documented ROF before discharge, but this was not used as a specific discharge criterion in our patients.Patients who received IVAPAP supplementation demonstrated an overall reduction in the time to ROF compared with control. They demonstrated a statistically significant decrease in time to return of bowel function with an average time of 1.87 days versus 2.24 days in the control group (p = 0.64). A total of 6.76 mg of hydromorphone was used in the initial 30-h period in the control group and 6.34 mg used in the IVAPAP group . There was no gender difference in baseline pain scores . Pain improvement (as shown by a decreased score) was analyzed initially (2 h postoperatively) and latently (beyond 2 h). A significant decrease was observed for the initial period at the initial 2-h postoperative pain check , but no further change was observed for the latent period  (p = 0.66).The pain and nausea scores were measured at strict 2-h intervals on a scale of 0 to 100 using a visual analog scale for the first 24 h postoperatively. The median pain score was 25.5 (SD = 16.2) in the control group and 29.1 (SD = 16.1) in the IVAPAP group over the first 24 h postoperatively. The difference was not statistically significant ( = 0.79) . The sevp = 0.29). The rescue medications were converted to oral morphine equivalents and the placebo group used a mean of 29.45 OME, while the IVAPAP group required a mean of 21.45 OME for rescue medications showing no statistically significant difference between the two groups (p = 0.64).A total of 24 (26%) patients needed rescue pain medications either IV Hydromorphone or Fentanyl in the initial 24 h postoperative period, and of those, 14 (31%) were in the IVAPAP group, and 10 (22%) were in the control group. While a numerically larger number of patients in the IVAPAP group required rescue medication in the initial 24 h postoperatively compared with the control group, it did not reach statistical significance .20 Furthermore, adequate absorptive capacity of the gastrointestinal tract and the availability of an oral route for medication administration may be limited even further depending on the type of surgery performed. Further limiting this patient population is the inability to use nonsteroidal anti-inflammatory drugs, as a consistent method of pain relief in our LRYGB patients. According to the Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient, NSAIDs should be strictly avoided after bariatric surgery, because of their implication in anastomotic ulceration/perforation after LRYGB.21 NSAID use postoperatively has been shown, in a study by Wilson et al.,22 to significantly increase the risk of postoperative development of marginal ulcerations in RYGB patients. This further illustrates the importance of developing multimodal pain regimens combining both centrally and peripheral targeted mechanisms to decrease opioid reliance and maintain a safe and acceptable side effect profile. Our study echoed this safety profile with only one adverse event stemming from IVAPAP.The benefits of oral acetaminophen, when used in conjunction with narcotic pain medications, have a limited efficacy in our postoperative patient population secondary to impaired absorption as well as altered pharmacokinetics when given in conjunction with intravenous morphine.23 This study identified no significant difference in postoperative narcotic use or difference in VAS pain score in the immediate postoperative period, except for the first 2 to 4 h. This initial decrease in pain scores is corroborated by findings of Wininger et al.,16 which shows an initial decrease in pain scores in the 1000 mg IVAPAP patient population over the placebo group.IVAPAP has been shown by studies both prospectively randomized and retrospective studies to decrease postoperative narcotic use and improve patient satisfaction.et al. study for initial postoperative pain evaluations.Both study arms demonstrated similar PCA and rescue pain medication usage. An explanation for this effect may be that overall low utilization of pain medications failed to distinguish a statistical difference as the study may not have been adequately powered for such low usage. However, we found a significant difference in postoperative VAS scores in the initial postoperative period, which agreed with the Wininger et al. evaluating perioperative pain management among bariatric surgery patients.12 In this study, we did not evaluate intraoperative narcotic administration between these groups, however, several studies have shown the benefits of perioperative IVAPAP usage with a reduction in overall postoperative pain, shorter LOS, and earlier ambulation postoperatively.17Another explanation includes a decrease in the number of narcotics required intraoperatively and during the PACU duration of monitoring. Improved postoperative pain secondary to preoperative administration of IVAPAP has been confirmed in a recent observational study by Bamgbade 25 we are seeking to further improve our postoperative pain control by also adding IVAPAP to our protocol. We wanted to see if we could further reduce our postoperative narcotic use and need for “rescue pain medications.” With our relatively low utilization of the PCA postoperatively, this could have been a reason why we saw such a small difference in narcotic utilization between the treatment group and control group. With the narcotic use among both groups being so similar, a larger sample size may be required to see if a true difference exists. Several studies, both retrospective and prospective, have shown that these catheters can lead to a decrease in overall narcotic usage and pain scores.25 No difference in nausea scores or antiemetic usage was seen during this study, which is consistent with the findings of previous studies.26This study also utilized On-Q pain catheters in our multimodal pain approach. While these catheters have been shown in several studies to improve postoperative pain control on their own,Despite the prospective, randomized nature of this study, there were some limitations. This study was limited to a single institution. A single surgeon has a particular approach that may not represent other clinical practices, and therefore, the generalizability of this one study is limited. Further limitations are that a large percentage of patients were excluded for a variety of reasons, most notably due to inadequate documentation resulting in a high degree of missing data. During the trial, the routine use of upper GI swallow studies on postoperative day 1 was discontinued and changed to a more selective approach triggered by an abnormal postoperative course, such as tachycardia or persistent nausea and vomiting. This change had no effect on our trial as both study arms had equal distribution of receiving upper GI's, and 22 patients (12 control and 10 treatment) did not undergo routine postoperative upper GI.12 Additional investigation into the intraoperative usage of narcotics could give us further insight into our results. Many of the studies that have been reviewed in the bariatric literature fail to look into this fact, but there are several studies that have shown that preoperative IVAPAP usage decreases intraoperative pain medication requirements.Future directions may examine the use of a single preoperative dose of IVAPAP compared to a complete 24-h dosing regimen looking at the same outcomes discussed here with the addition of postoperative time to ambulation. This would allow us to further confirm or refute some of the recently published data in regard to fast-track protocols in postoperative bariatric management.In conclusion, a multimodal approach to pain management in our bariatric patient population has shown to be beneficial in more areas than just consumption of opioids postoperatively. Addition of IVAPAP to standard opioid PCA significantly reduced the LOS following LRYGB, while also promoting a shorter time to ROF compared to patients who received narcotic medications alone.


Existing literature offers little guidance for therapists who provide core stabilisation exercise (CSE) and proprioceptive neuromuscular facilitation (PNF) training to treat chronic low back pain (CLBP). Studies conducting a head-to-head comparison of CSE and PNF training for CLBP are needed.To compare the effects of CSE and PNF training on pain-related outcomes and trunk muscle activity in CLBP patients.Forty-five CLBP patients, ranging from 18 to 50 years of age, were randomly divided and assigned to either a four-week CSE, four-week PNF training, or control group. Pain-related outcomes, including pain intensity, functional disability and patient satisfaction, as well as superficial and deep trunk muscle activity were assessed before and after the four-week intervention, and at a three-month follow-up.P < 0.01). Following the four-week intervention, both CSE and PNF training groups demonstrated significant improvement in deep trunk muscle activity, including the transversus abdominis (TrA) and superficial fibres of lumbar multifidus (LM), compared to the control group (P < 0.05).Compared to the control group, those in the CSE and PNF training groups showed significant improvements in all pain-related outcomes after the four-week intervention and at three-month follow-up (Four-week CSE and PNF training provided short-term and long-term effects on pain-related outcomes, along with increased deep trunk muscle activity in CLBP patients. Chronic low back pain (CLBP), defined as individuals who experience pain between the 12th rib and inferior gluteal folds for at least 12 weeks, is a global health problem causing suffering, disability and work absenteeism .While CLBP is a major problem worldwide, there is no consensus as to specific causes and over 90% of those with CLBP are diagnosed with non-specific low back pain (LBP) . SeveralSeveral interventions, such as exercises and physical modalities, including therapeutic ultrasound which is frequently used to improve lower back symptoms and function , have beProprioceptive neuromuscular facilitation (PNF) training is known to improve proprioceptive function within muscles and tendons of the lumbar region, thereby increasing trunk muscle activity and coordination in response to neuromuscular stimuli , 18–19. Numerous researchers have reported the effectiveness of CSE –17 and PDesigned as an assessor-blinded and randomised controlled trial, the study was approved by the Ethics Committee for Human Research at Mae Fah Luang University (REH 60139) based on the Declaration of Helsinki.Between October 2018 and March 2019, 45 eligible participants with CLBP seeking treatment from Mae Fah Luang University Hospital in Chiang Rai, Thailand were invited to this study. Eligibility criteria consisted of history of CLBP for over 12 weeks, patient age of 18 to 50 years, and pain intensity assessed by over two numerical rating scale (NRS) scores. All participants were screened for illness history and underwent physical examination by a medical doctor unaware of the intervention. Patients were excluded if they had specific spinal pathology , malignancy, neurological compromise, history of lumbopelvic surgery, pregnancy, or regularly received CSE, PNF, trunk strengthening, or ultrasound therapy. Participants provided informed consent before participation.A formula of repeated-measure analysis of variance (ANOVA) was employed for sample size estimation. Our sample size of 45 was estimated to have a 90% chance of detecting differences between groups of two scores on the 11-point NRS at four weeks of intervention . An alphUsing simple randomisation by drawing lots, eligible participants were assigned to one of three 15-member groups: CSE, PNF training or control. Randomisation results were concealed in a sealed and opaque envelope. The research assistant performing randomisation was not involved in recruiting participants or providing interventions. Members of each group participated in three weekly 30 min sessions over four weeks at the Physical Therapy Laboratory. Interventions were performed by a neutral researcher, unaware of the outcome measurement. Participants used treatment diaries to keep track of the interventions.Under physiotherapist supervision, participants practiced recruitment of deep trunk muscles, particularly transversus abdominis (TrA) and lumbar multifidus (LM) muscles, together with the diaphragm and pelvic floor muscles, reducing superficial trunk muscle activity in order to improve function of deep trunk muscles and control inter-segmental lumbar spine movement during activities . InitialParticipants performed 15 repetitions of each PNF training for three sets, with a 30 s rest between repetitions and a 60 s rest after each set. In week 1, participants practiced rhythmic stabilisation (RS), a 10 s hold of alternating isometric contractions of the trunk flexor and extensor muscles in a sitting position against maximum force provided by a physiotherapist. For week 2, participants performed a combination of isotonics (COI) focused on alternating concentric, eccentric and isometric contractions of the trunk muscles in a sitting position; this included a 5 s resisted concentric contraction of the trunk flexor muscle, followed by a 5 s resisted eccentric contraction of the trunk flexors in the return to trunk neutral position and a 5 s resisted isometric contraction of the trunk muscles in a neutral position. The same method was applied for trunk extensors. For weeks 3 and 4, participants were trained in alternately performing the chop and lift (CL) patterns of the upper extremities with maximum resistance .The physiotherapist in the CSE and PNF groups considered each participant’s ability to perform the exercise prior to prescribing exercise progression.2 was applied as treatment for CLBP  to 10 (extreme pain). Participants circled the numerical value representing their pain level; for CLBP, a clinically significant change is two scores .Secondary outcomes consisted of functional disability, patient satisfaction and neuromuscular response of trunk muscles. The 24-item Thai version of the Roland-Morris Disability Questionnaire was used to evaluate functional disability of LBP. The total score ranged from 0 (no disability) to 24 (maximum disability) . The gloSurface electromyography  was used to measure activations of rectus abdominis (RA), TrA, iliocostalis lumborum pars thoracis (ICLT) and superficial fibres of LM muscles. Skin was prepared to achieve 5 kΩ of impedance before bilateral attachment of eight pairs of surface electrodes over the noted muscles. Electrode placement was in accordance with previous literature , 29. GroP < 0.01).Maximum voluntary isometric trunk flexion was performed in a crook lying position , trunk ePain intensity, functional disability and patient satisfaction were measured at three periods: baseline assessment, four-week intervention, and three-month follow-up. Activations of RA, TrA, ICLT, and superficial fibres of LM muscles were measured at baseline assessment and four-week intervention only.The data was expressed as mean, standard deviation and the 95% confidence interval. The SPSS version 20  was used for statistical analysis based on the intention-to-treat approach using the last observation carried forward. The data was found to be normally distributed using the Shapiro-Wilk test. A 2 × 3 (group × time) repeated measures ANOVA was employed to compare between-group differences for pain intensity, functional disability, and patient satisfaction. If significant interaction effects were shown, multiple comparisons would be applied. Within-group comparisons of those outcomes were tested using one-way repeated measures ANOVA.t-test was used for within-group comparison. A P-value of less than 0.05 was determined as statistically significant.For trunk muscle activity, one-way ANOVA was used for between-group comparison and paired Forty-five out of 75 CLBP patients met the study’s inclusion criteria, with no attrition rate. Twenty-five patients were excluded from the study due to their specific LBP conditions and five patients were declined . All bas = 7.58; P < 0.001), functional disability  = 2.67; P = 0.04) and patient satisfaction  = 9.97; P < 0.001). Both CSE and PNF training groups showed significantly greater reduction in pain intensity and functional disability than the control group after the completion of the four-week intervention period (P < 0.001), and at three-month follow-up period (P < 0.05). The CSE and PNF training groups also had better patient satisfaction than the controls (P < 0.01) (P < 0.05) (Significant interaction effects were found on pain intensity (F < 0.01) . The CSE < 0.05) .P < 0.001), functional disability (P < 0.001), patient satisfaction (P < 0.001) (P < 0.05) (P < 0.001). Compared to baseline, the control group had only better patient satisfaction (P < 0.001)  , and act < 0.05)  and 3 af< 0.001) .This study aimed to compare the effects of CSE and PNF training on pain-related and neuromuscular outcomes in CLBP patients. Overall, compared to the control group, our findings showed that after a four-week intervention, both therapies improved pain intensity, functional disability, and patient satisfaction, as well as activation of TrA and superficial fibres of LM muscles. At a three-month follow-up, it was observed that achieved pain-related outcomes persisted. Greater improvement in those outcomes from baseline to follow-up period were also observed in both CSE and PNF training groups.While CLBP can have several causes, weakness and poor coordination of trunk muscles, particularly deep trunk muscles , and poor trunk proprioception are associated with persistent LBP –7. PreviThis study found short-term effectiveness of CES on pain intensity, functional ability, and patient satisfaction. The findings are in accordance with the meta-analysis study of Wang et al.  which inThis study presented long-term effects of CSE on pain-related outcomes. While we do not know if there was a sustained improvement effect of CSE on deep trunk muscles, it is speculated that better activation of trunk muscles may result in persistent effects for improving pain-related outcomes. The present findings are inconsistent with previous studies finding no greater effectiveness of CSE compared to general trunk exercises –39. The Patients in the PNF training group had significant improvements in all pain-related outcomes in short- and long-term follow-ups, concurring with the previous study’s findings regarding pain intensity, functional disability and patient satisfaction in 4 and 12 week follow-ups . IncreasThis study has a few key strengths. As an assessor-blinded randomised controlled trial, measurement and selection bias were minimised . All parThis study had some limitations. Our population consisted of working-age CLBP patients, whose results may not correlate with other age groups, such as adolescents and older adults, or other LBP conditions, such as spondylolisthesis, spondylosis, and herniated nucleus pulposus. We only investigated effects of CSE and PNF training on pain-related outcomes and electromyographic activity of trunk muscles; future studies should consider other physical or psychological outcomes, such as patient-specific activity or fear avoidance belief. Furthermore, CSE and PNF training were compared to a control group that received therapeutic ultrasound and performed general trunk exercises. Other interventions, such as McKenzie’s exercise, could be considered. Also, long-term effects of CSE and PNF training on trunk muscle activity and irradiation were not investigated; further studies on this should be conducted.Four-week CSE and PNF training programmes provide both short- and long-term improvements in pain-related outcomes, including pain intensity, functional disability and patient satisfaction in CLBP patients. Following both interventions, increased deep trunk muscle activity was also demonstrated.