P < 0.001), and the median pain intensities according to PainVision were 43.5 (14.3–98) and 36.5 (9.3–58.5), respectively (P < 0.001). There was a positive correlation between VAS and pain intensity (r = 0.584), but no correlation between VAS score and age (r = −0.174) or vessel diameter (r = −0.107). Peripheral venous administration of oxaliplatin induced vascular pain, measured both subjectively and objectively, in patients with colorectal cancer, regardless of vessel diameter.Oxaliplatin is a key chemotherapy drug in patients with colorectal cancer. Administration of oxaliplatin via a peripheral vein often causes vascular pain. However, no studies have evaluated vascular pain in patients with colorectal cancer in relation to peripheral venous administration of chemotherapy with or without oxaliplatin. We evaluated oxaliplatin-induced vascular pain using subjective and objective methods. We determined if oxaliplatin induced vascular pain in patients with colorectal cancer using a Visual Analog Scale (VAS) and a PainVision PS-2100 device. We compared VAS score between chemotherapy regimens with or without oxaliplatin, and between genders. We also examined the correlations of VAS score with pain intensity examined by the PainVision PS-2100, and with age and vessel diameter. A total of 98 patients with colorectal cancer were enrolled in this study, including 78 patients who received oxaliplatin via peripheral venous administration and 20 who received chemotherapy without oxaliplatin. The median VAS scores in patients with and without oxaliplatin were 36.5 (interquartile range 9.0–60.0) and 0 (0–4.0), respectively ( CAPOX , as well as FOLFOX, is recommended as a first- and second-line chemotherapy for metastatic CRC, based on the phase III NO16966 trial designed to compare CAPOX with FOLFOX42. However, CAPOX therapy with peripheral venous administration of oxaliplatin has been reported to cause vascular pain4, and the low pH and hyperosmolarity of the solution, as well as small vein size and rapid infusion rate, are known to be associated with infusion phlebitis5. The development of vascular pain and phlebitis following intravenous infusion of antineoplastic agents subsequently increases the risk of discontinuation of chemotherapy6. Co-infusion of dexamethasone8, prewarming the peripheral blood vessels9, premedication with oxycodone6, and changing the dose rate have all been investigated as ways of reducing oxaliplatin-induced vascular pain. To determine which techniques are most effective, it is necessary to objectively evaluate vascular pain. Clinical trials using objective assessment methods would lead to minimization of vascular pain and improvement in patients’ QOL. However, vascular pain has usually been evaluated by subjective methods, such as questionnaires and visual analogue scale (VAS). The VAS is the most widely used tool for evaluating pain intensity10. Patients were asked to indicate a point along a 100 mm scale bar depending on the strength of their pain, with ‘no pain at all’ (0) at the left end of the scale and the worst pain (100) at the right end of the scale bar. The VAS score is considered to be a good indicator of subjective pain. Few studies have assessed oxaliplatin-related vascular pain using objective evaluation methods3.Oxaliplatin has been a key chemotherapy drug for the treatment of colorectal cancer (CRC) since the establishment of the FOLFOX  regimen11. PainVision PS-2100  is a device designed to assess patients’ sensory nociception, including perception, quantitatively and objectively, by measuring the stimulating electric current14. PainVision can evaluate pain within a few minutes without causing additional pain to the patients. In this study, we aimed to assess oxaliplatin-induced vascular pain using the PainVision system and to clarify the relationship between vessel dimeter and vascular pain in patients with CRC.Pain is difficult to quantify because the patient’s pain threshold can be influenced by their mental conditionA total of 98 patients received chemotherapy for metastatic CRC between April and September 2014. The cohort included 57 men and 41 women, aged 33–87 years . The demographics and characteristics of the study patients are shown in Table Seventy-eight patients  received chemotherapy including peripheral venous oxaliplatin. The venipuncture site was the median cubital vein in 39 and the median vein of the forearm in 39.Twenty patients  received chemotherapy without oxaliplatin, including 12 patients who received irinotecan and eight who received neither irinotecan nor oxaliplatin. The venipuncture sites were the median cubital vein in nine and the median vein of the forearm in 11. There was no significant difference between the groups in terms of gender or venipuncture site.P < 0.001 by Kruskal–Wallis test for the three groups comparison). Pairwise comparison of the three groups showed no significant difference in VAS scores between patients without irinotecan and oxaliplatin and those with irinotecan (P = 0.385), but the VAS score was significantly higher in patients receiving oxaliplatin compared with those without oxaliplatin (P < 0.001)  VAS scores and vascular pain in patients without irinotecan and oxaliplatin, with irinotecan, and with oxaliplatin were 0.0 (0–4.0), 0.0 (0–0), and 36.5 (9.0–60.0), respectively (P = 0.767) . Forty-three of the 57 male patients received oxaliplatin, and the median male VAS score was 24 (0.0–53.0). There was no significant difference in VAS scores between male and female patients with CRC administered peripheral venous chemotherapy   and 79.6 (144.6), respectively  Fig. .Figure 3The mean of age and vessel diameter were 67 years (33–87) and 3.3 mm (1–7), respectively.P = 0.086, and r = −0.107, P = 0.296, respectively)  Fig. .15. However, no studies have reported on the evaluation of vascular pain during peripheral venous administration of chemotherapy, with or without oxaliplatin in patients with CRC. It is possible to distinguish between vascular pain and acute neuropathy in that the former is asymmetrical and originates at a puncture site, whereas the latter is symmetrical and occurs at the tips of the extremities. Assessment of pain can vary greatly depending on the mood and physical state of the patient at the time of assessment; thus, it is best to objectively evaluate pain. Pain evaluation by VAS is associated with a margin of error of approximately ±20 mm10. Therefore, a method for objective assessment is also required when evaluating drugs designed to ameliorate vascular pain. We assessed subjective pain by VAS and objective pain using the PainVision device. VAS and PainVision were both fast and easy systems to apply. The results indicated that peripheral venous administration of oxaliplatin increased the VAS score, which correlated with the Pain intensity. This is mainly attributable to the relationship between VAS scores >8 and high pain intensities.We previously reported on the subjective and objective assessment of oxaliplatin-induced peripheral neuropathy7, prewarming peripheral blood vessels16, premedication with oxycodone, and altering the dose rate have all been investigated as countermeasures against oxaliplatin-induced vascular pain6. The effects of many of these countermeasures on vascular pain were assessed by VAS. However, we considered that the additional use of the PainVision system would also allow the efficacies of these countermeasures to be assessed more objectively.Co-infusion of dexamethasone16. Furthermore, blood flow is known to increase with increasing vessel diameter17, and Hagen Poiseuille’s equation showed that blood flow increased in proportion to the fourth power of the vessel diameter18. It is possible that an increase in blood flow may decrease the osmotic pressure and reduce the contact time between the anticancer drug and the vascular endothelium. We therefore examined the relationship between the VAS score for vascular pain and blood vessel diameter in patients received peripheral venous chemotherapy, but found no significant correlation.Heating the blood vessels is thought to reduce vascular pain19, while pain sensitivity is also thought to decrease with increasing age. However, the current study found no significant differences in VAS scores in relation to either gender or age.Sex-related differences in the experience of both clinical and experimentally induced pain have been widely reportedAlthough the results of the current study provide valuable information on oxaliplatin-induced vascular pain, the frequency with which patient-reported vascular pain occurs remains unclear. Further studies are needed to clarify its causes and possible countermeasures. It is also necessary to assess countermeasures against vascular pain based on objective and subjective evaluations. We are currently conducting a clinical trial to establish and validate new hypotheses regarding the relationship between vessel diameter and vascular pain. On the basis of our findings and unpublished data, we have developed a system for alleviating vascular pain. Objective evaluation of pain is necessary to accurately evaluate this system and we are investigating a means of achiving this using PainVision and VeinViewer . We plan to publish our findings in as timely a manner as possible.This study confirmed that peripheral venous administration of oxaliplatin chemotherapy induces vascular pain in patients with CRC, irrespective of blood vessel diameter.This single-center study was performed at Fukuoka University Hospital between April 2014 and September 2014. Ninety-eight patients with histologically proven metastatic CRC were enrolled in this study. We only included patients with CRC in this analysis because this is the only condition for which oxaliplatin may be prescribed in Japan. Patients who did and did not receive oxaliplatin were evaluated. This evaluation was carried out immediately after the first infusion to exclude the effects of oxaliplatin-induced neuropathy. Patients with poor performance status and mental health who were unable to undergo PainVision and VAS assessments were excluded. Patients unable to feel pain due to peripheral sensory neuropathy or musculoskeletal pain were also excluded. Informed consent was obtained from all patients prior to study entry. This study was approved by Fukuoka University Hospital’s Institutional Review Board (No. 13-4-07). All procedures were performed in accordance with the Declaration of Helsinki.2 oxaliplatin on day 1 and 2000 mg/m2 capecitabine on days 1–14, every 3 weeks), 12 who received CAPOX therapy ,and five who received SOX therapy .Seventy-eight patients received oxaliplatin-based chemotherapy, including 61 who received CAPOX plus bevacizumab therapy , six who received SIRB therapy , and six who received XELIRI therapy .Twenty patients received non-oxaliplatin-based chemotherapy, including eight who received capecitabine plus bevacizumab . The patient was required to push the stop button when they first detected the electric stimulation and the current at this point was defined as the minimum perceived current. This procedure was repeated three times and the minimum sense current value (current perception threshold) was obtained from the average value. The minimum perceived current was recorded as the current perception threshold. The sensitivity of the nerve can be evaluated based on the current perception threshold. The patient was then asked to push the stop button when they considered that the current stimulus was equal to the oxaliplatin-induced vascular pain, and this current was defined as the pain-equivalent current. This measurement was also repeated three times to obtain the average pain-equivalent current value. Pain intensity was then calculated as follows:The PainVision system can measure pain intensity objectivelyBecause this was an exploratory observational study, vascular pain was assessed in all patients with CRC who underwent chemotherapy within the study period. Given that no data were available to enable this, we were not able to calculate the required sample size. Data were collected and analyzed using SAS version 9.3 . We investigated the reliability of the PainVision device in terms of its internal consistency by quantitatively assessing vascular pain using the VAS and PainVision system twice each. Data are reported as mean ± standard deviation (SD), median (interquartile range 25–75%), or number of participants (percentage).Three groups were compared by Kruskal-Wallis test. Pairwise comparison of the three groups was performed only if Kruskal-Wallis test was significant. A family-wise error rate was controlled by the closed testing procedure.20. Specifically, the correlation coefficient between Pain intensity and VAS score was computed using residual values of the mixed-effects model including sex as a fixed effect and subject as a random effect. A P value < 0.05 was considered statistically significant.The relationship between vascular pain (VAS score and Pain intensity) and vessel diameter after adjusting for sex and subject was assessed by partial correlation analysis


As the most complained oral problems in Indonesia, the therapy of orofacial pain has to be constantly evaluated. The objective of the current study was to evaluate the effectiveness of orofacial pain therapy in Indonesia. This study recruited 5412  participants from 27 districts in West Java province. Half of the participants (2714) were recruited from those who were treated at community health centers whilst the rest were those who were treated at private dental clinics. A Likert-scale questionnaire that consists of nine questions that were divided to three subsections was used. The first subsection of the questionnaire evaluated the participants' post-therapy basic oral functions (three questions), and the second part evaluated the participants' post-therapy pain intensity and frequency (three questions), whilst the last part evaluated the participants' post-therapy activities (three questions). All data were then cross-tabulated and correlated by using Spearman correlation. The current study revealed that out of 5412 participants, 4023 (74.33%) participants claimed that the therapy has enabled them to perform their work activity as usual, whilst 2576 (59.2%) claimed that the therapy has decreased the intensity of the pain moderately. A significant (p < 0.01) correlation (r = 0.1) between the type of dental facility visited and the total score of the therapy effectiveness was revealed. The therapy of orofacial pain in Indonesian sample was proven to be effective. Further study evaluating the reasons underlying the current results is of importance. As one of the most complained dental problems, orofacial pain has affected its sufferer at so many levels. Not to mention that almost every epidemiological study about the impact of orofacial pain revealed the detrimental effect of orofacial pain in daily activities, work activities, and social activities –3. AsideIn a study conducted by Shueb et al. (2015) about the impact of chronic and acute orofacial pain on 146 patients that suffered from one of the following: temporomandibular disorders (n=41), acute dental pain (n=41), trigeminal neuralgia (n=21), and persistent dentoalveolar pain (n=22) by using the Oral Health Impact Profile (OHIP)-49, it was revealed that all pain disorders showed a significant (p<0.001) impairment compared to the control group  .Considering the detrimental impact of orofacial pain on the patient's quality of life, assuring that orofacial pain patients are receiving effective therapy is considered to be of importance, as pain elimination will improve patients' oral function, which in return will also improve patient's quality of life. A literature study by Katz (2002) revealed how patients' quality of life is impaired when pain is not effectively treated . AnotherIn regard to the health care system, in Indonesia, there are two types of dental facilities, those that are government facilities and those that are private facilities provided by private parties. In relation to this, a study performed by Al-Hussyeen 2010) about the factors affecting the utilization of dental health services revealed that patients are more likely to use private dental practice services due to its high quality of dental care, and those who utilized the service of dental public clinics found postoperative complications to be the discouraging factor for its future utilization  about th.Unfortunately, regardless of the impact of orofacial pain in patient's quality of life and the importance of effective therapy for the patients as well as the health care system, our literature study showed no record of previous study(ies) that evaluated the effectiveness of orofacial pain therapy in public and private dental facilities. Therefore, the aim of this study was to evaluate the effectiveness of orofacial pain therapy in Indonesian sample and to compare the effectiveness of the therapy given in a private dental clinic and public dental facility.The current study was conducted at West Java province, Indonesia, and recruited 5412  participants  that werAll recruited participants should fulfill the following inclusion criteria: age between 18 and 45 years old, currently having an occupation, receiving the  therapy of orofacial pain (surgery excluded) they had prior to the survey (within the period of six months), and having been living in the province for at least two years. Ten calibrated interviewers interviewed the participants by using a validated questionnaire. In order to avoid any potential fatigue that might affect the results of the interview, one interviewer can only interview ten participants per day.Prior to the start of the study all participants signed an informed consent regarding their participation in the study. An ethical clearance was obtained from the Profession and Research Ethics Committee of Medical Committee Faculty of Dentistry Dental Hospital Padjadjaran University. To confirm, every procedure and ethical aspect of the current research have been conducted in full accordance with the World Medical Association Declaration of Helsinki. All participants gave their written consent for their participation in the current study as well as the usage of any of their photograph(s) that was taken during the study that was related to the study procedure, in all possible publications related to the study.A validated questionnaire  with a t not at all: if the participants think that they are still having the pain just as often as they used to prior to the therapy; a little bit: if the pain occurs about 3/4 of the rate that they used to; moderately: if the pain occurs about 1/2 of the rate that they used to; and a lot: if the pain occurs about 1/4 of the rate that they used to). The last part of the questionnaire evaluated the patients' ability in performing their work activity, social activity, and daily activity. Every question was provided with four Likert-scale option type of answer, which were “not at all”, “a little bit”, “moderately”, and “a lot”. After the questionnaire was completed, all recorded answers were scored.The first section of the questionnaire comprised three questions that were composed for the purpose of oral function evaluation whilst the questions in the second section were composed to evaluate pain intensity as well as pain occurrences. For the pain occurrences question (during the interview) the interviewer gave the participants a standardized range for each answer  was 7.1, the mean score for the second subsection (pain reduction) was 7.3, and the mean score for subsection 3 (activity performance) was 8.1. When the participants were asked about their ability in performing their usual work, social, and daily activity after the therapy was given it was revealed that most of the participants were in the “7 to 9” level of scoring .Aside from the scoring of the questionnaire, the types of the therapy provided by both dental facilities were also recorded . An analAnother analysis performed in the current study was the correlation between the sex of the participants and the total score of the questionnaire. There was a significant (p<0.01) positive correlation (r=0.1) between the sex of the participants and the total score. It was revealed that more female  participants claimed that the therapy has improved their oral function better, reduced pain intensity and occurrences more effectively, and enabled them to perform their activities better compared to the male  participants . As for A significant (p<0.01) positive correlation (r=0.1) was also found between the type of dental facility  and the total score of the questionnaire. The therapy being given in the private dental clinics seemed to have more participants  with the total score of ≥19 compared to those who visited the community health centers . There was no significant difference found between age and the type of dental facility that the participants have visited when it comes to preferred dental facility type.On the survey about the prevalence of orofacial pain in West Java province, Indonesia, in 2016, it was revealed that most participants who experienced orofacial pain of any type complaint about the interference they experienced on three basic oral functions: chewing, speaking, and jaw movement (opening and closing). (1) This particular research result was the main consideration for choosing these three oral functions to be evaluated in the current study. As for the evaluation of activities, previous studies have emphasized about the interference of orofacial pain on these activities , 13.The first analysis of the study revealed the mean total score of the questionnaire. The facts that the total mean score was 22.45 and the subsection analysis showed a score as high as 8.1 for the ability to perform activities as per usual were solid indicators of the fact that the orofacial pain therapy given was considered to be highly effective. Considering the high prevalence of orofacial pain in Indonesian sample obtained from previous survey, (2) this particular result is expected to serve as an indicator that the West Java government has used the epidemiological information about the high prevalence of orofacial pain as a scientific background in the planning stage of orofacial pain management and implemented effective measures in reducing the high prevalence. It is important to note how the therapy has highly affected the participant's ability to perform their work activity as usual, especially as we were investigating a productive age group and that interfered work ability and lost productivity have been one of the highlights when it comes to pain impact assessment –16 in thIn the current study, we evaluated the type of orofacial pain therapy being conducted in both types of dental facilities . And likAnother result of the current study was the improved oral functions after the therapy, one of which was the chewing function. In a study by Choi et al. (2009) about pain disability on orofacial pain patients, chewing function was found to be one of the most interfered oral functions in orofacial pain patients  amongst In another study conducted by Bennet et al. (2005) about the impact of pharmacological approach on patients with fibromyalgia pain, it was revealed that the pain decreased has also impacted patients' ability to work and to function socially . These pThere are several significant correlations found in the current study, one of which was the significant correlation between the type of dental facilities visited and the overall improved functions being evaluated in the study. It was revealed that more patients who visited private dental facilities and being treated in this particular type of dental facilities claimed that the therapy allowed them to perform their work, daily, and social activities as per usual in the “a lot” category, compared to those who visited community health center. This particular result might indicate the high effectiveness of the therapy as well as the participants' high level of perceived satisfaction when it comes to the quality of the therapy in private dental facilities.In a study conducted by Hancock et al. (1999) about the perception and experiences of patients who went to private dental facilities compared to those who went to public dental facilities, it was revealed that those who went to private dental facilities claimed that they are more satisfied with the treatment being given, compared to those who went to public dental facilities , which iThe variability of results elaborated above indicates the need of further studies that thoroughly investigates the correlation between different types of dental facility and the effectiveness of the orofacial therapy. Yet, in regard to therapy efficacy, our study has provided scientific information on how orofacial pain patients who visited private dental practice were more satisfied with the therapy compared to those who visited the community health centers. Lastly, in relation to the results of the current study, it is concluded that therapy being given to orofacial patients in West Java province is considered to be highly effective in eliminating orofacial pain, restoring oral function, and improving participants' daily, work, and social activities. It is hoped that the result of the current study can be used by the government of the West Java Province as one of the scientific backgrounds in preparing better health quality service.


Discrepancies in patients’ responses to various outcome measures challenge clinicians’ evaluation of treatment outcomes. Therefore, we aimed to 1) evaluate the concordance of outcome measures after spine injection, 2) determine the patient variables that lead to discordant responses, and 3) suggest practical outcome measure for spine injections with good responsiveness. From October 2014 to November 2014, 164 patients with neck or low back pain who visited our outpatient clinics and had spine injections on the previous visit were enrolled. We asked patients to report changes in their symptom in the form of outcome measures: numeric rating scale, Oswestry disability index, neck disability index, residual symptom percentage and global perceived effect. The responses were categorized into three groups according to the degree of change; not improved, minimally improved, and significantly improved. The concordances of these categorized answers were evaluated. When “significantly improved” was considered as true improvement, 46 (28%) of the 164 patients had discordant responses to the four measures. There was no significant patients’ variable that affects discordance in the outcome measures. Good agreement was shown between the global perceived effect and residual symptom percentage, while the Oswestry disability index had poor agreement with the other measurements. The calculated numeric rating scale and residual symptom percentage also had low levels of agreement. However, patients with severe pre-treatment pain tended to have better agreement. In conclusion, this result suggest that the residual symptom percentage may be a more practical for clinicians and better represent patients’ improvements after spine injection. Low back pain and neck pain are common causes of disability in middle- to old-aged individuals. Since only 10% to 15% of these patients require surgery or are eligible for surgery, conservative management is recommended in most patients. Conservative management may include oral medications, image-guided injections, exercise, or physical therapy. Among these, spine injections have been reported to be effective in localizing and managing low back and neck pain .As pain is a subjective symptom, its assessment is complicated. Various outcome measures have been developed to measure pain. Some tools are intended to rate the intensity of pain itself, e.g., the numeric rating scale and visual analog scale, while other tools are intended to assess functional status, e.g., the Oswestry disability index, neck disability index, and Roland Morris disability questionnaire. Clinicians are interested in the effectiveness of their treatment; surgery, injections or medications. However, it always been their task to measure improvement and decide the next step.There have been several studies that evaluated or compared the responsiveness, an instrument’s ability to detect change over time, of various outcome measures. These studies often conclude that these measures have good reliability and responsiveness –5. HowevIn clinical practice, it is often observed that some cases show confounding results after spine injection. For example, some patients have told us that their symptoms got much better after spine injections; likewise, the global perceived effect and residual symptom percentage were improved. However, their post-injection pain intensity or functional scores, such as the numeric rating scale and Oswestry disability index, were not decreased when compared to their pre-injection values. We hypothesized that discordance in these results may be due to properties of the outcome measurements or patient variables, such as age or sex. The residual symptom percentage is an easily asked and answered measure in clinical practice, while disability or functional score measurements require more time and effort. The residual symptom percentage has grossly good agreement with the global perceived effect in our experience. However, only a few studies have reported the responsiveness and reliability of self-reported pain reduction and compared it with calculated pain reduction , 8, 10Therefore, the purposes of our study were to 1) evaluate the responsiveness of outcome measures after spine injection, 2) determine the patient variables that lead to discordance in outcome measurements, and 3) suggest practical outcome measure for spine injections with good responsiveness.This retrospective study was approved by the institutional review board, and the requirement of informed consent was waived. From October 2014 to November 2014, 605 patients visited our outpatient pain clinic. Among them, 189 patients who received a spine injection during their previous visit were included in the study. The inclusion criteria were: (1) patients who visited our clinic for either neck or low back pain with or without radiculopathy, (2) those who received spine injections at the time of their last visit, and (3) patients who completed the self-reported questionnaire at the time of the visit for their pain evaluation.Twenty-five patients were excluded based on the following exclusion criteria: patient who had (1) complaint of both back and neck pain (n = 6), (2) recurred symptom more than one year after the previous injection (n = 1), and (3) incomplete self-reported questionnaires or missing medical records (n = 18). As a result, one-hundred and sixty-four patients  were enrolled in this study.Every patient was asked to complete a set of written questionnaires to record a self-reported pain and disability measures, before visiting clinicians for interview. First, the patients scored their pain intensity with the numeric rating scale ranging from 0 to 10, with 0 indicating no pain and 10 indicating the worst pain imaginable. For the patients with back pain, a degree of disability due to back pain was measured using the translated Korean version of the Oswestry disability index, which is based on the Oswestry disability index, version 2.0. This measure consists of nine sections and has a total score of 45, as sexual life was excluded from the original version. Oswestry disability index measures a degree of disability in everyday life with nine items including walking, sitting, standing, sleeping, etc., while the item related to sexual life was excluded from the original version. Each item was scored with scale ranging from 0 to 5, while 0 indicating the least amount of disability and 5 indicating the most severe disability. On the other hand, a degree of disability due to neck pain was measured using the translated Korean version of the neck disability index. Similar to Oswestry disability index, neck disability index measures a degree of disability in ten items, which includes lifting, reading, working, driving, etc., and also scored with scale of 0 to 5. During the interview, each patient was asked to answer two additional measures. One was the global perceived effect, which is a self-assessed 5-point scale , While the other measure was residual symptom percentage, which is the remaining percentage of the symptom when considering the symptoms before injection as 100%.During the interview, the radiologist clearly identified the affected nerve root or segment using clinical findings and imaging studies, and determined the method of approach for the spine injection; epidural, transforaminal or facet joint injection. All spine injections were performed under biplane fluoroscopic guidance by one of four radiologists with 10 years, 4 years, 1 year, and 1 year of experience with spine injections.For fair comparison between the different outcome measures, the collected samples of numeric rating scale, Oswestry disability index, and neck disability index are converted into a tractable form by leveraging following formula.Notice that the converted measure indicates the portion of residual pain or a degree of disability after the injection. Now, to evaluate the concordance among the outcome measures, all the five outcome measures were categorized into three groups: “not improved”, “minimally improved”, and “significantly improved”. The numeric rating scale, Oswestry disability index, and neck disability index were categorized according to converted residual pain or disability based on equation above: converted measure percentage greater than 70% was considered “not improved”, between 70% to 50% was considered “minimally improved”, and less than 50% was considered “significantly improved”. This categorization was based on previously proposed ‘minimally important changes’ by Ostelo et al . The resPaired t-tests were used to compare datasets obtained at the initial evaluation to those obtained at the follow-up after the injection. Analysis of variance (ANOVA) was conducted to compare the means of the measures indicating different levels of improvement to the global perceived effect. Chi-square tests were performed to compare sex and previous experience of a spine injection between groups categorized based on concordance. ANOVA was conducted to compare differences in the time interval between the two visits and the patients’ ages.The intraclass correlation coefficient was used to determine the level of inter-measure agreement for improvement after the injection according to the previously mentioned categorization of improvement.The concordance correlation coefficient was used to determine the level of agreement between the converted numeric rating scale change and residual symptom percentage. A visual representation of the data was created using a Bland-Altman plot.All statistical analyses with the exception of the concordance correlation coefficient calculation and the Bland-Altman graph were performed using Statistical Package for the Social Sciences (SPSS) version 20.0 for Microsoft Windows . The concordance correlation coefficient calculation and plotting of the Bland-Altman graph were performed using MedCalc . Statistical significance was defined as P < 0.05.Among 164 patients, 122 had low back pain with or without lumbar radiculopathy, and they underwent spine injection at the lumbar level. Forty-two patients complained of neck pain with or without cervical radiculopathy, and they received a spine injection at the cervical level. The median interval between the patient visit after injection was 56 days (interquartile range: 73.41–99.34 days).Outcome measures before and after the spine injection are summarized in Tables The converted residual pain or disability index were significantly different between patients’ global perceived effect, in each of the outcome measure, except for Oswestry disability index Tables  and 4. TThe outcome measures have different percentages of improvement Tables  and 6. GTables The effects of a previous injection experience (other than the injection patient had on their last visit), sex, age, and time interval to concordance are described in Tables The intraclass correlation coefficients of the measurements are summarized in The concordance correlation coefficient between the converted numeric rating scale change and residual symptom percentage was 0.26, with a precision of 0.32 and an accuracy of 0.81. The concordance correlation coefficient was 0.60 and 0.51, in neck pain and lower back patient consecutively, when the initial numeric rating scale was higher than 7. It still showed higher concordance (concordance correlation coefficient = 0.53) in all patient with initial numeric rating scale was higher than 7, while concordance correlation coefficient was 0.21 when the initial score was equal to or less than 7 . Fig 2 sWe found that outcome measurements do not always show concordant response for improvement after spine injection. Residual symptom percentage showed good agreement to global perceived effect while numeric rating scale, Oswestry disability index and neck disability index show poor agreement in patient with either neck or low back pain. The concordance correlation coefficient between the residual symptom percentage and the numeric rating scale was very low, although it had higher concordance in patients with severe pain before the spine injection.Many studies have evaluated the outcomes and efficacy of spine injections for patients with low back pain or neck pain. These studies often use a number of validated measures to assess treatment outcomes. However, most of these validated measurements did not distinguish between methods of treatment or were only performed in patients treated with surgery or rehabilitation programs. Only a few studies have evaluated the responsiveness of outcome measures after spine injections. Surprisingly, most clinicians in the field of spine intervention have been using these outcome measures without skepticism. Tomkins-Lane et al. have evaAs demonstrated in our study, each of the outcome measure has a distinct response to treatment. As discussed above, Tomkins-Lane et al.  have repThe perception of improvement can be considered an integrated response to patients’ interpretation and judgment of the changes in their own status, which may not include only the relief of pain, but also improvements in emotional state, functional state, and quality of life . HoweverMany previous studies have validated outcome measure used to evaluate chronic back pain, which are useful for evaluating the severity of pain, and disability and functional status before treatment. However in some cases in our study, the Oswestry disability index and numeric rating scale did not show ‘clinically significant changes’, even though the patient reported that they have been improved after spine injection. This finding was confusing when interpreting the results. As we hypothesized, the residual symptom percentage and global perceived effect had high agreement between responses. Although the residual symptom percentage showed a discrepancy in the degree of improvement compared to the converted pain change, there was tendency of pain change between the other two measures. Additionally, in patients with severe pre-treatment pain, there was higher agreement between these measures. Our findings suggest that the residual symptom percentage can be a better representation of improvement after spine injection. We suggest using this measure as a single standard post-treatment outcome measure in clinical practice, especially after spine injection.Our study has several limitations. First, this was a retrospective study. The time interval between the first visit and the follow-up was different between the patients. This may have affected the responses of the measures based on memory of the initial pain and its progress. Second, this study did not classify patients by chronicity. Acute and chronic pain may have different natural courses of improvement and differences in the pain itself. Third, the severity of spinal degeneration was not considered in our imaging study. In our clinic, candidates for spine injection are divided into two groups. One group includes patients with minor degeneration who are not candidates for surgery. The other group includes surgical candidates who need a spine injection to delay the operation or bridge conservative management for pain control. These differences in patient condition may have also have affected the response to the management. Fourth, there was small number of patient with aggravated pain, which was insufficient to prove statistical significance in symptom aggravation.In conclusion, among the measures studied, residual symptom percentage showed high agreement to the global perceived effect in response to improvement, while the numeric rating scale and functional outcome measures did not. Comparison of converted numeric rating scale change with residual symptom percentage highlights the fact that the residual symptom percentage better represents improvement than changes in the numeric rating scale in patients, who have lesser pain and recommended for spine injection. Therefore, this result suggest that the residual symptom percentage may be a more practical for clinicians and better represent patients’ improvements after spine injection. Further studies are necessary with detailed pain classification and patient wih wide range of pain change, especially aggravated pain, in study centers with variable clinical background.


Pain neuroscience education (PNE) has been shown to reduce pain or psychological symptoms in patients with chronic pain and preoperative knee osteoarthritis; however, the evidence of its effectiveness in hospitalized patients who have undergone high tibial osteotomy (HTO) is unknown. This study was performed to determine whether the implementation of a newly developed hospital-time PNE provided by physical therapists to patients after HTO can result in meaningful improvements.n = 67) and those who underwent rehabilitation only . The patients were pseudo-randomized by their baseline demographic factors using a propensity score-matching method. The PNE was based on a psychosocial model and began 1 week postoperatively in a group setting; five 1-h weekly sessions were conducted. The primary outcome was the walking pain score as measured by a numerical rating scale. The secondary outcomes were the pain catastrophizing scores as measured by the PCS, self-efficacy as measured by the Pain Self-Efficacy Questionnaire, and physical function. Measurements were taken at baseline (before surgery) and before discharge from the hospital (5 weeks postoperatively) to identify any intervention effects.In total, 119 patients aged ≥45 years with knee osteoarthritis who were scheduled to undergo HTO were analyzed. Patients with a low Pain Catastrophizing Scale (PCS) score of < 21 were excluded. The patients were classified into two groups: those who underwent a combination of PNE and rehabilitation  patients completed the PNE. In total, 44 patients in the intervention group and 52 patients in the control group were analyzed. Five weeks following surgery, the rehabilitation itself had also significantly decreased catastrophizing, and the difference between the two groups had only a small effect size (d = 0.44).These findings provide preliminary evidence that physical therapist-delivered PNE during hospitalization may help to at least slightly reduce pain catastrophizing in patients with catastrophizing prior to knee arthroplasty.ClinicalTrials.gov (UMIN000037114) on 19 June 2019.This trial was retrospectively registered with  Knee osteoarthritis (KOA) is a widespread chronic condition and one of the most common causes of musculoskeletal disability among all high-risk health problems . The preSurgical treatments such as knee arthroplasty or high tibial osteotomy (HTO) for patients with severe KOA are commonly performed, and HTO is performed in younger patients than is knee arthroplasty . A higheA study of 4400 patients who underwent knee arthroplasty showed that 35% had unexplained chronic pain 15 years following surgery . AnotherThe intensity of acute postoperative pain or the impairments caused by pain catastrophizing among patients who have undergone knee arthroplasty is associated with a risk of developing a chronic pain state and poor outcomes , 9. PainIn a comparison of the effects of patient education according to the contents of the education program, pain neuroscience education (PNE) provided a significantly better understanding of the neurophysiology of pain and a reduction of pain catastrophizing compared with pacing and self-management education . AdditioThis study was performed to evaluate the effectiveness of a hospital-time PNE intervention combined with physical therapist-prescribed rehabilitation in patients undergoing HTO with respect to improvements in pain and pain-related psychological and physical function. Our hypothesis was that the intervention would result in an improvement in pain-related psychological factors at discharge (5 weeks postoperatively) compared with rehabilitation alone.We performed this quasi-experimental study using data from two independent cohorts  at Fukuoka Rehabilitation Hospital, Nishi-ku, Fukuoka-shi Fukuoka, Japan from April 2014 to January 2018. The patients who underwent PNE combined with rehabilitation were recruited from 2016, and the patients who underwent rehabilitation alone were recruited from 2014 to 2016 retrospectively. We considered the possibility of bias in that the baseline characteristics  of the participants were more favorable than those of nonparticipants  ts Table . The intFive weeks of postoperative education on the neuroscience of pain along with rehabilitation improved patients’ pain catastrophizing compared with patients who underwent rehabilitation only. To the best of our knowledge, this is the first study to show that a combination of postoperative rehabilitation and PNE can contribute to improvements in patients’ catastrophizing, which is a risk factor for chronic pain after HTO.Intervention studies using the cut-off PCS have not been unified at > 16 points  or > 23 The short-term effects of the addition of PNE to physiotherapy interventions on pain have been observed in patients with chronic pain  but not The mean difference in the PCS score between the two groups was 3.8 points, which is a small effect size. Lluch et al.  reportedThe present study showed no significant difference in the strength or walking ability of the operative knee between the intervention group and the control group. Louw et al.  and BeauOur study has some limitations. First, quasi-experimental designs are viable alternatives to randomized clinical trials. The patients in our study were not randomly assigned to the two treatment conditions, and we cannot be certain whether the differences were due to the intervention or to pretreatment differences between the groups. For example, we were unable to control all potential confounders such as physical activity, educational history, and economic aspects. Second, history is another internal validity threat to quasi-experimental designs. Our control group was treated 1 to 2 years prior to the patients who received PNE. Although the surgical and implantation procedures may have varied throughout the study period, we are unaware of evidence indicating that the differences found in this study were due to differences in surgical techniques over this relatively short time interval. This aspect should be taken into account when interpreting the results. Third, the patients were not blinded to the treatments, which could have resulted in overestimation of the benefits. The PCS score that proved effective in this study was based on a questionnaire survey, and the possibility of describing good results after the intervention in the PNE group cannot be denied. Fourth, the differences in the effect of PNE might have been only due to an increase in contact hours with the patients. Fifth, this study included a mixture of highly catastrophizing and non-catastrophizing patients. High catastrophizing is generally accepted to be present in patients with a PCS score of > 30 points . In the Physical therapist-prescribed rehabilitation combined with postoperative PNE, consistent with a biopsychosocial approach in patients undergoing HTO, conferred small benefits in pain catastrophizing compared with rehabilitation alone. Further studies will need to provide PNE intervention timing and long-term verification that PNE prevents high rates of opioid prescription and lowers health care costs.


Acute pain is always the most common complaint in Emergency Department admissions and options for analgesia are limited. Nitrous oxide/oxygen possess many properties showing it may be an ideal analgesic method for the Emergency Department; it is quick-acting, well-tolerated, and does not mask signs and symptoms. The aim of this study is to evaluate the safety and analgesic effect of the fixed nitrous oxide/oxygen mixture for trauma patients in a busy emergency environment.The randomized, double-blind, prospective, placebo-controlled study will be carried out in the Emergency Department of General Hospital of Ningxia Medical University. The target research objects are trauma patients who present to the Emergency Department and report moderate to severe intensities of acute pain. A total of 90 patients will be recruited and randomly assigned into the treatment and control group. The treatment group will receive conventional pain treatment plus nitrous oxide/oxygen mixture and the control group will receive conventional pain treatment plus oxygen. Neither patients, nor investigators, nor data collectors will know the nature of the gas mixture in each cylinder and the randomization list. Outcomes will be monitored at baseline(T0), 5 min (T1), and 15 min (T2) after the beginning of intervention and at 5 min post intervention (T3) for each group. The primary outcome is the level of pain relief after the initial administering of the intervention at T1, T2, and T3. Secondary outcomes include adverse events, physiological parameters, total time of the gas administration, satisfaction from both patients and healthcare professionals, and the acceptance of patients.Our previous studies suggested that a fixed nitrous oxide/oxygen mixture was an efficacious analgesic for the management of burning dressing pain and breakthrough cancer pain. The results of this study will provide a more in-depth understanding of the effect of this gas. If this treatment proves successful, it could help to generate preliminary guidelines and be implemented widely in trauma patients with pain in Emergency Departments.ChiCTR-INR-16007807. Registered on 21 January 2016.Chinese Clinical Trial Register, The online version of this article (10.1186/s13063-018-2899-6) contains supplementary material, which is available to authorized users. Despite there are extensive research on the etiology of pain, barriers to pain management, advanced analgesia approach, and evidence-based guidelines for the pain management such as the World Health Organization three-step analgesic ladder, acute pain remains a common complaint observed in the Emergency Department (ED) with a high prevalence of up to 90% –3. Over Efforts to treat acute pain are priorities for ED healthcare to consider. Patients expect analgesia rapidly in the ED, which is not met in many ED . SeveralHowever, patients with unrelieved pain lead to a stress response consisting of increased heart rate and blood pressure, impaired immune function, systemic vascular resistance, and altered release of neuroendocrine, pituitary, and other hormones . These rNitrous oxide/oxygen is a self-administered inhaled gas reserved in a pre-prepared cylinder. Its analgesic effect has been known for nearly two centuries . It has Evaluating the clinical use safety of the fixed gas by physiological parameters and adverse effects.Assessing the satisfaction of both patients and healthcare workers with pain treatment.Investigating patients’ acceptance for the new analgesia method.The primary aim of the current study is to determine the clinical analgesic effect of the fixed nitrous oxide/oxygen mixture on trauma patients with acute pain when compared with the control group. It is measured by pain relief level. Secondary objectives of this trial include:This is a single-center, prospective, randomized, double-blind, placebo-controlled, two-arm, superiority study. It was designed to test the analgesic effect and safety of inhaling premixed nitrous oxide/oxygen use in adult trauma patients with moderate to severe acute pain. This protocol was drafted using the SPIRIT guidelines  see Add and follThis study will be carried out in the ED of General Hospital of Ningxia Medical University. This institution is an urban, public, 4500-bed, tertiary-care teaching hospital located in Northwest China, with an ED census of 179,117 annually.All trauma patients who present to the ED will be invited to participate. The specific inclusion criteria are: patients who speak Chinese; aged ≥ 18 years; report moderate to severe intensity of acute pain upon admission ; are able to take deep breaths to use the self-managed device; are willing to participate in the study and sign informed consent. Patients are ineligible if they have considered contraindications to using the premixed gas . Other All participating clinicians will be associate chief physicians, will have worked in the ED for > 5 years, and will be willing to participate in and receive training from the originator who conceived and designed the protocol. In this trial, two fixed clinicians who meet all the above criteria will be included.All patients entering the ED will receive regular assessments by the clinician. The patients who meet all pre-specified inclusion and exclusion criteria will be introduced to the study. Investigators will explain the purpose, benefits, and potential risks of the study in detail to the patients. If the patients agree to participate in this study, they will be asked to sign an informed consent form and then be recruited. Subsequently, the relevant treatment will be carried out immediately. During the implementation of the intervention, the patients are randomly allocated to inhale either a fixed concentration of premixed nitrous oxide/oxygen or oxygen through a specially designed facemask with a one-way valve. The treatment group will receive nitrous oxide/oxygen mixture in addition to conventional pain treatment and the control group will receive oxygen in addition to conventional pain treatment. In this study, the oxygen cylinder is designed exactly the same as the nitrous oxide cylinder and oxygen is safe and readily available in the selected ED. We chose oxygen plus conventional pain treatment as a comparator to ensure the full consistency between treatment group and control group and the double-blind design. Gas inhalation will be administered continuously up to a maximum inhalation time of 15 min. Practitioners will be permitted to use other pain management forms in accordance with patients’ pain intensity after finishing the intervention. The trained investigator will successively include participants until they reach the target sample size and the project manager will assign participants to interventions according to the randomization list.Generally, both nitrous oxide/oxygen and oxygen are considered safe interventions with no severe side effects for the participants. If side effects occur  during the implementation of nitrous oxide/oxygen, they are usually short-lived and mild . If any There are many strategies to improve the adherence of the intervention. Before the start of the intervention, investigators will detail the duration of the intervention, the method of using the device, possible adverse effects, and give psychological support to participants. During the treatment, the patients’ physiological parameters are monitored and patients are asked if they feel uncomfortable or not. If they are uncomfortable, this is address immediately to ensure the ongoing safety of patients is accomplished. Adherence of intervention protocols will be ascertained by accomplishment of the intervention. We planned to develop a Supervision Adherence Form (SAF) for this trial to enable collation of patients’ adherence to facilitate reporting.All participants will be randomly allocated into the intervention or control group in a ratio of 1:1. The randomization list of each ED patient will be generated by a computer, which is calculated by a statistical expert from the Faculty of Medical Statistics and Epidemiology, Ningxia Medical University. A sealed envelope will be used to store the randomization schedule which will be restricted in a dedicated research office to maintain confidentiality. In order to make sure of “double-blind” conditions, no data collectors or investigators have access to the data distribution. Only the project manager who will be responsible for gas distribution can consult this information. Ningfeng Oxygen Company packages the two gas mixtures in strictly identical-looking gas cylinders, one containing nitrous oxide/oxygen and the other oxygen. Therefor, all the gas cylinders will be identified only with a label (A or B). Patients given the letter A will be treated using a canister with the appropriate letter containing premixed nitrous oxide/oxygen. Those with the letter B will be given oxygen. Before and during the treatment period, the patient, the investigator, and the data collector are also blind to what is in each canister and what the letters A and B stand for. The rules were that the cessation of blinding would take place by the project manager only, after the completion of all the trials.The investigator will record participants’ characteristics, demographic data , and physiological parameters . Other information regarding pain score, diagnosis of traumatic injury, total length of gas inhalation, analgesic prescription, adverse effects, satisfaction of patients and healthcare professionals, as well as the acceptance from patients will be recorded by the researcher.Self-assessment of pain severity will be measured with the NRS. The NRS is a tool with great reliability and validity that is frequently used for assessing pain level from zero (painfree) to ten (worst pain intolerable) . The phyAny observed adverse effects of the fixed nitrous oxide/oxygen mixture and oxygen will be carefully evaluated and recorded by the investigator after the beginning of the gas administration. The prospectively occurred adverse effects include gastrointestinal adverse effects , respiratory adverse effects , and any other discomfort  . If any Both patients’ and healthcare providers’ satisfaction with pain administration under the new analgesia will be investigated by a five-point satisfaction scale  . MoreoveThe clinical demographic data, details of trauma type, and analgesic prescription will be obtained from medical records using a standardized case report form.The primary outcome measure will be the level of pain relief after the initiation of the intervention, which is assessed and recorded by the data collector according to the pain level provided by patients using a self-assessment scale (NRS).Secondary outcome measures include physiological parameters, adverse events, overall satisfaction from both patients and healthcare professionals, acceptance from patients, and total time of the gas administration.β = 0.10) for two-tailed testing with 5% type-1 error rate of the measure. We separately calculated a minimum requirement of 30 patients or 24 patients for total with the formula [Based on our previous studies on cancer breakthrough pain and burn-dressing pain , 34, thi formula , 37. In In this trial, participants will be recruited at the ED of General Hospital of Ningxia Medical University. This medical center is the largest hospital in Ningxia Hui Autonomous Region. It is well-known in the northwestern region of China for its comprehensive disciplines, powerful technology, advanced medical equipment, outstanding specialties, and strong multidisciplinary advantages. Furthermoremore, according to the ED census data of 2016, there is a sufficient patient source in this hospital. Thus, in this selected clinical center, it is feasible to reach the target sample size.As soon as a participant is enrolled, the research team are responsible for achieving a low rate of loss to intervention. Patients have the right to withdraw from the study at any time and this will not affect their subsequent treatment. The Data Monitoring Committee (DMC) will discuss and analyze the reason of dropout with the data collectors, which will be documented on a standardized pro forma.All members involved in the research team will receive group training sessions before the study. Training will include study design (e.g. require double-blind), intervention process , assessment of the outcome measures (e.g. standardized procedures to assess), and recorded data (e.g. training for the use of a unified data collection form in detail). Furthermore, the trained data collectors and investigators are fixed during the implementation of interventions and through the double-entry method for data quality control. The members of the DMC and the auditor will inspect this database regularly to promote data quality (see “Data monitoring” and “Auditing”). Using a Microsoft Access database  to accomplish all study data input.Throughout the trial, participants are anonymized. All participants’ personal information (e.g. name and patient identification number) will be kept in a separate locked cabinet and will be entered into the password-protected Microsoft Access database. Only research team members can access this personal data with reasonable request and consent of the project manager. A separate code, generated by pre-randomization, will enable anonymized data to be identified and this unique identifier will be maintained by the project manager. Anonymized trial data will be stored securely in another Microsoft Access database. The trial data collectors, the investigator, and the members of the DMC can access the trial data for the final statistical analysis.This trial will be overseen by a DMC, which is independent from the sponsor and competing interests. Members consisted of one clinician, two nurses working in the ED, one pain management specialist, and a senior academic statistician who acts as the committee’s chair. The DMC will meet regularly to monitor the trial progress and guarantee protocol adherence. They are also responsible for checking for the reason of the participant withdrawal from this trial, assessing safety issues, and if there are any reasons that the trial should discontinue or make amendments.The trial funder will apply audits annually and inspect the source data to verify the accuracy, completion, validity, and safety of the data. The auditing will potentially include the utilization of funds, the essential documents, the trial progress, and the participants’ medical records.t test or non-parametric test and using the Mann–Whitney test to compare means of continuous variables if applicable. Chi-squared tests or Fisher’s exact test will be performed to compare the proportions of categorical variables. The analysis of physiological parameters and scores at baseline, T2, and T3 were performed by analysis of covariant (ANCOVA) adjusting for the respective baseline value on the two groups . We considered all P values < 0.05 to be statistically significant.SPSS version 22.0  will be used to conduct the statistic analysis, initially according to the intention-to-treat principle. All patients randomized should be included in the analysis and missing data will be handled using multiple imputation. Descriptive statistics will be adopted to describe the population demographic data by medians , means (standard deviations), and proportions , as appropriate. The comparison of means will be assessed by Student’s The findings of this study will be shared with healthcare workers, patients, the general public, and relevant departments through open-access articles, public talks, conferences, and final reports. Any modifications of this protocol and changes to eligibility criteria or outcomes will be communicated with the DMC, clinicians, trial participants, and research ethics committee review board. There are no professional writers to be employed to complete the manuscript. Authorship eligibility guidelines which comply with the International Committee of Medical Journal Editors (ICMJE) guidelines  will be The commitment to manage a patient’s pain and relieve suffering is the foundation of a healthcare professional’s obligation. Pain is not just a clinical symptom but also an evidence of potential pathology. In acute trauma environments, there is a temptation to ignore pain and its unique management, but all treatments lay the attention on the underlying pathology . The chaIn trauma patients, we usually give priority to injury mechanisms and assess the patient’s signs of life, including the level of consciousness. Nevertheless, opioids may interfere with this assessment and necessitate continuous monitoring for some patients using these drugs , 39. OpiTo the best of our knowledge, this is the first randomized controlled trial in a busy emergency environment to evaluate the safety and analgesic effectiveness of the fixed nitrous oxide/oxygen mixture in patients with trauma in China. Pain is a natural accompaniment of acute injury to tissues, which is predictable in the case of acute trauma. If this treatment seems to be beneficial, this study could help to generate preliminary pain guidelines in patients with acute trauma and improve patients’ overall satisfaction with ED. We believe that the results of this study could be considered as the introduction of pain management and be disseminated to international journals and conferences.Recruitment of patients began in November 2017.Additional file 1:SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents. (DOC 115 kb)Additional file 2:CONSORT 2010 checklist of information to include when reporting a randomized trial. (DOC 195 kb)


A well-known supportive treatment for acute nonspecific back pain, elastic back support belts, are valued for their ability to accelerate natural self-healing, but there are concerns of a deconditioning effect due to their reliance on passive stabilization.To evaluate the systematic effects of elastic abdominal belts on the trunk musculature, a total of 36 persons with acute lumbar back pain (no longer than one week) were divided into two groups: an abdominal belt wearing group (B) and a non-abdominal belt wearing control group (C). All were examined over a period of three weeks at three time points: T1 just after assignment, T2 one week later, and T3 further two weeks later. Surface EMG (sEMG) was used to record trunk muscle activation when walking on a treadmill at walking speeds of 2, 3, 4, 5, and 6 km/h. Similarly, pain intensity (VAS) and functional impairment (ODI) over time were recorded in both groups.Over the observation period, a slight advantage for decreased pain intensity  and decreased functional impairment  was observed for the belt group. For the belt group both oblique abdominal muscles exhibited significantly lower sEMG throughout the observation period , T2, (T3), internal abdominal oblique muscle: T1, (T2), (T3)) and the sEMG for the back muscles ranged from unchanged to slightly elevated for this group, but never reached statistical significance.The reduced abdominal amplitude levels in the belt group likely result from the permanent elastic stabilization provided by the belt: the required elevated intra-abdominal pressure to enhance spinal stability is then provided by lessened abdominal muscle activity complemented by the belt’s elastic support. With regard to the back muscles, the belt, due to its movement-restricting effect, tends to activate the paravertebral musculature. In this respect, the effect of elastic abdominal belts on the trunk muscles is not uniform. Therefore, the present results suggest that the effect of elastic abdominal belts appears to be more of a temporary neutral alteration of trunk muscle coordination, with some trunk muscles becoming more active and others less, and not a case of uniform deconditioning as is suspected. In addition to their common use in preventing back injury, e.g. during heavy load carrying in industrial settings, elastic lumbar support belts are often applied as a therapeutic device to accelerate the relief of suffering from acute back pain, one of the most common and expensive diseases in Germany . But theDespite intensive investigation of the efficacy of elastic lumbar support belts as an aspect of relief of acute back pain questions remain because causes of low back pain are not directly visible using typical physiological diagnostic techniques. The bulk of this research has relied on somewhat subjective data such as missed work days, compensation claims, and questionnaires obtained from acute back pain patients, regarding pain relief, functional restoration, and return to work . As a reOne way of measuring the physiological effects of elastic back support belts in the treatment of non-specific acute low back pain is to make inferences based on changes in muscle function. Only a few such physiological studies on changes in trunk muscle function have been published as yet. These studies as a group utilized different methodologies and as yet have not provided a consensus . There iOwn investigations in healthy subjects already provided hints that argue against the suspected deconditioning effect of elastic lumbar support belts , which iAccording to own previous results on the effects of elastic lumbar support belts in healthy volunteers during walking  we hypotThe study was conducted as a comparative observational study over a three-week period. The study was approved by the Ethics Committee of the Friedrich-Schiller-University Jena (4205–09 / 14). The patients were recruited via press calls, referrals from treating physicians as well as posters.Study participants included patients of both sexes between the ages of 30 and 60, who, at the time of recruitment had acute local back pain in the area between the iliac crest and the costal arch lasting no longer than one week. Exclusion criteria included permanent, or more than a week lasting pain, a BMI > 30, past surgery of the spine, the inability to implement the experiment mentally and/or physically (including a thorough check of ability to habituate to treadmill locomotion) as well as radiating pain in the legs or pain outside the defined region. Recurrent low back pain less than three times per year did not lead to exclusion from the study if the last pain episode was more than 3 months prior.In the period 02/2015–04/2016, 284 potential study participants were contacted via the mentioned recruiting channels. Due to the inclusion and exclusion criteria, 38 persons could be included in the study. The most common reasons for exclusion from the study were longer-lasting or chronic low back pain and nonspecific pain sites. Furthermore, a total of two participants due to illness-related drop-out  had to be excluded from the analysis.After admission to the study subjects were assigned to the group belt (B) or control (C) in an alternating fashion. This was done separately for both sexes, with the initial assignment made to the C group. The composition of the two groups is shown in In agreement with the sex-specificity of human anthropometric characteristics, study participants differed between sexes for height and weight , 16, butAt the beginning of the first investigation time participants were habituated to the treadmill locomotion. Only when a natural gait pattern  was achieved was the actual measurement preparation and examination begun. After successful treadmill habituation participants were instrumented . The examination was carried out by asking patients to walk at speeds of 2–6 km/h in a 1 km/h gradation on a treadmill. Per walking speed always at least 40 strides were completed. The sequence of walking speeds was individually randomized  and then maintained for that participant for each of the three study sessions .The Trials were performed at three time points: immediately after assignment or contact (T1), one week later T2) and two further weeks later (T3). For the group with belt, T1 involved two scenarios: a complete examination without the elastic lumbar support belt (T1-1) and after a five minutes rest time another complete examination with the elastic lumbar support belt on (T1-2). For the investigation, the abdominal elastic lumbar support belt Lumbotrain (Bauerfeind AG) was used in the respective size  and gender-specific design. Its ventral and dorsal height was 17 cm and 23 cm , respectively. It comes with a triangularly shaped reinforcement element that is placed at the middle of the back with its downwards pointing angle over the tailbone. The Lumbotrain can be fastened in the front by pulling finger pockets evenly forward and fixing both sides in place with Velcro fasteners. The belt is made of a bi-elastic knit that stretches in horizontal and vertical directions and can be worn directly on the skin and also over a thin shirt. Patients were asked to wear the elastic lumbar support belt daily for a minimum of 4 hours, as recommended by the manufacturer. Wearing of the support is recommended during any kind of physical activity, but subjects were instructed to remove it during prolonged times of inactivity, i.e. during sitting or lying down. By this the German guidelines for the treatment of low back pain that among other things recommend physical activity were implicitly considered [ and two At each examination, participants’ current pain intensity was requested before and after the treadmill testing (VAS 1–10). After completion of the treadmill testing, the degree of functional impairment was assessed using the Oswestry Disability Inventory (ODI).As a physiological measure, the surface EMG (sEMG) of six superficial trunk muscles was measured simultaneously from both body sides. The electrodes  were positioned according to the international recommendations , 18 and In addition, one electrode pair was positioned along the heart axis to allow the elimination of QRS complexes through registration of cardiac activity. To detect the individual steps, pressure sensors were fastened in the heel area of the shoes. Secure seating of all electrodes was monitored throughout the entire examination and loose electrodes were replaced.The signals were amplified , digitized , DeMeTec) and stored on hard disk for further processing .For the data analysis, the sEMG signals were band pass filtered between 20 Hz and 300 Hz and a 50 Hz notch filter was used to eliminate interferences from the power grid. The inevitable heart activity disruptions were individually and separately eliminated for each sEMG channel using a template-based algorithm . Based oFor the analysis, the sEMG data, the scores in the ODI, and the details of the pain intensity before and after the treadmill testing were used. From the amplitude curves, the mean (time independent) SEMG amplitude levels were calculated.The values for the pain and the ODI data were subjected to an ANOVA which took into account the trial numbers  as well as the application of the elastic lumbar support belt (without/ with) as the between subject factor.All sEMG data were covariance analyzed to identify the possible main effects "belt" , "Trial" , "walking speed" , as well as "gender"  and their interactions.2 (η2p), η2p ≥ 0.06: mean effect, η2p ≥ 0.14: large effect [All parameters were further statistically tested both in the course and between the two groups at all investigation times. In order to address the multiple test problem, i.e. to perform a correct statistical testing of the individual values, the accumulation of the type I statistical error had to be considered, which required a correction of the significance level . Howevere effect ; single e effect ).2p = 0.189) could be demonstrated, but it was not possible to detect a systematic effect of the main effect "belt" .In the ANOVA, a general effect of the Trial  and 2.54 ± 1.88 (C). However, the belt group subsequently showed a more marked reduction in the pain level compared to the baseline level , which wFor the values in the ODI also no systematic differences between the groups could be proven. Likewise, the values see  indicateIn the ANOVA neither systematic effects of body side (p: 0.119–0.990) nor gender (p: 0.087–0.906) could be determined. The only exception to this was the data of OE, which showed a gender dependency (p: 0.007–0.062), independent of trial number (p: 0.209–0.923) or group affiliation to the belt or control group (p: 0.280–0.858). Therefore, the individual tests regarding existing differences between the Trials and the group differences were generally calculated with pooled data of both sexes and exemplarily with the values of the left side of the body.With increasing walking speed an increase of mean amplitude values could be observed for all investigated trunk muscles. The RA showed the lowest levels with maximum mean amplitude values of less than 5 μV , while the OI showed the highest values of about 24 μV , T2, T3, OE: T1 (T2), T3, see The results for the grand averaged amplitude curves confirm the data of the mean amplitude values see : for theIn the presented study, it could be shown that for patients with acute back pain over a three week period a noticeable reduction of back pain, and improved restoration of functional disability could be observed. These improvements were slightly augmented by wearing an elastic lumbar support belt. As for objective measures, systematic effects on the activity characteristics of trunk muscles during walking were observed using sEMG. While the subjective positive effects on pain reduction and functional impairment have already been described in the literature , 7, sEMGPain intensity at study enrollment was lower than in other studies , 23, shoThe initial values for the functional disability (ODI) with 22.5 (C) and 24.8 (B) were also lower than described in the literature  but are The differentiated effect of the elastic lumbar support belt on the amplitude levels already described in the summary of the results, at first sight appears contradictory to the outcome of improved symptomology. Closer analysis of the passive stabilizing properties of the elastic lumbar support belt suggests that the function of the abdominal muscles in acute back pain plays a key role: previous studies on back pain patients have demonstrated compensatory increases in activity and co-contraction indices, especially for abdominal muscles , 4. By tIn contrast, it was not possible to identify general, but only punctual differences in the amplitude curves for the back muscles, in which the belt group always had the higher amplitude values than the control group. These momentary differences were accompanied by non-significant, but slightly elevated mean amplitude levels at T2 for MF and T3 for all back muscles, and were consistent with biomechanical model calculations that could not identify one single muscle, but the well-coordinated action of all trunk muscles to improve spinal stability . As indiIn this study we have not investigated tasks performed in other belt studies of healthy volunteers, such as manual lifting , squat lComparing both our studies for the back muscles, acute back pain patients, in contrast to healthy subjects, show phase specific elevated amplitudes of their back muscles while wearing belts. Differences between acute low back pain patients and healthy subjects are not surprising because different intermuscular co-ordination is seen during acute back pain . DiffereThus, first of all, there was clearly no sign that wearing a lumbar compression elastic lumbar support belt leads to a general deconditioning of the back muscles. The amplitude levels of the abdominal muscles were significantly reduced in the belt group with no specific stride phase attribution, most probably caused by the passive elastic support of the belt. Over the observation period all patients showed a reduction of their pain level and improvement of their functional impairment that was slightly augmented in the belt group. The observation period of three weeks is consistent with the natural course of acute low back pain and the observed results demonstrated a repeatable effect of the belt. Future studies should be based on a broader database and involving other common activities like twisting, bending and light lifting, and eventually include patients with recurrent back pain.For the study, only 36 people could be included in the analysis, which makes broad generalization from the results impossible. The 36 patients who were analyzed were selected from a total of 284 patients who responded to the recruitment effort, representing a 12.7% inclusion rate—higher than in other studies . Also, tS1 Dataset(ZIP)Click here for additional data file.


High molecular weight (HMW) hyaluronic acid (HA) is a treatment option for knee osteoarthritis (OA). The efficacy of HMW-HA in knee OA is investigated extensively, but the effectiveness in patients in the working age is unknown. Nevertheless, the number knee OA patients in the working age is increasing. Surgical treatment options are less eligible in these patients and productivity losses are high. In this study the effectiveness of intra-articular HMW-HA added to regular non-surgical usual care in everyday clinical practice (UC) compared to UC over 52 weeks in symptomatic knee OA patients in the working age was investigated.In this open labelled randomized controlled trial, subjects aged between 18 and 65 years with symptomatic knee OA (Kellgren and Lawrence I-III) were enrolled and randomized to UC + 3 weekly injections with HMW-HA (intervention) or UC only (control). The primary outcome was the between group difference in responders to therapy according to OMERACT-OARSI criteria after 52 weeks. These criteria include the domains pain, knee related function and patient’s global assessment (PGA). Function was evaluated with the KOOS questionnaire. Pain was assessed with the Numeric Rating Scale. Secondary outcome comprised the between group difference on the individual responder domains, as analysed with a random effects model. Odds Ratios (OR) were calculated by logistic regression analysis. Sensitivity analyses were performed.p = 0.006) and 54.5% versus 34.2% (p = 0.015) was responder to therapy respectively. The results of the secondary outcome analyses show that scores on individual responder domains over all follow-up moments were statistically significant in favour of the intervention group in the domains pain during rest , knee related function  and PGA .In total, 156 subjects were included . Subjects in the intervention group (HMW-HA + UC) were more often responder compared to the controls (UC). Depending on whether pain during rest or pain during activity was included in the responder domains, 57.1% versus 34.2%  contains supplementary material, which is available to authorized users. Knee osteoarthritis (OA) is a chronic degenerative disease of the knee joint, causing pain, joint stiffness and functional impairment –3. The lThe initial pharmacological treatment for patients with symptomatic knee OA generally includes rapid-acting pain medication like acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs have shown to be effective in pain reduction and functional improvement in the symptomatic treatment of knee OA –9.Treatment with NSAIDs is related to an increased risk of serious gastrointestinal and cardiovascular side effects, indicating limited use of NSAIDs only , 11. TheAn alternative treatment for knee OA patients is intra-articular injection therapy with hyaluronic acid (HA) . Intra-aLimiting the results of meta-analyses to high quality trials only, the effect on pain is still clinically relevant in favour of intra-articular HA , 18. TheThe effectiveness of HMW-HA in knee OA patients in the working age has not been evaluated yet. Relevance lies in the fact that the number patients with knee OA in the working age is increasing and surgical treatment options like unicompartmental or total knee arthroplasty (TKA) are less eligible in these patients, especially when they are involved in a physically demanding occupation , 22. TheThe aim of this study was to assess the effectiveness of intra-articular HMW-HA added to usual care (UC) compared to UC over a period of 52 weeks in symptomatic knee OA patients in the working age. We hypothesized that adding HMW-HA in patients with knee OA has a clinical relevant effect.Alongside this effectiveness analysis, a parallel economic evaluation was performed which was published previously . In thiswww.trialregister.nl, NTR1651). The study protocol is available from the corresponding author on request.The current effectiveness evaluation and the previously published cost-effectiveness evaluation are both part of the VIScosupplementation for Knee osteoarthritis (VISK) study. The VISK study is registered at the Dutch trial register , is required to facilitate the parallel economic evaluation of the VISK study , 27.Inclusion of eligible subjects took place between May 2009 and May 2010 in 2 hospitals  in The Netherlands. Consecutive knee OA patients at the outpatient orthopaedic department meeting the inclusion criteria were considered eligible. Patient’s age was set between 18 and 65 years, the latter being the pensionable age in The Netherlands at the inclusion period. Inclusion criteria were: pain > 3 months, mean pain severity ≥2 on the numeric rating scale (NRS), Kellgren & Lawrence (K&L) grade I to III in medial and/or lateral compartment.Exclusion criteria were: intra-articular HA injections < 1 year, intra-articular steroid injection < 3 months, arthroscopy < 6 months, tibial osteotomy < 1 year, synovectomy, scheduled knee surgery < 1 year, varus/valgus deformity > 12 degrees, chondrocalcinosis, dermatologic knee disorders, allergy to HMW-HA components, (planned) pregnancy or lactation, inflammatory arthritis, severe hip OA, non-knee related regular analgesic use, daily oral steroid therapy, poor general health, conditions interfering with functional assessments, alcoholism, patients unable to attend follow-up and insufficient command of the Dutch language.The sample size was calculated to detect a between group difference of 20% in the primary outcome parameter which was defined as response to therapy at 52 weeks according to OMERACT-OARSI criteria . A powerRandomization took place after informed consent was signed. Concealed randomization was performed by computer generated lists with randomly assigned blocs of 2, 4, 6, 8 or 10 subjects. An independent employee not involved in any other part of the study performed the randomization. Stratification took place for radiologic degree of knee AO (K&L grade I/II versus grade III) and per orthopedic surgeons responsible for injections .The statistician and investigator responsible for assessment and analyses of the data were blinded for the treatment allocation. Due to the study design included subjects and orthopedic surgeons administering the study intervention could not be blinded.Subjects in the intervention group received 3 weekly intra-articular injections with Hylan G-F 20  added to usual care or usual care only. Hylan G-F 20 is the HMW-HA derivative with the highest molecular weight available for clinical use  , 31. A nThe primary outcome was defined as response to therapy at 52 weeks follow-up according to OMERACT-OARSI criteria. This variable presents the results of changes after treatment in three symptomatic domains  as a single variable . ResponsThe secondary outcome comprised the between group difference over the whole follow-up period of the 3 individual primary outcome responder domains: pain, function, and PGA.For the primary outcome, the difference in percentage of responders according to OMERACT-OARSI criteria between study groups after 52 weeks follow-up was calculated . In the In order to minimize bias in favor of the intervention group, drop-outs and subjects lost to follow up were (regardless of their study results) considered non-responders in the intervention group, and (vice versa) responders in the control group in the final analyses.Logistic regression analysis with responder as dependent variable and the intervention as independent variable were performed to calculate odds ratios (OR) including 95% confidence intervals (95%CI) after 52 weeks follow-up. The number needed to treat (NNT) to attain 1 responder was calculated (PASW statistics 17.0).For the secondary outcome, scores on individual responder domains  were analyzed over all follow-up moments by means of a random effects model with random intercept and slope. The baseline values of the variables and the treatment group were included in the model. In this way we obtained for each outcome an estimate for the between group difference in score on the relevant questionnaires  over the whole follow-up period, including associated 95% CI .Sixteen subjects divided over both study groups received knee related surgery during follow-up. This number was not foreseen and we therefore performed 2 additional sensitivity analyses to assess possible beneficial clinical effects on pain and function as a result of the surgery. These analyses were not specified in the VISK study protocol a priori. In these sensitivity analyses, subject receiving knee related were considered non-responder irrespective of their study results.  In the fIn total, 156 patients were included of which 77 subjects  8.6 range 20.9–64.6) in the intervention group and 79 subjects  in the control group. The study flowchart is shown in Fig. p = 0.006). With pain during activity included, 54.5% of the subjects was responders to therapy in the intervention group versus 34.2% of the controls (p = 0.015).In Table p = 0.010), knee related function  and PGA . The intervention group also scored lower on the pain during activity score, but this difference was not statistically significant .Over the whole follow-up period, we found statistically significant better scores in the intervention group in the domains pain during rest, knee related function, and PGA Figs. , 3 and 4Nine surgical procedures related to the study knee were performed in the intervention group during follow-up, versus 7 in the control group. Despite a slight decrease in the between group differences in responder percentages, the results of both additional analyses are still statistically significant in favour of the intervention group Table .At baseline, more subjects used pain medication because of knee complaints in the intervention group with (53%) compared to the control group (42%). This difference decreased over time, resulting in similar usage of pain medication for both groups at final follow-up. The difference in pain medication users was not statistically significant on any of the time points during follow-up.p > 0.001, number needed to harm (NNH) 4.0). The difference decreased at 13 weeks, and at 26 weeks the percentage of subjects reporting flares was similar in both groups. None of the between group differences on the following time points after 6 weeks were statistically significant. No septic arthritis of the study knee occurred in any of the subjects during follow-up.In the intervention group, more subjects reported any knee treatment related adverse events (AE) at 6 weeks (45% versus 18%. This difference was mainly due to flares or flare like symptoms of the study knee in this period (36% versus 10%), The amount of non-treatment related AEs was similar in both groups during follow-up. An additional file shows the percentage of patients experiencing treatment and non-treatment related adverse events per study group per time point during study follow-up  was statistically significant and in favour of the intervention group. Subjects in the intervention group experienced more episodes of transient knee pain and/or swelling during the first 6 weeks.In our study we specifically choose to include subjects in the working age (mean age 54) with a higher involvement in paid work (75%) . By doinTo date, 2 other studies compared HMW-HA added to usual care to usual care only , 35. Thep= > 0.001) in the control group. No septic arthritis occurred. These results on local adverse events (AE) are similar compared to other studies [Intra-articular injections with HMW-HA are frequently accompanied by transient pain or swelling of the knee. The procedure itself also includes a risk of inducing septic arthritis , 17. At  studies , 35. In The follow up of the VISK study was 52 weeks. Optimal pain decrease after administration of intra-articular HMW-HA is seen at about 3 months though , 18. A sThis study has limitations that need to be addressed. The study design of the VISK study did not include a placebo group. Previous research showed that placebo effects in intra-articular HA studies are above average . It is tThe target population of our study can be described as secondary care patients with symptomatic and mild to moderate knee OA. We therefore included subjects with K&L grade I-III and a minimal VAS pain score of 2. Patients who were more likely to benefit from surgical therapy like TKA or osteotomy, or from rheumatologic treatment where excluded in this study . We aimed to avoid measuring effects strongly related to other factors than the intervention itself  and to avoid possible harm due to the intervention . Applying these criteria may have consequences for the generalizability of the results. It is for example uncertain if the effectiveness results also extend to other patient groups who might benefit from HMW-HA treatment, like knee OA patients not fit for surgery who are in need of surgical therapy.We conclude that intra-articular injections with HMW-HA added to usual care is effective in patients in the working age. It results in more responders to therapy and improvement in pain, function and PGA.Additional file 1:Adverse events per study group per time point. Displays the amount of subjects experiencing treatment related and non-treatment related adverse events and their nature. (DOCX 20 kb)