Central sensitisation, in addition to high levels of fear-avoidance and pain catastrophisation may exist in a subgroup of patients with shoulder pain. Pain neuroscience education (PNE) has been shown to positively influence sensitivity of the nervous system, as well as reduce fear and catastrophisation prior to lumbar and total knee surgery. To date, no study has examined the application of PNE prior to shoulder surgery.This study examined the response to preoperative PNE in patients preparing for shoulder surgery.An exploratory pre–post case series was conducted. Twelve patients scheduled for surgery completed various pre-education measurements including shoulder pain, fear-avoidance, pain catastrophisation, beliefs and expectations regarding surgery, active shoulder flexion and pressure pain thresholds for the involved and uninvolved shoulder and the dominant-sided knee. Patients underwent a standard 30-min, one-on-one PNE session with a physiotherapist prior to surgery.p = 0.125), pain catastrophisation (p = 0.250) and pain pressure threshold of the uninvolved shoulder (p = 0.68) and knee (p = 0.097). Fear-avoidance (p = 0.013), active shoulder flexion (p = 0.013) and pain pressure threshold for the involved shoulder (p = 0.004) significantly improved.Following education, all measures improved with some failing to reach significance: self-reported pain (A small patient group improved beyond minimal detectable change and/or minimal clinical important difference after education. No significant shifts of the preoperative beliefs occurred after education.Preoperative PNE may be beneficial to a subgroup of patients scheduled for shoulder surgery. It is now well established that a patient’s beliefs and cognitions, especially regarding pain, influence his or her pain experience and outcome related to treatment  may potentially decrease the chance of developing chronic pain and disability. For example, preoperative PNE for patients undergoing lumbar surgery and total knee replacements in the United States has shown to yield significant improvements in patient surgical experiences and healthcare utilisation at 6-month, 1-year and 3-year follow-up compared with no preoperative PNE , awaiting shoulder surgery. Patients meeting the inclusion criteria were sent to a physiotherapist by the surgeon for one preoperative PNE session prior to surgery. Inclusion criteria were that patients had to (1) be scheduled to have shoulder surgery in the next 2 weeks, (2) indicate their willingness to participate in the study and (3) have the ability to read and understand English, as the study included the use of an English educational booklet.Because all potential participants for our study had been screened and cleared for their orthopaedic surgery, the only exclusion criterion was an unwillingness to participate in the study.Prior to PNE and after completion of the consent and demographic intake forms, patients were asked to complete self-report surveys related to shoulder pain, fear-avoidance, pain catastrophisation, fear of movement and their beliefs about surgical outcome. Patients were also asked to complete the CSI once, prior to PNE, to measure for CS in order to further describe the study population.Pain: Self-reported shoulder pain was measured using a Numeric Pain Rating Scale (NPRS), which has been shown to be a valid and reliable measure in patients with shoulder pain Moseley , 2005. WPain catastrophisation: Pain catastrophisation was measured using the Pain Catastrophising Scale (PCS). The PCS is a self-report questionnaire that assesses inappropriate coping strategies and catastrophic thinking about pain and injury. The PCS has been used in previous pain science studies Moseley  and demoFear of movement: To evaluate the participant’s pain-related fear of movement and (re)injury, the original 17-item Tampa Scale of Kinaesiophobia (TSK) was used  with six statements regarding shoulder surgery. The statements were used in a similar PNE study for lumbar surgery and total knee arthroplasty and adapted for shoulder surgery : Active shoulder flexion of each patient’s ‘affected’ arm was assessed with a goniometer, with the patient in a seated position. To allow consistency of pre- and post-PNE measurements, skin marks were placed for the goniometric measurements. There is good reliability and validity of goniometric shoulder AROM measurements  using a digital pressure-pain algometer. The algometer had a 1-cm2 round rubber tip that was placed over the three predetermined points of (1) the deltoid insertion of the affected shoulder, (2) the deltoid insertion of the unaffected shoulder and (3) the posterior midline of the dominant-sided knee. Before applying pressure, the examiner instructed each participant: ‘I am going to begin applying pressure to your skin. I want you to tell me the moment the sensation changes from comfortable pressure to slightly unpleasant pain’. Pressure was then applied at a rate of 5 N/s. The examiner stopped applying pressure and recorded the measurement when the participants said ‘now’. Three consecutive PPT measurements were taken at each point with 20 s rest between measurements, and the mean of the three trials was used for analysis. Various studies have reported a 15% reduction in PPT as a significant clinical change  followed standardised protocols  for the study was, and therapists administering the PNE were kept blinded to the pre- and post-PNE measurements. All self-report outcome measures were repeated immediately after the PNE so that they could be compared with pre-PNE scores.The 30-min PNE programme used in this study was an adaptation of the programme developed for lumbar surgery and total knee arthroplasty . Descriptive statistics were calculated for means and frequencies for the sample population and patient beliefs. A significance level of 0.05 was set for all analyses. Paired-samples This study was approved by the Internal Review Board (IRB)/Ethics at Southwest Baptist University on 31 January 2017. Patients provided written and verbal consent to participate in the study.n = 8 [66.7%]). Additional diagnoses included labral tear, fracture and shoulder osteoarthritis. The mean CSI score for the sample was 33.83 and five patients (41.7%) met or exceeded the score (40 points) indicative of the cut-off for CS.The mean age of the 12 study participants was 61.7 years , and the average number of months that the participants reported being in pain was 26.1 months . Eight of the study participants (66.7%) were female, and half (50%) of the involved shoulders were on the right side. One hundred per cent of the participants were having shoulder surgery on the involved shoulder for the first time, and three participants (25%) had received shoulder surgery on the other, uninvolved, side previously. The most common pre-surgical diagnosis was rotator cuff tear (p > 0.0005). Therefore, an exact sign test was conducted to determine any effect of the PNE on the NPRS. There was no statistically significant median decrease in the participant’s reported pain rating after receiving the PNE . Three patients reported a reduction on the NPRS of 2 points after PNE, exceeding the MCID.The difference in scores for the pre- and post-PNE pain ratings was not normally distributed, as assessed by Shapiro–Wilk’s test (t (11) = 2.954; p = 0.013; d = 0.853; Participants showed a decrease in the TSK following PNE (33.17 ± 7.14) compared with before PNE , a statistically significant mean decrease of 4.0 points  = 1.22; p = 0.250), which did not meet or exceed the MDC (Participants showed a decrease in the PCS following PNE (7.50 ± 6.52) compared with before PNE , but this difference was not found to be statistically significant. The mean decrease was 1.50 points  = 2.966; p = 0.013; d = 0.856; Participants showed an increase in the flexion AROM of the involved shoulder following the PNE (130.4 ± 30.45) compared with before the PNE , a statistically significant mean increase of 5.3°  = 3.574; p = 0.004; d = 1.03; Participants showed an increase in the PPT at the involved shoulder following PNE (4.29 ± 2.77) compared with before PNE (3.4 ± 2.34), a statistically significant increase of 0.89 kg of force  = 0.477; p = 0.648). Similarly, PPT at the knee increased following PNE (5.59 ± 2.95) compared with before PNE (4.93 ± 2.77), but this difference was not found to be statistically significant and did not meet MCID  = 1.81; p = 0.097).Pressure pain threshold at the uninvolved shoulder following PNE increased (4.66 ± 3.52) compared with before PNE (4.46 ± 2.85), but this difference was not found to be statistically significant, and it did not meet the MCID  was conducted; it should be part of the next phase along with comparing PNE with other or no treatment.For this patient cohort, PNE does not appear to significantly influence pain, self-reported pain ratings, fear-avoidance, pain catastrophisation or patient beliefs. A small group of patients was observed to experience clinically meaningful shifts in pain catastrophising and fear-avoidance. Preoperative PNE for shoulder surgery appears to result in significant reduction in nerve sensitivity on the shoulder being operated on.


A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice.Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use.Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients’ cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy.This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care. According to the Italian Oncologic Pain Survey (IOPS) study group,4 BTcP should be defined “as a relevant change in pain intensity of severe intensity in patients who receive an effective treatment with opioids.”4(p963) Nevertheless, despite this unique definition, BTcP encloses a wide range of manifestations that differ, among other features, in intensity, duration, frequency, and triggering events. BTcP represents a clinically relevant condition with a negative impact on the patient’s quality of life. In the majority, it is difficult to achieve an acceptable degree of relief because patients with cancer have complex pain syndromes. These patients often require more intense therapeutic protocols and, therefore, more time may be required to achieve adequate pain control.5Breakthrough cancer pain (BTcP) is a common event that affects a considerable proportion of patients with cancer.At present, several gaps exist in the knowledge of BTcP management. These partially unanswered questions, among others, concern the optimal drug administration route, pharmacokinetics, the balance between rapid-onset and slow-onset opioids, and the eventual difference of BTcP response deriving from clinical features, such as stage, primary site, or metastases.6 Nevertheless, to our knowledge, no authors have yet tried to explore the issue of BTcP management using these techniques.In this analysis, it was thus hypothesized that the unique BTcP definition might actually enclose diverse pathologic entities, possibly with peculiar clinical needs and specific responses to drugs. To explore this supposition, we used novel multiparametric artificial intelligence algorithms that can simultaneously analyze different clinical features and identify the existence of shared patterns. These so-called unsupervised learning algorithms have already been extensively used, for example, for the identification of breast cancer subtypes.8 that enrolled 4,056 patients from 32 centers with opioid-controlled basal pain suffering from BTcP. This work is therefore a secondary analysis of the IOPS group survey that aims to identify novel subtypes of BTcP through the use of unsupervised learning algorithms.To fulfill this purpose, we used data that were collected by the IOPS group in a large, multicentric national study5 In brief, local ethical committees approved the protocol, and written informed consent was obtained from each patient. Interviews were performed in different settings, in particular, oncology, pain therapy, palliative care, and radiotherapy. Patients were ≥ 18 years of age; diagnosed with cancer at any stage; had stable background pain in the last week with an intensity of, at most, 4 on a numerical scale from 0 to 10; and had episodes of BTcP with an intensity ≥ 5, clearly distinguished from background pain. The definition of BTP was a transitory pain exacerbation of moderate to severe intensity that occurs spontaneously or is predictably well distinguished from background pain. Exclusion criteria were the absence of a cancer diagnosis, uncontrolled background pain , or no relevant increases in pain intensity (< 5) that could be interpreted as BTcP episodes. Patients who were unable to provide information about the data required for the study as a result of either cognitive failure or terminal disease were also excluded. A comprehensive list of clinical variables was collected for each patient that consisted of basal pain and BTcP site, duration, frequency, intensity, relieving factors, triggers, drugs, primary cancer site and stage, and concomitant symptoms for a total of 1,086 variables. Interviews were registered by collecting personnel in a closed online form and centrally stored.Details concerning the enrollment of patients are extensively described in the main paper from the IOPS group.9 to correct P values for multiple comparisons. Features with less than 5% of missing data and associated with a corrected P value of < .1 and, for categorical features, a log2 odds ratio greater than 1 were used to build a multivariable logistic regression. To investigate the correlation—simultaneously for all patients and on the same scale—between the amount of opioids used and BTcP therapy satisfaction, all doses of opioid drugs were converted10 to equivalent intravenous morphine doses and expressed as a total daily dose: one for BTcP-directed opioids and for basal pain opioids. Doses were converted to intravenous morphine doses and not to oral morphine doses because intravenous morphine has been increasingly used in different clinical settings and would provide more interpretable graphics in Results. Moreover, to explore the interaction of fast-acting and long-acting opioid dosages, we calculated for each patient the BTcP opioids–to–basal pain opioids ratio (OpR). A polynomial logistic regression was used to catch nonlinear relationships between opioid doses and therapy satisfaction.The association of each clinical feature with satisfaction toward BTcP therapy was investigated using a simple logistic regression. Therapy satisfaction was expressed as a binomial outcome. We used the false discovery rate method11; as features were also composed of non-numeric variables, we used the Gower metric12 for dissimilarity matrix calculation. Partitioning around the k-medoids13 algorithm was used to compute clusters using the dissimilarity matrix as an input. The algorithm was run different times using a range of cluster numbers (2-30). Silhouette statistics14 were calculated for each run, and the optimal number of clusters was manually picked as being that with the best trade-off between silhouette statistics and reasonable clinical interpretation. We used complete-linkage hierarchical clustering with 12 clusters, along with Rand index calculation, to explore the replicability of clusters with a different algorithm.Features defining the clinical characteristics of BTcP were selected to perform clusters computation. Features with missing data that accounted for more than 5% of patients were excluded. The above-mentioned features were used to calculate a dissimilarity matrix using a cluster packaget-Distributed stochastic neighbor embedding15 algorithm was used to project dissimilarities between patients in a bidimensional space, with closer points representing patients with more similar clinical BTcP features. An online tool allows for the repetition of the performed classification on new sets of patients.16t-Test, Mann-Whitney test, and χ2 test were used to assess the association of parametric, nonparametric, and categorical features, respectively, with each cluster. The false discovery rate method was used to correct P values for multiple comparisons. Therapy satisfaction was investigated separately for each cluster, as previously described, for all samples.17 The following packages were used for the analyses: dplyr,18 cluster,11 Rtsne,19 ggplot2,20 gmodels,21 Rmisc,22 epiR,23 mgcv,24 knitr,25 RColorBrewer,26 and mgcViz.27Data were imported and analyzed using R (v3.5.2).A total of 4,016 patients were enrolled in the study during a period of 24 months. Men accounted for 54.8% of the total, and mean age was 64.6 years . The majority of visits were performed for oncologic (52.0%) and pain therapy (29.5%) purposes. Together, inpatient (37.3%) and outpatient (34.3%) settings accounted for more than one half of visits. The most common cancer primary organs were the lung (24.0%), breast (11.3%), pancreas (8.3%), and colon 7.5%. Mean Karnofsky performance status was 48. According to the inclusion criteria, basal pain was generally controlled; mean basal pain numeric rating scale was 3.0. Patients’ characteristics are listed in To investigate whether subtypes of BTcP exist, we used BTcP features to build an unsupervised clustering model. The number of BTcP episodes, BTcP peaks duration, BTcP type, BTcP intensity, number of days since the beginning of BTcP episodes, the eventual benefit from pharmacotherapy, the eventual benefit from rest, and whether BTcP was enhanced by movements were the eight BTcP-defining variables selected for the final model, which was built with the k-medoids algorithm. We chose 12 as an optimal trade-off between the average width of clusters silhouette  and highlighted a peak of satisfaction within a ratio range of 0.40-0.45. What seems clear, though, is that such an optimal level exists. This possibly suggests that, instead of starting BTcP opioid titration with the lowest possible dosage, as proposed previously,28 titration could start immediately with an optimal opioid dosage. Moreover, cluster analysis reveals that this ratio might not be the same for all patients: Some patients might benefit from a higher BTcP opioid dosage (cluster 2 and 7), whereas others might benefit from a lower one (cluster 11). Finally, for some patients, we did not observe an upper threshold for this ratio , perhaps pointing out patients for whom a strong BTcP opioid dosage increase is required.Some of our findings might already provide some indication for future clinical practice. First, it seems that an optimal ratio between BTcP opioids and basal pain opioids exists. Using our same data, another group proposed 0.20 (one fifth) as the optimal ratio.16 that allows for the classification of new patients according to our algorithm and returns a proposed BTcP therapy which depends on the patient cluster optimal OpR and basal opioid dose. We suggest that this tool might be used in the future to prospectively validate the clinical importance of our clusters in clinical practice and to compare our proposed opioid dosages in settings different from ours.The interpretation is made difficult by the multiple associations and, at this stage, is not mature enough to suggest any immediate change in clinical practice. However, we made available an online free toolThe presence of distinct BTcP phenotypes, each one associated with specific clinical features, could also be a reflection of diverse underlying pathophysiologic mechanisms: Our work suggests that preclinical research might gain insight into these possible differences and help the development of a tailored therapy also for BTcP.The main limitation of our study is the appropriateness of collected data for the scope of our work. We believe that a prospective study specifically designed for the investigation of BTcP clusters—possibly with long-term follow-up and therapy success outcomes and not limited to a single timepoint evaluation—might enable a clearer identification of distinct clusters. Moreover, our approach lacks an external validation of cluster consistencies and reproducibility. Nevertheless, these limitations do not interfere with the main scope of our paper, which was to offer a proof of concept for an innovative approach for BTcP management.In conclusion, this work identifies criteria for optimal BTcP opioids therapy personalization and offers a reproducible classification for the enrollment and stratification of patients in future BTcP trials.


This study aimed to evaluate the effect of kinesiology taping (KT) on lumbar proprioception, pain, and functional disability in individuals with nonspecific chronic low back pain (CLBP).n = 15) and placebo group (n = 15). KT was applied with 15–25% tension for 72 h, and placebo taping was used without tension. Lumbar repositioning error was measured by a bubble inclinometer at three different angles  in upright standing. Pain and disability were assessed by the Short-Form McGill Pain Questionnaire and Oswestry Disability Index, respectively. All measurements were recorded at baseline and 3 days after taping.Thirty individuals with nonspecific CLBP participated in this double-blinded, randomized clinical trial from July 2017 to September 2018. The participants were randomized into two groups: KT (p < 0.05). Only the total score of pain was significantly different between the groups 3 days after taping and improved more in the KT group with a large effect size (p < 0.05). However, lumbar repositioning errors were similar between the groups after 3 days (p > 0.05). Also, only constant error of 15° extension showed a moderate correlation with disability .Pain and disability scores reduced 3 days after taping in the KT group with large effect sizes (KT can decrease pain and disability scores after 3 days of application. Although placebo taping can reduce pain, the effect of KT is higher than placebo taping. The findings do not support the therapeutic effect of KT and placebo taping as a tool to enhance lumbar proprioception in patients with nonspecific CLBP.IRCT20090301001722N20.The study prospectively registered on 21.05.2018 at the Iranian Registry of Clinical Trials:  It is known that proprioception is necessary for the control of human movement . ProprioIt is challenging to measure proprioception because of its complex function. In previous studies, proprioception has been measured by force–plate analysis , electroIn recent years, the use of a therapeutic tool called kinesiology tape (KT) has increasingly become popular to use for musculoskeletal disorders. KT is made up of colorful elastic cotton strips with an acrylic adhesive that may be stretched to up to 140% of their original length . KT is aThe compressive and stretching effect of KT provides additional cutaneous stimulations, and these stimulations transfer more information regarding the joint position and movement to the central nervous system (CNS) for integration resulting in increased proprioception , 14. HowSome studies have shown improved proprioception through augmented cutaneous sensory stimulations provided by KT , 15, whe. It was hypothesized that applying KT on the lumbar spine would improve lumbar proprioception, pain, and disability compared to the placebo group in individuals with nonspecific CLBP.As yet, there is a lack of research exploring the effect of KT on lumbar proprioception. The purpose of the present study was to explore the short-term effect of KT on lumbar proprioception, pain, and functional disability in individuals with nonspecific CLBP. The associations between pain intensity, disability, and lumbar RE were also evaluated in these individualshttps://www.irct.ir/. All participants signed a consent form before entering the study.This study was a parallel double-blinded (assessor and participants), prospective randomized trial. The study was conducted at the Tehran University of Medical Sciences in accordance with the principles of the Declaration of Helsinki. The Ethical Committee at the Tehran University of Medical Sciences has approved this study, and it was prospectively registered at the Iranian Registry of Clinical Trials: IRCT20090301001722N20 at the website A total of 43 individuals were screened for this study. Thirteen were excluded for the reasons presented in Fig. Individuals were randomly assigned to either placebo group (KT without tension) or experimental group (KT with tension) according to a randomization scheme generated by a computer. Individuals with odd numbers were allocated to the placebo group, and individuals with even numbers were allocated to the KT group. The allocation of the participants was concealed by using sequentially numbered, sealed, and opaque envelopes. Blinded investigator (investigator 1) conducted the data collection and analysis, and investigator 2 conducted enrolling participants and intervention to minimize potential sources of bias. Also, all participants were unaware of their group. Figure In this study, waterproof, adhesive tape  with a width of 5 cm and a thickness of 0.5 mm was used. The experimental group received a standardized KT application in sitting position for 72 h. We had chosen applying this method of KT (star shape) in sitting position following the method used by previous similar studies , 18. FouThe placebo group received a single I-strips of the same tape without tension transversely on the maximum pain point of the lumbar region (placebo taping) Fig. b. After Assessments were taken at baseline and 3 days after the intervention. All participants completed measures of pain intensity by the Short-Form McGill Pain Questionnaire (SF-MPQ) , functioThe SF-MPQ consists of three parts, including 15 descriptors of pain , Visual Analogue Scale (VAS), and present pain intensity (PPI). Descriptors are rated based on pain severity on a four-point scale . The scores of sensory and affective (S/A) part are calculated by summing sensory and affective item values, as the total score. The second part is VAS, which is a 10-cm horizontal line ranging from “no pain” to “worst possible pain.” Patients present the severity of their pain by marking the line. After that, pain intensity was calculated from zero to the marked point by the patient in centimeters. The third part of the SF-MPQ is the PPI, which is a six-point verbal rating scale ranging from none (0) to the worst excruciating (5). The patients choose the word that best describes the overall intensity of their pain at the present time; then, the questionnaire is completed. The MPQ as a multidimensional tool is designed to assess sensory, affective, and evaluative dimensions of pain .Considering the effects of KT on various aspect of pain  , it seemIn addition, lumbar RE, as an indirect measure of proprioception, was determined using a bubble inclinometer because of its reasonable price, the facility of application, accessibility, and non-invasiveness. Results of previous studies showed that measuring the lumbar range of motion  between the target position and the actual measured angles that CE indicates error towards a particular direction (positive or negative and the absolute error (AE) was the unsigned deviation from the target position, thus reflecting absolute repositioning error, irrespective of error direction. Both errors were assessed before and after the intervention.The sample size calculation was performed using G*Power version 3.1.9.2 . This wasmall (d =  0.2), medium (d =  0.5), and large (d ≥ 0.8) [p < 0.05.Statistical analyses were performed using IBM SPSS Statistics for Windows, version 22.0 . The normality of data was assessed, and all variables followed a normal distribution. In this study, all variables  were presented as mean (standard deviation). All variables were compared between the groups using independent sample t-tests. Paired t-tests were also applied to find the differences between before and 3 days after the taping in each group. Cohen d was reported as the estimates of effect size, with the classification of d ≥ 0.8) . The cord ≥ 0.8) . The lev, VAS, PPI), or disability (ODI) (Table The demographic characteristics of the participants are shown in Table I) Table .Table 1P > 0.05). After 3 days of taping, the pain , VAS, and PPI) and functional disability scores significantly reduced in the KT group with large effect sizes (d > 0.8), also PPI significantly decreased in the placebo group with a large effect size . However, the difference between the groups was significant only for the total score of pain (S/A) 3 days after taping and improved significantly more in the KT group than the placebo group with large effect size (P < 0.05) , VAS and PPI), functional disability or RE (AE and CE) at the angles (45° and 60° flexion and 15° extension) between the groups at baseline (5) Table .Table 2P > 0.05) (Table No significant between-group or within-group differences were observed for the RE (AE and CE) in any of the angles (45° and 60° flexion and 15° extension) at 3 days (5) Table .P = 0.02) , VAS and PPI) and disability scores significantly improved after 3 days of taping in the KT group with large effect sizes, but no significant differences in RE (AE or CE) were found in any of the three angles (45° and 60° flexion and 15° extension). In the placebo group, only PPI was significantly reduced after 3 days of placebo taping without tension. Also, only the total score of pain (S/A) showed significant differences between the groups with a large effect size.Participants in the KT group had mild to moderate pain levels and showed approximately 23% reduction of pain over 3 days; therefore, possibly over a longer period, a greater reduction would have been achieved. However, KT is typically worn for 3–5 days.There are several studies investigated the effect of KT on pain and disability in individuals with LBP , 30, 31;Some physiological mechanisms of KT effects have been proposed. Pain reduction after applying KT with tension may be due to lifting the skin and enhancing subcutaneous space and, as a result, reduced activation of pain receptors, also possibly activates descending inhibitory system. Also, in the gate control theory of pain, tactile stimulation of KT would reduce the afferent signal of large-diameter non-nociceptive fibers resulting in a reduction of pain , 38, 39.The previous studies never evaluated the effects of KT on pain using SF-MPQ as a multidimensional tool in individuals with nonspecific CLBP, and they measured pain by VAS , 32, 34 Also, there were no significant differences (between-group or within-group) for lumbar RE (AE and CE) in the angles (45° and 60° flexion and 15° extension). To the best of our knowledge, this is the first study to evaluate the effect of KT on lumbar proprioception in patients with LBP. Several studies have evaluated the effect of KT on proprioception in peripheral joints, especially knee and ankle in injured or non-injured individuals , 13–15 tA systematic review reported that patients with LBP have impaired lumbar proprioception compared with controls when measured actively in sitting positions . In our The potential mechanism by which KT improves proprioception is not yet understood. Some authors have hypothesized that cutaneous feedback supplied by KT could be increased. Applied pressure and stretching due to KT application on the skin at extremes of motion, similar to joint mechanoreceptors, can also stimulate cutaneous mechanoreceptors and signal information of joint movement or joint position , 14, 44.It seems that tactile stimulation of KT was not enough for improvements of proprioception may be due to short-term assessment or method of taping in our study. There are direct relationships between impaired proprioception, pain, and reduced quality of life . In the It has been proposed that proprioceptive deficits may lead to trunk muscle dysfunction also may cause alterations in normal afferent inputs from the affected muscles. In neutral posture, muscle afferents could be considered as primary contributors to position sense because ligaments are under minimal tension , 5. In cThe tension of KT is described as one of the critical factors for successful implementation. Theoretically, both 75 and 100% of tension are used to support weak muscle or correction of joint position, 25–50% for muscle activation in weak muscles positioned from the origin to the muscle insertion, 15–25% for muscle inhibition caused by overuse or muscle overstretching placed from the insertion towards the muscle origin, and 0–15% for reduction of edema . The besBesides, the moderate positive correlation between CE of 15° extension and disability in these patients indicates that those with higher disability display a greater RE. Previous research suggests that spinal RE is the largest among individuals with higher disabilities. Also, there is a positive correlation between functional disability and RE , 9. ThosIn the current study, some limitations should be considered while interpreting the findings. First, we compared the effects of KT with a placebo group, but the placebo taping was not a real placebo due to the volume of tape used, which should be thinner than KT with less stimulation of subcutaneous afferent sensory fibers. Also, the lack of a non-taping group is another limitation of the current study. Moreover, we only examined the short-term effects of star shape taping with 15–25% tension; however, higher tensions may have different effects on lumbar RE. Therefore, future studies should compare different methods of taping with non-taping, also assess longer follow-ups in patients with CLBP.The use of KT would be beneficial to decrease the level of pain and disability in individuals with nonspecific CLBP. Also, taping without tension even with one strip, such as placebo taping, may reduce pain in these patients. Since the placebo treatments are important tools that can be used by the medical community to complement regular therapies, the use of placebo taping can be helpful. Considering lumbar RE may assist therapists in identifying poor posture awareness and proprioception impairments among these patients.The findings suggest that star-shaped KT reduces pain and disability scores after 3 days of application with large effect size in patients with nonspecific CLBP. It also seems that KT may affect another aspect of pain  compared to placebo taping, while placebo taping may only improve PPI in these patients. The short-term effect of KT over the low back region cannot improve lumbar proprioception when measured by active lumbar RE. Therefore, the findings do not support the hypothesis that lumbar taping would improve lumbar repositioning errors.


H. pylori, or gross endoscopic lesions, patients were evaluated for disaccharidase deficiency frequency. Disaccharidase were compared between patients with and without histologic duodenitis. Lastly, relationships between individual gastrointestinal symptoms or symptom complexes were evaluated. Lactase deficiency was found in 34.3% of patients and disaccharidase pan-deficiency in 7.6%. No individual symptoms or symptom complexes predicted disaccharidase deficiency. While duodenitis was not associated with disaccharidase deficiency, it was only present in 5.9% of patients. Disaccharidase deficiency, particularly lactase deficiency, is common in youth with abdominal pain and multiple deficiencies are not uncommon. Disaccharidase deficiency cannot be predicted by symptoms in this population. Further studies are needed to assess the clinical significance of disaccharidase deficiency.Abdominal pain has been associated with disaccharidase deficiencies. While relationships with individual symptoms have been assessed, relationships between disaccharidase deficiencies and symptom complexes or inflammation have not been evaluated in this group. The primary aims of the current study were to assess relationships between disaccharidase deficiency and symptoms or symptom complexes and duodenal inflammation, respectively. Patients with abdominal pain who underwent endoscopy with evaluation of disaccharidase activity levels were identified. After excluding all patients with inflammatory bowel disease, celiac disease,  Most of these children will fulfill criteria for an abdominal pain-related functional gastrointestinal disorder as defined by Rome IV criteria with the two most common being irritable bowel syndrome (IBS) and functional dyspepsia (FD)6. IBS is defined as pain in association with a change in stool frequency, a change in stool form, or a change in pain with defecation4. FD is defined by epigastric pain or burning, early satiety, or postprandial bloating4.Chronic abdominal pain is common in children and adolescents affecting up to 19–38% of the pediatric population9. These may be primary deficiencies in patients with normal duodenal histology and presumably genetic in origin or may be secondary to mucosal injury with villous atrophy and/or inflammation. With DS deficiency, ingestion of the corresponding disaccharide can result in malabsorption with subsequent osmotic diarrhea, cramping, and increased gas with bloating following bacterial digestion of the sugar10. Despite these physiologic and symptom consequences, previous studies have not been able to correlate DS deficiencies with specific symptoms in youth with abdominal pain8.Disaccharidase (DS) deficiencies have also been implicated in children with chronic abdominal painThe primary aims of the current study were to, (1) assess the frequency of DS deficiency in children and adolescents with chronic abdominal pain, (2) to assess relationships between DS deficiencies and specific symptoms or groups of symptoms corresponding to symptoms generally associated with DS deficiency, IBS, and FD, respectively, and, (3) to assess relationships between duodenal inflammation and DS activity and deficiencies. In addition, we evaluated whether reports of specific food intolerances correlated with DS deficiencies. We hypothesized that DS deficiency would be common in youth with chronic abdominal pain but would not be associated with specific symptoms or symptom complexes.Helicobacter pylori. Patients with H. pylori on histology as determined by a board-certified pediatric pathologist and patients with endoscopic findings of erosions, ulcers, or nodular gastritis were also excluded. Microscopic inflammation did not otherwise preclude inclusion. When present inflammation within duodenum was further classified as chronic (increased lymphocytes or plasma cells), acute , or eosinophilic . All histologic evaluations for inflammation and villous atrophy had been performed as part of routine care by board certified pediatric pathologists. All patients within the abdominal pain clinic undergo a standardized comprehensive history for the presence of gastrointestinal symptoms. Gastrointestinal symptoms are captured electronically and patients are required to answer the complete set of symptom questions. In addition, all patients are asked if there are specific foods or types of foods which are associated with increased pain. Patients’ medical records were utilized to assess relationships between DS deficiencies and symptoms and reported food triggers. All DS activity analyses were performed in a commercial clinical laboratory  utilizing the modified Dahlqvist method to assess enzyme activity levels. Both actual DS activity levels and whether levels were normal or abnormal per reference laboratory normal ranges were recorded and analyzed. Normal values include lactase > 15 μmol/min/g protein, sucrose > 25 μmol/min/g protein, maltase > 100 μmol/min/g protein, and palatinase > 5 μmol/min/g protein. This study was approved by the Institutional Review Board Children’s Mercy Kansas City which also waived informed consent and assent for this retrospective study. All research was performed in accordance with relevant guidelines/regulations.This study was a retrospective, single-site study of all children and adolescents evaluated in an abdominal pain clinic who had undergone endoscopy for a primary indication of abdominal pain who also had evaluation of duodenal disaccharidase (DS) activity at Children’s Mercy Kansas City from 2016 to 2019. The abdominal pain clinic evaluates patients 8–17 years of age with a pain duration of at least 8 weeks. Electronic medical records were reviewed and patients were excluded for a previous diagnosis of inflammatory bowel disease or celiac disease. All diagnoses had been assigned by a board-certified pediatric gastroenterologist based on clinical, laboratory, and histologic findings. All patients with celiac disease had an elevated tissue transglutaminase antibody level. Patients’ medical records were also reviewed for gross endoscopic findings and histologic findings including identification of Statistical analyses were performed using SPSS version 23 . The frequencies of DS deficiencies were compared between those with and without specific individual symptoms by chi square analysis. The ability of three separate sets of symptoms designated set 1 , set 2 , and set 3  to predict DS deficiency were assessed by logistic regression. Frequencies of DS deficiency were compared between patients with duodenitis and those without duodenitis by chi square analysis. The frequencies of DS deficiencies in patients reporting an increase in pain with dairy ingestion as compared to those not reporting an increase in pain were compared by chi square analysis. A p value < 0.05 was considered significant.Patients ranged in age from 8 to 17 years with a mean age of 13.4 ± 2.9 years and 72.4% were female. The pain duration ranged from 2 to 204 months with a mean of 33.2 ± 35.7 months. The pain was continuous in 28.8%, daily intermittent in 40.5%, several days/week in 20.7%, and weekly in 9.9%.Lactase deficiency was present in 34.3%, sucrase deficiency in 7.6%, maltase deficiency in 10.9%, palatinase deficiency in 7.6%, and pan-deficiency in 7.6%. The prevalence of DS deficiencies did not differ between patients with and without duodenitis, however, duodenitis was only present in 5.9% of patients .Frequency of gastrointestinal symptoms are shown in Table For patients reporting increased pain with eating, a specific food or food type which increased pain was identified by 61.4%. The most common were dairy in 28.9%, fried or greasy foods in 20.5%, spicy foods in 13.3%, sugar or sweets in 6.0%, and gluten or bread in 4.8%. Lactase deficiency alone was seen at an increased frequency in patients reporting increased pain with dairy consumption  or inappropriate processing of the sample (e.g. delay in freezing of the sample). While this is possible in some cases, pan-deficiency is also seen frequently even with meticulous biopsy procedures and immediate processing of the sample7. Pan-deficiency may also result from a combined deficiency of lactase, which is common, and sucrase-isomaltase which accounts for sucrase and palatinase activity as well as 80% of maltase activity13.DS deficiency, particularly lactase deficiency, is common in children and adolescents with chronic abdominal pain, even in patients with normal duodenal histology. The low prevalence of duodenitis in the current study precluded meaningful evaluation of any association of duodenitis and DS deficiency. While normal histology may indicate a primary or genetic deficiency, it is also possible that the DS activity levels were subject to alteration due to microbiome composition or differences in dietary intake as suggested by animal models8. In addition, we found that symptom complexes consistent with either IBS or FD did not improve this predictive ability, nor did a complex of symptoms which have generally been associated with DS deficiency . Previous studies have reported some associations between congenital sucrase-isomaltase deficiencies and IBS but no clear association of lactase deficiency with IBS16. A previous study utilizing the 13C-sucrose breath test in children found no association between sucrase deficiency and specific symptoms [17]. The lack of association between specific symptoms and DS deficiency in patients with chronic abdominal pain should not be surprising as there are a variety of factors which affect symptoms directly related to disaccharide ingestion as well as a variety of factors affecting symptom which may not be directly related such as dysmotility, visceral hyperalgesia, and psychosocial functioning. In addition, the frequency or severity of symptoms related to disaccharides are dependent on the degree of enzyme deficiency, the amount ingested, other components in the diet, and gastrointestinal motility18. A recent study in mice provided a possible link between disaccharide malabsorption and visceral hyperalgesia as oral administration of foods containing fructo-oligosaccharide or lactose gavage led to increased abdominal sensation in association with an increase in colonic mast cells19. Whether DS deficiency and malabsorption is a contributor to the development of visceral hyperalgesia in humans remains to be determined but it represents an important area of inquiry.Similar with previous studies, we found that no individual symptoms predicted the presence of DS deficiency21. Despite this, there is a lack of compelling evidence that restriction of individual disaccharides improves symptoms18. Specifically, randomized studies assessing lactose restriction have produced mixed results but generally do not support significant benefit18.While the clinical significance of identified DS deficiency requires further evaluation, the practice of obtaining mucosal specimens for DS analysis frequently leads to a change in therapy, either dietary restriction or enzyme replacement. This is particularly true of patients with lactase deficiency where changes in treatment were recommended in 85% of patients. In the current study, perceived dairy intolerance was the most common reported food resulting in increased pain. In these patients there was an increased frequency of lactase deficiency but not other DS deficiencies suggesting that milk intolerance may be related to lactose malabsorption in at least some patients. The higher reporting of dairy intolerance in the current study is consistent with previous studiesThe strengths of the current study include inclusion of a group of patients with prospectively collected standardized and comprehensive gastrointestinal symptom histories with analysis of DS relationships to sets of symptoms. The primary weakness is that DS analysis is not universally performed with endoscopy and thus the patients are pre-selected based on the clinical judgement of the ordering clinician.In conclusion, DS deficiency occurs commonly in youth with abdominal pain and normal histology. Neither individual gastrointestinal symptoms nor complexes of symptoms corresponding to “usual” DS malabsorption symptoms, IBS, or FD were predictive of DS deficiency. While an increased frequency of lactase deficiency in patients reporting increased pain with dairy would suggest a relationship to symptoms, well-designed prospective studies are needed to assess the efficacy of disaccharide restriction, either individually or as a group, in improving pain and whether DS activity levels are predictive of response.


Cancer-related pain is a complicated symptom that often coincides with fatigue, depression, and anxiety. Although many safe treatments are available, inadequate control of Cancer-related pain continues to lead to suffering in cancer patients. This study’s aim is to describe pain control, and the pattern of change in opioid and adjuvant medication prescriptions, before and after referral to the Palliative Care Center.We conducted a prospective cohort study in adult cancer patients the Palliative Care Center between January 1, 2016 and December 30, 2017. We measured pain intensity and other associated symptoms via the Revised Edmonton Symptom Assessment System (ESAS-r) and documented detailed analgesics and adjuvant medication history before starting any palliative care and on days 0, 3, 6, and 14.p < 0.001 for all. Morphine was the most common opioid administered; the percentage using it increased from 20.4% (n = 49) before referral to 49.6% (n = 119) on day 6 (p < 0.001). The median morphine equivalent daily dose decreased from a median (interquartile ranges) of 60(31–93) mg/day before referral to 34(22–66) mg/day on day 6 (p < 0.001). There was also a statistically significant increase in the percentage of patients taking adjuvant medications, from 38.8% before referral to 84.2% on day 6 (p < 0.001). Comparing D0 to D6, the number of patients using Gabapentinoids significantly increased from 57(23.75%) to 79(32.9%) (p < 0.001), amitriptyline dramatically increased from 14 (5.8%) to 44 (18.3%) (p < 0.001), and other antidepressant drugs increased from 15 (6.2%) to 34 (14.1%) (p < 0.001).The analysis included 240 patients whose cancer-related pain, anxiety, and depression scores meaningfully improved by day 6. The changes in the median (interquartile ranges) of Cancer-related pain, anxiety, and depression scores from day 0 to day 6 were: 6 (4–8) to 3 (1–4); 6 (4–9) to 2 (1–4); and 3 (2–6) to 2 (1–4), respectively, with After referral to the Palliative Care Center, patients’ pain and other symptoms scores decreased significantly, even with lower median morphine equivalent daily doses, arguably through more appropriately directed opioid use. This is evidence for the effectiveness of the comprehensive program at the Palliative Care Center in Kuwait.The online version contains supplementary material available at 10.1186/s12904-021-00717-2. Cancer-related pain (CRP) is a common symptom in cancer patients. It can relate directly to either malignancy or anticancer treatment. In a systematic review of 52 studies, the prevalence of CRP was 59% in patients undergoing anticancer therapy, and 64% in those with advanced or metastatic disease , 2. UndoGuidelines published by various organizations, such as the World Health Organization , 6, the Although guidelines exist, and several relatively safe treatment modalities are available, many cancer patients are still suffering from inadequate CRP control . A systeCRP is a complicated symptom that is frequently reported alongside other symptoms such as fatigue, depression, and anxiety. The relationship between pain, anxiety, and depression is complex and bidirectional –18. CoexThe role of adjuvant medications in CRP management is debatable. Many studies have successfully used combinations of adjuvant analgesics, with and without opioids, to manage the majority of cancer pain , 20. TheAddressing patients’ in-depth, physical, emotional, and spiritual suffering is the core of palliative care. Therefore, to improve the quality of life in cancer patients, the early integration of palliative care with oncology is highly recommended , 26.A palliative care team’s interdisciplinary approach focuses on the impeccable assessment of total pain by taking a holistic approach to CRP management , 16.To the best of our knowledge, no one has well documented CRP control before and after referral to the Palliative Care Center (PCC) in Kuwait. Given the limited amount of published data from Kuwait, we consider this study a benchmark for determining the adequacy of CRP management.The PCC is a specialized tertiary medical center that focuses on treating the complex symptoms and quality of life of cancer patients. A multidisciplinary team cares for the patients. The head of the team is a specialist in palliative medicine, and the other members are physicians with palliative care training, primarily from internal medicine or oncology, nurses, nutritionists, physiotherapists, psychosocial workers, and spiritual advocates. Outpatient clinics, inpatient admissions, and ambulatory consultations of PCC are covering all patients in Kuwait.The primary aim of this study was to describe patients’ pain control, and the pattern of changes in their opioid and adjuvant medication prescriptions, before and after referral to the PCC.We conducted a prospective cohort study of all new patients referred to the PCC in Kuwait from January 1, 2016 to December 30, 2017.We enrolled all adult patients (18 or older) with cancer diagnoses and CRP, referred to either the inpatient or the outpatient clinic of the PCC, in the study. Patients were eligible if they were able to rate their pain and other symptoms and provided informed consent to participate in the study. We excluded patients if they were younger than 18 years old, had no evidence of cancer or CRP, could not describe their pain, refused to participate, or who went missing during follow-ups.The study collected demographic data regarding patient age, sex, nationality, as well as data on their clinical history, including cancer diagnosis, metastasis, documented active anticancer treatment or palliative status, pain characteristics, and referring health care facility. This study defined CRP as any pain that could be anatomically or physiologically linked to cancer or its treatment. The study included mild, moderate, and severe pain, either intermittent or continuous. In addition to the clinical assessment of pain, we utilized the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale. It comprises two parts: the first part is pain history over the prior week, and the second part is a sensory examination. It discriminates neuropathic pain from nociceptive pain . The LANThe study measured pain intensity and other associated symptoms using the Revised Edmonton Symptom Assessment System (ESAS-r) during the first consultation, before starting any palliative care plan (D0), and then again on Day 3 (D3), Day 6 (D6), and Day 14 (D14).The ESAS is a validated tool for the assessment of symptoms in a palliative care setting. Patients rate the severity of their symptoms over the previous 24 h from 0 (no symptom) to 10 (worst). The ESAS has a high test-retest reliability of > 0.8 and has been validated in many clinical settings, particularly in cancer patients , 32.The ESAS has consistently been used to assess anxiety and depression. It has a good association with the Hospital Anxiety and Depression Scale . We routThe ESAS has been revised to improve the ease with which patients can understand and complete it. Because of the diversity of Kuwait culture, which includes more than ten nationalities, we used validated English and Arabic versions .This is the most-validated cancer pain classification system, and it enables standardized reporting based on the ESAS score. It allows both clinicians and researchers to use a common language in or between various different clinical settings . This syWe recorded detailed histories of the patients’ opioid and non-opioid analgesics and adjuvant medications, including their type, dose, route, regularity, frequency, and as-required doses in the 24 h before or after referral on D0, D3, and D6. We calculated the oral morphine equivalent daily doses (MEDDs) according to standard recommendations , 39.The pain management index (PMI) is a measure of the appropriateness of analgesic therapy . It is a.We obtained written and informed consent from all participants. We discussed the aim of the study and its expected outcomes with each patient, and guaranteed the privacy of their dataWe performed revisions and coded the raw data, and utilized Statistical Package for the Social Sciences Version 20  for all our data entry, manipulation, and analysis.We used descriptive statistics, including means, standard deviations, medians, interquartile ranges (IQRs), and percentages, to summarize patient characteristics. We tested the normality of different variables by applying the Kolmogorov-Smirnov and Shapiro-Wilk tests. For parametric variables, we compared continuous variables of repeated observations using paired t-tests for two groups, and one-way ANOVA for more than two groups. For non-parametric distributions, we used the Wilcoxon signed-rank test to compare two quantitative variables, and the Friedman’s test to compare more than two quantitative variables.We compared the categorical variables using either Chi-square tests or Fisher’s exact tests, when appropriate. To ease comparisons, we focused on comparing the ESAS-r scores from D6 to the D0 baseline. Supplementary file A total of 467 newly-referred patients arrived at the PCC during the study. We excluded 175 (37%) patients because they did not have pain, could not report their pain, or refused to participate, and we lost 52 (21.67%) patients during follow-ups to the study. Figure Testing the normality of the ESAS-r scores, opioids and adjuvant medications’ doses and MEDDs with the Kolmogorov-Smirnov and Shapiro-Wilk tests revealed that they had a non-parametric distribution. We used the Wilcoxon signed-rank test to compare two quantitative variables, and Friedman’s test to compare more than two quantitative variables. Other variables, such as age, were normally distributed.n = 114, 47.5%). The most common cancers were gastrointestinal  followed by thoracic , genitourinary , breast , and head and neck cancer . Overall, 85.4% (n = 205) of the patients had distant metastasis, especially in their livers , lungs , bones , brains , and adrenal glands . A total of 209 (87.1%) patients were referred to us after declarations from their oncologists for best supportive care, and only 31 (12.9%) were still actively on anti-cancer treatment. Only six (2.5%) patients had curative intent , while 25 (10.4%) had palliative intent . Inpatients represented 69.6% (n = 167) of the total, while outpatients represented 30.4% (n = 73). The Kuwait Cancer Control Center was responsible for more than 97% of the referrals to the PCC (n = 234), especially in the medical oncology department   men and 118 (49.2%) women. Most of the patients were Kuwaiti , followed by neuropathic pain , visceral pain , and somatic pain  , nearly one-third had severe pain , and only 9.2% (n = 22) had mild pain , anxiety , depression, and worsening of well-being . Before referral, most patients had 8 (IQR: 7–8) symptoms by ESAS-r , ranging from 3 to 10 , with similar scores on D3 and D14 (Supplementary File 1).After referral to palliative care, patients’ pain and other symptom scores decreased significantly. Pain, anxiety, and depression scores all improved statistically significantly from D0 to D6  .Furthermore, there was a statistically significant increase in the patients’ use of adjuvant medications. Before their referrals, 61.2% of the patients were not taking any adjuvant medications but, by D6, 84.2% were receiving at least one adjuvant medication, and this change was statistically significant (p = 0.002). The data for D3 and D14 was similar (See Supplementary File 1). In addition, the doses and the varieties of antidepressant drugs increased. The median doses of commonly used antidepressant drugs also increased. Amitriptyline doses increased significantly, from 25 mg/day in D0 to 50 mg/day in D6. The same pattern held for duloxetine (from 30 to 60 mg/day) and escitalopram (from 5 to 10 mg/day)  to 44 (18.3%) (p < 0.001), other antidepressant drugs increased from 15 6.2%) to 34 (14.1%) (p < 0.001), and anxiolytics (benzodiazepines) increased from 10 (4.2%) to 27 (11.2%) , and Alpha-2 adrenergic antagonists (mirtazapine), following standard recommendations for palliative care .p < 0.001), and from 8 (IQR: 0–13) to 5 (IQR: 2–10) mg/day for patients only on as-needed opioids (p = 0.027)  mg/day before referral to 34 IQR: 22–66) mg/day on D6 for patients on regular opioids , or the PCC, based on their primary doctor’s preference. Before referral, pain clinic services, and occasionally oncologists, were in charge of the patients’ pain management. However, an available pain clinic service may be more concerned with physical pain treatment rather than total pain management, which requires a holistic approach to achieve better outcomes. Moreover, one of the most important differences might be that the PCC team spends more time communicating and educating patients and family members about pain and symptom assessment, and their management plan, than other health care providers , 21. ThiLower MEDDs were not demonstrating under treatment of pain in our study; arguably, it indicated more appropriately directed opioid use, since number of patients receiving opioids during the follow-up periods was increased. Similarly, a Korean study also reported pain treatment with low MEDDs (median 60 mg/day) . This beThe relationship between anxiety, depression, and pain intensity is debatable. Some studies have reported no relationship between psychological distress and pain , while aIn addition, conflicting results have been reported regarding the role of adjuvant medications. In two meta-analyses that examined 11 studies in which opioids were used in more than 80% of patients with CRP, neither study was able to demonstrate any benefits in terms of improved pain scores or reduced opioid doses , 24. On Recently, there has been a marked increase in the prescription patterns of psychotropic drugs  , 56, espAlthough Kuwait has only recently introduced palliative care services, the palliative care team at the PCC was able to achieve good pain and other symptom control in more than 95% of its patients through a holistic approach. This is supported by the Lancet Oncology Commission’s 2018 discussion about the need to complete the integration of palliative care and oncology in order to promote patient-centered care, improve survival, control symptoms, improve family satisfaction, and increase quality of life .Since the PCC is the only available and standalone building offering palliative care services in Kuwait, this study can be considered to be a national survey that describes the actual pain control situation and pattern of change in all analgesic and adjuvant medication prescriptions before and after referring cancer patients with CRP for a two-year prospective audit.Many adjuvant medications were used for indications other than pain, so it is difficult to say that every medication in this study was used only for pain relief. A longer follow-up period may be more appropriate in assess the long-term control of pain, other symptoms, and the effect of adjuvant medications. We excluded patients without pain from the study, which may not have allowed for a fair comparison of patients’ characteristics, other symptom prevalence, and severity.The results of this study will help researchers to design future clinical trials aimed at improving the understanding the role of adjuvant medications, including anxiolytics and antidepressant drugs, in pain control. Early integration of PCC into oncology practice should be implemented to provide better symptom control and quality of life for cancer patients.After their referrals to the PCC, patients’ pain and other symptoms scores decreased significantly, even with lower MEDDs, arguably through more appropriately directed opioid use. This is evidence for the effectiveness of the comprehensive program at the Palliative Care Center in Kuwait.Additional file 1: Table S1. Comparison between ESAS-r scores, Opioid/non opioid analgesics and Adjuvant Medications before and after referral to Palliative Care Centre for D0, D13, D14


It is a relatively uncommon condition but important to recognise as it is a potentially treatable cause of bone pain. This article provides guidance to primary care teams on the diagnosis and management of patients with PDB based on a recent clinical guideline.2 Paget’s disease has a strong genetic component and particularly targets people of British descent.2 In some families, it is inherited as an autosomal dominant trait, most commonly because of mutations in the SQSTM1 gene whereas, in others, there is familial clustering with no clear pattern of inheritance.3 Emerging evidence indicates that susceptibility to PDB is accounted for, in part, by inheritance of variants in genes that cause upregulation of osteoclast activity. Environmental factors also contribute, however, as evidenced by a reduction in prevalence and severity of the disease over the past 5 0 years. 2 Suggested environmental triggers include viral infections and calcium and vitamin deficiency during skeletal growth and skeletal trauma. The viral hypothesis has been studied experimentally but the data are conflicting and the role of other environmental factors has not been rigorously studied.1PDB is caused by increased osteoclast activity that is coupled with increased, but disorganised, bone formation, causing the affected bones to become deformed and more susceptible to fracture. Paget’s disease is rare below the age of 50 but becomes progressively more common thereafter and males are affected more often than females (1.4:1).4 In about one-fifth of patients, it is discovered as an incidental finding with an isolated elevation in alkaline phosphatase level (ALP) in a patient with otherwise normal liver function tests or by an abnormality on skeletal imaging. Rarely, PDB may present with osteosarcoma (0.3% of patients), which usually presents with a local increase in swelling and pain at an affected site.The most common presentation is with bone pain but PDB can also present with bone deformity, deafness, or pathological fractures.1 If bone scans are not readily available, then plain X-rays of the abdomen , both tibias, the skull, and facial bones may be considered since X-rays of these sites have been found to detect PDB in >90% of patients.5 The main purpose of performing imaging is to identify which bones are affected to help decide if a patient’s symptoms might be due to PDB or another cause. Patients who present with imaging suggestive of PDB should be asked if they have pain or discomfort localised to the affected site. The key investigation is ALP, which gives an indication if PDB is metabolically active, but liver function tests, calcium, phosphate, vitamin D, and creatinine are helpful in the differential diagnosis from other conditions such as renal osteodystrophy, primary hyperparathyroidism, and osteomalacia  is reserved for the management of bone pain where bisphosphonates are contraindicated because long-term treatment has been associated with an increased risk of certain types of cancer. Although bisphosphonates can improve bone pain significantly in PDB, many patients require additional analgesics to control the elements of pain that may not be due to increased metabolic activity.Bisphosphonates are the treatment of first choice and are indicated in patients with pain localised to an affected site with evidence of increased metabolic activity. Usually this is manifest by an elevation in ALP but when a single bone is affected the ALP may be normal; here a radionuclide bone scan can be useful in assessing if there is local disease activity. In the UK, three bisphosphonates have marketing authorisation for the treatment of PDB . Zoledro1Apart from fracture repair, the most common indication for orthopaedic surgery is arthroplasty for osteoarthritis. Surgery can be technically difficult in PDB due to deformity and the presence of sclerotic bone, but outcomes are generally excellent and having PDB is not a contraindication to referring a patient for joint replacement.Research is now in progress (ISRCTN11616770) to determine if intervention with bisphosphonates in asymptomatic patients with early disease can halt progression and prevent complications.


Complete removal of pain with regional anesthesia has been reported to cause fatal respiratory depression in opioid-dependent patients, which leads us to choose general anesthesia. We hereby report three cases of chronically opioid-treated cancer patients operated under spinal anesthesia without respiratory event.Case 1: a 32-year-old female treated with high-dose morphine for her cancer pain was planned for cesarean section. Case 2: a 65-year-old female on moderate dose of oxycodone was planned for surgery of her femoral bone fracture. Case 3: a 65-year-old male on low-dose oxycodone was planned for intramedullary nailing for metastatic femoral bone tumor. In all three cases, spinal anesthesia was chosen. Continuous respiratory monitoring revealed no apnea or bradypnea.Spinal anesthesia was safely performed without respiratory depression in chronic opioid users for cancer pain. Recently, the number of patients coming to the operating room with opioid analgesics is increasing, as opioids are used more regularly in both cancer and non-cancer pain. It is often believed that sudden and complete removal of pain with neuraxial anesthesia causes respiratory depression in opioid-consuming patients, since pain itself is considered to antagonize the respiratory depressant effect of opioids . Case reWritten informed consent for case report was obtained from patient herself in case 1, and from family members of the deceased in cases 2 and 3. Institutional IRB approval for submission was gained in October 2019 (#3564).This manuscript adheres to the applicable EQUATOR guideline.2, and non-invasive blood pressure (BP) measurement. Respiratory rate (RR) and end-tidal CO2 were continuously monitored with capnography  attached to a nasal cannula supplying 2 L/min oxygen during the surgery. Capnography revealed no apnea nor bradypnea  on admission 37 kg) was diagnosed with rectal cancer with liver and bone metastasis at 24 gestational weeks. Cancer pain due to bone metastasis of T12, L3 spine  was diagnosed with recurrence of esophageal cancer and metastasis of lung and bone. She was receiving intravenous oxycodone which was gradually increased for 18 days to 4.5 mg/h for her pain due to metastasis of her right sacral bone. Femoral trochanteric fracture was diagnosed after tumbling on the floor and she was planned for intramedullary nailing. As her preoperative chest x-ray revealed narrowing of the trachea due to lung metastasis   diagnosed with femoral metastasis of gastric cancer was planned for elective intramedullary nailing. He was receiving oral oxycodone 20 mg/day for more than 50 days. His bone cancer pain was under control. Regional anesthesia was chosen as the surgery was a simple procedure. He took the regular morning dose of oxycodone before surgery and lumbar anesthesia was performed with 2.6 ml hyperbaric 0.5% bupivacaine, and he was free from pain (no record of anesthesia level). Continuous RR and end-tidal COAnalgesic effect of opioid, the major drug in pain treatment, has always been balanced with its side effect, especially respiratory depression. Existence of pain is known to stimulate respiration, thus antagonizes the respiratory depressant effect of opioids . Abrupt In the case of chronic opioid users, the problem becomes more complex. In patients with long-time opioids, they are likely to have developed tolerance to both the analgesic effect and also the respiratory depressant effects. However, the level of tolerance may vary. The level of tolerance depends, possibly on the total dose or duration of opioids, but we have no clinically measurable method.Few case reports show us the risk or respiratory arrest after complete and sudden abolition of pain by regional anesthesia , 3. Our 2 monitor when used in spontaneously breathing patients, it is strongly recommended for early detection of apnea or bradypnea [Our clinical observation of no respiratory depressant events shows that, under continuous and intent monitoring, choice of regional anesthesia in chronic opioid-consuming patients with clear indication for neuraxial block can be safely managed. Especially in long-time opioid users, we experience the need for escalated dose of postoperative opioid  or even radypnea .In conclusion, regional anesthesia which may completely abolish the cancer pain in patients under chronic opioid analgesia can be safely administered. As presence or level of tolerance to respiratory depressant effect of opioids cannot be detected preoperatively, continuous monitoring is mandatory.


Post-trauma chronic pain characterized by central pain is a symptom following traumatic brain injury (TBI). Studies on the effect of repetitive transcranial magnetic stimulation (rTMS) on central pain and the association between central pain and spinothalamic tract (STT) have been reported, but few studies have examined the effect of rTMS in patients with mild TBI with central pain through changes in diffusion tensor imaging (DTI)-based metrics of STT before and after rTMS. This case series aimed to investigate the therapeutic effect of rTMS in TBI with central pain and the changes in diffusion tensor imaging (DTI)-based metrics of the spinothalamic tract (STT) before and after rTMS. This study included four patients who complained of severe pain in the left or right side of the body below the neck area after a car accident. We performed numeric rating scale (NRS), bedside sensory examination, electrodiagnostic study, and DTI-based metrics of the STT before and after rTMS. According to the guidelines of the diagnosis and grading for neuropathic pain, all patients had neuropathic pain corresponding to “probable grade.” In all patients, rTMS was applied to the contralateral M1 cortex on the more painful side. There were no medication changes and other interventions during the rTMS. After rTMS, NRS decreased, bed sensory testing improved, and DTI-based STT metrics increased in all patients compared to before rTMS. Post-trauma chronic pain is one of the symptoms following traumatic brain injury (TBI). The overall prevalence of chronic pain in patients with a TBI varies depending on the cause of pain, but it is known to range from 22% to 95%, with higher prevalence in patients with a mild TBI ,2. AfterBased on previous studies, medications such as amitriptyline, an adrenergic antidepressant; lamotrigine, an antiepileptic drug; and GABAergic drugs have been widely used in clinical trials to treat central pain ,8. AsideThe development of diffusion-based tractography enabled the visual reconstruction of the STT three-dimensionally, and differences in left and right STT were reported in tractography derived from diffusion tensor imaging (DTI) in patients with central pain . In addiIn this study, we performed rTMS in patients with a mild TBI and central pain to evaluate the pre-rTMS and post-rTMS outcomes, to confirm pain relief through self-report by patients, bedside sensory examination, as well as changes in DTI-based metrics of the STT. This study aimed to investigate the effect of rTMS on central pain symptoms in patients with mild TBI through diffusion-based tractography and DTI metrics of STT.The institutional review board of the Jeonbuk National University approved this case report and waived the requirement for informed consent (IRB number CUH 2019-01-047).This study presents four patients  with mild TBI who had no specific findings on conventional brain MRI. They were injured with their heads shaken by an in-car accident in which all vehicles rotated due to side collisions. Right after the car accident, all patients had a brief change in mental status  or loss of consciousness for <10 min, but had no neurologic sequelae such as motor deficits or cognitive impairment. All participants had no particular medical history before the accident. They commonly had pain starting 1 or 2 days after the car accident, which persisted despite continued treatment in other hospitals .All four patients presented to our hospital with severe pain in the extremities and body. Their pain distribution was commonly more severe on one side (left or right) of the whole body below the neck. All patients expressed that the weather heavily affected their pain. They complained of abnormal sensations, such as burning or sharp pain, from normally non-painful touch and hot or cold stimuli. We asked the patients to express their pain intensity through a numerical rating scale (NRS), which is expressed as a score from 0 to 10, 0 means no pain, and 10 means maximum imaginable pain . Moreove2; slice gap = 0 mm; and a slice thickness = 3 mm (acquired isotropic voxel size = 0.9 mm × 0.9 mm × 3.0 mm). After DTI, the spinothalamic tract (STT) was reconstructed to visualize the sensory fibers by applying the fiber tracking technique using the DTI studio software v.1.02 . Fiber tracking was performed with fractional anisotropy (FA) threshold of 0.20 and a tract turning angle of 60°. We performed reconstruction by selecting three regions of interest (ROIs) from the brain MRI axial slice: the seed ROI was set at the posterolateral medulla, the first target ROI was set at the point near the ventral posterior lateral nucleus of the thalamus, and the second target ROI was set at the primary somatosensory cortex [We conducted brain diffusion tensor imaging (DTI) to investigate the cause of pain. We acquired 49 contiguous slices parallel to the anterior commissure-posterior commissure line. Imaging parameters were as follows: acquisition time = approximately 3 min; acquisition matrix = 128 × 128; field of view = 220 mm × 220 mm; TR = 6600 ms; TE = 95 ms; parallel acquisition factor GRAPPA = 2; bandwidth = 1562 Hz/Px; EPI factor = 128; b = 1000 s/mmy cortex . Subsequy cortex ,18,19. Ty cortex ,22. BefoTo confirm the possibility of neural compromise, nerve conduction study (NCS), electromyography (EMG), and motor and sensory-evoked potential (MEP and SEP) studies were performed .Recently, the guidelines have been reported to confirm that the pain complained of by patients is neuropathic pain. According to the guidelines of the diagnosis and grading for neuropathic pain, all patients had neuropathic pain corresponding to a “probable grade” because the confirmatory test was not evaluated fully ,24 Figu.We applied rTMS to all patients as a treatment for central pain. The following rTMS protocol was employed based on a previous study: a series of 10 trains  at a stimulation rate of 20 Hz and at an intensity of 80% of motor threshold using an 8-shaped coil on the M1 cortex  ,25,26. rAfter the end of the rTMS, follow-up NRS scale of pain and bedside sensory examination of patients were checked between 3 and 6 days, and follow-up DTI, NCS, EMG, MEP and SEP were performed within 3 months.Of the four patients, patients 1 and 2 reported high satisfaction with pain relief after the first session; thus, they underwent an additional session on the side opposite to the first session. Bedside sensory examination, including non-painful stimuli such as touch, pinpricks, and temperature tests, showed improvement in paresthesia, like a burning or sharp sensation, in all patients. Moreover, pain relief was reported by all patients, with the NRS decreased from 9 to 4 in patient 1, from NRS 8 to 5 in patient 2, from NRS 7–8 to 4 in patient 3, from 5 to 1 in patient 4 .Before rTMS, the FA and TV values of the contralateral STT on the more painful side were generally lower than on the other side in all patients. The FA and TV values after rTMS was applied were increased compared to the results before rTMS .The patients had nonspecific findings of NCS, EMG, MEP, and SEP before and after rTMS. In all patients, no adverse effects such as headaches or dizziness from applying rTMS were reported.Central pain after TBI has a relatively late onset, ranging from several weeks to several months. Pain occurs in various locations, but the central pain of supraspinal causes is known to occur mainly in the hemi-side, or the hemi-side generally shows worse conditions. Central pain is generally characterized by neuropathic pain, which is a stimulation-independent pain similar to pricking, throbbing, and burning sensations, accompanied by responses from physical examination including allodynia, hyperpathia, and paresthesia ,6. PatieTwo common pathophysiological processes are assumed to be the cause of painful overreaction for central pain itself and for somatic stimulation, which accompanies central pain. First, the hypothesis of “irritative lesions” suggests that hyperactive cells at or near the lesion increased the activity in the normal nociceptive pathway. Second, the hypothesis of “denervation or hypersensitivity” suggests that although neurons are far from the lesion, as the nociceptive processing pathways have lost their normal synaptic input, they become hyperactive and hypersensitive . The twoRecently, visualization of the STT to reflect the damage at the thalamic level has become possible from the development of tractography derived from DTI. There has been a report of left- and right-side STT differences in tractography of patients with central pain ,30. The Studies on the effect of rTMS on central pain and the association between central pain and STT have been reported. The mechanisms of rTMS to the motor cortex for neuropathic pain can be explained by a reduction in pain-related thalamic hyperactivity, regional cerebral blood flow changes, activation of descending pathways, and restoration of intracortical inhibition. However, consensus on the exact mechanism has not yet been achieved ,10,31. AWe enrolled patients with probable neuropathic pain via the neuropathic pain grading system and investigated the efficacy of rTMS in central pain relief through self-report by patients, bedside sensory examination, as well as recovery of STT using tractography. Evaluating the integrity of STT through diffusion-based tractography may be an appropriate assessment option for assessing and following up on the degree of central pain. Additional randomized controlled trials will be needed in the future to more clearly verify the results of this study.


Objectives: To evaluate the feasibility and clinical value of CT-guided iodine-125 (125I) brachytherapy for pain palliation in patients with breast cancer and bone metastases after external beam radiotherapy failure.Methods: From January 2014 to July 2016, a total of 90 patients, who had received the standard therapies for bone metastases but still suffered moderate-to-severe pain, were retrospectively studied. About 42 patients were treated with both 125I brachytherapy and bisphosphonates (Group A), and 48 patients were treated with bisphosphonates alone (Group B).Results: In Group A, 45 125I brachytherapy procedures were performed in 42 patients with 69 bone metastases; the primary success rate of 125I seed implantation was 92.9%, without severe complications. Regarding pain progression of the two groups, Group A exhibited significant relief in “worst pain,” “least pain,” “average pain,” and “present pain” 3-day after treatment and could achieve a 12-week-remission for “worst pain,” “least pain,” “average pain,” and “present pain.” The morphine-equivalent 24-h analgesic dose at 3 days, 4 weeks, 8 weeks, and 12 weeks was 91 ± 27, 53 ± 13, 31 ± 17, and 34 ± 12 mg for Group A, and 129 ± 21, 61 ± 16, 53 ± 15, and 105 ± 23 mg for Group B. Group A experienced a lower incidence of analgesic-related adverse events and better quality of life than Group B.Conclusion: The CT-guided 125I brachytherapy is a feasible and an effective treatment for the palliation of pain caused by bone metastases from breast cancer after external beam radiotherapy failure. Approximately 65–75% of patients with advanced breast cancer develop bone metastases , which mChemotherapy and endocrine therapy are the currently used common baseline treatments for patients with advanced breast cancer and bone metastases . Neverth125I) brachytherapy has advantages in regard to disease control in patients with solid tumors  was treated with both 125I brachytherapy and bisphosphonates, and Group B (n = 48) was treated with bisphosphonates alone. This study was approved by The Ethics Committee of the Guangdong Provincial People's Hospital.In this retrospective study, we used data from patients with breast cancer and bone metastases who experienced moderate-to-severe pain. The radiological assessment of bone metastases includes enhanced CT, PET/CT, and radionuclide bone imaging. There were two groups in this study. Group A  underwent resection of primary tumors, which had been histologically diagnosed as breast cancer; (b) bone metastases were the only possible cause of pain; (c) score of at least four points on the “worst pain” item of the Brief Pain Inventory (BPI) in the 24 h prior to completing the inventory ; (d) fou125I seeds  were cylindrical titanium packages being 0.8 mm in diameter and 4.5 mm in length. The central source of the particle was an 125I radionuclide silver rod with a diameter of 0.5 mm and length of 3.0 mm. The matched peripheral dose was 100–140 Gy, and the average energy was 27–35 KeV. The radius of effective antitumor activity was 1.7 cm. Each seed had an initial activity of 0.0296 Gbq and a half-life of 59.6 days; about 93–97% of the brachytherapy dose was delivered within 3–5 months.The radioactive 125I seed implantation, 5-mm thick CT sections were obtained for all patients. A computerized treatment planning system (TPS)  was used to create a treatment plan for each patient. The gross tumor volume, planned target volume (PTV), and the surrounding vital organs were carefully delineated in every CT slice. PTV was defined as a 0.5–1.0 cm extension around the gross tumor volume. According to the three orthogonal diameters within the targeted tumor site and a prescribed matched peripheral dose, the TPS calculated the position of the brachytherapy applicator and the number of seeds to be implanted . Several 5-mm axial slices were obtained to delineate the upper and lower borders of the tumors. After achieving anesthesia with local infiltration of 5–15 ml of 1% lidocaine , an 18 G spinal needle  was inserted into the farthest tumor edge, ~5 mm or less from the tumor border. A clip implant gun  was then attached to the applicator for implantation. The  the TPS . If the The BPI short-form (BPI-SF)  was completed by each patient to obtain a measure of pain intensity  and pain interference . Patients completed the BPI- SF by the assistance of a study coordinator who was familiar with focal painful metastases. When multiple metastases were treated in one patient, the response was recorded for the painful area that was mostly treated. The BPI-SF was administered pre- and post-procedure. All patients underwent dynamic enhanced CT and clinical hematological examinations within 3–5 weeks after the procedure to evaluate the safety and efficacy of the therapy. The percentage of intra- and post-procedural complications was recorded according to the Toxicity Criteria of the Radiation Therapy Oncology Group .p < 0.05. For pain palliation analyses, patients were analyzed according to their groups. Changes from baseline in the BPI-SF score were analyzed using the analysis of covariance with the treatment group and randomization stratification parameters as factors and the baseline value as a covariate. Pain palliation endpoints were analyzed using a step-down approach, in which the primary and secondary endpoints were tested sequentially to preserve the family-wise type I error rate using the following order: 12 weeks, 8 weeks, 4 weeks, and 3 days with the BPI-SF score . The BPI-SF score of worst pain at 12 weeks was defined as a primary endpoint. Each hypothesis was tested at a significance level of 0.05 (two-sided). Statistical significance at each step was required to test the next hypothesis.Statistical analyses were performed using SPSS version 25.0 statistical software (IBM Corp.). Values are presented as the mean ± SD. We compared the characteristics of patients using the Pearson's chi-squared test. Statistical significance was set at 125I brachytherapy procedures were performed by experienced radiologists in 42 patients with 69 bone metastases. Thirty-nine (92.9%) of the 42 patients met the TPS criteria after the first procedure. Three patients who did not meet the TPS criteria received additional implantations. The final 125I brachytherapy achievement rate was 97.6% (41/42 patients), and the total number of implanted seeds was 1,410, with an average of 20 ± 6 seeds per lesion (range: 10–35). As shown in In Group A, a total of 45 0 between Groups A and B.The BPI-SF score for pain intensity is summarized in 0 and T1. There was a significant difference in the score for “worst pain,” “least pain,” “average pain,” and “present pain” between Groups A and B at T1, as shown in In Group A, the score for “worst pain,” “least pain,” “average pain,” and “present pain” was decreased at 3 days after therapy. In Group B, there were no changes in the score for all pain intensities during T0, the score for “worst pain,” “present pain,” “average pain,” and “least pain” was falling from T2 to T4 in Groups A and B. Regarding the pattern of pain remission, Group A achieved a continuous decline in the score for all pain intensity indices from T2 to T4, whereas Group B showed a reduction in the score from T2 to T3 and then rebounded at T4. There were statistical differences in the score for all pain intensity indices between Groups A and B at T4, and no statistical differences in the score for all pain intensity indices between Groups A and B at T2 and T3, as shown in In comparison with T0, there was no significant difference in the baseline of mean morphine-equivalent 24-h dose between Groups A and B (p = 0.261). In addition to patients experiencing pain relief, the mean morphine-equivalent 24-h dose of Group A was decreased gradually from T0 to T4, whereas that of Group B was decreased from T0 to T3 and rebounded at T4. In both groups, there were statistical differences in the mean morphine-equivalent 24-h dose at T1 and T4, but no statistical differences in the mean morphine-equivalent 24-h dose at T2 and T3.The prescribed dose  of analgesics is shown in The incidence of adverse reactions (AEs) to analgesics is summarized in The score for interference by bone pain in daily life is summarized in 125I seeds was found after tumor volume shrinkage. No severe complications, such as massive bleeding and vital organ radiation injury, occurred after 125I brachytherapy.Procedure-related complications are summarized in Bone pain is the most common clinical symptom in patients with breast cancer and bone metastases . AccordiRegional therapies for relieving pain are indicated. In clinical practice, radiotherapy due to its minimal invasion is preferred to surgical resection. A prospective clinical trial of 1,016 patients performed by the Radiation Therapy Oncology Group showed that single and multiple EBRT fractions provided equal palliation of bone pain caused by metastatic lesions and also showed that 53 and 83% of patients achieved complete pain relief and partial relief, respectively, with durable responses (ranging from 12 to 28 weeks) . General125I brachytherapy in combination with bisphosphonates provided more efficient pain control than bisphosphonates alone in patients with breast cancer and bone metastases after external beam radiotherapy failure. After 3 days of treatment, Group A showed a significant greater decrease in visual analog scale score for pain intensity as compared to Group B, especially for “worst pain,” “worst on average,” and “present pain.” We suggest that this may be because 125I seeds provide a cytocidal effect without causing radioedema by continuously emitting low doses of X- and γ-rays  . This may be explained by the modality of radiation release of 125I seed. We should argue the role of 125I brachytherapy in the regional control of bone metastases and the prevention of SREs in a long-term follow-up study.How do our findings affect clinical practice? We found that t tumors , 9. We d125I brachytherapy and the clinical benefit of treatment in regard to the prevention of SRE, progression-free survival, and overall survival.Our findings should be considered in the context of the limitations of this study. This was a retrospective study with a small sample size. Large sample sizes are needed to confirm our results. Further studies should also aim to study the optimal dose of 125I brachytherapy in pain palliation for patients with breast cancer and bone metastases after the failure of the EBRT. After CT-guided 125I brachytherapy, patients achieved a 12-week extension in pain palliation, which resulted in less analgesic consumption, shorter hospitalization, and a better quality of life.In conclusion, the results of our study demonstrated the effectiveness of CT-guided 125I brachytherapy is a feasible and an effective treatment for the palliation of pain caused by bone metastases from breast cancer after external beam radiotherapy failure.CT-guided The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The Ethics Committee of the Guangdong Provincial People's Hospital approved our study.125I brachytherapy procedures. JH, FY, and QM analyzed the data and drafted the manuscript. WZ, QG, and ZZ were the study coordinators. RX and WZ constructed the 125I brachytherapy treatment plans. All authors read and approved the final manuscript.JH, QM, and XC conceived and designed the study. JH, XC, and ZM performed all of the The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.