Background: Isometric paravertebral muscle training (IPMT) may improve mobility, pain, and quality of life (QOL) in cancer patients with spinal metastases. However, this regimen remains unproven in patients with unstable spinal metastases (USM), a population at high risk for clinical exacerbation with such interventions. Thus, we conducted this exploratory, non-blinded, randomized controlled trial (NCT02847754) to evaluate the safety/feasibility of IPMT and secondarily assess pain, bone density, pathologic fracture rate, and QOL. Methods: All patients had histologically/radiologically confirmed USM (per Taneichi score) and underwent non-operative management with 5–10 fractions of palliative radiotherapy (RT). Randomization (1:1) groups were IPMT  or muscle relaxation ; both lasted 15 min/day and started concurrently with radiotherapy. The primary endpoint was feasibility (completion of training programs three months post-RT). Secondary endpoints were pain response  and opioid consumption, bone density and pathologic fracture rate, and QOL . Results: Sixty patients were randomized and 56 received protocol therapy. Mean survival in both groups was 4.4 months. There were no adverse events with either training regimen. Altogether, ≥80% of the planned sessions were completed by 55% (n = 16/29) in CON and 67% (n = 18/27) in INT. Regarding the post-radiotherapy home-based training, ≥80% of planned sessions were completed by 64% (n = 9/14) of the INT cohort. There were no differences in pain scores, opioid consumption, or bone density between arms . No difference was observed between groups regarding new pathological fractures (INT: n = 1 vs. CON: n = 3) after three months (p = 0.419). There were no QOL differences between arms . Conclusions: IPMT is potentially feasible for high-risk USM patients. Future trials adequately powered for relevant endpoints are thus recommended. The spine is a very common area of metastatic disease ,2; thus,Whereas stable spinal metastases are often treated with palliative radiation therapy (RT) alone, management of unstable spinal metastases (USM) represents an interdisciplinary challenge ,5,6,7. AIn order to improve QOL in cancer patients, numerous short- and long-term effects of targeted physical training measures have been reported, with practical and clinically meaningful improvements in pain and mobility ,16,17,18Despite these encouraging results, this regimen remains unproven for USM; as a result, most prospective trials in this population remain reluctant to implement such interventions, since IPMT in this high-risk population could lead to clinical exacerbation, including increasing the risk of pathologic fracture.To address this knowledge gap, we conducted this exploratory randomized study, the first of its kind to date, to evaluate the feasibility of IPMT (as compared to muscle relaxation) and secondarily determine effects on pain, bone density, pathologic fracture rate, and quality of life .This exploratory randomized controlled trial (NCT02847754) was approved by the Heidelberg University Independent Ethics Committee (S-223/2016) . The goaFrom December 2016 to November 2018, 60 patients with histologically confirmed cancer and USM of the thoracolumbar segments were considered for this study. USM was defined based on computed tomography (CT) and/or magnetic resonance imaging (MRI) assessment based on the well-recognized Taneichi score ,22,25. SOther inclusion criteria were ages 18–80 years, Karnofsky performance score ≥ 70, ability to provide written informed consent, and an established indication for palliative RT. In order to address potential confounding by bisphosphonates or anti-RANKL agents, one of these compounds was required to be delivered if the patient was not already receiving one such agent. Exclusion criteria were previous RT or surgery to the given irradiation site, spinal cord compression according to the Bilsky score, myeloma/lymphoma histology, involvement of the cervical spine, and/or inability/refusal to complete the given exercise regimen.Complete details of IPMT (INT group) are presented elsewhere . BrieflyMuscle relaxation (CON group) was also performed for an estimated 15 min (once daily) during palliative RT as above. These exercises comprised of progressive muscle relaxation for the face, arms, abdomen, and legs. The back was excluded to avoid training effects on the paravertebral muscles. Muscle relaxation was similarly performed with 1:1 supervision and could voluntarily be continued following completion of RT (corroborated by an audio CD).Palliative RT was delivered in either three-dimensional conformal (3DCRT) or intensity-modulated (IMRT) techniques. Stereotactic body radiation therapy (SBRT) was not allowed for this study. For both techniques, the involved vertebra was treated to a dose of 20 Gy in 5 fractions or 30 Gy in 10 fractions. If IMRT was utilized, simultaneous integrated boosting (SIB) was allowed to 30 Gy for a 5-fraction regimen and 40 Gy for a 10-fraction regimen. Treatment planning was based on parameters in the Radiation Therapy Oncology Group (RTOG) 0631 study  and QUAN0), the end of RT (t1), three months post-RT (t2), and 6 months post-RT (t3). During therapy, the treating clinicians documented these parameters, but diaries were used to document patient-reported information subsequently.Both the primary and secondary endpoint-related parameters were measured at the start of RT  the primary endpoint of this randomized investigation was feasibility, which referred to completion of the training program at three months following the end of RT. The total number of completed and aborted/canceled training units and adverse events during training was recorded.The initial secondary endpoint was the pain score, as measured by the Visual Analog Scale (VAS). Pain level was measured by subjective patient reporting on the VAS scale with a range of 0–100. During clinical examination by the study physician, neuropathic pain was also monitored, as well as pain medication usage ; non-opioid analgesics were also recorded).Additional secondary endpoints were bone density and pathologic fracture rate. Bone density was assessed in the irradiated (and unirradiated) vertebral bodies by a single physician with CT imaging  and Syngo Osteo CT workstation in manually selected regions of interest; Hounsfield units were used for bone density measurements. Pathologic fractures were diagnosed by means of CT and/or MRI imaging and comparing to baseline imaging tests. New fractures were, by definition, not present on initial imaging, whereas progressive fractures referred to visibly increasing size and/or number of fracture gaps, dislocation of fracture fragments, or increasing sintering of the compression fracture (if applicable).The final secondary endpoint was QOL, assessed using the EORTC QLQ BM22 questionnaire, specially designed for patients with bone metastases. This module (range 0–100) comprises of 22 items and four scales for the measurement of pain in various parts of the body (painful sites), pain characteristics , functional impairment , and psychosocial aspects  . FatigueOwing to the exploratory nature of this trial and lack of literature-based reference values, a complete power calculation was not possible; however, with 30 patients in each group, it was possible to detect a standardized mean-value effect of 0.8 with 80% power at a significance level of 0.05 .p-values of the corresponding statistical tests comparing the treatment groups were reported. The VAS was adjusted for concurrent medications. Analysis of covariance (ANOVA) with repeated measurements, with treatment group as a factor, and pain medication as a covariate, were done. The Wilcoxon signed-rank test was used to detect possible differences between groups after 3 and 6 months. Graphical visualization includes the mean course over time. Finally, we compared the groups for overall survival, using Kaplan–Meier estimates and log-rank tests. Overall survival (OS) was defined as time from randomization until death, or censored at last contact.All statistical analyses were done using SAS software Version 9.4 or higher . All variables were analyzed descriptively by tabulation of the measures of the empirical distributions. According to the scale level of the variables, means and standard deviations (SD) or absolute/relative frequencies, respectively, were reported. Additionally, for variables with longitudinal measurements, the time courses of individual patients were summarized by treatment groups. Descriptive Sixty patients were randomized, and 56 patients started on protocol-based management . One patp > 0.20 for all). Of note, ten patients in the INT cohort and 14 subjects in the CON group initially wore an orthopedic corset (p = 0.396). Additionally of note, the Spinal Neoplastic Instability Score (SINS) [p = 0.007), whereas the Mizumoto score was similar .Baseline characteristics were balanced between the two arms . Most paet p = 0.96. Additp = 0.839) (The median follow-up was not yet achieved in both arms. Eleven patients (40.7%) in the INT group died of disease within three months of RT, versus six patients (20.7%) in the CON group. The mean OS was 4.4 months for both groups (= 0.839) .RT was altogether tolerated well. No patient in either arm experienced grade ≥3 acute or late events according to the Common Terminology Criteria for Adverse Events v.4.03.0–t1) there were no adverse events with protocol therapy. In the CON arm, 16 patients (55%) completed ≥80% of the planned relaxation sessions; the remainder were unable owing to deterioration in the general condition or clinical (non-protocol-related) complications. In INT, 18 (67%) patients completed ≥80% of the planned training sessions. The mean total number of completed training units was 7.8 (SD 3.3), and the mean number of potentially feasible units was 10.1 (SD 2.1).During the supervised training (t1–t2). The specified number of home training sessions was 36 (3× weekly over 12 weeks). In the INT arm, 14 participants were lost to follow-up during the period of t1–t2; of these subjects, 11 died and 3 were unknown. From t1 to t2, ≥80% of planned sessions were completed by 64% (9/14) of patients. In INT, 14 analyzed participants completed 39.6 (SD 21.1) of the prescribed 36 training sessions.Similarly, no adverse side effects were reported during post-radiotherapy home-based training (tNo difference in pain response was observed between the two groups after 3 and 6 months .1) (p = 0.958) and three months (t2) following RT (p = 0.666). There were no statistical differences in neuropathic pain between both arms at 3 (p = 0.826) or 6 months (p = 0.965).There were also no differences in OMED consumption at the end of RT (t0–t2 showed no significant influence on pain level (p = 0.120). The covariate evaluation of the interaction between group and time showed no significance, because the temporal changes were parallel (p = 0.970). Also, the group effect was not significant (p = 0.316). The pain response in the period t0–t2 showed a clear temporal dependence (p = 0.009)  .p = 0.826) or 6 months following RT completion (p = 0.965). Within the CON group, from t0 to t2 there was a significant increase in bone density (p = 0.006) (There were no differences in bone density between arms at 3 (= 0.006) .p = 0.079). No pathologic fractures in either arm were de novo; 1/14 and 3/18 cases were progressive in INT and CON, respectively (p = 0.419). There were no differences at 6 months (p = 0.243). Of note, no cases of salvage surgery for pathologic fractures were necessary in either arm.At initial presentation, there was a trend towards more pathologic fractures in the INT arm .Additionally, there did not seem to be differences in 3-month pathologic fractures based on use of an orthopedic corset , with a further positive trend between 3 and 6 months (p = 0.057). However, there was no evidence of treatment effect between t0–t2 (p = 0.478) or t0–t3 (p = 0.753)  .p > 0.05 for all). There were also no differences in all dimensions of fatigue between groups at each recorded time point . Emotional distress was also similar (p = 0.235).At all recorded time points, there were no significant QOL differences between groups, including pain characteristics, functional impairment, or psychosocial aspects , and QOL. Hence, the statistically equivocal results in most of these parameters cannot be used to conclude that IPMT offers no benefit as compared to passive muscle relaxation. Rather, this study demonstrates its safety and feasibility, in efforts to further utilize this regimen in larger studies to adequately test other such endpoints.This being said, pain response may be less impacted by IPMT and more by RT technique, as shown in promising randomized trials of ablative versus fractionated RT ,32. Herep = 0.120). However, within the time period t0–t2, pain response within that group was clearly evident (p = 0.009). Similarly, examination of the supervised training units from t0 to t1 showed significant pain relief .The covariate analysis of pain response during t0–t2 showed no influence of OMED on VAS values in the INT group (p = 0.079) , no de novo fractures occurred. Only existing fractures showed a visible increase in INT (1/14 cases) and CON (3/18) (p = 0.419).Despite the numerically increased initial fracture rate in the INT arm  would be blurred between cohorts based on other factors known to contribute to QOL.The utility of this investigation impacts future studies in patients with spinal metastases. Historically, patients with stable spine metastases were often restricted from such activities, with even tighter restrictions in USM cases. In the more recent era, many protocols do not specify whether these exercise regimens are allowed. For instance, the RTOG 0631 protocol does not make a specific recommendation on this matter. Although that study pertains to SBRT instead of a traditional 5–10 fraction regimen as utilized herein, further work must be done to verify whether IPMT is safe for well-selected USM cases undergoing SBRT .The difficulty of planning a fixed number of training sessions in the palliative setting is well acknowledged, and as a result there was no precedent to how many high-risk USM patients could complete these sessions. This was a major reason why this randomized trial was exploratory in nature and why formal power calculations could not be made. All patients herein experienced systemic progression at some point during follow-up, which  often requires temporary or prolonged stationary accommodation and may not be conducive to continuing the training program.In addition to the above, there are several limitations meriting elaboration. Along with the small sample sizes, short follow-up/patient survival, and single-center nature, studies of the palliative population encompass inherently heterogeneous patients, and the effect on subgroups thus cannot be reliably analyzed. This also makes the results difficult to extrapolate to other work, along with the fact that the particular assessment methods  and frequencies thereof may differ from other work, hence also limiting generalizability. Second, corticosteroid doses were not accounted for, which may impact pain levels and “pain flares”. Third, reasons for opioid usage as well as subjective pain relief are inherently difficult to assess, and are known limitations of any palliative study despite the prospective nature. Fourth, because the patients were included with a Karnofsky index >70%, it may not necessarily include a representative population reflective of clinical practice. Nevertheless, these shortcomings do not diminish the requirement to construct similar randomized trials powered for other endpoints, especially given that the safety and feasibility of IPMT in the high-risk USM population has been supported by these randomized results.IPMT is potentially feasible for high-risk USM patients. Future trials adequately powered for relevant endpoints are thus recommended.


Foot orthoses are widely used to manage plantar heel pain (PHP). However, the evidence concerning the effect of foot orthoses on PHP is not conclusive. The study aims to identify the characteristics of patients with PHP likely to achieve a positive outcome after customized foot orthoses and to verify the concept that patients who respond positively to anti-pronation taping would achieve a positive prognosis after wearing foot orthoses for six months.This is a prospective observational cohort study. Seventy-four patients with PHP underwent a baseline examination and received anti-pronation taping to their painful feet. The taping effects on pain and function were assessed at the 7-day follow-up visit. Then, all patients received an intervention for their PHP with customized foot orthoses for six months. Outcome was assessed with a numeric pain rating scale, the patient-specific functional scale, the foot function index, and the global rating of perceived change. Significant reduction of pain, increase of function, and perception of a meaningful improvement were considered a positive response.Of 74 patients, 49 had a positive response to the customized foot orthosis treatment. Five predictors were identified: (1) the average pain intensity decreased by over 1.5 points with taping, (2) the range of ankle plantarflexion > 54 degrees, (3) the strength of ankle plantarflexors on the symptomatic side was equal to or stronger than that on the other side, (4) the range of hip internal rotation < 39 degrees, and (5) the range of hip external rotation > 45 degrees. The presence of three or more predictors increased the rate of achieving positive outcome from 66 to 89%.The predictors of customized foot orthosis outcome in patients with PHP are related to several physical measures of a lower extremity. Findings of the study can be used to screen and select patients with PHP for foot orthosis intervention. Moreover, patients who respond positively to anti-pronation taping would also benefit from the customized foot orthoses. However, since there was no control group in the current study, it is inappropriate to draw conclusions about the effectiveness of the foot orthoses treatment.12617000119392).The trial was retrospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN  Plantar heel pain (PHP) is a highly prevalent foot disorder, accounting for 8–20% of both nonathletic and athletic populations –3. FirstMultiple extrinsic and intrinsic predisposing factors regarding PHP have been reported, inclusive of excessive foot pronation, prolonged weight-bearing activity, limited range of ankle dorsiflexion, unfavorable environment for shock absorption, high body mass index and history of previous lower limb trauma , 6–9. ExVicenzino et al. proposed the concept of a ‘treatment direction test (TDT)’ to identify patients who respond to using foot orthoses in treatment. They claimed that anti-pronation taping could be used to assess and determine the effectiveness of wearing foot orthoses –16. One In the past two decades, several studies have identified clinical predictors to enhance clinical professionals’ decision-making process in managing many musculoskeletal disorders, such as low back pain, patellofemoral pain syndrome and neck pain, by classifying patients into specific treatment-based subgroups –19. HoweThis is a prospective observational cohort study of 74 patients diagnosed with plantar heel pain by a physiatrist in a general hospital. Inclusion criteria for participants consisted of age older than 20 years, a symptom over the plantar heel or the plantar fascia area, a pain score of 3 points or high on an 11-point (0–10) numeric rating scale (NRS), and a symptom duration of at least 4 weeks. Patients were excluded when they had one of the following situations: (1) symptoms associated with the neurological system, (2) having lower extremity trauma in the past six months, (3) receiving lower extremity surgery in the past six months, or (4) had received corticosteroid injections or other interventions (including taping and foot orthoses) for PHP in the past three months. Before participating in this study, all patients signed an informed consent form that was approved by the Institutional Review Board of Taipei Veterans General Hospital (2013–01-026B). This trial was retrospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12617000119392).To record stable baseline symptoms, we advised all patients to maintain but not to increase their usual activity level at least 2 weeks before the baseline examination. Both a standardized history taking and physical examination were performed on all patients by an experienced physical therapist. A numeric rating scale (NRS) was used to assess the severity of pain . The FooThe passive range of motion of each lower limb joint was measured with a goniometer –26. The In order to determine the predictive value of the taping effect on the response from foot orthoses, all patients received customized biomechanical anti-pronation taping (BAPT) before wearing the foot orthoses. BAPT was applied with rigid adhesive tapes  by a physical therapist. The BAPT method consisting of two taping components, the arch taping and the calcaneal taping, is depicted in Fig. At the follow-up visit for taping effect, patients reported the changes over the period of BAPT treatment by completing the NRS for pain, FFI, PSFS and the global rating of change (GROC) scale. The GROC scale is a self-administered measure which can be utilized to evaluate the individual’s perception of change after a treatment , 40. RanAfter being assessed for the effectiveness of BAPT, all patients received an individualized foot orthosis intervention for six months. A pair of heat-moldable customized foot orthoses  was given to each patient. All patients were instructed to maintain their usual activities within the limits of symptoms and to wear the foot orthoses for as much time as possible in their day-to-day activities. Subjects were asked to return for follow-up six months later. The response of the foot orthoses was evaluated with the NRS for pain, PSFS, FFI for function, and the GROC scale for perceived effect at the 6-month follow-up visit. The assessor and treatment provider was the same physical therapist.At the 6-month follow-up visit, patients would be classified into either the success or nonsuccess group based on their reported outcomes. The criteria for inclusion of the success group were: (1) reducing the pain intensity by more than two points  or more According to the rule of thumb recommended by Peduzzi et al.  and Harrp < 0.15 were entered into a multiple logistic regression to derive significant predictors for a positive outcome from the use of customized foot orthoses. A significance level of 0.05 was used for this multiple logistic regression.We used SPSS version 20.0  to determine whether any potential predictor variables and anti-pronation taping response identified patients who benefited from the 6-month foot orthosis treatment. Firstly, univariate analyses including independent t tests for continuous variables and chi-square tests for categorical variables were used to determine the significant differences of independent variables between the success and the nonsuccess groups. The method to derive the optimal cutoff point of each significant continuous variable in the independent t test was the Receiver Operating Characteristic (ROC) curve. Then the variables that demonstrated significant between-group differences at Seventy-five patients with PHP participated in this study from March 2013 to June 2016. One patient dropped out from the study due to the incapability of returning for the first-week follow-up. The average age of all subjects was 48.4 ± 14.5 years. The process of recruiting and retaining subjects is shown in Fig. p = 0.347, Nagelkerke R square = 0.511).Eight potential demographic, self-reported and physical examination variables which demonstrated significant between-group differences in the univariate analyses were retained as prediction variables. The accuracy statistics and 95% confidence intervals (CIs) for all eight potential predictors entering into the logistic regression are presented in Table The pre-test rate of success with 6-month foot orthosis intervention was 66%. Considering the current clinical predictors, if the patient exhibited at least three predictors, the positive likelihood ratio (+LR) was 4.3  with an 89%  post-test rate of success  the average pain intensity decreased by over 1.5 points after BAPT, (2) the range of ankle plantarflexion > 54 degrees, (3) the strength of ankle plantarflexors on the symptomatic side was equal to or stronger than that on the contralateral side, (4) the range of hip internal rotation < 39 degrees, and (5) the range of hip external rotation > 45 degrees.The first predictive factor emerged from the final logistic regression model was that the average pain intensity decreased by over 1.5 points with taping. Based on this result, we verified that patients who respond positively to anti-pronation taping would also benefit from the customized foot orthoses. The decrease in pain with taping can be partly attributed to the reduction of excessive foot pronation during walking. Excessive or prolonged foot pronation during the stance phase of gait has been recognized as a risk factor of developing PHP , 6, 9. OThe second significant predictor for positive outcome was ‘the range of ankle plantarflexion > 54 degrees’. According to a previous study reporting the normative values of joint range of motion, the mean value of ankle plantarflexion was 56.5 degrees for general population . GreaterThe strength of ankle plantarflexors on the symptomatic side equal to or stronger than that on the contralateral side was the third predictor of positive response found in the present study. The ankle plantarflexor strength has been considered as an essential factor contributing to the step length and walking velocity , 6. TherThe last 2 significant predictors identified from the current study were both pertaining to the hip mobility. One predictor was ‘the range of hip internal rotation < 39 degrees’, and the other was ‘the range of hip external rotation > 45 degrees’. This clinical presentation with increased external rotation and decreased internal rotation ranges of motion at the hip was found in a study to be a risk factor associated with medial tibial stress syndrome . A possiThere were several limitations in our study. Firstly, because of the use of a single group design, we are unable to infer the effectiveness of foot orthoses for patients with PHP. The second limitation was that the current clinical predictors may not be generalized to the whole population because women accounted for 77% in this study population. More importantly, after identifying the preliminary clinical predictors, these significant predictors must be validated by well-designed randomized controlled trials in future.This study identified five significant predictors that determined which patients with PHP would respond positively to customized foot orthoses. These predictors for the effect of customized foot orthosis in patients with PHP are related to several physical measures of a lower extremity. The clinical prediction rule derived from this study can be used to screen and select patients with PHP for foot orthosis intervention. Moreover, we verified the concept that if a patient had a positive ‘treatment direction test’ (i.e. improvement on pain after receiving anti-pronation taping), we could assume this patient would benefit from the foot orthoses intervention. From the current study results, a reduction of pain intensity by over 1.5 points after application of an anti-pronation taping is an objective indicator of favorable outcome following foot orthoses treatment. However, since there was no control group in the current study, it is inappropriate to draw conclusions about the effectiveness of the foot orthoses treatment.


Patient-reported outcomes are increasingly used in evaluations of joint replacement surgery, but it is unclear if symptoms of osteoarthritis  influence health perceptions similarly before and after surgery.In this prospective study based on a hospital-based arthroplasty registry, patients with primary total hip or knee arthroplasty  completed the WOMAC Pain and Function scales, and the SF12 Physical and Mental Component Scores (PCS and MCS), before surgery and one year later. Associations between WOMAC and SF12 scales were examined using mixed linear regression models.All patient-reported outcomes improved following total joint arthroplasty, but the associations between symptom scales and global health perceptions were altered. Mental health scores at a given level of pain or function were lower after surgery than before, by about 4–5 points, a clinically meaningful and statistically significant difference. In contrast, the associations between WOMAC scales and the PCS remained stable. These findings were observed in both cohorts of patients.After total joint arthroplasty, mental health scores were lower than would have been expected given the symptomatic improvement. This suggests that relationships between patient-reported outcomes are context-dependent, and that care should be exerted when interpreting changes in patient-reported outcomes over time. Patient-reported outcomes (PROs) such as pain and functional ability, perceptions of physical and mental health, and quality of life in a global sense, are increasingly used to assess the impact of joint replacement surgery –4. PROs PROs are often understood to be linked causally; e.g., specific symptoms such as pain or impairment determine global perceptions of health, which in turn contribute to perceived quality of life . If the In this study, we examined the stability of the relationship between patients’ symptoms  and global perceptions of physical and mental health, by comparing the periods before and after hip or knee replacement surgery. We do not focus on the absolute changes in PROs brought on by surgery, but rather on the impact of surgery on the associations between PROs.This prospective study used data collected by the Geneva Arthroplasty Registry . The regFor this study we included all patients who underwent primary elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) between 2010 and 2016, and who had a health status and functional outcome measurement performed pre-operatively and one year after surgery. We included one or two primary THAs or TKAs in a given patient, but excluded revision procedures.The main dependent variables were mental and physical health status, measured by the Short Form 12-item (SF12) questionnaire . This inThe main independent variables were the timing of the measurement  and the patients’ pain and function, measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 12-item questionnaire . This inDescriptive variables included patient sex and age , the American Society of Anesthesiologists (ASA) score  . Patient age, sex and comorbidities were abstracted from the patient’s medical file.We included all eligible patients from the Registry, without an a priori sample size determination. We compared study participants to those who were excluded due to incomplete data, and compared the characteristics of patients who underwent primary THA and TKA. We reported the means and standard deviations (SD) of the SF12 and WOMAC scores at both points in time. We kept separate the analyses of THA and TKA patients, in order to verify the generalizability of the findings.2 from the linear model).To describe associations between each WOMAC score and each SF12 score, we obtained scatterplots for each pair of variables, overlaying baseline and follow-up measurements. To represent the associations without imposing a pre-conceived shape we obtained non-parametric regression functions  . As visuj for each patient j, and also a random factor vk(j) for each joint k in patients who had successive operations of both joints (knees or hips). The “joint” random factor vk(j) was nested within the “patient” random factor uj. Both random factors were used to model the intercept only, assuming that each patient (and each joint) has a given tendency to yield higher or lower SF12 scores, and that these individual tendencies are normally distributed with a mean of 0 and a variance estimated from the data. To facilitate the interpretation of the intercepts, we have centered the WOMAC scales at 50, and to magnify the slope coefficients we divided the centered scores by 10. As a result, the fixed intercepts correspond to patients with a WOMAC score of 50 (instead of 0), and the slope coefficients correspond to a difference in SF12 scores for an increment of 10 points on the WOMAC scale. E.g., for the MCS and the WOMAC Pain score, we used the following model:We used mixed linear models to estimate the change in intercept and slope between baseline (Time = 0) and follow-up (Time = 1). To account for the lack of independence of repeated observations, we included a random factor u0 is the mean intercept, uj and vk(j) are the individual and side-specific random effects, both centered at 0, and fixed coefficients b1, b2, and b3 represemt the effects of scientific interest. Thus b0 is the mean preoperative value of MCS projected for patients with a WOMAC Pain score of 50, b1 is the mean change of MCS at follow-up (again for a post-operative WOMAC Pain score of 50), b2 is the increment of MCS for 10 additional points of the WOMAC Pain score at baseline , and b3 is the change in this slope at follow-up. If the relationship between the pain score and the mental health score remained unchanged at follow-up, the coefficients b1 and b3 would be null.The fixed coefficient bWe also estimated intraclass correlation coefficients from the mixed linear models, as ratios of random intercept variance to the sum of random intercept variance and residual variance.Analyses were performed using SPSS version 22 and Stata version 13.During the study period, 1969 THAs and 1834 TKAs were performed at the hospital , and 990The differences between arthroplasties that were included in the analysis and those which were excluded due to unavailable questionnaire data were generally small, with few exceptions. In THA patients , the non-participants were on average younger , more likely to smoke  and more likely to have an ASA score of 3 ; differences were small and statistically non-significant in terms of sex, body mass index, and prevalence of heart disease, diabetes, and high blood pressure. In TKA patients, the non-participants were also younger , had a higher body mass index , were more likely to be women , to smoke  and to have an ASA score of 3 ; differences were small and non-significant as to comorbid conditions.Among study participants, TKA patients were older than THA patients (mean 71.5 years (SD 9.4) vs 68.6 (11.9)), they were also more likely to be female, obese, non-smokers, and more likely to suffer from diabetes or high blood pressure . Pre-opePerceptions of mental and physical health both improved following joint replacement. Before surgery, mean MCS scores were around 45 in both patient groups, and increased by 2–3 points at one-year follow-up . The PCSNon-parametric regression analyses showed positive associations between the WOMAC Pain and Function scores and the MCS at both points in time, in patients with THA  left andFor the PCS plotted as a function of the WOMAC Pain and Function scores in patients with THA , right aIn stratified linear regression analyses, in both patient groups, the predicted values of the MCS at 50 points of the WOMAC scores were about 5–6 points lower at follow-up than pre-operatively  and patients’ perceptions of mental health following total joint arthroplasty. Mental health scores were influenced to the same extent by pain and function after surgery as before (same slopes in the linear regression model), but their absolute level was lowered after surgery at a given level of pain and function (lower intercepts). For physical health, the absolute scores at mid-range values of pain and function were unchanged after surgery (same intercepts), but the associations became slightly stronger (steeper slopes). These results suggest that relationships between PROs are context-dependent, and that one should be careful when interpreting changes in PROs over time, especially if the changes are induced by surgery.Total joint arthroplasty delivered very substantial pain relief and functional improvement, and increased physical health scores by more than a standard deviation on average. The improvement was less impressive for mental health , corroborating previous reports . Yet, afWe observed no such systematic shift for post-operative perceptions of physical health. For an average patient, the improvement in PCS was exactly of the amount that could be predicted from the cross-sectional association observed before surgery, as though change in pain and function fully explained the improvement in perceived physical health. Furthermore, the slope of the association and the proportion of explained variance in physical health increased somewhat after surgery. This may reflect a patient’s greater focus on symptoms of osteoarthritis during postoperative rehabilitation.The relationships beween symptom scales and measures of mental and physical health changed in a similar way for patients with both types of joint replacement, THA and TKA. This suggests that these phenomena may have general validity. It would be interesting to see if other types of interventions that have a notable impact on chronic symptoms and functional limitations , induce similar shifts in associations between PROs.We can propose several possible explanations for our findings. The downward shift in MCS scores may be attributed to unfulfilled expectations. Pain and functional impairment may be less tolerable to some patients after total joint arthroplasty than before, because they may have expected better results from a surgical intervention that is often understood to be of last resort . Other fOf note, recent studies have shown a similar phenomenon: the presence of severe pain and dysfunction decreased the global perception of health  more strongly after total hip  or knee between symptom scales and health perceptions, which makes information bias less likely. In another analysis of the same patient cohorts, we observed that the self-rated health item remained completely unchanged after total joint arthroplasty [Finally, it is possible that the measurement properties of the instruments changed following surgery and that what we have observed are variants of information bias . Previouroplasty , which pA strong feature of our study is the inclusion of large unselected cohorts of patients, which yields precise estimates and grants real world relevance to our results. As the same patients were assessed at baseline and at follow-up, confounding by stable patient characteristics cannot explain the observed changes.The main limitation of our study is the lack of a clear mechanistic explanation for the observed results, which cannot be inferred from observed data. Qualitative interviews with patients before and after joint replacement surgery may improve our understanding of the contextual determinants of patients’ reports, and of the mechanisms that caused the observed changes in relationships between psychometric PRO scales. Nevertheless, the consistency of the findings in two cohorts of patients indicates that the phenomena are real. Another limitation is that we were unable to include in this analysis all possible determinants of the MCS and PCS, such as psychiatric and somatic comorbidities. However, to the extent that such determinants remain stable over the 1-year period, they would not have influenced the comparison of pre-operative and post-operative associations between WOMAC scores and SF12 scores. Finally, the study participants represented about one half of all eligible patients, mostly due to failure to return the self-report questionnaires. Study participants were somewhat older but healthier than the non-participants. However, we believe that it is unlikely that this selection process would have modified the patterns of association between health status and symptom scales, which is the main theme of this analysis.Our results may not influence clinical decisions for individual patients, but they are relevant for the measurement of PROs as indicators of the quality of care provided by surgeons or hospitals. Clinical outcomes were not influenced in the same way even by a highly effective intervention, and their relationships were context-dependent. This suggests that measurement of multiple PROs, some disease-specific and others generic, is to be preferred in order to capture the complexity of each patient’s experience. Our results also illustrate a novel manifestation of response shift, one that affects relationships between PROs.We found that perceptions of mental health were lower after total joint arthroplasty of the hip and knee than may have been expected based on symptom relief, whereas the perceptions of physical health were as predicted by symptom relief. The reasons for these phenomena should be explored, in order to facilitate the interpretation of post-intervention PRO scores.Data collection in the Geneva Arthroplasty Registry, and the use of the data for research were approved by the Research Ethics Commission of canton Geneva (CER 05–017). All patients have provided written informed consent for inclusion in the Registry.


The Korean Triage and Acuity Scale (KTAS) was developed based on the Canadian Emergency Department Triage and Acuity Scale. In patients with pain, to determine the KTAS level, the pain scale is considered; however, since the degree of pain is subjective, this may affect the accuracy of KTAS. The purpose of this study was to evaluate the accuracy of KTAS in predicting patient's severity with the degree of pain used as a modifier.A retrospective observational cohort study was conducted in an urban tertiary hospital emergency department (ED). We investigated patients over 16 years old from January to June 2016. The patients were divided into the pain and non-pain groups according to whether the degree of pain was used as a modifier or not. We compared the predictive power of KTAS on the urgency of patients between the two groups. Acute area registration in the ED, emergency procedure, emergency operation, hospitalization, intensive care unit admission, and 7-day mortality were used as markers to determine urgent patients.Overall, 24,253 patients were included in the study, with 9,175 (37.8%) in the pain group. The proportions of patients with KTAS 1–3 were 61.4% in the pain and 75.6% in the non-pain groups. Among patients with KTAS 2–3, the proportion of urgent patients was higher in the non-pain group than the pain group (p<0.001). The odds ratios for urgent patients at each KTAS level revealed a more evident discriminatory power of KTAS for urgent patients in the non-pain group. The predictability of KTAS for urgent patients was higher in the non-pain group than the pain group .Considering the degree of pain with KTAS led to overestimation of patient severity and had a negative impact on the predictability of KTAS for urgent patients. Emergency department (ED) overcrowding has become a global trend due to an increased number of patients visiting the ED and boarding patients waiting for hospital admission., 2 It isSeveral countries have devised triage tools since the early 1990s. The Canadian Emergency Department Triage and Acuity Scale (CTAS), the Australian Triage Scale (ATS), the Emergency Severity Index (ESI), and the Manchester Triage Scale (MTS) based on the 5-level classification systems have greatly influenced triage in modern emergency rooms.–8 The CTThe KTAS consists of five acuity levels; from level 1 (resuscitation) to level 5 (non-urgent). Screening with the KTAS occurs first with the serious and life-threatening conditions  among patients, with a critical first look. In most patients who are not in a very critical condition, the KTAS assessment starts with the main complaint of the patient; the KTAS then takes into account additional modifiers such as the vital signs, the level of consciousness, pain severity, injury mechanism, and blood sugar. Depending on which consideration is applied, the KTAS level can be evaluated diversely even in the same patient. In such a case, it is recommended that the more acute KTAS level be selected. Where pain severity is used as a modifier, the acuity level is determined depending on the location of pain, chronicity, and pain score. For example, in patients presenting with abdominal pain, if the onset of pain is acute and the pain score is moderate, the KTAS level is rated as 3. However, the degree of pain is a subjective factor that can be influenced by the patient's age, sex, race, psychological condition, and accompanying symptoms.–19 To miDespite these concerns, there is no research on the accuracy of triage when pain severity is used as the modifier in determining the final level of KTAS. The purpose of this study was to evaluate the accuracy of KTAS in predicting patient's severity when the degree of pain was used as a modifier.This was a retrospective observational cohort study conducted in the ED of an urban tertiary university hospital with 2,000 beds, with more than 90,000 patients visiting the ED yearly; the hospital had separate adult and pediatric EDs, and patients aged over 16 years were treated in the adult ED. The adult ED was divided into an acute (with 17 beds) and recovery (with 26 beds and 10 clinic chairs) areas. We studied patients who were treated in the adult ED from January to June 2016. All data was collected anonymously, and this study was exempt from the obligation to obtain informed consent by the hospital’s institutional review board committee. When an emergency patient arrives at the ED, the triage nurse classifies the patient's severity using KTAS 1–5 . Triage nurses were staff with more than four years of experience in the ED, and who had completed the 6-hour KTAS training program run by the KTAS committee under the Korean Emergency Medicine Association. Patients arriving with very urgent conditions such as unconsciousness and vital sign instability enter the acute area of the adult ED directly from the triage room . On the We divided the patients into the pain and non-pain groups depending on whether the degree of pain was used or not used as a modifier in the KTAS evaluation. Patients who did not complain of pain and those whose consciousness was not clear were excluded because the evaluation of pain may not be reliable.This study was approved by the hospital’s institutional review board (IRB) . All data were collected anonymously. This study was exempt from obtaining informed consent by the IRB committee.We extracted basic patient characteristics and medical information from the hospital information system. Non-medical problems mean that the patient’s disease was caused by external factors such as trauma, poisoning, and environmental factors. Complaint category referred to the body system that corresponds to the symptoms that the patient complains. The time from arrival to area registration was investigated in terms of the time required for triage and initial assessment. ED length of stay (LOS) was the time from ED arrival to hospitalization or discharge.The lack of a complete standard reference for determining urgency has always been a problem in validation studies for triage tool., 20 A crComparisons between the two pain groups were performed using chi-square analysis for categorical variables and Mann–Whitney U test for continuous variables because of the positive skewness in the data distribution. The distribution of KTAS and the proportion of urgent patients were compared between the two groups. Some differences in patients’ characteristics in both groups can affect urgency, and we have adjusted these characteristics. Potential factors were identified by using the Akaike information criterion (AIC) stepwise selection method and the adjusted odds ratio was presented through multivariable logistic regression. To evaluate the discriminative ability of KTAS, the adjusted odds ratios (OR) of each KTAS level compared to KTAS 3 for urgent patients were calculated. Since the number of patients with KTAS 3 was the greatest, KTAS 3 was used as a reference. InfluencFrom January to June 2016, a total of 28,425 adult patients visited the ED . Among tWe compared the patient characteristics, KTAS data, and treatment outcomes between the two groups . PatientOnly 9.2% patients in the pain group were treated in the acute area, compared with 34.1% in the non-pain group (p<0.001). The number of patients who received emergency procedures in the ED was also higher in the non-pain group . However, emergency operations were performed more in the pain group . Patients in the non-pain group had higher rates of hospitalization, ICU admissions, hospital 7-day mortality, and composite index .The proportions of urgent patients in each KTAS level were compared between the two pain groups and shown in Correlation between KTAS and urgent patients are shown in When the severity was classified using KTAS in emergency patients with pain, pain severity was used as a modifier in 53.4% of patients and their severity was lower than that of patients who were evaluated regardless of pain severity. The predictive power of KTAS in urgent patients was higher in the non-pain group for several severity indicators. We found that the acuity level was overestimated in the pain group patients. The ideal triage tool should be able to constantly evaluate the urgency of the patient; hence, the same triage level should indicate the same urgency. In particular, when the ED is overcrowded, it is critical to ensure that the limited resources are preferentially provided to more urgent patients; this underscores the importance of triage as a starting point in determining severity. Several factors may be related to the accuracy of triage. We have confirmed that pain severity as a modifier in KTAS is a factor affecting accuracy. The cause of over-triage by applying the degree of pain to KTAS evaluation can be considered diversely.At the time of arrival at the ED, patients are often anxious, due to the unfamiliar ED environment and the uncertainty of their health conditions, and this anxiety can worsen their pain., 22 As rTo prevent over-triage in patients with pain, there is a need to more aggressively apply objective indicators such as facial distortion and vital signs to calibrate the patient's pain level. However, as reported by Guru et al., pain scores for the same patient differ between medical staffs. For otheIt is also necessary to evaluate whether the 4 and 8-point boundary distinguishing between mild, moderate, and severe pain in KTAS is appropriate. In ATS and MTS (similar to KTAS), the triage levels of patients with pain is determined according to the three stages of severe, moderate, and mild pain. However, the boundaries for dividing the degree of pain differs; compared to KTAS, ATS applies the lower scores of 4 and 7-point while MTS has the higher scores of 5 and 8-point. KTAS appThe severity of patient was overestimated and the accuracy of KTAS for predicting urgent patients was reduced when the patient's pain level was used as a modifier in the severity classification. In order to adequately consider the patient's pain level to the severity classification, the degree of pain should be accurately assessed and, if necessary, KTAS guideline should be supplemented, to correct the overestimation. A future research using a prospective observational study would be necessary to estimate the ability of KTAS in predicting urgent patients with patient’s level of pain as a modifier more accurately.S1 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S2 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S3 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S4 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S5 AppendixICU, intensive care unit; KTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S6 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S7 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S8 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S9 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S10 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S11 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.(DOCX)Click here for additional data file.S12 AppendixICU, intensive care unit; KTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.; All 490 patients with KTAS 5 in the non-pain group did not admit to ICU, so the statistics were not calculated.(DOCX)Click here for additional data file.S13 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal. All 557 patients with KTAS 5 in the pain group did not expire within 7-day, so the statistics were not calculated.(DOCX)Click here for additional data file.S14 AppendixKTAS, Korean triage and acuity scale; OR, odds ratio; CI, confidence interval; The reference value for complaint category is Gastrointestinal.; All 167 patients in the non-pain group with KTAS 1 were severe, so the statistics were not calculated.(DOCX)Click here for additional data file.


The control group was treated with 50% N2O 2 minutes before dressing change until the end. Pain, anxiety, vital signs, and the highest concentrations of N2O inhaled were recorded at 1 minute before N2O inhalation (T0), dismantling of outer (T1), inner dressings (T2), debridement (T3), drug-smearing (T4), bandaging (T5), and 10 minutes after completion of the procedure (T6).In this single-blind prospective randomized controlled trial, 70 stable adult burn patients were randomized to 2 groups during May 2015 to January 2016. The experimental group was titrated with N2O concentrations of the experimental group were mainly 60% to 70% at T2 (87.9%), T3 (87.9%), and T4 (81.8%).The pain and anxiety scores in the experimental group performed significantly less than the control group during T2-T6. The systolic blood pressure in T2 and the heart rate at T2 and T3 varied significantly between the 2 groups. The highest N2O titration significantly reduced pain and anxiety in burn patients, with minimal side effects.N Anxiety induced by a painful experience with a poor dressing change can lead to bad compliance with rehabilitation, increased pain, and a loss of trust in the burn team. If left untreated, anxiety can also escalate into fear, insomnia, depression, and helplessness, which may cause patients to be psychologically unable to cope with their disease. Therefore, exploration of safe and effective analgesic and anxiolytic drugs is the goal of burn care.Pain is the most common clinical symptom in burn patients, which is especially more intense and unbearable in wound dressing. The incidence of side effects of opioids can be as high as 76% to 92% in patients with acute pain. Nonsteroidal anti-inflammatory drugs (NSAIDs)are widely used analgesics. They are weak when used alone, but have synergistic effects with opioids. Side effects, particularly gastrointestinal bleeding, may limit its use in severely burned patients.Opioids are still the main treatment for moderate and severe burn pain. However, opioids can cause a multitude of side effects with a high incidence, such as constipation, itching, nausea, respiratory depression, and so on. Patients often are not treated effectively because physicians in China are worried about the possible complications. Nitrous oxide (N2O), a colorless, slightly fragrant inhalation anesthetic may be more appropriate than the aforementioned drugs for acute burn pain in China due to its safety, and rapid analgesic and anxiolytic action.The use of opioids, NSAIDs to control pain and anxiety in China is not extensive due to lack of clinical awareness.2O is 0.47, which is extremely stable in the blood without combination with any substances. N2O quickly diffuses through the alveolar-capillary membrane and acts within 30 to 40 seconds after inhalation. The analgesic effect peaks in 5 minutes. Transient breathing cessation eliminates 99% of the N2O from the alveoli, and patients fully recover after administration of 100% pure oxygen for about 5 minutes. Nitrous oxide is not metabolized via liver, and 99% is expelled via lungs, and 0.004% through gastrointestinal tract. Two major types of established N2O analgesia are available. The first type involves 50% N2O (Entonox) inhalation, which is used to induce painless labor or abortion,,15 endoscopy, and in the emergency department. Rapid inhalation alleviates pain and anxiety promptly. However, this approach may increase discomfort in adult patients, and the probability of adverse reactions such as nausea and vomiting. The second type of analgesia entails N2O titration, which slowly increases the dosage from 0% to 70% to determine the appropriate dose. It provides individualized treatment of patients using the minimum effective dose, without excessive sedation. The treatment is mainly used in dental procedures.,19The blood gas distribution coefficient of N2O ameliorated burn pain and anxiety in pediatric population–22 in contrast to conflicting findings in the adult population. Yuxiang L found that 50% N2O has a positive effect on dressing pain relief. However, do Vale et al reported that the use of 65% N2O resulted in no additional benefit. Moreover, a British survey of nurses in 11 countries showed that pain sensation in wound treatment is not constant, and the most acute pain is felt during removal of the dressings, followed by debridement. Due to the biological differences between individuals, the concentration of N2O required may vary in patients at different stages of dressing. Therefore, we hypothesized that N2O titration is more appropriate than administering fixed N2O concentration during burn dressing. However, studies investigating this approach in adult burn patients are limited.Evidence suggests that N2O and N2O titration, to explore the efficacy and provide a rationale for the development of a model of N2O analgesia during burn dressing in stable patients.This study compared the analgesic and anxiolytic effects of 50% N22.1In this single-blind prospective randomized controlled trial approved by the Fujian Medical University Union Hospital Ethics Committee (2015 ky018) and Chinese Clinical Trial Registration (ChiCTR-IPR-15006507), the subjects included hospitalized burn patients at the Burn Center of Fujian province between May 2015 and January 2016. Informed consent was obtained from all individual participants included in the study.The inclusion criteria were: 18 to 65 years of age; NRS ≥4 during the last dressing change; burn wounds not affecting ECG monitoring; absence of burn surgery; lack of formal psychotic history, and barrier-free communication.The exclusion criteria were: pregnancy, intestinal obstruction, air embolism, epilepsy, pneumothorax, obstructive respiratory system disease, and acute upper respiratory tract infection; ENT diseases, drug dependence, pulmonary fibrosis; exposure to opiates within 6 hours or chronically; unstable vital signs; and psychological and emotional instability.t test sample sizes, a significance level of 5%, and power of 90%, the dropout rate was set at 20%. According to the preliminary experimental results involving 5 cases in each group, pain was 2.42 ± 1.31 in the experimental group and 3.58 ± 1.42 in the control group during the removal of intimal dressing. A minimum of 70 patients were needed. Finally, 107 patients were recruited for the study, and 70 patients met the eligibility criteria. Following baseline evaluation in the hospital, patients were randomized by an independent researcher using an Excel-generated randomization table with 35 patients in each group. Group assignment was concealed using opaque envelopes, which were opened after the completion of the baseline assessment. In the experimental group, a patient with SpO2 < 90% underwent skin graft. In the control group, 2 patients were delirious and one of them was treated with additional analgesia, and excluded from the study.Based on the 2 independent sample A total of 65 patients finally completed the study including 33 in the test group and 32 in the control group Fig. .2.22O analgesia system , which delivers a continuous flow of 0 to 70% was used for the intervention. Patients were covered with a mask and trained in deep breathing as well as administered 100% O2 for 2 minutes before dressing change. Subsequently, patients in the control group (C group) inhaled 50% N2O starting from 2 minutes before dressing change until the end. Patients in the experimental group (E group) inhaled 30% N2O initially, and the N2O concentration was increased from 5% to 10% every 1 to 2 minutes until patients were sedated completely. The concentration of N2O was adjusted by nurses based on physician recommendations to ensure optimal sedation according to the patients’ facial expression and body language. Patients’ minute ventilation remained unchanged during the procedure. Minute ventilation of patients was calculated by multiplying the tidal volume with respiratory rate. The tidal volume was determined as kg × (7 ∼ 10 mL/kg).An effective N2.3,26 We also used an ECG monitor  to assess the vital signs. We also monitored adverse reactions of patients and inhalation of the highest concentration of N2O in the experimental group.A Numerical Rating Scale (NRS) (0–10) and Visual Analog Scale for Anxiety (VASA) were used to assess pain and anxiety, respectively, with zero indicating painless or anxiety-free condition, and 10 suggesting the worst possible pain or anxiety. The 2 scales are widely used in clinical and research studies, with high reliability and validity.2.42O and N2O titration. The secondary outcomes included description and analysis of the highest concentration of N2O inhaled in the experimental group, and the vital signs and adverse reactions among the 2 groups during T0-T6.Our primary goal was to characterize and compare the pain and anxiety of patients during the T0-T6 using 50% N2.52O analgesia was conducted by 2 doctors and 2 nurses with at least 5 years of related work experience, and who were trained in the theory and practice of N2O analgesia. Pain, anxiety, vital signs, side effects, and the highest concentration of N2O were recorded at 1 minute before N2O inhalation (T0); following removal of the outer dressing (T1); removal of the inner dressing (T2); debridement (T3); medication (T4); bandage (T5); and 10 minutes after dressing change (T6) by 2 other trained nurses who were nonparticipants. Doctors and nurses providing the study interventions and outcome assessors were not be blinded in this study, but they did not know the research hypothesis. According to the different dressing lengths, the measurement frequency during T1 to T5 was set to 2 to 5 minutes after each step. The final values of each step were expressed as mean .Patients admitted to the hospital were randomized into groups blindly, following signed informed consent and completion of a general information questionnaire. Intervention was implemented once during days 2 to 7 of wound treatment. The whole process of dressing treatment and N2.6P < 0.05 using a 2-tailed test. Normally distributed data were expressed as means ± SD. Otherwise, they were described using median (interquartile range [IQR]). Materials were described in medians and quartiles. Qualitative data were expressed as frequencies (percentages). Descriptive statistics, independent sample t test and χ2 test, Fisher exact probability method, or nonparametric tests were used to compare the general information and pain, anxiety and vital signs at T0 in both the groups. Repetitive measurement and analysis of variance (RMANOVA), and generalized estimating equations (GEEs) were used to test the interaction of intervention measures and time. RMANOVA or Wilcoxon (W) test was used to analyze data in pairs of groups. Multivariate analysis of variance (MANOVA) and Mann-Whitney U test were used to compare data in pairs between the two groups. χ2 was used to compare the side effects. Both primary and secondary outcomes were analyzed in each study protocol.Data input was analyzed using Epidata3.0 software. SPSS19.0 was used for statistical analysis. Data analysis was done by a statistician who was blinded for the randomization allocation. Statistical significance was considered at an alpha value of 0.05 and 33.12, compared with the control group (33.2 ± 18.7) cm2. Burn depth was a priority with second- and third-degree cases . The dressing time was within 20 minutes. No statistical significance was found in age, sex, marital status, education, occupation, income, residence, provider payments, burn area and depth, preliminary treatment time, dressing time or weight between the experimental (E), and control (C) groups (P > .05), as shown in Table Subjects’ age ranged from 18 to 65 years. Males accounted for 78.5% . A majority of the subjects were married . The education level of the 2 groups was mostly below senior middle school . Professionals included mainly workers and farmers . Patients were mostly residents in the countryside . Flame burns accounted for the majority of cases . The total burn area of the experimental group was 34.3 ± 21.5 cm3.22O titration concentration in the experimental group ranged from 30% to 70% during T1 to T5: mainly 50% to 65% in T1 (90.9%), 60% to 70% in T2 (87.9%), T3 (87.9%), T4 (81.8%), and 40% to 60% in T5 (72.7%), as shown in Table The N3.3Z = −4.771, P = .685; F = 3.596, P = .063).The median pain scores (NRS) were <3 in the 2 groups at T0. The anxiety scores (mean ± SD) were 4.70 ± 1.07 in the E group and 5.31 ± 1.51 in the C group at T0. The differences in pain and anxiety between the 2 groups at T0 were not statistically significant .The median pain scores of the 2 groups increased initially followed by a decline during T0 toT6. The worst pain occurred at T2 , which scored 3 in the E group and 4 in the C group. The pain scores of the E group were significantly lower than in the C group at T1∼T6. Pain at T2 was higher than at T0 in the E group, and pain at T1∼T4 was higher than at T0 in the C group (P < .01). The anxiety scores of E group were significantly lower than in C group at T1∼T5 (Table The mean anxiety scores of the 2 groups declined significantly each time after dressing change compared with the scores before dressing (T5 Table .3.4P > .05). Furthermore, no statistically significant differences were found in the heart rate (HR), diastolic blood pressure, respiration, and blood oxygen saturation (SpO2) between the 2 groups at T0-T6  was not significantly different between the 2 groups at other times (T6 Table .3.5P > .05) (Table Two patients (6.1%) in the experimental group exhibited dizziness and nausea, respectively. A total of 3 patients (9.4%) showed adverse effects in the control group, including dizziness, nausea, and abnormal excitement, respectively. The differences between the 2 groups were not statistically significant P > .0  and T3 (debridement). It has been reported that 30% of N2O induced analgesia with 15 mg morphine administered subcutaneously. Therefore, every 10% of N2O is equivalent to the effect of 5 mg morphine administered subcutaneously. As shown in Table Burn patients experience severe procedural pain, which is assessed by NRS without analgesia. conducted a double-blind randomized study showing that the pain scores by VAS during the burn dressing change were only 1.65 ± 1.34 versus 9.39 ± 0.74 during inhalation of 50% N2O in the experimental group and oxygen in the control group suggesting that the analgesic effect of 50% N2O was superior to the that of N2O titration found in our study. The pain scores in Liyuxiang's study represented the average scores during the entire dressing. Our study, by contrast, measured the pain at every step of the dressing. Therefore, we found that although 50% N2O was effective, the analgesic effect was not adequate during the removal of the inner dressing, debridement, and drug-smearing steps.Interestingly, Liyuxiang et al Patients who need repeated wound management exhibit excessive anxiety due to painful dressing changes and risk of infection. Anxiety in turn reduces the pain threshold and increases the sensitivity to pain, leading to a vicious cycle of pain-anxiety-worse pain, which ultimately affects the condition itself. Therefore, accurate evaluation of anxiety in burn patients is necessary for effective analgesia.Pain is a complex sensation combined with sense and mood, resulting in individual variation in psychological and emotional responses. Anxiety is the most prominent and common psychological stress reaction in acute pain. Physicians focus on the treatment of anxiety and pain together. N2O is a sedative and anxiolytic. Zacny et al showed that dental patients with high, moderate, or low anxiety showed significant enhancement in mood following N2O titration. A double-blind clinical trial of Manouchehrian and Bakhshaei showed that 50% N2O significantly decreased anxiety during parturition under spinal anesthesia in a cesarean section. This study also concluded that titration or 50% N2O effectively relieved anxiety, although the anxiolytic effect of titration was better than that of 50% N2O. This finding may be attributed to the larger reduction of pain and the high concentrations of laughing gas in the titration group. Starting from T1, the concentration of laughing gas, which was >50% increased in the experimental group, resulted in a stronger anti-anxiety effect.Results showed that moderate anxiety in the 2 groups before dressing was consistent with the results reported by Tan et al. Therefore, in addition to the direct evaluation, vital signs are recognized as indirect indicators of pain for the evaluation of treatment safety. N2O is nonirritating and does not increase airway secretions. It has almost no effect on breathing and patients exhibit a self-preservation reflex during N2O inhalation. Under conditions lacking oxygen, N2O has almost no effect on heart or blood vessels. Our study suggests that blood pressure, breathing, and HR varied smoothly between the 2 groups, and SpO2 showed almost no variation in the 2 groups, indicating safety. The SBP of the trial group in T2 was lower than in the control group. The HR of the control group at T2 and T3 exceeded 100 times/min, and was higher than in the experimental group. The differences were clinically significant. The findings suggest that N2O titration analgesia was better than 50% N2O.Severe acute pain stimulated the sympathetic nerve, promoted blood catecholamine levels and increased the angiotensin II secretion, triggering a series of organ- and tissue-specific reactions, such as accelerated HR, elevation of blood pressure, tachypnea, and increased oxygen consumption. showed that 50%N2O was most likely associated with mild side-effects including dizziness, nausea, and excitement, which ranged from 4% to 8%. The study of Zier et al found that adverse reactions or complications in patients who inhaled N2O ≤50% and >50% accounted for 1.9% and 3.5%, respectively. Most other studies showed that exposure to 50% N2O or N2O titration resulted in side effects up to 18%.–45The incidence of adverse reactions, which included dizziness, nausea, and excitation in the 2 groups, was lower than 10%, and consistent with previous studies. Onody et al4.1The small sample size, focusing only on stable patients and single-center study, might introduce a selective bias. Multicenter and randomized controlled studies with large samples are needed.It is a single-blind study, and the intervenors and investigators were not blinded to the study groups during dressing change and data collection, which may introduce subjective bias. Therefore, double-blind trials are needed.This study lacked a blank control, and therefore, only indirectly evaluated the baseline analgesic effect of the 2 modes of nitrous oxide analgesia compared with other studies.2O were unknown. Additional follow-up studies are needed to explore the long-term role of nitrous oxide in burn patients.This study only conducted analgesic interventions with research subjects. The end point of observation was only 10 minutes after dressing. Therefore, the overall effects and adverse reactions subsequently or after repeated use of N52O titration is a more appropriate intervention as analgesia during burn dressing compared with 50% N2O exposure. However the role of N2O sedation and analgesia in burn medicine in China is still at the initial stage. Further analysis of the analgesic effects in different populations  is needed. Appropriate protective measures  and professional operating procedures and guidelines are imperative. Relevant training in titration technology, technical expertise, and evidence-based medicine remains to be developed and improved.In summary, NConceptualization: Lin Li, Qiong Pan, Le Xu.Data curation: Lin Li, Qiong Pan, Renqin Lin, Jiaxi Dai, Xinyan Chen, Meiyun Jiang, Zhaohong Chen.Formal analysis: Lin Li, Qiong Pan, Le Xu, Renqin Lin, Jiaxi Dai, Xinyan Chen, Meiyun Jiang, Zhaohong Chen.Funding acquisition: Le Xu, Xinyan Chen.Investigation: Lin Li, Qiong Pan.Methodology: Lin Li, Qiong Pan.Project administration: Le Xu.Writing – original draft: Lin Li, Qiong Pan.Writing – review & editing: Le Xu, Renqin Lin, Jiaxi Dai, Xinyan Chen, Meiyun Jiang, Zhaohong Chen.Resources: Zhaohong Chen, Lin Li, Le Xu.Software: Lin Li, Qiong Pan.Supervision: Lin Li, Le XuSupervision: Lin Li, Le Xu, Xinyan Chen


Prostate cancer is a male malignant tumor disease with high prevalence in recent years. Patients with advanced prostate cancer are more likely to have bone metastasis and strong bone pain, and even lead to pathological fracture, which has a serious impact on the quality of life of patients. Acupuncture has good clinical efficacy in treating pain caused by prostate cancer. This review hopes to adopt meta-analysis to evaluate the efficacy and safety of acupuncture in the treatment of pain caused by prostate cancer and provides evidence for its application in clinical practice.We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet, Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2018. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata 13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of epididymitis.This systematic review will evaluate the efficacy and safety of acupuncture for pain caused by prostate cancer. Owing to the fact that all of the data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. Furthermore, all data will be anonymously analyzed during the review process trial.PROSPERO CRD42018111550 The secretion of prostaglandin could accelerate the bone resorption around the tumor. Due to the intense sensibility of the nerve endings, sharp pain hence generates. According to vast research, it has proved that acupuncture could be efficient in analgesic therapy.,5 Recent years have witnessed great promotion of the living standard, which also accompanied with the increasing morbidity of prostate cancer, and this has caused great impact on people's life and quality of life. Meanwhile, with the increasing progress of modern medicine, we could focus on not only prolonging lifespan of the cancerous person but also the impact to the quality of life.,7 Enormous clinical literatures have indicated that acupuncture has positive effect on ameliorating pain and improve the quality of life in patients who suffer from advanced prostate cancer.,9Prostate cancer is a male malignant tumor disease which has a high prevalence in recent years. Meanwhile, the morbidity also has significant difference across the world, which we found that the highest incidence, comparing with the lowest incidence, is about 25 times. In the United States, the morbidity of the disease ranks first in all male malignancies, accounting for about 29%. During 2004 to 2008, the morbidity of this cancer had been turned to 152.9 per 100,000, which was counted after the rise of age.,12Prostate cancer is the most common malignant tumor of the male genitourinary system, accounting for the fifth place in the global cancer rate. According to the WHO Global Cancer Epidemiology Statistics (GLOBOCAN 2008), the global morbidity of prostate cancer ranks second in males who suffer from malignancy in 2008 (ranking only second to lung cancer), accounting for 14%.,14 The morbidity of the symptom is about 70% to 90%. According to the statistics that was announced by WHO in 2003, there are about 10 million new patients with cancer in the world every year, and 300 to 1000 million patients with cancer fail to receive timely and effective treatment.Cancer pain is one of the most important symptoms in patients who suffer from advanced cancer; it greatly deteriorates the physical and psychological health and thus the quality of life of patients. Meanwhile, studies in the United States have found that using large doses of anesthetics for a long period of time is vulnerable to promoting tumor angiogenesis, accelerating tumor growth, and increasing the spread of cancer cells. Besides, patients who accept the treatment are always accompanied with constipation, nausea and vomiting, dizziness, drowsiness, rash, high blood pressure, coma, and other adverse reactions, so far, as to further aggravating the pain.,18At present, aiming at the symptom, the medical community mainly adopts the “three-step” analgesic drug therapy recommended by WHO, which means that the patients need long-term high-dose anesthetics to release the pain. It can relieve pain caused by prostate cancer to some extent. On the basis of TCM theory, acupuncture can regulate the balance of qi and blood by stimulating acupuncture points, which aims at improving physiological function. Meanwhile, vast studies have shown that acupuncture tianshu (ST25), zusanli (ST36), and taichong (LR3) can adjust the production of neurotransmitter, mainly 5-hydroxytryptamine, and reduce nerve sensitivity. By preliminary database searching, we found that the randomized controlled trials about acupuncture for curing pain caused by prostate cancer have been increasing. However, most clinical trials confront with the inferior quality of the studies with small sample size and the insufficiency of evidence-based exploration because of the limitation of the size and number of clinical centers. Therefore, we expect to adopt meta-analysis to evaluate the efficacy and safety of acupuncture in the treatment of prostate cancer, to provide evidence for its clinical application.As one part of traditional Chinese medicine (TCM), acupuncture therapy has been widely used in clinical trials of pain caused by prostate cancer in recent years. The process of analgesia by acupuncture is complicated. Vast studies have proved that acupoint stimulation can accelerate the secretion of various mediators and opioid peptides from peripheral nerve to central nervous system, such as spinal cord, low brainstem, diencephalon, limbic system, and cerebral cortex, which together form the “anti-pain system” of the human body and produce acupuncture analgesic effects. With the deepening of the research and animal experiment on the mechanism of acupuncture and analgesia in recent years, there have been increasing reports on the application of acupuncture to various acute and chronic pain treatments.Acupuncture has its unique advantages in the treatment of cancer pain. The operation is convenient; it could dredge the meridians and regulate the balance of qi and blood, which achieve the goal of relieving pain caused by qi stagnation and blood stasis and meridians impassability.2http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018111550) The protocol follows the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) statement guidelines. We will describe the changes in our full review, if needed.This systematic review protocol has been registered on PROSPERO as CRD42018111550 , ductal adenocarcinoma, urothelial carcinoma, squamous cell carcinoma, and adenosquamous carcinoma. Meanwhile, the patients who were recruited should have the symptom of pain caused by prostate cancer, including bone pain caused by bone metastasis. However, the patients who suffer from pain caused by other factors would be excluded. Patients who suffer from cognition impairment and other severe mental illness will also be excluded. In addition, the inclusion criteria will not be restricted by region, country, nation, and origin.2.1.32.1.3.1The patients who were included by experimental group should accept the conventional treatment and acupuncture therapy that includes conventional acupuncture, electropuncture, ignipuncture, plum-blossom needle, and massaging acupoints. Pharmacoacupuncture and acupoint injection will be rejected, as their methods and theories are different from TCM. The duration and frequency of therapy are not limited.2.1.3.2The patients who belong to control group should be treated with conventional therapy or combined with simple analgesics. However, once they had accepted acupuncture combined with medication or other therapy of TCM, the trials will be rejected.The following treatment comparisons will be investigated:1.Acupuncture versus no treatment2.Acupuncture versus placebo/sham acupuncture3.Acupuncture versus drug therapy4.Acupuncture versus other active therapies5.Acupuncture with another active therapy versus the same therapy alone2.1.42.1.4.1Adopting numerical rating scale (NRS) of pain criteria as the main evaluation, the specific division are as follows: painless 0 points; mild pain 1 to 3 points; moderate pain 4 to 6 points; severe pain 7 to 9 points; and severe pain 10 points, 0 to 10 points representing the patient's pain level. “Significantly effective” denotes that the patient's pain level is reduced by at least two or three levels, or the patient is painless; “Effective” denotes that the patient's pain level is reduced by one grade or the patient presents moderate and mild pain; and “Invalid” denotes that the patient's pain does not have any relief, and there is even a tendency to aggravate.2.1.4.2Secondary outcomes are as follows:1.International prostate symptom score, the patient self-evaluation form;2.Quality-of-life scores for patients with prostate cancer before and after treatment: A scale, designed by the University of California, USA, to evaluate the condition and living quality of patients who suffer from advanced, hormone-insensitive prostate cancer. It specifically includes nine aspects: physical strength, pain, fatigue, appetite, family/marriage, constipation, mood, defecation, and overall feelings. Each item is calculated with 100 points, and the lower the score, the worse the situation.2.22.2.1Database search: Searching PubMed, Cochrane Library, AMED, EMbase, WorldSciNet, Nature, Science online and China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), and China Resources Database. The temporal interval is limited from the time that the databases created to November 2018, and the combination of keyword and free word retrieval is adopted. The search terms include “acupuncture,” “acupuncture,’, “electro-acupuncture,” “fire needle,” “plum blossom needle,” “skin needle,” “prostate cancer,” “prostate cancer,” “pain,” “Random Control.”2.2.2We will search ongoing experimental studies related to the disease through the WHO International Clinical Trial Registration Platform, ClinicalTrials.gov, and Chinese clinical trial studies. As for these ongoing experiments, we will try to contact the trial author to help provide the most up-to-date clinical data. Besides, we also tempt to adopt the manual searching which mainly aims at relevant literatures, earlier than the database mentioned above, such as “China Rehabilitation Medicine Journal,” “Chinese Acupuncture,” “Chinese Journal of Physical Medicine and Rehabilitation,” “Acupuncture Clinical Journal,” and “Chinese Journal of Urology.” Search strategy for Medline is shown in Table 2.32.3.1Initial evaluations were independently performed by two investigators through filtrating the titles and abstracts of each documents in the Endnote database, eliminating duplicates and documents that were clearly inconsistent with the study. After the preliminary assessment, to screen out eligible trials, the full text of the selected literature would be evaluated, which mainly aims at whether there were problems just like uncontrolled studies, no randomization, inconsistent assessment criteria, and similar data. When the two researchers could not reach a consensus, the third judge would make the final judgment. The primary selection process is shown in a PRISMA flow chart Fig. .2.3.2There will be two investigators independently extracting information from the included literature, mainly contents that are author (year), sample size, disease stage, patient age, intervention factors, control factors, intervention time, observation index, NRS score, symptoms ratings, quality-of-life scores, etc. The extracted literature data is filled in a unified data statistics table.2.3.3Two investigators independently assess the quality of the included literature by using the Cochrane Collaboration's bias risk assessment tool. The assessment includes random sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other possible biases. According to the relevant standards in the Cochrane Intervention System Evaluation Manual, it is divided into low risk, high risk, and unclear.2.3.4For continuous variable outcome, mean difference (MD) or standardized mean difference (SMD) and 95% confidence interval (95% CI) will be recorded. For dichotomous outcomes, we will use the relative risk (RR) and 95% CI records.2.3.5We will only extract the first experimental period data of crossover trials to avoid carryover effects. With multiple intervention groups, we will combine all similar experimental groups and control groups into 1 group to prevent a unit of analysis issue.2.3.6In the event of data loss during the screening and extraction of literature data, primarily, we would actively look for the cause of the loss, and then we would contact the experimental research author by telephone, mail, etc., to retrieve the lost data. If the loss could not be retrieved, we will only extract and analyze the useful data, and the situation would be indicated.2.3.7P < 0.05. Heterogeneity test would be analyzed by using chi-square test. When P ≥ 0.1, the difference was considered to be not statistically significant. When P < 0.1, I2 > 50%, the random-effect model would be used, as for the other situation, the fixed-effect model would be adopted.The analysis of the data will adopt RevMan 5.3 software. As for the two categorical variables, we select RR or odds ratio (OR) and 95% CI. As for the continuous variables, we select weighted mean difference (WMD) or standard mean difference (SMD) and 95% CI, the difference would be statistically significant when 2.3.8If there is significant heterogeneity between a group of studies, we will explore the reasons for the existence of heterogeneity from various aspects, such as the characteristics of the patients and the degree of variation of the interventions. Necessarily, sensitivity analysis or subgroup analysis would be adopted to explain the heterogeneity.2.3.9The forest map and funnel plot would be drawn and analyzed by RevMan 5.3 software, and the funnel plot would be used to analyze the potential publication bias.2.3.10We will perform sensitivity analysis for primary outcomes to test the robustness of the review conclusions, and we will still evaluate the impact of methodological quality, sample size, and missing data.2.3.11The quality of evidence for the main outcomes will also be assessed with the Grading of Recommendations Assessment approach. The evaluation included bias risk, heterogeneity, indirectness, imprecision, and publication bias. And each level of evidence will be made “very low,” “low,” “erate,” or “high” judgment.3 Recent years have witnessed an increase in the study of treating cancer pain; vast researches have indicated that analgesics have great efficiency in ameliorating pain, but the pesticide effects are short, and there are kinds of adverse reaction, such as kidney damage, liver damage, cardiovascular and cerebrovascular damage, and digestive disease.,24 Generally speaking, numerous patients who suffer from cancer could not gain satisfied control effect. Moreover, these patients need long-term use of analgesic drugs to ameliorate pain, which also directly increase the cost of therapy for patients.At present, pain has been the fifth vital sign, together with respiration, blood pressure, pulse, and body temperature. In 1996, the American Pain Association first proposed the concept of pain and its control, which indicated that an effective pain relief program for patients is a basic requirement for clinical medical work. It has been a difficulty problem to the treatment of pain caused by prostate cancer and its bone metastasis in the middle and advantaged stage, which has belonged to refractory cancer pain. In recent years, acupuncture therapy has been widely used in clinical trials of pain caused by prostate cancer, and the recent studies have shown that the therapy could ameliorate the pain caused by prostate cancer to some extent and improve the quality of the life.Acupuncture, possessing thousand years of history in China, has proved that it is a safe, feasible, and effective treatment. The clinical operation and theory of acupuncture have been inherited and carried forward by the majority of clinicians, especially in the treatment of pain. This therapy could ameliorate vast kinds of pain efficiently, and the selection of acupoint is convenient, besides, there are not adverse reaction which could insure the security.As far as we know, there has no comparison made of the effectiveness of acupuncture in the treatment of pain caused by prostate cancer. Therefore, we will use systematic review and meta-analysis to evaluate the efficacy and safety of acupuncture for the treatment of pain caused by prostate cancer. We expect that the review could provide a basis for acupuncture treatment of pain caused by prostate cancer and offer more and better options for treatment to patients. In addition, the literature on acupuncture therapy on pain caused by prostate cancer is relatively inadequate and the overall quality is a little low, which may affect the authenticity of this study.Data curation: Jisheng Wang, Yi Lei, Fei Chen.Formal analysis: Jisheng Wang, Binghao Bao.Funding acquisition: Haisong Li.Project administration: Bin Wang.Supervision: Haisong Li, Bin Wang.Validation: Haisong Li.Writing – original draft: Jisheng Wang, Yi Lei.Writing – review & editing: Xudong Yu, Hengheng Dai.