Charlson Comorbidity Index (CCI) is positively associated with all-cause readmission in patients with heart failure (HF) in western countries. However, there is a scarcity of strong scientific evidence supporting the correlation in China. This study aimed at testing this hypothesis in Chinese.  We conducted a secondary analysis of 1,946 patients with HF in Zigong Fourth People’s Hospital in China between December 2016 to June 2019. Logistic regression models were used to study the hypotheses, with adjustments for the four regression models. We also explore the linear trend and possible nonlinear relationship between CCI and readmission within six months. We further conducted subgroup analysis and tests for interaction to examine the possible interaction between CCI and the endpoint. Additionally, CCI alone and several combinations of variables based on CCI were used to predict the endpoint. Under the curve (AUC), sensitivity and specificity were reported to evaluate the performance of the predicted model., CCI was an independent prognostic factor for readmission within six months in patients with HF . Trend tests revealed that there was a significant linear trend for the association. A nonlinear association was identified between them and the inflection point of CCI was 1. Subgroup analyses and tests for interaction indicated that cystatin played an interactive role in the association. ROC analysis indicated neither CCI alone nor combinations of variables based on CCI were adequate for prediction.In the adjusted II modelCCI was independently positively correlated with readmission within six months in patients with HF in Chinese population. However, CCI has limited value on predicting readmission within six months in patients with HF.The online version contains supplementary material available at 10.1186/s12872-023-03151-9. Heart failure (HF) is one of the most life-threatening conditions in cardiovascular patients in China. A recent national epidemiologic survey in 2012–2015 revealed that the number of patients with HF has reached 89 million in China .It has become a consensus that cardiovascular and non-cardiovascular comorbidities are frequently observed in more than half of patients with HF , such ashttps://physionet.org/content/heart-failure-zigong/1.2/) [Pertinent data were obtained from an online open-source database of patients with HF in China, which is available in PhysioNet ng/1.2/) , 11. Theng/1.2/) . In pres.2/ , 11.ng/1.2/) , 14.Fig.CCI was calculated by summing all comorbidity points described in the database . DemograThe endpoint was all-cause readmission within six months calculated from the date of index hospital admission. All-cause readmission was defined as readmission for any cause after discharge from HF. Data on hospital admissions within six months was obtained at mandatory follow‐up visit or a telephone call.http://www.R-project.org. The R Foundation) All statistical inferences were made of two-sided test, and a value of P<0.05 was considered to be statistically significant. Continuous variables that approximated the normal distribution were expressed as means ± SD, while variables with a skewed distribution were expressed as median . For categorical variables, we report frequencies and percentages. Comparisons of the baseline characteristics between no-readmission and readmission groups were examined by independent T-test for normally distributed variables, Mann Whitney U test for nonnormally distributed variables and Chi square (χ2) test for categorical variables. Next univariate and multivariate logistic regression analyses were performed. Based on the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guideline [https://www.evalue-calculator.com/) [Data were analyzed using R version 4.1.0   The E-vaor.com/) . FinallyA total of 1,946 patients with HF were included in the study. The percentage of readmission within six months were 39.62%. The proportion of < 60 years, ≥ 60 and < 90 years, and ≥ 90 and < 110 years of patients were 8.84%, 54.06% and 37.10%, respectively. The proportion of male was 41.73%. The distribution of CCI in overall participants is shown in Fig. There were no significant differences in age, sex, BMI, admission way, body temperature, respiration, type II respiratory failure, GCS, WBC, HSCRP, ALB and LVEF between readmission and no readmission groups. Compared with no readmission group, CCI, proportion of urban resident, proportion of cardiology ward on admission, discharge day, proportion of grade IV of NYHA, proportion of grade IV of Killip, proportion of both left and right HF, cystatin, hs-TnT and BNP in readmission group were higher than no readmission group. Pulse, SBP, DBP, GFR and HGB were lower in readmission group as compared to the no readmission group. The baseline characteristics of the 1,946 included patients are shown in Table In univariate analysis, CCI, occupation, admission ward, discharge day, pulse, SBP, DBP, NYHA, Killip, type of HF,GFR, cystatin and HGB were associated with readmission within six months (P < 0.05). The results of the univariate analyses are presented in Supplementary Table SOR = 1.20, 95% CI: 1.09–1.32, P < 0.001). In the adjusted I and II models, ORs of the positive association were listed as follows: OR = 1.19, 95% CI: 1.08–1.31, P < 0.001 and OR = 1.14, 95% CI: 1.03–1.26, P = 0.011. In fully-adjusted model, CCI was also positively related with the endpoint . Trend tests revealed that there was a linear trend for the association between CCI and readmission and the linear trend tests were significant in the four models (P for trend < 0.05). OR for the difference between CCI <  = 1 and CCI = 2 group appeared quite different from that between CCI = 2 and CCI > 2 group. This suggested a possible threshold effect in this relationship which becomes more noticeable when the threshold is exceeded. The results of multivariate analysis and trend test are shown in Table 2In non-adjusted model, CCI was positively correlated with readmission within six months (P for LRT = 0.007 < 0.05). The correlation was significantly negative before the inflection  while the correlation became significantly positive after the inflection . As a result, we concluded that the correlation between CCI and readmission was nonlinear.Adjusted smooth curve fitting showed that the relationship between CCI and readmission was nonlinear Fig. . The thrOR > 1). The interaction analysis revealed that cystatin played a significant interactive role in the association between CCI and readmission (P for interaction = 0.042). The patients with cystatin < 1.55 mg/l had a much worse prognosis  than those with cystatin ≥ 1.55 mg/l . No other significant interaction was observed in other subgroup analyses.The subgroup analyses and tests for interaction of the correlations between CCI and the endpoint are presented in Supplementary Table SORs for four logistic models between raw data and combined five imputed replications. In other words, we concluded that the data for cystatin, occupation, GFR, WBC, HGB, hs-TnT, BNP and ALB appeared to be missing at random, which would not significantly alter the results of raw data. A summary of imputed data compared with the initial incomplete data is illustrated in Supplementary Table SWe found that some variables for HSCRP and LVEF, cystatin, occupation, GFR, WBC, HGB, hs-TnT, BNP and ALB were missing in raw data and the numbers of missing were 1038, 1323, 40, 26, 62, 26, 27, 77, 34 and 96, respectively. Dummy variable and MI were used to handle missing values. The results of the MI indicated that there was only a slight difference in CI: 51.67–56.68%). The specificity and sensitivity were 79.15% and 28.02%, respectively. Besides, neither CCI plus every single covariate nor the combinations of variables in logistic models displayed good performance for predicting readmission (AUCs < 70.00%). The results of ROC analysis are listed in Supplementary Table SThe AUC for CCI alone predicting readmission with six months was only 54.18% . This is consistent with the literature reported previously. We further found a curvilinear correlation between them (LRT P > 0.05) and the inflection of CCI was 1. This is the first study to explore the threshold effect between them in patients with HF. Based on the previous results, we think that CCI > 1 appears to have a more strongly connection to readmission. Also, we first found cystatin played a significant interactive role in the association between CCI and readmission and it was suggested that the patients with cystatin < 1.55 mg/l showed higher readmission rate. However, there are no reports on this problem and it is required to investigate it further. Although our study demonstrates a causal relationship between CCI and readmission, it needs to be noted that CCI alone or the combinations of variables based on CCI was inadequate for predicting readmission. According to a previous meta-analysis, most AUCs for readmission predictive models in external validation cohort in patients with HF was below 0.75 and the most common predictors in the model were BNP/pro-BNP and renal insufficiency [In our study, the patients with higher CCI had a greater likelihood of readmission with six months than those with a lower CCI . E-values estimated in our study suggest that a confounder must have relative strong associations with both CCI and readmission within six months simultaneously (relative risk ≥ 1.34) to completely dilute the observed association . Sixth, In Chinese population, CCI was independently positively correlated with readmission within six months in patients with HF. However, CCI has limited value on predicting readmission within six months in patients with HF. As this study has several limitations, the principal conclusions of this paper need to be taken with caution.Additional file 1: Table S1. Results of univariate analysis. Table S2. Subgroup analysis and tests for interaction. Table S3. Results of multivariate analysis based on five multiple imputations. Table S4. The ROC analysis for CCI predicting readmission.


The primary objective was to compare the serum brain-derived neurotrophic factor (BDNF) level in the patients with two types of pain: fibromyalgia (FM) and non-FM nociceptive pain (non-FM NP). The secondary objective was to investigate the effect of duloxetine on serum BDNF in FM patients and assess the direction of BDNF changes’ relation to clinical parameters’ alterations.Methods: This is a study on 73 patients (50 FM and 23 non-FM chronic non-inflammatory pain patients). Serum BDNF was first compared between both groups. Patients with FM, then prospectively, underwent standardized FM treatment with duloxetine maximized to 60 mg/day. The Revised Fibromyalgia Impact Questionnaire (FIQR), Short-Form Health Survey (SF-12), pain visualized analog scale (pain VAS), Beck Depression Inventory-II (BDI-II), polysymptomatic distress scale (PSD) and serum BDNF were measured and compared at baseline and 4 weeks after treatment in FM group.P value = 0.77). Using linear mixed model, we showed that duloxetine reduced BDNF level significantly in FM patients, even after adjusting for depression, pain and severity of the disease (P < 0.01). The FIQR, BDI-II, PSD, and pain VAS improved significantly after duloxetine treatment.The mean of adjusted BDNF level in the FM group had no significant difference than the non-FM NP group ((5293.5 ± 2676.3 vs. 6136.3 ± 4037.6; Non-significant BDNF level difference between FM and non-FM nociceptive pain suggested that peripheral BDNF is not a pathophysiological feature of FM. The decreased BDNF level parallel with improvement of PSD/pain scores after duloxetine treatment indicates BDNF alteration in the pain modulation process, regardless of cause and effect. Fibromyalgia (FM) is a chronic pain disorder consisting of musculoskeletal pain and hyperalgesia, commonly accompanied by sleep disturbance, fatigue, anxiety, depression, gastrointestinal symptoms and headache . RecentlBrain-derived neurotrophic factor (BDNF), as the most abundant and widely distributed neurotrophin in the central and peripheral nervous system, has been known to be involved in axonal growth, synaptic plasticity, and neuronal repair , 8. ReceOn the other hand, the strong clinical link between pain and depression adds more complexity to the relationship between BDNF and FM nociplastic pain. Pain and depression frequently coexist in patients and have mutual effects . Given mIn order to elucidate the complex relationship between BDNF, pain, and depression in the nociplastic FM and chronic nociceptive pain, it seems reasonable to explore the effect of approved medications for FM and depression on the BDNF level in the painful conditions and also to assess the relationships of BDNF changes with the clinical indices’ improvement. Numerous studies have investigated the effect of antidepressants on the BDNF level of patients with depression. Although the majority claim the increased level of BDNF after the treatment, some have elucidated different results –22. SimiConsidering the mentioned debate, we sought to compare the serum BDNF level in the patients with two different types of pain: nociplastic FM pain and nociceptive pain (non-inflammatory chronic rheumatic pain). We also investigated the effect of the FM-approved antidepressant, serotonin–noradrenaline reuptake inhibitor (SNRI), duloxetine, on the serum BDNF in patients with FM and also assessed the direction of serum BDNF changes to the clinical symptom severity.This prospective study was conducted in the academic outpatient rheumatology clinic, Razi hospital affiliated with Guilan University of Medical Sciences (GUMS), from May 2019 through October 2019. The study protocol was approved by the ethics committee of Iran University of Medical Sciences (IUMS) in accordance with the World Medical Association’s code of ethics .53 FM patients and 23 patients with non-FM chronic nociceptive pain disorders (non-FM NP) were consecutively included. The diagnosis of all participants was made by two rheumatologists (A.B and B.GH), who were experts in diagnosing and managing FM and chronic pain disorders. Patients with a new diagnosis of FM based on the 2016 American College of Rheumatology (ACR) were eligible in the FM group. Patients in the non-FM chronic pain group were subjects with a chronic painful non-inflammatory condition such as osteoarthritis, tendinitis  and had no concurrent diagnosis of FM at the time of enrollment. In order to avoiding the confounding factors, only female patients were selected in both FM and non-FM groups. Systemic inflammatory rheumatic diseases were not recruited in the non-FM NP group because several reports imply inflammation’s influence on the BDNF level and function [Participants were excluded if they were pregnant or breastfeeding. Patients with major comorbidity, including systemic inflammatory rheumatic disease, malignancies, multiple major surgeries or trauma injuries, neurological or psychiatric disorders except for depression/anxiety, chronic liver or renal diseases and hypersensitivity to duloxetine were excluded. Written informed consent was obtained from all patients, and they were informed that their level of care wouldn’t be affected if they quit the study.The sample size was calculated using G*Power 3.1. To calculate the effect size, we used the study result by Laske et al., which showed an effect size of 0.96 with 80% power . ReducinDemographic data  was obtained from all participants. The contact telephone number was also received to remind patients of their appointments. All the patients were asked to fill out the Revised Fibromyalgia Impact Questionnaire (FIQR), Short-Form Health Survey (SF-12), pain visualized analog scale (pain VAS), Beck Depression Inventory-II (BDI-II), polysymptomatic distress scale (PSD) at the initial visit. An experienced medical assistant offered help if patients did not understand the meaning of the questions.The FIQR is a 21-items questionnaire with an 11-point numeric rating scale for each question which assesses clinical symptom severity and disease impact in patients with FM . The totFM patients were assigned to receive Cymbalta®  (duloxetine) for 4 weeks. The regimen for duloxetine started with 30 mg (mg) per day for the first week and was titrated to 60 mg per day for the next 3 weeks if no adverse effect was reported. The FM group was asked to complete the mentioned questionnaires again 4 weeks later to assess the changes in the scores after treatment with duloxetine. Of the FM group, 50 patients completed the 4 weeks of the treatment.Peripheral venous blood samples (10 ml) were gathered from all participants into tubes with no anticoagulation. Patients were on 8 hours of fasting, and the samples were taken at 8 to 11 am. The time gap between sample collection and centrifuge was kept under 30 minutes to reduce platelete-derived BDNF. The samples were centrifuged at 2000 rounds per min for 10 minutes and was stored at − 80 degrees Celsius until analysis. The analysis of all samples were performed after 4 weeks from the day that the last participant was recruited . Serum lDescriptive statistics were used to calculate the mean ± standard deviation for continuous variables and frequency for categorical variables. To check the normality of variables, we used the Kolmogorov-Smirnov test. Skewed variable distributions were transformed by taking the cube root. Levene’s test was used to check if samples had equal variances.Paired t-test and Wilcoxon signed-rank test were used to compare two related groups for normally and non-normally distributed data, respectively. To compare two unrelated groups, we used an independent t-test for normally distributed data and Mann-Whitney U for non-normally distributed data. For comparing the relationship between two continuous data, Pearson or Spearman was used for normally and non-normally distributed data, respectively. A univariate linear model, adjusted for FIQR, BDI-II, and VAS, was used to compare the serum BDNF level between case and control groups.A linear mixed model was developed to compare the serum level of BDNF before and after treatment with duloxetine, adjusted for FIQR, BDI-II, and pain VAS. The equation of LMM consists of two levels:The equation in level 1The equation in level 2.bi1 = β10.ij denotes individual is serum BDNF level at time j where j = 1,2 represents measurement times. In level 1, only time-varying covariate (time) is included and it indicates each individual’s growth trajectory of outcome measure b1i. Each individual’s response at baseline (b0i) is allowed to differ by releasing its random effect in level 2 (υi0). In level 2, the regression coefficient  represents that each participants’ initial status (intercept) will be associated with their covariates. The regression coefficient (β10) indicates the time effect. Several variance-covariance structures were examined for obtaining the best fit. To make this selection, we used Bayesian information criteria (BIC), which would show the least value. Autoregressive of Order 1 Ar (1) was chosen based on this criterion. Parameters were estimated by the method of restricted maximum likelihood (REML).Note: yStatistical calculations were performed using the IBM SPSS Statistics for Windows, version 24 , and statistical significance was evaluated at the level of 0.05.p value > 0.05). As expected, the FM patients had significantly higher mean scores than the non-FM NP patients in the FIQR scores , the BDI-II scores , and the PSD scores . The health status was also considerably worse in the FM patients  and  for mental and physical components, respectively. , this difference was non-significant even after adjusting for FIQR, BDI-II, and pain VAS as covariates  . When assessing all participants, an overall trend of decrease in the level of serum BDNF with increasing the level of FIQR, BDI-II, PSD, and pain VAS was seen. This relationship was not statistically significant . A similar relationship was also noted in the FM group except for the pain PSD and pain VAS, which were statistically significant  (Table There was no significant relationship between the serum level of BDNF and age (5) Table .Table 2Cp value< 0.01)   Table . Using a1) Table .Table 3CThis study showed that the mean adjusted serum level of BDNF l for disease severity and depression in the FM group did not significantly differ from the non-FM NP group. Surprisingly, duloxetine decreased serum BDNF level significantly in the FM patients even after adjusting for the disease severity, depression, and pain level. Decreasing serum BDNF after treatment with duloxetine was associated with the improvement of the disease severity, depression, and pain level.To the best of our knowledge, this is the first study comparing serum BDNF levels between different types of pain: nociplastic FM pain with prominent neuroplasticity and pain centralization, nociceptive pain with prominent peripheral explanation for pain and low pain centralization. We found that the FM group had a lower serum level of BDNF rather than the non-FM NP group. Even so, this difference turned out to be non-significant when adjusted for depression, disease severity, and pain as the main cofounders. Contrary to the previous studies which compared BDNF level in the FM patients with the healthy subjects without pain, we chose the non-FM group from patients with NP to elucidate the role of serum BDNF more clearly in the different pain types. Most previous studies implied an increased peripheral and CSF level of BDNF in FM patients compared to healthy controls –15, and Notably, we found that the basal serum level of BDNF did not correlate significantly with symptom severity, PSD scores or fibromyalgianess, depression and pain severity regardless of the diagnosis (FM or non-FM NP). However, some small inverse correlations between BDNF and pain/PSD values were seen only in the FM patients. These findings were congruent with the Haas et al.’s study , which sApart from BDNF level assessment in the different pain groups, we assessed the effect of duloxetine treatment on the BDNF level in our FM patients. This is the first study that has prospectively evaluated serum level of BDNF alteration in FM patients after treatment with an antidepressant. Surprisingly, we found that serum BDNF reduced after treatment with duloxetine in the FM patients. This effect remained even after adjusting for the disease severity, depression, and pain level. There have been a few retrospective studies on the issue in FM papulation that have suggested independence changes of the BDNF to antidepressant medications –15, 30. It is noteworthy that one of the weak points in the data comparison of the BDNF level in different studies is the numerous factors that affect the measurement or interpretation of BDNF. Circulatory BDNF is measured in the serum or plasma. Plasma contains platelets accounting as the major peripheral reservoir of BDNF. The studies based on the serum level of BDNF typically showed a higher level than the plasma level. This discrepancy was probably due to the coagulation process prior to centrifugation in the process of obtaining serum samples. So, it seems the BDNF storage in serum or plasma is representative of the different sources. It has not been known that serum BDNF mainly originates from the platelet release or is derived from CNS with passing through the brain-blood barrier. There is still debate whether the plasma and serum level of BDNF are related together and whether the circulating levels of the BDNF reciprocate its CNS level. However, due to the difficulty in the CNS measurement of BDNF level, most studies prefer to use plasma or serum samples .There are some limitations to this study. First, only female patients were recruited, and therefore the study findings cannot be generalized to men with painful conditions. Second, we evaluated our patients in a tertiary care setting; thus, they probably do not reflect the general population of FM or non-FM NP. Third, the non-FM NP was a relatively small group with 23 patients due to strict inclusion criteria of not having concurrent FM for entering the patients into this group. The tracing of any symptom connoting nociplastic features of pain such as unrefreshed sleep or sleep disorders, fatigue, migratory and non-consistent pain, various somatic symptoms etc., led to the exclusion of the patients from the non-FM NP group. So, this strict criteria for inclusion of patients into the non-FM NP led to the low numbers of patients in this group. Fourth, a relatively short time (1 month) for the second BDNF checking after duloxetine prescription limited us in the extrapolation of our results to long-term effects of antidepressant treatment. Because of the aforementioned serum BDNF changes involved in brain neuroplasticity after starting antidepressants, which may need long-term therapy, the results may be different in various time points’ sampling of serum BDNF. Finally, interpretations of all BDNF intergroup and intragroup comparisons were based on the peripheral (serum) BDNF, which might not be representative of the central nervous system BDNF changes.In conclusion, we found no significant adjusted serum level of BDNF difference between nociplastic FM and the nociceptive pain process. This finding re-emphasizes that peripheral BDNF is not a pathophysiological feature of FM and may weaken the theory of exclusive role of peripheral BDNF in nociplastic pain. FM as a heterogenic condition having both prominent pain and depression seems unpredictable to BDNF level measurements regarding different situations and treatments. The decreased serum level of BDNF after treatment with duloxetine in FM patients supports the overall role of BDNF in pain modulation, probably through complex pain pathways. It seems hard to formulize these relationships until elucidation of the precise peripheral and central neurobiological signatures in FM and other pain conditions.


Results: A total of 243 consecutive cases of TSCPC were included. Of these, 144 (59.26%) were treated with CW-TSCPC and 99 (40.74%) with MP-TSCPC. Using the univariable model, the risk for postoperative pain was observed to be lower in MP-TSCPC compared with CW-TSCPC , but this did not hold using the multivariable model . Simultaneously conducted anterior retinal cryotherapy was associated with a higher risk for postoperative pain . Conclusions: We found that the occurrence of postoperative pain was not different in CW-TSCPC compared with MP-TSCPC in a multivariable model. In cases of simultaneous anterior retinal cryotherapy, the risk for postoperative pain was significantly higher.Background: As the number of surgical options in glaucoma treatment is continuously rising, evidence regarding distinctive features of these surgeries is becoming more and more important for clinicians to choose the right surgical treatment for each individual patient. Methods: For this retrospective data analysis, we included glaucoma patients treated with either continuous wave (CW-TSCPC) or micropulse transscleral cyclophotocoagulation (MP-TSCPC) in an inpatient setting. Pain intensity was assessed using a numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain) during hospitalization. CW-TSCPC was performed using OcuLight Although various risk factors for glaucoma development have been identified ,2,3, intWith the development of new surgical options, evaluating distinct features of available treatment options is of high interest for clinicians to personalize surgical glaucoma treatment for each individual patient. These features are not only limited to surgical success in terms of intraocular pressure control, but also involve complication rates and surgery-related patient discomfort. Knowledge about these outcome parameters is scarce, but can profoundly support clinicians in decision-making. In the end, patient-related life quality should be the ultimate aim of glaucoma management ,8.Intraocular pressure can be lowered using medication, laser or surgery. A reduction in intraocular pressure can be achieved by increasing the outflow of aqueous humor or by decreasing its production. Cyclodestructive procedures target the ciliary body, where aqueous humor is produced. Various methods have been used for cyclodestruction, including diathermy, cryotherapy, ultrasound and laser. Laser cyclophotocoagulation was first introduced in 1972 by Beckman and colleagues ,11,12. MPostoperative pain is a common early postoperative complication after CW-TSCPC. Until now, pain after MP-TSCPC has been studied only as a secondary outcome parameter, with a tendency towards low or no pain postoperatively . In thisWe retrospectively included all cases of CW-TSCPC and MP-TSCPC performed between January 2018 and December 2020 at the Medical University Graz. Exclusion criteria were insufficient or inconclusive data documentation as well as bilateral simultaneous treatment. Electronic and paper records were retrieved for data analysis. Pain was assessed via a numerical rating scale (NRS) , a ratin® Six . In CW-TSCPC, laser energy is applied continuously over a fixed time. The desired effect is cyclodestruction with subsequent reduction of aqueous production. Settings were either fixed through the procedure, or adjusted until audible feedback (“plop”) was recognized. The approach used depends on a surgeon’s preferences. MP-TSCPC was performed using the IRIDEX Cyclo-G6 System . In MP-TSCPC, laser energy is applied in an on/off fashion, with pulses of laser energy interrupted by pauses, which serve as cooling time and aim to reduce collateral damage. All procedures were performed under retrobulbar anesthesia in an operating theatre and inpatient setting. Lidocaine 2% was used for retrobulbar anesthesia. Patients experiencing pain during the operation received Alfentanil, which is a synthetic opioid analgesic drug that acts fast and lasts for approximately 15 min. Patients stayed in hospital overnight and were released on the first postoperative day. During this period, patients were monitored for post-operative pain. Until September 2019, the majority of operations were CW-TSCPC, thereafter MP-TSCPC. Total applied laser energy was calculated in Joule for MP-TSCPC  = watt × treatment duration in seconds × duty cycle) and CW-TSCPC  = watt × treatment duration per spot in seconds × total count of treated spots). Anterior retinal cryotherapy was performed using Keeler Cryomatic MKII . Twelve spots at −80 °C for 15 s were applied, three spots in each quadrant of the treated eye. Anterior retinal cryotherapy is performed in cases of proliferative retinopathy, where panretinal photocoagulation is impossible due to media opacities [CW-TSCPC was performed using OcuLightpacities .p-values. In sensitivity analyses, the models were repeated, including only the first documented surgery per patient. A p-value of p < 0.05 indicates statistical significance. Statistical analyses were performed using SAS 9.4 .In descriptive statistics, continuous parameters are presented as mean and standard deviation (SD) or median, minimum and maximum. Categorical parameters are presented as frequencies and percentages. To evaluate the occurrence of postoperative pain equal to or greater than NRS 3 between the MP-TSCPC and CW-TSCPC, generalized estimating equations (GEE) with logit as link function and working independence correlation structure were used, accounting for repeated surgeries on the same patient . The modIn total, 259 cases of TSCPC were identified. After excluding 16 patients with insufficient or inconclusive documentation or simultaneous bilateral treatment, 243 cases of TSCPC in 200 patients remained. Of these, 144 were treated with CW-TSCPC ; mean age, 71.4 years; SD, 15.6) and 99 were treated with MP-TSCPC (52 (52.5%) female; mean age, 68.8 years; SD, 16.0) . Glaucoma subtypes treated were: neovascular glaucoma (59 (41.0%) in the CW-TSCPC group and 37 (37.4%) in the MP-TSCPC group), pseudoexfoliation glaucoma (25 (17.4%) in the CW-TSCPC group and 22 (22.2%) in the MP-TSCPC group), primary open angle glaucoma (18 (12.5%) in the CW-TSCPC group and 15 (15.2%) in the MP-TSCPC group), secondary glaucoma due to surgery, inflammation or trauma (27 (18.8%) in the CW-TSCPC group and 18 (18.2%) in the MP-TSCPC group), and other, less frequent glaucoma subtypes, including but not limited to pigmentary glaucoma, aphakic glaucoma and glaucoma due to various syndromes. Simultaneous anterior retinal cryotherapy was performed in 49 cases (35 (24.3%) in the CW-TSCPC group and 14 (14.1%) in the MP-TSCPC group) and simultaneous intravitreal injection was performed in 5 cases (4 (2.8%) in the CW-TSCPC group and 1 (1.0%) in the MP-TSCPC group). Preoperative pain greater than or equal to NRS 3 in the affected eye was mentioned in 5 cases (2 (1.4%) in the CW-TSCPC group and 3 (3.0%) in the MP-TSCPC group). Postoperative pain greater than or equal to NRS 3 was reported in 52 cases (38 (26.4%) after CW-TSCPC and 14 (14.1%) after MP-TSCPC). Pain intensity, assessed via maximum NRS values in cases with relevant postoperative pain (NRS ≥ 3) was comparable between groups (4.8 (SD 1.1) in the CW-TSCPC group and 5.1 (SD 1.4) in the MP-TSCPC group). p = 0.017), but this did not hold using the multivariable model  (p < 0.001). Of 52 patients with postoperative pain, 22 were treated using simultaneous anterior retinal cryotherapy. When cases with combined anterior retinal cryotherapy were excluded, the risk for postoperative pain was not different between the laser groups . Older age was protective . Sex, laterality, previously performed TSCPC, total applied laser energy and preoperative intraocular pressure did not show statistically significant impacts upon occurrence of pain equal to or higher than NRS 3. No difference in intraocular pressure on the first postoperative day was found between patients experiencing pain with NRS ≥ 3 and other patients . Using the univariable model, the risk for postoperative pain was observed to be lower for MP-TSCPC compared with CW-TSCPC  . SimultaIn this retrospective data analysis, we evaluated postoperative pain after CW-TSCPC and MP-TSCPC. Postoperative pain greater than or equal to NRS 3 was reported after 26.4% of CW-TSCPCs and after 14.1% of MP-TSCPCs. Nevertheless, using a multivariable model we did not find a laser variant to be a significant risk factor for postoperative pain. Combined anterior retinal cryotherapy and age were significant contributors to the occurrence of postoperative pain. In our study, the largest group of patients had neovascular glaucoma. Other studies investigating transscleral cyclophotocoagulation had varied study population compositions in terms of the type of glaucoma and favoring, e.g., primary open angle glaucoma . This map = 0.002). Tan et al. [Quigley at al.  investign et al.  reportedn et al. . This waHere, we found that older patients experienced less postoperative pain. The mean age of our patients was approximately 70, which was considerably higher than in other studies ,15,16. IThe highest postoperative pain in our study was associated with simultaneously conducted anterior retinal cryotherapy. Studies about postoperative pain after anterior retinal cryotherapy are scarce. Steel et al.  reportedThis study has several limitations, with its retrospective nature being one of the most important. Pain is influenced strongly by cultural factors and should be investigated in different populations. Reporting pain can be influenced by mental diseases, which were not included in our analysis. We did not investigate other comorbidities causing pain. As the mean age was approximately 70 years, several diseases, e.g., degenerative disorders of the spine, may have contributed to the intensity of pain. Still, as age was not different, this should have affected both groups in the same way. We did investigate preoperative pain, and interestingly this was quite rare in both groups, with 1.4% and 3% in the CW-TSCPC group and the MP-TSCPC group, respectively. Finally, we did not assess treatment success. Whether a sufficient laser energy application in terms of treatment success would also lead to a higher rate of postoperative pain remains unclear. Glaucoma and glaucoma therapy put a financial strain on healthcare systems worldwide ,31,32,33Our data do not indicate a difference in postoperative pain between MP-TSCPC and CW-TSCPC. Postoperative pain was shown to be highest for simultaneously conducted anterior retinal cryotherapy. Patients should be informed about postoperative pain as part of the informed consent, especially in cases with combined anterior retinal cryotherapy. Postoperative pain can be managed with on-demand pain medication.


Chronic pelvic pain (CPP) is defined as recurrent or continuous pain in the lower abdomen or pelvis, either non-menstrual or noncyclical, lasting for at least 6 months. There is strong evidence that up to 85% of patients with CPP have serious dysfunctions of the musculoskeletal system, including abdominal myofascial pain syndrome (AMPS). AMPS is characterized by intense and deep abdominal pain, originating from hyperirritable trigger points, usually located within a musculoskeletal band or its lining fascia. In the literature, there are few studies that address AMPS.To evaluate and compare the efficacy of therapeutic ultrasound (TUS) and injection of local anesthetic (IA) to improve pain in women with abdominal myofascial syndrome secondary to CPP.Randomized controlled clinical trial.Tertiary University Hospital.A randomized clinical trial was conducted, patients were allocated to two types of treatment: group TUS (n = 18), and group IA (n = 20). The instruments used for evaluation and reassessment were the Visual Analog Scale, Numerical Categorical Scale, McGill Pain Questionnaire, and SF-36 quality of life assessment questionnaire. They were evaluated before starting treatment, 1 week after the end of treatment, and at 1, 3, and 6 months.TUS and IA were effective in reducing clinical pain and improving quality of life through the variables analyzed among study participants. There was no significant difference between groups.Limitations: absence of blinding; exclusion of women with comorbidities and other causes of CPP, the absence of a placebo group, the difference between the number of sessions used for each technique, and the COVID-19.Treatment with TUS and IA were effective in reducing clinical pain and improving quality of life in women with AMPS secondary to CPP.We declare that this clinical trial has been registered under the number [(ReBEC) no. RBR-39czsv] on 07/18/2018 in the Brazilian Registry of Clinical Trials. Chronic Pelvic Pain (CPP) is defined as perceived painful symptoms originating from organs/structures pelvic pain, typically lasting more than 6 months. It is often associated with negative consequences from a cognitive, behavioral, emotional and sexual point of view, as well as with symptoms suggestive of urinary, intestinal, pelvic floor dysfunction, myofascial or gynecological . ChronicStudies have frequently demonstrated the importance of the musculoskeletal system in the genesis and perpetuation of CPP –6. In a AMPS is characterized as intense and deep abdominal pain, originating from hyperirritable trigger points (MTrPs) in the abdominal muscles, which can be classified as either active or latent –13. Acti2, but for the treatment of a trigger point in myofascial pain syndrome, the most often used intensity is from 1 to 1.5 w/cm2. The application time for MTrP with TUS in myofascial syndrome varies from 4 to 10 min  on 07/18/2018.The first study participant was recruited on 07/22/2018.We included women between 18 years of age and non-menopausal women with a clinical diagnosis of abdominal myofascial syndrome with the presence of only one active trigger point and pain above 4.4 (moderate pain) on the Visual Analog Scale (VAS) and without previous treatments.Women who present with the following were excluded: pregnant women, with hip prostheses, neoplasms in the abdominal-pelvic region, severe osteoporosis, copper intrauterine device, abdominal varicose veins, cognitive deficits that make it difficult to understand the questionnaires, women with anticoagulation or hemorrhagic disorders, and local or systemic infections, allergies to anesthetics, acute muscle trauma, extreme fear of needles, and history of complaints of chronic musculoskeletal pain, such as fibromyalgia, chronic fatigue, or diabetes. Exclusion criteria also included those who used chronic pain relievers, anti-inflammatory drugs, tricyclic antidepressants, and aspirin within 3 days before the injection. All patients with suspected interstitial cystitis, irritable bowel syndrome, or other disease that justifies or contributes to CPP will also be part of the exclusion criteria for endometrioma or hernia as evidenced by ultrasound of the abdominal wall and abdominal wall infections, as well as women who went missing after starting treatment.The patients were recruited and treated at the CPP outpatient clinic of a tertiary university hospital. After AMPS confirmation, following the diagnostic criteria , 16, patThe active trigger point was measured using a tape measure, and to determine its exact location, the distance from the point to the various abdominal anatomical structures was measured. The clinical pain threshold was then assessed using the VAS, Numerical Categorical Scale (NCS) and McGill Pain Questionnaire. Quality of life was assessed using the SF-36 quality of life questionnaire.After a sequence of evaluations, the patients started the TUS treatments or injection of local anesthetic, according to the results of the randomization process.After the completion of treatments, participants were reevaluated with the same parameters at 1 week and 1, 3, and 6 months after intervention, and patients in both groups were instructed not to use central analgesics or nonsteroidal anti-inflammatory drugs for 72 h before the reevaluation.Measuring pain The instruments used in both stages have already been validated and are applicable in both scientific research and clinical applications. The clinical measurement of pain will be performed using one-dimensional and multidimensional scales [l scales . The Vl scales . It col scales  correspol scales .As for the multidimensional scale, the most important and widespread is the McGill Pain Questionnaire , 41. IClinical measurement of quality of life This measure is being carried out through the generic questionnaire to assess the quality of life Medical Outcomes Study SF-36, developed by the World Health Organization, translated and validated in Portuguese [rtuguese , 43 anrtuguese . It coDemographic data Women were assessed for demographic data .2 for 5 min in the region of the active trigger point [At each session, patients underwent palpation examination of the active trigger point, previously measured for the realization of treatment with TUS at the same point at each session. Treatment with TUS was performed by a previously trained physical therapist, once a week, for 10 consecutive weeks, with a frequency of 1 MHz and intensity of 1 W/cmer point , 33 To At each session, patients underwent palpation examination of the active trigger point, previously measured for the administration of lidocaine at the same point at each session. This procedure was performed by doctors with experience at the CPP outpatient clinic of the Hospital das Clínicas of the Ribeirão Preto Medical School of the University of São Paulo, and then 2 mL of 1% lidocaine was administered, without a vasoconstrictor , 28, 29Based on the objectives of this phase, the sample size calculation was performed to test two experimental proportions with samples of the same size  = 90%Based on the literature , it waThus, we have a determined sample size that is equal to 22 individuals for each group, pointing out that the response rate is different between groups, with the conditions of significance and power of the test considered, at 5 and 90%, respectively. Based on this calculation, the proposal is to include 30 subjects in each group and make the first analyses of the test’s power and effectiveness when 50% of the group is included, that is, 15 individuals in each group. Women who agree to participate and meet the inclusion criteria will be invited to return to the clinic, and the choice of treatment will be established by drawing through a computer and placed in envelopes that will be opened at the time of the first appointment.https://www.sealedenvelope.com/randomisation/internet/): group A, TUS, and group B, injection of local anesthetic. The JCRS researcher generated the random allocation sequence, and the MCDVB researcher enrolled the participants and designated the participants for the interventions.Randomization was performed through a sequence generated using an online tool for the two treatment groups, using blocks of random size of four  version 9.4 program.The study was approved by the Research Ethics Committee of the University of Sao Paulo, and informed consent was obtained from all study participants (no. CAAE 80822717.1.0000.5440). Consent forms were obtained from all study participants, and that the patients were all over 18 years of age, and that they were literate and therefore no consent form was required to be signed by parents, guardians or legal representatives. We follow all the guidelines of the Declaration of Helsinki.Overall, 42 patients were screened for the study, four of these patients did not accept to participate because they were not available to attend the scheduled procedures. Thirty eight women were randomized for the study : 19 patients completed the treatment and reevaluation protocol ; 2 patients completed the treatment but did not attend the reevaluations , one at the 3 months post treatment and the other six months post treatment; 17 patients abandoned treatment : 2 patients did not complete the treatment protocol due to the COVID-19 pandemic , 5 patients dropped out due to treatment results – worsening  or improvement  of symptoms with the onset of treatment and 10 patients abandoned treatment for reasons unrelated to the treatment itself, such as work, studies, family problems, and other health problems  .Table IA, injection of local anesthetic; TUS, therapeutic ultrasound; SD, standard deviation; P *, p value; BMI, body mass index; N, sample number.Tables When comparing the VAS and NCS scores between treatment sessions, it was possible to observe a significant improvement in all treatment sessions, for both injection of local anesthetic and TUS. We observed mainly in the TUS group an important reduction in pain in the first 4 treatment sessions.P > 0.05).Treatment with TUS was shown to be equally effective with local anesthetic injection treatment in reducing clinical pain and improving quality of life at all times of reassessment, with no statistically significant difference between groups  effects of the TUS. The thermal effects are increased blood flow. The nonthermal effects include increased vascular permeability, blood flow and fibroblastic activity, tissue regeneration, increased speed of motor and sensory nerve conduction, and reduced muscle spasms. These effects could justify the improvement of AMPS symptoms –49.When a physical or pharmacological treatment is performed, many things can explain the clinical improvement of patients; the placebo effect is one of them, and scientific evidence has shown that it exists. Medicines or physical agents applied are important, but we must also integrate other elements, such as the therapist-patient relationship. This is a true biopsychosocial phenomenon produced by the context in which an intervention is carried out. Placebo and nocebo responses are changes in patients’ symptoms due to their participation in the therapeutic meeting. This infinity of signs inherent in any intervention is perceived and interpreted by patients and can create positive or negative expectations . There In some studies, adverse events were found during treatment with TUS in experimental models, but no serious adverse events in humans have been reported. These adverse events in experimental models were cell lysis, increased free radical formation, and decreased blood flow due to constriction of arterioles forming thrombi –55. TheThe injection of local anesthetic is a treatment with proven efficacy in AMPS , 25 and In the study by Aguilera et al. , it wasThe first limitation of the study was the absence of blinding; however, due to the differences in the forms of treatment, this limitation cannot be minimized, but we emphasize that the data analysis was performed by a researcher blinded to the types of treatment. The second limitation is the exclusion of women with comorbidities and other causes of CPP. Considering this fact, we cannot affirm that both interventions work in the same way, since most women followed up in a clinic specializing in chronic pain have associated comorbidities and more than one painful region that can also be justified by the somatization process, but these exclusions were necessary to avoid bias in the interpretation of the results. The absence of a placebo group was the third limitation, but the ethical implications of not treating a patient with chronic pain prevented us from forming this group. The fourth limitation presented in this study can be considered the difference between the number of sessions used for each technique, influenced by the long interaction and doctor-patient relationship in TUS sessions. The COVID-19 pandemic was the fifth limitation presented in the study, because with the pandemic, outpatient care was suspended, thus preventing data collection and recruitment of new patients.TUS was as effective as the injection of local anesthetic in reducing pain and improving the quality of life of patients with CPP secondary to AMPS; however, further studies should be carried out with a larger number of patients and with a longer follow-up.


Pain is a subjective complaint that comprises a vast majority of emergency department (ED)A prospective cross-sectional sample of eligible patients was recruited from two centers in Saudi Arabia. Pain scorings were performed using validated online questionnaires during patients' ED stay.Pain rating scores by physicians was lower than that by patients . Additionally, severe pain rating (8–10 rating) was given less frequently by physicians compared with that by patients . Comparing the ratings by physicians with those by patients, underestimation was observed in 70.1%, overestimation in 16.9%, and matching rating in 13.0% cases. The most frequent analgesic medication administered was paracetamol (79.2%), followed by diclofenac (26.0%), morphine (10.4%), and ketorolac (9.1%). The medications were administered mainly intravenously (87.0%) and, to a lesser extent, intramuscularly (31.2%). Majority of patients (62.5%) reported not to have sufficient pain relief after treatment.Most physicians tend to underestimate the level of pain perceived by their patients, which often leads to under-treatment and lower patient satisfaction. The present study revealed a significant difference in pain ratings between patients and physicians. •There was a significant difference between patient and physician pain ratings•Pain ratings by physicians were lower than those of patients•Comparing the physicians' with patients' ratings, underestimation was 70.1%•Comparing the physicians' with patients' ratings, overestimation was 16.9%,•Comparing the physicians' with patients' ratings, matching rating was 13.0%. Pain estimation; Pain score; Emergency department. ADespite these methods, many published studies , 13, 14 Numerous factors, such as personality type, professional experience, communication, and overcrowding in the ED can influence healthcare providers' pain assessment , 17, 18.Although there has been a lot of research on this subject, very few of these have focused on the ED, and there are none in our community. Therefore, the aim of this study was to determine whether there is a significant difference in pain rating scores between patients and their physicians in the ED, and to evaluate patient satisfaction with the pain control before discharge or admission to the ward.22.1This prospective cross-sectional study was conducted at two hospitals, between September 2020 and October 2021. A convenience sample encompassing 77 patients above 14 years of age who presented to the ED with complaints of acute abdominal, flank, or back pain were invited to participate in the study. Hemodynamically unstable patients, intoxicated patients, pregnant women, and patients with pain of more than 72 h duration, any type of analgesia within the preceding 4 h, and language barriers that can affect NRS understanding were excluded from the study.2.2Data were obtained using two self-administered online questionnaires. Both questionnaires were developed by the investigators, guided by a literature review , 22. The2.3Categorical data are presented as frequencies and percentages, whereas continuous data are presented as mean and standard deviation (SD). Differences between physicians' and patients' ratings of the severity of pain perceived by patients were categorized as underestimation, matching rating, or overestimation. Due to the low frequency of matching ratings and overestimations, physicians' and patients' characteristics were compared by physicians' underestimation status (present versus absent). Chi-square or Fisher’s exact test, as appropriate, was used to examine differences in categorical variables, whereas Student’s t-test or Mann Whitney U test, as appropriate, was used to examine differences in continuous variables. Differences in patients' ratings before and after treatment were compared using the Wilcoxon signed-rank test for continuous data and the McNemar test for categorical data. To detect independent predictors of physicians' underestimation, multivariate logistic regression was performed using backward elimination of all variables included in the univariate analysis Tables –3 with a2.4Ethical approval was obtained from the Institutional Review Board of Princess Nourah Bint Abdulrahman University (IRB log number 20-0132). Both the physicians and patients who agreed to participate provided written informed consent.3As shown in 4Multivariate analysis showed that none of patient and physician characteristics were independently associated with physicians' underestimation of patients' pain. While patients tend to overestimate their pain, physicians' rating was probably more objective than patients' rating as all patients whose rating was underestimated by physicians experienced improvement and underestimation was significantly associated with higher degree of improvement.Since pain is a personal experience; it must be managed according to a set of objective principles . DoctorsPatients complaining of pain account for 60–70% of all visits to the ED . The preThe present study showed the most frequent severity reported by patients were moderate pain (54.5%), followed by severe (26.0%) and mild (18.2%). However, according to a study done by Baharuddin et al.  44.8 % oThe average rating of the severity of pain by physicians was 6.3 ± 2.0. A study by Kamarul et al.  reportedThis study has some limitations. Increasing the number and variability of patients and the background of treating physicians would have made the results more generalizable. The presumed patient and physician factors leading to pain underestimation were not proven in this study . To overcome this phenomenon, we suggest giving more emphasis on pain estimation and management in medical school and residency training, utilizing a standardized approach based on frequent assessment and re-assessment of unified modules, and promoting a more empathetic approach to patients presenting with pain among healthcare providers.5Most physicians tend to underestimate the level of pain perceived by their patients, which often leads to under-treatment and lower patient satisfaction. The present study showed a significant difference in pain ratings between patients and physicians. There were also substantial disparities in the mean pain scores of patients upon arrival compared to those of physicians. Consequently, requesting pain ratings is a crucial step towards effective pain management in emergency medicine.Malak Alotaibi: Conceived and designed the experiments; Performed the experiments; Wrote the paper.Muna Aljahany: Conceived and designed the experiments; Performed the experiments; Contributed reagents, materials, analysis tools or data; Wrote the paper.Zaid Alhamdan, Mashael Alsaffar, Abdulrahman Almojally and Wajdan Alassaf: Contributed reagents, materials, analysis tools or data; Wrote the paper.The authors are grateful to Princess Nourah bint Abdulrahman University for supporting this research through sabbatical leave program.Data will be made available on request.The authors declare no conflict of interest.No additional information is available for this paper.


Chronic postsurgical pain (CPSP) after hepatectomy is highly prevalent and challenging to treat. Several risk factors have been unmasked for CPSP after hepatectomy, such as acute postoperative pain. The current secondary analysis of a clinical study sought to extend previous research by investigating more clinical variables and inflammatory biomarkers as risk factors for CPSP after hepatectomy and sifting those strongly related to CPSP to build a reliable machine learning model to predict CPSP occurring. Participants included 91 adults undergoing hepatectomy who was followed 3 months postoperatively. Twenty-four hours after surgery, participants completed numerical rating scale (NRS) grading and blood sample collecting. Three months after surgery, participants also reported whether CPSP occurred through follow-up. The Random Forest and Support Vector Machine models were conducted to predict pain outcomes 3 months after surgery. The results showed that the SVM model had better performance in predicting CPSP which consists of acute postoperative pain  and matrix metalloprotease 3 (MMP3) level. What's more, besides traditional cytokines, several novel inflammatory biomarkers like C-X-C motif chemokine ligand 10 (CXCL10) and MMP2 levels were found to be closely related to CPSP and a novel spectrum of inflammatory biomarkers was created. These findings demonstrate that the SVM model consisting of acute postoperative pain and MMP3 level predicts greater chronic pain intensity 3 months after hepatectomy and with this model, intervention administration before CPSP occurs may prevent or minimize CPSP intensity successfully. Chronic post-surgery pain after hepatectomy remains a daunting challenge, casting a shadow over the patient's heart. Approximately 40% of post-hepatectomy patients suffered from unbearable CPSP , for thovia blood sample to predict the occurrence of CPSP  are also identified as key factors in CPSP predictive model , we performed a secondary analysis on the prospective clinical trials (NCT05492669) in Medical Center: West China Hospital   and scre2 60% to maintain BIS within 40–60. Systolic arterial blood pressure was maintained within 20% of baseline values; when hypotension (MAP <55 mmHg) occurred, patients were treated with intravenous phenylephrine. The incision was infiltrated with 0.25% ropivacaine 20 ml at the end of the procedure. Following the completion of the surgical procedure, the patients were extubated in the operating room and admitted to the post-anesthesia care unit (PACU).Anesthesia procedures were performed in accordance with standardized criteria. For premedication, patients received 50 mg flurbiprofen axetil by intravenous infusion 30 min before the surgery initiation. Intravenous access to the upper limb was performed and standard monitoring was performed, including electrocardiography, pulse oximetry, blood pressure, and the bispectral index (BIS). Then anesthesia was induced by propofol 1.5–2 mg/kg, midazolam 2 mg and sufentanil 0.2–0.3 μg/kg. Tracheal intubation was facilitated with cis-atracurium 0.2 mg/kg. Whole anesthesia progress was maintained with remifentanil 0.1–0.2 μg/kg/min and desflurane or sevoflurane in a mixture of air 40% and OObservations of pain were conducted every 10 min using the numerical rating scale (NRS), and those who scored higher were treated with sufentanil 0.1 µg/kg every 10 min. Aldrete scores were recorded prior to leaving the PACU. It was only possible to discharge patients from the PACU if the Aldrete score was at least 9 and there was no evidence of pain or PONV .Patients received intravenous analgesia with PCIA for the first 72 h post-operatively. In case pain occurs, patient may press the PCIA button repeatedly until feeling relief. Mephedrone 5 mg would be administered if the NRS score of the participant was >3 after taking the maximum dose (10 ml/h).The day before the operation, all patients received an explanation of how to rate pain intensity on NRS, identifying 0 as “no pain” and 10 as “worst imaginable pain”. In the final assessment of NRS grade, face-to-face follow-ups were conducted 1 day after surgery and telephone follow-ups were conducted 3 months after surgery. Acute postoperative pain is defined as the pain that occurs during movement  at postoperative 24 h, and CPSP as the pain that occurs at 3 months after surgery.In the above 3-months follow-ups, the patients suffering from CPSP also received an explanation of ID pain . The iteBlood samples are collected at 24 h after surgery for subsequent measurement, which are labelled, centrifuged, frozen, and stored locally at −80° in line with experimental standards. Levels of 8 plasma biomarkers including VEGF, IL-1β, IL-6, CXCL10, TNF-α, MMP2, MMP3 and MMP9 are measured using Human Premixed Multi-Analyte Kit .Permuted importance approach in random forest was applied for elimination of some variables that were not predictive for CPSP to improve model accuracy. Permuted importance for a particular variable was calculated by comparing the difference in the prediction accuracy of the out-of-bag data to the prediction accuracy when the variable was noised up by randomly permuting its values. The higher the predictive power variable obtained, the larger importance value it earned. Variables were ranked from high to low according to their permuted importance score and those with the highest scores were selected. Variable selection of this study was performed using R, version 3.6.1.Through the building and cross-validating of predictive models to classify CPSP risk, multiple machine learning algorithms to identify important biomarkers and clinical variables can be employed. After comparison, Support Vector Machines (SVM) and Random Forest were selected. Model building were performed using R, version 3.6.1.The SVM algorithm was selected considering the limitations of small sample sizes and imbalanced dataset. For SVM model building, limited by the sample size, only 2 features were allowed to avoid over-fitting. The tuning hyperparameters of the SVM included the following: radial, cost, gamma. The SVM classifiers with final features and hyperparameters were trained and tested in Set 1 by 10-times cross-validation (CV) algorithm. SVM models with different sets of features and sets of hyperparameters were compared by AUC; finally, the one with the highest value was selected as the final SVM classifier. In the process of constructing the SVM model, we set radical as kernel, cost as 20 and gamma as 0.01 by the result of automatic parameter tuning. The generalized performances of this final predicting classifier were validated in Set 2, including accuracy, sensitivity, specificity receiver operative curves (ROCs), and its corresponding AUC.Random forest was selected for its excellent performance on handling an imbalanced dataset containing multiple types of data. Multiple decision trees were built based on bootstrap sampling of the Set 1 by 10-times cross-validation (CV) algorithm. It could give a prediction whether a patient would develop CPSP by providing a probability, and the probability was determined by the ratio of the decision trees that gave positive results to the total number of decision trees. In the process of constructing the RF model, we set ntrees as 280 and mtry as 3 by the result of manual parameter tuning, considering the predictive performance of the RF model and AUC. The generalized performances of this final predicting classifier were also validated in Set 2 as previously mentioned.Participants were selected from a clinical trial recruiting between June 2019 and June 2021. Participant flow through the study was shown in 91 individuals undergoing hepatectomy were included in the analyses. 70 (77.0%) were male; 21 (23.0%) were female. The mean ± SD. age of all participants was 54.1 ± 11.0 years (range 27–78 years). The average duration of surgery was 3.2 ± 1.2 h, and the average duration of anesthesia was 4.4 ± 1.2 h. The average volume of bleeding was 289.8 ml, which varying from 10 to 1,200 ml. Open hepatectomy was performed in 76 patients (83.51%), while laparoscopic hepatectomy was performed in 15 patients (16.49%). Of these, the incision length varied from 23 to 30 cm for open procedures, with an average of 26.82 cm.All participants reported having acute postoperative pain. Of these, 33 (36.2%) reported mild pain (NRS 1–3), 46 (50.6%) reported moderate pain (NRS 4–6), and 12 (13.2%) reported severe pain (NRS > 6).There were 49 (53.8%) participants who reported no pain 3 months after surgery, 40 (44.0%) participants who reported mild pain, and 2 (2.2%) participants who reported moderate pain. Pain distribution and characteristics were shown in More recently, the six-item ID Pain was developed as a brief, self-administered screening tool for detecting neuropathic pain in primary care settings . Among tTo explore the effect of each biomarker and clinical variables, random forest was performed for them shown in 91 patients were randomized into two independent sets: 64 patients for model building and cross validation in train set (Set 1), and 27 patients in test set (Set 2). Two groups share similar physical and clinical characteristics.SVM model for CPSP risk were ﬁrst trained and tested in Set1 by cross validation. The model with best performance was selected, and this model included 2 features from biomarkers and clinical variables of our interest. NRS at the first postoperative day seemed to be the most signiﬁcant one as identiﬁed by random forest shown in The ﬁnal SVM model was validated in Set 2. It predicted CPSP risk with accuracy = 0.857, sensitivity = 0.800, speciﬁcity = 0.923, AUC = 0.892. The validated results are shown in The performances of the ﬁnal SVM classiﬁer were compared with that of random forest model . As shown in In the current study, the overall prevalence of CPSP at 3 months after hepatectomy was 53.85% (49 in 91). Findings from this study proved that the inflammatory biomarkers MMP3 and NRS at 24 h postoperatively correlated significantly with the risk of CPSP. Machine Learning model combining MMP3 and NRS for CPSP risk forecasting showed reasonable predictive values. Within the limitations of a medium-sized study, the AUC of the final SVM model showed sound performance for predicting CPSP risk.Previous studies had underscored that learning machine methods could better predict the occurrence of multiple diseases , 21 due SVM was considered a “black box” algorithm, which might create a challenging dilemma for those responsible for a potential decision-making medical error. Interpreting how the model reached its predictions was therefore necessary to enable researchers to assess whether their predictions were trustworthy . AccumulMeanwhile, this study also demonstrates the importance of other biomarkers  and clinical variables  in patients after hepatectomy, although they were not entered into the SVM model implemented by the machine learning algorithm. In mice with spinal nerve ligation (SNL), CXCL10-activated CXCR3 was found to mediate p38 and ERK activation in DRG neurons and enhance neuronal excitability, which contributed to the maintenance of neuropathic pain . BMI wasThere were some limitations of this study. First, the sample size was small limiting statistical evaluation and constraining our choice in machine learning model; secondly, only 2 factors were applied to construct the SVM model to avoid overfitting but was susceptible to type I error and unfitting; additionally, limited by the numbers of the events, this model simplified CPSP as a binary outcome, while the NRS was a 10-level graded event and pain also varied in character, which were topics of our ongoing study; what's more, only biomarkers that have been widely studied recently were included in this study, and other biomarkers were also worthy of further exploration. These limitations could be overcome in future with larger sample sizes.In summary, using a machine learning framework, a SVM model of CPSP risk was established which integrated MMP3 and NRS as representative of cytokines and clinical variables. The SVM classiﬁer was validated in Set 2 and conﬁrmed to have reliable predictive performance. Additionally, our study provided important insights into biomarkers of CPSP risk and had identiﬁed 24 h postoperative biomarker levels such as VEGF, MMP3 and CXCL10 and clinical variables to be closely related to CPSP. Further study will need to validate this ﬁnding and will need to consider the incorporation of more biomarkers and clinical variables to improve predictive accuracy.


Bone marrow harvesting is associated with significant postoperative pain that may have potential negative consequences for the patient and health care system. In the current absence of uniform guidelines, there exists considerable variability amongst providers with respect to perioperative analgesia, especially opioid administration. In this initiative, we explored the potential for preoperative bilateral quadratus lumborum blocks in combination with a standardized perioperative analgesic protocol to manage pain with the goal of reducing perioperative narcotic usage and thereby improving opioid stewardship.n = 32). The pre-implementation group (n = 19) was reviewed retrospectively while the implementation group (n = 13) was evaluated prospectively. Patient demographics, pain scores, and opioid consumption were evaluated.Adults who underwent bone marrow donation from 2018 to 2020 were included in this analysis (p < 0.001) and total opioid consumption . The number of patients who received any opioids decreased from 84.2% (16/19) before implementation to 23.1% (3/13) after implementation.Patient characteristics were equivalent except for anesthesia type with an increased number of patients in the implementation group undergoing spinal anesthesia. The implementation group showed significantly reduced median intraoperative (20.0 mg vs. 0.0 mg; This change in practice suggests that implementation of a standardized perioperative protocol, including bilateral quadratus lumborum blocks, for bone marrow harvest patients leads to reduced perioperative opioid administration without compromising immediate perioperative pain control. Bone marrow harvesting (BMH) is a safe and effective method for collecting hematopoietic stem cells , 2. ClinBecause pain is often the most common postoperative complication , 6, poteAt our institution, we noticed differing amounts of opioids were administered to patients intraoperatively, whether prophylactically or triggered by a change in vital signs, during BMH. We also noticed that patients were treated with intravenous or oral opioids in the PACU, despite infiltration of local anesthetic at the end of BMH. Based on these observations, we sought alternative approaches to managing pain after BMH, improving opioid stewardship, and reducing provider variability in treating pain.In this quality improvement (QI) initiative, we set out to create a standardized protocol through multiple tests of change that would reduce variability between providers and thereby produce consistent perioperative outcomes. We also explored alternative approaches to treating postoperative pain, including quadratus lumborum (QL) fascial plane blocks. These procedures are low risk and have been used to successfully treat postoperative pain in a variety of procedures, including lower abdominal surgery, hip arthroplasty, caesarian section, pelvic fractures, and lumbar laminectomies . We postn = 19) included adults undergoing BMH between January 31, 2018, and January 21, 2020. Data collection for the baseline group was collected retrospectively. The implementation group (n = 13) included patients undergoing BMH between January 22, 2020, and October 6, 2020. Data for the implementation group was collected prospectively. All patients were adults 18 years and older who underwent BMH at our academic medical institution. This study was designed as a QI analysis of our practice and approved by the Institutional Review Board at the Medical University of South Carolina. From 2018 to 2020, a total of 46 patients underwent BMH at our institution; patients under the age of 18 were excluded from the analysis. The baseline group  to limit or avoid using opioids during the QL blocks and when inducing anesthesia (if safe/possible), and to eliminate standardized opioid orders in the PACU. To decrease provider variability, we designated an anesthesia physician liaison to manage donors perioperatively, limited the anesthesia attendings who staffed the cases, and created a standardized protocol for anesthesia and BMH physicians to reference. The timeline for implementing these tests of change is outlined in At the beginning of the project, we identified several stakeholders, including the QI physician champion, harvesting physicians, RAPS physicians, and perioperative nursing leadership. The QI physician champion became the anesthesia physician liaison to the bone marrow transplant team. This team included two harvesting physicians who consistently performed all bone marrow harvests starting September 16, 2019 (a decision made by the BMH team before implementing this QI initiative in January 2020 but continued with adherence throughout). The lead QI physician champion discussed incorporating regional anesthesia options with the bone marrow transplant team at their weekly meeting before starting a new protocol or changing to an established practice. The anesthesia liaison and nurse coordinator for the bone marrow transplant team also communicated and collaborated during the project.All patients undergoing BMH in the implementation period underwent lateral QL blocks bilaterally before being transported to the operating room. A lateral QL technique was chosen because the approach is the most superficial and easiest to visualize with ultrasound. For the block, the patient was most often in the supine position. Using ultrasound, the QL muscle was identified and 20 mL of ropivacaine (0.375–0.5%) was deposited between the trans vs. abdominis aponeurosis and the QL muscle. This process was repeated on the opposite side. The RAPS attending provided sedation as needed, which consisted of midazolam, dexmedetomidine, and, infrequently, fentanyl.1 Patient demographics, anesthesia type, procedure duration, PACU duration, and PACU pain scores were analyzed in each group.To assess pain control, we used perioperative opioid use as a proxy measure. Perioperative opioid use included intraoperative intravenous opioids given by the anesthesia team based on vital sign chances consistent with pain and intravenous or oral opioids given in the PACU based on patients’ description of pain. The primary calculation excluded intravenous opioids given to sedate patients for the preoperative QL block or as part of inducing anesthesia to blunt a hemodynamic response to direct laryngoscopy. Opioid administration in all phases of care was collected for both groups and converted to oral morphine milligram equivalents (MME) using a standardized equianalgesic dosage conversion calculator.The median, inner quartile range, and range for intraoperative MME, PACU MME, and total MME received by donors before and after implementation were calculated. The median was selected as the distribution of MME’s was skewed. Univariate associations were evaluated with categorical variables using the Fisher’s exact test, and associations with continuous variables were evaluated using the Wilcoxon rank sum test. All analyses were conducted in SAS v. 9.4  .p = 0.002) which was driven by protocol change. PACU times were also significantly longer in the implementation group  attributable to the patients recovering from the spinal anesthetic.Patient demographics and clinical characteristics for the groups before and after implementation are reported in p < 0.001 for both parameters). PACU consumption also decreased after implementation, though the change was not statistically significant (p = 0.073). The number of patients who received any opioids decreased from 84.2% (16/19) before implementation to 23.1% (3/13) after implementation. In all cases, median opioid consumption dropped to zero after implementation. The median intraoperative, PACU and total opioid consumption by time are shown in Among all patients in the implementation group, only one received an intravenous opioid mid-procedure to treat delirium. The patient underwent spinal anesthesia and infusion of propofol. He was treated with one dose of fentanyl to keep him still and comfortable during the procedure. As his spinal level of anesthesia was adequate for the procedure, opioids were not administered to manage procedural pain.In the PACU, only two patients received intravenous opioids. These patients underwent longer harvests with larger total harvest volumes, which can increase postoperative pain . InteresIn this QI initiative, we introduced a novel use of a well-established procedure, QL blocks, to successfully manage postoperative pain. We also standardized the process for perioperative anesthetic management, educated care team members on the appropriate use of opioids, initially decreased variability between anesthesia providers, and increased new provider involvement with excellent adherence to an accessible provider protocol. During this approximately 9-month initiative, we significantly and sustainably reduced opioids given to patients undergoing BMH, implicating that our initiative improved pain control in these patients.Early in project development and based on ongoing revisions of the perioperative protocol due real-time outcomes, we surprisingly found that the quadratus lumborum blocks and multimodal medications provided sufficient analgesia during the procedure. After this was repeatedly observed, we made a continued effort to educate providers on the benefit of the components of the protocol and the potential lack of need for additional opioid administration in the operating room. This was particularly true for patients undergoing general anesthesia, who did not have anticipated vital sign changes secondary to pain with incision despite lack of intravenously administered opioids. This observed principle was not applicable for patients undergoing spinal anesthesia, as incisional pain was masked by the spinal level of analgesia therefore intravenous opioids were unlikely to be given to these patients.Our results support the growing body of literature that describes QL blocks as an effective modality for pain management of the lower back. The distribution of the blockade among all anatomic variations of QL blocks is cited as T7-L2 , 25. TheIn QI work, the success of new processes may depend on one person who can consistently oversee the process, or on effective protocols that minimize variability between personnel . One sucn = 7) was 0%. Therefore, inclusion of the induction opioid would have further increased the observed difference between the two groups. We recognize that we cannot fully eliminate perioperative opioid administration. Opioids are often needed for complex cases . The comA notable barrier encountered was the lack of buy-in from nurses in the PACU who managed patient recovery after spinal anesthesia. Because donors who underwent spinal anesthesia had a longer recovery time in the PACU (median duration 184 min), their care required more time from nurses, especially with staffing constraints during the pandemic. Although shorter-acting spinal medications could have addressed this issue, these medications were not readily available due to production delays. This issue also highlights the importance of including a broad spectrum of stakeholders in multi-departmental QI projects. Another barrier that others could face is the lack of a regional anesthesia–specific service to perform the QL blocks. To address this issue, the supervising anesthesiologist could perform the blocks in the operating room either before inducing anesthesia or between inducing anesthesia and starting the surgery.Our study is not without potential limitations. The project was designed as a QI analysis of our practice comparing a prospective patient group with a retrospective data set. Additionally, a power calculation was not performed. In QI initiatives the primary aim is not to show a statistical difference in the groups but to improve the quality of a process or patient experience. Finally, decreased opioid administration alone may not be an indication of decreased pain.In future work, we plan to develop a perioperative protocol specific to our pediatric donors and to obtain formal postoperative satisfaction surveys. Also, we are now performing BMH on adult-related donors in operating rooms at the children’s hospital. This effort aims to improve patient satisfaction by limiting their transport across our medical campus after their procedure and before their family member’s bone marrow transplant within the same day. We will also continue to evaluate and improve our ambulatory spinal protocol. Although general and spinal anesthesia have similar safety margins, each approach may have unique benefits. Specifically, in this patient population, spinal anesthesia causes less postoperative nausea and vomiting, whereas general anesthesia provides airway protection . Midway In this initiative, we used a standardized protocol and QL blocks to reduce variability between providers and significantly reduce perioperative opioid use related to BMH. Our approach also improved perioperative pain control in patients undergoing the procedure. These findings may alleviate donor concerns about pain associated with BMH. This project highlights another successful application of QL blocks for pain management, further supports their use in procedures involving posterior iliac crests and reinforces the role of regional anesthesia in opioid sparing anesthetics.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by QI Analysis via the IRB at the Medical University of South Carolina. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.NM designed the project, collected and evaluated data, and was the primary author for the manuscript. EH was involved in the development of the project, data collection, and manuscript revisions. DR helped with data evaluation and manuscript revisions. JD helped the manuscript and subsequent revisions. BW helped with the statistics and results. MH helped with project design, mentored our team, and was involved in manuscript revisions. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Distal radius fractures (DRFs) are very common injuries associated with aging, and the number of fractures is increasing with the increase in the elderly population. General anesthesia or brachial plexus block (BPB) is required for fracture fixation, and acute postoperative pain control is necessary after operation. Early pain control can improve patient satisfaction and functional outcomes. In this study, we report the clinical differences in postoperative pain, according to the method of anesthesia . Volar plating was used to treat 72 patients older than 60 years who had comminuted DRF. Patients were randomized to either group A (36 patients), who underwent general anesthesia, or group B (36 patients), who underwent BPB. We compared these two groups prospectively for acute postoperative pain using a visual analog scale (VAS) at 2, 4, 6, 12, and 24 h after surgery. The VAS scores of each group were: 6.8 ± 2.5 in general anesthesia and 0.5 ± 2.3 in BPB at 2 h, postoperatively; 6.5 ± 2.4 in general anesthesia and 0.5 ± 2.4 in BPB anesthesia at 4 h, postoperatively; 5.2 ± 2.4 in general anesthesia and 1.5 ± 2.4 in BPB anesthesia at 6 h, postoperatively; 4.5 ± 2.5 in general anesthesia and 3.4 ± 2.7 in BPB anesthesia at 12 h, postoperatively; and 3.5 ± 2.5 in general anesthesia and 3.2 ± 2.7 in BPB anesthesia at 24 h, postoperatively. DRF patients with BPB anesthesia showed a lower VAS score than those subjected to general anesthesia in early postoperative period. As a result, the effect of BPB anesthesia on acute pain management after surgery was excellent, which resulted in a lower pain score compared with general anesthesia in DRF patients undergoing volar plating. Distal radius fractures (DRFs) are very common injuries, and the number of fractures is increasing with the increase in the elderly population, as the density of bone decreases with age ,2. SeverTypical methods of anesthesia used to perform surgery for DRFs include general anesthesia (GA) and brachial plexus block (BPB). BPB is superior to GA in decreasing postoperative nausea, vomiting, reducing the need for perioperative opiate consumption, and shortening the stay in the postoperative care unit ,5,6. BPBThe advantages and benefits of BPB compared with GA have been reported previously . HoweverThis is a case-control study conducted with prospectively applied data and approved by the institutional review board. We included 72 patients who underwent operation for DRFs from November 2019 to April 2021. The inclusion criteria were: (1) female sex, (2) 60 years of age and over, (3) patients who did not have an underlying life-threatening disease (ASA 1 or ASA 2), (4) no cognitive impairment, and (5) understanding of the VAS score before operation.A randomized number was generated using an automated computer program. Randomization was performed when the patient arrived in the operating room using randomly numbered and sealed envelopes. The envelopes were placed in the operating room and only opened when the patient arrived, and neither the patient nor the involved physicians were aware of the randomization. Patients who refused randomization or already preferred one of the anesthetic techniques were excluded from the study. Finally, patients were randomized to either group A (36 patients), who underwent general anesthesia, or group B (36 patients), who underwent BPB anesthesia.The average age of 36 patients who underwent operation under GA (Group A) was 71.2 ± 14.5 years. The average age of another 36 patients who were treated surgically under BPB (Group B) was 69.5 ± 15.8 years. The right wrist was injured in 14 patients and the left wrist was injured in 22 patients in Group A, and the right wrist was injured in 22 patients and the left wrist was injured in 14 patients belonging to Group B .In Group A, induction was performed using intravenous lidocaine 40 mg, fentanyl 0.5 mg/kg, propofol 1 to 1.5 mg/kg, and rocuronium 0.6 mg/kg for neuromuscular blockade. A supraglottic airway was inserted based on patient size. Anesthesia was maintained with oxygen, medical air, and 1 minimum alveolar concentration of desflurane under monitoring of bispectral index (40 to 60). During skin closure, neuromuscular blockade was reversed with 0.2 mg/kg pyridostigmine and 5 mg/kg glycopyrrolate .Ultrasound-guided axillary BPB was performed in-plane with a 25 gauge 6 cm plane needle. An anesthetics mixture was prepared including 20 mL of 0.45% ropivacaine and 3 mL of 2% lidocaine with 5 mg of dexamethasone as an adjuvant. All axillary block approaches require the patient to be positioned supine, with the arm abducted 90 degrees and the head turned toward the contralateral side. The axillary artery pulse was palpated, and its location was marked as a reference point. Using a high-frequency linear array ultrasound transducer, the axillary artery and vein were visualized in cross-section. The brachial plexus was identified surrounding the artery. The needle was inserted superior  to the transducer and advanced inferiorly  toward the plexus under direct visualization. Local anesthetic mixture was then injected around each nerve. The effect of BPB was evaluated with a temperature test using an alcohol swab; then, sedation was performed using 2% propofol 50 μg/kg/min after checking anesthesia status [A single surgeon (J-H N) performed volar plating in all the investigated patients. The volar approach  was used along the flexor carpi radialis tendon. Fractures were fixed using a volar locking plate system  after achieving anatomical reduction. Following volar plating, the PQ muscle was repaired via insertion as close as possible using absorbable sutures with the forearm in supination at the end of the operation. Postoperatively, the wrists were immobilized using a short-arm volar plaster splint.After the operation, all patients were evaluated for acute postoperative pain based on the VAS score at 2, 4, 6, 12, and 24 h after the operation. We evaluated the sensory recovery over time after surgery in group B as follows: (1) time of restoration of sensory awareness of patients; (2) time of pain initiation; and (3) time when patients’ senses recovered fully without any numbness or hypoesthesia on affected hand. A self-report questionnaire form including these items was handed out to the patients before the surgery. The patient was allowed to fill the questionnaire after the surgery, and the physician confirmed it.Postoperative pain medications were designed based on our previous experiences and currently available literature on acute pain management. Patients were prescribed a nonsteroidal anti-inflammatory drug (NSAID); celecoxib 200 mg orally twice per day. Rescue medication was prescribed through intravenous short-acting narcotics; tramadol 50 mg to 100 mg every 4 to 6 h. There were no differences between groups.t-test; a = 0.05). The analysis indicated that a sample size of 35 patients per group was required.A power analysis was performed using the software package G power (version 3.1.9.4.)  . Power at-test was used to compare continuous variables. The significance of the VAS score at 2, 4, 6, 12 and 24 h in each group was determined via paired t-test. A chi-square test was used to compare categorical variables. A significant level of p < 0.05 was used for all comparisons. The results were presented as mean ± standard and as number for discrete variables.Statistical analysis was carried out using SPSS . The independent The VAS scores after operation of each group were as follows: 6.8 ± 2.5 in Group A and 0.5 ± 2.3 in Group B at 2 h postoperatively; 6.5 ± 2.4 in Group A and 0.5 ± 2.4 in Group B at 4 h postoperatively; 5.2 ± 2.4 in Group A and 1.5 ± 2.4 in Group B at 6 h postoperatively; 4.5 ± 2.5 in Group A and 3.4 ± 2.7 in Group B at 12 h postoperatively; and 3.5 ± 2.5 in Group A and 3.2 ± 2.7 in Group B at 24 h postoperatively . The paiThe results of sensory recovery over time after surgery in group B indicated that (1) the average time required to restore patients’ senses was 10.5 ± 2.8 h; (2) patients’ pain started in 12.4 ± 3.9 h; and (3) the average time required for complete recovery of patients’ senses was 19.2 ± 4.1 h .Many patients experience strong pain after volar plate fixation of displaced radius fractures ,12. DRF The followup results of the pain score up to 24 h postoperatively revealed that patients in the BPB group suffered less pain than those in the GA group at all time points. Therefore, faster rehabilitation and recovery can be expected via effective pain control using BPB. However, rebound pain is a disadvantage of BPB and has been reported in several studies. Galos et al.  reportedBPB can be performed at different anatomical sites such as interscalene, supraclavicular, infraclavicular, axillary nerve regions, and the humeral canal ,18. In aOne of the strengths of this study was the monitoring of sensory changes in the BPB group over time. The mean time required to restore patients’ senses was 10.5 ± 2.8 h, and the mean time need to trigger pain was 12.4 ± 3.9 h. This finding can be interpreted in relation to the result of a rapid increase in the VAS score 6–12 h after surgery in patients subjected to BPB. Therefore, we suggest that to control this pain pattern after DRF surgery, an appropriate pain reliever should be used approximately 12 h after surgery, when rebound pain is triggered.Patients with fractures involving the upper extremity are at high risk for developing complex regional pain syndrome type I (CRPS I) , with reThis study had some limitations. First, we investigated patients’ pain based on VAS, which is a subjective score. It was a challenge to mask the surgeon, anesthesiologist, and patients continuously after the operation. In addition, only the results of the short-term pain scale up to 24 h after surgery were compared in this study. A study including long-term clinical outcomes and functional scores is required to confirm the effect of BPB over GA.The effect of BPB anesthesia on acute pain management after surgery was excellent, which resulted in a lower pain score compared with general anesthesia in DRF patients undergoing volar plating. In addition with our local anesthetic regimen of BPB anesthesia, we could expect to reduce the rebound pain of BPB.