In both cohorts, the analysis showed that CCI was slightly superior in predicting e-LOS in complicated patients. The accuracy of CCI was even better when considering a subgroup of patients who experienced at least two complications. The results of this population-specific analysis suggest that CCI is preferable in weighting postoperative morbidity burden.The comprehensive complication index (CCI) and the Clavien-Dindo Complication (CDC) scoring system are two metrics designed to quantify the burden of postoperative morbidity. We performed a retrospective study retrieving data from a multi-institutional Italian register. The aim was to compare the performance of the two metrics in predicting excessive length of hospital stay (e-LOS) of patients who underwent liver resections for hepatocellular carcinoma. A total of 2669 patients were analyzed. A derivation (Background: We aimed to assess the ability of comprehensive complication index (CCI) and Clavien-Dindo complication (CDC) scale to predict excessive length of hospital stay (e-LOS) in patients undergoing liver resection for hepatocellular carcinoma. Methods: Patients were identified from an Italian multi-institutional database and randomly selected to be included in either a derivation or validation set. Multivariate logistic regression models and ROC curve analysis including either CCI or CDC as predictors of e-LOS were fitted to compare predictive performance. E-LOS was defined as a LOS longer than the 75th percentile among patients with at least one complication. Results: A total of 2669 patients were analyzed . The odds ratio (OR) was 5.590  for CCI and 5.507  for CDC. The AUC was 0.964 for CCI and 0.893 for CDC in the derivation set and 0.962 vs. 0.890 in the validation set, respectively. In patients with at least two complications, the OR was 2.793  for CCI and 2.439  for CDC with an AUC of 0.850 and 0.673, respectively in the derivation cohort. The AUC was 0.806 for CCI and 0.658 for CDC in the validation set. Conclusions: When reporting postoperative morbidity in liver surgery, CCI is a preferable scale. Hepatic resection offers the best chance of long-term survival for patients with resectable hepatocellular carcinoma (HCC) ,2. AlbeiThe Clavien-Dindo classification (CDC), originally described in 2004 , is the Despite that CCI and CDC scoring systems are closely related metrics, CCI allows a longitudinal assessment of morbidity because the addition of a complication, appearing at a later time-point, is added to the score. By this computation CCI appears more precise to capture the overall morbidity burden ,9. HowevPatients who underwent liver resection for HCC with curative intent between 2007 and 2018 were identified from an Italian multi-institutional database. Patient data were retrieved retrospectively from this dataset, promoted by the Hepatocarcinoma Recurrence in the Liver Study (He.Rc.O.Le.S.) group. The study protocol followed the ethical guidelines of the 1975 Declaration of Helsinki (as revised in Brazil 2013). The Ethical Committee of the coordinating center  reviewed and approved the protocol (211218HSG-R) on 21 December 2018. Inclusion criteria were: (1) first diagnosis of HCC without any previous treatment; (2) age ≥ 18 years; (3) HCC diagnosis confirmed at histology. Exclusion criteria were: (1) surgery as a down-staging therapy for transplant; (2) patients who eventually underwent liver transplantation; (3) mixed primary liver cancers . All data were anonymized prior to submission to the coordinating center. Data collection was performed using the same electronic database at all centers.Centers were randomly selected to be included in either the derivation or validation set to obtain a similar number of patients in the two cohorts.Results are reported according to principles of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) .Age, sex, and liver function were recorded at the first office visit. The presence of cirrhosis and its severity (Child-Pugh score) was evaluated and graded by expert hepatologists. Presence of HCV or HBV infection and serum biochemical values of bilirubin, albumin, platelets, and international normalized ratio (INR) were also recorded at baseline. The American Society of Anesthesiologists (ASA) class was assessed during the preoperative patient evaluation. The number and diameter of nodules were assessed through preoperative radiologic imaging and confirmed by intraoperative ultrasound. The extension resection was defined as minor when ≤3 liver segments were resected and major when >3 segments, according to the Brisbane nomenclature . The defThe primary endpoint was to assess the performance of CCI and CDC to predict LOS and e-LOS in patients undergoing liver resection for HCC.The secondary endpoint was to find an optimal CCI cut-off value capable of predicting e-LOS.Sample description was performed using median and interquartile range (IQR) for numeric variables and number and proportion for categorical variables, for both derivation and validation sets.The distribution of CCI in each CDC category was explored graphically using boxplots, while the association between each score and LOS was represented with a scatter plot, again in both datasets.After excluding patients who died within 90 days , the association of each score with LOS (log-transformed) was analyzed using linear regression. We fit univariate models, including CCI or CDC as the only covariate, and multivariate models, adjusted by type of surgery (major vs. minor), open vs. laparoscopy, age (per year), ASA score (1–2 vs. 3–4), Child grade (A vs. B), duration of surgery (>4 h vs. ≤4 h), center volume (high vs. medium/low) on the derivation set. We evaluated and compared the goodness-of-fit of the models including CCI or CDC using the R-squared and the root mean squared error (RMSE) indexes. This was done on the derivation set and, on the validation set without refitting the models. The whole linear regression analysis was repeated considering, in both sets, only the subgroup of patients with at least two postoperative complications.The association of both scores with e-LOS was analyzed using logistic regression. Again, we fit univariate and multivariate models  on the derivation set excluding patients who died during hospital stay. The discriminatory ability of the models to identify patients with e-LOS was evaluated using the area under the ROC curve (AUC) index both on the derivation and validation (without refitting the models) sets. Again, the whole logistic regression analysis was repeated considering, in both sets, only the subgroup of patients with at least two postoperative complications.Finally, considering only the subset of patients with at least one postoperative complication in both sets, we built an ROC curve to find the optimal cut-off (corresponding to the maximum Youden index) of CCI to be used in order to identify patients with e-LOS. We repeated the analysis within strata defined by minor/major surgery, open/laparoscopic surgery, presence/absence of cirrhosis and Child grade A/B. The R software version 4.0.1 was used for all the analyses.The analysis was carried out in May 2020, and at that time the records of 2917 patients, collected in the 25 centers, were entered into the register. A total of 248 records were excluded because of missing information on LOS, CDC or CCI, resulting in 2669 patients available for the final analysis. The final sample size of the derivation and validation cohorts were 1345 and 1324 records, respectively.n = 451), and 7.0% (n = 95) had a CDC ≥ 3. The overall median CCI was 0 (IQR: 0–20.9) and the mean 8.6 (±16.0 SD), while considering only patients with at least one complication the median CCI was 20.9 (IQR 20.9–26.6) and the mean 25.5 (±18.1 SD). The overall median LOS was 7.0 days (5.0–9.0 IQR), 10.0 days (IQR 8.0–15.0) among complicated patients, and e-LOS was thus considered as LOS ≥ 15 days. A total of 260 patients (19.3%) had only 1 complication, and 191 (14.2%) had at least 2 complications. The 90-day mortality was 1% (14 cases). Patients included in the validation set presented similar complication rate (40.4%), multiple complication rate (13.1%), median CCI , and median LOS . In this cohort, patients had a better underlying liver function (97% of Child-Pugh Grade A), lower rate of cirrhosis (56.1%), fewer underwent major surgery (20.1%), and the majority was operated in high volume centers (77.9%).The main characteristics of the two cohorts are summarized in The ability of CDC and CCI to measure postoperative morbidity was evaluated in terms of association with postoperative LOS and e-LOS. 2 and lower RMSE, also in the validation set. Larger differences between the performance of CCI vs. CDC models were observed in the subset of patients with at least two complications  change, per 10 units of CCI increment, was 0.27 (95%CI: 0.25–0.28), corresponding to an average 31% increment of LOS, while for category increment of CDC it was 0.29 (95%CI: 0.27–0.31), corresponding to an average 34% increment of LOS. The goodness of fit of the CCI model was slightly superior to the CDC model as indicated by the higher Rications .The coefficients of all covariates included in the linear models are shown in At the multivariate logistic regression for e-LOS in the derivation set, the odds ratio for 10 units of CCI increment, was 5.60 (95%CI: 4.20–7.44) vs. 5.51 (95%CI: 4.15–7.30) for CDC category increment with a moderately higher discriminatory ability for the CCI model even in the validation set (AUC = 0.893 for CCI vs. 0.890 for CDC). CCI showed an even higher ability to discriminate patients with e-LOS than CDC in the subset of patients with at least two complications . The oddThe performance of CCI, evaluated by the ROC curve methodology, to identify—amongst patients with at least one complication—those with e-LOS is reported in This was confirmed even when subgroups were analyzed, although slightly different cut-points were found .In grading a complicated postoperative course, the CDC scoring system  accountsA comparison of the two scoring systems has been already applied in several studies investigating broad case-mix and heterogeneous populations ,18,19,20The present study advocates that both CCI and CDC scoring systems perform well in predicting the duration of hospitalization after liver resection for HCC. However, CCI was slightly superior to CDC in predicting both overall LOS and e-LOS in complicated patients, in both the derivation cohort and in the validation one. In the validation set there were less cirrhotic patients, less CDC 0, longer LOS, less laparoscopic cases, and less anatomical resections but more high-volume centers. Center volume has been repeatedly described as a variable affecting morbidity. Since we conducted a multi-institutional study, we randomly assigned centers to the validation or the derivation cohort to limit this bias. However, the two cohorts were partially not homogeneous. Hence, all multivariate models were adjusted for several confounders including center volume.Although the overall difference within metrics performance was marginal in the overall sample, the association between CCI and LOS held stronger than CDC especially in the subset of patients with at least two complications. This suggests that CCI better captured any event affecting longer hospitalization. These statements are supported by the results of the linear regression analysis showing that the CCI models were always slightly better than the CDC models. Similarly, the multivariate logistic regression analysis suggested that the areas under the ROC curves of the CCI models were always greater than the CDC models suggesting that CCI had a better ability to discriminate patients with longer LOS. Therefore, the overall findings imply that CCI is a more accurate system in grading the morbidity burden, eventually affecting the duration of hospitalization.It can be argued that our results indicate a marginal advantage of CCI over CDC in predicting LOS and e-LOS in complicated patients. This can be partially explained by the low proportion of patients who experienced at least two complications (14.2%). Accordingly, when more than 85% of the population has no or only one complication, the two scores overlap by definition and so the comparison is futile . For thiDespite the slightly better performance of CCI, this metric has some hindrances in predicting e-LOS. In fact, CCI was not evenly distributed through the scale and the dissemination tends to cluster in values embodying each grade of CDC for patients facing only one adverse event. Moreover, in patients with a postoperative course characterized by more severe complications (CDC > II), a wider spectrum of CCI values was present. This might be because severe complications are often coupled with additional minor ones. Otherwise, low-grade complications may not necessarily prolong hospitalization. Similar uneven CCI distribution has been described by Kim et al.  in a serThe ROC curve analysis of CCI for complicated patients with e-LOS found a score of 22 as the optimal cut-point for defining patients who experienced a delayed hospital discharge. Thus, this CCI cut-off value can be used to dichotomize the study population into low- and high-risk of having e-LOS. A CCI score greater than 22, would mean that a patient had at least two minor complications, according to CDC , or a major one (CDC ≥ III). The CDC grade IIIA—which often defines “major” or “severe” morbidity —correspoFew authors compared the performance of CCI and CDC in other homogeneous surgical procedures, namely, gastrostomies, intestinal resections, cystectomies, liver transplantations, esophagectomies and pancreatectomies ,28,29,30The retrospective study design implies several drawbacks. First, the duration of hospital stay in absence of a priori definition of discharge criteria, may be affected by social and logistic factors, and by the confidence of a single patient to go home safely. However, since there is no gold standard for measuring clinical outcomes and comparing clinical implications of different complication grades, we considered LOS as a surrogate marker for surgical outcome, as in other studies ,20,26,27Even if both scales performed well in predicting LOS and e-LOS of patients undergoing liver resection for HCC, CCI was moderately superior to CDC. The results of this population-specific analysis suggest that CCI is preferable in reporting postoperative morbidity even though CDC metrics maintain acceptable accuracy.


A recent study showed that chiropractic patients had fewer days with bothersome (activity-limiting) low back pain (LBP) when receiving care at regular pre-planned intervals regardless of symptoms  compared to receiving treatment only with a new episode of LBP. Benefit varied across psychological subgroups. The aims of this study were to investigate 1) pain trajectories around treatments, 2) recurrence of new episodes of LBP, and 3) length of consecutive pain-free periods and total number of pain-free weeks, for all study participants as well as for each psychological subgroup.n = 319) seeking chiropractic care for recurrent or persistent LBP used 52 weekly estimates of days with bothersome (activity-limiting) LBP. First, a generalized estimating equations analysis was used to compare the pain trajectory before and after the initial treatment in every new treatment period. Thereafter, a time-to-event analysis (using Cox regression) estimated time to/risk of a new LBP episode. The analyses were performed on i) all study participants and ii) separately for each psychological sub-group  classified by the West Haven-Yale Multidimensional Pain Inventory.A secondary analysis of data from a randomized controlled trial of patients  compared to the control group. There were no differences in the time to/risk of a new episode of LBP in either of the subgroups.Data support the use of MC in a stratified care model targeting dysfunctional patients for MC. For a carefully selected group of patients with recurrent and persistent LBP the clinical course becomes more stable and the number of pain-free weeks between episodes increases when receiving MC. Understanding how subgroups of patients are likely to be affected by MC may help align patients’ and clinicians’ expectations based on realistic outcomes.NCT01539863; February 22, 2012.Clinical trials.gov;  Low back pain (LBP) is a recurrent and persistent non-communicable condition ranked highest in in the world in terms of disability and resulting in a major societal burden , 2. Secon = 163) reported 12.8  fewer days with activity limiting LBP compared to the control group (n = 158) and received 1.7  more treatments.Manual treatments performed by chiropractors have been found to be effective in reducing pain intensity and disability for patients with LBP and are recommended in current practice guidelines , 9. AbouIn a secondary analysis of the data from the RCT it was found that psychological sub-groups defined by the Swedish version of the West Haven-Yale Multidimensional Pain Inventory (MPI-S) could identify responders and non-responders to MC .The MPI-S is a comprehensive patient-reported screening instrument based on the cognitive behavioral model which was developed to capture and measure the experience of chronic pain . The SwePatients who were classified as dysfunctional reported statistically and clinically significantly fewer days with bothersome (activity-limiting) LBP  in the MC group compared to the control group. On the other hand, patients who were classified as adaptive coper reported a worse outcome where the number of days with bothersome (activity-limiting) LBP was higher  in the MC groups even though they received a greater number of treatments  compared to the control group. There is now compelling evidence that stress the importance of careful the selection of patients for MC to include those who have recurrent or persistent low back pain, a dysfunctional psychological profile and a good initial response to manual therapy.It is imperative that we undertake research and implement preventive strategies with clear and precise definitions of target populations and disease states. The definition of new episodes for a recurrent disorder such as LBP requires a clear definition of ‘recovery’. De Vet et al. suggested that an episode of LBP should be defined as at least 24 h of pain with at least four pain-free weeks before and after . The preThe optimal dose of treatments for the long-term management of recurrent and persistent LBP has not been established. In fact, we are not sure whether the effect of MC is a matter of dose (a higher number of visits yielding a reduction of pain irrespective of when the visits occur) or timing (preventing the number of episodes or reducing the number of days within each episode by timing the treatment before or in the early stage of the new event). If the effect of MC is related to the timing of visits, patients who consult at different stages in their long-term pain trajectory and pain around the treatments would have different outcome profiles (i.e. MC treatments should take place before the recurrence of pain and control treatments after the recurrence of pain). The previous secondary analysis of these data, which considered outcome in relation to psychological sub-groups , suggestThe pain trajectory before and after a single visit or the first visit in every new treatment period.The time to and risk of a new episode following the first recovery period.The length of consecutive pain-free periods and total number of pain-free weeks during the study period.The overall aim of this project was to explore how MC affects the bothersome (activity-limiting) LBP around treatment periods, new episodes of LBP and pain-free periods between episodes as compared to patients receiving care when experiencing a symptomatic relapse. The specific objectives were to compare the following for i) all participants in the trial as well as the ii) psychological subgroups defined by the MPI-S instrument:This study is a secondary analysis of data from a pragmatic, multicenter, investigator- and assessor- blinded randomized controlled trial with a two-arm parallel design –24. The Patients with recurrent and persistent LBP, who had responded favorably to an initial course of chiropractic care, were recruited in a consecutive sequence between 2012 and 2016 from chiropractic clinics that were part of a nationwide practice-based research network in Sweden. Patients were screened in a three-stage procedure, i.e. at the first visit (baseline 1), the fourth visit (baseline 2), and at study start (baseline 3). See Table One of the key components and inclusion criterion of the trial was to select patients who reported clinical benefit from chiropractic care during the initial treatment. Initial clinical benefit was assessed at the 4th visit using the global perceived improvement scale . If the patients stated that they were “definitely improved” by the fourth visit, initial clinical benefit was considered evident. Previous research has shown that using the global perceived improvement scale in this way can predict a favourable long-term outcome from chiropractic care at 3, 6, and 12 months –37. AccoOnce patients were screened at the 3 baseline steps and considered candidates for the study, they were invited to partake in the study and asked to sign an informed consent form with information about the trial. It was also made clear to patients in the written information that they were free to withdraw from the project at any point without detriment to their relationship with the clinician.The MC group received regularly scheduled treatments, 1–3 months apart during the 52 weeks of follow-up. If the patient had a relapse of pain, a more intense period of visits was scheduled until the patient once again was suitable for a MC plan. The control group was instructed to seek care only if they experienced a symptomatic relapse. In such cases a period of frequent visits would be scheduled until maximum benefit was reached, after which the patients were again instructed to seek care if the LBP reoccurred. Content of care within the two treatment arms were similar, consisting of spinal manipulation, information/advice and soft tissue treatment, as was the level of attention given to the patients [The two arms of the trial have been described as MC  and control . patients . Both grA statistician at Karolinska Institutet generated 40 permuted blocks of 10 participants with a 1:1 allocation ratio according to a randomization schedule. Each clinician received 10 opaque, sealed envelopes containing information about the procedure the patient had been randomly allocated to. The envelopes were opened in front of the patient at the initial visit of the study. Clinicians were instructed to inform patients that 1) the two treatment arms were different procedures currently being used in practice, and 2) there was no evidence to suggest that one strategy was more effective than the other .“On how many days during the past week were you bothered by your lower back (i.e. it affected your daily activities or routines)? Please answer with a number between 0 and 7”. If the patient failed to respond to the weekly SMS, an automatic reminder was sent after 48 h. If the patient failed to respond after 2 weeks, a research assistant called the patient to answer any concerns that may have caused the patient not to respond.The primary outcome of the trial was number of days with bothersome (activity-limiting) LBP. It was recorded weekly using an automated text message system (SMS-track®) –40 that At follow-up the chiropractor filled in a questionnaire where they were asked to review each patient’s clinical record and document the dates of all visits during the study period. This information was then used to model the trajectory analysis.pain-free week was classified as a week with ≤1 day with activity-limiting LBP in the time-to-event analysis. The classification of pain-free weeks as “≤2 days with bothersome (activity-limiting) LBP” instead of “<2 days with bothersome (activity-limiting) LBP” minimized the risk of misclassification of weeks with temporary short (< 24 h) exacerbations of LBP as episodes. Thus, a new pain episode was defined as a week with ≥2 [To apply the definition by de Vet et al. . as clos with ≥2  days of treatment-period was defined as a single visit or as the first of a series of visits with an interval of ≤2 weeks apart, followed by ≥3 consecutive weeks without any visits to the chiropractor (1 month between visits). MC visits were scheduled 1–3 months apart according to the normal procedures used in clinical practice [A practice  as reporpractice . The defpractice . In the pain-trajectory was defined as “the number of days with bothersome (activity-limiting) LBP per week, during a 7-week period around the week of a single visit or the first visit in a new treatment period” (3 weeks before and 3 weeks after the treatment). The trajectory (mean number of days with pain) for each of the 7 weeks for all single visits or new treatments periods for per group was estimated.A The MPI-S subgroups have been extensively described in the previous publication, which reported the sub-group evaluation of effect of MC . PatientThe data from the RCT was analyzed with an intention to treat analysis. Estimates in this study were reported with arithmetic means and 95% confidence intervals. Only individuals who had > 12 weeks of complete SMS data and follow up data for number and dates of visits were included in the analyses.p < 0.20 were considered for the regression model. The best model structure was further decided based on goodness of fit values . All remaining variables in the final models, chosen based on the best goodness of fit, ended up with significance levels of p < 0.05. Data were also analyzed using a Mixed Model framework. The results of the two procedures were very similar; GEE was chosen rather than the mixed model framework because of its ease of use. Results were presented in graphs, with lines representing mean values and estimated group differences for each week of days with bothersome pain, illustrating pain trajectories for the control and intervention groups.Data relating to the first objective were analyzed in a longitudinal model which looked at the pain trajectory around the initial visit of each treatment period. Mean number of days with bothersome (activity-limiting) LBP was calculated for each group and for each week during the 7-week treatment period . If two visits were separated by 3 weeks without visits , the analysis would then double count the last 3 weeks –7 in theData relating to the second objective of this study were analyzed in a time-to-first event model using Cox regression in a survival analysis, estimating the Hazard Ratio of experiencing new LBP episodes. Only individuals who initially reached a recovered state (≥4 consecutive weeks free from bothersome LBP), were included in the Cox regression.In the third objective, differences between groups for i) time-to-event and ii) length of consecutive pain-free periods and total number of pain-free weeks were tested using ANOVA.Data were analyzed for all participants , in linAs previously reported, 321 participants were randomly allocated into the two study groups after the initial inclusion procedure . During Two hundred and fifty-four participants had at least one treatment and could be included in the longitudinal pain trajectory analysis. A total of 1103 treatment-period sequences were identified during the 12-month study period  and were used for the analyses. In all, 250 participants reached at least one recovered state and could be included in the time-to-first-event analysis.The trajectory analysis captured a sample with fewer females than the samples in the total and the survival analyses. There were also somewhat fewer individuals classified as adaptive copers in the control group for the trajectory analysis than for the total and the survival analyses. Other than these differences the samples across analysis groups and across treatment groups were similar. Descriptive data for the participants included in each analysis are reported in Table The pain trajectories around the visits were different for the two treatment groups, when all participants were included. The control group showed a steeper increase of pain during the weeks prior to the visit and reached the highest number of days with pain in the week of treatment, when the largest mean difference between groups can be seen (0.46 bothersome (activity-limiting) days with LBP per week; 95% CI =0.16, 0.76). The MC group had a less dramatic trajectory, reporting fewer days with bothersome (activity-limiting) LBP compared to the control group. The pain trajectory for all participants is reported in Fig. In the adaptive coper and interpersonally distressed subgroups the estimates across the seven measurements were similar, with no apparent difference between the control and MC groups with regards to their LBP trajectories. The trajectories for adaptive coper and interpersonally distressed subgroups are shown in Figs. The LBP trajectory for the dysfunctional subgroup demonstrates great differences between treatment groups throughout the treatment period, with the largest mean difference around the visit . Like the analysis with all participants, the control group had a steep increase in LBP up to the week of the treatment and a decreasing trend after the visit; in comparison the MC group had a flat trajectory. The LBP trajectory for the dysfunctional subgroup is reported in Fig. In Supplementary Material There were no mean differences between treatment groups in the Hazard Ratio of new episodes or time-to-event in any of the analyses . Results are reported in Table There were no differences between treatment groups in the mean length of pain-free periods or in the mean total number of pain-free weeks when all participants were included in the analysis. When the data were stratified according to the MPI-S subgroups, MC resulted in 9.8 CI95% 3.3, 16.3) more pain-free weeks (mean) compared to control in the dysfunctional sub-group during the 12-month study period. In the adaptive coper and interpersonally distressed sub-groups the mean differences were small and uncertain . The results are reported in Table .3, 16.3 This study is the first to investigate how patients benefit from MC using an in-depth analysis of the clinical course of LBP. It answers questions about how MC affects the number of days with bothersome (activity-limiting) LBP over time by exploring the trajectory around the visit to the chiropractor, the time to and risk of new episodes, and length of pain-free periods .We found that patients receiving MC had flat LBP trajectories around each new treatment period, as their appointments were unrelated to their symptoms, as opposed to the control group, who were encouraged to call in ‘when needed’. The MC group also had fewer days of bothersome (activity-limiting) LBP than patients receiving the control intervention, who demonstrated more acute episodes.However, in the adaptive coper and interpersonally distressed groups there were no differences for any of the reported outcomes and the entire difference between MC and control groups was attributed to the dysfunctional subgroup. In the dysfunctional subgroup, there were no differences in the time to/risk of first new episode although MC patients reported more pain-free weeks than the control group. In other words, the clinical course was stabilized by reducing the number of days with LBP per week of each new episode and by increasing the total number of pain-free weeks in the dysfunctional group. As the number of days with bothersome LBP has been shown to correlate with pain intensity , it is lThe use of weekly SMS with exceptionally few missing data points allows for a detailed analysis of the LBP trajectories with a low risk of recall bias. Therefore, the data used in this trial can be considered robust and of high quality. The inclusion procedure and execution of the MC protocol have been carefully designed to incorporate all the available evidence in the field and to mimic the procedure used in clinical practice as closely as possible. The multi-center pragmatic design with clinics distributed across the country and a high number of involved clinicians allows us to generalize the results to normal clinical practice within the Nordic countries. Although it has been used previously in several trials, measuring the number of days with bothersome (activity-limiting) LBP is novel. A limitation with regards to the clinical relevance of the findings is the lack of knowledge of the exact properties of the primary outcome  concerning how it correlates with other health measurements (other than pain intensity). However, the benefit of the measurement is that it reports only the kind of pain that is relevant to the patient. Another potential concern is the way we have classified LBP episodes in this study, which may result in a risk of systematic error that could have underestimated the length and prevalence of LBP episodes. It is known that LBP has a highly individual trajectory and often fluctuates over time rather than being constantly present , 44. We not receive MC as it worsened their situation [This study demonstrated that, among dysfunctional patients, MC reduced the number of days of activity limiting LBP in each new episode and people enjoyed more pain-free weeks. At most, the mean difference among dysfunctional patients was 0.86  fewer days with pain in each new episode while also enjoying 9.8  more pain free weeks, resulting in a total of 30.0  fewer days with pain for the entire 52 week period . These eituation . It is tIrrespective of the mechanism is seems that the effectiveness of MC among dysfunctional patients could depends on the timing of visits to the chiropractor, i.e. independent of pain ideally before or early in a new episode. If this is an important part of the mechanism, patients with regular LBP episodes could be more successfully scheduled according to a structured MC program because of improved precision in the timing of treatments due to predictability of the pain trajectory. If this rationale holds true these patients may benefit most from the intervention through a reduction of the impact of the most severe periods of pain, perhaps reducing the risk of sick leave, presenteeism and limitations on the activities of daily living.However, at this point in time the mechanisms behind MC are unknown and remain a question for future projects. Future research should therefore focus on replicating the findings from this trial and understanding why MC has a positive effect on dysfunctional patients but appears to have the opposite effect for adaptive copers. A suitable approach would be to conduct an RCT on dysfunctional patients, randomizing them to a chiropractic maintenance care program or a program consisting of psychological support, advice and reassurance to tease out if it is mainly the physical component of the treatment that ‘works’ or if it is the psychological component that is responsible for this outstanding result. Another important avenue for future research relates to health economic evaluations of MC to better understand and model the societal consequences of MC. To establish if the procedure is cost-effective is imperative for policy makers and health care funders and a key component when implementing the procedure on a large scale.The message for the patient should be that MC is not a cure that prevents new episodes but rather a management strategy that may reduce bothersome (activity-limiting) LBP over time for a carefully selected group of patients with a dysfunctional profile. Patents who adapt well to their pain, who experience only little interference, have an active lifestyle and do not experience high levels of distress are not suited for MC and should be cared for on an episode to episode basis. Such a message could potentially align expectations to realistic outcomes and may result in a higher degree of trust and a more effective therapeutic alliance between the clinician and the patient, both of which are important for a successful treatment outcome –48.Chiropractic Maintenance Care reduces the number of days of bothersome (activity-limiting) pain within each new LBP episode among patients classified as dysfunctional (by the MPI-S instrument). MC stabilizes the clinical course and increases the number of pain-free weeks between episodes. Understanding how subgroups of patients are likely to be affected by MC may help align patients’ and clinicians’ expectations with realistic outcomes and can be used as a framework in the selection and execution of appropriate care plans. MC is not a cure that prevents new episodes but rather a management strategy that reduces bothersome (activity-limiting) pain over time for a carefully selected group of patients with recurrent and persistent LBP.Additional file 1. Pain trajectories around visits, difference in mean (adjusted) number of days with bothersome pain between groups .


Caregivers’ responses to pain behaviors of patients with chronic pain have an essential role in how patients perceive their pain condition. The current study investigated the mediating role of pain catastrophizing on the link between perceived caregiver responses and patient pain behaviors.The sample of this cross-sectional study consisted of 200 patients with chronic pain . Participants responded to measures assessing their perception of their caregiver responses to their pain, their pain catastrophizing thoughts, and their pain behaviors.The mediation analyses showed that perceived distracting responses were negatively related to pain catastrophizing level in patients, which in turn was positively associated with expressing pain behaviors. Besides, perceived caregiver negative responses were positively associated with catastrophizing thoughts, which in turn was positively related to expressing pain behaviors.Patients’ perceptions regarding how their caregiver responds to their pain condition can be related to their thoughts about their pain and how they react to their pain situation. Investigating the external sources that might have an impact on patients’ reactions to their pain, especially when those external sources are caregivers who, in most situations, are with the patients for a prolonged duration, is essential. Chronic pain resulting from musculoskeletal conditions never occurs in isolation. Studies on chronic pain have been shown that family factors, including the relationship with other family members and their reactions to pain, have substantial impacts on pain intensity and pain-related disability . ChronicTo understand the patients’ pain-related experience, family caregivers may rely on pain behaviors. Pain behaviors, such as distorted walking, aim to reduce pain intensity or prevent further injury . Howeversolicitous responses that demand patients to take rest or stop their current activities may convey the notion to patients that there is a serious threat and therefore increase the pain catastrophizing thoughts  perceiving more caregivers’ solicitous responses is related to higher levels of pain catastrophizing in patients. In turn, higher pain catastrophizing is related to more pain behaviors; (2) perceiving more caregivers’ distracting responses is related to lower levels of pain catastrophizing in patients. In turn, lower levels of pain catastrophizing are related to fewer pain behaviors; and (3) perceived more caregivers’ negative responses are related to higher levels of pain catastrophizing in patients. In turn, higher pain catastrophizing is related to more pain behaviors. The data were collected from four physiotherapy clinics in Esfahan, Iran. Nurses and front desk staff at these clinics identified the eligible patients and notified one of the researchers who were present at the clinic (FA) and also invited the patients to participate in the study. First, the researcher explained the study and checked the eligibility of the patients. Inclusion criteria were having musculoskeletal pain on most days for at least 3 months, being over 18 years of age, fluent in reading and writing in Persian, having at least one caregiver, and living with their caregiver. Exclusion criteria were declaring a medical history of major psychiatric disorder, concussion, or head injury, and declaring current drug and alcohol abuse. Furthermore, patients with other illnesses and disorders who experienced pain as one of their symptoms such as patients with cancer, AIDS, shingles, stomach ulcers, and nerve damage were excluded due to the difference in the causes and symptom presentations of these disorders with the causes and symptom presentations in chronic musculoskeletal pain disorders. Two-hundred and fifty patients were eligible to participate in the study. Twenty patients did not agree to participate in the study. The main reasons were that they declared intense pain, and they did not seem in good health to fill out the questionnaires. Twenty-three patients returned the questionnaires without answering the questions. Seven patients fill out <40% of the questions. Therefore, their data were removed from the final dataset. Finally, the data of 200 patients were analyzed.All participants declared consent before participating in this study. The study was approved by the Psychology Department’s Research Ethics Board.Patients reported sex, age, duration of pain, usage of analgesic medicines, and pain location .To assess perceived caregiver responses, the significant other section of the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) was used . This sePain behaviors were measured by the Pain Behavior Checklist . The PBCL had 17 items . Patients reported the estimation of their pain behaviors on a seven-point Likert-type scale . A higher average score showed higher levels of pain behaviors. It was shown that the PBCL has acceptable reliability and validity . In the To assess pain catastrophizing of patients, the Pain Catastrophizing Scale (PCS) was used . The PCSc and composed of the direct effect of the independent variable on the dependent variable (weight c’) and the indirect effect of the independent variable on a dependent variable through a denoted variable (weight ab). In addition, the effect of an independent variable on a defined mediator was presented by weight a. Lastly, weight b expressed the effect of a denoted mediator on a dependent variable while excluding the effect of the independent variable. In the mediation analyses, we used a bootstrap test  to assess the significance of the indirect effect  should be significant to be able to calculate the indirect effect  is not a prerequisite for mediation analysis. Therefore, even when the total effect is not significant, but the indirect effect (path ab) is significant, it is still valid to call the observed indirect effect, a mediating effect (c′) and indirect effect (ab). Therefore, in some cases, when the direct effect is positive and indirect effect is negative (or the other way around), they would neutralize each other, and the total effect will potentially become non-significant; (b) the traditional step approach to calculate mediation analyses indicated that step 1 for conducting a mediation analysis is calculating the association between X and Y. Based on the traditional model, if no association is found in step 1, the mediation analysis should be stopped. However, currently, statisticians consider this step as illogical because there are many new approaches to calculate the indirect effect directly .It should be noted that based on the traditional view of mediation analyses, total effect  and the rest  were male. The mean age of the patients was 44.6 years (SD = 13.8). The average duration for pain was 61.21 months (SD = 72.9). About half of the patients were taking analgesic medicines (61.5%). The current study asked patients to specify their relationship with their caregivers. Almost half of the caregivers were spouses . Thirty-five percent of patients identified their daughters as their caregiver (n = 70). Ten percent of patients (n = 20) identified their mothers as their caregivers , 3.5% of the patients identified their sons as their caregivers (n = 7), 3% (n = 6) indicated that their sister is their caregiver, and 2% (n = 4) identified other family members  as their caregiver. In addition, based on patients’ report, 71.5% (n = 143) of caregivers were women and 28.5% (n = 57) were men. In addition, the mean age of caregivers was 37.0 (SD = 13.3). Six percent of the patients (n = 12) had back pain, 8.0% (n = 16) had pain in legs, 16.0% (n = 32) experienced pain in knees, 2.0% (n = 4) had pain in neck, 7.5% (n = 15) experienced pain in two locations, and 60.5% (n = 121) had pain in more than two locations.Our samples consisted of 200 patients with chronic musculoskeletal pain. About two-thirds of the patients were female . Besides, caregiver perceived distracting responses and patient pain catastrophizing were significantly but negatively correlated (p < 0.05). Finally, there were significant and positive correlations among perceived caregiver negative responses, patient pain behaviors, and patient pain catastrophizing (p < 0.01). Specifically, the results of the Pearson correlation analyses showed that caregiver perceived solicitous responses and pain behaviors of patients were significantly and positively correlated (c) was significant, F = 0.594, p < 0.001, R2 = 0.002. The direct effect of perceived caregiver solicitous responses on patient pain behaviors (weight c’) was also significant . However, the indirect effect (weight ∗ba) did not reach a significant level , showing the lack of significant mediation role of patient pain catastrophizing in the link between perceived caregiver solicitous responses on patient pain behaviors.Results showed that the total effect of perceived caregiver solicitous responses on patient pain behaviors (weight c) was not significant, F = 6.01, p > 0.001, R2 = 0.032. The direct effect (weight c′) did reach to a significant level . Importantly, indirect effect (weight ∗ba) was significant , indicating a significant mediating effect of patient pain catastrophizing on the relationship between perceived distracting responses on patient pain behaviors. This indicates that perceiving distracting responses from caregivers were negatively related to pain catastrophizing in patients ; in turn, pain catastrophizing was positively related to expressing pain behaviors .The total effect of perceived caregiver distracting responses on patient pain behaviors (weight c) was significant, F = 22.416, p < 0.001, R2 = 0.113, and the direct effect of perceived caregiver negative responses on pain behaviors (weight c’) was not significant . In addition, the indirect effect (weight ∗ba) was significant , indicating that patient pain catastrophizing plays a mediating role in the association between perceived caregiver negative responses and pain behaviors. This analysis indicates that perceiving the caregiver’s negative responses was positively related to expressing pain behaviors ; in turn, pain catastrophizing was positively related to expressing pain behaviors . Analyses showed that the total effect of perceived caregiver negative responses on pain behaviors  and pain behaviors in patients with chronic pain. Our findings showed that perceived distracting response from caregivers is negatively related to lower levels of catastrophizing thoughts in patients, which in turn is positively related to expressing pain behaviors. This means that higher levels of perceived distracting responses from caregivers are related to a decreased level of pain catastrophizing thoughts in patients, which in turn is related to a decreased level of expressed pain behaviors. Interestingly, perceived more negative response from caregivers is related to higher levels of catastrophizing thoughts, which in turn is related to expressing more pain behaviors. We did not find any mediating role for pain catastrophizing in the relationship between perceived caregiver solicitous responses and expressed pain behaviors.The current study showed that the relationship between perceived caregiver distracting responses and patients’ pain behaviors is mediated by patient pain catastrophizing. Specifically, it was found that higher levels of perceived caregiver distracting were related to lower levels of pain catastrophizing in patients, which were related to fewer pain behaviors in patients. This is in line with the nature of caregiver distracting responses, which aim to distract the patient’s attention from the pain and help them to engage in another activity . It has The results also showed that perceived caregiver negative responses are related to higher levels of pain catastrophizing, which in turn is related to expressing more pain behaviors. This is similar to the findings of other studies that found negative responses by caregivers are associated with more negative outcomes in patients with chronic pain, including anxiety , depressAdditionally, in this study, it has been observed that while perceived caregiver solicitous responses were slightly and positively related to expressing pain behaviors, they were not related to pain catastrophizing, and pain catastrophizing did not mediate the link between perceived caregiver responses and pain behaviors. These results are partially in line with the studies that have shown that caregivers’ solicitous responses are positively associated with expressing more pain behaviors and, consequently, higher levels of disability . HoweverWhen interpreting the result of this study, some limitations need to be taken into account. First, this study is only based on patients’ perceptions of their caregivers’ responses. While it is the patients’ cognitions and perceptions of their caregivers that impact their responses and behaviors than how caregivers respond to them, it is still important to investigate the responses to pain behaviors based on caregivers’ reports. Future studies may benefit from the comparison of patients’ understanding of caregivers’ reports and caregivers’ reports. Second, this is a cross-sectional study, and therefore, it is impossible to assess the causal effect. Third, we set limited inclusion and exclusion criteria to prevent problems associated with the selective sampling of participants, but it resulted in heterogeneity in data and influenced the generalizability of the findings. Future studies are advised to be more exclusive in inclusion criteria to improve the generalizability. Besides, only participants with chronic musculoskeletal pain were recruited in this study, which might limit the generalizability of the findings to patients with other types of pain . Finally, some factors, such as relationship quality, have not been investigated in this study, which can play an important role in understanding how caregivers’ responses impact patients’ cognitions.Despite the above-mentioned limitations, this study has an important clinical implication. The results show that patients’ perceptions of their caregivers’ responses impact their cognitions and also related to how they express their pain. Therefore, when it comes to pain treatment and developing interventions for these patients, it is important to evaluate these perceptions and invite the caregivers to the intervention sessions to help the caregivers understand the meaning and impact of their responses on their patients with chronic pain. Besides, helping patients to have a better understanding of how external sources can impact their thoughts and behaviors can also increase the level of control over their pain management and pain coping strategies.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by the ethics committee of the Department of Psychology at Shahid Beheshti University. The patients/participants provided their written informed consent to participate in this study.SM was involved in analysis and writing. FA was involved in data acquisition, analysis, and writing. NE was involved in data acquisition and writing. MD and AK were involved in the design, data acquisition, analysis, and writing. 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.


The analgesic consumption between arms was statistically significantly different. A median of the proportion of days when the patients used analgesics was 8% and 32.5% during radiotherapy (p = 0.047) and 0% and 20.8% during three months after radiotherapy (p = 0.006) for the acupuncture and control arm, respectively. Results point out lower analgesic consumption and milder pain in acupuncture arm. Acupuncture consequently offers another alternative to standard treatment leading to a reduction in the toxicity of oncological treatment.This prospective randomized open-label trial aimed to evaluate the role of acupuncture in the treatment of pain related to curative and adjuvant (chemo)radiotherapy of head and neck cancer. Patients in two arms (30 patients in each arm) underwent standard oncology therapy and standard supportive care with or without acupuncture. The stratification factors were the type of treatment and chemotherapy indication. The toxicity assessed was represented by pain rated on a 10-point pain scale and analgesic use. Average pain (AP) and the worst pain during the day (WP) were significantly lower in the acupuncture arm during radiotherapy (AP median 0.16 vs. 1.36,  The treatment of head and neck cancer is very challenging. The main methods used in curative therapy of head and neck cancer include surgery and radiotherapy or chemoradiotherapy ,2,3. RadThe use of acupuncture in the treatment of pain in cancer patients has proven useful in several studies ,8. The pWe conducted a single institutional prospective open-label randomized study (NCT03751566) focused on the use of acupuncture as a treatment modality for adverse effects of radiotherapy or chemoradiotherapy in patients with head and neck cancer . The stuThis article presents the results of the assessment of pain grade during oncologic treatment and the usage of analgesics. The study also evaluated other acute side effects , the consumption of antiemetics and chronic toxicity. The results of these evaluations will be part of other separated reports.This prospective single-institution study was conducted in the Masaryk Memorial Cancer Institute in Brno, Czech Republic. The study duration was two years; patients with head and neck cancer indicated to curative or adjuvant radiotherapy were enrolled from March 2016 to June 2018. A total of 439 patients was evaluated for eligibility. Inclusion criteria were age > 18 years, Karnofsky performance status over 60%, physical and intellectual ability (as assessed subjectively by the investigator) to manage the therapy diary for toxicity records. Exclusion criteria were enrollment in another clinical trial and palliative intent of the treatment with a lower prescribed dose of RT. Sixty-two eligible patients agreed with enrollment. The patients were randomized to control or intervention arm by permuted stratified block randomization (block size 4). The stratification factors included the type of RT (curative/adjuvant) and the application of concurrent chemotherapy (yes/no). Two patients randomized into the control arm changed opinion with participation in the study immediately after randomization, were excluded and replaced by others to achieve a total number of 60 participants. A CONSORT diagram detailing patient flow is presented in All patients finished the treatment as planned according to the protocol. No deaths or serious adverse events were reported during the study. Two patients (one in each randomized arm) were lost from follow-up and did not have any control examination after the termination of treatment.The primary endpoint was reducing acute toxicity in acupuncture arm assessed from the perspective of pain with the pain level on the Likert scale (see below) as the endpoint. Reduction of usage of analgesics and antiemetics, acute toxicity of nausea, skin and mucous membrane, and chronic toxicity were secondary outcomes.Clinicaltrials.gov accessed on 6 March 2021—NCT03751566.Trial Registration: The patients in both arms underwent standard treatment. It included curative or adjuvant radiotherapy with concurrent chemotherapy in some patients. According to the nature of treatment and the risk factors involved, radiotherapy of up to 60–70 Gy was applied. A single dose was either 2 Gy or 1.6 to 2.12 Gy when a simultaneous integrated boost technique was applied. The whole treatment usually lasted 6–7 weeks. Radiotherapy was administered via a linear accelerator using the RapidArc dynamic delivery technique.2) or on days 1, 22, and 43 (100 mg/m2). Two patients in whom cisplatin was contraindicated had a regimen with weekly-administered carboplatin (AUC 1.5). Two patients received radiotherapy with concomitant targeted therapy cetuximab.Chemotherapy was administered to selected patients (10 in the acupuncture arm and 8 in the control arm) upon the assessment of risk factors. The most common concomitant chemotherapy regimen was cisplatin administrated weekly —diagnostician TCM + one-year course, The science of acupuncture points and pathways at the Academy of TCM in Brno; one-year course, basic course of acupuncture in Institute for Postgraduate Medical Education in Prague; finished with an exam and received a certificate). As per the study protocol, it was initiated upon the first symptoms of toxicity of the oncologic treatment. During radiotherapy, acupuncture was applied 1–3 times per week, usually twice per week for 10–20 min. After the end of the radiotherapy period, acupuncture was applied usually once in 14 days over the period of 1–2 months, in some patients only once a month. After the end of radiotherapy, the frequency of acupuncture application depended on the stage of development of acute toxicity and the patient’s ability to attend the application. The application was individualized; at the beginning of each acupuncture session, the evaluation of radial pulses and the tongue was done to identify appropriate acupoints; points LI4, LU7, ST36, KI7 were mostly included. A whole-body acupuncture approach was applied, except for the irradiated skin, including ear acupuncture.Two pain parameters were assessed: average pain during the day and the worst pain during the day. The patients rated their pain and recorded it in their toxicity diaries using a 10-point pain scale , where 0 was no pain, and 10 was the worst pain the patient could imagine. Patients filled in the toxicity diary daily or when the condition changed.Patient and treatment characteristics were described using standard summary statistics, i.e., median and interquartile range (IQR) for continuous variables and frequencies and proportions for categorical variables and differences between arm were compared using Fisher exact test or Mann–Whitney test as appropriate. Due to the comparability of the toxicity progression between individual patients, particularly considering the different lengths of RT, time was rescaled to a uniform scale. The timeline is expressed in percentages during RT period or days during three months following the termination of RT. The area under the curve (AUC) of the time course of toxicity was calculated for each patient and standardized on a unit scale. The AUC value shows the average toxicity for each patient per unit of time, i.e., one percent of the RT period or one day after the end of RT. The toxicity parameters were evaluated separately in some critical moments of the treatment and post-treatment period—the start, the mid-point, the three-quarters and the end of RT, 14 and 30 days after the end of RT. The analgesics’ usage was evaluated using the proportion of patients receiving analgesics at a considered moment. The statistical comparisons between control and acupuncture arms were accomplished by the Mann–Whitney test and displayed using box plots. All statistical analyses were performed employing R version 4.0.2 , and a sp = 0.026). In the control arm, the majority of patients were current or former smokers (83%). In the acupuncture arm, patients with advanced cancer stage slightly predominated (p = 0.088). The occurrence of different severity types of comorbidities was similar in both treatment arms. Demographic and treatment characteristics of study patients are summarized in A total of 60 patients was enrolled in this single-institutional prospective study (30 in each arm). Due to stratification, the proportion of patients undergoing curative and adjuvant therapy was similar in both arms (35% and 65%). Likewise, patients who received concomitant chemotherapy, were equally represented in both arms (approximately 70%). The study included mostly men (77%). The patients’ median age was 59 years. In the acupuncture arm, patients were statistically significantly younger (p < 0.001) and the worst  pain during RT, and for the average  and the worst  pain during three months following the termination of RT  for both pain parameters are shown in on of RT C.A separate evaluation at critical moments of the treatment was performed to demonstrate the influence of acupuncture. Specifically, at the start, in the middle, in the three-quarters and at the end of RT, then 14 days after and one month after the end of RT. The patients in the acupuncture arm reported a statistically significant lower pain level in all monitored moments except the start of RT A. The dip = 0.001 and p < 0.001) and three months after the end of RT (p = 0.004 and p = 0.003).A proportion of days with pain level above three on a 10-grade scale was analyzed for each patient B. ExceptAnother objective of this study was to evaluate the need for analgesics during RT and whether analgesics’ usage was lower in the acupuncture arm patients. In total, analgesics’ usage in the acupuncture arm was lower both during RT and during three months after the end of RT A. The prp = 0.047 during RT and p = 0.006 after the end of RT  and 8.0% (IQR 0.0–51.5%) during RT and 20.8% (IQR 0.0–28.7%) and 0% (IQR 0.0–13.9%) during three months after the termination of RT in the control and acupuncture arm, respectively. These differences between arms reached statistical significance nd of RT C.p = 0.161 during RT, p = 0.322 during the first three months after RT) than in the control group, the difference observed was not statistically significant. The usage of weak opioids was statistically significantly lower in the acupuncture arm  than in the control arm  and the worst pain during the day  in favor of the patients enrolled in the acupuncture arm. A United States study by Miller et al. [One of the main symptoms against which acupuncture is used and the most well-known indication of acupuncture is pain. This study proved a statistically significant manifestation of the difference in pain assessment, both average pain  and during three months after the end of RT (p = 0.006). The largest difference in the amount used analgesics was observed for the weak opioids which patients use only in more intense pain. This pain was observed mainly in the control group, therefore, consumption of weak opioids was higher. On the other side, non-opioids are commonly used as first-line analgesics even with mild pain. The use of strong opioids was not common and involved very high pains. Concerning the pain maximum was similar in both arms, the consumption of analgesics did not differ either.The other objective of this study was lowering the usage of analgesics. Usage of analgesics was statistically significantly lower both during RT (A randomized sham-controlled trial  from 202Both the intensity of pain during the treatment and analgesics usage were lower in the acupuncture arm during this study. Since pain has a major impact on the quality of patients’ life and their tolerance of the treatment, the results presented here indicate that acupuncture during RT applied to the head and neck area is clinically significant.We are aware of some limitations of the study. Firstly, patients were stratified into arms according to treatment characteristics, however, other patients’ characteristics are different between arms. Mainly, patients in the control arm are older and more often smokers. On the other side, there are patients with more advanced diseases in the acupuncture arm. All these facts may bias the results. The subjectivity of pain assessment and the impossibility of blinding used intervention are other disadvantages that may be considered when planning further studies.In conclusion, acupuncture is a well-tolerated, feasible and effective treatment of radiotherapy-related pain in head neck cancer patients and leads to lower usage of mild opioids. The use of acupuncture can have an impact not only on improving the quality of life but also on reducing the side effects and costs of analgesic therapy. Further research is needed for the inclusion of acupuncture in the standard-of-care treatment process in this group of patients.


This study aims to explore the efficacy and safety of “U” route PELD on chronic pain patients with LSS combined with DH.  Degenerative LSS combined with DH patients who underwent “U” route PELD were reexamined, and 80 patients were recruited and followed up for 2 years. The other 80 healthy individuals who were age- and sex-matched to the patients without chronic pain were enrolled as healthy controls. Minimum dura sac cross-sectional area (mDCSA) by MRI, Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and modified MacNab outcomes were assessed. Emotional evaluation of pain catastrophizing and depression was documented with Pain Catastrophizing Scale (PCS) and Beck Depression Inventory (BDI), respectively, for patients before and after surgery and healthy individuals. p < 0.001), either low back and leg VAS or ODI decreased over time (p < 0.001), and the excellent-to-good rate was improved from 88.75% to 93.42% during postoperative 2 years (p < 0.05). Complications of dural tear, nerve root, or dysesthesia were reported in 5 patients, and all recovered after conservative therapy. The scores of pain catastrophizing were reduced after operation (p < 0.001), but no significance of BDI was found between patients and healthy controls (p > 0.05).  All patients were of the age range from 47 to 85 years, with an average of 59.5 ± 9.76 years. Symptoms duration was 114.6 ± 22.77 months, operation time was 87.7 ± 25.20 minutes, and the average hospital stay was 5.8 ± 2.81 days. Four patients quit, and hence, a total of 76 patients completed the follow-up. The results indicated that mDCSA was improved significantly after operation ( The “U” route PELD seems an alternative to LSS combined with DH treatment, which might reach a better decompression and effectively improve chronic pain conditions. Still, the complications were potential and required further consideration. Chronic pain is defined as the pain that persists beyond normal healing time. It usually lasts for more than 12 weeks . The mecTraditionally, the decompression plus fusion surgery is regarded as the standard procedure for LSS treatment . During To reach this question, patients diagnosed with LSS combined with DH who underwent “U” route PELD in our department were enrolled. The minimum dural sac cross-sectional area (mDCSA) was frequently measured to assess the severity of spinal canal stenosis , and theThis retrospective trial was approved by the Institutional Review Board of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. Protocols in detail were provided to each subject, and informed consent was obtained before the study. Eighty consecutive patients who received “U” route PELD during January 2014 and July 2018 were enrolled.All included patients met the inclusion criteria: (1) patients with the diagnosis of degenerative LSS and combined DH  on mono or double segments, with the imaging evidence of magnetic resonance images (MRI) and computed tomography (CT); (2) patients presented unilateral low back pain, limp, and sciatica that were consistent with the imaging evidence and have received conservative treatment more than 12 weeks but failed in symptoms relief; (3) patients agreed to accept “U” route PELD over other spinal surgeries; and (4) patients had lumbar MRI imaging in our hospital at pre- and postoperation. The exclusion criteria were (1) patients with spinal instability, including dynamic instability or more than grade II spondylolisthesis; (2) patients had a spinal surgical history; (3) patients with peripheral nerve disease, systematic infection, bleeding diathesis, or high risk of bleeding that cannot tolerate the surgery; (4) patients with mental illness and were uncooperative; and (5) patients lost to the follow-up.All surgeries were performed by two senior and experienced surgeons, and all procedures were equipped with the transforaminal endoscopic spine system . The following steps were performed in sequence in the “U” route procedures of PELD: (1) Patients who underwent the surgery were on the lateral position on an operating table on the contralateral side. The affected disc and pedicle were determined by the surgeon, who also designed the operation puncture length and angle under the guidance of C-arm fluoroscopy, and the skin entry was normally 10–12 cm from the midline. (2) After subcutaneously local anesthesia with 1.0–1.5 mL of 0.5% lidocaine, an 18-gauge puncture needle was inserted to the superior articular process (SAP) of the distal segment under fluoroscopic guidance. (3) The stylet was retreated, and then another 20 mL of 0.5% lidocaine was injected via the needle for further anesthesia, a guidewire passed through the needle, and then the needle was removed. (4) A skin incision about 0.8 cm diameter was made by a serial dilation with a cannulated obturator, and a working channel was rotated over the obturator. (5) The surgeon replaced the guidewire and obturator with a guide bar; a trepan was rotated along the working channel to SAP. Then, the position of the working channel was confirmed under the C-arm fluoroscopy. (6) An endoscope and two irrigation channels were inserted, and the ipsilateral-posterior hypertrophic and/or ossific LF were resected under endoscopic visualization after the foraminoplasty performance . (7) The2) at preoperation and were measured for all patients, the sagittal and axial T2-weighted images were obtained, and mDCSA at the most constricted lumbar spinal level of the surgical intervertebral disc was measured three times by the software of INFINITT Picture Archiving and Communication System (PACS)    and dynal Korea) . The aveA battery of self-reported questionnaires related to pain was filled before and after the operation to evaluate symptoms improvement. Low back and leg pain were estimated with VAS and the disability with ODI for the involved patients at preoperation, and postoperative 1-day, 1-week, 1-month, 3-month, 6-month, 1-year, and 2-year follow-up. The recovery condition was evaluated with modified MacNab criteria (excellent to poor) at postoperative 6-month, 1-year, and 2-year follow-up. Pain catastrophizing and depression of the patients were assessed with PCS and BDI at preoperation and postoperative 2-year follow-up, and the other 80 healthy individuals whose age and sex matched with the patients also completed PCS and BDI to detect the emotional changes of the patients. VAS is an 11-graded (0 to 10) visual scale to measure pain intensity, where 0 corresponds to no pain and 10 indicates the worst pain that almost cannot endure. ODI (0 to 100) assesses physical impairment related to pain. PCS  includes three subscale that assesses aspects of helplessness (PCS/h), magnification (PCS/m), and rumination (PCS/r). BDI is a 21-item instrument for the severity of depression measurement.t-test or using Mann-Whitney U test if non-normally distributed, the Wilcoxon test was used for data analysis within groups, and the post hoc test was used for multiple comparisons. Qualitative data were presented as frequency and were analyzed using two-tailed chi-square tests or Fisher's exact test. Statistical analyses were performed using SPSS 25.0 software , and p value <0.05 was considered significant.For continuous variables, data were presented as means ± standard deviations and were compared with Student's Eighty patients receiving “U” route PELD were aged from 47 to 85 years old, with an average of 59.5 ± 9.76 years. The symptoms duration was 114.6 ± 22.77 months, and there were 2 cases operated at L2/3, 5 cases at L3/4, 39 cases at L4/5, 29 cases at L5/S1, 2 cases at L3/4 and L4/5, and the other 3 cases were at the levels of L4/5 and L5/S1. The operation time was 87.7 ± 25.20 minutes, and the average hospital stay was 5.8 ± 2.81 days .p < 0.001). The VAS of low back decreased significantly after the operation. It was reduced from 5.2 ± 2.82 to 0.8 ± 1.07 at postoperative 1-day follow-up, and to 0.4 ± 1.04 at the last follow-up (p < 0.001). The VAS of leg pain decreased from 4.1 ± 2.34 to 0.2 ± 0.57 at postoperative 1-day follow-up, and to 0.1 ± 0.38 at the last follow-up (p < 0.001). ODI decreased from 57.5 ± 21.76 to 9.48 ± 11.48 at postoperative 1-day follow-up, and to 4.7 ± 7.12 at the last visit (p < 0.001). The results showed a significant improvement in pain reduction and the physical function of the patients after surgical treatment.As seen in Figures p < 0.001; PCS/m p < 0.001; PCS/r p < 0.001; PCS/t p < 0.001). Moreover, the preoperative PCS score was higher in LSS combined with DH patients than healthy individuals , but no significance of PCS between patients at postoperation and healthy controls  was found. However, we found no significant difference of BDI between the patients and healthy individuals either at pre- or postoperation .PCS and BDI were assessed for both patients and healthy individuals, as seen in There were 2 patients out of touch at postoperative 1-year follow-up, and 2 patients died, so the remaining 76 patients completed the 2-year follow-up. The complications are shown in p=0.029).The patients have evaluated the postoperative recovery condition with modified MacNab criteria at postoperative 6-month, 1-year, and 2-year follow-ups, and the outcomes are shown in detail in This retrospective study was designed to explore the therapeutic and safety of “U” route procedure of PELD for LSS combined with DH treatment. Most subjects involved in this study presented symptoms reliefs, with significant improvements in mDCSA on MRI. Despite the complications that occurred and 1 patient needed revision surgery, the “U” route PELD achieved identically feasible and safe for LSS combined with LDH therapy after comprehensive evaluations of VAS, ODI, and modified MacNab outcomes, and pain catastrophizing improvement was also observed.Earlier studies have suggested that LSS patients should be decompressed under open surgery after the failure of a series of nonoperative therapies, but the open surgery remains challenging. It was reported the patients were evaluated a poor long-term outcome after decompressive laminectomy for LSS, 23% of patients received repeated surgery, and 33% of patients complained of severe back pain , and disTESSYS PELD procedure, as a more minimally invasive technique than MED, was introduced to treat DH in the last decade. Due to the improvement of the PELD procedure and operative instrument, TESSYS was gradually indicated for LSS –15. HoweA published study reported postoperative 1-year clinical outcomes of 270-degree spinal canal decompression using TESSYS-ISEE technique for the patients with LSS combined with DH with a sample of 32 cases, a procedure similar to “U” route described in the present study . Neverth2; a further constriction would cause increased pressure on the nerve root [2, which is lower than the reported critical size. We found mDCSA at the surgical level was statistically enlarged by the “U” route PELD. Still, there is a limitation that the mDCSA was measured at postoperative 3-month follow-up. The long-term postoperative changes of mDCSA were not detected in this study.mDCSA was frequently measured to assess the severity of spinal canal stenosis and was considered a more powerful variable in predicting the canal condition compared with diameters . A smallrve root . The preBesides, the mDCSA was a strong predictor of clinical symptoms and quality of life of LSS patients , 17. AltA biopsychosocial model of chronic pain has been widely adopted, and epidemiologic studies suggested that chronic pain increases the risk for depression, anxiety, and pain catastrophizing , 21. TheThe occurrence of complications of nerve root injury, dysesthesia, and dural sac tear was inevitable in the “U” route PELD. The foraminoplasty and decompression were all performed under endoscopic visualization, so the mechanical tear and nerve root injury resulted from surgical tool compression could be avoided. The nerve root injury and dysesthesia might be caused by thermal injury when using high-speed endoscopic burr and side-firing laser in the process of undercutting of SAP . The patThe novelty of the present study was exploring the therapeutic effect of the “U” route PELD on LSS with DH and detected the improvement of emotion in these chronic pain patients. Despite being a preliminary study, “U” route PELD seems promising with a superior clinical outcome within postoperative 2 years. The posterior interlaminar approach is also indicated for central spinal stenosis but cannot completely remove the ventral disc protrusion. Therefore, the posterior interlaminar approach was not included in the comparison in this study. The investigation of the superiority of the posterior interlaminar approach of PELD for central LSS treatment without DH would be carried out shortly.In conclusion, “U” route procedure of PELD seems a feasible and safe PELD procedure for LSS combined with DH treatment, which achieves significant improvements in mDCSA, clinical symptoms, and pain catastrophizing. However, the risks of complications and inadequate decompression are potential. This is a retrospective study with preliminary results, and a more confirmative conclusion needs randomized trials with a larger sample size in the future.


Percutaneous nephrolithotomy is a procedure used for management of refractory renal calculi. Oral and parenteral opioids, along with local anesthetic infiltration, neuraxial anesthesia, and paravertebral blocks are the most common methods of managing intra-operative and post-operative pain for these patients. The erector spinae plane block with catheter (ESPC) is a newer interfascial regional anesthetic technique that can be used to manage peri-operative pain in these patients.Three patients complained of significant flank pain were scheduled for percutaneous nephrolithotomy under general anesthesia in the prone position.Patients were diagnosed with large renal calculi.Patients received ESPC in the pre-operative holding area at the level of the T7 transverse process. The ESPCS were bolused with a solution of 30 mL 0.25% bupivacaine with 4 mg dexamethasone prior to surgery. Patients also received oral tramadol 50 mg and acetaminophen 1 g as part of the multimodal pain protocol prior to surgery. After the procedure, the patients were bolused with 0.25% bupivacaine or started on an infusion of 0.25% bupivacaine to manage their pain.No opioid or other pain medications, other than the local anesthetic solution given in the ESPCs, were used during the intra-operative or post-operative period for management of pain in these patients. Visual analogue scale (VAS) scores were below 4 for all patients in the post-operative period, and patients did not report any issues with post-operative nausea or vomiting.These patients were compared to 3 prior patients who had undergone percutaneous nephrolithotomy without ESPC. The 3 patients without ESPC placement reported increased VAS scores, had increased opioid/pain medication consumption intraoperatively and postoperatively, and had increased incidence of perioperative nausea when compared to our ESPC patients. Our report shows that ESPC, in combination with a multimodal pain protocol, can be a good option for management of patients undergoing percutaneous nephrolithotomy. A nephrostomy tube is usually inserted after PCNL to provide adequate urinary drainage, hemostasis, and access for possible complications. However, nephrostomy tubes can cause significant postoperative pain and prolonged hospitalization which can lead to patient dissatisfaction.The main sources of acute postoperative pain after PCNL are visceral pain originating from the kidney and ureter, and somatic pain from the incision site. Visceral pain is primarily transmitted through the T10 to L2 spinal nerves and incisional pain is conducted via T8 to T12 due to the incision site often at the 10th to 11th intercostal space.In recent years, the erector spinae plane block (ESPB) has been gaining popularity as a regional acute pain technique for an assortment of procedures/pathologies.In this case series, we report three cases of ESPC used for intraoperative and postoperative pain management of PCNL procedures. Each patient received an ESPC that helped achieve satisfactory analgesia while decreasing opioid consumption and PONV.22.1A 59-year-old female  was scheduled for left PCNL due to a 9 mm stone in the left renal pelvis.2.2The ESPC was performed using ultrasound at the level of T7. The T7 transverse process was located using the inferior angle of the scapula as a landmark. A curvilinear 5-2 MHz ultrasound probe was placed on the patient's back in a cephalad-to-caudal fashion at the level of T7. The trapezius and erector spinae muscle were visualized on the left side, and a 19G Tuohy needle was advanced (in-plane to the ultrasound probe) in a caudal direction toward the left-sided transverse process of T7. After confirming that the tip of the needle was below the erector spinae muscle with a small bolus of our local anesthetic solution (30 mL of 0.25% bupivacaine with dexamethasone 4 mg), we injected 20 mL of the solution into the space, noting the caudal spread of the injectate on ultrasound. Then, a 20-gauge epidural catheter was inserted through the Tuohy needle and advanced 5 cm into the space. Placement of the catheter under the erector spinae muscle was confirmed by injecting the final 10 mL of the local anesthetic through the catheter while visualizing the spread of the solution on ultrasound. The catheter was then secured using the LOCKIT Plus catheter securement device, which allows for mechanical securement of the catheter while maintaining its patency. Additionally, it provides easy access for visual inspection of the insertion site via a transparent window.2.3The PCNL was performed in the prone position using general anesthesia. The patient received acetaminophen 1 g in the preoperative area as part of a multimodal pain protocol . She underwent general anesthesia and received no opioid or other pain medications during the 118-min procedure; she was extubated without complication at the end of the case. Pain scores in the Post-Anesthesia Care Unit (PACU) were assessed by nursing using visual analogue scale (VAS) scores and recorded in the medication administration record (MAR). All medications given for pain and PONV were recorded in the MAR as well.The patient remained in the PACU for 231 min and reported VAS scores of 0/0/0/0/0. She received ondansetron 4 mg intraoperatively and 4 mg prophylactically in PACU due to a patient-reported history of severe PONV. The patient was given an additional 10 mL bolus of 0.25% bupivacaine 1-h prior to discharge, and the catheter was removed with the tip intact. The patient was discharged home from the PACU without complications and reported no pain at all.2.4The patient returned to the hospital for a left-sided ureteral stent exchange 15 days later and reported that she had no residual pain in the days following her previous procedure.33.1A 66-year-old female  presented for left PCNL due to a 1 cm left renal stone.3.2In the preoperative holding area, the patient underwent ESPC with catheter placement at T7 using a technique identical to Case 1. She was given 30 mL of the 0.25% bupivacaine and dexamethasone 4 mg solution.3.3The patient received acetaminophen 1 g and tramadol 50 mg prior to surgery as part of the multimodal pain protocol. She underwent general anesthesia for her 85-min procedure; intraoperatively, the patient received no opioid or other pain medications. She received ondansetron 4 mg prophylactically to prevent PONV.Upon arrival in PACU, the patient admitted to having mild pain and reported a VAS score of 4. The ESPC was bolused with 5 mL of 0.25% bupivacaine, after which she reported VAS scores of 0/0. The patient was admitted overnight for observation due to concern for bleeding at the surgical site. The ESPC was connected to a continuous infusion in PACU; the settings for the infusion were 6 mL an hour of 0.25% bupivacaine with a patient-controlled bolus of 4 mL every 20 min as needed. The patient did not use the patient-controlled bolus function and reported having minimal pain overnight. She reported VAS scores of 0/0/0/1/0. She was discharged the following afternoon without complications after removal of the catheter with the tip intact.44.1A 71-year-old female  underwent right PCNL for a 7 mm renal stone.4.2As in Case 1 and Case 2, the patient underwent preoperative placement of ESPC. She was given 30 mL of the local anesthetic solution prior to surgery as in Case 1 and Case 2.4.3Patient received acetaminophen 1 g and tramadol 50 mg as part of the multimodal pain protocol. The 116-min procedure was performed under general anesthesia; she received no intraoperative opioid or other pain medication. She did receive a prophylactic dose of ondansetron 4 mg to prevent PONV.In the PACU, the patient reported VAS scores of 0/0/0/0/0/0/0 and denied PONV. One-hour prior to discharge, the ESPC was bolused with 10 mL of 0.25% bupivacaine and the catheter was removed with the tip intact. She was discharged after a 237-min stay in PACU without pain.5Neuraxial and regional blockade have commonly been used for relieving pain from a myriad of surgical procedures and pain syndromes. ESPC placement has emerged as an effective regional technique, providing excellent analgesia with reduced opioid requirements.[For patients undergoing PCNL procedures, much of the pain produced is visceral in nature secondary to the large size of the renal calculus with subsequent stretching of capsular fibers involving the T10 to L2 dermatomes.In order to further assess the potential benefit of the ESPC, we retrospectively examined the medical records of the three previous patients at our institution who underwent PCNL without ESPC. The first patient we examined received acetaminophen 1 g and tramadol 50 mg as part of the preoperative multimodal pain protocol. She received fentanyl 200 mcg and ketamine 100 mg intraoperatively, and, in PACU, she received hydromorphone 0.5 mg IV and reported VAS scores of 5/0/0/0. She also required ondansetron 4 mg and haloperidol 1 mg for PONV in PACU. The second patient received acetaminophen 1 g and tramadol 50 mg preoperatively, fentanyl 200 mcg intraoperatively, and ketorolac 30 mg and one hydrocodone/acetaminophen 5 mg/325 mg pill in PACU. Her VAS scores in PACU were 3/3/2/2. The third patient received acetaminophen 1 g and tramadol 50 mg preoperatively, fentanyl 100 mcg intraoperatively, and two hydromorphone 0.5 mg IV pushes in PACU. She also required two hydrocodone/acetaminophen 10 mg/325 mg pills for pain during her 1-day admission as well as ondansetron 4 mg on two separate occasions for PONV. Her VAS scores in PACU and on the medical floor were 5/6/2/0/0/6/3/6/3/7/3/3. The patients we examined without ESPC placement had increased VAS scores post-operatively, increased opioid/pain medication consumption intraoperatively and postoperatively, and increased incidence of perioperative nausea when compared to our ESPC patients (see Tables In our experience of patients who underwent ESPC for PCNL at our institution, intraoperative and postoperative opiate usage, PONV requiring treatment, and VAS scores were all effectively decreased. Our case report shows that ESPC for PCNL can be an effective method to manage intraoperative and postoperative pain in combination with a multimodal pain protocol.Conceptualization: Sandeep Krishnan.Data curation: Sandeep Krishnan.Formal analysis: Sandeep Krishnan.Investigation: Andrew Resnick, Michael Chait, Sandeep Krishnan.Methodology: Sandeep Krishnan.Project administration: Sandeep Krishnan.Supervision: Sandeep Krishnan.Writing – original draft: Andrew Resnick, Michael Chait, Sandeep Krishnan.Writing – review & editing: Andrew Resnick, Michael Chait, Steven Landau, Sandeep Krishnan.