Aim: There needs to be more general agreement on the most effective treatment for the emergency patient with Symptomatic Irreversible Pulpitis (SIP). This equivalence randomised clinical study compared the clinical efficiency, as an urgent treatment, of pulpotomy (POT) and pulpectomy (PEC) in the permanent teeth with SIP. The primary outcome was pain management, and the secondary outcome was the patient’s perception of duration, comfort, and satisfaction. Material & Methods: 80 patients were blindly and randomly allocated into two equal parallel groups, the control group treated by PEC and the test group by POT. Data were collected through numerical rating scales (NRS) during the intervention and 6, 24, and 72 h post-op. Non-parametric tests were used to analyse the data. The Brunner-Longer models were adopted for longitudinal data and the analysis of variance (ANOVA)-type statistical was used. Results: The mean preoperative pain levels for the whole sample scored 5.8 ± 2.8 and significantly decreased to 2.1 ± 2.4 at 6 h, 1.5 ± 2.1 at 24 h, and 1.3 ± 2 at 72 h, without any differences between the groups. No significant differences were found in the patient’s perception of treatment discomfort or duration between the groups. Three days after the intervention, patient satisfaction was high, with 9.2 ± 1.7 and 9.1 ± 2 in the PEC and POT groups, respectively. Self-reported pain was the only variable penalising the patient’s final satisfaction. Conclusions: The current randomised control trial (RCT) showed that both pulpectomy and pulpotomy effectively eliminate pain and achieve high levels of patient satisfaction. Furthermore, the patient’s perceptions of the duration and discomfort of the two treatments were similar. Given that pulpotomy is a faster and more straightforward technique, it may be recommended as a viable and pragmatic option for treating emergency patients with symptomatic irreversible pulpitis. Pain emergencies are a significant problem in the dental office, and the cause is often endodontics. Although data on general prevalence are lacking, most general dentists would likely see daily deep caries or traumatic pulp exposures causing pulp affection .Most endodontic emergencies come from Symptomatic Irreversible Pulpitis (SIP), a condition without a clinically precise definition beyond the lingering pain elicited by mild thermal stimuli  and the Traditionally, the preferred treatment option has been pulpectomy, even with complete instrumentation , and thiNot long ago, the concept of minimally invasive endodontics was put forward ,12 and sBecause they are not scheduled, emergencies interrupt the dental team agenda and are often a source of stress for the operator, and sometimes even frustration for the patient, who feels the operator’s burden and rush ,16. WhenThe long-term efficacy of complete root canal treatment is universally accepted as the gold standard in SIP treatment .The improvement in the patient’s quality of life by root canal treatment has also been reported . HoweverPOT and PEC were previously compared in reducing postoperative pain in SIP patients, and both appeared to be equally valid ,20,21,22This randomised clinical study aims to compare the clinical efficiency of POT and PEC for pain control in emergency SIP patients. It also compares the two therapies regarding the patient’s perception of treatment duration, comfort, and satisfaction.This multicenter clinical trial is a parallel-arm, single-blind, randomised, comparative study. It aims to compare two alternative techniques for managing symptomatic irreversible pulpits: POT and PEC. The study does not have an external funding source.The study population was all patients consecutively attending two private dental clinics due to pain caused by SIP between 1 December 2020 and 31 July 2022.Patients were randomly assigned to one of two parallel groups. The experimental group was treated with POT, and the control group was treated with PEC.This randomised clinical trial has been designed according to the Consolidated Standards of Reporting Trials statement (CONSORT 2010).Any patient presenting SIP, whatever its cause, in any tooth whose preservation was considered viable, was included in the study. Patients of any age, of either sex, in ASA I or II health status, and without contraindications to receiving an endodontic procedure under local anaesthesia were included. Haemorrhage after pulp exposure was considered an essential criterion for patient inclusion in the investigation.Exclusion criteria before the procedure were allergy to non-steroidal anti-inflammatory drugs or local anaesthetics, pregnant or nursing women or with contraceptive treatment, psychotropic drug abuse, or medication that may alter painful perception taken 15 days before the intervention , major mental disorders , patients younger than 18 years, or patients uncooperative or with cognitive difficulties. The clinical exclusion criteria were a negative response to the cold pulp vitality test or absence of bleeding after pulp exposure .https://www.random.org/lists, accessed on 15 November 2020). A block randomisation method was followed to allow equal allocation for both treatments per operator/centre. Before each procedure, the operator telephoned a secretary to find out the patient’s group assignment. The secretary did not participate in the investigation but managed the randomised list of interventions.The random assignment of participants to one of the two treatment modalities, PEC or POT, was performed immediately before the intervention following a simple software-generated random number procedure using the “List Randomizer” application  for complete PEC and −6 (range: −10 to 3) for POT .The difference in medians (Δ = 4.5) estimates the shift of one distribution versus the other. The standard deviation in each group was calculated by the Wan-2014 method, with ±2.88 and ±3.40, for the PEC and POT groups, respectively.These estimates show that Eren’s work’s effect size is large (d = 1.43). Therefore, a minimum of 80 patients (40 per group) is needed to detect significantly different pain reductions of 2 and 4.5 points (large effect with d = 0.8) in the groups with a statistical power of 90%. The statistical power calculations were performed by a statistician external to the investigation .In this study, the predictive variable was the intervention used to treat a tooth with SIP. The study’s primary outcome was the patient’s perception of pain after the intervention three days later. The secondary outcome was patient satisfaction three days later. Other secondary outcomes were the patient’s perception of the duration of treatment received and the degree of discomfort experienced. Data were measured from 0 to 10 on an 11-point NRS, verbalised by the patient.Dropouts were defined as the patients who did not respond to all questionnaire responses up to three days after the intervention.Once the patient was in the dental office, the diagnosis of SIP was confirmed by anamnesis, clinical, and radiographic examination. Firstly, the patient’s medical and dental history was recorded, particularly the pain characteristics. A visual examination of the tooth and the surrounding area was performed, including soft tissue palpation, periodontal evaluation, mobility, and percussion testing. Then, a periapical radiograph was taken to evaluate the periodontal and periapical structures.To diagnose SIP, patients must present with severe, spontaneous, radiating pain that persists for 30 s or more after the removal of the stimulus, as defined by the recent American Association of Endodontists (AAE) and European Society of Endodontology (ESE) Consensus ,24. AfteOnly after a positive response to the vitality test will the patient be informed about his potential participation in the study. In case of verbal acceptance, the patient signed the Study Consent document.The Ethics Committee of San Juan Hospital of the University Miguel Hernández, Alicante, Spain, approved the study with application nº 20/047, agreed on 25 November 2020. The study was registered on Clinicaltrials.gov with the identifier: NCT04654845. All interventions performed in this study followed the institutional and national research committee’s ethical standards, the 1964 Helsinki Declaration, and its later amendments or comparable ethical standards.The operator then requested the type of procedure assigned to the particular patient by calling the appropriate telephone number. A secretary external to the investigation was the custodian of the randomised allocation list.Once the procedure number was assigned and before anaesthesia was performed, the patient was asked the first three questions about their current pain, anxiety, and chewing pain in that area. The patients were blinded to the intervention they were about to receive.Anaesthesia was equally performed in both groups using 1.8 mL cartridges containing 4% articaine chlorhydrate (40 mg/mL) and 1:100,000 epinephrine . The anesthetic technique used on each tooth was appropriate for its location. Thus, the first-choice anesthetic techniques used were the inferior alveolar nerve block in the lower molars and second premolars, and the infiltrative techniques were used for the rest of the teeth.Before starting the procedure, a new vitality test was performed to check the degree of anaesthesia achieved. Depending on the case, the operator determined whether or not to complete the anaesthesia with additional techniques, such as intraligamentary or intrapulpal anaesthesia.Isolation of the tooth with a rubber dam.Accessing to pulp chamber with a diamond bur.Confirmation of the presence of pulp bleeding.Removal of pulp tissue of the chamber with a round tungsten carbide bur.Use of cotton pellets soaked with sodium hypochlorite (NaOCl 5.25%).Waiting until the hemostasis is achieved.Placement of Teflon tape (PTFE) condensed on the chamber floor.Placement of a temporary restoration .Occlusal reduction, verifying the absence of contact with 200μ articulating paper .For the experimental group (POT), the following clinical sequence was carried out:Isolation of the tooth with a rubber dam.Accessing to pulp chamber with a diamond bur.Confirmation of the presence of pulp bleeding.Removal of pulp tissue of the chamber with a round tungsten carbide bur.Irrigation with sodium hypochlorite (NaCl at 5.25%) throughout the procedure, according to the operator’s preference.Determination of the working length for each canal using an Electronic Apex Locator  and a Pre-K file .Root canal preparation using rotary cutting instruments with a reciprocating system  up to WL and up to a minimum apical diameter of #25.Placement of Teflon tape (PTFE) condensed on the chamber floor. Calcium hydroxide was not used so as not to create differences between the two groups due to its anti-inflammatory effects.Placement of a temporary restoration .Occlusal reduction, verifying the absence of contact with 200 μ articulating paper .For the control group (PEC), the clinical sequence consisted of the following steps:In both groups, patients were advised to avoid chewing on the treated side to prevent coronal fractures of the tooth under treatment.Before leaving the office, the preferred form of contact, text message or phone call, was agreed by the patient to obtain the investigated data further.The operator recorded the patients’ perception data in an ‘Intervention Document’ form assigned to each procedure/patient. At the end of the treatment, the operator filled out the form with the procedure data.Before the intervention: the patient’s perception of current pain, anxiety, and pain sensation when chewing on the diseased side.Immediately after the intervention: the patient’s perception of the duration of treatment and the degree of discomfort during treatment.At the time intervals after the intervention: the patient’s perceived pain at 6, 24, and 72 h.The patient’s global satisfaction with the treatment 72 h after the procedure.To better understand how patients should describe their perceived degree of pain, the NSR included in the “Intervention Document” was explained to them in the preoperative phase. The numerical pain perception scale scored pain from 0 to 10, with 0: no pain, 1–3: mild, 4–6: moderate, 7–9: severe, and 10: the worst pain imaginable. Patients were asked to state the number that best represented the perceived duration of the pain they were experiencing at the time of assessment. Patient responses to the NSR were collected on the following four occasions: The patient’s perception at the postoperative intervals was obtained by phone calls or messages. The patient must indicate the NSR score in the same way as they did when in physical presence in pre- and immediate postoperative pain assessment.Age.Gender.The number of teeth involved .The cause of SIP .The presence of primary acute apical periodontitis (AAP) with a percussion test before the intervention, in terms of Yes or No.Whether preoperative non-steroidal anti-inflammatory drugs (NSAIDs) had been taken by the patient, Yes or No.The time elapsed from pulp exposure to the end of the intervention in minutes.The postoperative chewing pain in terms of Yes or No.The operators collected the following procedure data:The operators ticked the relevant boxes on the ’Intervention Form´ and filled in the five NSR scores submitted by the patient 6, 24, and 72 h after the intervention; then, a third investigator, blinded to the clinical cases, transferred data to the ´Data Table.´ Once this table with the whole sample of 80 interventions/patients was completed, it was statistically analyzed.The Mann-Whitney test was used to compare the rating distributions in the two groups, and the Wilcoxon test to compare the pain distributions between different follow-up moments. Brunner-Langer’s non-parametric longitudinal data models were used to analyse the evolution of the pain level throughout the study. A between-subjects factor (the group) and a within-subjects factor (moment of assessment) were included. The analysis of variance (ANOVA)-type statistic (ATS) was calculated to evaluate the main effects and interaction.The choice of this methodology was justified by the ordinal nature of the data and its lack of normal distribution. This model is a non-parametric ANOVA with repeated measures and maximum statistical power.The Mann-Whitney and Wilcoxon tests with Bonferroni correction were used for multiple comparisons between groups at different measurement moments or between moments within each group. Spearman’s non-parametric correlation was used to assess the degree of non-linear association between different questionnaire ratings.A multiple linear regression model was used to analyze the outcome satisfaction related to other variables. The input method for the variables in the model was stepwise. The significance level used in the analyses was 5% (α = 0.05).Eighty patients (40 men and 40 women) with a mean age of 50.7 years  were included in the study between 1 December 2020 and 31 July 2022. The study ended when the calculated sample size of 80 patients was reached. All patients in the study reported their degree of pain and satisfaction at all necessary moments (up to 3 days after the intervention), so there were no dropouts .The patterns of pain decrease during the follow-up time can be seen in Sixty percent of the patients required supplementary anaesthesia, with a homogeneous distribution of 24 patients in each group. No statistically significant association was found between the need for supplementary anaesthesia and the evolution of pain perception or the final patient satisfaction.p < 0.001), especially in women who seemed to feel more anxiety before treatment (p = 0.024). Fifty patients (62.5%) had previous experience with endodontic treatment, but the patient’s previous experience did not condition the magnitude of the perceived pain or the time it takes to subside (p = 0.286).Patients reported a mean score of anxiety before treatment of 3.2 ± 3.4, and a weak-moderate relation (r = 0.39) was found with preoperative pain perception (p = 0.706). Most patients  did not need painkillers after treatment. No significant differences were found between the two treatments and the need or not to take subsequent medication (p = 0.099).Thirty-seven patients had taken NSAIDs before the intervention, with 17 in the PEC group and 20 in the POT group. No statistical correlation was found between previous NSAID intake and the evolution of post-treatment pain (p = 0.052); therefore, the pain reduction was more significant than when no AAP symptoms were present previous to the intervention (p = 0.033). Regardless of the presence or absence of AAP, the pain evolved similarly after treatments in both groups (p = 0.614). Twelve patients (15%) still had postoperative chewing pain, but this was not statistically related to the type of intervention (p = 0.201).Patients reported a mean score of chewing pain before treatment of 6.5 ± 3.3. Thirty-three patients  presented AAP concomitant with SIP. Twenty patients were treated with PEC and 13 with POT. Before the intervention, pain in patients with AAP was higher  can be seen in Three days after the treatment, the mean patient satisfaction scored 9.2 ± 1.7 and 9.1 ± 2.0 in the PEC and POT groups, respectively. The homogeneity between them .The mean intervention time in minutes, from pulp exposure to finalisation of the treatment, was 13.4 ± 6.1 for the control PEC group and 7.4 ± 3.0 for the test POT group. In both groups, the longer the pulp was exposed, the longer it took the patient to reach pain levels lower than score 3 . A weak-moderate correlation (r = 0.4) was also found between the patient’s perceived duration and the time taken from pulp exposure to the end of treatment in both groups, especially in the PEC group (p = 0.034). Patients perceived both interventions as short duration with a median of 3 (1.0–3.0) for all the samples. However, The mean level of discomfort perceived by the patients was 1.5 ± 1.9 with no statistically significant differences between the two groups. All teeth received a complete root canal treatment at a second appointment, irrespective of the group they belonged to during the investigation.The present study aimed to test the null hypothesis that both of the interventions investigated were equally effective in eliminating pain in emergency SIP patients. Data collection was set up to three days post-treatment to capture the most immediate decrease in severe pain. The patients’ satisfaction and perceptions of the duration and discomfort of both interventions were also studied.According to the results, both interventions appeared to be equally effective in eliminating pain in emergency SIP patients. Regardless of the procedure, patients benefited from a significant reduction in pain within 6 h of the intervention, with no statistical differences between the two groups. Since the homogeneity of the test and control groups was statistically confirmed, due to the lack of differences in the pain perceived by the patients after receiving one type of treatment or another this study failed to reject the null hypothesis. The atypical scores, outliers in Although the patient’s satisfaction with the treatment depends on factors beyond the mere technical procedure, such as duration, comfort, cost, or personal rapport, the treatment outcome is satisfaction’s first and foremost cause. In this case, the satisfactory outcome meant pain dissipation. When this outcome was not achieved in either group, higher pain scores correlated significantly with lower patient satisfaction. This study found that self-reported satisfaction with treatment was similarly high in both groups.Even though POT can be performed faster than PEC by about half of the intervention time, patients scored the perceived duration and discomfort of both interventions similarly.In this RCT, SIP was diagnosed by pain anamnesis and cold vitality testing. The precise diagnosis of the pulp status is challenging for clinicians since there is no precise correlation between the symptoms and the pulp tissue histopathological status severity ,26. ThusSome studies considered the type and intensity of pulp bleeding as indicative of the pulp status and its reversibility . In the Although both scales are validated and widely used , in thisPain in chewing is the classic symptom of the AAP patient. In this study, patients who had SIP and AAP experienced higher preoperative pain and subsequent higher reduction of pain scores than those without AAP. Some authors have found a positive relationship between occlusal reduction and pain decrease three days after endodontic treatment . In a stIn the same randomised study, the patients’ preoperative pain levels averaged around eight points on a VAS scale . HoweverPOT is a faster technique than PEC ,39. SomeOn the other hand, the patient’s perception of the duration of the treatment is an independent variable. We find no differences between the groups if we look exclusively at the patient-centred results. In the end, a few minutes seem unimportant to the patient. Similarly, no differences were found in the patient’s perception of discomfort between the procedures, even if one was shorter than the other. It has already been shown in other studies that root canal treatment is not as poorly perceived as one might think in terms of its lack of comfort . NeverthWhen talking about efficacy, we think of the ability of a procedure, under ideal conditions, to achieve the desired results, eliminating pain and obtaining patient satisfaction. However, effectiveness means producing the desired effect in real-world settings, with less controlled factors and a wider range of circumstances. In this regard, clinicians prefer the most effective procedure, as simple and fast as possible, especially when dealing with an emergency with no previous appointment. Since POT is more straightforward and shorter than PEC, it could be considered a more effective procedure for treating SIP emergencies. POT is even considered by various public health systems as the treatment of choice for irreversible pulpitis in adults due to its better cost-benefit ratio . HoweverMoreover, a POT is considered an effective and less invasive treatment in the VPT approaches ,38,39,41Regarding study limitations, since the study findings are restricted to large size differences, it cannot be concluded that POT is the “technique of first choice” without having scientifically weighed the cost, availability, and accessibility of both treatments as the relevant factors in choosing the best option. Additionally, the study only looks at short-term outcomes and does not address the seven-day success rate of the two treatment techniques following the standard method . DependiHowever, the study provides valuable information on the comparable efficacy of POT and PEC and the superior effectiveness of POT for the emergency treatment of irreversible pulpitis.The current randomised controlled trial compared two endodontic treatment techniques for emergency patients with symptomatic irreversible pulpitis. The results demonstrated that both pulpectomy and pulpotomy effectively eliminate pain and achieve high levels of patient satisfaction. Furthermore, the patient’s perceptions of the duration and discomfort of the two treatments were comparable.Given that pulpotomy is a faster and more straightforward technique, it may be recommended as a viable and pragmatic option for treating emergency patients with symptomatic irreversible pulpitis.


However, improvement in the experimental group was significantly higher than in the other groups immediately after and at the one-month follow-up after interventions (p < 0.05). DLPFC c-tDCS can prime the immediate effects of CBT and also the lasting effects on the reduction in the fear of pain, fear of movement, and disability in LBP patients.Many studies have shown that low back pain (LBP) is associated with psychosomatic symptoms which may lead to brain changes. This study aimed to investigate the effect of the concurrent application of cognitive behavioral therapy (CBT) and transcranial direct electrical stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on fear of pain, fear of movement, and disability in patients with nonspecific LBP. This study was performed on 45 LBP patients  in three groups: experimental ), sham (c-tDCS turned off after 30 s), and control (only received CBT). In all groups, CBT was conducted for 20 min per session, with two sessions per week for four weeks. Fear of pain, fear of movement, and disability were evaluated using questionnaires at baseline, immediately after, and one month after completion of interventions. Results indicated that all three different types of intervention could significantly reduce fear and disability immediately after intervention ( Low back pain (LBP) is one of the most common disabling musculoskeletal disorders, which involves about 70 to 85% of individuals in different countries ,2,3. EviEvidence indicates that patients with chronic LBP who experience high levels of pain-related anxiety have significantly higher levels of disability ,11,12. ITranscranial direct current stimulation (tDCS), is a noninvasive neuromodulatory technique that recently gained popularity for various purposes ,20. In aMultiple sessions of a CBT program or sham tDCS with CBT reduces pain-related anxiety, fear of movement, and disability in LBP patients with high pain-related anxiety.Multiple sessions of concurrent CBT with c-tDCS over the left DLPFC will be more effective for the reduction in the pain-related anxiety, fear of movement, and disability in LBP patients with high pain-related anxiety compared to CBT alone or concurrent CBT and sham c-tDCS of the left DLPFC.Multiple sessions of concurrent CBT with c-tDCS over the left DLPFC will have a more lasting effect on the reduction in the pain-related anxiety, fear of movement, and disability in LBP patients with high pain-related anxiety compared to CBT alone or concurrent CBT and sham c-tDCS of the left DLPFC.Therefore, in keeping with the reviewed studies, this study aimed to investigate the short-term and lasting effects of concurrent CBT and c-tDCS over the DLPFC on pain, pain-related anxiety, and fear of movements in patients with LBP with high pain-related anxiety. We hypothesized the following:Fifty-six patients with nonspecific LBP were assessed against the inclusion and exclusion criteria. Overall, 8 patients were excluded and 45 CLBP patients  with high pain-related anxiety, aged between 18 and 45 (33.00 ± 1.74), participated in this study .Inclusion criteria were as follows: (1) suffering from LBP for more than six weeks or having recurrent LBP with at least three episodes lasting more than one week (subacute LBP) ,31; (2) Exclusion criteria included reporting any history of neurological diseases, such as Parkinson’s disease, Alzheimer’s, and cerebellar disorders; reporting any history of psychological illnesses; the presence of any signs of radiculopathy or root lumbar spinal cord involvement; structural deformities in the spine, such as scoliosis, kyphosis, or lordosis; and any abnormalities in the vestibular system ,34,35.All patients provided written informed consent before inclusion in this study. This study conforms to the consort checklist criteria. Eligible individuals were randomly based on computer coding assigned into three groups: (1) concurrent left DLPFC c-tDCS and CBT ; (2) concurrent sham c-tDCS and CBT (sham stimulation group); (3) CBT alone (control group).This is a randomized, parallel, double-blind sham-controlled study. From a pool of 56 LBP participants who were referred from neurological clinics by a neurologist, 48 LBP participants with high pain-related anxiety met the inclusion and exclusion criteria. The participants were randomly assigned to three groups following a computer-generated list of random numbers  and was performed following the ethical standards laid down by the Declaration of Helsinki. This study was registered as a clinical trial on the Iranian Registry of Clinical Trials (IRCT20150302021294N6).® II, ActivaTeK™Inc., Gilroy, CA, USA) was applied for 20 min using large electrodes (5 × 7 cm) [In both the experimental and sham stimulation groups, 2 mA c-tDCS (ActivaDose × 7 cm) ,37. In t × 7 cm) ,39 to av × 7 cm) . In the  × 7 cm)   approach” was used ,41, whicAll participants received 8 sessions of CBT administered by a psychologist expert in this field of work . Eight dIn addition, participants were given homework assignments at the end of each session to practice the various techniques presented during the previous sessions. The therapist also collaborated with each patient to generate specific intersession goals  after each session. From the second session, a review of the homework assignments and intersession goal accomplishment; problem-solving discussions; a brief review of materials covered in the previous session; the presentation and practice of new skills; and the collaborative establishment of new homework/goals for the next session were performed by the therapist in each session .Persian translation of the TSK, as a valid and reliable scale ,46, was Persian translation of the PASS, as a valid and reliable scale , was useTo measure the disability level, the Roland–Morris questionnaire, which is a valid and reliable questionnaire ,50, was p > 0.05).p < 0.01) .RM-ANOVA shows a significant main effect of “Time” and also the “Group” × “Time” interaction effect for PASS, TSK, and RMDQ scores ( < 0.01) . Accordi < 0.01) . The finIn this study, for the first time, the short-term and lasting priming effects of multisession concurrent c-tDCS of the left DLPFC and CBT on pain-related anxiety, fear of movement, and disability level of LBP patients with high pain-related anxiety were studied. The findings in the current study indicated that there was a significant decrease in the PASS, TSK, and Roland–Morris questionnaire scores immediately after the interventions in sham and intervention groups. Also, it showed that the combination of c-tDCS and CBT programs was more effective in the reduction in pain-related anxiety, fear of movement, and disability compared to CBT programs alone. The results of the present study showed that the significant improvement in kinesiophobia, pain-related anxiety, and disability after treatment remained for one month postintervention.p < 0.001). This finding is in line with the findings of other studies that concluded that CBT can significantly reduce the pain severity, fear of pain, and disability and also improve the quality of life in patients with chronic LBP [In this study, for the first time, the short-term and lasting priming effects of multisession concurrent c-tDCS of the left DLPFC and CBT on pain-related anxiety, fear of movement, and disability level of LBP patients with high pain-related anxiety were studied. We hypothesized that CBT alone could reduce pain-related anxiety, fear of movement, and disability. The findings in the current study supported this hypothesis and indicated that there was a significant decrease in the PASS, TSK, and Roland–Morris questionnaire scores immediately after the interventions in all groups . In this regard, several review studies concluded that although CBT, as compared to the other interventions, is an effective intervention in the treatment of chronic pain syndromes such as chronic LBP, its effect on fear, anxiety, and pain is not long-lasting [The findings in the current study also supported the second hypothesis with the fact that the combination of c-tDCS and the CBT program was more effective in the reduction in pain-related anxiety, fear of movement, and disability compared to the CBT program alone , while in CBT alone and CBT with sham c-tDCS groups, the results were not significant after one month (p > 0.05). Middlkoop et al. (2010), in their systematic review study, stated that the tDCS technique along with CBT can modulate the central nervous system and so increase the effects of CBT in nonspecific chronic LBP patients [The results of the present study showed that the significant improvement in kinesiophobia, pain-related anxiety, and disability after treatment remained for one month postintervention (patients . There ipatients ,23,47. Ipatients ,54,55. Rpatients . Howeverpatients . There ipatients ,29. Therpatients . The resThe findings of this study have to be seen in light of some limitations. One of the limitations of this study was the age of the participants, who were young adults. Therefore, the results cannot be generalized to middle-aged or older CLBP adults. Therefore, we recommend conducting further studies to investigate the effect of DLPFC c-tDCS on pain-related anxiety, fear of movement, and disability levels in middle-aged or older patients with LBP. In addition, the current study considered only a one-month follow-up. Longer follow-up assessments are also recommended in further studies. Moreover, the main outcome measures for anxiety, fear, and disability were not in quantity in the current study. Conducting future studies is suggested to quantify the outcome measures.The findings in this study provided evidence for the priming effects of multiple-session c-tDCS over the left DLPFC on the effects of CBT on pain-related anxiety, fear of movement, and disability in LBP patients with high pain-related anxiety. The findings in the current study indicated significant decreases in PASS, TSK, and Roland–Morris questionnaire scores immediately after the interventions in all groups. However, these immediate effects were more in the c-tDCS and CBT group compared to the CBT alone and the sham groups. The findings in this study also confirmed the lasting effects of c-tDCS along with CBT in LBP patients with high pain-related anxiety.


We have read with great interest the retrospective study recently published by Crettenand et al. in this journal . We acknOverall pain control should be carefully planned in order to reduce early postoperative pain and also to prevent the onset of potential chronic pain syndromes. Nowadays, we have numerous analgesic options within ERAS programs. However, analgesia should not only result in lower pain scores (NRS or VAS), but also in better quality of recovery . This caWe wonder why another retrospective study is needed as numerous RCTs focusing on the topic of peripheral nerve block  versus thoracic epidural analgesia (TEA) or opioid-based systemic analgesia have been published. The availability of valuable alternatives to TEA is not new per se ,4.TEA is still considered to be the gold standard, serving as a comparator for alternative techniques . This isAcute severe pain in the immediate postoperative period is often considered to be related to the persistence of postsurgical pain after various procedures. Unfortunately, no information was provided if pain scores were assessed in rest or during coughing or mobilization. This is of importance, as sufficient analgesia is needed for mobilization to reduce postoperative complications. Looking at the pooled data of 3 series in our institution, we found median numeric rating scores of 0 [IQR 0 to 2] at rest and 2 [0–5] during mobilization ,9. FinalPatients with CWI received significantly more opioids during the first 3 days postoperatively, illustrating that CWI alone does not provide sufficient analgesia. Unfortunately, the quantity of opioids administered in both groups was not reported. A specification would be helpful as we only know that more than half of the patients with CWI needed the concomitant administration of a strong opioid. Also, as described in the methods, the dose of morphine hydrochloride administration was set to 0.1 mg/kg. However, the administration of morphine had to be adapted to renal function. As renal function is often impaired after renal surgery, there are other better options like methadone or hydromorphone. Finally, patients receiving increased doses of postoperative opioids were at higher risk for chronic use. This is of importance as around 11 to 26% of all open renal surgery patients will develop chronic pain postoperatively . FurtherFinally, the earlier removal of CWI was only carried out due to the design of the protocol, as the elastomeric pump was programmed to deliver ropivacaine for 72 h. Hence, the statement that adequate oral pain control was achieved earlier for CWI reflects the study design rather than its superiority. However, we acknowledge that the removal of TEA and the switch to oral analgesic treatment remains challenging and is often neglected. We recently showed that the administration of oral opioids to reduce and remove TEA is of no advantage compared to the use of placebo . In the We were surprised to read that CWI resulted in a 40% overall cost reduction, being even more shocked to discover that there were no data or details supporting that statement in the paper. The total time in the operating room (OR) is similar in both groups , despite the longer induction time in the TEA group (12 min). The author’s statement in the discussion, that the 40% cost reduction is due to reduced OR time, is therefore not supported by the data provided. Knowing the overall cost of one minute OR time in our tertiary institution (from the same country), a difference of 3 min in OR time  will not result in significant cost savings. Even taking into consideration an additional daily visit by a trained analgesia nurse and the cost of consumables (for both groups), neither an additional half-day hospitalization nor reduced nursing workload is likely to result in a difference of CHF 11,200 per patient. We wonder if the use of other, unreported resources, such as intermediate care or prolonged post-anesthetic care stays, could be an issue. Therefore, a detailed description of generated costs would be helpful.As correctly stated by the authors as a limitation, they included a low number of patients in the study but also needed a long observation period of nearly 10 years. This introduces important biases such as different surgeons and the development  of surgical and perioperative techniques over a decade. It also needs to be clarified whether TEA and CWI were equally distributed over the observation time.From our point of view, CWI is a possible alternative to TEA for patients with contraindications or for patients at risk for hypotension, but at the expense of higher early postoperative opioid consumption and poorer analgesia. Still, epidural analgesia provides superior pain control and potentially offers benefits including early mobility, improved cardiopulmonary function and reduced risk of venous thromboembolism ,17. The


In the subgroup analysis, for patients whose limb lengthening was less than 10 mm after THA, the pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 24 and 48 h . However, in patients whose limb lengthening was more than 10 mm after THA, there was no significant difference between the pain intensity at activity and rest in the two groups at postoperative 6, 24, and 48 h (p > 0.05). PNB did not show superiority in terms of pain reduction in patients whose limb lengthening was more than 10 mm after THA. Further investigations on methods for reducing pain in patients whose leg length is increased by more than 10 mm are needed.The effect of peripheral nerve block (PNB) according to leg lengthening following total hip arthroplasty (THA) has not been studied yet. The purpose of this study was to investigate the effect of PNB according to the change in leg length after THA. From January 2016 to August 2021, 353 patients who underwent unilateral THA for osteonecrosis of the femoral head or osteoarthritis of the hip joint were retrospectively reviewed. The patients were divided into two groups for comparison: 217 patients who controlled postoperative pain using only intravenous venous patient-controlled analgesia (IV PCA) (PCA group) and 136 patients who controlled postoperative pain using PNB and IV PCA (PCA + PNB group). We further divided the patients into two groups (leg lengthening after surgery < 10 mm and >10 mm) and compared them. After propensity score matching, the PCA and PCA + PNB groups, with 134 patients each, were compared and analyzed. The pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 6, 24, and 48 h ( Restoring the normal hip biomechanics in total hip arthroplasty (THA) is the most important factor to obtain excellent surgical outcomes and functional recovery ,2,3,4. ISeveral studies have shown that peripheral nerve block (PNB) after THA has excellent advantages in terms of pain control, as well as in decreasing the risk of various postoperative complications in patients ,16,17. TWe hypothesized that the increased leg lengthening during THA could cause more postoperative pain after surgery. As such, it was assumed that the effect of PNB would be better for patients with significant leg lengthening. The purpose of this study was to investigate the effect of peripheral nerve block according to the change in leg length after THA.After Institutional Review Board approval was obtained, electrical medical records were retrospectively reviewed. We collected data from 544 patients who consecutively underwent unilateral THA performed by a senior experienced orthopedic surgeon in a tertiary hospital from January 2016 to August 2021. Patients who had hip fracture, inflammatory hip arthritis, rheumatoid arthritis, any infection history of hip joint, revision surgery, and patients who need special devices due to severe instability, anatomical deformity, and bone defects were excluded. Patients requiring excessive soft tissue release due to an LLD > 30 mm were also excluded. Finally, among the 544 patients, 353 patients who underwent unilateral THA for osteonecrosis of femoral head or osteoarthritis of the hip joint were enrolled in this study. The patients were divided into two groups: 217 patients who controlled postoperative pain using only intravenous venous patient-controlled analgesia (IV PCA) (PCA group), and 136 patients who controlled postoperative pain using PNB and IV PCA (PCA + PNB group). Propensity score matching was performed for age, sex, body mass index, American Society of Anesthesiologists score, and diagnosis among these groups. Furthermore, demographic data, radiologic data, and clinical outcomes were assessed in all patients.All the THA procedures were performed by a single surgeon (KKP) with the patient in a lateral decubitus position and stabilized with the aid of a pelvic positioner. All the surgeries were performed using a posterolateral hip approach and the short external rotators were repaired. Cementless acetabular cups and tapered wedge stems were used in all cases. All the cases used ceramic liner and ceramic head. In all cases, hip stability was assessed after final acetabular cups, liner, and final femoral broach with trial head and neck component were implanted. To minimize LLD, preoperative template method was routinely conducted using standard hip radiographs with magnification markers. The femoral component size and osteotomy level were determined. Intraoperatively, the uninvolved lower limb was used as a reference, considering the relative difference at the patella in the lateral decubitus position . To optiThirty minutes before the end of the surgery, IV fentanyl 1 µg/kg and palonosetron 0.075 mg were administered to the patient for postoperative analgesia and antiemetic effects, respectively. All the patients were administered IV PCA for 48 h postoperatively, which comprised fentanyl 7 µg/kg and palonosetron 0.075 mg , delivered as a 2 mL/h background infusion and 0.5 mL doses on patient demand, with a 15 min lockout time. In the ward, all the patients were administered celecoxib 200 mg orally and acetaminophen 1 g intravenously every 12 h. All the patients started postoperative exercise following the same rehabilitation protocol. Alongside this, bedside exercises  were performed 0–6 h after the operation. Standing with a walker ambulation was permitted on postoperative day 1 following the same protocol for all patients. Additional pain control was administered as rescue medication  through intramuscular injections.Preoperative and postoperative LLD of the hips of the patients were measured in full-length antero-posterior standing radiographs on the day before surgery and 3 months after surgery, respectively. As landmarks for LLD measurement, bilateral radiologic teardrops at the pelvis and the centers of the lesser trochanters at the femurs were used. The distance between these two landmarks was measured in terms of the change in leg length before and after THA. The degree of measurement reliability was evaluated using intraclass correlation coefficients (ICC). Calculation of the ICC was performed by two experienced orthopedic surgeons . For the ICC, values less than 0.2 were considered to indicate poor agreement; 0.21 to 0.40, fair agreement; 0.41 to 0.60, moderate agreement; 0.61 to 0.80, good agreement; and above 0.80, excellent agreement .Clinical outcome assessment was performed before surgery and 3 months after using the Harris Hip Score and Western Ontario and McMaster Universities Osteoarthritis index. The pain intensity at rest and during activity was evaluated using an 11-point numeric rating scale . Pain scores were assessed at three-time points, 6, 24, and 48 h after surgery.t-test  or Mann–Whitney test . Categorical variables were compared using the chi-square test or Fisher’s exact test. p-value < 0.05 was considered statistically significant in all cases. After propensity score matching, continuous variables were analyzed using Wilcoxon signed rank test, and categorical variables were analyzed using the McNemnar’s test. The analysis of data and propensity score matching were performed using the SAS software .Descriptive statistics were performed, and normality distribution was assessed by the Shapiro–Wilk test. Continuous variables were analyzed using the Student’s p = 0.7000) and limb lengthening after surgery .After propensity score matching, two groups of 134 patients each were compared and analyzed. The baseline characteristic of the patients, diagnosis, preoperative LLD, and limb lengthening after surgery are presented in p = 0.0001, 0.0009, and <0.0001, respectively). However, there was no significant difference in the pain intensity at activity between the two groups at postoperative 6, 24, and 48 h (p > 0.05). In addition, there was no significant difference between the two groups in terms of preoperative and postoperative clinical scores.We further divided the patients into two groups according to leg lengthening (<10 mm and >10 mm) and compared them. After propensity score matching, the pain intensity at rest in postoperative 6 h after surgery in the group with more than 10 mm of leg lengthening was higher than that in the group with less than 10 mm of leg lengthening. There were no statistically significant differences between groups in terms of pain intensity at rest and activity .p = 0.0165 and 0.0015, respectively). However, there was no significant difference in pain intensity at activity between the two groups at postoperative 6, 24, and 48 h (p > 0.05)  .p > 0.05)  .For all patients, we calculated the total count of rescue medication prescribed during the first two postoperative days, converting the total dose of rescue medication into a total morphine equivalent dose, in mg, using converting factors . The aveThis study investigated the analgesic effect and early postoperative functional outcomes of PNB according to change in leg length after THA. The principal finding of this study was that immediate postoperative pain intensity in the first 48 h of THA was significantly lower in PCA with PNB than in PCA alone. In particular, in the subgroup analysis according to leg lengthening < 10 mm or > 10 mm, there was no statistical difference in the pain reduction effect of PCA with PNB compared to the PCA alone. In addition, the effect of PNB on rescue medication was not affected by the difference in leg lengthening after THA. It can be assumed that the pain relief effect of PNB was greater in patients whose leg lengthening after THA was less than 10 mm.The pain relief effect of PNB in THA at early postoperative period is well known, and PNB has been considered an essential component of pain management ,22,23,24In the case of hip diseases requiring THA, shortened leg length can be found in many cases, and proper leg length restoration is very important for obtaining excellent surgical outcome . AlthougBenedetti et al. investigated that leg lengthening of up to 20 mm after THA did not significantly alter the symmetry of hip movement in hip kinematics . We confLeg lengthening after THA is often accompanied by soft tissue release such as capsule, tendon, and muscle, which can then cause an increase in soft tissue tension and nerve stretching. Therefore, longer leg lengthening after THA can cause more postoperative pain. Also, the hip capsule contains a moderate and diffuse density of nociceptive fibers; therefore, the patients with leg lengthening >10 mm after surgery could feel more pain than the patients with little change in leg length. However, the hip is diffusely innervated by branches of the femoral, sciatic, obturator, and gluteal nerves, and perforating muscular branches, which hinder the control of postoperative pain with a single PNB. Therefore, in case of THA requiring leg lengthening > 10 mm, considered to require more soft tissue procedures, other methods besides PNB, such as intraoperative periarticular injection, should be applied to achieve good results in reducing postoperative pain.This study has several limitations. First, this study was a single-center, retrospective comparative study. Since this was not a randomized controlled study, selection bias could exist. To minimize the bias, propensity score matching was performed to analyze the pain reduction effect of PNB according to leg lengthening after THA. Second, the results of this study were primarily derived from the patient’s subjective pain scale. The bias from the pain scale and survey cannot be overlooked, as it is a subjective index. Third, the information on the total amount of fentanyl could not be accurately obtained because some patients discontinued IV PCA due to side effects of it. Fourth, the different types of THA implants by manufacturers and changes in medial offset after THA can also affect postoperative pain, but we did not consider these aspects, so this is a limitation of the current study.In conclusion, PNB has overall beneficial effects for early postoperative pain relief after THA. However, PNB did not show superiority in terms of pain reduction in patients whose leg lengthening was >10 mm after THA. Further investigations of methods for reducing pain in patients whose leg length is increased by more than 10 mm are needed.


A high discrepancy between the number of tender and swollen joints (e.g. ΔTSJ ≥ 7) has previously been used as an indication for the presence of changes in central mechanisms in patients with moderate-to-high disease activity. In this study, we explored whether the ΔTSJ can also be used to obtain insights into the underlying pain mechanisms in patients with on average well-controlled disease activity.A 2 year retrospective analysis of routinely obtained 28-joint DAS (DAS28) components was performed on 45 patients with low inflammatory activity at the group level. All patients underwent pressure pain threshold (PPT) and electrical pain threshold (EPT) measurements and completed four self-report questionnaires .Patients with a ΔTSJ ≥ 3 at least once in the past 2 years showed significantly lower EPT and PPT values and higher levels of pain and disability on the SF-36v2 compared with the ΔTSJ < 3 group. Furthermore, GPQ scores were significantly higher in those with ΔTSJ ≥ 3, while CSI and PCS scores were similar.These findings suggest that in patients in the ΔTSJ ≥ 3 group, mechanisms other than inflammation (only) underlie the pain. Moreover, our findings suggest that among the multiple potential underlying psychological mechanisms, pain catastrophizing (as measured by the PCS) and psychological hypervigilance (as measured by the CSI) do not play an important role. These findings could be useful in the clinical management of the patient. Depending on the dominant mechanism underlying the (persistent) pain, patients might respond differently to treatment. Key messagesUsing routinely obtained DAS28 measurements, indications on the dominant pain mechanism might be obtained.Depending on the dominant pain mechanism, patients with RA may respond differently to treatment.The pharmacological treatment of RA has shown significant progress, with a growing number of patients achieving minimal disease activity according to the 28-joint DAS (DAS28) . DespiteUnderstanding the dominant mechanism underlying pain in RA patients could be useful, because different subgroups of patients might respond differently to treatment approaches . TherefoTo assess the dominant underlying pain mechanism, a useful approach within daily clinical care is to monitor the difference between tender and swollen joint counts (ΔTSJ). Previous studies have provided indications for the feasibility of this approach, showing that the ΔTSJ can differentiate RA patients with an FM clinical phenotype (RA-FM) from a larger group of RA patients , 20. GivIn addition to the ΔTSJ, there are several instruments and tools available to gain insights into the involvement of central mechanisms underlying persistent pain. Quantitative sensory testing (QST) with standardized stimuli has been proposed as a valuable method for assessing central mechanisms . By measIn this cross-sectional study, we aimed to explore how routinely obtained DAS28 measurements can provide insights into the mechanisms underlying pain in RA patients with mostly well-controlled disease activity. We recruited a targeted sample of 46 RA patients and conducted QST measurements and standardized self-report questionnaires. Initially, we performed a retrospective analysis of DAS28 measurements over 2 years to investigate the numbers and variability of tender and swollen joint counts over time. Based on insights gained from this analysis, we stratified the patients into groups using historical ΔTSJ values, aiming to create approximately equal-sized groups with and without a ΔTSJ discrepancy. Finally, we compared the outcomes of the QST measurements and self-report questionnaires {CSI, GPQ and the pain catastrophizing scale (PCS) } betweenPatients diagnosed with RA were included for QST and questionnaire measurements from September 2020 until August 2022. In total, 46 patients from the rheumatology department of the Medisch Spectrum Twente (MST) hospital in Enschede, The Netherlands were included. Owing to the exploratory nature of this study, no a priori power analysis was conducted. All QST and questionnaire measurements were performed at this outpatient location. All patients received written information before the study, signed an informed consent and were compensated for their time at the end of the study by provision of a voucher. Patients who were diagnosed with diabetes or PsA, who had an implanted stimulation device or who were pregnant were excluded. All these criteria were evaluated by asking patients for these conditions. The study was approved by the medical ethical committee united  and was conducted in accordance with the 1964 Helsinki Declaration and its later amendments.Patients were recruited in two subsequent phases. Using the existing clinical dataset on outpatient RA patients, initially patients who had shown a ΔTSJ ≥ 4 at least once in the last 18 months were selected and contacted. After ∼20 patients had been included, additional patients were recruited from the remainder of the dataset (i.e. patients without a ΔTSJ ≥ 4 in the past 18 months). An attempt was made to match the patients from this second selection as closely as possible on age and sex to the patients already included. Importantly, the exact criterion on which we wanted to stratify the patients was not known before the analyses.In total, five questionnaires were filled in by the patients at the end of the measurement session. A standardized case report form was developed to obtain general characteristics of the patient. This included a question to rate the level of pain perceived at that moment on an NRS ranging from 0 (no pain) to 10 (worst pain imaginable). The CSI  consistsRheumatology Advances in Practice Online.Measurements were performed by one of two trained experimenters. For photographs of the equipment used for the quantitative sensory testing, see 2 probe using a battery-powered, hand-held algometer . Patients were asked to indicate whenever the induced sensation became annoying for the first time, after which the examiner would stop applying pressure. Three subsequent measurements were performed and averaged into a single value.Pressure pain thresholds were evaluated bilaterally at the supraspinatus muscle and at the lateral epicondyle . At thesElectrical pain thresholds (EPTs) were evaluated at the right upper arm at the intermediate part of the deltoid muscle  using paAfter all patients had been included and measured, their DAS28-ESR measurements  over time were evaluated retrospectively. These routinely collected measurements were obtained from the electronic health records of the patient. For the analysis, a maximum of the four most recent DAS28 measurements in the past 2 years were considered. In most patients, DAS28-ESR measurements were not conducted on the day of the present study. As a best proxy for current disease activity and for disease activity classification , the most-test [on log10-transformed data if a significant (P < 0.05) Shapiro–Wilk value was found] or a Mann–Whitney U test if the log10-transformation did not result in a normal distribution. For categorical variables, a χ2 test was used. Correlations were calculated using a two-tailed Pearson correlation coefficient. Statistical analyses were performed using MATLAB 2019b (The MathWorks Inc.).For continuous variables, group-level differences between the groups with and without a ΔTSJ discrepancy were evaluated using Student’s unpaired For 33 of 46 patients, at least four DAS28-ESR measurements were conducted in the past 2 years. Of the remaining 13 patients, 11 had three available DAS28-ESR measurements; 1 patient (no. 27) had one available measurement and 1 patient  did not have any DAS28-ESR measurements over the past 2 years. Of the 45 included patients, 31 patients had a ΔTSJ ≥ 1 at least once over the past 2 years. In total, 25, 22, 21 and 17 patients had at least one ΔTSJ of ≥2, ≥3, ≥4 and ≥5, respectively. For a more detailed overview of the observed ΔTSJ in the four most recent DAS28-ESR measurements, see Rheumatology Advances in Practice Online.Using a ΔTSJ ≥ 3 for stratification resulted in a total of 23 patients without (ΔTSJ < 3) and 22 patients with a discrepancy (ΔTSJ ≥ 3) in their joint counts. For a full overview of baseline characteristics of the patients, see Rheumatology Advances in Practice Online.For an overview of responses to the questionnaires and pain threshold measurements, see n = 45), significant moderate to strong correlations were found between the CSI and the PCS  and between the GPQ and the CSI . The GPQ was correlated significantly, but more weakly than the CSI, with the PCS . The GPQ was correlated significantly with the PPTs measured at the left  and right  lateral epicondyle. Between the GPQ and the PPT measured at the left (r = −0.39) and right (r = −0.29) supraspinatus muscle and the EPT (r = −0.30), near-significant (P < 0.075) correlations were found. In the ΔTSJ < 3 group (n = 23), a significant correlation was found only between the CSI and the GPQ questionnaires . In the ΔTSJ ≥ 3 group (n = 22), statistically significant correlations were also found between the CSI and the PCS . Additionally, in this group the GPQ was significantly correlated with the PPT measured at the left  and right  lateral epicondyle and on the left supraspinatus muscle . Lastly, a near-significant correlation (P < 0.075) between the GPQ and EPT was observed (r = −0.45). For a full overview of all correlations, see In the total sample  cut-off in ΔTSJ of ≥3 in patients with well-controlled disease activity, patients can be identified who display lower EPT and PPT values and higher GPQ scores and who also report higher levels of pain and disability. These findings suggest that mechanisms other than joint inflammation alone underlie the pain in these patients. Moreover, finding no differences in CSI and PCS scores suggests that commonly believed psychological processes of pain catastrophizing and psychological hypervigilance do not play an important role.Rheumatology Advances in Practice Online). However, we observed lower levels of inflammation and swollen joints overall, which aligns better with the well-controlled patients commonly encountered in current clinical practice, in which treat-to-target principles are adopted [Previous studies examining tender and swollen joint counts, in addition to ΔTSJ, have focused primarily on patients with high inflammatory activity, as indicated by an elevated ESR and/or a high baseline number of swollen joints , 19, 20  adopted .In this retrospective analysis of DAS28 outcomes collected during routine clinical practice over a 2 year period, we found that eight (18%) patients exhibited a ΔTSJ ≥ 7 at least once during the last 2 years or within the last four visits. This contrasts with previous studies, where such discrepancies were typically observed in only one measurement , 20. Not2). Our retrospective analysis did reveal such minor variability, as evidenced by 31 (67%) patients exhibiting at least one discrepancy (ΔTSJ ≥ 1) over time.We expected initially to observe random or natural variability in both swollen and tender joint counts over time, which would also lead to discrepancies between measurements. Variations in the severity of inflammation, such as those caused by life events or changes in medication, can result in fluctuations in the number of swollen and tender joints over time. Additionally, the way in which joint assessments are conducted could influence the outcomes. For instance, the number of swollen joints can vary depending on visual inspection performed by different clinicians or nurses, and the assessment of painful joints relies on the subjective experience of the patient following gentle pressure applied by the clinician or nurse  zero during one visit and then increase to nine during the next visit. This indicates that the ΔTSJ of a patient is not consistently high, suggesting caution when interpreting a single measurement of ΔTSJ.Earlier studies used a ΔTSJ ≥ 7 as a grouping variable to identify RA-FM patients , 20 or aRheumatology Advances in Practice Online) resulted in lower EPTs and PPTs at the left and right lateral epicondyle in the ΔTSJ ≥ 3 group compared with the ΔTSJ < 3 group. PPT measurements at the supraspinatus muscle showed no significant differences between the groups, although a near-significant difference was observed on the left side, which was, for most patients, the non-dominant, more sensitive side [Using a ΔTSJ ≥ 3 , higher physical disability and pain levels in the ΔTSJ ≥ 3 group could be observed compared with the ΔTSJ < 3 group. These findings, obtained by using a substantially lower ΔTSJ cut-off and by including historical measurements, are similar to the earlier studies, whereby a ΔTSJ cut-off of ≥7 was used to identify patients with characteristics of RA-FM [Furthermore, it was found that when using a ΔTSJ ≥ 3  justifies and provides insights for designing a prospective study that could investigate the relationship between the pain threshold measurements and questionnaires with the ΔTSJ over time. Such a prospective study might also provide insights into the developmental trajectories of the underlying pain mechanisms in patients.By grouping RA patients using a ΔTSJ based on the most recent DAS28-ESR measurements during a 2 year period rather than a single measurement, at a group level patients could be identified with lower EPTs and PPTs and higher GPQ scores, while also displaying higher levels of pain and disability. These findings suggest that in these patients, mechanisms other than solely inflammatory mechanisms underlie the (persistent) pain. Our results also suggest that among the multiple potential underlying mechanisms, pain catastrophizing and psychological hypervigilance do not play an important role. These findings could be useful in the clinical management of the patient because, depending on the dominant mechanism underlying the (persistent) pain, patients might respond differently to treatment.Rheumatology Advances in Practice Online.rkad076_Supplementary_DataClick here for additional data file.


Mindfulness‐based interventions have a positive impact on pain, craving, and well‐being in both patients with chronic pain and those with opioid use disorder (OUD). Although data are limited, mindfulness‐based cognitive therapy (MBCT) might be a promising treatment for patients with chronic noncancer pain combined with OUD. The aim of this qualitative study was to explore the feasibility and process of change during MBCT in this particular population.In this qualitative pilot study, 21 patients who were hospitalized for rotation to buprenorphine/naloxone as agonist treatment for chronic pain and OUD were offered MBCT. Semistructured interviews were conducted to explore experienced barriers and facilitators to MBCT. Patients who participated in MBCT were also interviewed on their perceived process of change.Of 21 patients invited to participate in MBCT, 12 initially expressed interest but only four eventually participated in MBCT. The timing of the intervention, group format, somatic complaints, and practical difficulties were identified as the main barriers to participation. Facilitating factors included having a positive attribution toward MBCT, an intrinsic motivation to change, and practical support. The four MBCT participants mentioned several important mechanisms of change, including reduction of opioid craving and improved coping with pain.MBCT offered in the current study was not feasible for the majority of patients with pain and OUD. Changing the timing of MBCT by providing it at an earlier stage of the treatment and offering MBCT in an online format may facilitate participation.  MBIs can cultivate specific mindfulness skills, such as self‐awareness, acceptance, and self‐compassion Garland, . During MBIs have repeatedly been shown effective in improving coping with negative emotions, both in patients with mood and anxiety disorders  based on the Dutch Medical Research Involving Human Subject Act (WMO), as MBCT is already part of regular clinical care at our department. According to the WMO, studies on regular clinical care are exempted from ethical approval, as long as burden for participation is minimal. The regional ethical committee assessed the study protocol (protocol no. 2015‐1551) and concluded that it met these criteria for exemption.All patients scheduled for BuNa rotation were informed on the possibility to participate in the study during hospitalization  . The MATE is a clinician‐administered interview used in Dutch addiction care  participating in MBCT were still collected. Hereafter, patients who decided to participate in MBCT started the 8‐week MBCT. Subsequently, the MBCT participants were invited for a second semistructured interview on their perceived process of change during MBCT.2.6Patients were interviewed in a semistructured manner. In the first interview, prior to start of MBCT, patients were asked (1) whether they wanted to participate in MBCT, (2) their motives for (not) participating, and (3) possible barriers and facilitators to participation. Questions were followed by probes to gain more insights about the barriers and facilitators, and were asked in an open nondirective manner, allowing patients to speak freely. Some patients who first agreed to participate in MBCT and later changed their mind were interviewed twice  out of the 21 patients did not want to participate in MBCT. The primary reasons for this were having already participated in an MBI before, having too much pain, too much travel distance and time, and not being interested in psychosocial interventions. Three patients out of this group were interviewed to further explore their barriers to participation. The study flow is also described in Appendix Twelve patients initially expressed interest in MBCT, but eight of these patients refrained from participating in the 3 months before the start of MBCT. From these eight patients, two patients were only interviewed during their first moment of choice (when being positive about participation), two were interviewed only during their second moment of choice (when refraining from participation), and four were interviewed at both these timepoints. In Appendix Four patients (19%) participated in MBCT. Three out of these patients were interviewed prior to MBCT about barriers and facilitators. One patient participated in all eight sessions, two patients participated in seven sessions, and one patient participated in six sessions. All four patients attended the silent day. All four patients were interviewed to explore their perceived process of change.3.2n = 15) can be seen below in Table Fifteen of 21 patients participated in at least one qualitative interview. The baseline demographic and clinical characteristics of the interviewed population  or fentanyl (six patients), with an average oral morphine equivalent dose of 169 mg.3.3From analysis of the interviews, three categories of barriers and facilitators emerged: (1) personal characteristics, 2) psychosocial factors, and (3) MBCT training factors , which was confirmed by her partner.3.3.3.2Two patients mentioned that participation in MBCT had no direct effect on their pain. One patient, however, said that MBCT helped in creating a feeling of calmness, and that this feeling reduced pain levels. He had realized that having stress also led to headaches. All patients expressed that they became better in dealing with pain, either by letting it go, by looking for distractions, or by accepting it. Patients also became aware of the influence of stress on pain. One patient expressed that the body scan meditation was helpful in focusing on where in the body she felt pain and accepting it. Another patient experienced his daily life was less affected by pain than prior to MBCT, and that he was part of society again.A patient expressed that when being stressed, he normally would crave for opioids. MBCT helped to reduce stress and in this way reduced craving. This patient also expressed an increased ability to cope with craving by reflecting on the craving, realizing why he was craving for opioids, and being aware of the negative consequences of giving in to the craving. Patients also said MBCT helped to focus on something else when experiencing craving or opioid withdrawal symptoms, such as a body scan meditation.4This pilot study investigated the feasibility and perceived process of change of MBCT as an add‐on treatment after agonist treatment with BuNa in patients with chronic pain and prescription OUD. An important finding is that most patients (17 out of 21) chose not to participate in MBCT. Although MBCT can have beneficial effects, offering MBCT in its current format does not seem particularly feasible for this patient population. By understanding the barriers to participation and reducing these barriers, more patients may choose to participate in MBCT in the future.4.1We offered MBCT 3 months after initiating BuNa treatment. A frequently mentioned barrier to participation was that MBCT was offered late within the treatment process. Offering MBCT earlier might mean that patients could use mindfulness skills to deal with difficult moments of increased pain or craving during pharmacotherapy. Indeed, in a recent pilot study, 15 patients participated in Mindfulness‐Oriented Recovery Enhancement (MORE) during methadone substitution therapy. Unlike our population, these patients were primarily using illicit opioids at baseline, but they also all had chronic pain. The MORE group was compared with a group being offered counseling. In both treatment arms, there was little dropout during this period (Cooperman et al., Other barriers included mental complaints and the fear that pain and mental complaints would get worse with MBCT, and not wanting to participate in a group. Regarding these fears, giving patients the opportunity to try out a single MBCT session may be a solution to take some worries away.There were also practical barriers to participation: having other responsibilities, limited social support, too much pain, and too many mental complaints. Having limited time and practical/social support have also been identified as barriers in other studies on feasibility of MBIs in patients using opioids for chronic pain (Zgierska, Burzinski, Cox, Kloke, Singles, et al., Ultimately, next to patients who experienced these difficulties, there was also a subset of patients in our study who were simply not interested in MBCT. For some patients, psychoeducation aimed at understanding their pain better may be a first step toward an MBI. For other patients, a psychological intervention may just not be the most fitting treatment.4.2While our study gives insight in the barriers and facilitators to participation, we are limited in drawing conclusions about the effectiveness of the intervention. The four MBCT participants indicated that changes in their pain coping, opioid craving, and an increased sense of functioning contributed to their recovery process. They all perceived MBCT as useful. Improved pain coping has also been reported in another qualitative study in 21 patients with chronic low back pain and long‐term opioid use participating in an MBI (Zgierska, Burzinski, Cox, Kloke, Singles, et al., 4.3A strength of our study is the representative sample of patients from clinical practice that we asked to participate in our study, allowing us to investigate the barriers to participation in depth. A limitation, however, is that due to the limited number of MBCT participants, data saturation was not achieved regarding our questions on the process of change during MBCT.5Although the participants who completed the MBCT were generally positive, MBCT in the current form is not feasible for the majority of the patient population. We identified multiple barriers to MBCT participation, including timing of the intervention and practical difficulties. Changing the timing of the MBCT by providing it at an earlier stage of the treatment and offering MBCT in an online format may facilitate participation. Furthermore, psychoeducation and giving patients the opportunity to try out a single MBCT session might support them to make a decision toward participation too.Karen Lathouwers, Anne E. M. Speckens, and Arnt F. A. Schellekens designed the study. Anne E. M. Speckens was the principal investigator for this study regarding the MBCT. Arnt F. A. Schellekens was the responsible physician and principal investigator for BuNa rotation. Karen Lathouwers, Linda Cillessen, and Anne E. M. Speckens conducted the qualitative interviews. Karen Lathouwers and Sander Dekkers collected quantitative data. Karen Lathouwers, Linda Cillessen, Imke Hanssen, Hannah Ellerbroek, Sandra A. S. van den Heuvel, Sander Dekkers, Anne E. M. Speckens and Arnt F. A. Schellekens contributed to data analysis. Hannah Ellerbroek, Imke Hanssen, and Karen Lathouwers developed the initial draft of the manuscript after which all authors read, revised, and supplemented the draft of the manuscript and agreed to the final version.The authors declare no conflicts of interest.https://publons.com/publon/10.1002/brb3.3005.The peer review history for this article is available at Supp InformationClick here for additional data file.Supp Information 2Click here for additional data file.


Widespread pain hypersensitivity and enhanced temporal summation of pain (TSP) are commonly reported in patients with complex regional pain syndrome (CRPS) and discussed as proxies for central sensitization. This study aimed to directly relate such signs of neuronal hyperexcitability to the pain phenotype of CRPS patients.Twenty-one CRPS patients and 20 healthy controls (HC) were recruited. The pain phenotype including spatial pain extent (assessed in % body surface) and intensity were assessed and related to widespread pain hypersensitivity, TSP, and psychological factors. Quantitative sensory testing (QST) was performed in the affected, the contralateral and a remote (control) area.P < .001, contralateral: t(35) = 3.19, P = .005, control: t(31) = 2.65, P = .012). Additionally, patients showed increased TSP in the affected area  = 4.57, P = .009) compared to HC. TSP was even more enhanced in patients with a high compared to a low spatial pain extent  = 5.67, P = .008), suggesting pronounced spinal sensitization in patients with extended pain patterns. Furthermore, the spatial pain extent positively correlated with the Bath Body Perception Disturbance Scale .CRPS patients showed decreased pressure pain thresholds in all tested areas (affected: t(34)  = 4.98, Overall, we provide evidence that the pain phenotype in CRPS, that is, spatial pain extent, might be related to sensitization mechanism within the central nociceptive system. This study points towards central neuronal excitability as a potential therapeutic target in patients with more widespread CRPS. Complex regional pain syndrome (CRPS) is characterized by persisting pain disproportionate to the initiating event.,,,,CRPS patients commonly present with allodynia and hyperalgesia to mechanical stimuli which are not necessarily restricted to the affected area.This study was part of a larger study including patients with CRPS, neuropathic pain after spinal cord injury, and low back pain, as well as age- and sex-matched healthy controls (HC), which were recruited between November 2019 and April 2022. The results presented in this manuscript are based on a consecutive sample of all patients with CRPS (N = 21) and 20 age-matched HC. CRPS patients were recruited at the Department of Physical Medicine and Rheumatology of the Balgrist University Hospital in Zurich, Switzerland, and diagnosed by an experienced rheumatologist (FB). All patients needed to fulfill the clinical Budapest CriteriaAs previously stated, this study was part of a larger study, which comprised a comprehensive test battery (two visits of 3 hours each) including the evaluation of clinical pain characteristics, neurophysiological assessments, experimental pain paradigms, and psychological and pain questionnaires. The presented data in this manuscript are based on (1) psychological questionnaires ,The PCS consists of 13 items, where participants have to reflect on past painful experiences and choose from different negative thoughts and feelings which are presented on a numerical scale from 0  to 4 .http://www.whocc.no/atc_ddd_index/].Pain characteristics included the spatial pain extent and the pain intensity. CRPS patients were asked to mark their painful areas by shading the corresponding area on two standardized body charts  on A4 papers. Here, only painful areas associated with CRPS were considered for further analysis. The borders of each area were marked manually by the investigator and run through a custom-made analysis software calculating the percentage of the marked body area (pixels) in relation to the entire body surface.The participants were measured in three different areas: their affected area, the contralateral homologous body site and in a remote, pain-free body area (control area). The contralateral and control area were measured to detect possible spinal and supraspinal sensitization, respectively.The QST protocol was performed by trained experimenters based on the German Research Network on Neuropathic Pain (DFNS).TSP was assessed in response to twelve consecutive pinprick stimulations  applied at a frequency of 0.33 Hz only to the affected and control area. The order of measurement area was randomized. The stimulation intensity was set individually at an intensity of 4 on a numeric rating scale (NRS) from 0 to 10 . The intensity of NRS 4 was assessed by a staircase method just before the TSP paradigm, with an upper limit of stimulation intensity at 512 mN. During the TSP protocol, participants were instructed to rate each stimulation on the NRS.All statistical tests were performed at an α level of 0.05 in R Studio statistical software (R version 4.1.2 for Windows). Missing data were excluded from further analysis (N/A).t-test or Wilcoxon signed-rank test in the case of normal or non-normal distributed data, respectively. Additionally, the pain characteristics  and psychological factors  of CRPS patients were analysed using Pearson  or Spearman  correlations with the corrplot function from the corrplot package in R studio. Multiple comparison correction was applied using the Benjamini-Hochberg method.Demographics and questionnaire scores were tested for normality by a Shapiro Wilk test. The sex proportion within CRPS patients and HCs was compared by a Chi-squared test. Age, height, weight, and psychological factors  were compared between CRPS patients and HCs using an unpaired t-test or Wilcoxon signed-rank test). The t-tests or Wilcoxen signed-rank tests were corrected for testing in multiple areas by the Benjamini-Hochberg method. Within the CRPS patients only, the z-scores of the different measurement areas were compared using a repeated measure ANOVA or Friedman test for either normally or not normally distributed data, respectively. Paired t-tests served as post-hoc test and were corrected for multiple comparisons using the Bonferroni method. Finally, the relationship between widespread pain hypersensitivities (significant gain of function in control area) and pain characteristics  or psychological factors  was investigated. The pain intensity and the psychological factors were normally distributed and thereby analyzed using Pearson correlations. The spatial pain extent was not normally distributed and after inspection of the descriptive statistics, two phenotypic subgroups were identified . A histogram of the spatial pain extent can be found in t-test. Multiple testing within pain characteristics or psychological factors was corrected using the Benjamin-Hochberg method. In addition, a possible confounding effect of pain medication on widespread pain hypersensitivities was investigated by dividing patients into two subgroups according to whether they regularly take pain medication (yes/no). For this purpose, QST measures with a significant gain of function in the control area were compared between the pain medication subgroups by an unpaired t-test.QST z-scores were tested for normality by the Shapiro Wilk test and compared between CRPS patients and HCs  and psychological factors  with TSP was tested within the CRPS patients by including these factors as interaction effect with the stimulation subblock . Pain intensity and psychological factors were included as numeric vector, whereas the spatial pain extent was included as phenotypic subgroup . Testing within multiple areas and pain characteristics or psychological factors was corrected using the Benjamin-Hochberg method. Lastly, a potential confounding effect of pain medication on TSP was investigated by including the pain medication subgroup (yes/no) as factor into the model (subblock*medication). As previously, the P values were corrected for testing in multiple areas using the Benjamin-Hochberg method.The differences in TSP between CRPS patients and HC was analyzed by general linear mixed models in order to keep the information of temporal aspect of TSP. The 12 stimulations of the TSP protocol were divided into four subblocks of three stimulations each to reduce the model’s dimensionality. The models were set up using the R package lme4P < .001), HADS-depression (t(23) = 4.42, P < .001) and PCS scores (t(33) = 4.88, P < .001) compared to HC. CRPS-specific characteristics are presented in P = .048). The HADS and PCS, however, did not correlate with the spatial pain extent . Patients with a higher HADS and PCS score reported higher spontaneous pain intensities . The BBPDS score did not correlate with the pain intensity .The demographics of the study population and information regarding psychological factors are shown in There were a few dropouts due to non-tolerance of the protocol encountered , PPT (N = 1)). Furthermore, in two CRPS patients no control area could be assessed because it was either affected by pain (independent spreading pattern) or a frozen shoulder condition.P < .001, MPS: t(34) = 2.54, P = .048, P = .002). A gain of function in the contralateral  = 2.65, P = .012). There was no statistical difference between CRPS patients and HC for the remaining QST parameters (P > .05).CRPS patients showed a significant gain of function by means of decreased PPT and increased mechanical pain sensitivity (MPS) in the affected area compared to HC (PPT: t(34) = 4.98, alateral  as well alateral  of CRPS P = .009; MPT: F = 4.89, P = .015). Post-hoc analyses revealed that PPT was lower in the affected compared to the contralateral (t(17) = 2.99, P = .025) and control area (t(15) = 3.39, P = .012). In addition, MPT was lower in the affected compared to the control area (t(16) = 2.88, P = .033). There was no statistical difference between the stimulation areas for the remaining QST parameters (P > .05).Within the CRPS cohort, PPT and MPT were different between the three measurement areas  = 7.13, P = .066) or any of the psychological questionnaire scores . In addition, there was no difference in widespread pain hypersensitivity between CRPS patients with a high (>5%) compared to a low (<5%) spatial pain extent (t(14) = 0.68, P = .510). Finally, there was no difference in widespread pain hypersensitivity whether the patients regularly took pain medication or not (t(10) = 0.01, P = .993).Widespread pain hypersensitivity, assessed by a significant gain of function (decrease in PPT) in the control area, did not correlate with pain intensity  = 13.30, P < .001) and HCs  = 5.51, P = .002; control area: F = 5.62, P = .002). subblock*cohort = 4.57, P = .009), but not in the control area  = 2.08, P = .107). Post-hoc tests within the affected area are illustrated in subblock*area = 0.38, P = .769).TSP was observed for both CRPS patients  = 16.25, All results regarding the interaction effect between the TSP-subblock and pain characteristics or psychological factors are illustrated in The aim of this study was to better characterize the clinical pain phenotype of CRPS patients and relate it to signs of central sensitization and psychological distress. In line with previous work, this study provides additional evidence that central sensitization might contribute to the pathophysiology of CRPS,,,,Central sensitization is proposed to be a pathophysiological mechanism in CRPSRegardless of probable central hyperexcitability, a potential coexistence of peripheral sensitization, such as irritable primary nociceptive neurons, might additionally lower pain thresholds in the affected area.In addition to mechanical hyperalgesia, mechanical hypoesthesia was present in the affected area of CRPS patients (by means of reduced VDT). The combination of mechanical gain and loss of function was previously described in patients with CRPS.Increased TSP was seen in the affected area of CRPS compared to HC, supporting the hypothesis of a sensitized central nervous system in CRPS. TSP is considered to indicate increased excitability of second-order neurons located in the dorsal horn of the spinal cord.Since some pain characteristics  might indicate central sensitization,,,Both spatial pain extent and pain intensity did not relate to widespread pain hypersensitivity . Regarding spatial pain extent, these findings are in line with studies investigating patients with fibromyalgia and knee osteoarthritis.The spontaneous pain intensity correlated with psychological factors such as depression, anxiety, and pain catastrophizing whereas the spatial pain extent correlated with perceptual disturbances of the affected area. In line with these findings, previous systematic reviews in chronic pain conditions discussed the association between psychological factors and greater pain intensity.Furthermore, a relationship between CRPS severity and body perception disturbances has previously been reported.,The sample size of patients with CRPS was rather small with a large variability in terms of pain characteristics  and CRPS duration. On the one hand, this heterogeneity made it possible to investigate possible differences in terms of underlying mechanisms between these patients; on the other hand, it also limits the generalizability of the observed results. It would be of great interest to investigate whether these results are consistent in a larger patient sample reporting more homogeneous pain characteristics. Furthermore, the data presented are a subset of a larger test battery. The additional tests performed on the participants may have influenced the results presented by, for example, sensitizing the tested areas. Moreover, this study comes with the limitation that patients maintained their intake of pain medication during the period of study participation, potentially confounding our primary readouts. Nevertheless, we found no significant effect of pain medication on pain sensitivities assessed by QST or TSP. Finally, previous literature has mainly reported a pronounced ipsilateral spread of sensitization in patients with CRPS.To conclude, CRPS patients showed widespread pain hypersensitivity as means of decreased PPT in the control area and increased TSP in the affected area, corroborating previous studies indicate a potential presence of central sensitization in these patients. Most importantly, patients with high spatial pain extent showed increased TSP and body perception disturbances compared to patients with low spatial pain extent. Hence, the spatial pain extent itself might provide a clinically relevant measure for signs of sensitization mechanism within the central nervous system and may provide a marker for therapeutic success.pnad040_Supplementary_DataClick here for additional data file.


Many patients during manual therapy after anterior ligament reconstruction will experience severe pain, which has a negative impact on their rehabilitation. However, there is rarely an analgesic method for these patients during rehabilitation. Nitrous oxide with rapid analgesic and sedative effects is often used to relieve pain in minor procedures. The purpose of this study is to determine whether or not nitrous oxide analgesia decreases pain compared to oxygen during manual therapy after anterior ligament reconstruction.This single-center, randomized, double-blind and controlled trial will recruit 120 patients. Patients ≥ 18 years old undergoing manual therapy after anterior ligament reconstruction (1 month post-operative) with acute pain (VAS ≥ 4) are included. The main exclusion criteria included the following: pulmonary embolism, intestinal obstruction, pneumothorax. Patients will be randomly allocated to the intervention group (A) and the control group (B) in a ratio of 1:1. Doctors, therapists, patients, and data collectors are all blind to the study. The manual therapy will be performed by therapists. Nurses who implemented the intervention handed the doctors envelopes containing the patients’ codes and allocation of A or B. Group A will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment  given as 30-min treatment sessions, once daily, and group B will receive oxygen plus conventional treatment  under the same conditions. Assessments will be taken 2 min before the intervention (T0), 5 min after the beginning of the intervention (T1), and 5 min after the intervention finished (T2). The primary outcome is pain score. Secondary outcomes include vital signs, side effects, joint range of motion, adjuvant analgesia need, therapist and patient satisfaction, and whether willing to receive the same gas again.We expect nitrous oxide inhalation to have a beneficial effect on the pain of patients who receive manual therapy after anterior ligament reconstruction.If this treatment appears beneficial, it could improve patients’ satisfaction and quality of life potentially and even be implemented widely in hospital and rehabilitation settings.https://www.chictr.org.cn.ClinicalTrials.gov identifier, ChiCTR2200061175 , The online version contains supplementary material available at 10.1186/s13063-023-07732-z. Anterior cruciate ligament (ACL) reconstruction is one of the most common operations in orthopedic . ACL rec2O), as an analgesic and sedative, which has the advantages of simple handling, fast onset, good effect, and few adverse reactions, is commonly used in various painful procedures . Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist.