This double-blinded, randomized and sham-controlled pilot clinical trial aimed to investigate the preliminary clinical efficacy and feasibility of combining mindfulness meditation (MM) and transcranial direct current stimulation (tDCS) for pain and associated symptoms in patients with fibromyalgia syndrome (FMS).n = 10) or no intervention . Patients in the bimodal therapy groups received a week of training in MM prior to the stimulation. Participants reported pain intensity, the primary outcome, by filling in a pain diary daily throughout the whole study. They were also evaluated for quality of life, pressure pain sensitivity, psychological wellbeing, sleep quality and sleep quantity. Assessments were performed at three time points .Included FMS patients (age: 33 to 70) were randomized to three different groups to receive either ten daily sessions of anodal tDCS over the left primary motor cortex paired with MM for 20 min , sham tDCS combined with MM (sham + MM, Participants in the active + MM group did not exhibit reduced pain intensity following the bimodal therapy compared to controls. Patients in active group demonstrated clinically meaningful and significantly higher quality of life following the therapeutic intervention than other groups. There was no significant difference among groups regarding pressure pain sensitivity, sleep parameters and psychological scales. The combined treatment was well tolerated among participants, with no serious adverse effects.This study was the first to pair these two effective non-pharmacological therapies for pain management in FMS. In the light of an underpowered sample size, repetitive anodal tDCS combined with MM did not improve pain or FMS-associated symptoms. However, patients in the active + MM group reported higher quality of life than the control groups. Studies with more participants and longer follow-ups are required to confirm our findings.www.drks.de], identifier [DRKS00023490].[ Fibromyalgia syndrome (FMS) is a heterogeneous primary pain condition, characterized by persistent and widespread non-inflammatory musculoskeletal chronic pain. FMS has an incidence rate of 2-5% in the worldwide population, with the majority of the patients consisting of women . FMS carvia surface electrodes for effective, safe and non-invasive brain stimulation in humans  and mindfulness meditation (MM). tDCS comprises the application of a weak direct electric current to the scalp delivered n humans , 7. Despn humans , 9. The n humans –14, withn humans , 16. Nevn humans  failed tn humans . Prefronn humans . Howevern humans . Recent n humans , 20. Latn humans  showed tn humans .Mindfulness meditation is a cognitive training practice, which fosters the ‘detached, non-judgmental and non-elaborative’ awareness of the present moment. Over the decades, there has been a significant surge in the scientific evidence supporting the effectiveness of MM in FMS and other chronic pain conditions –26. ParrThe analgesic effects of anodal tDCS in chronic pain patients have been shown to be boosted when it is combined with other non-pharmacological interventions , 31. ConThe primary aim was to test the feasibility and efficacy of two weeks of the tDCS and MM intervention in pain reduction in FMS patients following a one-week training in meditation in a pilot clinical trial. We hypothesized that the participants in the active stimulation group pairing anodal tDCS at left M1 and MM will report greater pain relief than those who received a combination of MM and sham stimulation and those who received no therapeutic intervention. The no treatment group served as a control for symptom variability in FMS patients. We also examined the impact of the bimodal therapy on pain sensitivity, quality of life, psychological wellbeing and sleep.www.drks.de (DRKS00023490). All experimental procedures conformed to the ethical standards of the 1964 Declaration of Helsinki and its revisions.All participants were informed prior to inclusion about the protocols in detail. Written informed consent was signed before participation. This pilot clinical trial was approved by the Ethics Committee of the University of Göttingen under the registration number 33/8/20 and is registered at Patients diagnosed with FMS were recruited through the outpatient pain clinic of the Department of Anesthesiology, University Medical Centre, Göttingen, reports in local newspapers, advertisements in the hospital, social media and patient support groups for fibromyalgia and rheumatological conditions. Individuals from 30 to 70 years old were considered suitable to participate if they fulfilled the preliminary American College of Rheumatology Diagnostic Criteria 2010 for FMS with a widespread pain index ≥ 7 and a symptom severity score ≥ 5 . FinallyGraphPad 2021 software. The patients in sham + MM or NoT were invited to receive the active tDCS treatment following the completion of the study.The study was a monocenter, parallel, randomized, placebo-controlled clinical trial to test the efficacy of ten daily 20-minute sessions of anodal tDCS over the left M1 paired with MM over two weeks (Monday to Friday) in patients with FMS. The included participants were randomized to 3 intervention groups: active + MM (n = 10), which received anodal tDCS paired with MM; sham + MM (n = 10), which received sham tDCS combined with MM; and NoT (n = 10), which received neither tDCS nor MM. Randomization was performed after inclusion using the randomizer function from The study was double blind, as both patient and experimenter were unaware of the tDCS protocol (sham or active). Blinding was maintained and executed by the study leader, who programmed the stimulators and was not involved in experiments. However, there was no blinding with regard to the NoT group. Pressure algometry was performed by the blinded experimenters, unblinding occurred after completion of the study.For the participants in the active + MM or sham + MM groups, the study had four phases (a) 1 week baseline period; (b) 1 week (Monday to Friday) of daily MM training; (c) 2 weeks of daily bimodal therapy intervention (Monday to Friday) groups and (d) one month of follow-up period, as illustrated in baseline). They did not have any further scheduled appointment at the hospital apart from Tacute and T4weeks evaluations limited to questionnaire data and pressure algometry and taken at similar time points as for the groups receiving the therapeutic interventions.The NoT group did not receive any meditation training or bimodal therapy. Participants in the NoT group also filled in the pain and sleep diary daily over the whole study period of 9 weeks and all other measurements likewise at the baseline visit (Tbaseline), within 5 days (Tacute) and after 4 weeks (T4weeks) following the last stimulation session. The level of mindfulness was measured on the first and the last day of the MM training.Pain intensity, sleep quality and sleep quantity were rated daily in a diary by the participants for the whole duration of the study. All other outcome variables were measured one week before the start of MM training  was used to assess pain intensity, as self-reported by the patient. This 11-point scale comprising integers ranged from 0 to 10; 0 meaning no pain and 10 indicating the worst imaginable pain. Patients rated their pain on the NRS twice a day (after waking up in the morning and before going to sleep in the evening) throughout the whole study. The pain scores were averaged to give one NRS mean value for each study week. When a patient missed one NRS value on a particular day, the missing value was given the score for the other time of the same day. Some patients reported their pain as a range of values  and the NRS score was taken as the mean . The reproducibility and validity of the NRS has been shown, making it a reliable measure for pain assessment as a clinical outcome in many studies –35. At lQuality of life and functional capacity of patients was assessed using the German version of the Fibromyalgia Impact Questionnaire  . The lat2 probe bilaterally at 8 sites: bilateral mid-trapezius, lateral epicondyle, mid-thigh and tibialis anterior muscles. The same experimenter performed the PPT at the three time points for one patient. The pressure was gradually increased by 50 kPa/s until the patient said ‘Stop’ or when their perception first changed from pressure to pain. The maximal stimulation pressure was 1,000 kPa to avoid tissue damage. We administered the pressure algometer in the same order for all patients- right tibialis, right midthigh, right epicondyle, right mid-trapezius, left mid-trapezius, left epicondyle, left mid-thigh and left tibialis. For each site, PPT was measured twice with at least a 30s interval (Pressure pain threshold (PPT) is a reliable and reproducible measure of pain sensitivity for FMS , 43. Theinterval  and the The validated German version of the Depression, Anxiety and Stress Scale- 21 Items (DASS), comprising three self-report subscales, was used to evaluate depression (Cronbach’s α ≥ 0.91), anxiety (Cronbach’s α = 0.78–0.82) and stress (Cronbach’s α = 0.81–0.89) of the participants , 46. EacThe NRS was used to assess sleep quality, as reported by the patient. This 11-point scale comprising integers ranged from 0 to 10; 0 meaning no restful sleep and 10 indicating the maximum restful sleep. Participants rated their sleep quality of the preceding night every morning just after waking up in the diary. The scores were averaged to give one NRS mean value for each week.The number of hours the participant slept the previous night was recorded in the diary by the patient every morning just after waking up. The sleep quality scores were averaged to give one mean value for each week.The German version of the 14-item short-scale of the Freiburg Mindfulness Inventory (FMI) served as a monitor whether the patients were able to engage in mindfulness practice and learn how to meditate . The FMIn = 10) and sham + MM (n = 10) groups underwent the 5-day long MM training. The MM training intervention was the same for both groups. The brief MM training and meditation protocols were designed and instructed by a meditation teacher who had more than 20 years of training in teaching mindfulness. The training was designed based on the guide for mindfulness practice as defined in Kabat-Zinn  as tools. Following each meditation training session, we encouraged patients to ask questions and report difficulties experienced during the meditation. On the last two days of MM training, the electrodes, the cables and the rubber bandages were placed on the head of the subject (without stimulation) to mimic the conditions for the combined MM and tDCS intervention. Additionally, prior to every meditation session during both the training week and bimodal therapy weeks, a 5-min nature sound audio – consisting of birds chirping, river flowing and forest sounds – was played to relax the participants.Previous studies applying mindfulness training in chronic pain often use 8-week long mindfulness interventions –29. ZeidIn addition to the FMI each participant was asked after the last two MM training sessions, whether “they had the feeling that they were truly meditating” (adapted from ) to assevia a pair of surface electrodes connected to a NeuroConn DC-Stimulator Plus . The anode  was placed over the left M1, which was defined as the point 5 cm from Cz in the direction of the left preauricular notch measured with a measuring tape. The anode size was large; therefore, the area it covered encompassed a broad area of the motor cortex. The reference electrode  was placed over the right supraorbital frontal area. The dimensions of the electrodes were based on a previous study (A constant direct current was applied daily for 20 minutes over two weeks (Monday to Friday) us study . To fix us study .For the active anodal tDCS of M1, a constant current of 2 mA with 15 s ramp up at the beginning and 15 s ramp down at the end was applied for 20 min. Stimulation with 2 mA intensity has been shown to be safe for use in both healthy individuals  and chroWe noted the resistance value from the stimulator at 5 minutes following the start of the stimulation and it was ensured that the resistance was below 10 kΩ . The mea2 = 1.80, p = 0.180), suggesting a successful blinding.To estimate the success of blinding in the study, we implemented the end-of-study guess approach, which is a commonly used method in tDCS studies –61. PartDuring the two treatment weeks, each session started with 5 minutes of body scan exercise followed by 20 minutes of guided MM identical to the audios used for the last three days of meditation training. The stimulator was switched on immediately after the body scan and the start of stimulation was paired with the start of the 20-minute meditation. We included the body scan exercise to ensure that participants were actually already meditating at the onset of stimulation.IBM SPSS 28.0 and graphs were plotted in GraphPad Prism 9. Normality of raw data or residuals was verified with the Shapiro-Wilk test and visually with normality plots. Non-parametric tests were used where parametric assumptions for tests were violated or data could not be transformed to meet the assumptions. For mixed model ANOVA (MANOVA) analyses, the sphericity assumption for the repeated factor was checked with Mauchly’s test and Greenhouse- Geisser corrections were applied to the degrees of freedom for deviations from sphericity. The homoscedasticity assumption for independent groups was assessed with Levene’s test and the variables were corrected to baseline if the assumption was violated. Effect size was computed as eta squared η2 and was interpreted based on Cohen’s benchmark categorization   . Data wePost hoc analyses were conducted using Least Significant Difference (LSD) test following Bonferroni correction to test how pain intensity changes over time compared to baseline measure.To test the effects of the bimodal therapy on the primary outcome variable - NRS pain intensity - we used a two-way MANOVA, with WEEK , second week of stimulation (Stim2), four follow-up weeks ) as the repeated factor and GROUP  as the independent factor. baseline, Tacute, T4weeks) and GROUP as repeated and independent factors, respectively. For each DASS subscale, To test the effects of the MM training on mindfulness level (n = 20), a two-way MANOVA was conducted for FMI scores, with DAY (day 1 and day 5 of MM training week) and MM GROUP  as factors.The data for the sleep quantity and quality were analyzed in the same way as for NRS pain intensity. For the FIQ and PPT measures, two-way MANOVAs were run with the respective outcome variable as the dependent variable, with TIME  and whether they showed ≥ 14% reduction in FIQ scores. The Fisher-Freeman-Halton Exact test was used for both analyses owing to violation of Chi-squared test assumptions.To test the clinical relevance of pain improvement over time across groups, the number of patients in each group exhibiting ≥ 20% decrease in NRS compared to baseline was counted. A three-way contingency table analysis for proportions was carried out with GROUP, follow-up weeks and whether they showed sufficient decrease in NRS as categories. A similar analysis was done for the clinical relevance of quality of life. However, the categories included GROUP, TIME  = 0.36, p = 0.703) and any interaction between GROUP and TIME  = 0.87, p = 0.553). However, there was a significant medium main effect of WEEK  = 2.85, p = 0.025, η2 = 0.095) , with no other significant pairwise comparisons  . By postparisons . This shp = 0.248; PostStim2: p = 1.00; PostStim3: p = 0.249; PostStim4: p = 0.510). Nevertheless, visual representation of the percentage of patients with clinically relevant pain decrease across group and time illustrated the following: (1) the percentage of patients in active + MM group was always higher than sham + MM group at each follow-up week and (2) the percentage of patients in NoT group fluctuated over time, demonstrating no consistent pattern , which accounted for 22% of the total variation in the data .Acute (PostStim1) baseline-corrected pain intensity correlated positively with acute baseline-corrected FIQ scores  but not TIME  = 0.021, p = 0.885) and TIME-GROUP interaction  = 2.10, p = 0.142). Following pairwise comparisons with Sidak post hoc test, MM + active group (p = 0.002) and NoT groups (p = 0.017)  = 4.34, = 0.017) .acute and T4weeks, we found a significant association between proportion of patients with ≥ 14% decrease in FIQ and group at Tacute (p = 0.003) but not at T4weeks (p = 0.272). Bonferroni corrected pairwise comparisons between groups for patients with ≥ 14% FIQ reduction at Tacute showed that significantly lower number of patients in sham + MM and NoT groups demonstrated a clinically relevant improvement in quality of life than in active + MM . For the PPT, no significant difference for the main interaction between TIME and GROUP was observed  = 0.848, p = 0.501).For the PPT, the MANOVA failed to show any significant difference among the three groups  = 0.318, GG  = 2.74, p = 0.083) and no significant GROUP-WEEK interaction  = 0.87, p = 0.553. Nevertheless, we found a large significant main effect of WEEK  = 4.78, p < 0.001, η2 = 0.150). Post hoc analysis showed the overall sleep quality of participants in the study (N = 30) was higher at PostStim4 than baseline (p = 0.003). Regarding sleep quantity, we did not find any significant results  = 0.643, p = 0.534; WEEK: FGG  = 2.21, p = 0.072; interaction: FGG  = 1.33, p = 0.235).The MANOVA to test whether the bimodal therapy was associated with improvement in sleep quality revealed no differences among groups . Based on the visual representation of the data  the percentage of patients with normal anxiety and depression level is higher in active + MM than in other groups at Tacute and T4weeks; (3) the percentage of patients with normal stress levels is higher in active + MM than in other groups only at Tacute but is equal between active + MM and sham + MM at T4weeks.We did not find any significant association between symptom severity of each of the DASS subscales and group at Tthe data , we can p = 0.082). No main effect of group  = 0.297, p = 0.593) or significant interaction between group and time  = 3.81, p = 0.067) was found.No significant differences were observed in mindfulness level as assessed by the 14-item FMI questionnaire after the week of MM training compared to before  = 3.38, Out of the 20 participants who underwent the one-week MM training, 85% (n = 17) reported that they felt that they truly meditated on each of the two last days of training. Only one patient reported not having the feeling of meditating on both days.None of the participants discontinued the stimulation or required a medical intervention during or following stimulation. acute) but not at T4weeks.The main objective of this proof-of-concept pilot clinical trial was to test the effectiveness and feasibility of ten daily sessions of 2 mA anodal tDCS of the left M1 paired with MM over two weeks (Monday to Friday) to reduce pain and to improve associated symptoms in FMS patients briefly trained in MM. We compared the effects of active tDCS during MM to sham tDCS during MM and NoT on NRS pain intensity (primary outcome), associated FMS symptoms  and quality of life of patients. Contrary to our hypothesis, the active + MM group did not show reduced clinical pain over time compared to sham + MM and the NoT groups. Patients in all three groups exhibited reduced pain intensity immediately after the two-weeks of intervention period compared to baseline indicating a non-specific effect. Among the secondary outcomes investigated in the study, we only found significantly higher quality of life in the active + MM group compared to the control groups. In a responder analysis, a larger number of FMS patients showed clinically meaningful improvement in FIQ scores in the active + MM group compared to the other groups immediately after treatment (Tvia long-term potentiation mechanisms (Repetitive anodal tDCS over the left M1 received a level-B recommendation as probably effective in pain reduction in FMS patients , 19. Deschanisms , 65. Thichanisms –68. Howechanisms , 70. Howchanisms  failed tchanisms . It is ichanisms . Elevatechanisms . FurtherMoreover, investigating the neural mechanisms underlying mindfulness meditation-induced pain reduction using fMRI in an experimental pain induction task in healthy individuals, Zeidan et al.  found siPrevious clinical studies testing the efficacy of pairing tDCS with MM or other non-pharmacological interventions demonstrated improvement in pain, quality of life and/or disease-related symptoms in chronic pain conditions, such as FMS, neuropathic pain and knee osteoarthritis among others. Combining MM and tDCS in knee osteoarthritis reduced pain intensity, pain sensitivity and disease-symptoms as well as enhanced conditional pain modulation in the active treatment group, compared to sham , 75. FMSConcerning the pressure pain thresholds, our lack of significance among the groups is in line with most of previous studies failing to demonstrate an effect of tDCS on pain sensitivity in FMS , 21, 76.The higher quality of life observed in the active group, compared to the sham and NoT groups, despite the lack of other group effects might allow some speculation on other possible mechanisms involved in the combination of MM and tDCS in fibromyalgia patients. FMS patients exhibit a hyperactive sympathetic nervous system , 84. TheThis study used a one-week MM training prior to the intervention in a clinical cohort using a standardized training procedure. The MM training was chosen as a clinically feasible although limited training yet sufficient to establish a different and MM-based setting for the concurrent stimulation. Zeidan et al.  demonstrTwo strengths of our methodology are the inclusion of the NoT group and a MM training phase. The pain and symptoms experienced by FMS patients are variable, with fluctuating intensity over time and the course of the condition . This haAn important limitation of published literature , 75 or oThe findings of this trial must be interpreted in the light of our study limitations. The underpowered sample size indeed hampers the quality of the efficacy investigated. No monotherapy groups were included in our clinical trial, making it impossible to elucidate how the effects of this bimodal intervention on clinical outcomes compare to tDCS only and MM only intervention effects. Since we were interested in proof of concept in a fairly typical clinical sample, patients were allowed to continue their medication and non-pharmacological treatment regimens throughout the study; however, participants were told not to change the dosage and type of medication or therapy. Participants were taking different types of medication in different doses including NSAIDs, tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective norepinephrine reuptake inhibitors, owing to the heterogeneity of FMS symptoms. Medication withdrawal in FMS trials is a challenge for patients and has its own bias in “selecting” specific patients. Furthermore, the treatment was administered as a group therapy, which allowed for interaction between the participants either during or after the sessions. This could have led to additional non-specific psychological influences on patients, i.e., one participant complaining about their situation might negatively influence another, or positive group experiences reducing subjective symptoms. It is important to note the lack of age-matched groups in the study. However, a study comparing the differences in effects of anodal tDCS over M1 between young and elderly adults shows no significant differences in corticospinal excitability . FurtherFinally, the challenges associated with a clinical trial run during the global COVID-19 pandemic should not be overlooked. Strict hygiene guidelines were put forth during our experiments such as constant wearing of masks and distance between patients. Some participants reported discomfort and difficulty in breathing attributed to the wearing of masks during meditation. Other confounding factors associated with the pandemic, which could not be controlled for in this study, were subjects receiving COVID-19 vaccination, illness or demise of participants’ relatives as well as the fluctuating nature of the outbreak.Two weeks of an innovative bimodal intervention, concurrently combining tDCS and MM failed to improve clinical pain and associated symptoms in FMS patients briefly trained in meditation, without any serious adverse effects. All patients reported a non-specific decrease in pain intensity immediately after the two weeks of intervention compared to baseline and this decrease was observed in all groups, even the one not receiving any treatment. Still FMS patients in the active group reported clinically meaningful enhanced quality of life than those in the control groups immediately after the stimulation. The major limiting factor in this study was the underpowered sample size. Future research with larger samples and extended follow-ups is required to further test the efficacy as well as to unravel the potential mechanisms underlying therapeutic effects of a combined MM and tDCS therapy.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the University Medical Center Göttingen. The patients/participants provided their written informed consent to participate in this study.PR: study design, writing the manuscript and proofreading. PR and SK: data collection and analysis. PR, SK, FP, and AA: data interpretation. FP and AA: supervising study design. AA: supervising clinical trial and data analysis. All authors contributed to the article and approved the submitted version.


To assess the clinical efficacy and safety of ibuprofen plus traction, reposition, and hip spica cast in the treatment of developmental dysplasia of the hip (DDH).  Between January 2019 and July 2020, 60 children with DDH treaded in department of orthopedics of our institution were assessed for eligibility and recruited. They were assigned at a ratio of 1 : 1 to receive either traction + reposition + hip spica cast plus analgesia pump (observation group) or traction + reposition + hip spica cast plus analgesia pump and oral ibuprofen (control group). The outcome measures included clinical efficacy, pain scores, unexpected pain calls, the dosage of analgesia pump, and adverse events. P > 0.05). The patients given oral ibuprofen were associated with significantly lower pain scores at 24 h and 72 h postoperatively versus those without oral ibuprofen (P < 0.05). Analgesics with oral ibuprofen resulted in fewer unexpected pain calls versus analgesics without oral ibuprofen within 72 h postoperatively (P < 0.05). The application of oral ibuprofen in the analgesia pump showed great improvement in lowering the dosage of analgesia pump versus the absence of ibuprofen (P < 0.05). The incidence of adverse events was similar between the two groups of patients (P > 0.05).  The two groups had similar clinical efficacy ( Traction + reposition + hip spica cast plus analgesia pump and oral ibuprofen effectively mitigated postoperative pain in children with DDH and reduces analgesic drug dosage with a high safety profile. Developmental dysplasia of the hip (DDH) is a serious congenital disorder of the skeletal system that results from developmental malformation of the hip joint due to abnormality of the femoral head to the acetabulum within the joint capsule and is associated with severe pain and dysfunction , 2. The Traditional Chinese medicine classifies it as “bone arthralgia,” “rheumatic arthralgia,” and “joint running.” “Su Wen·Bi Lun” states “three qi of wind, cold, dampness intermingle, and all the five internal organs would be affected.” Traditional Chinese medicine manipulation can directly act on the muscles and bones of the affected part, which can enhance muscle tension and stability, improve joint movement, local microcirculation, and improve tissue metabolism, exerting good efficacy and safety for conservative treatment of early hip dysplasia , 7.Traction + reposition + hip spica cast is a common clinical treatment for DDH. The osteotomy of the acetabulum and femur frequently required in surgery is frequently associated with intense postoperative pain. Research has demonstrated moderate to severe postoperative pain in approximately 35% of cases and inadequate postoperative analgesia in 70% of cases. The postoperative pain decreases the treatment satisfaction of patients and families and limits postoperative functional recovery, leading to delayed recovery and discharge. The postoperative pain results in a state of stress that suppresses the immune function, and persistent pain inflicts irreversible damage to the physiological functions of the child, which requires timely and effective analgesia , 9. ThusBefore enrollment, the investigators obtained the informed consent from the patients. The protocol was approved by the hospital ethics committee (SH-WU20190102). All procedures were in line with guidelines of the Declaration of Helsinki.http://www.randomizer.org/). For the blindness of the study, randomization procedures and assignments were conducted by independent assistants who were not involved in screening or evaluating participants.Between January 2019 and July 2020, 60 children with DDH treaded in our institution were assessed for eligibility and recruited. They were assigned (1 : 1) to receive either traction + reposition + hip spica cast plus analgesia pump (observation group) or traction + reposition + hip spica cast plus analgesia pump and oral ibuprofen (control group) . RandomiInclusion criteria were as follows: children with a clinical diagnosis of developmental dysplasia of the hip, with X-ray manifestations of hip subluxation or complete dislocation, and with traction + reposition + hip spica cast. Exclusion criteria were as follows: children with allergies to opioid analgesics and nonsteroidal drugs, whose parents were not cooperative, and with significant abnormalities in routine examinations and tests on admission.Procedure: all children were subjected to skin traction after admission, with an average traction duration of 2–9 days, and the skin traction was released 1 day before surgery. After general anesthesia, the surgeon moved the affected hip to feel the tension of the adductor muscles and performed a trial hip repositioning. The effectiveness of hip repositioning was evaluated intraoperatively by hip arthrography, using an average dose of 1.35 (0.8–1.5) ml of contrast agent Uvexan , with a needle entry point 2 cm below the adductor tendon of the hip joint. The effectiveness of hip repositioning was evaluated by using Bowen's standard chart after imaging: the proximal femoral epiphysis was below the Hilgenreiner line (H line), 2/3 of the horizontal radius of the femoral head was within the Perkin line, and the femoral head was located below the outer edge of the glenoid hip after repositioning. In the case of unsuccessful repositioning or poor repositioning suggested by hip arthrography, simple incisional repositioning was performed through a small anterior incision. A 2-3 cm surgical incision was made 1-2 cm below the anterior superior iliac spine in the direction of the dermatome, the subcutaneous tissues were separated to the deep fascia, accessed along the space between the broad fascial tensor and sutures, the rectus femoris muscle was cut at the anterior inferior iliac spine and reflexed to expose the joint capsule, the iliopsoas tendon was cut, and the joint capsule was incised obliquely from superior to inferior to the transverse acetabular ligament. The intraarticular fatty tissue and round ligaments were removed, the hip joint was repositioned by flexion and abduction, and the joint capsule was sutured. The rectus femoris muscle was reconstructed and the incision was closed layer by layer. All procedures were performed by 2 senior surgeons. Postoperatively, all cases were immobilized in a hip spica cast after successful repositioning for 5–14 weeks. The hip spica brace was worn all day for 14 weeks after removal of the hip spica cast and then changed to half-day wear until 1 year .Atractylodes 10 g, and honey-fried licorice root 10 g. It was added or subtracted according to the symptoms; for those with severe pain, red peony 10 g and salvia 10 g were added; for those with yin deficiency and fire, Dendrobium 10 g and Ophiopogon japonicus 15 g were added; for those with qi deficiency, 10 g of Astragalus and 10 g of Codonopsis were added. The abovementioned traditional Chinese medicines are uniformly decocted by the decoction room of the hospital, one dose per day; it is decocted in 400 ml of water and taken twice in the morning and evening. The course of treatment is 4 weeks.On the basis of the treatment of the two groups, modified Gancao Fuzi decoction was given: cassia twig 20 g, Paofu tablet 10 g (fried first), ① Clinical efficacy: Excellent: the function and shape of the affected part were completely restored with anatomical repositioning or close to anatomical repositioning. Good: the functional repositioning was achieved, and the function and shape were basically restored. Poor: the function repositioning was failed, with obvious deformity in shape and significantly compromised function. Total clinical efficacy = (excellent + good)/total number of cases × 100%. ② Pain score: Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) was used for pain assessment: the total score was 10 points, with 0–3 points for no pain or mild pain, 4–7 points for moderate pain, and 8–10 points for severe pain. Higher scores indicated more intense pain. ③ Unexpected pain calls: the number of unexpected pain calls was recorded for both groups within 72 h after surgery. ④ Analgesia pump dosage: the analgesia pump was removed at 48 h postoperatively in both groups, and the dosage of analgesia pump medication was recorded by our medical staff after removal. ⑤ Adverse events: the adverse events that occurred during treatment were recorded including vomiting, urinary retention, and respiratory depression.t-test. Normally distributed measurement data are represented by mean plus and minus standard deviation  and analysed using the chi-square test. Differences were considered statistically significant at P < 0.05.SPSS 22.0 was used for data analyses, and GraphPad Prism 8 was used for image rendering. The measurement data were expressed as (P > 0.05)  .P < 0.05)  .P < 0.05)  .P < 0.05)  .P > 0.05) (The incidence of adverse events was similar between the two groups of patients ( > 0.05) .The pathological changes of DDH involve structures such as the acetabulum, femoral head, joint capsule, surrounding muscles, and ligaments, and the specific pathogenesis remains yet unclear. Studies have shown that the traditional swaddling position forces the baby's hip joint to be in a straight position, which makes the acetabulum and femoral head mismatch during the development of the acetabulum and eventually progresses to DDH. Another study shows that some women need to use relaxin to relax the pelvic ligaments during childbirth, but relaxin can enter the fetus through the placental barrier, which may lead to relaxation of the ligaments around the acetabulum and become a potential risk of DDH in infants and young children. Adductor tension contracture is an important pathological change in children with DDH aged 0–6 months, and most hips can be reduced after release of the adductor muscle , 15.The prevalence of developmental dysplasia of the hip varies between different geographic regions and races, and the prevalence in China is about 1–3 per 1,000, with the incidence in girls being about 3–6 times higher than that in boys . CurrentThe related pathological changes of hip dislocation are mentioned in the literature of traditional Chinese medicine, and DDH is called “hipbone displacement.” “The Essentials of the Bone-Setting Heart Method” states “for people with hip bone displacement, the buttocks would move obliquely,” which points out the clinical characteristics of hip dislocation. “Prescriptions for Universal Relief” proposed to judge whether hip dislocation occurs by comparing the length of both the lower limbs.μ receptors in the brain and K receptors in the spinal cord to achieve analgesia, but they may generate adverse events such as respiratory depression, nausea and vomiting, urinary retention, and drug dependence in children, especially in pediatric patients with immature liver enzyme systems, resulting in difficulties in the clinical selection of drug doses [Intraoperative osteotomies of the acetabulum and femur are associated with intense postoperative pain, which inhibits the body's immune function and elicits irreversible damage. Therefore, perioperative analgesic treatment is of great clinical importance. In the choice of the analgesic method, it has been found that single analgesic methods are insufficient for satisfactory results, which are attributable to the inadequacy of pharmacological analgesia by one mechanism of action alone to deal with postoperative pain originating from different signaling pathways transduction. Ibuprofen inhibits cyclooxygenase and reduces the synthesis of prostaglandins and activation of peripheral receptors to exert analgesic and anti-inflammatory effects, but it is prone to platelet inhibition and other adverse reactions. Analgesia pump drugs are opioids that bind to ug doses , 26. TheHere, the eligible patients given oral ibuprofen were associated with significantly lower pain scores at 24 h and 72 h postoperatively and fewer unexpected pain calls within 72 h, postoperatively versus those without oral ibuprofen, suggesting that the combined ibuprofen analgesia was effective in mitigating the pain of the children and reducing the number of severe pain episodes. Moreover, the application of oral ibuprofen in the analgesia pump showed great improvement in lowering the dosage of the analgesia pump versus the absence of ibuprofen, indicating that ibuprofen can effectively reduce the amount of opioid medication to attenuate the damage to the children. Furthermore, the similar incidence of adverse events between the two groups herein highlighted the safety profile of ibuprofen in postoperative analgesia.To sum up, traction + reposition + hip spica cast plus analgesia pump and oral ibuprofen effectively mitigated postoperative pain in children with DDH and reduced analgesic drug dosage with a high safety profile.


The value of pulsed electromagnetic field (PEMF) in postoperative pain management, due to the inconsistent findings so far, remains unclear. We extended the evaluation of PEMF on postoperative pain and intravenous (IV) analgesic use to a group of post-appendicectomy Asian patients.This is a double-blinded, randomized trial. Adults with a clinical diagnosis of acute appendicitis were enrolled. Patients were allocated randomly to receive an active-PEMF device or an inactive device after the surgery in addition to the standard postoperative pain management. The primary outcome measure was the 12-h cumulative postoperative pain intensity measured at four different time points using the visual analogue scale. The secondary outcome measure was the total amount of IV fentanyl used (in mg) via PCA over the first 12 postoperative hours. The primary analysis in this trial compared the two study groups for the reported cumulative pain score (both at rest and on movement) and the cumulative amount of IV fentanyl uses over the first 12 postoperative hours using the Wilcoxon rank sum test. Analyses were performed based on the intention-to-treat principal. Multiple imputation was used to handle the missing data assuming that the data were missing at random.W = 1832.5 ~ 1933.0, p-value 0.6192 ~ 0.2985 for resting pain score comparison; W = 1737.0 ~ 1804.5, p-value 0.9892 ~ 0.7296 for movement pain score comparison). For the secondary outcome measure of 12-h total fentanyl use, a comparison between the PEMF vs. placebo arm also revealed no statistically significant difference across all the 20 imputed datasets .One hundred eighteen subjects were randomized; 58 were allocated to the active-PEMF group and 60 to the inactive control group. Pooled mean pain score of both intervention groups by time point declined in a similar fashion over the course of 12 postoperative hours. The 12-h cumulative postoperative pain score at rest and on movement did not differ significantly after the procedure.  and Thai Clinical Trials Registry .The online version contains supplementary material available at 10.1186/s13063-022-06810-y. Acute appendicitis is one of the most common indications for surgery in patients admitted to the hospital for acute abdominal pain , 2. UrgeEvidence suggests that pulsed electromagnetic field (PEMF) when applied to injured tissues has the properties of increasing the release of anti-inflammatory cytokines, endogenous analgesic agents, and opioid precursor proteins in these tissues as well as reducing pro-inflammatory cytokines and endogenous hyperalgesia agents, thereby reducing pain and improving tissue healing , 11.{RohThe value of PEMF on postoperative pain management, due to the inconsistent findings so far, remains unclear. In this study, we extended the evaluation of PEMF on postoperative pain and intravenous (IV) analgesic use to a group of post-appendicectomy Asian patients. We hypothesized that, if PEMF therapy does improve postoperative pain in appendicectomy, IV fentanyl use via PCA is expected to reduce while the perceived postoperative pain will at least remain (if not reduced concurrently). The logical framework of the study hypothesis is provided as Supplementary Material .We undertook a prospective, randomized, double-blinded, placebo-controlled trial. The study took place in the Hospital Tengku Ampuan Rahimah, Klang  Malaysia. The study protocol was reviewed by and registered with the National Medical Research Register, Malaysia  prior to the enrolment of the first subject. Additional registration of the study protocol to the Thai Clinical Trials Registry was also performed retrospectively (Study ID: TCTR20191102002). All patients provided signed informed consent. The trial started its recruitment on 1st August 2015 and ended on 31st December 2015 for accomplishing the intended sample size.All adults examined in the emergency department and suspected to have acute appendicitis were assessed for possible inclusion in the study. Patients were excluded if one of the following criteria were present: age less than 19 years or more than 50, pregnancy or a positive pregnancy test, had underlying chronic pain or history of long-term opioid use, appendicectomy lasted more than 3 h or inability to understand information about the protocol or to sign the informed consent form. The on-duty medical officers from the anaesthesiology department enrolled the eligible patients. Patients eligible for inclusion to the study were informed of the protocol and invited to participate.After informed consent was obtained, patients were individually and randomly assigned to either the active PEMF group or the control group (inactive PEMF) according to the randomization schedule prepared prior to the trial initiation. A simple randomization with a 1:1 allocation ratio in this study. The on-call medical officer taking care of the postoperative recovery room performed the random assignment  before the operation and performed the placement of the trial device onto the enrolled subjects after the operation. Opaque, sealed, identical and sequentially numbered envelopes (SNOSE) were used.www.graphpad.com/quickcalcs/randomize1/ was used.The randomization schedule  was generated by a trial researcher not involved in the care of the trial subjects prior to the trial start. The same researcher also prepared the numbered envelopes according to the computer-generated schedule. A free, web-based randomization schedule generator from Immediately after the appendicectomy, either an active or an inactive PEMF device was placed on the surgical wound on top of the dressing for 12 h  is a battery-powered 12-cm elliptical coil radiofrequency energy generator . The surface of the device was cleaned and disinfected using 70% isopropyl alcohol wipes prior to application. All visible soil (if any) were first removed via the first wipe. A second wipe was then performed to disinfect the device’s surface area. The wipe contacted the whole device surface for at least 3 s during the disinfection process.Appendicectomy was performed according to surgeons’ standard practice (via a McBurney incision). All patients also received general anaesthesia according to the standard protocol. Anaesthesia was induced with IV fentanyl (1–1.5 μg/kg to a maximum of 100 μg) and propofol (2–3 mg/kg), followed by a muscle relaxant of the anaesthesiologists’ choice. All patients then receive IV morphine 0.05 mg/kg intraoperatively. Surgery was commenced after the patient was successfully anaesthetized. No local infiltration of any anaesthetic agents was performed on the incised skin. All patients were supplemented with patient-controlled analgesia (PCA) with IV fentanyl postoperatively for 12 h.The primary outcome measure of this study was the 12-h cumulative postoperative pain intensity measured at four different time points using the visual analogue scale (VAS). The secondary outcome measure was the total amount of IV fentanyl used (in mg) via PCA over the first 12 postoperative hours. Participants were asked to report their pain intensity based on the VAS. Pain intensity was evaluated at 0, 4, 8, and 12 h after surgery. The requirement for PCA IV fentanyl postoperatively was recorded by a research assistant.The VAS is a unidimensional measure of pain intensity . It is aPCA is a pain control system which allows a patient to self-administer a predetermined dose of analgesic medication for pain relief . FentanyThe patients and the surgeons, nurses and other healthcare workers including the acute pain service (APS) team involved with direct patient care were blinded to the allocation group. The APS team provided all pain-related clinical management to all study subjects. The research assistant who collected the PCA data was also blinded to the allocation. The identification of treatment was concealed by using an identical yet inactive device.https://cran.r-project.org/package=MKpower).This study was based on the notion that PEMF therapy would reduce postoperative pain and analgesia use in appendicectomy. We estimated the required sample size based on the Wilcoxon rank sum test using the Monte-Carlo simulation technique. In the simulation, we assumed that the mean cumulative pain score in the control group vs. the intervention was 1.0 and 2.0 respectively. The expected difference of cumulative VAS pain score was 1.0. . A commoBased on the simulation, we found that a sample size of 80 patients (in the ratio of 1:1 for intervention and control group) would give an 80% power to establish whether PEMF treatment was superior to placebo in relation to postoperative pain reduction. With the additional consideration of potential dropout (10%) and rounding to the nearest full number, we determined that the target sample size should be 100 (50:50 for control and intervention).To assess the hypothesized effect of PEMF on postoperative pain, we compared the two study groups for their reported cumulative pain score (both at rest and on movement) and the cumulative amount of IV fentanyl uses over the first 12 postoperative hours using the area-under-the-curve (AUC) approach. For each subject, the AUC for pain scores and IV fentanyl uses were calculated by summing their values over the12 postoperative hours. The distribution of AUC for pain score and IV fentanyl uses between the two study groups were compared using the Wilcoxon rank sum test with continuity correction. Analyses were performed based on the intention-to-treat (ITT) principal. All reported p values are two-sided and were not adjusted for multiple testing. We used R version 3.3.2 for all the analyses.mice package in R was used to handle the missing data assuming that the data were missing at random. Baseline variables , trial variables  and outcome variables (pain score and fentanyl use at each time point) were used to form the imputation models. Predictive mean matching with auto-generation of the predictor matrixes was used. Twenty imputed datasets were generated for subsequent analyses. For visual assessment, the mean pain scores and IV fentanyl uses for each time point across the imputed datasets were pooled according to the Rubin rules and plotted on a line graph. For results of the Wilcoxon rank sum test, pooling was not done due to the expected non-normal distribution and small sample size. Instead, we directly reported the test statistics (W) and p-values of each analysis performed on the 20 imputed datasets and summarized them by range.There were 21 subjects (17.8%) with at least one missing data on the primary outcome measure (pain score on one of the 4 time points) and 28 subjects (23.7%) with at least one missing data on the secondary outcome measure (IV fentanyl use on one of the 3 time points). Multiple imputation by chained equations from the To assess the stability of the conclusion to the missing-at-random assumption, a best-case and worst-case sensitivity analysis was undertaken. Under the best-case analysis, all PEMF subjects with missing data were assigned with the 1st quartile value of pain score and IV fentanyl use from the PEMF subjects with observed data of the same time point. All placebo subjects with missing data were assigned with the median value of pain score and IV fentanyl use using the same approach. Under the worst-case analysis, missing data were imputed in the reverse fashion using 3rd quartile value for PEMF subjects and the median value for the placebo subjects.A total of 118 subjects were enrolled and randomized: 58 were assigned to the active-PEMF group and 60 to the inactive PEMF (control) group. 11 subjects from the intervention group and 5 subjects from the control group discontinued the assigned treatment before study completion due to the following reasons: accidental device off, PCA not initiated due to patient factor, data collection/documentation error, accidental add-on analgesia exposure, PCA machine malfunction, and allergic to IV fentanyl. Ultimately, 47 subjects from the intervention group and 55 subjects from the control group completed the study per protocol. Per the ITT principal, all assigned subjects were included for analysis of primary and secondary outcome measures see Fig. .Fig. 2CoTable W = 1832.5 ~ 1933.0, p-value 0.6192 ~ 0.2985 for resting pain score comparison; W = 1737.0 ~ 1804.5, p-value 0.9892 ~ 0.7296 for movement pain score comparison; see Supplementary Material Pooled mean pain score of both intervention and placebo groups by time point declined in a similar fashion over the course of 12 postoperative hours Fig. . The pooW = 1676.5 ~ 1859.0, p-value 0.7344 ~ 0.5234; see Supplementary Material For the secondary outcome measure of 12-h total fentanyl use, a comparison between the PEMF vs. placebo arm also revealed no statistically significant difference across all the 20 imputed datasets (This randomized controlled study involving 118 post-appendicectomy patients indicates no significant effect PEMF has on both the patient-reported pain intensity measures (i.e. resting and moving) over the initial 12 h post-procedure. Similarly, the secondary outcome measure – postoperative use of IV fentanyl via PCA – also did not show any difference in between the intervention arm vs. the placebo arm. Hence, the previously reported effect of PEMF (as an adjunct intervention) on postoperative pain intensity and analgesia use in other surgical settings cannot be verified. These findings imply that adjunct PEMF use for postoperative pain management may not be recommended at this juncture given the current state of (inconsistent) evidence. Further efforts to understand the reasons of the inconsistent results remain critical.A review of the existing evidence pool suggested several potential reasons for the inconsistent results. Firstly, a notable feature among the existing evidence on PEMF and its effect on postoperative pain is their small sample sizes in general. Besides the study reported by Stocchero et al. (2014) , the stuSecondly, trials with subjective outcome measures, such as pain score in this context, also have been reported to have the potential of exaggerated effect sizes especially if concealment or blinding is inadequate. This is in contrast to trials with objective outcome measures such as mortality, as there was little evidence that inadequate concealment and lack of/ineffective blinding would significantly distort the estimated effect sizes. Furthermore, the difference in the subjective experience of pain may also result in large variations in patient-reported VAS pain scores and their need of pain medications. As reported by Svaerdborg and colleagues  in theirLastly, there is also a possibility that biological and clinical factors that influence postoperative pain outcomes might also affect the efficacy of PEMF. For instance, different surgical conditions and related procedures might bring about a different mix of pain aetiologies, thereby affecting the effect of PEMF on cellular mechanisms that induces pain during the acute postoperative period. Hence giving rise to the possibility that PEMF efficacy might differ in different surgical conditions and procedures. Biologically, genetic factors are known to play a significant role in influencing one’s responses to pain and analgesia , 26. TheFindings from this study nevertheless should be interpreted with the following limitations. First, different PEMF devices may have slightly different settings. The differences may affect the efficacy and contribute to the inconsistent findings. The potential effect of the different device settings on effectiveness has been previously demonstrated . This stIn conclusion, this study did not verify the effect of PEMF on postoperative pain previously reported. Given the currently available evidence, a recommendation to using PEMF as a routine part of postoperative pain management is not warranted especially for pain management during the immediate postoperative period and of use for short durations. Future larger-scale study may be required to provide more convincing evidence regarding the effect of these devices. A high-quality systematic analysis of the currently available evidence might be required to clarify the current evidence gap in order to better inform future study design and focus.Additional file 1: Supplementary material 1. Logical framework of the study hypothesis.Additional file 2: Supplementary Material 2. AUC for pain score comparison with Wilcoxon rank sum test - results across all the 20 imputed datasets.Additional file 3: Supplementary Material 3. Sensitivity analysis using the best-case-worst-case approach.Additional file 4: Supplementary Material 4. Comparison of 12-hour total fentanyl use (AUC)  results across all the 20 imputed datasets.Additional file 5: Supplementary Material 5. Best-case-worst-case analysis for 12-hour total fentanyl use.Additional file 6: Supplementary Material 6. Annotated version of Figure 2.


Treatment modalities like electrosurgery and lasers have emerged as effective painless alternatives to scalpel methods for a frenectomy. The present case series involves ten patients, diagnosed with abnormal frenal attachments. Frenectomy was performed by 980 nm diode laser and scalpel methods. Scalpel frenectomy was performed as described by Archer and Kruger. Laser-assisted frenectomy was performed by a hemostat-guided incision using a 980 nm diode laser tip in a paintbrush motion. It was observed that Visual Analogue Scale (VAS) pain scores in patients who underwent scalpel frenectomy were comparatively higher than the laser-treated patients. In contrast, wound healing scores were higher in the scalpel group, suggesting early wound healing in the scalpel-treated patients. Aberrant frenal attachments are minor congenital malformations , 2 that Postoperative bleeding, pain, and speaking discomfort are a few unpleasant events associated with conventional scalpel methods –10. To oP. Mirko et al.  identifiTen patients with a positive blanch test, inadequate vestibular depth, and midline diastema were diagnosed to have maxillary pathological frenal attachments , 12, 13.Patient-reported pain perception is recorded by Wong–Baker Faces Pain Rating Scale .A wound healing assessment is made using the Early Wound Healing Index .The following parameters were assessed in all ten patients on days 1, 7, and 30 as outcome measures. Five out of the ten patients opted for scalpel frenectomy. The procedure was explained, and informed consent was taken. Infiltration anesthesia is given in the vestibule region of teeth #11 and #21 with 2% lignocaine and 1 : 80,000 adrenaline. Frenectomy was performed by the classical method , 17. FreThe clinical photographs of scalpel frenectomy are illustrated in μm tip was moved in a paintbrush motion from the base to the apex of the frenum. Remnants of charred tissue were removed using sterile gauze dipped in saline, and the laser plume was removed with a high vacuum suction tip. Two of the five patients who underwent laser-assisted frenectomy did not require sutures and a periodontal pack. The other three patients required sutures as the area of the wound was large.Another five patients opted for a laser-assisted frenectomy . The patient, operator, and assistant used laser safety protective eyewear. The maxillary frenum region was anesthetized by infiltration anesthesia using 2% lignocaine and 1 : 80,000 adrenaline. Laser power settings were adjusted at 1 W continuous wave, contact mode, and a 300 Clinical images of the laser-assisted frenectomy procedure are illustrated in Among the scalpel-treated patients, on the postoperative days 1, 7, and 30, patient P1 gave pain scores of 2, 0, and 0, whereas the second patient, P2, gave pain scores of 8, 4, and 2. The third patient, designated as P3, gave pain scores of 6, 2, and 0. P4 gave pain scores of 4, 2, and 0, whereas P5 gave pain scores of 2, 0, and 0, respectively.Among the laser-treated patients, on the postoperative days 1, 7, and 30, patient P1 gave pain scores of 2, 0, and 0; P2 gave pain scores of 6, 2, and 0; P3 gave pain scores of 6, 2, and 0; P4 gave pain scores of 2, 2, and 0; P5 gave pain scores of 4, 2, and 0, respectively.In the scalpel-treated patients, early wound healing scores (EHS) were examined on postoperative days 1, 7, and 30. Here, P1 gave EHS scores of 5, 10, and 10; P2 gave EHS scores of 6, 10, and 10; P3 gave EHS scores of 6, 10, and 10; P4 gave EHS scores of 6, 10, and 10; P5 gave EHS scores of 3, 8, and 10, respectively.Similarly, in the laser-treated patients, EHS scores were examined on postoperative days 1, 7, and 30. P1 gave EHS scores of 1, 3, and 10; P2 gave EHS scores of 1, 3, and 10; P3 gave EHS scores of 1, 3, and 10; P4 gave EHS scores of 1, 3, and 10; P5 gave EHS scores of 1, 3, and 10.Average pain scores among all the patients and a summary of outcome parameters are given in From the above observations, pain scores in patients who underwent scalpel frenectomy were comparatively higher than in the laser-treated patients. In contrast, wound healing scores were higher in the scalpel group, demonstrating early wound healing in scalpel-treated patients and delayed wound healing in laser-treated patients.Management of high frenal attachments requires patient motivation and acceptance. Electrosurgery and lasers emerged as alternative treatment modalities to overcome the undesirable effects associated with scalpel frenectomy methods. Randomized clinical trials –10 compaIt was noted that the pain scores of scalpel-treated patients are higher than the laser-treated patients, reconfirming the results of previous studies –10. A feHowever, wound healing in laser-treated patients is observed to be delayed, consistent with a few studies , 18, andTherefore, to overcome this drawback, a few studies  used adjThe aspect of wound healing following laser therapy needs to be evaluated further in randomized controlled clinical trials using larger sample sizes and reliable wound healing assessment tools.Evaluation of pain scores indicates that a diode laser is an effective alternative for frenectomy, offering patients a painless and bloodless experience. EHS indicated delayed wound healing in laser-treated patients, recommending a need for research in the direction of adjuncts for wound healing following laser therapy.


The effects of early integration of point-of-care ultrasound (PoCUS) into patient care are uncertain. This study aims to investigate the effects of early PoCUS on patients with acute flank pain.Adult non-traumatic patients with acute flank pain receiving PoCUS were enrolled. Expert physicians reviewed the medical records and made the “final diagnosis” for the cause of acute flank pain. The primary outcome was the relationship between the door to ultrasound (US) time and length of stay (LOS). The secondary outcomes included the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the sonographic diagnosis, compared with the final diagnosis.vs. 217 min, p < 0.0001). Patients in the late POCUS group (> 120 min) had a trend to receive more CT scans. The disease distribution, sensitivity, specificity, PPV, and NPV were similar in patients receiving early or late PoCUS for target diagnoses. After adjusting for the confounders, early PoCUS  had a positive impact on shorter LOS. In addition, the effect of early PoCUS became more prominent  on LOS in less than 3 h.Eight hundred and eighty-eight patients were included in the analysis. Patients receiving early PoCUS (≤120 min) had a shorter LOS (128 Early integration of PoCUS is significantly related to shorter LOS in patients with acute flank pain without increasing morbidity and mortality. Our results suggested “PoCUS early” in these patients to possibly alleviate emergency department crowding.Trial registration NCT04149041 at the ClinicalTrial.gov. Acute flank pain is a common symptom in the emergency department (ED). Acute ureteral obstruction from an impacted stone is the most frequent cause. However, a variety of diseases may manifest as acute flank pain, mimicking renal colic. Among them, pyelonephritis and myofascial pain are frequently encountered.Besides a detailed medical history and physical examination, kidney-ureter-bladder (KUB) radiography and urinalysis are frequently used for the evaluation of acute flank pain although they exhibit a limited diagnostic value for urolithiasis , 2. CurrWith the advance of PoCUS, it can be used as an extension of the doctor’s hand to look inside and find out the possible etiology. The effects of early integration of PoCUS into actual patient care are uncertain. This study aims to investigate the effects of early PoCUS in the evaluation of ED patients with acute flank pain.The retrospective study was conducted at the ED of the National Taiwan University Hospital (NTUH), a tertiary medical center in Taiwan, between July 2015 and July 2017. The study protocol was approved by the Institutional Review Board of the Ethics Committee of the NTUH (201907173RIND) with a waiver of informed consent and registered at ClinicalTrials.gov (NCT04149041).PoCUS was included in emergency residency US training since 2012, and all of the residents passed the hand-on assessment. The instructors were certified by the Taiwan Society of Ultrasound in Medicine and had more than 10 years of experience in sonographic examinations. All ultrasonographic examinations were written in a standard report form including indication, sonographic findings, sonographic diagnosis, and management.Two US machines  equipped with 2–5 MHz curvilinear transducers were set up and placed on standby for use.Adult non-traumatic patients (more than 20-year-old) presenting with acute flank pain referred for PoCUS were eligible. Patients aged less than 20 years, with pregnancy or trauma were excluded.Clinical data were retrospectively obtained from the electronic medical records, including age, sex, body mass index (BMI), comorbidities, vital signs on arrival, time of visits, door to physician time, door to US time, door to KUB time, door to CT time, door to urinalysis time, ED LOS, and patient disposition, as well as the sonographic reports. The time of visits was categorized into weekday visits or weekend/holiday visits, as well as dayshift visits (8 a.m. to 8 p.m.) or nightshift visits (8 p.m. to 8 a.m.).After patient discharge, expert ED physicians not involving PoCUS training reviewed the medical records and made the “final diagnosis” for the cause of acute flank pain . The diagnostic criteria for urolithiasis included the presence of stones in the urinary tract in KUB, PoCUS, CT, or other imaging studies besides history and physical examination.The primary outcome was the relationship between the door to US time and LOS. The secondary outcomes included the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the sonographic diagnosis, compared with the final diagnosis.All data were analyzed by SAS software . Categorical data were expressed in counts and proportions and compared using a Chi-square test, while continuous data were expressed in medians and interquartile ranges (IQRs), and examined using Wilcoxon’s rank-sum test.The linear regression model was applied to investigate the relationship between the door to US time and LOS. Covariates in the model included age, sex, BMI, comorbidities, time of visits, and door to physician time. Further, the patients were divided into two groups by the door to US time ≤120 min (early) or > 120 min (late). Between-group differences for the parameters were investigated.The logistic regression model was applied to investigate the early use of PoCUS (≤120 min) associated with shortened LOS (≤240 min) . CovariaDuring the study period, 899 patients with acute flank pain received PoCUS. After excluding 11 patients without available documentation, 888 patients were included in the analysis (Table p < 0.0001) after adjusting for age, sex, BMI, comorbidities, time of visits, and door to physician time.We investigated the relationship between the door to US time and LOS using a linear regression model. The results showed that the shorter the door to US time, the shorter the LOS . There were no significant differences in age, sex, body max index, comorbidities, vital signs on arrival, time of visits, door to physician time, door to x-ray time, door to urinalysis time, CT rate, and ED discharge rate between the two groups  or more than 120 min (late) , acute pyelonephritis (15%), myofascial pain (14%), and miscellaneous diagnoses. There was no significant association between the door to US time and final diagnoses Table . The patFurthermore, the logistic regression model was applied to investigate the factors associated with LOS less than 4 h. After adjusting for the confounders, early PoCUS  had a positive impact on shorter LOS. By contrast, patients with malignancy  had longer LOS. In addition, the effect of early PoCUS became more prominent  on LOS in less than 3 h.The sensitivity, specificity, PPV, and NPV were similar in patients receiving early or late PoCUS for target diagnoses Table . The preAcute flank pain is a frequently encountered complaint at the ED. Compared with non-contrast CT, US has the advantage of bedside accessibility and a lack of ionic radiation. Our study investigated the effect of PoCUS on patient-centered outcomes. The results showed that the earlier use of PoCUS was associated with shorter ED LOS in patients with acute flank pain. An earlier PoCUS did not harm the diagnostic accuracy including sensitivity, specificity, PPV, and NPV.Urolithiasis is the most frequent cause among patients with acute flank pain. Previous studies have suggested that US is the ideal initial imaging test in the ED setting for patients with suspected urolithiasis without changing patient outcomes and morbidity , 6. ModeThere have been still some concerns regarding the use of PoCUS for the diagnosis of urolithiasis. PoCUS has limited ability to visualize stones less than 3 mm , or in tIn recent years, PoCUS has become a required milestone competency in residency practice –16. PoCUMoreover, diseases of the abdominal aorta represent a category of life-threatening conditions, which present with flank pain . In our There were limitations in this study. First, because our study was a retrospective design, some US images and records were missing. However, the missing data was only 1% and the results were representative of the large-scale study. Second, there were no absolute guidelines for how early to use US in patients with acute flank pain. It depended on physicians’ clinical discretions, which may result in selection bias. However, the distribution of etiologies was similar in patients receiving US in 120 min or later. Also, the diagnostic accuracy of PoCUS was similar between these two groups. Third, the factors influencing the LOS were multifactorial, occurring in the input, throughput, and output , althougEarly integration of PoCUS for ED patient care is significantly related to shorter LOS in patients with acute flank pain without increasing morbidity and mortality. Our results suggested “PoCUS early” in these patients to possibly alleviate ED crowding. However, many factors are involved in ED patient flow that further investigations should be explored.


Background: Obesity is a growing public health concern and is one of the leading causes of human suffering and disability worldwide. The number of overweight and obese people is dramatically increasing, and local data showed that low back pain (LBP) is more common in people with obesity, prolonged sitting jobs, psychological disorders, and lack of exercise.Methods: This study was conducted in a cohort of 300 adult patients of either gender who visited a pain management clinic with LBP. Patient data were retrieved from the hospital software program and recorded in a pre-designed proforma. The data included the patient’s age, gender, weight, height, BMI, comorbidities, site of pain, duration of pain, distribution of pain, severity of pain, history of spinal trauma, previous spinal surgery, and working diagnosis.Results: Out of 300 patients with LBP, 185 (61.7 %) were female and 115 (38.3%) were male, of these, 224 (74.6%) were overweight or obese. One hundred and three (34.3%) had axial back pain and 197 (65.7%) patients had lumbar radicular pain. Linear regression analysis showed that 17% variability in pain scores in both genders can be explained by the increase in BMI. There is a statistically significant relationship, i.e. P=0.0005, exists between pain score and BMI.Conclusion: This study showed the strong association between obesity and LBP in the Pakistani population. Approximately, 75% were overweight or obese in our LBP population-based cohort and this association was stronger among women than men. Low back pain (LBP) is a great public health issue and the second most common cause of seeking advice from a physician . It is tObesity is a growing public health concern worldwide. Globally, the number of overweight and obese people is dramatically increasing. The data from the United States national health and nutrition examination survey 2017-2018 showed that the age-adjusted prevalence of obesity is 42.4%, while the age-adjusted prevalence of severe obesity is 9.2% among adult patients, aged 20 and above. The general prevalence of obesity is the same in men and women, however, the prevalence of severe obesity is more in women and adult patients, aged 40-59 years . PakistaObesity is considered a risk factor for LBP due to underlying biological plausibility. Putting on more weight causes increased mechanical loading on lumbar vertebrae that results in a series of changes . It has To date, studies on the association between obesity and LBP in low and middle-income countries are scarce. This study was conducted to determine the association of LBP and BMI in the Pakistani population and the frequency of common LBP conditions among such patients.This study was conducted in a cohort of 300 adult patients who visited the pain management clinic with chronic LBP. Exemption from the Ethics Review Committee of Aga Khan University (ERC# 2018-0426-364) was granted for this study.Study design: A retrospective observational studyPatient data were retrieved from the hospital software program PMCS (Pain Management Clinic System) and recorded in a pre-designed proforma for a period from 1st January 2017 to 31st May 2018.Inclusion and exclusion criteria2), normal weight (BMI 18.5 to 24.9 kg.m2), overweight (BMI 25 to 29.9 kg.m2), obesity (BMI 30 to 39.9 kg.m2), morbid obesity (BMI 40 to 49.9 kg.m2), and super obesity 50 to 59.9 kg.m2.All adult patients of either gender presenting to the pain management clinic of Aga Khan University Hospital with a history of chronic LBP for more than 3 months were included. Patients with missing data and follow-up patients were excluded from the study. All patients were included in this retrospective observational study by reviewing data in the electronic medical record, PMCS by one of the authors as per the availability. The patients’ medical records were also reviewed for any additional information and all the information were recorded in a pre-designed proforma. The data included the patient’s age, gender, weight, height, BMI, comorbidities, site of pain, duration of pain, distribution of pain, the severity of pain, history of spinal trauma, and previous spinal surgery and working diagnosis. BMI  is categStatistical analysesStatistical analyses were performed using Statistical Packages for Social Science version 19 . Mean and standard deviation was computed for quantitative variables while frequency and percentage were estimated for qualitative variables. A P-value of ≤ 0.05 was considered significant.Three hundred patients were included during the study period. One hundred and eighty-five 61.7 %) patients were female while 115 (38.3%) were male. The mean age of the study patient was 51.24±18.12 years and most of them had hypertension (36.3%) followed by diabetes (30.3%)  patients were underweight (BMI < 18.5 kg.m2), 71 (23.67%) had BMI within normal range (18.5 to 24.9 kg.m2), 91 (30.33%) were overweight (BMI 25 to 29.9 kg.m2), 118 (39.33%) were obese (BMI 30 to 39.9 kg.m2), and 15 (5%) were morbidly obese (BMI 40 to 49.9 kg.m2). The difference in mean numerical rating pain score (NRS) scores among the different BMI categories of patients is statistically significant (P=0.0005). The mean NRS pain score of overweight, obese, and normal-weight patients was statistically significant (P=0.001)  patients had axial pain (confined to the low back only), and 197 (65.7%) patients had lumbar radicular pain (pain radiating down the leg). Among patients with radicular pain; 40 (20.3%) patients had pain radiating to the lower limb up to the knee while in 157 (79.7%) patients, pain radiates up to the ankle or foot. Thirty-four (11.3%) patients had a history of spine trauma. Fourteen (4.7%) patients had a history of spine surgery.Subgroup analysis showed that overweight and obese patients are more prone to have lumbar radicular pain, spinal stenosis, disc degenerative disease, and sacroiliac joint pain as compared to normal-weight patients. Ninety-three (31%) patients had a working diagnosis of lumbar radicular pain (Sciatica), 81 27%) patients had disc degenerative disease, 31 (10.3%) had non-specific back pain, 26 (8.7%) had spinal stenosis, 11 (3.7%) had metastatic cancer pain, 15 (5%) had sacroiliac joint pain, four (1.3%) had failed back surgery syndrome, six (2%) had lumbar facet joint pain while 33 (11%) had miscellaneous causes of back pain . Linear regression analysis shows that 17% variability in NRS pain scores in both genders can be explained by the increase in BMI. Regression coefficient 0.11 shows that with each unit change in BMI there will be an 11% increase in pain score. There is a statistically significant relationship, i.e. P=0.0005, exists between pain score and BMI  also exists between pain score and BMI regarding the distribution of pain . Analysis showed that 28% variability in NRS pain score is related to the increase in BMI in patients with axial back pain while 12% in patients with lumbar radicular pain Figure .Results regarding various BMI categories and comorbid conditions of study patients showed that one hundred and sixty-seven (55.66%) patients had one or more disease conditions with chronic LBP. Out of 118 obese patients with LBP, 55 (46.61%) had diabetes mellitus while nine out of 12 hypothyroid patients were overweight or obese.Among the 300 patients included in this study, data showed a strong association between overweight and obesity with LBP. In the subgroup analysis, we found that 30.33% of LBP patients were overweight, 39.33% were obese, and 5% were morbidly obese. Current literature also showed a significant association of obesity with LBP. A person with a high BMI has two times increased probability of having LBP as compared to an individual with a normal BMI . The relA recent study mentioned that high BMI is strongly associated with an increased prevalence of LBP . The finThere are several mechanisms proposed that can explain the relationship between obesity and LBP. First, the increased mechanical load on the back due to obesity causes a higher compressive force on the spine during various physical activities. Second, obesity makes the person vulnerable to have injuries and systemic chronic inflammation. This will lead to increased production of cytokines and activation of pro-inflammatory substances , interleukin-6 (IL-6), and blood levels of IL-6) which are elevated in obese patients and causing pain . There iA previous study showed that the gender difference was less evident for the increasing prevalence of LBP, however, the current study demonstrated an increased incidence of LBP in women . SimilarMany case-control studies have demonstrated a positive relationship between increased BMI and lumbar disc herniation in both genders. Lumbar disc herniation is an important cause of LBP and lumbosacral radicular pain . SubgrouA systematic review has shown that increased body fat is positively related to generalized pain with LBP, knee pain, and foot pain. There is also a positive relationship between increasing body fat and generalized body pain and single-site joint pain in the lower back . SeveralStrengths of the studyThe current study includes a nationally representative population-based sample of a lower and middle-income country (LMIC). This study may contribute as a reference for future research on LBP and LMIC. The findings of the study have important implications for the prevention and management of LBP in the Pakistani population, however, further research via longitudinal studies needs to be done.Limitation of the studyThe current study has its limitations as it was a single-center study with a relatively small sample. In addition, data was retrieved from the pre-designed software program therefore some of the common risk factors like smoking and the mechanical lifestyle of a person were missed.The current study shows the strong association between obesity and LBP in the Pakistani population. Approximately 75% were overweight or obese in our LBP population-based cohort and this association was stronger among women than men. The study highlighted the importance of obesity as it may increase the risk of LBP, lumbar radicular pain, spinal stenosis, disc degenerative disease, and sacroiliac joint pain.


A total of 37.9% of patients experienced significant but not long-lasting (four weeks on average) complete pain relief. A total of 44.1% of patients experienced prolonged, subjectively satisfying pain relief of more than four weeks to three months. A total of 18% of patients had complete and sustained relief for more than six months. A significant correlation exists between circumferential, large area contrast distribution including the zone of action between the disc and affected nerve root contrast distribution pattern with excellent pain relief. Our results support the value of CT-guided contrast injection for achieving a good efficacy, and, if necessary, indicative repositioning of the needle to ensure a circumferential distribution pattern of corticosteroids for the sufficient treatment of radicular pain in degenerative spine disease.Acutely manifesting radicular pain syndromes associated with degenerations of the lower spine are frequent ailments with a high rate of recurrence. Part of the conservative management are periradicular infiltrations of analgesics and steroids. The purpose of this study is to evaluate the dependence of the clinical efficacy of CT-guided periradicular injections on the pattern of contrast distribution and to identify the best distribution pattern that is associated with the most effective pain relief. Using a prospective study design, 161 patients were included in this study, ensuring ethical standards. Statistical analysis was performed, with the level of statistical significance set at  Low back pain (LBP) with a radicular component in the vast majority of cases represents a clinical manifestation of degenerative spine disease. Despite the fact that most patients presenting with radicular back pain belong to this category, more serious underlying conditions, such as malignancy, infection, fractures, cardiovascular disease and cauda equina syndrome must be ruled out before standard treatment is initiated ,2. DiffeIn general, approximately 70% of patients suffering from radiating LBP without further neurological deficits caused by intervertebral disc herniation recover without surgery within six weeks . HoweverReviewing the findings of numerous studies in this context, for example, the large ten-year observational study of Weber and colleagues  and the As a consequence, patients presenting with severe or progressive neurological deficits require surgery without question , whilst Based on a number of magnetic resonance imaging (MRI) studies, it has become apparent that the majority of radicular conditions associated with herniated discs regress spontaneously, which explains the significant percentage of patients experiencing spontaneous relief after few weeks without treatment ,11,12,13In context of those studies, it has been postulated that patients suffering from disabling pain without major neuromuscular deficit, whose condition did not improve over a period of six weeks under conservative management, are in need of complementary treatment ,17,18. AThis study, therefore, investigated the hypothesis that good clinical efficacy of CT-guided periradicular injections is not exclusively, but causally, linked to the individual pattern of contrast agent dispersion at hand and that the latter must be used to optimize the needle positioning when the perineural opacification appears insufficient. More specifically, characteristic distribution patterns were reviewed in the context of the individually experienced pain relief with the aim to identify the distribution pattern associated with most effective pain relief.Our study, investigating prospectively included cases from January 2018 to December 2019, was approved by the institutional ethics committee . Informed consent of each patient regarding the scientific use of radiological and clinical data was obtained in writing, either from the patient or his/her legal representative.A total of 161 patients with lumbosacral CT-guided periradicular injections were enrolled in this study. The visual analog scale (VAS) was used as outcome measure. Sample size estimation was based on a pre-study observation of the treatment effect and eventually performed using the freely available tool G*Power, setting the significance level to 0.05 and power to 0.8, as reported earlier . The patIn all cases, the periradicular infiltration was performed under CT-guidance using a Philips Brilliance Big Bore, equipped with 16 detector rows. The patient was placed in prone position for the intervention. An unenhanced scan of the spinal level of interest was performed using a priorly mounted radiopaque skin marker for further reference. The trajectory and depth required for the intra-foraminal navigation of the needle were evaluated using a few cross-sectional CT images at the level of interest. The paravertebral puncture site was marked on the skin surface. After surgical disinfection, the procedure was performed under sterile conditions.Using CT control images for close to real time navigation, a 22 G (0.7 mm) spinal needle was safely placed in the posterior part of the neuro-foramen. Negative needle aspiration—to avoid intravascular injections—was followed by the injection of approximately 1 mL of contrast agent .without primarily apparent nerve root contact or;spatially confined, non-circumferential spread along the nerve root or;extensive surface contact with at least partially circumferential distribution, including the intraspinal portion of the nerve root.The contrast agent distribution pattern in each intervention was assessed by two experienced radiologists  in a consensus approach, according to the following categories:In case of discrepancies (n = 13), the distribution pattern was re-evaluated together. All of those 13 cases had discrepant assessments as follows: one reader evaluated spatially confined, non-circumferential spread, whereas the other reader evaluated at least partially circumferential distribution. Consent was reached in all cases, and the distribution pattern was eventually rated as spatially confined, non-circumferential.After the desired needle position was achieved and the contrast agent distribution was rated to be sufficient , a combination of 1 mL Triamcinolonacetonid 40 mg  and 2 mL Bupivacainhydrochlorid 0.5%  was applied. Subsequently, each patient was instructed to maintain bed rest until the next day, mainly to avoid falls related to bupivacaine-induced transient paresis.Treatment efficacy was assessed using a visual analog scale (VAS)-based questionnaire at two time points; first, 24 h after injection, and at routinely performed follow-up appointments between 3 months and up to 12 months post-procedure. All patients had a long-term follow up after CT-guided percutaneous infiltration as follows: 15.5% by telephone interview and 84.5% via in-hospital appointment for reassessment.p = 0.05.The strategy of the statistical analysis was reviewed and approved by Dr. Gussew, which we thankfully acknowledge. The analysis was performed using SPSS 23.0, with the level of statistical significance set at First of all, Gaussian vs. non-Gaussian distribution of the data was assessed. Related to the comparatively heterogeneous composition of our patient collective, group comparisons  and correlative analysis  were performed using the whole dataset in the first step. Additionally, the following subgroups were formed and analyzed further.Patients who received pharmaceutical therapy only, pharmaceutical and physical therapy or surgery as initial treatment were analyzed as a separate cohort. For each subgroup, the treatment effect according to VAS and technical success were assessed independently.Furthermore, correlative analysis to elucidate the relation between treatment success according to VAS and technical–procedural success was performed.Patients who had acute (<6 weeks), subacute (6 weeks–6 months) and chronic pain (>6 months) prior to CT-guided percutaneous infiltration were each analyzed as separate subgroups. For each subgroup, the treatment effect according to VAS and technical success were assessed independently.29.8% had LBP accompanied by a diffuse radiating component;55.3% had LBP and dermatome-related radiating pain with matching dysesthesia;14.3% had LBP and dermatome-related radiating pain with additional motor deficits. In greater detail, of those 23 patients:8.07% (n = 13) had a L4 syndrome with accompanying knee extensor muscle weakness;6.21% (n = 10) had a L5 syndrome with accompanying foot drop;0.6% (one patient) suffered from dermatome-matching dysesthesia only.The individually evaluated, distinct pain syndromes of the included patients are summarized in the following categories:In three cases of known allergy to iodinated contrast agent, we refrained from using contrast agent. The clinical and demographic characteristics of 161 patients are summarized in A total of 18.6% of patients underwent micro-discectomy after a conservative approach was chosen initially but did not result in sufficient pain relief. For reasons of clarity, only the first CT-guided percutaneous infiltration in each of the 161 patients was evaluated, although a number of individuals were treated repeatedly. On average, 1.5 injections/patient were performed (range 1–5 injections/patient). The treatment success of the CT-guided percutaneous infiltrations is presented for the overall collective and subgroups under the respective headings, as follows.p = 0.001) in clinical success reflected by VAS decrease when comparing the three contrast agent distribution patterns as grouping variables. p = 0.001) between technical success (contrast agent distribution pattern) and treatment efficacy (post-treatment decrease in VAS score). As pre- and post-interventional VAS scores, as well as contrast agent distribution pattern, emerged to be not normally distributed, Kruskal–Wallis was used for group comparisons and Spearman’s Rho was performed for correlative analysis. Kruskal–Wallis test revealed a statistically significant difference  complete pain relief. A total of 44.1% of patients experienced a longer, subjectively satisfying pain reduction of more than four weeks, up to three months. A total of 18% of patients had complete and persisting relief of more than six months.p = 0.001) in clinical success reflected by VAS decrease when comparing the three distinct first-line therapies as a distinguishing variable. p = 0.001), pharmaceutical + physical therapy group  but only a relatively weak association  in the surgery-first group.Kruskal–Wallis was used for group comparisons, and Spearman’s Rho was performed for correlative analysis. Kruskal–Wallis test revealed a statistically significant difference (p < 0.001) in clinical success reflected by VAS decrease when comparing the three distinct first-line therapies as a distinguishing variable. p < 0.001), subacute group  but only a relatively weak association  in the chronic group.Kruskal–Wallis was used for group comparisons, and Spearman’s Rho was performed for correlative analysis. Kruskal–Wallis test revealed a statistically significant difference (This study demonstrates a significant correlation between contrast agent distribution pattern, indicating local drug distribution, and pain relief after periradicular infiltration.To the best of our knowledge, evidence regarding the association between different distribution patterns of contrast agent in CT-guided percutaneous infiltrations of lumbar or sacral nerve roots, which are compromised by herniated discs or osteoligamentous degeneration, is scarce, and prospective investigations, in particular, are lacking.Furthermore, the distinct subset of patients who had prior spinal surgery for severely disabling disc herniation and presented again with a similar syndrome has not yet been included in systematic investigations exploring the efficacy of percutaneous CT-guided infiltrations. In this context, our study provides important insight on the value of minimally invasive CT-guided procedures for pain treatment in previously operated patients.Although class I evidence for the superiority of image-guided percutaneous infiltrations over conservative medical treatment for pain management remains wanted, a number of meaningful retrospective studies have demonstrated the great value of the minimally invasive treatment for patients suffering from radiating back pain due to lumbosacral neural impingement ,24,25. AInterestingly, a number of previous studies failed to show a significant correlation between the quality of contrast agent distribution and clinical effect in image-guided percutaneous infiltrations ,33. HoweIn accordance with this hypothesis, our results demonstrate a direct, significant correlation between treatment efficacy and quality of contrast agent distribution in CT-guided percutaneous infiltrations. More specifically, our study indicates that circumferential, extensive contrast agent distribution, including the impact zone between the herniated disc and the affected nerve root, as such representing the best achievable level of contrast agent distribution, is associated with excellent pain relief and is, per se, largely independent of long pre-existing pain duration or even episodes of prior surgery. This corresponds well with the main findings of the few previously published investigations, which found an extensive, perineural contrast agent dispersion in fluoroscopy to be associated with good clinical results when performing transforaminal corticoid injections ,35.The local inflammatory response, initiated at the very moment the immune-privileged disc content extrudes into the immunologically unrestricted epidural space, is an important component of the resorption process of the herniated disc tissue . In detaIn light of the latter investigations, the results of our study validate and substantiate the necessity of contrast agent injection, and if necessary, repositioning of the needle to achieve a continuous circumferential distribution pattern, prior to periradicular application of corticosteroids for treatment of LBP in herniated disc disease. In general, a precise and early treatment is recommendable. On the one hand, it achieves early pain relief and enables the patient to perform synergistic physical therapy; on the other hand, it restores blood–nerve barrier integrity at the earliest possible time point, which prevents inflammatory nerve root remodeling, and thus, chronified radicular pain.Our results emphasize that, although symptoms may be chronified in patients suffering from osteoligamentous degeneration, they still benefit from periradicular infiltrations. As mentioned above, a precise periradicular drug delivery represses local inflammation, reduces perineural edema and initiates pain relief, also in chronic pain, due to permanent nerve compression ,44. PrevSomewhat unexpectedly, periradicular infiltrations in patients who had preceding spinal surgery also yield respectable results and should not be considered a strictly palliative approach only. Previously damaged nerve roots may already have undergone inflammatory remodeling to some extent; however, suffering a second disc herniation induces recurrence of the inflammatory cascade and most certainly requires local anti-inflammatory treatment to contain and at least partially reverse the structural inflammatory conversion of the affected spinal segment. Additionally, as suggested quite recently by Moen et al., patients who suffered lumbar disc herniation exhibit a distinctly pro-inflammatory serum profile even one year after herniation, which strongly suggests a persisting local and systemic inflammatory condition in the aftermath of the neural impingement .Recent investigations indicate that periradicular infiltrations using ozone as therapeutic agent also bear great potential ,49. OzonTake-home points:application of contrast agent in periradicular infiltrations is helpful for improving the distribution of corticosteroids along the affected nerve root;a circumferential distribution is associated with good treatment efficacy;periradicular infiltrations, as a complementary treatment for both conservative therapy and surgery, help to significantly reduce pain for the majority of patients in the early phase and potentially up to six months, only a minority experiences permanent and sufficient pain reliefin comparison to the natural course, periradicular infiltrations improve outcomes and are a safe, effective and, therefore, justifiable complementary treatment.Limitations: Our study, although performed with a prospective design, is limited by the clinical heterogeneity of the included patients, the small number of included patients and the small final number of patients in each subgroup. More specifically, the assessment of the overall extent of spinal degeneration is not reflected well in our study. A superior way of appropriately addressing this aspect in a future study is the scoring proposed by Eksi et al. [i et al. , who not