While spinal cord stimulation (SCS) is a well-established therapy to address refractory persistent spinal pain syndrome after spinal surgery (PSPS-T2), its lack of spatial selectivity and reported discomfort due to positional effects can be considered as significant limitations. As alternatives, new waveforms, such as burst stimulation and different spatial neural targets, such as dorsal root ganglion stimulation (DRGS), have shown promising results. Comparisons between DRGS and standard SCS, or their combination, have never been studied on the same patients. “BOOST DRG” is the first prospective, randomized, double-blinded, crossover study to compare SCS vs. DRGS vs. SCS+DRGS. Sixty-six PSPS-T2 patients will be recruited internationally in three centers. Before crossing over, patients will receive each stimulation modality for 1 month, using tonic conventional stimulation. After 3 months, stimulation will consist in switching to burst for 1 month, and patients will choose which modality/waveform they receive and will then be reassessed at 6 and 12 months. In addition to our primary outcome based on pain rating, this study is designed to assess quality of life, functional disability, psychological distress, pain surface coverage, global impression of change, medication quantification, adverse events, brain functional imaging and electroencephalography, with the objective being to provide a multidimensional insight based on composite pain assessment. Spinal cord stimulation (SCS) is a well-established therapy to alleviate severe intractable neuropathic pain ,4,5,6,7 First, pauci-discriminative stimulation of billions of sensory epicritic fibers of the dorsal columns using electrical impulses makes it very complex for SCS to be selective in terms of pain coverage for patients . This laIn parallel with neural spatial targeting improvements, new available waveforms including burst paradigms have changed the modulation of the temporal resolution of the signal, allowing for “paresthesia-free” stimulation ,31. ReceIn a recent review, Linderoth and Foreman  presenteTo address these challenges, we designed a randomized controlled trial (RCT) with a 3-month crossover design, where SCS, DRGS or SCS+DRGS (DUAL) will be proposed to a single patient presenting with refractory chronic lower limb neuropathic pain  and/or documented neuropathic refractory back pain. After the crossover period, all patients will be switched to burst waveform with 1-month follow-up, and at 4-month follow-up, they will be asked to choose SCS, DRGS or SCS+DRGS with tonic conventional or burst waveform.The BOOST DRG study is a randomized, controlled trial comparing the efficacy of SCS vs. DRGS vs. combination of SCS+DRGS (DUAL) and TCS vs. burst in a crossover design in patients with chronic lower limb neuropathic pain and/or neuropathic back pain.The primary objective of this study is to compare the efficacy of SCS vs. DRGS vs. DUAL on global pain relief in patients with chronic lower limb neuropathic pain and/or neuropathic back pain.Secondary objectives are to compare pain intensity, pain surface and paresthesia coverage surface to assess positional or postural effects on paresthesia, to compare changes in quality of life, functional disability and psychological state, to assess patient satisfaction and, finally, to compare the effects of stimulation modalities on brain imaging based on fMRI and EEG. Using this study data, we will extract baseline factors associated with long-term stimulation efficacy. These predictors will be included in a predictive model.This protocol is reported in accordance with the SPIRIT 2013 guidelines for protocols of clinical trials .The BOOST DRG study is divided into two phases.Phase A (Pilot study) is a randomized, double-blinded, crossover, six-arm study evaluating the feasibility and comparing the efficacy of three stimulation modalities: SCS, DRGS and DUAL (SCS+DRGS) on 12 patients during 3-month follow-up, which will be conducted only in Poitiers University Hospital (France). According to the phase A results, in terms of feasibility and safety, a second phase is planned, following the same design and including a larger sample of patients, internationally, to take into account the variability of practices.Phase B (Main study) is a prospective, multicentric, randomized, double-blinded, crossover, six-arm study comparing the efficacy of three stimulation modalities: SCS, DRGS and DUAL stimulation (SCS+DRGS) on 54 patients, conducted in the Poitiers University Hospital (France), the Colmar Louis Pasteur Hospital (France) and in Genève Tower Hospital Pain Clinic/Lausanne University Hospital (Switzerland).TM contact percutaneous lead for SCS and one or several QuattrodeTM lead(s) for the DRGS, enabling use of the three different stimulation modalities in the same patient. The leads will be connected to a single external pulse generator. Patients will be randomized in 6 different arms in a 1:1:1:1:1:1 ratio: SCS alone, DRGS alone and DUAL stimulation. During the 3-month crossover period, patients will be under the tonic conventional stimulation (TCS) waveform, whatever the stimulation modality. Each stimulation modality will be administered for 1 month. Patients will be assessed at the end of each stimulation modality period, corresponding to the 1-month, 2-month and 3-month follow-up visits. At the end of the crossover period, stimulation modality will not be changed and will be switched to the burst waveform for 1 month. Patients will be assessed at the end of this 1-month period, corresponding to the study’s 4-month follow-up visit. Patients will then decide which stimulation modality and waveform they prefer and will be assessed at 6 months and 12 months.Phase A and phase B have the same design. Patients will be implanted with the OctrodePatient flow and the study design are presented in The study population comprises patients suffering from chronic lower limb neuropathic pain and/or neuropathic back pain. A patient must meet all inclusion criteria and none of the non-inclusion criteria and the exclusion criteria to be eligible for the study.The patient, aged between 18 and 80 years old, presents with refractory chronic lower limbs neuropathic pain or/and neuropathic back pain for at least 6 months, with VAS ≥ 5/10. The patient’s symptoms are stable for at least 30 days. Pain medication dosage(s) are stable for at least 30 days and the patient is refractory to other treatment modalities . The patient is eligible for SCS after a pre-implantation assessment by a multidisciplinary team, as described by the French National Authority for Health (Haute Autorité de Santé (HAS)). The patient is covered by French national health insurance. The patient understands and accepts the constraints of the study and has given written consent to the study after receiving clear and complete information.The patient has a coagulation disorder, had corticosteroid therapy within the past 30 days, had radiofrequency therapy within the past 3 months, was diagnosed with cancer in the past 2 years or had surgery within the past 6 months. The patient is or has been treated with SCS, subcutaneous or peripheral nerve stimulation, an intrathecal drug delivery system. The patient requires closer protection, i.e., minors, pregnant women, nursing mothers, subjects deprived of their freedom by a court or administrative decision, subjects admitted to a health or social welfare establishment, major subjects under legal protection and, finally, patients in an emergency setting. The patient participates in any interventional study on health product or any study able to interfere with the current study endpoints. Women of childbearing potential not using an effective contraception are not expected to be included in this study. For Poitiers University Hospital only, patients who have magnetic brain imaging (MRI) contraindications will not be included.The patient is unable to appropriately use stimulation equipment, the patient has failure of the trial phase, defined as pain reduction <50% between the inclusion visit and 7 days after lead implantation or the patient presents with any medical condition judged as relevant/significant by the investigator.TM contact percutaneous lead for SCS and one or several QuattrodeTM lead(s) for the DRGS, depending on the pain (bi)lateralization and the pain topography  of the spinal cord, able to provide significant paresthesia generation in the adequate dermatome, if electrically stimulated) , during The foramen, using a trans-grade approach , to targEpidural fat and scar tissue formation could play a substantial role in the energy delivered from the IPG to dorsal column or DRG. This will be explored by following impedance throughout the study and will be taken into account as a potential limitation. To reflect daily practice, impedance will be measured at each contact level according to the user’s manual (between 200 and 3000 Ω) in this clinical study. In case of impedance higher than 3000 Ω, the contact will be automatically deactivated. In this case, we will activate contacts with whom the patient will experience the best pain relief. Some TCS patterns will be tested thanks to the patient’s cooperation, by using various predetermined combinations to achieve good pain coverage and validate the “sweet-spot” location. This will be facilitated by an integrated operating room including several of the new computer-assisted and imaging-assisted technologies  designing an operative theater .After completion of lead programming testing, the leads will be permanently implanted and secured with appropriate anchoring, at the final vertebral level. Very specific attention will be given to the DRG(s) anchorage. The rest of the procedure will be performed as already described in our previous published works ,54.Potential lead migration should be documented by imaging in case the patient experiences inadequate pain relief and/or for coverage after initial positive outcome. In case of lead displacement, documented by X-ray, a revision surgery will be recommended to check hardware dysfunction, including lead migration or fracture. This complication will be reported as an adverse event. Pain rating and outcomes will be analyzed taking the adverse event into account.During the trial phase, both SCS and DRGS will be used separately and/or simultaneously. The trial will be performed for a period of 7 days to assess the benefits of stimulation according to HAS guidelines prior to definitive implantation of the IPG. IPG implantation will be based on the following criterion: at least 50% reduction of pain assessed with a visual analogic scale (VAS).Following surgical implantation of the leads, after 24 h of strict bed rest to avoid secondary early lead displacement, lead programming will be performed according to the TCS by testing a series of programming combinations designed to obtain coverage of the painful territory.In case of SCS/DRGS trial failure, the leads will be removed, and the patient will be managed according to standard practice . If the patient is explanted, he/she will be excluded from the study.TM System implant, depending on their electrical consumption , and in view of preserving MRI compatibility, so as to be able to explore implanted patients with functional imaging during phase B.Subjects who succeed in the lead trial (at least 50% reduction of pain) will receive a PROCLAIMIn case of inadequate pain relief, impedance and lead position by radiographic imaging will be performed during the visits planned in the protocol or in supplementary visit. After ensuring that reprogramming cannot achieve pain relief and lead position by radiographic imaging, surgery could be performed to explore the failure to relieve pain by SCS or DRGS such as lead connection, defective lead or scar tissue formation.To achieve SCS placement, the implanter should place the lead according to the cranio-caudal projection of the conus terminalis to anticipate/estimate a priori optimal lead placement.TM. They differ in terms of amplitude, pulse width and frequencies. TCS delivers a constant stream of pulses:Pulse width: between 100 μs and 500 μs;Frequencies: between 30 Hz and 100 Hz;Amplitude: adapted to individual participant perception, the objective being to achieve a comfortable level of paresthesia. The minimum amplitude step size is 0.1 mA.Different waveforms will be used for the purpose of this study, including TCS and BurstDRTM stimulation:TM mode of constant-current stimuli with 5 spikes at 500 Hz per burst;40 Hz BurstDRPulse width and interspike intervals of 1 ms;The minimum amplitude step size is 0.05 mA;Intermittent dosing: ratio from 1:3 (30-s ON and 90-s OFF) to 1:12 (30 s ON and 360 s OFF) .BurstDRThe stimulation delivered by the IPG to the spinal or dorsal root ganglion target could depend on many parameters. First, it is well documented that CSF thickness varies according to the vertebral level and that the perception threshold is also impacted by the postural changes . PositioRandomization is carried out at the IPG implantation visit. Subjects are assessed prior to randomization, during the inclusion visit and the lead implantation visit, and at 1-month, 2-month, 3-month, 4-month, 6-month and 12-month follow-up visits. Assessments are performed by appropriately trained and delegated study staff independently from industry. Details about which information will be collected at each visit can be found in The primary outcome is the proportion of patients having a reduction of 50% on global VAS, assessed with a 5-day pain diary between baseline (before lead implantation) and after each period of the crossover phase. Patients record their global, back and leg pain using a pain diary once a day, for a 5-day period within one week prior to each scheduled study visit.2), percentage of pain covered with paresthesia and lead selectivity (percentage of paresthesia covering pain); paresthesia discomfort measured by an 11-point numeric rating scale (NRS) while sitting, standing and lying down; health-related quality of life measured by the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire; functional disability measured by the Oswestry Disability Index (ODI); anxiety and depression symptoms measured by the Hospital Anxiety and Depression Scale (HADS) and the Pain Catastrophizing Scale (PCS); and patient satisfaction measured by the Patient Global Impression of Change Scale (PGIC). Safety will be evaluated by adverse events (AE), serious adverse events (SAE) and device deficiencies from inclusion to 12-month follow-up.Secondary outcomes that will be compared between treatments and waveforms are changed between baseline and each follow-up visit in each of the following scores: pain intensity (VAS), pain surface  signal and Fractional Anisotropy (FA) resting state condition (stimulation switch off). Effects of stimulation on brain electrical activity will be measured by EEG signal of the posterior cingulate cortex (PCC), the pregenual anterior cingulate cortex (pgACC) and ventromedial prefrontal cortex (vmPFC), pgACC/vmPFC with stimulation switched on.Regaining functional capacity: having at least a 30% decrease in Oswestry Disability Index (ODI) percentage.Adequate global pain relief: having at least a 50% decrease in the Visual Analogic Scale (VAS).Improvement in quality of life: having at least a 0.2 increase in the EuroQol-5 Dimensions (EQ-5D) questionnaire.Decrease in psychological distress: having a decrease of at least 1.4 points in the Hospital Anxiety and Depression Scale (HADS) depression score.2): pain surface and its properties will be assessed using a pain mapping tool.Decrease of at least 30% in pain surface  score of at least 6/7.Drug intake: drug intake will be measured using the Medication Quantification Scale (MQS) and a reduction of at least 3.4 points will be considered as meaningful.We will also evaluate stimulation efficacy using a published and clinically validated composite factor that allows for the multidimensional evaluation of patients . PatientAt the screening and baseline visits, the following additional pieces of information are collected: general information, such as age, gender, date of birth, demographic and socioeconomic status; history of the disease, such as date of onset, date of management and etiology; medical and surgical history; analgesic treatments, concomitant medications and non-drug treatments; mapping of the thoraco-lumbar and lower limb painful areas; neuropathic pain assessment by clinician-administered diagnostic questionnaire ); and thoraco-lumbar MRI and brain imaging.Patients who proceed to device implantation have the following information collected: mapping of the thoraco-lumbar and lower limb painful areas and paresthesia areas and recording of the various stimulation programs and stimulation parameters. The NeuroMapping tool is a validated quantitative tactile interface allowing the patient to delineate painful zones in the back and legs and to precisely map objective changes in pain coverage and SCS or DRGS performances ,61.Unscheduled patient visits could occur between scheduled study follow-up visits due to patient discontinuation from the study or device programming and management of any complication.To minimize selection bias, the randomization list will be prepared using the random selection program Ennov Clinical. Randomization numbers will be assigned in strict sequence; when a subject is confirmed as eligible for randomization, the next unassigned randomization number in sequence will be given. Randomization allocation will be concealed from the evaluator and subject, using a centralized automatic web-based data management system dedicated to the study and accessible to investigators by username and personal password (CS Online 7.5.10.11). Once assigned, the randomization assignment for the subject cannot be changed. Early departure from the study does not give rise to placement or reassignment of the rank of inclusion.Due to the paresthesia generated by the TCS waveform, during the crossover period, patients will be under TCS waveform, whatever the type of stimulation. Consequently, patients will not be able to distinguish if they are under DRGS, SCS or DUAL stimulation. At the 3-month follow-up visit, all the patients will be switched to the burst waveform for a 1-month period while keeping the last allocated stimulation type in the randomized crossover arm. Patients will keep their stimulation in order to achieve optimal comparability between TCS and burst parameters.To allow for investigator blinding, the evaluator will be different from the person who programs the IPG.In the ACCURATE study , the autWith a level of significance at 0.05 and a power of 90%, we found that a number of patients set at 48 should be adequate to demonstrate a significant difference between the success proportions in SCS, DRG and DUAL stimulations in a six-arm crossover design.Considering the possibility of a potential dropout , and Statistical analysis will be conducted using R software .Data from phase A (12 patients) and phase B (54 patients) will be pooled (66 patients) for the main analysis.Normality of distributions will be tested using the Shapiro–Wilk test. Either parametric or non-parametric methods will be used depending on the normality test results.Our primary objective is to compare the efficacy of SCS, DRGS and DUAL stimulation at the crossover period based on the “50% VAS decrease” outcome.Since our primary endpoint is a binary variable, we will use a mixed-effects logistic regression model, where the fixed effects are as follows: the treatment effect, the period effect and their interaction. The random effect is the random subject intercept. Fixed effects, their 95% confidence intervals and their significant level will be reported. Models will be estimated using restricted maximum likelihood estimation using the lmer function from the lmerTest package.In case of significant effect of period and treatment, a two-step procedure will be conducted to assess pairwise differences between treatment effects. First, treatment effects will be estimated using a mixed-effects model as previously described, using data from each pair of treatments. Next, we will apply Holm–Bonferroni method to keep family-wise error under the 0.05 significance level.p-values following the pairwise comparisons.In case the period effect is not significant, a Cochran Q test will be used to test the differences between the three groups. If the null hypothesis of the Cochran Q test is rejected, a McNemar test will be conducted for pairwise comparisons of the three groups. A Holm–Bonferroni correction will be applied to the p-value is significant, a pairwise comparison procedure with Holm–Bonferroni correction will be conducted.For the secondary outcomes, a two-factor repeated measure ANOVA (treatment + period factors) will be used to compare the continuous outcomes between the three treatments and a mixed effect logistic/multinomial regression model will be used to compare the categorical outcomes similarly to the analysis of the primary outcome. If the omnibus test’s At the 4-month period, the proportions of patients preferring the DRGS, the conventional SCS or the DUAL stimulation will be compared using a Chi-squared test.t-test or Mann–Whitney test depending on the variable distribution. A Holm–Bonferroni correction will be applied on the pairwise comparison.Continuous outcomes at 4-month of burst DRGS, burst SCS and burst DUAL stimulations will be compared using an ANOVA or a Kruskal–Wallis test. In case the ANOVA  is significant, a pairwise comparison will then be conducted using independent The categorical outcomes will be compared using a Chi-squared test or an exact Fisher test when the Chi-squared assumptions are not met. A generalized mixed-effects model with a patient specific random intercept will be used to estimate the global treatment effect including the 6-month and 12-month follow-ups. The link function used in the model will depend on the type of the studied outcome .The relationship between performance (percentage of pain covered with stimulation) and “induced” pain relief  will be estimated by Kendall’s tau and its 95% confidence interval. The correlation between selectivity (percentage of paresthesia covering pain) and paresthesia discomfort will also be estimated using Kendall’s tau.Mean energy consumption will be compared between the different types of stimulation using repeated measures ANOVA or a Friedman test.t-test or a Wilcoxon signed-rank test using data from the last crossover period compared to the 4-month data using burst stimulation. VAS decrease will be compared between all the SCS modalities at 6-month and 12-month follow-ups using a two-factor ANOVA .Tonic stimulation will be compared to burst stimulation using patient last crossover stimulation modality. The comparison will be conducted using a paired A sub-analysis of the sample will be conducted in order to assess the effect of burst waveform on the brain signals visualized using brain imaging data with and without burst stimulation.Two interim analyses are planned. The first interim analysis will be conducted on data from the first 12 patients included (after the “Tonic” crossover period). In this first interim analysis, we will analyze only the safety criteria, the objective being to assess study feasibility. The second interim analysis will be conducted on data from the first 33 patients included (after the “Tonic” crossover period) and will be exclusively descriptive. No hypothesis testing will be conducted. This analysis will be conducted on primary and secondary outcomes. As the study is of long duration (3.5 years), we decided to include a second interim analysis to communicate the results to the scientific community by clearly indicating that this is an interim analysis and that the final analysis will be conducted on the total sample of 66 patients. This may lead to other projects and accelerate the progress of research on the stimulation of several anatomical targets. These results will have no impact on study completion. The final analysis on 66 patients will be considered for the report and the publications.p-values will be conducted as the interim analysis results do not influence in any way the course or the conduct of the study.Only data from the crossover period will be used in the interim analysis. The statistical methods used in this interim analysis will be similar to the methods used in final analysis described above. No adjustment of the final analysis A significance level of 0.05 will be considered in this study (after taking into account multiple testing corrections) and all tests will be two-sided.All the analyses will be conducted based on an Intention-To-Treat (ITT) principle using complete cases. No missing data imputation will be conducted. An initial safety analysis will be conducted on the first 12 patients to assess the initial safety of implementing patients with both DRG and SCS stimulations. A final safety analysis will be conducted on the 66 patients. Frequencies of adverse events and deviations from protocol will be compared between the treatments following an ITT analysis.Long-term stimulation efficacy will be defined as being a “good responder”, according to the composite factor described in the t-tests or Wilcoxon test. The link between nominal qualitative variables and the long-term outcome will be tested using a Chi-squared test or an exact Fisher test depending on the number of patients per modalities. The link between ordinal variables and the long-term outcome will be tested using Cochran–Armitage test. Variables that are significant at a 5% level will be included in a multivariate logistic regression model where we will adjust for the type of stimulation and waveform by including interaction terms between the factors and the type of therapy.The link between stimulation efficacy and each clinical, sociodemographic and psychological factor at baseline will be tested in a bivariate analysis. The link between quantitative variables and the long-term efficacy will be analyzed using Based on a crossover design, our study is meant to provide evidence of SCS, DRGS or DUAL efficacy for treatment of chronic lower limb neuropathic pain and/or neuropathic back pain. The results will indicate comparative efficacy on pain characteristics, quality of life, functional disability, psychological distress and patient profile. In addition, mechanisms of action will be explored under “static conditions”  thanks to fMRI and under the influence of implanted stimulation  using live multisource-EEG analysis. Ultimately, our study aims to provide new insights and opportunities using burst waveforms applied to the DRG, marking a world first. Our sequencing will comprise three distinct phases, which should facilitate comparisons between stimulation spatial targets (SCS vs. DRGS vs. DUAL), comparisons between temporal waveforms (TCS vs. burst) and will ultimately respect patient preference regarding stimulation modalities, thereby documenting the variability of choices through incremental therapy personalization. Possible simultaneous synergy between SCS and DRG on the same patient might catalyze patient outcomes, in terms of neural structure targeting, pain relief, coverage, cortical perception and, ultimately, electrical consumption. That said, technological innovation using existing devices, which have not been intentionally designed for these challenges/this study, will underscore new technical limitations and reinforce the need for new device developments.Within-subject comparisons will help to identify responder characteristics depending on stimulation target (SCS/DRG) and/or stimulation modality (TCS/burst).From a technical standpoint, the lead trial procedure dedicated to identifying responders (whether the patient uses SCS and/or DRGS) will help us to avoid losing any potential patient, who could be identified as a non-responder with one of the two techniques. Additionally, the choice to implant the leads under awake anesthesia will facilitate optimal paresthesia coverage, since the initial phase will optimize sweet-spot coverage thanks to patient intra-operative feedback provided by objective tactile interface and mapping data ,61. It bThe A/B/A + B comparative design will compare two different spatial neurostimulation targets, using the same technology, delivered to the same patient, in a double-blind manner, which is quite rare in neurostimulation studies . HoweverOur study is also intended to build a composite score based on NRS, pain mapping, EQ-5D, ODI, HADS and PCS. This score will provide a comprehensive and global picture of patient health evolution through the follow-up period, as previously reported in recent works ,64. In aSome authors would insist on the subjectivity, and consequently the lack of reliability, of patient’s reported outcomes in comparison between two techniques or two modalities, especially as the double-blind design remains difficult to maintain in a study in which one strategy can be perceived by the patient and the other not. This could euphemize the added value and even the rationale of composite indexes. In our opinion, a need for objectivity fully justifies combining patient clinical data with a functional imaging approach and live exploration of the neural networks involved during stimulation.Identification of cortical mechanisms of action would also provide substantial knowledge about SCS- and DRGS-related induced cerebral plasticity. Recently, MRI studies have suggested that decreased brain activity in the medial thalamus, the insula, the somatosensory cortex and the anterior cingulate cortex after SCS is associated with good outcomes ,69,70,71While most SCS indications are dedicated to back and leg pain neuropathic components in refractory PSPS-T2 (FBSS) patients worldwide ,5,6,8, DIn parallel, while we may suppose that DRGS could become a good indication for PSPS-T2 after clinical validation, several technical considerations need to be discussed. Indeed, a significant proportion of PSPS-T2 patients, who have undergone several (and sometimes major) spine surgeries, develop epidural fibrosis at the foraminal level, corresponding to the potential targeted DRG area to be stimulated. Posterior instrumentation at adjacent levels can become serious technical obstacles to DRG trans-grade approach and represent an impossible Everest to climb, even for experienced implanters. To overcome these potential barriers, we will perform ultra-selective transforaminal anesthetic blocks using contrast agents before implantation to determine whether the foramen is accessible for an implant and to confirm that the nerve root is free of entrapment. The relevance of such a procedure, as recommended or as a mandatory DRGS pre-implantation test, will be discussed in light of our results. This might also help to develop an extra-foraminal needle approach and/or a surgical minimally invasive technique to target DRG “from outside to inside of the spinal canal” for some difficult cases. The choice to consider DRG implantation in PSPS-T2 patients in this study should bring valuable information.Applying burst at the DRG site appears of major interest and has not been published yet, alone or in combination with burst SCS. Many speculations will legitimately arise from this synergistic concept, with an emphasis on electrical consumption. Even though DRGS requires usually very low energy , the combination with burst SCS could override IPG capabilities. Moreover, the existing sources have not been developed to generate DRG burst stimulation. While DRG remains a structure that is highly sensitive to aggressive stimulation, in case of overstimulation, it would respond immediately, with a painful sensation for the patient, which might not be compatible with permanent burst applied to DRG. This potential concern would appear even more striking insofar as it remains strictly impossible to generate two different synchronous burst programs on two different leads (at two different sites in this study) at the moment using existing devices. A final interest of this study will be to clarify, depending on the results, the need, or not, to develop a new generation of IPGs to bridge these gaps.Despite potential interest, this study has several limitations. First, as mentioned above, the comparison between TCS (involving a paresthetic effect) versus burst  will not be performed under strict and homogeneous blinded conditions, by sequentially testing the different stimulation modalities. However, burst will be applied for the three groups  between the 3rd and the 4th month after randomization, which will allow for the comparison of paresthesia-free conditions as a second step, in a second phase. This should not interfere with our main endpoint, at 3-month follow-up, involving TCS and paresthesia for each group of stimulation, in a strict double-blind manner. Second, this crossover design will not allow us to determine long-term efficacy of each stimulation modality, since multiplying the number of modalities to evaluate implies proportionally decreasing the length of the follow-up period for financial and ethical reasons. An alternative point of view would counterbalance this loss of potential valuable information with the fact that this design can also be considered as “added value” for the patient, who will be able to choose his preferred spatial target and waveform, thereby enhancing treatment adherence. Following this perspective, we will collect maximal follow-up for the stimulation modality, which will reflect the patient’s preference. Third, the absence of wash-out period will not allow us to claim that one modality could not induce a carryover effect. However, the 1-month period used for each modality should cancel out this potential carryover effect. Fourth, mechanisms of actions will be assessed at the supraspinal level, even though some modulations can occur at the spinal level. In their in vitro simulation study, Zannou et al. ,75 interThe BOOST DRG study seeks to provide clinical comparative evidence of SCS, DRGS or SCS+DRGS combination efficacy, using either tonic conventional or burst stimulation, in patients presenting with refractory chronic lower limb neuropathic pain or/and neuropathic back pain. Patient assessment will be based on multiple criteria including pain intensity, pain mapping, quality of life, functional disability, psychological distress, catastrophizing and differential cerebral mechanisms of action explored with functional brain imaging coupled with 128-channel MRI-compatible EEG.Our ambition is to capture the potential added value of one novel SCS temporal modality, burst, potentially combined with new spatial targets focusing on DRG, and to bring new insight for patient pain assessment in RCTs, by using multi-dimensional composite objective measurement tools, as a new “high-fidelity” standard for pain studies.


The intervention group showed significantly less pain relief after 4 and 12 weeks. The EQ-5D submodality pain showed significantly inferior results for the intervention (1.5 (0.58)) compared to the sham group (1.1 (0.33)) (p < 0.014) after eight weeks. No significant intergroup differences were observed for RDQ, ODI or BDI-II. Additional rESWT alongside conventional guideline therapy in aLBP does not have any significant effects on pain intensity, physical function, or quality of life. To the best of our knowledge, this is the first study with a high level of evidence reporting the efficacy of rESWT in aLBP treatment and will be a future basis for decision-making.The aim of this study was to investigate the effect of radial extracorporeal shockwave therapy (rESWT) primarily on acute lumbar back pain (aLBP), and secondarily on physical function and quality of life. This randomized, placebo-controlled, single-blinded trial with 12-week follow-up (FU) randomized 63 patients with aLBP 1:1 into two groups receiving either rESWT (intervention) or sham rESWT (placebo) with a manipulated shockwave head not delivering any shockwaves. Both, rESWT and sham procedure were carried out eight times for four weeks. Both groups received additional analgesics and physiotherapy twice a week. Primary patient-reported outcome measure (PROM) was the visual analogue scale for aLBP (VAS-LBP). Secondary PROMs included the Oswestry disability index (ODI), Roland and Morris Disability Questionnaire (RDQ), EuroQol EQ-5D-3L, and the Beck Depression Index (BDI-II). Primary endpoint was a between-arm comparison of mean changes in VAS-LBP from baseline to final FU. At randomization, there were no differences between the two groups in relation to age and PROMs. Both groups showed significant improvement in all PROMs at final FU. VAS-LBP declined by 60.7% ( Acute low back pain (aLBP), with a lifetime prevalence of up to 85% among 18–74-year-olds, is one of the most common types of pain associated with the musculoskeletal system ,3. The cInitially, ESWT found its way into medicine as a treatment option for urolithiasis (focused ESWT) . ExtracoIt has not yet been investigated whether rESWT is also effective in the treatment of nonspecific aLBP. The aim of this study was to investigate the effects of rESWT on nonspecific aLBP, physical function, and quality of life.It was hypothesized that rESWT is more effective in improving acute low back pain and physical function than sham rESWT, each combined with a standardized analgesic and physiotherapeutic regimen.n = 912) were assessed for eligibility. Those who did not meet the inclusion criteria  or had at least one exclusion criterion  and those who declined to participate in the trial were excluded , all patients with aLBP who visited the outpatient department in our hospital over the course of one year  received shockwave therapy (rESWT). The EMS Swiss DolorClast® Classic device with Evo Blue handpiece  was used to administer rESWT, with the patients in the prone position. Low-energy impulses were applied to determine points of maximum tenderness (PMTs). Following this, 400 shockwave impulses (8 Hz) at an energy flux density of up to 0.28 mJ/mm2 were delivered to all PMTs using a 36-mm applicator head. Finally, all paravertebral lumbar muscles were again treated with 500 low-energy impulses (10 Hz) of up to 0.18 mJ/mm2.All the patients were blinded, whereas the principal investigator was not. The blinded patients were then randomly assigned 1:1 into two groups by the principal investigator, using the sealed opaque envelope technique . Once a n=26), a second shockwave head was manipulated by EMS Electro Medical Systems that did not deliver any shockwaves. The “treatment” procedure in the sham group remained the same as in the intervention group (rESWT). The treatment procedure lasted for 15 min. Both groups received treatment twice a week over a period of four weeks . Additionally, all patients received oral analgesics (ibuprofen 600 mg 3 q/day). Three patients (two in the control and one in the intervention group) with individual contraindications for ibuprofen did receive different analgesics. Furthermore, physiotherapy was prescribed for all patients twice a week, and they were followed up for 12 weeks.In the sham group  of 14.6–20.0 mm on the visual analogue scale for low back pain  ,16,17,180) and after 1, 2, 3, 4, 6, 8, and 12 weeks.The primary patient-reported outcome parameter was the pain intensity of aLBP, measured using the VAS-LBP . AdditioStatistical analysis was performed using IBM SPSS Statistics, version 26.0 . All outcome measures were analyzed in accordance with the manual for the respective questionnaire. For reliability analysis, Cronbach’s alpha was calculated to assess the internal consistency of the questionnaires’ subscales.p < 0.05.Data were then pooled by group to calculate the mean (standard deviation (SD)) for each outcome parameter. After testing for gaussian distribution using the Kolmogorov–Smirnov test, analysis of repeated measures with post hoc analysis according to Bonferroni was used for data comparison. The significance level was set at A total of 53 of the 63 enrolled patients were eligible for statistical analysis. Ten patients were lost to follow-up and did not complete all of the surveys, due to a loss of interest in the study after pain recovery. Since some of the patients missed appointments, the 27 patients in the intervention group (mean age 38.7 (12.91) years; 11 men, 16 women) received a mean of 7.4 rESWT treatments, and the 26 patients in the sham group (mean age 40.4 (11.61) years; nine men, 17 women) received a mean of 7.0 sham rESWT treatments.Before therapy, there were no significant differences between the two groups in the VAS-LBP, RDQ, ODI, EQ-5D-3L, or BDI-II scores .p < 0.001) in the intervention group and from 49.1 (21.81) to 6.7 (8.74) (p < 0.001) in the sham group. The intervention group showed significantly less pain relief after 4 and 12 weeks  after eight weeks ) in comparison with the sham group (1.1 (0.33); ht weeks . Althought weeks  or BDI-IFor reliability analysis, Cronbach’s alpha was calculated to assess the internal consistency of the questionnaires’ subscales. The internal consistency of EQ-5D-3L, ODI, RDQ and BDI-II is overall satisfying, with Cronbach’s alpha varying between 0.736 and 0.891.Acute low back pain, which is mostly managed in primary care, is a common cause of disability all over the world . To our In general, this result is contrary to previous studies that had investigated the effectiveness of shock wave therapy for chronic lumbar back pain. Han et al. found that pain intensity decreased significantly when ESWT was administered to patients with chronic low back pain. Lee et al. also reported that a combination of ESWT and physiotherapy was more effective in relation to VAS scores and dynamic balance activity in comparison with an exercise program and physical therapy ,22. NotaIn the present study, intragroup comparisons showed significant decreases in the VAS level, ODI, RDQ, and EQ-5D-3L in both the intervention group and the sham group at the end of the 12-week follow-up period. However, intergroup comparison revealed that these decreases were larger in the sham group than in the rESWT group. Wang reported that extracorporeal shock waves stimulate the expression of angiogenesis-related growth factors, including endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA), which induce neovascularization and improve blood flow in tissues, stimulating healing processes in inflammatory conditions in tendons, bones, and surrounding tissues, and resulting in pain relief . These gAlthough there is some evidence suggesting that the measurement properties of visual analogue scales are superior to those of other patient-reported outcome measures such as the numeric rating scale or brief pain inventory, the VAS is widely used in studies of low back pain. The MCID used in VAS surveys (0–100 mm) varies between 14 and 20 mm, depending on different studies ,16,18. INo complications were observed in the patients throughout the study, a finding that is in line with literature reports .n = 63), 10 patients dropped out during the ongoing study. The statistical analysis is therefore only based on 53 patients. However, it is unlikely that this small deviation could have led to an inconsistent result. Nevertheless, further research arising from the single-center data presented here is therefore needed in order to verify the findings in larger cohort studies based on a multicenter RCT.One limitation of the present study was that, although the aim was to enroll 56 patients and the enrollment target was met (2), and frequency of rESWT application (twice per week), are further possible variables that could be altered in future studies [A further limitation could be seen in the used shockwave technique. The use of radial ESWT instead of focused or defocused ESWT should be considered when assessing the effectiveness of ESWT as a treatment technique . The pre studies . In thei studies . Future In conclusion, systematic comparative studies on this clinically relevant topic are still very rare. This is the first randomized, placebo-controlled trial to analyze the efficacy of rESWT in the treatment of aLBP. From the clinical point of view, rESWT is already used in practice, but without sufficient scientific data. The present trial was conducted in order to help fill this information gap, focusing on whether rESWT might be an option in the treatment of aLBP. This approach is unique in the literature.Both study groups showed significant improvements in VAS, EQ-5D-L, ODI and RDQ throughout the therapy. However, additional administration of radial shockwave therapy in patients with acute lumbar back pain did not show any better or earlier reduction in pain intensity or improvement in physical function, in comparison with sham treatment. Larger multicenter studies are desirable to confirm the findings of this randomized controlled trial.


Low-intensity pulsed ultrasound (LIPUS) is a noninvasive modality to stimulate bone remodeling (BR) and the healing of hard and soft tissues. This research evaluates the biostimulatory effect of LIPUS on the rate of orthodontic tooth movement (OTM) and associated pain, when applied at 3-week intervals. 2 intensity output) was applied for 20 minutes extraorally and reapplied after 3 weeks for 2 more successive visits over the root of maxillary canine on the experimental side whereas the other side was placebo. A numerical rating scale- (NRS-) based questionnaire was given to the patients on each visit to record their weekly pain experience. Impressions were also made at each visit before the application of LIPUS . Models were scanned with a CAD/CAM scanner . Mann–Whitney U test was applied for comparison of canine movement and pain intensity between both the groups.  Twenty-two patients  having Angle's Class II division 1 malocclusion needing bilateral extractions of maxillary first bicuspids were recruited for this split-mouth randomized clinical trial. After the initial stage of alignment and leveling with contemporary edgewise MBT (McLaughlin–Bennett–Trevisi) prescription brackets  of 22 mil, followed by extractions of premolars bilaterally, 6 mm nickel-titanium spring was used to retract the canines separately by applying 150 g force on 0.019 × 0.025-in stainless steel working archwires. LIPUS (1.1 MHz frequency and 30 mW/cmp > 0.05).  No significant difference in the rate of canine movement was found among the experimental (0.90 mm ± 0.33 mm) and placebo groups (0.81 mm ± 0.32 mm). There was no difference in pain reduction between experimental and placebo groups ( Single-dose application of LIPUS at 3-week intervals is ineffective in stimulating the OTM and reducing associated treatment pain. As face and smile is the core of communication, people from different walks of life have become more aware of their dentofacial proportions and facial esthetics. More and more people are seeking fixed orthodontic treatment, but their prime concern is the lengthy course of treatment and discomfort associated with tooth movement . OrthodoAcceleration of bone remodeling under physiological conditions is highly desirable in orthodontic patients to reduce the treatment duration. Several surgical procedures (corticotomies), pulsed electromagnetic fields, direct electrical current, and biomolecule injections may accelerate bone remodeling, but the challenge here is to accelerate bone remodeling in a noninvasive manner –7. AmongIn this regard, low-intensity pulsed ultrasound (LIPUS) has been shown to enhance cell metabolism. Its efficacy for bone regeneration and healing of fractures has long been proven for which it is approved by the US Food and Drug Administration and the UK National Institute for Health and Care Excellence , 13. MecPain wearing orthodontic appliances experience varying degrees of pain. Nearly 99% of patients experience some form of discomfort. Patients experience it as soreness and a feeling of compression and stretch in the affected teeth. It results in a decline in oral health (often manifests as weight loss), compromising the masticatory performance and speech. More often they become indifferent to treatment outcomes and stop cooperating . TherefoThe aim of our research was to evaluate the effectiveness of a single dose of LIPUS on the tooth retraction phase of OTM and the pain associated with it.Male and female subjects with age between 15 and 30 years with a full set of permanent dentition and no missing or impacted teeth except for the third molarsNo systemic disease or pregnancyPatients having half cusp class II molar relationship, necessitating exclusively bilateral bicuspid extractionGood oral hygiene and complianceThis is a randomized clinical trial conducted in the Orthodontic department of Baqai Medical University, Karachi, Pakistan. The study duration was nine months from October 2015 to July 2016. Ethical approval was obtained by the Ethics Committee of Baqai Medical University. Written consent was taken from the patients and the guardians of minors prior to all diagnostic records. The sample size was calculated using power analysis, based on the tooth movement objective. The sample size was determined using power analysis, having 80% power; alpha which indicates significance level was set at 0.05. According to the sample size calculation, twenty-two Pakistani patients, ages ranging from 15 to 30 years (19.18 ± 2.00 years), were selected for the study. Subjects who fell under the following criteria were selected: Chronic use of nonsteroidal anti-inflammatory drugs, corticosteroids, and bisphosphonatesPatients with any metabolic bone diseasePatients with a previous history of fixed orthodontic treatmentThe exclusion criteria include the following:To ensure maximum efficacy, a split-mouth design best suited the study. The right and left sides of the patients who fulfilled the criteria were randomly divided into experimental and placebo groups by a simple randomization technique. Tossing a coin for each patient that enters the trial such that head for the experimental group and tail for the placebo group. Patients did not know which side was experimental or placebo; however, the clinician knew it. The experimental group received the LIPUS irradiation extraorally on the canine root; the transducer was kept at the placebo side for the same duration without turning it on. Blinding was satisfactory as US waves are inaudible and imperceivable.Treatment was initiated with banding and bonding procedures. Preadjusted edgewise MBT prescription brackets  of 0.22-in slot were glued following conventional steps of etching and bonding.For leveling and alignment, a series of NiTi wires were placed, starting from 0.014-in heat-activated nickel-titanium (NiTi) wire followed by 0.016-in NiTi, 0.017 × 0.025-in NiTi, and 0.019 × 0.025-in NiTi upgraded after every 21 days. The final working wire was 0.019 × 0.025 SS. First premolars were extracted on both sides on the 21st day of the final working wire placement. A week after extractions, the canine retraction was commenced. Prior to the beginning of canine retraction, proper leveling and alignment of incisors, bilateral symmetry, and correct angulation of both canines were ensured. The incisors were secured together with 0.010-in steel ligature to prevent inadvertent tooth movement during the retraction phase. A horizontal force was applied by stretching a 6 mm close coil NiTi spring up to 150 g through Orthodontic Dynamometer  and held with a ligature wire between the power arm of the canine and first molar. Patients were told to meticulously maintain oral hygiene and to inform immediately if spring is severed or displaced. They were also discouraged to take analgesics and also advised to note it down if taken for the severity of pain.Immediately after force application, LIPUS was applied extraorally on the experimental side . Ultrasoμs. The recommended intensity output for clinical use is 30 mW/cm2, which was applied for 20 minutes with a 2.5 cm lead zirconate titanate transducer.LIPUS  was used which generates a frequency of 1.1 MHz as it has been used successfully to accelerate BR . The LIPx and y coordinates were drawn on 3D images of the dental cast. Raphe line was taken for the y-axis and the medial end of the most prominent rugae was taken for the x-axis [x coordinate in both the groups and measurements on both sides were compared.To evaluate the effectiveness of the regimen, the experimental side was compared with the placebo side. A subtle method presented by Gebauer was selected, where e x-axis . The disFor pain measurement, numerical rating scale was used , 9. The U test was used for canine movement and pain comparison.The data were recorded, and the results were evaluated on SPSS 20.0 version. Since the data were not normally distributed, nonparametric Mann–Whitney Twenty-two patients were selected for the study and the whole process of data collection took seven months. Two patients were dropped out due to spring dislodgement during the retraction, reducing the sample size to twenty patients.U test reveals no statistically significant difference in canine movement among experimental and placebo groups. Over a period of 9 weeks, the canine achieved 2.72 mm ± 0.11 movement on the experimental side and 2.45 mm ± 0.98 mm on the placebo side. Moreover, the mean canine movement in experimental groups and placebo groups was 0.90 mm ± 0.33 mm and 0.81 mm ± 0.32 mm, respectively (There was no significant difference in canine movement among the two genders. Mann–Whitney ectively .Our study concludes pain intensity peaked within 24 hours after force activation and subsided at the end of 4th day at most stages of treatment. Females reported a slightly higher score of pain intensity, but the statistical test showed an insignificant difference in pain intensity among the two genders.No significant difference was found in the pain intensity between experimental and placebo sides at any stage of treatment .LIPUS has showed its potent clinical efficacy in soft and hard tissue healing in the field of medicine , 24. MorOur research showed no significant difference in the rate of canine movement among genders as well as among experimental and placebo sides. Since LIPUS has never been tested on humans for its rate accelerating and analgesic effects in orthodontic patients, therefore, direct comparison with similar researches was not possible. However, a marked acceleration in the rate of OTM has been reported in animals , 28. DahLIPUS delivers micromechanical stresses to the tissues. Most of the researchers have applied these micromechanical stresses either on daily basis or on alternate days for at least 28 days to assess the rate accelerating effect of LIPUS on OTM and healing effect on orthodontically induced root resorption , 28. HowOur study did not find any analgesic effect of LIPUS in the reduction of orthodontic pain. The analgesic effect of LIPUS on pain related to OTM has never been investigated previously; however, it has been found efficient in reducing lower back pain and improving the functional ability of patients . Ebadi eOur clinical trial did not reveal any favorable effect of LIPUS on the rate of OTM and pain. Due to scarce data available in this domain, more studies are required to understand its effectiveness and mechanism of action.Single dose of LIPUS applied at 3 weeks neither accelerates the orthodontic tooth movement nor reduces the pain associated with orthodontic tooth movement.


IntroductionOne of the most commonly performed surgery by a general surgeon is inguinal hernia repair. There have been numerous open surgical techniques and two laparoscopic techniques described in the literature for the treatment of inguinal hernias. The treatment outcome of all these surgeries remains the same which is reducing the hernia and preventing recurrence. Our aim was to compare laparoscopic versus open inguinal hernia repair with emphasis on postoperative pain.MethodsOne hundred and twenty patients with unilateral primary inguinal hernias were randomly divided into two groups. Each group included 60 patients. Group one was treated by open Lichtenstein repair, while the second group was treated by laparoscopic transabdominal preperitoneal (TAPP) mesh repair. The two groups were compared to assess the duration of surgery, postoperative pain, duration of hospital stay, return to normal activity, and work.ResultsLaparoscopic TAPP repair was found to have a longer operative time as compared to Liechtenstein open repair. In terms of other parameters such as postoperative pain duration of hospital stay, return to normal activity, and work the laparoscopic group was superior. After a one-year follow-up, none of the patients had any chronic pain or evidence of hernia recurrence.ConclusionLaparoscopic TAPP has a clear advantage over the conventional Liechtenstein open surgery especially in terms of reduced early post postoperative pain and return to normal activity. Inguinal hernias are one of the most common surgeries performed by a general surgeon. There are various surgical techniques for the treatment of inguinal hernias that have been described in the literature as well as modifications that have been applied to these techniques. Lichtenstein tension-free hernioplasty was first described in 1989 and is considered as the gold standard treatment for inguinal hernias ,3.Laparoscopic surgery, in general, is associated with less postoperative pain as it involves less surgical trauma in view of smaller incisions as compared to open surgery. Chronic pain is an important factor in the context of hernias as hernia repair involves the placement of a mesh during repair which can contribute to neuralgia. Hence, our study aims to compare laparoscopic transabdominal preperitoneal (TAPP) hernia repair with open Liechtenstein mesh repair with emphasis on early and late postoperative pain.This prospective randomized study included 120 patients diagnosed with primary inguinal hernia. Patients were randomly divided into two groups. The first group of 60 patients underwent open Lichtenstein tension-free hernioplasty while the remaining patients in the second group underwent laparoscopic transabdominal preperitoneal (TAPP) mesh repair.Inclusion criteria were patients with uncomplicated primary unilateral inguinal hernia aged from 18 to 90 years. Exclusion criteria included patients with bilateral inguinal hernias, complicated inguinal hernias, recurrent hernias, chronic liver or renal disease, unfit for major surgery, and history of chronic groin pain.All the surgeries were performed by two surgeons experienced in laparoscopic and open repair in order to avoid bias. Patients were kept nil by mouth for about six hours prior to surgery and received a single dose of antibiotic prophylaxis half an hour before surgery. The type of anesthesia used was spinal anesthesia for open cases and general anesthesia for laparoscopic TAPP. Epidural anesthesia was not administered in any of the cases. In all patients, a monofilament polypropylene mesh was used and fixed appropriately.During the postoperative period, all patients received intramuscular non-steroidal anti-inflammatory 12th hourly for one day postoperatively. The intramuscular injection was continued for an additional 24 hours if pain was severe [visual analogue scale (VAS) >IV]. Oral non-steroidal anti-inflammatory drugs (NSAIDs) were prescribed as and when required after 48 hours of surgery.All the patients were encouraged for oral feeds after eight hours, initially, the feeds were sips of liquids followed by normal diet after the resolution of postoperative ileus . The wounds were inspected for any seroma, hematoma or any infection. Patients were discharged after complete ambulation and tolerating normal diet.The pain experienced by the patients in the postoperative period was graded according to the visual analogue scale (VAS) ranging from no pain to the worst possible pain on the scale of 0 to 10. It was recorded on the first and seventh postoperative day. After discharge, patients were encouraged to take normal diet and return to their normal activities as early as possible. After discharge, patients were followed up at one week, one month, three months, and six-month intervals. In the initial follow-up, the patients were evaluated for short-term complications like seroma or hematoma and wound infection. During subsequent visits, chronic pain at the operated site, return to normal activity were noted.The two groups were compared regarding operative time, postoperative complications, postoperative pain, hospital stay, time to return to normal activity as well as work, and one-year recurrence rate. Data were analyzed using the chi-square test, a P value of <0.001 was considered significant. SPSS version 25 for mac was employed for statistical analysis.The age of patients ranged from 21 to 84 years with the mean being 48.7 in the open group and 42.17 in the laparoscopic group. There were more males as compared to females in both the open group and laparoscopic group. The right inguinal hernia was more common as compared to the left . Lap TAPP group had a significantly faster return to normal activity compared to the open group; . Most of our patients that underwent surgery had an active work life and the laparoscopic TAPP group had a significantly shorter time for return to work compared to the open group . After a 12-week follow-up for chronic pain assessment, none of the patients had any complaints of postoperative pain or neuralgia.The introduction of Lichtenstein tension-free hernioplasty considerably reduced the chances of hernia recurrence to as low as 1-4% making it a gold standard treatment. Since minimally invasive surgery is being used more commonly with most surgeries, it has the potential to be the new gold standard if done with expertise [In our study, the operative time for open surgery was significantly shorter as compared to laparoscopic TAPP. This may be due to the fact that setting up laparoscopic equipment takes a longer time as compared to open surgery. Scheuermann et al.  in theirIn terms of postoperative pain and duration of hospital stay, laparoscopic TAPP was at a clear advantage. Since patients undergoing laparoscopic surgery had less postoperative pain, this ensured that they would mobilize early and it resulted in early discharge from the hospital as compared to the open group. One of the reasons for chronic pain following hernia surgeries is entrapment of the sensory nerves. Dividing or preserving these nerves during surgery has been debatable with no clear advantage of one over the other ,9. LaparPatients that underwent laparoscopic surgery in our study returned to normal activity and work quicker as compared to the open group which were similar to findings by Neumayer et al. In this study, we did not take the cost factor into consideration but since patients in the laparoscopic group were sent home early, this may bring down the overall cost of hospitalization but further studies need to be done to check its statistical significance.One of the disadvantages of our study is that we did not have measures for long-term follow-up to look for recurrence as well as assess patients for pain after one-year following their surgery.Laparoscopic TAPP for primary unilateral inguinal hernia have a better outcome than open Lichtenstein repair, especially in terms of postoperative pain and early resumption of normal activity and work.


Neuropathic pain (NP) affects approximately 30% of patients with advanced cancer. The prevalence of neuropathic pain related to peripheral neuropathy (NP-RPN) in these patients is not known. The aim of the study was to evaluate NP-RPN prevalence in hospice patients and to find out whether the absence of this pain is sufficient to rule out peripheral neuropathy. The study included a total of 76 patients with advanced cancer who were cared for at inpatient hospices. All patients were asked about shooting or burning pain (of the feet and hands), were examined systematically for sensory deficits and had a nerve conduction study performed. NP-RPN was found in 29% of the patients. Electrophysiologically-diagnosed peripheral neuropathy was found in 79% of patients, and the diagnostic electrophysiological criteria for neuropathy were met by one half of the patients without NP-RPN. The severity of NP-RPN was correlated with the clinically assessed severity of sensory neuropathy and the Karnofsky score, but was not correlated with the intensity of the clinical signs of motor neuropathy. The presence of NP-RPN did not reflect greater prevalence of motor and sensory abnormalities in neurological and electrophysiological examinations. The absence of NP-RPN did not rule out polyneuropathy in hospice patients. Neuropathic pain (NP) is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system . Up to 1The access to these examinations is limited in people admitted to hospices. This is one reason that NP prevalence data concerning patients with end-stage cancer are lacking. In one systematic review, the prevalence of neuropathic pain as the predominant type of pain in patients with cancer-related pain ranged from 19% (if pure) to 39% (if mixed) . The preNP in cancer patients is a relatively broad term. It involves both central and peripheral causes of pain. Neuropathic pain related to peripheral neuropathy (NP-RPN) is just one type of peripheral neuropathic pain. Other types include: trigeminal or postherpetic neuralgia, peripheral nerve injury or radiculopathies . The mecThe number of patients with NP-RPN increases with cancer progression as there are more factors adversely affecting peripheral nerves. These include steroid-induced diabetes and nutritional deficiencies. Data concerning the prevalence of painful neuropathy in people with advanced cancer are lacking. It is only known that symptoms of peripheral neuropathy in the form of tingling/numbness in hands and/or feet are found in 40% of hospice patients . The ideNP is associated with damage to small nerve fibers. It has been demonstrated, however, that pain in painful peripheral neuropathy (not only cancer-related) is often accompanied by disorders of various sensory modalities, including touch, meaning that both small and large fibers were damaged .Compared to small fibers, damage to large sensory fibers is relatively simple to evaluate in a nerve conduction test. It is an objective, comparable, reproducible and readily accessible examination. Additionally, it enables objective assessment of motor fibers. On the other hand, the clinical assessment of small fiber function (quantitative sensation tests) is difficult; the examinations are very time-consuming, poorly standardized and require patients to stay focused for a long time and be fully cooperative. Novel neurophysiological techniques  or skin biopsies are poorly available and not well tolerated.According to the grading system for NP, proposed by the International Association for the Study of Pain (IASP), the final level of certainty requires confirmation of the lesion or disease of the somatosensory nervous system by objective tests, such as a nerve conduction study. Nevertheless, in practice, neuropathic pain is diagnosed mainly based on medical history and physical examination .The increasing life expectancy of people diagnosed with cancer, including those with advanced disease, is associated with increased prevalence of clinically significant peripheral nerve injury. The signs and symptoms of polyneuropathy may vary depending on the type of damaged nerve fibers. Being aware of their presence and knowing the grade and profile of this damage could help improve the quality of palliative care, particularly with respect to pain control—especially for neuropathic pain and in terms of physiotherapeutic management  ,21,22,23The study enrolled patients with advanced cancer who were hospitalized in inpatient hospices in Chojnice, Bydgoszcz, Sopot and Gdansk (Poland). The inclusion criteria included age over 18 years and a diagnosis of an advanced cancer. Patients with implanted cardioverter-defibrillators and patients in poor overall condition that prevented informed consent were excluded. A total of 80 patients were enrolled; none refused participation. In four patients, complete clinical and neurophysiological examination could not be undertaken and so 76 records were available for analyses.Medical history concerning disease duration, risk factors for neuropathy, reported neuropathic symptoms, used medications and body weight reduction within the past 6 months was collected from all patients. Information about the type of cancer and previous therapy as well as current treatment was derived from the medical records.NP-RPN was diagnosed based on a medical interview by asking patients about the presence of shooting or burning pain in the feet (or in the feet and hands). This question was based on item 36 of the EORTC (European Organisation for Research and Treatment of Cancer) quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy (QLQ-CIPN20). The severity of symptoms was assessed on a 4-point scale  . NP-RPN All patients had their height, weight and BMI (body mass index) measured. The cancer patient performance status was determined using the Karnofsky scale. Cachexia was defined as body weight reduction by over 5% within 6 months or over 2% in patients with baseline BMI <20, according to the consensus 2011 .Patients were examined for muscle strength  according to the Lovett scale and for the patellar and Achilles reflexes in order to assess motor fiber function.The sensory examination began from the hallux and proceeded upwards if any abnormalities were found. Various sensory modalities were tested: pain sensation using a disposable sterile Neurotip pin, temperature sensation using Tip-Therm, position sense, vibratory sense using a 128 Hz tuning fork and touch sensation using a 10 g monofilament.The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0) were used for the clinical evaluation of the stage of poly-neuropathy. The NCI-CTCAE is a descriptive terminology which can be utilized for adverse event (AE) reporting. A grading (severity) scale is provided for each AE term. This is a 5-point scale .-The median and ulnar nerves in the upper extremity (orthodromic method);-The sural nerve in the lower extremity (antidromic method).All electroneurographic examinations were conducted using standard methods with a Dantec Keypoint device v.2.32 . Prior to the examination, skin temperature was controlled on the dorsal aspect of the foot; if lower than 27 degrees Celsius, the foot was warmed. The electrophysiological examination of the sensory nerves included:-The median and ulnar nerves in the upper extremity;-The peroneal nerve in the lower extremity.The motor nerve examination included:The electrophysiological examination was conducted using the non-dominant upper extremity. In patients with breast cancer, the test was conducted on the upper extremity contralateral to the site of cancer. The lower extremity was tested on the right side. The motor fiber assessment included terminal latency, conduction velocity and M-wave amplitude. The sensory fiber assessment included conduction velocity and reflex amplitude. Widely accepted criteria for identification of abnormalities were used . PolyneuThe study protocol was approved by the Ethics Committee of the Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Poland (KB 268/2015 dated 21 April 2015 with amendment dated 20 October 2015 and 25 September 2018). All patients expressed written consent to the participation in the study.t-test and the Mann–Whitney U-test, an alpha of 0.05, a beta of 0.10 . However, such analysis design required inclusion at least 522 patients.Statistical analyses were conducted using a licensed version of the statistical software STATISTICA, version 13.1 , developed by Tibco Software, Inc (2017), Palo Alto, CA, USA. The null-hypothesis for statistical analyses in this study was that patients with and without neuropathic pain related do not differ in relation to values of parameters analyzed, both clinical and electrophysiological. The sample size was calculated post hoc with the assumption that parameters studied will differ between groups analyzed by 20% with 25% of standard deviation (un-paired variables). We assumed also the use of the Student’s p-value of <0.05. The results were presented as the mean ± standard deviation, or n, %. The statistical significance of the differences between the groups was verified using the Student’s t-test and the Mann–Whitney U-test for quantitative variables , and the Fisher’s exact test was used for categorical variables. Rank Spearman correlations were calculated.The normal distribution of the study variables was checked using the Kolmogorov–Smirnov test. The statistical significance level was set at a Of the 76 patients included in the final analysis, NP-RPN was found in 29% . ElectroThe clinical characteristics of patients with and without NP-RPN differed in relation to opioid use but without statistical significance . That isHowever, there were no statistically significant differences in the clinical and electrophysiological parameters between the analyzed sub-groups . The onlThe severity of NP-RPN correlated with the clinically assessed severity of sensory neuropathy diagnosed according to the NCI–CTCAE v.4.0 both in the entire study group and in the sub-group of patients with NP-RPN . HoweverThe present study revealed that NP-RPN occurs in nearly 30% and peripheral neuropathy in nearly 80% of hospice in patients with advanced cancer. Interestingly, NP-RPN was not more common in patients after chemotherapy or in patients with diabetes or a history of excessive alcohol use, although this could result from a small sample size . It is dCompared to other patient groups, the NP-RPN rate in this study was similar to the rates reported for diabetic patients (21–60%)  and loweIt is surprising that NP-RPN severity was not found to be correlated with other clinical signs  and nerve conduction studies  and amounted to 0.12–0.28, making it impossible to accept a null hypothesis when the p-value was ≥0.05. The third study limitation was that we had no possibility to determine the type and doses of previous chemotherapy, and perhaps if treatment with drugs of low neurotoxicity had been excluded, the effect of chemotherapy on the occurrence of neuropathic pain might have been confirmed. The fourth limitation was related to the use of norms of ENG parameters validated for patients with neurological disorder but not for hospice patients (to our best knowledge not available until now). Moreover, it was impossible to complete data about the type and doses of analgesics, which might have otherwise enabled analysis of treatment efficacy. That is why it is necessary to design a multicenter study to recruit more patients.The greatest limitation in this study was the inability to objectively assess small fibers function, which is the main reason of neuropathic pain. The second limitation of our study was the inclusion of an insufficient number of patients, which affected both the power and statistical significance of the observed differences. The insufficient number of patients enclosed the post-hoc calculated power of the analyses, which did not reach statistical significance (In this preliminary single center study, NP-RPN was reported in about 30% of hospice patients. However, its diagnosis did not reflect the greater prevalence of motor and sensory abnormalities found in neurological and electrophysiological examinations. NP-RPN did not achieve sufficient values of diagnostic test parameters, and therefore the diagnosis of NP-RPN cannot be used as a biomarker of polyneuropathy in hospice patients.


Moderate-to-severe pain is reported in up to 75% of the patients in the first 48 hours after cardiac surgery. Evidence suggests that distraction is an effective nursing intervention for controlling short-term and transient pain. Distraction can be achieved by various techniques, including progressive muscle relaxation, meditation, and rhythmic breathing (RB). The present research aimed at evaluating the impacts of RB on the severity of sternotomy pain after Coronary Artery Bypass Graft (CABG).  This randomized, controlled clinical trial was conducted on 60 patients after CABG surgery at the open-heart surgery Intensive Care Unit (ICU) of Kowsar Hospital, affiliated to Semnan University of Medical Sciences in Semnan, Iran. The patients were selected through convenience sampling and randomly assigned to two groups, including (1) intervention or RB and (2) control groups. RB was performed in the intervention group every 12 hours (9 a.m. and 9 p.m.) for three consecutive days after the surgery. The control group received only routine care for pain control  with no additional interventions. The severity of pain was measured every day in both groups of patients before and after the interventions using the Visual Analog Scale (VAS). p < 0.05). The changes in the mean pain score in the intervention group were also significantly different from the corresponding changes in the controls (p < 0.05).  The mean postintervention pain scores were significantly different from the mean preintervention scores in the intervention group (IRCT20120109008665N7, registered 3 September 2018. Based on the results, the severity of pain after the intervention was significantly lower in the RB group compared to the control. RB was found to be an effective technique for reducing the patients' pain and is therefore recommended as a post-CABG pain control technique. Iranian Registry of Clinical Trials: this trial is clinically registered with  Open-heart surgery is currently performed in many countries to increase the survival and quality of life of patients with cardiac diseases . CoronarSeveral factors contribute to the pain following open-heart surgery, including sternotomy, harvesting saphenous vein, harvesting internal thoracic artery, and inserting various drains . The patAccording to medical personnel, patients are not in great pain after sternotomy because the tissue damage that occurred is negligible and the patients are minimally mobile after surgery. Nevertheless, Lahtinen reported moderate-to-severe pain (pain score of 4 to 10) in up to 75% of the patients in the first 48 hours after cardiac surgery . Thus, eA variety of medicinal and nonmedicinal therapies have been proposed for pain management. Medicinal methods such as opioids are currently used to alleviate pain in cardiac patients but are not desirable as the first line of treatment because of their costs and adverse effects on different body parts, which increase patient mortality and morbidity . Hence, Studies indicate that distraction is an effective nursing intervention for controlling short-term and transient pain by increasing endorphins , 24. QuoRB is one of the distraction methods that make patients voluntarily distract themselves from a painful stimulus and thus help control their pain , 29. DisSeveral studies have reported the effect of RB on reducing pain , 33–37. Sternotomy site pain is the patients' most common complaint and probably the most severe postoperative pain experienced, which can be associated with increased patient morbidity and mortality . Patientn=((z1-α/2 + z1-β)2 × (δ12 + δ22))/(μ1 - μ2)2), the sample size was determined as 30 patients per group. Using G∗power, the effect size was estimated as 0.96 (means: difference between two independent means). A total of 67 patients entered the study, of whom seven withdrew for various reasons, and the data from 60 patients (30 per group) were ultimately analyzed. The patients who fulfilled the inclusion criteria were included in the study and were then randomly assigned to the groups using random blocks of A for the experimental group (RB) and B for the control group. Since patients who practice RB are easily distinguished and the researcher taught the patients how to breathe rhythmically, it was not possible to perform blinding. This parallel randomized, controlled nonmasked clinical trial was conducted between September 2018 and September 2019 on patients undergoing CABG surgery at Kowsar Hospital, affiliated to Semnan University of Medical Sciences in Iran. Following a preliminary study with ten patients from each group (RB and control), the mean and standard deviation of the severity of pain were found as 1.3 ± 0.65 in the RB group and 2 ± 0.8 in the control group. Then, taking into account 95% confidence interval and 80% test power and using equation , no previous history of CABG, no life-threatening arrhythmias, and no use of Cardiopulmonary Bypass (CPB). The exclusion criteria were as follows: having a history of diabetes, prolonged intubation (more than 24 hours after surgery), dependence on inotropic agents for hemodynamic stability after extubation, PaOIn terms of ethical considerations, the Ethics Committee of Semnan University of Medical Sciences approved the present research (IR.SEMUMS.REC.1397.138). This study was also registered in the Iranian Registry of Clinical Trials (IRCT20120109008665N7). After introducing himself to the patients, the researcher briefed the participants on the research objectives and procedures, assured them of the confidentiality of their information and their right to withdraw from the study at their own discretion and responded to their questions. The subjects then signed written informed consent forms for participation.RB technique was performed for the intervention group. RB was individually taught to the intervention group before surgery until they could perform it independently and correctly. The day after surgery, upon gaining full consciousness and hemodynamic stability, the patients were asked to close their eyes in the supine position, inhale through the nose, then hold their breath, and exhale through the mouth, while counting from 1 to 3 in each step. All the patients in the intervention group were trained to focus only on air entry and exit while breathing, and they were asked to perform RB once every five minutes, lasting one minute each time, for 20 minutes  . The patData were collected using a two-part questionnaire. The first part dealt with the patients' demographic details, including age, gender, education, body mass index (BMI), underlying diseases, duration of hospitalization before and after surgery, history of smoking and opioid use, amount of opioid injection, on-pump duration, ejection fraction, duration of mechanical ventilation, and the number of grafts and chest tubes. Surgery was performed using a cardiopulmonary pump in both groups. Also, the method of anesthesia, anesthesia medications, and fluid therapy during and after surgery were the same for all the patients. Any changes in routine instructions were recorded by the researcher.In the second part, the patients' pain score data were collected by the Visual Analog Scale (VAS). Pain was measured at 9 a.m. and 9 p.m. before and after RB performance in both groups for three days. The patients were asked to express their pain severity by choosing a number between 0 (no pain) and 10 (most severe pain). VAS categorizes the severity of pain into four groups: 0 = no pain, 1–3 = mild pain, 4–7 = moderate pain, and 8–10 = severe pain. In one study, Alghadir et al. confirmed the reliability of VAS with an intraclass correlation coefficient of 0.97 . In the t-test was used to compare the two groups in terms of age, BMI, smoking, on-pump duration, ejection fraction, mechanical ventilation, hospitalization before and after surgery, mean severity of pain before and after intervention, difference between the mean values preintervention and postintervention in each group, and the amount of morphine used. The Chi-square test was used to compare the absolute and relative frequencies in terms of the patients' gender, education, drug use, underlying diseases, number of grafts and chest tubes, and pain intensity between the two groups. The repeated-measures analysis of variance was used to assess the effect of time and the interaction effect of group and time on the mean severity of pain three days after surgery.Data were analyzed with a per-protocol approach in SPSS-19  at a significance level of 0.05. The study data were described, grouped, and compared in absolute and relative frequency tables. The results of the Kolmogorov–Smirnov test confirmed the normal distribution of the data. The independent sample For analysis of variance with repeated measures, the following statistical presuppositions were examined first: quantitativeness of the dependent variable, elimination of outliers, normal distribution of the dependent variable distribution, and confirmation of sphericity of the groups with Mauchly's statistics, and three factors of intervention (versus control), time point during the day (difference between before and after scores at 9 a.m. and 9 p.m.), and days  were entered into the analysis.p > 0.05). One-third of the patients in the intervention group and more than half in the control group had several underlying diseases, and hypertension was the single most frequent underlying disease in them.The present study recruited 60 patients after CABG surgery. The patients' mean age was 61.58 ± 9.7 years, and the majority (80%) were male. t-test results showed no significant difference between the two groups in the severity of pain in the first three days after surgery before beginning the intervention, except on the third night (p > 0.05). Meanwhile, the severity of pain after the intervention, as measured on both occasions (9 a.m. and 9 p.m.) in all three days, was significantly lower in the RB group compared to the controls (p < 0.05) (p < 0.05). None of the patients in both groups had severe pain (p < 0.05)  = 137.3, p < 0.001) (t-test results showed no significant difference between the two groups in the dose of morphine administered (p = 0.604).The independent  < 0.05) . The resere pain . There w < 0.05) . The res< 0.001) . The meaThe present findings on the effect of RB on post-CABG sternotomy pain control confirmed that RB was effective in reducing the severity of sternotomy pain after surgery in the intervention group. To the best of the authors' knowledge, this is the first study to investigate the effect of RB on post-CABG sternotomy pain.Allah” and performing RB on postoperative pain in orthopedic patients showed that, compared to the control group, the group reciting Allah, followed by the group performing RB, had lower mean severities of pain. They concluded that both methods can be used to reduce pain after orthopedic surgery [After the intervention, the severity of pain, as measured on both occasions (9 a.m. and 9 p.m.) in three consecutive days following the surgery, was significantly lower in the intervention group compared to the controls. The results of the repeated-measures ANOVA showed a significant difference between the two groups in the mean difference in the severity of pain over the three days, which was lower in the intervention group. In agreement with this result, several studies conducted on the effect of RB on pain have also shown that RB can help reduce pain and the number of analgesics administered after surgery , 33, 34. surgery . Lalegan surgery –37. The  surgery . The res surgery , 43. Bag surgery . The res surgery .Nevertheless, the results obtained by Slade showed that these techniques are less effective than expected in reducing pain . AccordiThe results showed no significant difference between the two groups in the dose of morphine administered (1.97 mg in the RB group and 2.57 mg in the control group), but this difference was clinically significant. Other studies reported a significant difference between their intervention and control groups in the number of analgesics received after surgery , 34, whiIn the present study, the severity of pain was significantly higher in the RB group than the control group at 9 p.m., three days before the intervention, but after the intervention, a significant reduction was observed in the severity of pain in the RB group compared to the controls. This important finding is indicative of the effect of RB on reducing pain, which was also confirmed by the repeated-measures ANOVA results.The results of pain intensity in patients in both groups also revealed that the pain intensity in the RB group significantly decreased after the intervention compared to that in the control group at 9 a.m. and 9 p.m. for three consecutive days. According to the results, although the effect of time on reducing patients' pain intensity should not be ignored, the intervention (RB) significantly affected patients' pain intensity.According to the researchers, it is necessary to consider factors affecting the perception of the severity of pain. The nature and severity of postoperative pain depend on the size and amount of incision and type of surgery. In addition, the perception of pain depends on ethnicity, culture, beliefs, personal experience of pain, and personality . The facThe main limitation of the present research included the reluctance of the patients to follow the instructions provided for performing the breathing exercises owing to their improper psychological status. Some measures were thus taken to encourage them to cooperate. A natural limitation of the present study was also associated with the subjective nature of pain, which caused differences in the degree of pain reported by different individuals because pain severity is a patient-reported outcome. The unicenter type of this study and its small sample constituted other limitations, which restricts the external validity of the findings and prohibits their generalizability to other centers. It is recommended that further research be performed with larger samples and more prolonged follow-ups to obtain more accurate results on the effects of rhythmic breathing on pain after CABG with sternotomy.The results confirmed that RB is effective in reducing the severity of sternotomy pain after CABG surgery. Given the importance of the management of pain as the fifth vital sign and to prevent the side-effects and problems caused by the lack of proper pain control, especially in patients after CABG, RB can be recommended as a simple, safe, and inexpensive method in the form of an independent nursing activity in conjunction with other medical measures for reducing the severity of pain in patients after CABG surgery.