Patients with chronic low back pain (CLBP) frequently present with kinesiophobia. Though large body of evidence reported the impact of kinesiophobia in patients with CLBP, there are paucity of studies in associating kinesiophobia to muscle endurance and position sense in patients with CLBP. The primary aim of the study is to compare the impact of kinesiophobia on lumbar extensor endurance, position sense in patient with CLBP, and asymptomatic individuals. Secondarily, we aim to examine the association between kinesiophobia and lumbar extensor endurance, position sense, pain intensity, and functional ability in patients with CLBP. Thirdly, we aim to assess the degree of association of various factors on CLBP, lumbar endurance, and position sense.This case-control study will have 200 patients with CLBP and 400 controls. Kinesiophobia, lumbar endurance, and lumbar position sense will be assessed with Tampa Scale, Soren’s lumbar extensor test, and lumbar repositioning test respectively. Secondarily, the pain intensity will be assessed with visual analog scale and functional ability with Patient-specific Functional Scale in patients with CLBP. Lumbar endurance and joint position sense will be compared between subjects with and without kinesiophobia. Kinesiophobia scores will be compared with lumbar extensor endurance and proprioception joint position errors, pain intensity, and functional ability. Simple and multiple binary logistic regression will be used to determine crude and adjusted odd’s ratio for kinesiophobia, lumbar position sense and kinesiophobia, and lumbar endurance.The finding from this study can be generalized as this study has adequate sample size and subgroup analysis by adjusting the variables to draw a valid conclusion. The finding of this study will help the working physician to include assessment of kinesiophobia as part of musculoskeletal evaluation for patient with CLBP in a prospective diagnostic intervention.NCT05079893. Registered on 14 October 2021.ClinicalTrials.gov The online version contains supplementary material available at 10.1186/s13063-022-06406-6. Chronic lower back pain (CLBP) is one of leading causes of disability for adults of working age . GloballThough there are numerous biological factors that contribute to LBP, psychological factors may play an unexpectedly large role in some patients with chronic LBP . New insKinesiophobia is described as an excessive, unreasonable, and crippling fear of performing a physical motion due to a feeling of vulnerability to a painful injury or reinjury . ClinicaThe mechanism can be described as follows: persons who catastrophically misinterpret innocuous bodily sensations, including pain, are likely to become fearful of pain, which results in at least two processes. First, pain-related fear is associated with avoidance behaviors and the avoidance of movement and physical activity in particular. Avoidance also means withdrawal from rewarding activities such as work, leisure, and family. Second, pain-related fear is associated with increased bodily awareness and pain hypervigilance. Hypervigilance, depression, and disuse are known to be associated with increased pain levels and hence might exacerbate the painful experience. This model is used to develop successful treatments –22.Thus, kinesiophobia is correlated to pain-related interference and triggers motor activity changes that influence activities related to pain and pain-related disability management and control . The preKinesiophobia may produce a wide variety of physical and psychological effects that indirectly influence back pain to be maintained or recur or cause changes in the somatosensory system –28. StudChronic LBP is also associated with decreased endurance of the trunk extensor muscles [TE]. In addition, studies reported TE in chronic LBP participants to be significantly weaker than asymptomatic participants. The multi-factorial dysfunctions consistently reported in literature is the deconditioning of the lumbar extensor musculature, i.e., thoracic and lumbar erector spinae, multifidus, and quadratus lumborum , 37.Long-term mechanical low back pain (LBP) results in inhibition and atrophy of the deep segmental muscles such as multifidus and overactivity of the longer superficial muscles of the trunk with resultant decreased dynamic activity and increased fatigability , 39. ThoMoreover, in the spine, proprioceptive information is provided by structures present in the spinal ligaments, facet joints, intervertebral discs , and parTo the best of our knowledge, till date there are no studies assessing the relationship between kinesiophobia, lumbar endurance, and lumbar position sense in subjects with CLBP. Therefore, the current study aims to compare the impact of kinesiophobia on lumbar extensor endurance, and position sense in patient with CLBP and asymptomatic individuals. Secondarily, we aim to examine the association between kinesiophobia and lumbar extensor endurance, position sense, pain intensity, and functional ability in patients with CLBP. Thirdly, we aim to assess the degree of association with various factors on CLBP, lumbar endurance, and position sense. Therefore, we hypothesized that kinesiophobia would impact the lumbar position sense and lumbar endurance as well.This is a case-control study where the patients with CLBP conditions and asymptomatic controls will be recruited from Thumbay Physical Therapy & Rehabilitation Hospital, Gulf Medical University, Ajman, United Arab Emirates. After obtaining ethical clearance, informed consent will be taken from all the recruited participants. The recruiting of participants for this study will be done from May 2022 to November 2022.As for the calculation of the sample size, the odds ratio taken is 2 with the prevalence of 70% kinesiophobia  among CLAdults aged between 18 and 59 years .Patient suffering from low back pain for at least 3 months and referred by an orthopedic doctor or general physician.Participants with enough physical autonomy to take part in physical activities such as performing lumbar endurance and lumbar positioning test required of the study.Low back pain patients with neurological deficit, any neurological disorder, post spinal fractures, history of spinal tumors, cauda equina syndrome, tuberculosis spine, any congenital spine anomalies, vestibular issue, joint instability in lower limb, cardiorespiratory problem, and hip arthritis.Patient under antidepressive medication and antihypertensive medicationPatient unwilling to participateAdults aged between 18 and 59 years.Either gender.History of (H/o) previous lower back injury.Participants with congenital spine anomalies, vestibular issue, joint instability in lower limb, cardiorespiratory problem, and hip arthritis.H/o inflammatory, infectious disease, and malignancy in the spinePatient under antidepressive medication and antihypertensive medicationThe initial screening of participants will be performed by a physiotherapist (examiner 1) during the first physical therapy appointment. Then, the participants will be instructed to fill a Tampa Scale for kinesiophobia which is a questionnaire consisting of socio-demographic information , pain characteristics (pain area and associated symptoms); fear-avoidance behavior and physical examination carried out by the examiner. The evaluation of pain intensity and function will be performed through self-reported questionnaires . The physiotherapist (examiner 2) who carries out the lumbar endurance and position sense will be blinded for the cases and control group.Three levels of specifications in reporting five outcome measures to be used in this study are provided in Fig. Fear of movement/injury or reinjury will be assessed using the Tampa Scale for Kinesiophobia (TSK), a scale with 17 self-reporting items with scores ranging from 17 (absence of fear) to 68 (highest fear) . Tampa SAll these experiments will be conducted in a laboratory setting. The subjects will be tested during a 1-h session and will be asked to undergo a body weight-dependent isometric back extension (Sorensen) test on a horizontal table . SorenseSubjects will be instructed not to perform any strenuous physical activity for 24 h prior to testing and to not drink or eat 2 h prior to testing (to minimize cutaneous input from a distended abdomen). For testing, subjects will be blindfolded to eliminate visual input and the room will be kept quiet to limit auditory input. Subjects will be asked to stand in a neutral position, with their knees straight and weight equally on both feet. The primary sensor digital inclinometer will be placed over the lateral chest (T12 level) and secondary sensor over the hemi-pelvis (S1 level) in the sagittal plane to measure lumbar reposition errors in flexion. A primary sensor (T12) and secondary sensor  in the frontal plane will be used to record lateral bending angle error. Velcro straps will be used to secure the digital inclinometer for testing. Dualer IQ digital inclinometers  will be used to measure lumbar joint position error. Digital inclinometers are reliable, fast, and high in measurement precision and allow clinicians to evaluate ROM and proprioception using dynamic inclinometry like that used in other goniometric protocols . The digFor neutral lumbar positioning (NLP) testing, subjects will be asked to maintain the lumbar spine in a neutral position with their eyes closed. The inclinometer will be calibrated to a starting position (0 degrees) by the examiner . The subFor target lumbar positioning (TLP), the examiner guided in a slow steady pace that subject’s lumbar spine reached to a predetermined target, 50% of the maximum ROM. This range will be chosen so that all subjects could achieve it. The spine will be maintained in the target position for 5 s, subjects will be asked to remember the position, and the lumbar spine will be guided to a neutral position . SubjectPain will be measured using a visual analog scale (VAS). The visual analog scale consists of a 10-cm line, with the left extremity representing (absence of pain) and the right extremity indicating (great pain) . As per Functional ability will be measured using Patient-specific Functional Scale [PSFS] where patients are asked to identify up to five important activities they are unable to perform or are having difficulty with as a result of their problem, e.g., putting socks on, shopping. Patients are asked to rate  the current level of difficulty associated with each activity, where “0” represents “unable to perform” and “10” represents “able to perform at prior level.” Patients select a value that best describes their current level of ability on each activity assessed . The PSFThe PECO model is provided for the reader below for comprehensive understanding of this study.P—Patient with chronic lower back painE—Primarily kinesiophobia and other confounding factorsC—Asymptomatic subjectsO—Lumbar position sense, lumbar muscle endurance, pain, and functional abilityLifestyle factors, such as excess weight, physical inactivity, poor diet, and smoking, are linked to low back pain chronicity and disability. Smoking was categorized as non-smoker, often inhale secondhand smoke, quit smoking in less than 1 year, and smoker. Alcohol consumption was divided as not drinking, ≤ 1 glass/week, 2–3 glasses/week, and ≥ 4 glasses/week. Physical activity including any form of physical exercise was categorized as none, ≤ 2 h/week, 3–6 h/week, and ≥ 7 h/week. Dietary habits were categorized into 3 groups: (1) intake of no or low vegetables with high meat, (2) intake of moderate vegetables with moderate meat, and (3) intake of high vegetables with no or low meat , 56.The statistical analysis will be computed using SPSS Statistics software, version 27 . The data analyses will be conducted by a statistician. Continuous variables will be summarized using standard measures of central tendency and dispersion, either as mean and standard error, or median and interquartile range. Dichotomous or categorical variables will be summarized by frequencies or denominators and percentage.Kinesiophobia, lumbar endurance, and joint position sense will be compared between patients and controls using appropriate statistical tools. Kinesiophobia scores will be correlated with lumbar extensor endurance and proprioception joint position errors, pain intensity, and functional ability. Chi-square test will be used to find the association between kinesiophobia and lumbar endurance and joint position sense. Spearman rank correlation will be used to find the correlation between kinesiophobia, pain, and functional ability. Simple and multiple binary logistic regression will be used to determine crude and adjusted odds ratio for kinesiophobia, lumbar position sense and kinesiophobia, and lumbar endurance.The current study can be helpful to identify whether kinesiophobia has any impact on the characterizes of patient with CLBP.The current study can be helpful to guide physician whether kinesiophobia be part of evaluation of patient with CLBP.This study is to be conducted in Thumbay Physical Therapy & Rehabilitation Hospital which is equipped with all advanced equipment necessary for physiotherapy assessment associated with this study. Sample recruitment is expected to start from May 25, 2022, at Thumbay Physical Therapy & Rehabilitation Hospital, and Thumbay University Hospital and Gulf medical University, Ajman, United Arab Emirates.Screening of individuals with and without chronic low back pain will be carried out by 4 experienced physiotherapists [2 males and 2 females] who are specialized in musculoskeletal and sports physiotherapy. In order to make the data collection uniform, all the therapists will be provided with the information about the study protocol including assessment methods using various assessment tools related to this study.As per the medical record obtained on the prevalence of lower back pain conditions in Thumbay Physical Therapy & Rehabilitation Hospital and Thumbay University Hospital, we assume that the estimated sample size can be achieved within the study period given in the trial. Furthermore, the investigators of the study will contact the various departments of Thumbay University Hospital to refer the patients with and without low back pain to meet the sample required.At least 80% of samples from the estimated sample size is anticipated for statistical analysis and reporting the study findings. Since the study covers a wide range of populations from various countries reporting to these medical centers, addressing confounding variables makes the study findings novel and generalizable.ClinicalTrials.gov Identifier: NCT05079893 Registered on 14/10/2021Additional file 1. Proforma[Data entry].


This study aimed to identify all of the characteristics of bee venom acupuncture (BVA) for the treatment of lower back pain (LBP) that are described in the Korean literature, and to provide English-speaking researchers with bibliometrics. Six Korean electronic databases and sixteen Korean journals on BVA treatment for back pain were searched up to February 2022. This report included and analyzed 64 clinical studies on BVA interventions for back pain and 1297 patients with LBP. The most common disease in patients with back pain was lumbar herniated intervertebral discs (HIVD) of the lumbar spine (L-spine). All studies used bee venom (BV) diluted with distilled water. The concentration of BVA for HIVD of L-spine patients with LBP ranged from 0.01 to 5.0 mg/mL; the dosage per treatment was 0.02–2.0 mL, and for a total session was 0.3–40.0 mL. The most used outcome measure was the visual analogue scale for back pain , and most of the papers reported that each outcome measure had a positive effect. Korean clinical studies were typically omitted from the review research, resulting in potential language bias. This study provides clinical cases in Korea for future development and standardization of BVA treatment for back pain. Lower back pain (LBP) is a highly uncomfortable and often chronic sensation in the back below the lower rib cage and above the gluteal fold . LBP is For the treatment of patients with acute LBP, the guidelines recommend reassurance on the favorable prognosis and advice on returning to normal activities, avoiding bedrest, as well as the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and weak opioids for short periods . For theBee venom acupuncture (BVA) involves injecting purified and diluted bee venom (BV) into acupuncture points . BVA is Two clinical trials in Western databases  investigated the treatment effect of BVA on LBP. In one randomized controlled trial (RCT), the BVA plus NSAIDs group showed a more significant effect on LBP than that of the control group  . In anotAs shown in Of the 64 included trials, 18 types of single medical conditions were reported in 61 papers, and complex medical conditions were reported in the remaining 3 papers. Six medical conditions—HIVD of L-spine patients with back pain, back pain, failed back surgery syndrome patients with back pain, lumbar spinal stenosis patients with back pain, car accident patients with lower back pain, and back sprain patients with back pain—were mentioned in more than two papers. The numbers of papers and patients by disease are shown in In total, 1295 participants from the 64 clinical studies were included in this review. The sample size per trial ranged from 1 to 208 (20.2 ± 33.1).The intervention used in all included studies was in injection form, using a syringe through which BV was dispensed and injected into the body. The BVA concentration range was 0.01–5.0 mg/mL, and the dosage per treatment and for the total sessions was 0.02–2.0 mL and 0.3–40.0 mL, respectively, for herniated intervertebral disc (HIVD) in lumbar-spine (L-spine) patients with back pain. The BV concentration was 0.05–0.5 mg/mL and the dosage per treatment and the total sessions were 0.03–1.0 mL and 0.51–5.1 mL, respectively, in patients with back pain. The concentration and dosage of BVA according to the participant’s medical condition  are shown in A total of 22 types of outcome measures were reported in the 64 included papers. This study is an analysis of Korean clinical trials published in Korean journals, and we found several clinical studies on BVA for back pain in the Korean literature. The first study on BVA for the treatment of LBP was published in 1999. Since then, such studies have been published yearly until 2020. In Korea, the Ministry of Food and Drug Safety introduced the Good Clinical Practice Guidelines for clinical trials in the late 1990s, and these guidelines seem to have significantly impacted the progress of clinical research, including research on bee venom ,86. ThusAlthough most studies have reported that BVA is effective for LBP, six studies reported side effects including fever , itchingAll 64 Korean clinical trials reported that BV was diluted with saline at a certain ratio and injected into the patients. The BV concentration used for each study was found to cover a wide range, from 0.01 mg/mL to 5.0 mg/mL. In particular, in the case of HIVD in L-spine patients with back pain, the concentration deviation was the largest. When a survey was conducted with 468 TKM doctors, it was reported that the BV concentration used without considering the disease was 0.1–0.3 mg/mL . As suchPain is mainly evaluated subjectively in patients. Inflammation-related biomarkers, such as interleukin-6, C-reactive protein, and tumor necrosis factor α, along with range of motion (ROM), are also used to measure pain. However, self-reported outcomes, including the VAS, numerical rating scale (NRS), and Oswestry disability index (ODI), are more appropriate to show the clinical effectiveness and patient satisfaction with therapies. Quality of life is also used as an indicator, because LBP lowers the overall physical and psychological health. Although symptom changes in patients confirmed whether the subjectively felt pain of the patient improved, it was not quantified in the same way as when using the VAS. To develop a therapeutic agent, clinical trials that evaluate the effectiveness of the commonly used evaluation tools are necessary.This study has several limitations. First, this review mostly included case or retrospective studies with low levels of clinical evidence and a relatively small sample size. A higher level of evidence from large-scale clinical studies is needed. Second, the VAS, ODI, and EQ-5D are validated questionnaires, although a meta-analysis was not performed considering the heterogeneity of the included RCTs and the individual variation of the study participants. Third, since this review searched only domestic Korean databases, clinical studies conducted in Korea but published in international journals might have been missing. Finally, the 64 included studies were conducted at university hospitals, and may differ from real-world data obtained at TKM clinics. Therefore, whether this study is representative of the use of BVA for LBP treatment in Korea is difficult to confirm. Nonetheless, many cases of BVA application for the treatment of back pain in Korea exist; the details of BVA summarized in this review could provide information to help in planning clinical trials for new drug development.This study showed the clinical research trend for BVA’s use in LBP treatment as published in Korean journals. BV was diluted to an appropriate concentration for clinical purposes, and was confirmed to be an effective treatment for patients with LBP. However, no side effects were reported in most studies, and large variations in the concentration, dose, and number of BVA treatments were noted. This study provides clinical evidence for the future drug development and standardization of LBP treatment using BVA.We searched six Korean bibliographic databases  up to February 2022. The Korean trials indexed in non-Korean databases such as PubMed and Embase were not considered.The search terms were as follows: “bee venom OR bee toxin OR apitherapy OR bee venom therapy OR bee venom acupuncture” AND “back pain” AND “clinical studies OR clinical trial”.We included all clinical studies  that evaluated the effects of BVA on back pain. All patients with back pain and without age- or sex-based restrictions were included. We included all types of BVA and all outcome measures  used for treating back pain. Non-clinical trials—including animal studies, experimental studies, surveys, and reviews—were excluded.Three authors  independently extracted data using a predefined data extraction form. Two independent reviewers (S.-H.S. and M.P.) collected data regarding author information, study design, sample size, medical conditions, interventions , adverse events, outcome measures, and main results. In cases of insufficient outcome data, the corresponding authors were contacted whenever possible. Any disagreements were resolved through discussions with G.L.


IntroductionIn this study, we investigated the correlation of severity of renal colic with clinical parameters like pain characteristics, haematuria and pyuria, laboratory parameters such as inflammatory markers, and radiological parameters including site and size of stone and hydronephrosis.MethodsThe Visual Analogue Scale (VAS) determined the pain severity. Detailed history and clinicodemographic profiling of the patient was done, laboratory investigations were done, ultrasound and non-contrast computed tomography of kidney-ureter-bladder were done and all the parameters were duly noted and correlated with the pain severity.ResultThe mean age of the 183 patients was 43.96 ± 15.16 years, and 62.8% were male. The patients’ mean VAS score at presentation was 8.57 ± 1.08. The mean VAS score was found to be statistically higher in patients having a first episode of renal colic, solitary kidney, pyuria, raised creatinine, severe hydronephrosis, and stones located at the renal pelvis. In addition, higher VAS scores led to more surgical interventions.ConclusionThe correlation of pain severity of renal colic with various parameters can aid in the development of quick diagnostic and therapeutic protocols for patients presenting to the emergency department with renal stone disease. This study shows that pain scores can correlate with various parameters and predict the outcome and complications in these patients. Acute renal colic is a syndrome of flank pain with associated symptoms caused by nephrolithiasis . It has Management of renal colic includes laboratory investigations like complete blood count, urine analysis, renal function tests, and inflammatory biomarkers. Radiological investigations include ultrasound of kidney-ureter-bladder and non-contrast computed tomography of kidney-ureter-bladder. It also includes pain management and resuscitation followed by definitive treatment either surgical or conservative .Pain management in renal colic possesses a challenge for emergency physicians. A number of studies have been done comparing the efficacy of various agents like non-steroidal anti-inflammatory drugs such as diclofenac and ketorolac, opioids, magnesium sulfate, lidocaine, nitrates, anti-muscarinic agents such as hyoscine butylbromide, etc. . HoweverIn our search of the literature, we found few studies correlating various parameters with pain severity. A study by Shih et al. reported the correlation of epidemiological and clinical parameters with pain severity. Other studies by Lallas et al., Dorfman et al., and Sasmaz and Kirpat reported a significant correlation of pain severity with hematuria and pyuria -10. GourIn this prospective observational study, we aim to determine the correlation of severity of pain of renal colic with clinical, radiological, and laboratory parameters to overcome the shortcomings of previous studies and fill in the literature lacunae. This research will aid in a better understanding and adequate control of pain and management of patients with renal calculi. This will help by not only decreasing their emergency department and hospital stay but also minimizing the complications, resulting in improved mortality and morbidity.Study design and settingThis prospective observational study was performed at the Emergency Medicine Department, All India Institute of Medical Science, Rishikesh, over a period of 18 months from October 2020 to March 2022.Selection of participantsParticipants were selected on the basis of inclusion and exclusion criteria. Patients included in the study were adults (more than 18 years) with unilateral flank pain attributed to renal colic with concomitant radiological evidence of renal stone disease who volunteered to participate in the study. Patients with concomitant abdominal pathology which mimics renal colic, pregnant females and patients with age less than 18 years, patients with bilateral or diffuse pain, and patients whose pain score cannot be assessed were excluded from the study.Sample size estimationSample size was calculated based on Cohen’s convention for sample size estimation. Medium effect size=0.25 was assumed at 80% power with a level of significance at 0.05. The estimated sample size came out to be 180.Method and measurementDetailed demographic profile of patients presenting to the emergency department with unilateral flank pain attributing to renal colic was noted by the principal investigator who was an emergency medicine resident. A thorough history and physical examination were done. Point-of-care ultrasound was done by the principal investigator after completing the academic training in point-of-care ultrasound and he had performed at least 25 scans under the supervision of a radiologist ,15. The The following were the criteria of clinical parameters:1. Severity of pain: Visual Analogue Scale (VAS) 0 to 10  2. Hematuria: more than or equal to 5 red blood cells per high power field 3. Pyuria: more than or equal to 10 pus cells per high power field 4. Hydronephrosis: Distension of renal pelvis and calyces due to urinary outflow obstruction. Grades - mild, moderate and severe according to the Society of Fetal Urology .OutcomesThe primary objective was to determine the correlation of severity of renal colic measured in terms of VAS score and compare it with various parameters.Ethical approvalEthical approval for the study was obtained from the Institute Ethics Committee, All India Institute of Medical Sciences, Rishikesh (AIIMS/IEC/20/664 Date:03/10/2020).Statistical analysisThe data was entered in an Excel sheet and analyzed with SPSS software version 23 . Various parameters were correlated with the VAS score. A p-value < 0.05 (two-tailed) was considered significant.A total of 183 patients were enrolled in the study after considering the inclusion and exclusion criteria, out of which 115 (62.8%) were males. Obstructive uropathy was diagnosed in 166 (90.7%) patients. The mean number of renal colic episodes in past was 1.01 ± 0.96. The pain was predominantly colicky and burning micturition  was the most common associated symptom after haematuria  and pyuria   score in the obstructive uropathy group was found to be significantly higher than in the non-obstructive uropathy group . Also, there was a statistically significant negative correlation between the number of renal colic episodes in the past and VAS . For every one-unit increase in the number of episodes in past, the VAS decreased by 0.18 units, signifying that the severity of pain was highest in the first episode and subsequently decreased with later episodes. Out of all the patients investigated, 29 (15.8%) had hypertension, which was the most common comorbidity followed by diabetes (n=168.7). Among the co-morbidities, the median VAS in the solitary kidney group was found to be significantly higher than in the other patients . We also found a significant correlation between the severity of pain and pyuria . No correlation was found between the severity of pain and haematuria (p=0.099) , lymphocytes  and monocytes . There was a weak negative correlation found with neutrophil fraction and a positive correlation was found with lymphocytes and monocytes. Also, there was a weak positive correlation between creatinine and VAS . For every 1 unit increase in creatinine, the VAS increased by 0.30 units  had varying degrees of hydronephrosis on the side of pain on bedside point-of-care ultrasound evaluation. Maximum number of patients were found to have moderate hydronephrosis . Stone was most commonly found in the upper ureter . Among radiological parameters, the mean VAS score was higher in the patients with severe hydronephrosis when compared with patients having mild, moderate, or no hydronephrosis on bedside point-of-care ultrasound (POCUS). Although the difference was minimal, it yielded a significant correlation . A similar correlation was also obtained with the VAS score when evaluated against hydronephrosis detected by non-contrast computed tomography of kidney-ureter-bladder (NCCT KUB) . Although, no trend of increasing severity of pain was observed with increasing hydronephrosis. Also, a significant correlation was found between the site of stone and VAS score , with the median VAS being highest when the stone was located in the renal pelvis when compared to stones located at other sites  Table .Our study was a prospective observational study to determine the correlation between pain severity of renal colic and various clinical, laboratory and radiological parameters. It was carried out in a tertiary care centre in north India, at the All India Institute of Medical Sciences Rishikesh.Our study found that among clinical parameters, the severity of pain did not correlate with age, gender, pain characteristics or associated symptoms. However, pyuria significantly correlated with the severity of pain (p=0.015). Similar results were also obtained by Sasmaz and Kirpat (p=0.003) . Higher The severity of pain was significantly higher in the non-obstructive uropathy group than in the obstructive uropathy group . Although small non-obstructing stones with a size of < 5 mm  or < 4 mm  are considered to be painless, there are few patients who present with ‘the small stone syndrome’. They have significant pain and are considered to be having a small stone without any radiological obstructive feature. Studies by Jura et al. and Golan et al. reported that these patients possess a challenge for the managing physician ,20.In our study, the mean number of previous episodes of renal colic was 1.01 ± 0.96 ranging from 0 to 4. The pain severity decreased with subsequent episodes (p=<0.001 correlation coefficient = - 0.27). This could be attributed to the development of pain tolerance. No previous study has reported such an association in the past.When compared with other co-morbidities, patients with solitary kidney experienced more severe pain. However, only three patients were enrolled in this group . No similar study was found regarding the correlation of severity of pain in patients with solitary kidney.Among laboratory parameters studied, VAS score has a weak positive correlation with lymphocyte count , and monocyte count . It also showed a negative correlation with neutrophils . We did not find any correlation of severity of pain with total leukocyte count. Sasmaz and Kirpat in an observational study found a very weak positive correlation with total leukocyte count  and neutrophil-lymphocyte ratio  .The mean C-reactive protein (CRP) was 3.71 ± 1.42. Alleemudder et al. found the mean CRP to be 15.9 (1-192) which was significantly higher than our results . We did There was a weak positive correlation between serum creatinine and VAS score  in our study.Among radiological parameters, 78.7% of patients had varied degrees of hydronephrosis on imaging. On grading, it was found that the severity of pain was significantly higher in patients having severe hydronephrosis . The severity of renal colic is correlated with the acuteness of obstruction rather than the degree of obstruction. Pathophysiologically, higher built up of upstream pressures resulting in more distension of renal capsule and ureteral lumen can cause more severe pain, particularly in an acute setting. Sasmaz and Kirpat found that the mean VAS score of the patients with hydronephrosis was statistically higher than those without hydronephrosis (p < 0.001) . HoweverThe mean stone size was found to be 11.79 ± 6.43 mm. There was no significant correlation between the size of the stone and the severity of pain (p=0.336). A similar study done by Sasmaz and Kirpat found no correlation between stone size and VAS pain score  . In a stIn our study, stones located in the renal pelvis were found to cause more severe pain when compared to stones at other locations . In a similar study by Lallas et al., 70.6% of ureteral and renal pelvic stones resulted in the presence of one or more stone-related symptoms compared with 16.9% of all caliceal stones (p = 0.0001). Also, it was observed that proximal ureteral stones caused the highest rate of symptoms (100%) . SplinteIn our study, 62 (33.9%) patients required surgical intervention. The most common intervention was DJ stenting , followed by percutaneous nephrolithotomy  and extracorporeal shock-wave lithotripsy . There was a significant correlation between the severity of pain and the need for surgical intervention in our study. Patients with higher VAS score were more likely to have a surgical intervention (P=0.001). This could be attributed to the more acuteness of obstruction to urinary flow that can be surgically relieved to ease the pain. Contrarily, a study by Gourlay et al. did not find any association between the severity of pain and the need for hospitalisation or rescue intervention within 60 days . A studyThus, this study implies that these correlations between pain severity and various parameters can help us make prompt clinical decisions for patients with acute renal colic rather than waiting for laboratory or imaging results.However, the limitations of this study include:1. Altered patient inflow due to the COVID pandemic.2. Hemodynamically unstable patients were excluded from the study.3. Anthropometric parameters and nutrition parameters were not included as it was not feasible in the emergency department.4. Procalcitonin was not included in biomarkers as it was not feasible to investigate in all the patients. Correlation with these can be evaluated in further studies.The correlation of pain severity of renal colic with various parameters can aid in the development of quick diagnostic and therapeutic protocols for patients presenting to the emergency department with renal stone disease. This study will not only help in better understanding of patients with renal colic but also the management of varied complications of renal stone disease. As the severity of pain increased with rising serum creatinine and pyuria and is positively correlated with hydronephrosis and stone location, the emergency physician can be more prompt in ruling out these complications in patients with severe renal colic.


Results: We enrolled 39 patients in the study. After ultrasonography, Neonatal Pain, Agitation, and Sedation Scale (NPASS) scores were significantly higher (p < 0.01), and all vital signs  were altered. Cerebral (p = 0.008) and mesenteric (p = 0.039) StO2 levels were significantly lower in the whole study group, MCA end-diastolic velocity decreased (p = 0.02), and the resistive index (p = 0.03) increased in patients whose NPASS score was >7 after ultrasonography. Conclusions: This study is the first to show that ultrasonography may cause pain in newborn patients, and alters vital signs and hemodynamic parameters. Therefore, precautions should be taken to protect newborn babies from pain during ultrasound applications, as they are already exposed to many noxious stimuli. Furthermore, pain scores should be considered in studies using ultrasonography and evaluating hemodynamic parameters to increase the reliability of the studies.Background: Ultrasonography is widely used in neonatological practice and studies investigating the hemodynamic effects of various treatment protocols or clinical situations. On the other hand, pain causes changes in the cardiovascular system; so, in the case of ultrasonography leading to pain in neonates, it may cause hemodynamic alterations. In this prospective study, we evaluate whether ultrasonographic application causes pain and changes in the hemodynamic system. Methods: Newborns undergoing ultrasonographic examination were enrolled in the study. Vital signs, cerebral and mesenteric tissue oxygenation (StO In recent years, ultrasonography (USG) has increased its popularity in neonatological practice . CranialAnother benefit of USG is providing information about visceral blood flow with Doppler studies. Doppler USG is frequently used to assess cerebral, renal, or mesenteric blood flow in clinical conditions such as patent ductus arteriosus and hypoxic–ischemic encephalopathy. Doppler USG is also used to evaluate the hemodynamic effects of drug applications or treatment protocols .2 levels decreased, and the heart rate increased significantly after echocardiography [However, a study conducted in 2017 showed that echocardiography causes pain in newborn babies and changes in vital signs . In 2022iography ,6. In anAcute and chronic pain is an important but underestimated issue in NICU . An infaExposure to stress or pain activates the sympathetic autonomic nervous system and prepares the body to a “fight or flight” response with the hypothalamic–pituitary–adrenal axis. The “fight” response is generated by the sympathetic nervous system by the production of adrenaline, and the “flight” response is generated by the hypothalamic–pituitary–adrenal axis with the secretion of steroidal stress hormones, primarily cortisol. However, newborn infants cannot produce these responses adequately—they can neither fight nor fly—and repetitive pain and chronic stress may cause a diversion of energy from essential brain development . PainfulAlongside the effects on neurological development, studies examining hemodynamic responses to pain have shown that acute pain causes alterations in heart rate, systolic and diastolic blood pressure, and even oxygen saturation values . IncremeNeonatal Pain, Agitation, and Sedation Scale Scoring (NPASS), which is recommended to be used in the evaluation of pain and sedation in newborns, has a criterion for a change in vital signs . NPASS iWhile USG and Doppler studies are used to investigate the hemodynamic effects of any factor, they have the potential to cause hemodynamic changes if they cause pain in a neonate. Therefore, if ultrasonographic application is proven to cause pain or agitation in this group of patients, it is also logical to consider administering analgesic agents. In light of this knowledge, our study primarily aimed to investigate whether USG applications cause a pain response and changes in vital signs in newborn babies. In addition, we aimed to investigate whether USG application causes changes in middle cerebral artery flow, and cerebral and mesenteric tissue saturation values measured with near-infrared spectroscopy (NIRS).This prospective, observational, self-controlled clinical study was conducted between January 2021 and February 2022 in a tertiary hospital’s neonatal intensive care unit with 1500 annual admissions. The institutional ethics committee approved the study, and parental consent was obtained for all the patients.All patients who had undergone consecutive abdominal and transfontanelle USG in the same session during the study period were included. Clinically stable infants with no hemodynamic problems  were chosen for enrollment. Newborn patients with transient tachypnea who have had mechanical ventilation are routinely screened with transcranial ultrasonography. In these patients, antenatal features such as intestinal echogenicity increment and Grade I hydronephrosis underwent abdominal ultrasonography. In indirect hyperbilirubinemia, patients with no risk factors for jaundice are routinely screened with cranial and abdominal ultrasonography for hemorrhage. Abandoned babies to be given to social services are routinely screened with ultrasonography. Patients who had undergone ultrasonography for these indications were included in the study.Patients under sedative medication, who had invasive or noninvasive mechanical ventilation support, cardiovascular instability, needed inotropic medication, had Grade II–III intraventricular hemorrhage or periventricular hemorrhagic infarction, major congenital anomalies, and congenital heart diseases were excluded from the study. Patients were evaluated after the fourth day of life to eliminate the effects of the transitional period and patent ductus arteriosus on neonatal hemodynamics. Patients who were too small or large for their gestational age and with fetal growth restrictions were also excluded from the study.The NPASS was used to evaluate the patients’ pain as recommended in our national neonatology society guidelines . The NPASS consists of five categories: crying/instability, behavioral state , facial expression, extremities tone, and vital signs. In each category, the observer scores the patient between −2 and 2. All scores are summed up, and the patient is scored between 10 and −10. Values below zero indicate a sedated patient, while positive and high values indicate a patient with agitation and pain. In general, scores between 1 and 3 are considered mild pain, 4–6 are moderate, and scores >6 are considered severe pain . E.D. recorded the babies and patient monitors on video with a smartphone before and after USG. To avoid intraobserver variability, two researchers, G.K. and S.T., calculated NPASS scores blinded from Doppler USG and NIRS values. In addition, G.K. and S.T. calculated the NPASS scores one week after the first calculation to avoid intraobserver variability. 2 levels recordings. Hand hygiene was ensured before beginning the USG procedure for all patients. The same radiologist (H.Ö.) performed all USG applications and Doppler evaluations while blinded from NPASS scores, vital signs, and StOIn our clinic, ultrasound gels were filled in 10 cc injectors and stored in the patient’s incubator to keep the gels constantly warm and ensure infection control by using personalized gels. In this way, radiologists and clinicians used each infant’s own gel for ultrasound applications. Ultrasonographic examinations and Doppler measurements were conducted with a pulse-wave Doppler ultrasound  with a 5–12 MHz pediatric sector transducer. Blood flow velocities were measured in the left or right middle cerebral artery (MCA). The measurements were performed through the anterolateral fontanelle. The probe was placed above the ear, 1 cm anterior and superior to the external auditory meatus, to find the temporal window. The orbit and the zygomatic arch were used for the horizontal position marker. The angle between the blood flow direction and the ultrasound beam was kept below 15° . MCA peaAfter the first Doppler measurement, routine cranial and abdominal control ultrasound examinations were performed. The second Doppler measurements were then performed. The resistive index was calculated using the formula of (PSV − EDV)/PSV . No analgesic treatment (pharmacologic or nonpharmacologic) was applied during the examinations, but optimal handling precautions were taken. The babies could not be swaddled or cuddled to not prevent abdominal ultrasonography. To minimize agitation and pain, all the babies were given pacifiers, and the incubators were not opened, so that the incubator temperature would not decrease. The application was made by opening one of the small incubator windows. 2, and systolic–diastolic blood pressure were recorded just before USG application and as soon as the USG had been completed. A multiparameter patient monitor  was used for vital sign monitoring. The patients’ heart rate, respiratory rate, SpO2) and mesenteric (StmO2) tissue oxygenation through an INVOS™ Oximeter . Cutaneous sensors were applied on the forehead for StcO2 and the infraumbilical area for StmO2 1 h before the first evaluation. Stable StcO2 and StmO2 values were recorded just before USG (before) and as soon as USG was finished (after). Fractional oxygen extraction (FOE) was calculated with the formula (SpO2 − StO2)/SpO2 [Near-infrared spectroscopy recorded cerebral (StcOO2)/SpO2 .2 levels were recorded, and the NPASS score was calculated again as before the USG.Ultrasonographic evaluations are planned during morning patient rounds in our clinic, and the radiology department is informed. One hour before the USG, NIRS probes were placed. When the radiologist was ready for USG, E.D. recorded the patient’s vital signs and NIRS values, and recorded the baby on the video with a smartphone to allow for G.K. and S.T. to calculate the NPASS score. Then, the radiologist produced the MCA Doppler USG, transfontanelle USG, abdominal USG, and again the MCA Doppler USG in the same order for all patients. As soon as the USG procedure had finished, vital signs and StOt-test was performed for dependent parametric variables. For statistical analyses, SPSS software version 20.0 was used. The variables were investigated using visual  and analytical  methods to determine whether they were normally distributed. Parametric results are expressed as mean ± standard deviations. The median values of nonparametric tests are reported with median and minimal–maximal values. Non-normally distributed dependent variables were compared with the Wilcoxon test, and the paired During a study period of 13 months, only one patient per week could be included in the study because of the radiologist’s availability. As a result of this, 44 patients were included in the study. However, two patients were excluded because of Grade II intraventricular hemorrhage, and two were excluded because of congenital heart disease . In addition, one of the patients was excluded because of clinical deterioration with apnea and the need for bag-mask ventilation. We included 39 successful evaluations in the study. Of the patients, 56% (n: 22) were male. The median gestational age was 37 weeks , and the median birth weight was 3000 g . The median postmenstrual age was 38  weeks. The median chronological age was 6  days . p < 0.01), respiratory rate 40.4 ± 5.9 to 46.6 ± 7.3; p < 0.02), and systolic blood pressure  and diastolic blood pressure  significantly increased after USG, while SpO2 significantly decreased .All vital signs were significantly altered after the USG application. Heart rate   . p = 0.807, p = 0.143, and p = 0.065, respectively)  .p = 0.022). In addition, in patients whose NPASS score was ≤7 and increased above 7 after USG, both EDV and RI were significantly decreased after USG   .p: 0.384).The mean duration of USG applications was 660 ± 111 s. There was no correlation between USG duration and pain scores observed after USG /SpO2, our patients’ FOE levels did not change, but there was a significant decrease in SpO2 levels. Therefore, we assume that oxygen extraction did not change after ultrasonographic application, but SpO2 decreased in our patients, which led to a decrease in StO2 levels. Nevertheless, the pathophysiology of StO2 and FOE responses to pain and noxious stimuli must be studied in further studies investigating oxygen delivery, consumption, and cerebral vascular resistance.In our study, both cerebral and mesenteric StOhat StO2  and FOE hat StO2 , but SpOdecrease  after no2 values rather than cerebral StO2, and this is the first study to evaluate mesenteric StO2 levels after ultrasonography. On the other hand, in light of the current literature, no study has evaluated StOIn our study, when infants were grouped according to NPASS scores after USG application, in the group of patients whose pain scores increased significantly , EDV vaOur study has several limitations. Studies with a larger number of patients may better evaluate if there is a significant change in PSV and FOE. Our study group was heterogeneous regarding gestational week and chronological age. A more homogeneous study group may provide better results because the response to pain and discomfort is different between infants of different gestational ages ,16 and eIn fact, NPASS, or other pain scoring systems or scales do not distinguish pain from agitation and discomfort. Therefore, in our study, the results may have not only been due to pain, but also due to the discomfort or agitation caused by the application . On the In conclusion, ultrasonographic application may cause pain, agitation, or discomfort in newborn patients, leading to alterations in vital signs, NIRS values, and MCA Doppler studies. Therefore, during ultrasound applications, precautions should be taken to protect newborn infants who are already exposed to many noxious stimuli in the NICU from pain. First, by forming a clinical or even national protocol on ultrasound indications, unnecessary ultrasound applications can be avoided, and the total number of ultrasound applications can be reduced. Although point-of-care ultrasonography has recently been encouraged and shown to be helpful in many scenarios in NICU , clinici


Despite advancements in pain management, children have remained undertreated for postoperative pain. Data regarding the practice of post-operative pain management in paediatric patients remains less available in the developing world. This study was aimed at evaluating practice of postoperative pain management in under five children.A prospective cross sectional one-year study was conducted on all paediatric patients who underwent major paediatric surgical procedures from February 1, 2020 to January31, 2021, at a tertiary hospital in Addis Ababa, Ethiopia.A single type of analgesic medication was used in 67.1% patients. Analgesic medications were administered on standing base only in 64.4% of patients. Patients' charts had no documentation of pain assessment both in the neonatal intensive care units and wards.32.89 % of assessed patients had moderate to severe pain record.Significant number of patients suffer from postoperative pain because of absence of proper pain assessment and inadequate administration of analgesic medication. Although every living organism is familiar with pain, it is a complex and multidimensional experience which is hard to clearly define specially in children –3 Cheng,The importance of adequate pain therapy is unquestionable. Although the Declaration of Montreal (September 2010) states that “Access to Pain Management is a Fundamental Right”, insufficient pain management remains to be a problem in 80% of population in more than 150 countries. Majority of victims of inadequate pain management are the elderly, pregnant, and breastfeeding women, children, drug addicted persons, and the mentally ill. Despite efforts to advance perioperative pain management of children, there are still a substantial number of children suffering from perioperative pain . InflammPain Management education in medical and paramedical schools in Ethiopia is poor. Absence of adequate studies and standard guidelines to pain management could be mentioned as the main reasons for poor pain management practice in the country .There was no study done on practice of postoperative pain management in under five children in Ethiopia, therefore, this study could be a stepping stone for further studies and could help to develop applicable pain management guidelines.Study area and design: A hospital based prospective cross-sectional study was conducted on a total of 235 paediatric post-operative patients operated from February 1,2020 to January 31, 2021 at Tikur Anbesa Specialized Teaching Hospital; Addis Ababa, Ethiopia, where full time paediatric surgical service is given by the paediatric surgical residents, fellows and consultants.Sampling and study population: The sample size was determined using the formula for single population proportion by assuming 5% marginal error and 95% confidence interval =0.05). The proportion (p) = 50% was taken as there was no research done in the same setting concerning pattern of postoperative pain management in under five childrenn = the required sample size, z = the value of the standard normal curve score corresponding to the given confidence by taking additional 20% contingency for non-response rate, the sample size is: 196 +20 % (non-response rate) = 196+39= 235 All patients who fulfilled inclusion criteria were included in the study.Inclusion criteria: All Paediatric patients under the age of 5 years that underwent major paediatric surgical procedures at Tikur Anbesa specialized Hospital in their first and second postoperative days during the study period were included and all selected cases responded to the questions.Exclusion criteria: Incomplete documentations and use of wrong type of assessment tool.Data management and interpretation: Data was collected using structured questionnaire and patients' post-operative pain was assessed using a standardized questionnaire with pain assessment tools: Neonatal /Infant pain assessment tools (NIPS) was used for neonates and infants, FLACC scale  for those between the age of 1year and 5 years and Collected data was analyzed using SPSS version 23, only 10 patients were excluded from analysis for gross incompleteness and use of wrong type of assessment tool.Interpretation of Mild, Moderate and Severe pain was made based on the standard values of the tools. .Ethical considerations: All methods were carried out in accordance with the ethical standards as laid down in 1964 Declaration of Helsinki and its later amendments for which reason, Ethical clearance was obtained from institutional review board of Addis Ababa University, College of Health Sciences School of Medicine and an informed consent was taken from parents /legal guardians of each patient before data collection.A total of 235 paediatric post-operative patients were assessed for post-operative pain using a standardized questionnaire with pain assessment tool of which half (50.7%) patients were between the age of 1 year and 5 years. Infants and neonates account for 31.1% and 18.2% of the cases respectively. 57.3% of the cases were male patients making male to female ratio 1.34:1 of these 39(17.3%) were admitted to the neonatal Intensive care unit (NICU) and 186 (82.6%) to the wards. The types of surgeries conducted during the study period were: 26.6% laparotomies, 14.6% stoma reversals, 14.6% epispadias/ hypospadias repair surgeries, 13.3 % stoma creations, 11.5% anorectoplasties, 11.1% pull-through procedures, 6.2% thoracotomies and 2.7 % tube thoracostomies and of which 74.6% of patients received intra operative local or regional blocks. Among this 66.7% were caudal blocks, 6.2% were intercostal blocks and 1.8% were rectal sheath blocks .Among the 225 patients operated and had complete documentation, paracetamol (PCM) was the only analgesic medication ordered in 149(66.2%) of the cases. Ibuprofen and PCM were ordered in 73 (32.4%) patients and in the case of the remaining 3 (1.3%) patients. there was no properly documented order.151 (67.1%) patients were given PCM only, 72(32%) were given PCM and Ibuprofen and two patients didn't take any kind of analgesic in the postoperative period .Regarding the frequency of order of analgesic Medications, in 98.67% ordered as standing dose but in three cases there was no order of analgesic medications at all and in the implementation of the orders only 64.4% of patients were given the analgesic medications on standing doses and also 34.6 % of the patients missed one or more doses. Two patients were not given any kind of analgesic medication in the first 48 hours post operatively .In respect to pain records and grade there was no any form of pain assessment mechanism in the wards or NICU but on subjective enquiry only 25.78% of patients didn't have any pain record during the assessment times. The remaining 74.2% had one or more records of pain. During the assessment of Grades of Pain felt by patients, it was found that there was no pain record in 25.78% of the patients. However, 74.2% of the patients had records of mild to severe pain in the first 48 hours after surgery .Out of the 80 patients who missed one or more doses of post-operative analgesic medication, the reason for 46.25 % of the parents not to give the medication was confusing the drugs for antipyretics and refraining from administering them in the absence of fever. The other 37.5 % were not informed about the frequency and dose of administration or were not given prescriptions. 20% of the patients were not given the drugs because they were on their NPO period and parents thought oral analgesics ordered were contraindicated. 8.75 % of the parents didn't know how to administer the drugs. The percentage of patients who felt moderate to severe pain is higher in the groups who were taking paracetamol only compared to those who were taking paracetamol and ibuprofen together .Among 145 patients that were given all the standing doses of analgesic medication 52 patients felt pain once and 39 patients felt more than once. Among the 39 patients that missed one dose of the post-operative analgesic medication, 25 patients felt pain once and only one didn't have any pain record during the assessments. Among the 145 patients who were given all the standing doses of analgesic medications only 7 patients felt moderate to severe pain. 54 patients had no pain record and 51 of the remaining 84 patients felt mild pain. Out of the 39 patients who missed one dose of analgesic medication 33 patients had moderate to severe pain. Among the 39 patients who missed more than one dose of post op analgesic medication, 32 patients had moderate to severe pain record.All patients who underwent thoracotomy and 83.3 % of those who underwent tube thoracostomy had non-zero records of pain.78.57 % of the former and 66.67 % of the later groups had high grade pain records in the first 48 hours after their procedure. 51% of the patients who underwent pull though surgeries ad 38.4 % of those who underwent anorectoplasties,18.18% of stoma creations and 26.08 % of stoma reversals had high grade pain records.There were four main findings in this study. First, there was no pain assessment mechanism in the wards and NICUs for post-operative paediatric patients. Second, higher number of patients missed one or more doses of analgesic medications ordered in their post- operative period. Third, significant number of patients who were not given all the doses of analgesic medications had higher grades of pain (moderate to severe) in their post-operative period. Fourth, majority of patients that had records of moderate and severe pain were taking a single modality of pain management in the post-operative period. Pain assessment records, including the characteristics of pain and the patient's analgesic response, guide the medical team for providing effective pain management. In this study, there was no any pain assessment done by ward and NICU nurses. There was no pain assessment tool attached in the charts of the patients. There was no documentation of analgesic medications given to patients on nurses' medication sheet. This study is comparable to a study done in Turkey on postoperative pain assessment records of nurses which showed that there was no pain assessment in any of the patient files with in the first 48 h . AnotherIn conclusion, though the number of patients with positive records of post-operative pain is higher, there is no pain assessment mechanism in the wards and NICUs for post-operative patients and significant number of patients missed one or more doses of analgesic medications in their post-operative period also positive records of pain were observed in patients who missed one or more doses of post-operative analgesics. Despite the number of patients with mild and moderate pain records most took only one type of analgesic medication. The knowledge of parents or legal guardians towards the proper administration of analgesic medications is limited making neonates and under-five children to suffer from post-operative pain. Thus, post-operative Pain assessment in children should be conducted on regular bases with assessment tools. Educating and supervising care givers on proper administrations of drugs should be routine with strict application of multimodal pain management protocols based on grade of pain and availability of drugs in the post-operative periods. We recommend further study to address the treatment outcome and adverse effects of the medications.


P < .05) on headache- and migraine-associated symptoms when administered during a migraine attack.Eptinezumab is an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody approved for the preventive treatment of migraine. In the phase 3 RELIEF study, eptinezumab resulted in shorter time to headache pain freedom and time to absence of most bothersome symptom  compared with placebo when administered during a migraine attack. The objective of this exploratory analysis was to examine the earliest time points that eptinezumab separated from placebo (N = 238) or placebo (N = 242) administered intravenously over 30 min within 1–6 h of migraine onset. Outcome measures included headache pain freedom/relief and absence of MBS, patient’s choice of photophobia, phonophobia, or nausea, at regular intervals from 0.5 to 48 h after infusion start. Censoring was applied at time of acute rescue medication use.RELIEF, a multicenter, parallel-group, double-blind trial, occurred from November 7, 2019, through July 8, 2020. Adults considered candidates for preventive treatment were randomized to eptinezumab 100 mg , with separation from placebo (P < .05) through hour 48. Eptinezumab separated from placebo (P < .05) at hour 1 in absence-of-photophobia (29.4% vs 17.0%) and absence-of-phonophobia (41.2% vs 27.2%) and through hour 48. Initial separation from placebo (P < .05) in absence-of-nausea occurred at end-of-infusion .At hour 1, more eptinezumab-treated patients achieved headache pain freedom (9.7%), headache pain relief (38.7%), and absence of MBS (33.2%) versus placebo  as early as 0.5–1 h following the start of infusion. Rapid resolution of headache- and migraine-associated symptoms by a peripherally acting, intravenously administered antibody suggest a peripheral site of pharmacological action for CGRP blockade.Preventive treatment with eptinezumab initiated during a migraine attack resulted in more patients achieving headache pain freedom/relief and absence of MBS, with separation from placebo (NCT04152083.ClinicalTrials.gov Identifier: The online version contains supplementary material available at 10.1186/s12883-022-02714-1. The agepriority . Despitepriority . In addipriority .Eptinezumab, a humanized IgG1 monoclonal antibody that binds rapidly, durably, and with high affinity to calcitonin gene-related peptide (CGRP) , is apprP < 0.001) [RELIEF, a phase 3, multicenter, double-blind trial in patients experiencing migraine 4–15 days/month, found that eptinezumab, when administered during a migraine attack, demonstrated benefit by reducing headache, migraine-associated symptoms, and rescue medication use compared with placebo . At 2 h < 0.001) .P < 0.05) was achieved at time of first assessment (0.5 h) or the earliest assessment thereafter in headache pain freedom, headache pain relief, absence of MBS, and absence of photophobia, phonophobia, and nausea individually.The objective of this exploratory analysis of the RELIEF study was to evaluate if separation from placebo (rd edition criteria) [Detailed methodology for RELIEF (NCT04152083) has been published . Brieflyriteria) , with orriteria) , 13 for Treatment  was administered intravenously over a period of 30 min on day 0 within 1–6 h of onset of the qualifying migraine with moderate to severe headache. Rescue medication (any acute medication to treat migraine or migraine-associated symptoms) was not permitted in the 24-h period prior to receiving study treatment or within 2 h of infusion start. After 2 h following infusion start, patients were permitted to take rescue medication if they continued to experience moderate or severe headache pain or had significant migraine-associated symptoms. Additionally, if initial migraine relief was achieved at 2 h, but headache- or migraine-associated symptoms returned within 2‒48 h of study drug administration, rescue medication was permitted. Rescue medication taken prior to 2 h post infusion start was considered a protocol deviation, but all patients were included in the analysis and censored at the time of use (< 5 patients per treatment arm within the first 2 h).The number of patients achieving headache pain freedom and headache pain relief was recorded at 0.5, 1, 1.5, 2.5, 3, 3.5, 4, 6, 9, 12, 24, and 48 h after infusion start. Headache pain was rated on a 4-point scale where 3 = severe, 2 = moderate, 1 = mild, and 0 = no pain. Pain was required to be 2 or 3 at baseline, with headache pain freedom defined as no pain (0) and headache pain relief defined as mild or no pain (0 or 1). Additionally, the number of patients who experienced absence of patient-selected MBS and absence of photophobia, phonophobia, and nausea individually was recorded at each time point. The individual analyses of absence of photophobia, phonophobia, and nausea were conducted in patients who experienced that symptom at baseline, whether or not they selected this symptom as their MBS.Use of rescue medication was recorded at each time point. The time to headache pain freedom/absence of MBS was censored at the time of first rescue medication if used prior to obtaining pain freedom/absence of MBS. Thus, for patients who reported pain freedom/absence of MBS without using rescue medication up to and including the time point where pain freedom/absence of MBS was reported, the first collected time point with pain freedom was included in the analysis (pain freedom obtained). For patients who reported taking rescue medication without having reported pain freedom/absence of MBS at an earlier time point, censoring was applied at the first time point where rescue medication was used. Finally, if a patient did not report pain freedom/absence of MBS during the 48 h and did not report taking rescue medication at any time point, censoring was applied at the time point of the last recorded observation during the 48 h.The percentage of patients with headache pain freedom, absence of MBS at 2 and 4 h, and rescue medication use within 24 h post infusion were secondary efficacy endpoints, with multiplicity control of the type 1 error. Headache pain freedom, headache pain relief, absence of MBS, and absence of photophobia, phonophobia, and nausea at all other specified time points were exploratory efficacy endpoints. Headache pain freedom/relief and absence of MBS were analyzed in all patients; absence of photophobia, phonophobia, and nausea was analyzed in patients experiencing the corresponding symptom with their qualifying migraine. If an assessment was missing at a given time point, it was assumed that no freedom/relief or absence was achieved, and no rescue medication was used at that time point.All measures were assessed descriptively or tested at a 2-sided 5% alpha with no adjustment for multiplicity. Each of these measures were compared between the eptinezumab and placebo groups at each of the specified time points using a Cochran–Mantel–Haenszel test, stratified for concomitant migraine preventive treatment use and region. The Mantel–Haenszel estimates of treatment difference, odds ratio, and associated confidence intervals were calculated for each comparison. Sensitivity analyses of all endpoints were conducted where use of rescue medication was allowed, that is, without applying censoring of data.and nausea) with their qualifying migraine (n = 278), the most selected MBS was nausea , followed by photophobia  and phonophobia .A total of 238 and 242 patients were randomized to and received eptinezumab 100 mg and placebo, respectively. Baseline demographics and characteristics have been reported previously  and showP < 0.05, all time points; Fig. P < 0.05, all time points).The percentage of patients achieving headache pain freedom, headache pain relief, and absence of MBS at each time point, with and without censoring for use of rescue medication, are detailed in Supplemental Table P < 0.05) in absence of photophobia from hour 1 through hour 48  was noted from hour 1 through hour 48 for absence of phonophobia in patients experiencing phonophobia with their qualifying migraine  was observed at 0.5 h after infusion start in patients experiencing nausea with their qualifying migraine, and while separation from placebo was not statistically significant at the 1-h time point, it was achieved from the 1.5-h time point through 48 h  observed at first time of assessment at 0.5 h following the start of the 30-min infusion , while absence of photophobia and phonophobia separated from placebo as early as 1 h . Treatment with eptinezumab also provided faster achievement of headache pain freedom, headache pain relief, and absence of MBS, with separation from placebo (P < 0.05) as early as 1 h following the start of the 30-min infusion. Importantly, eptinezumab decreased the need for rescue medication compared to placebo, but even when used, faster resolution or relief was still noted in eptinezumab-treated patients. Separation from placebo (P < 0.05) occurred until at least hour 24 for headache pain freedom, hour 6 for headache pain relief, and hour 9 for absence of MBS. The sustained efficacy through hour 48 indicates minimal breakthrough headache. These results are critical because preventive medications have historically taken several weeks to become efficacious.The results of the present analyses showed that initiation of treatment with eptinezumab during an active migraine—in patients eligible for preventive migraine treatment—provided faster resolution in migraine associated symptoms  compared to treatment with placebo. Absence of nausea—the symptom most often identified as MBS by patients experiencing nausea, photophobia, and phonophobia with their qualifying migraine—separated from placebo (The International Headache Society recommends headache pain freedom at 2 h as the primary efficacy parameter, with pain relief at 2 h as a secondary endpoint ; accordiAdministration of eptinezumab during an acute attack of migraine resolves migraine symptomatology quickly and may allow patients to return to their normal activities sooner. Although the mechanism of action is not completely understood, eptinezumab binds to CGRP, thus disrupting CGRP-induced trigeminal nociceptive transmission; in turn this improves acute migraine symptoms, and, over time, decreases migraine frequency . Of noteThere are several limitations to consider, including that this study includes exploratory endpoints that were preplanned and consists of other time points than those used for the secondary analyses. Further, the RELIEF study was done in a clinical trial setting limiting the overall generalizability of these results. Furthermore, patients reported a higher migraine severity than previously reported in similar acute migraine trial populations, which may limit the comparison to other acute trials.Compared to placebo, eptinezumab demonstrated faster achievement of headache pain freedom, headache pain relief, and MBS freedom, as well as reduced rescue medication use. Additionally, the rapid improvement in migraine-associated symptoms, in particular nausea, separating from placebo earlier than pain relief or freedom, suggest an important role of the peripheral blockade of CGRP in the resolution of nausea independent of pain relief, and in resolving acute migraine symptomatology.Additional file 1: Table S1. Time After Start of Infusion to Headache Pain Freedom, Headache Pain Relief, and Absence of MBS. Table S2. Time After Start of Infusion to Absence of Photophobia, Phonophobia, and Nausea.


Diabetic peripheral neuropathic pain (DPNP) is common and often distressing. Most guidelines recommend amitriptyline, duloxetine, pregabalin, or gabapentin as initial analgesic treatment for DPNP, but there is little comparative evidence on which one is best or whether they should be combined. We aimed to assess the efficacy and tolerability of different combinations of first-line drugs for treatment of DPNP.OPTION-DM was a multicentre, randomised, double-blind, crossover trial in patients with DPNP with mean daily pain numerical rating scale (NRS) of 4 or higher  from 13 UK centres. Participants were randomly assigned (1:1:1:1:1:1), with a predetermined randomisation schedule stratified by site using permuted blocks of size six or 12, to receive one of six ordered sequences of the three treatment pathways: amitriptyline supplemented with pregabalin (A-P), pregabalin supplemented with amitriptyline (P-A), and duloxetine supplemented with pregabalin (D-P), each pathway lasting 16 weeks. Monotherapy was given for 6 weeks and was supplemented with the combination medication if there was suboptimal pain relief (NRS >3), reflecting current clinical practice. Both treatments were titrated towards maximum tolerated dose . The primary outcome was the difference in 7-day average daily pain during the final week of each pathway. This trial is registered with ISRCTN, ISRCTN17545443.vs 0·2 [1·5]). Adverse events were predictable for the monotherapies: we observed a significant increase in dizziness in the P-A pathway, nausea in the D-P pathway, and dry mouth in the A-P pathway.Between Nov 14, 2017, and July 29, 2019, 252 patients were screened, 140 patients were randomly assigned, and 130 started a treatment pathway (with 84 completing at least two pathways) and were analysed for the primary outcome. The 7-day average NRS scores at week 16 decreased from a mean 6·6 (SD 1·5) at baseline to 3·3 (1·8) at week 16 in all three pathways. The mean difference was –0·1 (98·3% CI –0·5 to 0·3) for D-P versus A-P, –0·1 (–0·5 to 0·3) for P-A versus A-P, and 0·0 (–0·4 to 0·4) for P-A versus D-P, and thus not significant. Mean NRS reduction in patients on combination therapy was greater than in those who remained on monotherapy  Health Technology Assessment programme. Diabetic peripheral neuropathy affects about 50% of people with diabetes over their lifetime and approximately half of these present with neuropathic pain.Evidence before this studyClinicalTrials.gov databases from Jan 1, 2008, to April 30, 2020, for relevant peer-reviewed randomised controlled trials applying a careful analytical process to identify only class 1 and 2 studies. On July 12, 2022, we searched PubMed and Google Scholar with the key words “painful diabetic neuropathy” and identified two comparator randomised controlled trials published since April, 2020. Both trials were underpowered and used subtherapeutic doses of first-line drugs. The AAN report identified gaps in current knowledge including the following: few studies alone have investigated the effect of interventions on quality of life, patient functioning, mood, or sleep; there are few comparator studies of first-line drugs and their combinations; and scarce data is available on which patients respond to a specific intervention. The additional studies we identified did not address these limitations.The American Academy of Neurology (AAN) published a practice guideline on oral and topical treatments of diabetic peripheral neuropathic pain (DPNP). The panel searched the MEDLINE, Cochrane, Embase, and Added value of this studyOur large, multi-period crossover study compared the efficacy of three of the most prescribed first-line drugs for DPNP and their combinations not only for the primary outcome of pain relief, but also for important secondary outcomes including quality of life, mood, and sleep. We showed that all three treatment pathways and monotherapies had similar analgesic efficacy.Implications of all the available evidenceTo our knowledge, this was the largest and longest ever, head-to-head, multi-period crossover neuropathic pain trial. Our study can have an impact on future treatment guidelines, not only for DPNP, but also for chronic neuropathic pain treatment in general (estimated to affect 8–9% of the UK population) because current treatment guidelines are largely generic . Our study can also benefit general practitioners, diabetes specialists, pain specialists, neurologists, general physicians, other medical and allied health-care professionals managing DPNP, and patients by the provision of improved treatment pathways. Some of the first-line drugs might not be available in resource-limited countries due to cost and other reasons, but our study can give confidence that any of these drugs or drug combinations, if titrated carefully to maximum tolerated doses, can result in similar levels of pain relief.Most international guidelines recommend amitriptyline, duloxetine, pregabalin, or gabapentin as first-line agents for symptomatic analgesic therapy in patients with DPNP. Robust evidence exists for the efficacy of each drug based on Cochrane reviews and meta-analyses, but the best outcome for any monotherapy is 50% pain relief in fewer than half of patients, which is often accompanied by dose-limiting side-effects.study protocol is available online.OPTION-DM was a multicentre, randomised, double-blind, centre-stratified, multi-period crossover trial with active washout in patients with DPNP from primary and secondary care at 13 UK centres. The Yorkshire and the Humber Sheffield Research Ethics Committee (16/YH/0459) approved the trial, an independent Trial Steering Committee oversaw the trial, and a Data Monitoring and Ethics Committee monitored safety. The Eligible participants were aged 18 years or older and fulfilled the diagnostic criteria for diabetes according to WHO2 or higher, and stable glucose control over the preceding 3 months with glycated haemoglobin concentrations of 12% (108 mmol/mol) or lower. Included patients had sufficient cognitive and language skills to be able to comply with all the study requirements and be available for the duration of this year-long study.Inclusion criteria were the following: average daily pain intensity of at least 4 over 7 days on the numerical rating scale  while off pain medication, aspartate aminotransferase and alanine aminotransferase concentrations lower than twice the upper limit of normal, an estimated glomerular filtration rate (eGFR) of 30 mL/min per 1·73 mExclusion criteria included the following: a history of epilepsy, depression requiring antidepressant medications, pregnancy and breastfeeding, severe systemic disease, postural hypotension (systolic blood pressure drop >20 mm Hg on standing for 3 min), cardiac arrhythmias and conduction abnormalities on 12-lead electrocardiogram at baseline , prostatic hypertrophy based on clinical history  and review of medical records, other painful peripheral neuropathies , the concomitant presence of other painful medical conditions that were as severe as their DPNP, major amputations of the lower limbs, active diabetic foot ulcers, and substantial suicide risk.The OPTION-DM trial examined three 16-week treatment pathways: oral amitriptyline supplemented with pregabalin (A-P), pregabalin supplemented with amitriptyline (P-A), and duloxetine supplemented with pregabalin D-P; . AllocatEach pathway had two treatment phases, each with a 2-week initial titration period . During 2 or higher.2 received a pregabalin dosing schedule starting with 75 mg per day, then 150 mg per day, and with a final dose of 300 mg per day.After the screening visit, analgesic medications were washed out over a period of 1–2 weeks, after which baseline daily NRS pain was recorded in paper diaries for 1 week. Participants with an average NRS score of 4 or higher were eligible for randomisation.Participants recorded daily pain in paper diaries for the duration of the trial. The primary outcome was the difference in 7-day average NRS daily pain measured during the final follow-up week (week 16) between the treatment pathways.The trial was initially powered on a mean difference between treatment pathways of 0·5 points on the NRS scale, on the basis of the effect size previously reported for comparison of two active interventions in a four-arm neuropathic pain crossover trial.2 test across treatment groups, derived from a mixed effects logistic regression, with covariates being treatment group and period. Preplanned subgroup analyses according to baseline characteristics  were done descriptively by either Forest or Lowess plots and quantitatively by adding an interaction term in the statistical model; additional pre-planned analyses examined the change from baseline in pain among patients starting combination therapy compared with those who remained on monotherapy. Week-16 pain was the average pain between 106 and 112 days after the start of the treatment pathway or as close to this as possible within a window of –3 to +1 weeks, providing that this did not extend into the washout period and that scores were available for at least 4 of 7 consecutive days. Week-6 pain was scored analogously within a window of –2 to +1 weeks. Additionally, we assessed the effect of missing outcome data for the primary endpoint using multiple imputation, controlled multiple imputation,For the statistical analysis, we used a modified intention-to-treat approach, which included all eligible participants who started each treatment pathway. We analysed the primary outcome and other continuous outcomes using a linear mixed model, with treatment group, period, and the interaction between the two as fixed effects and participant as a normally distributed random intercept. If the interaction  effect was not significant, then it was removed, and a reduced model was fitted. Residuals were plotted against treatment, pathway, and fitted values, whereas random effects were visualised in a dotplot. We used linear contrasts to evaluate differences between treatment groups. We compared the percentage of participants reporting adverse events using a global χThe funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.Participants were recruited between Nov 14, 2017, and July 29, 2019. Follow-up continued until July 24, 2020. 252 patients were screened, with 140 randomly assigned to six treatment sequences, of whom 130 were included in the analysis . 130 patWe observed improvements in the 7-day average daily NRS pain at week 16 for all three treatment pathways, with no significant differences between them  of participants on the maximum dose at week 6 were 56 mg (53 [51%] participants) for amitriptyline, 76 mg (46 [46%]) for duloxetine, and 397 mg (59 [55%]) for pregabalin. For patients on combination treatments, the mean maximum tolerated doses per day and the number (percentage) of participants on maximum dose of the second-line drug at week 16 were 347 mg (21 [47%] participants) for A-P, 405 mg (23 [55%]) for D-P, and 52 mg (22 [47%]) for P-A.Averaged across all treatment pathways, mean reduction in pain was 2·6 (98·3% CI 2·2 to 3·0) at week 6  and 3·4 (2·9 to 3·8) at week 16 . Patients who started combination therapy  saw a further reduction of 1·0 (SD 1·3) points  between weeks 6 and 16, whereas those who remained on monotherapy saw a mean pain reduction of 0·2 (1·5) points  patients with outcome data responded to maximum tolerated monotherapy with an NRS of 3 or lower  and 120 (40%) achieved 50% reduction from baseline pain. Over the subsequent 10 weeks, combination treatment resulted in an additional 37 (19%) patients reaching an NRS of 3 or lower and 23 (14%) patients reaching 50% pain relief.We assessed the results of study questionnaires  for participants receiving maximum tolerated doses of monotherapies at week 6 and at the end of the treatment pathways at week 16. All treatment pathways showed similar improvement from baseline in the SF-36 domains, HADS, ISI, and BPI-MSF items .Table 3SOverall, we observed few pairwise differences in any of the questionnaire outcomes. The D-P pathway had lower scores for role limitation due to physical health than both P-A and A-P at week 6 but not at week 16, and higher insomnia (measured by the ISI score) than A-P at both week 6 and 16. However, these should be treated with caution given the number of secondary outcomes assessed. The PGIC questionnaire, completed at the end of each treatment pathway, showed that similar proportions of participants reported feeling “much improved” or “very much improved” . At the end of the study (week 50), the most preferred pathway was P-A (43%), followed by D-P (33%) and A-P .Assessing the planned subgroup analyses, we observed that patients with higher emotional distress at baseline showed greater improvement in pain scores with P-A and D-P compared with A-P . Using tThe OPTION-DM trial showed that all three treatment pathways  provided similar and significant pain reduction of 3·3 in NRS, or half the baseline pain intensity score. We found no statistically or clinically significant differences between the treatment pathways. To our knowledge, this was the first randomised, double-blind, comparator trial of neuropathic pain treatment pathways. Although head-to-head trials of individual monotherapies and combination treatments from the start could be designed, we felt that data on treatment pathways as a whole was most efficient and applicable to current clinical practice. This is because most patients are started on a monotherapy and will require a second agent added in combination within a few months. Therefore, OPTION-DM is a pragmatic trial, mirroring current neuropathic pain management pathways, allowing the outcomes of this study to be readily generalisable.To our knowledge, OPTION-DM is the longest blinded neuropathic pain trial to date,23Although other tricyclic antidepressants are available, we used amitriptyline as it is the most widely prescribed tricyclic worldwide and a first-line agent in most guidelines.Another strength of OPTION-DM is that it is, to our knowledge, the largest neuropathic pain crossover trial reported to date. All previous DPNP multiperiod, crossover trials had smaller sample sizes,Our trial also explored several secondary endpoints. The head-to-head comparison of the maximum tolerated doses of amitriptyline, duloxetine, and pregabalin showed similar efficacies for all three monotherapies, at the end of 6 weeks, although there were significantly less discontinuations due to TEAEs with pregabalin. However, monotherapy resulted in significant pain relief only in just over a third of participants , and 50% pain relief in about 40%. Many patients  required combination treatment that resulted in a mean 1 point additional improvement in NRS  and an aDespite large variations in the cost and availability of amitriptyline, duloxetine, and pregabalin across the world, it is reassuring that all three are similarly efficacious in relieving pain. This will have real power to inform future clinical guidelines for the management of DPNP as available guidelines provide conflicting recommendations.In this trial, the absence of a placebo group might be considered a limitation. However, these drugs are in common use all over the world, currently approved by regulatory and advisory bodies such as the National Institute for Health and Care Excellence on the basis of a large body of evidence for their efficacy from randomised placebo-controlled trials,5Another limitation of our study is the relatively high attrition, with only 59% of patients providing primary outcome data for all three pathways and 64% completing at least two pathways. The main reason for this was the long study duration (51 weeks), and thus the considerable demand on patients’ time . Nevertheless, our sensitivity analysis for the effect of missing data (including for-cause missing) suggests this primarily affected the precision of the difference rather than causing bias. Additionally, although a longer washout period  between treatment pathways would have been desirable, we felt this was unethical in this long and demanding trial and could have led to harm and even greater study discontinuations. Finally, although the study was not statistically powered to detect any carryover effect, this is unlikely to have had an effect on the primary outcome at the end of a long treatment period of 16 weeks.In conclusion, the OPTION-DM trial showed that all three treatment pathways delivered similar analgesic efficacy both in terms of statistical and clinical significance. The trial also showed that combination treatment, where needed, was well tolerated and led to significantly better pain relief. Taken together, this study has great potential to influence treatment guidelines for DPNP.Requests for deidentified patient-level data and the statistical code should be made to the corresponding author, stating the data fields required and purpose of the request . The data dictionary and statistical analysis plan can also be made available. Requests will be considered on a case-by-case basis and requestors will be asked to complete a data sharing agreement with the sponsor before data transfer. Study records will be stored for 25 years after the completion of the study before being destroyed.ST reports honoraria for educational meetings from Pfizer, Viatris, Wörwag Pharma, Novo Nordisk, Merck & Co, Eva Pharma, Hikma Pharmaceuticals, Abbott Laboratories, AstraZeneca, Nevro, Procter & Gamble Health, Astellas Pharma, and Berlin-Chemi; consulting fees from Bayer, NeuroPn Therapeutics, Wörwag Pharma, Angelini, Grünenthal, TRIGOcare International, Nevro Mitsubishi Tanabe Pharma Corporation, and Confo Therapeutics; and a research grant from Procter and Gamble Health paid to Sheffield Teaching Hospitals. UA reports honoraria for educational meetings from Eli Lilly, Napp Pharmaceuticals, Sanofi, and Boehringer Ingelheim. EBJ reports honoraria and research support from Novo Nordisk and Sanofi. SHA reports honoraria for educational meetings from Novo Nordisk, Eli Lilly, and Sanofi. PV reports honoraria from Merck and Sanofi. MJ reports honoraria for advisory boards and speaker fees from Grünenthal (2015 to present) and being a co-chairperson, since 2014, of the Chronic Pain Policy Coalition and a council (2012 to present) and ordinary member of the British Pain Society. DB reports grants and contracts from Novartis, Grunenthal, Bayer, and Air Liquide; and consulting fees from Bayer and Air Liquide. DLB has acted as a consultant on behalf of Oxford University Innovation for AditumBio, Amgen, Bristows, Latigo Biotherapeutics, GlaxoSmithKline, Ionis Pharmaceuticals, Eli Lilly, OliPass, Regeneron Pharmaceuticals, and Theranexus, over the past 2 years; has received research funding from Eli Lilly and AstraZeneca; has received an industrial partnership grant from the Biotechnology and Biological Sciences Research Council and AstraZeneca; and reports grants and contracts for several studies from the UK Research and Innovation, Medical Research Council (MRC), Action Medical Research for Children, MRC Research Grant, Wellcome Trust Senior Clinical Scientist Fellowship, Novo Nordisk Foundation, EU Horizon 2020, MRC Clinical Research Training Fellowship, and Wellcome Trust Strategic Award. DS reports membership of the advisory boards of Impeto Medical, PelliTec, and FeetMe. CC is a member of the NIHR Clinical Trial Unit (CTU) Support Funding Committee, NIHR CTU Standing Advisory Committee, NIHR Programme Grants for Applied Research Subcommittee, and Trial Steering Committees for other NIHR-funded trials. All other authors declare no competing interests.


Erector spinae plane (ESP) blocks are a regional anaesthetic technique used for pain relief in thoracic procedures. Our centre has recently begun using ESP blocks pre-medical thoracoscopy for analgesia.Nine patients undergoing MT from September 2021 to February 2022 were included. Opioid use and depth of required sedation was recorded. Pre and post pain scores and at home were recorded by interview and review of charts. A functional pain questionnaire was administered via telephone.Average greatest depth of sedation using propofol was 1.92 (standard error of mean [SEM] 0.27), with remifentanil 2.52 (SEM 0.46). 78% required oral analgesia on day 0 post discharge. 55% required oral analgesia on post-op day 1. Patients used an average of 3.33 mg oral morphine (SEM 2.35) in hospital, and 3 mg (SEM 2) on post-op day 1. Periprocedural pain scores were 0.66 (SEM 0.27). Pain scores in recovery were 1.56 (SEM 0.76). Pain scores 3–12 h post discharge were 3.56 (SEM 0.7), while pain scores on post-op day 1 were significantly higher at 5.56 (SEM 0.90) . Functional pain scoring showed patients doing activities of daily living well with a good ability to breathe and cough. All felt that their pain was well controlled on the day of the procedure and at home. No complications were reported.ESP blocks provide good analgesia. Pain scores showed significant analgesic effect lasting several hours. The project showed pain outcomes and patient acceptability were good for the use of regional anaesthesia. Established guidance for pain management for video-assisted thoracoscopic surgery (VATs) exists . A VAT pFeray et al.  suggest The erector spinae plane block is a regional anaesthetic technique, first described by Forero et al. . Local aNine patients underwent MT from Sept 2021 to Feb 2022. Local anaesthetic use, peri-and post-operative opioid use and depth of required sedation was recorded. Pain scores during procedure, in recovery and at home were recorded by an investigator-led functional pain questionnaire (described in case record form-Appendix 1) administered directly to the patient 1-h post procedure and via telephone 24 and 48 h post procedure.Five patients had single site ESP blocks with injections at spinal levels ranging between T5-7, using 20–35 mL total volume of 0.25% l-bupivacaine. Four patients had bi-level ESP blocks at T4 and 8, using 34–40 mL total volume of 0.25% l-bupivacaine. The average greatest depth of sedation required using propofol target controlled infusion was 1.92 (nanograms per milliliter) µg/mL (standard error of mean [SEM] 0.27), with remifentanil 2.52 μg/mL (SEM 0.46). 78% of patients required oral analgesia on day 0 post discharge (paracetamol and one instance of codeine with ibuprofen). A total of 55% of patients required oral analgesia on the postoperative day 1. Patients used an average of 3.33 mg oral morphine (SEM 2.35) in hospital, and 3 mg (SEM 2) on the post-operative day 1. Periprocedural pain scores  were 0.66 (SEM 0.27). Pain scores in the recovery room were 1.56 (SEM 0.76). Pain scores 3–12 h post discharge were 3.56 (SEM 0.7), while pain scores on the first postoperative day were significantly higher at 5.56 (SEM 0.90) . FunctioESP blocks thus appear to provide good peri-procedural analgesia for MT requiring simple oral analgesia or weak opioids after discharge, and are well tolerated with patient satisfaction. Pain scores increased over time in keeping with a significant analgesic effect lasting several hours from the ESP blocks then wearing off. Regional anesthesia is known to prevent chronic pain after surgery  and thorSupplementary MaterialClick here for additional data file.