Despite its widespread availability, the use of kilovoltage (kV) image guidance is often related to factors such as perceived adequacy of clinical patient setup and individual practice patterns. We sought to determine whether kV image guidance in the treatment of painful bone metastases would improve therapeutic efficacy.Under an Institutional Review Board approved protocol, hospital records of 164 patients having received radiation therapy to 257 individual painful osseous metastases were retrospectively reviewed. Marginal logistic regression analyses using the generalized estimating equation (GEE) approach were used to investigate potential associations between pain reduction and several patient, disease, and treatment related variables. Correlation of kV image guidance with pain reduction was analyzed by univariate and multivariate GEE logistic regression analysis.Median time to pain reduction was 3 days (range 0~109 days) from the start of radiation therapy. Pain reduction ≥ 50% was noted in 196 (77%) metastatic lesions with 136 (53%) demonstrating complete pain relief. Patients with metastatic lesions from non-small cell lung cancer experienced less pain relief (p = 0.007). Disease extension outside of bone was a negative predictor for pain reduction (p = 0.02). On univariate and multivariate logistic regression, kV image guidance demonstrated a statistically significant correlation with improved pain control in cases involving treatment of the lower extremities (p = 0.03) and those with fewer treatment fractions (p = 0.01), particularly in the setting of extra-osseous disease extension (p = 0.003).Kilovoltage image guidance in the treatment of painful bone metastases may offer greater pain control through improved patient setup, particularly for patients with tumors of the lower extremities, extraosseous disease extension, and fewer treatment fractions. While long-term cure is the optimal outcome of radiation therapy (RT), many cancer patients will relapse and present with metastatic disease while others will be discovered to harbor widespread metastases at the initial presentation. In fact, the incidence of bone metastases have increased, believed to result largely from improved overall patient survival owing to improved cancer treatments , 2. Of tCancer metastases to bone lead to a myriad of sequelae, or “skeletal-related events,” for patients, their families, and the healthcare system. Pain, often intractable, is the most common clinical symptom associated with osseous metastases and the mechanisms responsible for the bone pain are poorly understood but appear to be related to osteolysis . This boRadiation therapy is a longstanding source of relief for painful bone metastases. As with any external beam radiation treatment, accurate and reproducible patient positioning is vital. Image-guided radiation therapy (IGRT) is among the available tools for achieving this accuracy, and serves an important role in modern RT, particularly in cases treated with curative intent. However, despite the widespread availability of IGRT techniques such as orthogonal kilovoltage (kV) imaging, their use often depends on factors such as individual practitioner preferences, institutional practices, the perceived adequacy of clinical patient set up and prior authorization by insurance companies. We, therefore, sought to determine whether or not daily kV image guidance provided a therapeutic benefit in the palliative treatment of osseous metastases and which patient and disease related parameters predicted for this benefit. We hypothesized that a clinically relevant benefit of kV image guidance would be realized in cases presenting with extraosseous disease extension and in those involving treatment of sites that may be more difficult to reproducibly immobilize, such as the extremities.The studies involving patient data were reviewed and approved by the Rutgers University Ethics and Compliance Committee.Under an Institutional Review Board-approved protocol, hospital records of 255 patients who received RT for bone metastases were retrospectively reviewed. All patients were treated between 2004 - 2015 at the Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson University Hospital. Ninety-one patients were excluded because of the lack of recorded pain scores, incomplete RT records, inadequate post-treatment follow up, or death within 30 days of treatment completion due to progressive systemic disease. The final cohort consisted of 164 patients having received RT. Patient self-reported pre- and post-treatment pain scores were obtained for 257 individual osseous metastases.Standard baseline evaluation included a complete medical history and physical, radiologic, and pathologic assessments. Data extracted from the charts included patient age, ethnicity, use of systemic therapy, histology, site of metastasis, prior surgical resection, extraosseous extension, and radiation treatment variables such as total dose, number of fractions, dose per fraction, and kV imaging. Patients treated with SBRT were excluded from the analysis. To gather information regarding pain response and time to response, charts were reviewed for pain at the following time points: the initial patient consultation for RT, the first on‐treatment visit, halfway through RT, at the last on treatment visit during RT, and 4 weeks after RT completion at the first follow‐up. Patients were asked to quantify their pain on the Numeric Pain Rating Scale ranging from 0-10, with 0 representing no pain and 10 indicating severe pain. This pain scale is widely utilized and has been validated as an easily applicable, sensitive and reproducible means of assessing pain .™ Treatment Planning System  where target delineation, isocenter placement, beam placement and treatment planning were performed. Whether or not the osseous gross tumor volume (GTV) was contoured and utilization of kV imaging during treatment delivery were based on provider preference. All patients for whom conformal treatment planning was used also received megavoltage (MV) portal imaging on the first day of treatment delivery and every five fractions.At our institution, it is customary for all patients to undergo computed tomography (CT) simulation in order to obtain three-dimensional anatomy to help define treatment fields and to develop a patient-specific treatment plan. Patient set up during simulation is performed according to institutional standards, with use of immobilization devices such as knee/foot locks as needed. After CT scan acquisition, images were transferred to the Varian EclipseReduction in patient self-reported pain scores following RT were analyzed in the context of the aforementioned patient, disease, and treatment related parameters. Pain reduction for each osseous metastasis, measured by comparing pre- and post-treatment Numeric Pain Rating Scale scores, was dichotomized by the median in the sample  to facilitate statistical data analysis. “Good pain response” was defined as > 5 point decrease following RT and “poor pain response” was defined as ≤ 5-point decrease. To account for potential correlation between pain scores from multiple metastases within the same patient, marginal logistic regression analyses using the generalized estimating equation (GEE) approach were performed. Specifically, bivariate analyses using GEE logistic regressions were performed to assess the association of individual factors with pain reduction. Variables demonstrating a significant association with pain relief (p < 0.10) were subsequently used to build a multivariable logistic regression model based on the back-elimination principle. Significant factors in the multivariable model were defined by p < 0.05. Because kV imaging is a variable of interest, this variable was also kept in the back-elimination procedure during creation of the multivariable model. All statistical analyses were performed using SAS University Edition .3 (range 0.04 - 1729 cm3).Of the initial 255 patients identified, 91 were excluded from the study, resulting in a final cohort of 164 patients treated for 257 osseous metastases. The median patient age was 64.5 years, with 45.1% males and 54.9% females. The most common histology was breast (26.5%), followed by prostate (23.7%), and non-small cell lung (23%) cancers (NSCLC). Extraosseous disease was noted in 59.1%. The most common sites of disease were the spine (46.1%) and the lower extremities/pelvis (37.9%). Additional baseline patient characteristics are described in A total of 46% of patients underwent at least one kV image during RT. Of the patients that underwent kV imaging, the mean number of fractions for which kV image guidance was utilized was 80% ± 26.5%, the median was 90%, and the first and third quartiles were 70% and 100%, respectively. The median total dose was 2750 cGy (range 300~3750 cGy) delivered over 10 fractions (range 1~17). The median of baseline reported pain score was 8 (range 1~10). For patients receiving 1-5 fractions, the median pain reduction was 5 (range -3~10) with a median interval of 2 days (range 0~94 days) from the start of treatment, while for patients receiving 6-10 fractions, the median pain reduction was 6 (range 0~10) with a median interval of 10 days (range 0~109 days) from the start of treatment.92.6% (n = 238/257) of cases had any pain relief, 76.2% (n = 196/257) had ≥ 50% pain relief, and 52.9% metastases (n = 136/257) achieved complete pain relief. One hundred metastases (38.9%) received pain relief during treatment.There was noted to be a significant difference in pain reduction among different types of cancer Table 2.Though a difference in absolute pain reduction was not detected between metastatic lesions with and without extraosseous extension (p = 0.23) Table 2,For the entire patient cohort, utilization of kV image guidance for ≥ 90% of the delivered fractions did not yield a statistically significant improvement in pain reduction (p = 0.07). There was, however, a statistically significant improvement in pain response with ≥ 90% kV imaging for treatments delivered to the extremities, with even greater significance for the lower extremities  Table 4.The benefit of kV imaging also appeared to be dependent on fractionation insofar that 10 fraction regimens appeared to derive no statistically significant benefit from kV imaging (p = 0.74) in contrast to 5-fraction regimens (p = 0.01) Table 4.The only condition in which we detected an effect of fractionation was among patients who received kV imaging for < 90% of fractions - in these patients, regimens consisting of ≤ 5 fractions yielded less pain relief than those consisting of > 5 fractions (p = 0.03) Table 6.We hypothesized that in addition to overall pain reduction, the time interval between the start of palliative radiation and the realization of pain reduction may also be correlated with kV imaging and fractionation, with faster pain relief through increased kV image guidance and hypofractionation, particularly for sites that may be more difficult to accurately set up on a daily basis, such as the spine or extremities. However, we were unable to detect any association between pain relief and kV image use or fractionation for any particular disease site or for patients with extraosseous disease spread Table 7.While some physicians routinely contour the GTV for palliative cases, this practice is not universal. We analyzed whether or not contouring of the target volume improved pain reduction both in the entire patient cohort, and as well as among patients with extraosseous disease extension. However, we did not detect evidence of greater pain relief with target volume contouring in either patient population Table 2.We report the findings of our analysis, which did detect a correlation between improved pain relief and kV imaging. As hypothesized, the benefit of kV imaging was realized most in cases involving treatment of the lower extremities, which might be expected to be difficult to reproducibly immobilize on a daily basis. We also report improved pain control with kV imaging, particularly in cases with fewer fractions (5 vs 10 fractions). This finding is not unexpected in that regimens with fewer total fractions would conceivably provide less opportunity to “compensate” for fractions with inaccurate positioning. We also report that pain due to metastatic lesions from NSCLC may be less likely to respond to RT as compared to other types of cancer.Our study addresses the paucity of data with regard to the benefit of routine kV image guidance during conventionally fractionated RT, specifically in the setting of palliative radiotherapy for skeletal metastases. We report that RT remains a highly effective means of palliation for pain resulting from osseous metastases, with 93% of patients reporting pain reduction and 53% reporting complete pain relief. This is consistent with reports in the literature of complete pain relief ranging from 15 to 54% and partial pain relief ranging from 28 to 89% .Notably, though the time interval between radiotherapy and pain relief is classically thought to be several weeks, we found the median time to any pain reduction to be 3 days from the start of treatment. We attempted to collect data on pain medication use; however, as this information was not consistently available and given the inherent uncertainly associated with retrospectively correlating pain scores with pain medication use, with other complicating factors such as consistency and schedule of their usage, this data was ultimately excluded from the final analysis. Though a formal statistical evaluation of pain medication use could not be completed, it is our institutional practice to maintain patients on their pretreatment pain regimen during palliative radiotherapy and, within our cohort of patients, we did not detect an overt increase in pain medication use following radiotherapy that could explain the significantly shorter time to pain relief in the current study.Though we did not uncover a benefit of kV image guidance specifically with respect to cases with extraosseous disease extension, we did find that extraosseous disease extension was a significant negative predictor of pain reduction (Odds ratio 0.58 for > 5-point pain reduction). This result may not be entirely surprising since disease extension beyond bony confines would be expected to result in significant pain and these patients, specifically, may consistently derive benefit from palliative radiotherapy, whether or not kV image guidance is utilized, provided that adequate margins and accurate patient set up are ensured. In support of this finding, we did find that the interaction between kV imaging and pain reduction following regimens consisting of fewer fractions was most significant in cases presenting with extraosseous disease extension. Although others have investigated the time burden of IGRT in the treatment of bone metastases , to our While some physicians routinely contour the GTV for palliative cases, this practice is not universal. Though it was expected that contouring of the target volume would improve pain reduction, we did not detect evidence of greater pain relief with target volume contouring in either the entire patient cohort or the subgroup of patients with extraosseous disease extension.The implications of this study are manifold. Procurement of kV images during treatment is a time-consuming process that places a demand on staff and equipment while also exposing the patient to additional radiation as well as increasing the risks associated with longer time on the treatment table. However, despite these potential drawbacks of kV image guidance, our study suggests that there may be certain patients for whom the benefits outweigh the risks.Our findings suggest that while, for the majority of cases involving osseous metastases, palliative RT may be effectively delivered without the reliance on routine kV image guidance and without compromising efficacy, select groups of patients may be better served by incorporation of kV image guidance. Alternatively, and at a minimum, awareness of these difficult cases and mitigation of inaccurate treatment delivery through careful patient setup should be encouraged - this could prove to be useful information in countries lacking facilities capable of image guidance and in countries whose limited resources are taxed by sheer patient volume.The current report is not without its limitations. Most significantly, the retrospective nature of our study inherently places restrictions on the conclusions that may be drawn. Additionally, while the present work suggests a possible added benefit of daily kV image guidance, this was in the setting of a large academic center with experienced radiation therapists trained in the utilization of kV image guidance for accurate treatment delivery. The importance of accurate patient set up cannot be overstated. Furthermore, it is conventional to apply generous field margins in palliative cases, which would certainly obviate the need for image guidance, but comes with the inevitable consequence of radiation delivery to healthy tissue. Our study did not examine the effect of margin size on the benefit of kV image guidance, and it may be that kV imaging is not necessary after a certain margin size. It is also conceivable, however, that radiation field margins may be reduced, in order to decrease normal tissue exposure, to a point at which kV image guidance for accurate daily patient set up becomes critical for all sites, especially in cases with extraosseous disease extension. Additionally, in our analysis we chose to dichotomize the use of kV image guidance according to the proportion of fractions in which it was utilized (≥90% vs <90%). The 90% cut-off value was chosen as it was the median percentage of fractions incorporating kV imaging. This value also made it possible to evaluate patients who received image guidance for nearly every fraction while making allowances for differences in physician practices, changes in institutional processes, and the retrospective nature of our study. Future work examining the effect of margin size on the benefit of daily kV imaging, the effect of kV imaging on duration of pain relief, as well as the minimum proportion of fractions that must be delivered with kV imaging in order to improve outcomes, may aid in clarification of the role of kV image guidance in the palliative setting.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving patient data were reviewed and approved by the Rutgers University Ethics and Compliance Committee.AT is the lead author of this manuscript and performed the majority of data collection and manuscript preparation. BG, SJ and JS assisted with data collection. All authors assisted with manuscript preparation. S-EL provided statistical analysis. SJ is the corresponding author. The study was conceived by SJ. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: Prior trials investigating the treatment of symptomatic osteoarthritis (OA) with hyaluronic-acid-derived products injections have provided optimistic results. The study was directed to assess the effectiveness of an innovative hyaluronic-acid-based hydrogel (Hymovis®) in the treatment of symptomatic knee OA. Methods: A prospective, single-center, clinical trial was performed. Thirty-five patients with degenerative knee OA were included. Inclusion criteria were: age between 45–80, radiographic Kellgren grade II or III osteoarthritis, minimum 35 mm score on the Visual Analogue Scale (VAS), pain for at least 6 months and agreement to participate in the study. Patients received two injections at a one-week interval. The evaluator assessed the patients using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and VAS. Evaluation was performed before, at 2 and 6 months after the injections. Results: A significant improvement on the WOMAC Index pain subscale was observed at 6 months after the injection. At two months, pain subscale score decreased from 10.34 to 9.34. At six months, a significant decrement in pain parameters compared to baseline was observed . Median points on VAS significantly ameliorated after 6 months . Regarding physical function, a statistically significant difference compared to baseline was observed at the end of the study . WOMAC Index stiffness component did not differ from baseline at any time during follow-up. Conclusions: Pain relief installed with a delayed on-set but had a prolonged duration. The novel hyaluronic acid-based hydrogel (Hymovis®) had effective results, particularly after six months post-injections and offers a therapeutic advancement in the treatment of moderate to severe osteoarthritis. Knee osteoarthritis (OA) is a common chronic joint disorder and a leading cause of disability among the elder population . Pain deMost of the oral medications have weak or no effects when treating pain associated with knee OA. Acetaminophen is proven to have no effects on pain control irrespective of dose  and someIt was also described that usage of oral opioids  has a small benefit compared to their potential adverse events . As eldeBesides the highlighted anti-mechanical stress effects due to its molecular structure, other biological mechanisms of action have been described: inflammatory mediators inhibition, chondroprotection and stimulation of endogenous production of proteoglycans and glycosaminoglycans ,21. MostThree main types of HA products are described in the recent literature: HA with an intermediate molecular weight (MW) (500–730 kDa), HA with a high MW (≥1000 kDa) and highly modified HA (cross-linked) . In cont®4”, introducing a new HA derivative (Hymovis®) for sale. Being a new product, its outcomes are not widely published; for that reason, our principal aim was to assess the clinical effectiveness and outcomes of the new HA-based hydrogel Hymovis®.Recently, new technology was able to provide extended viscoelasticity and residence time to intermediate MW natural HA polymers, while maintaining its bio-tribological features . This teA prospective, single-centre, clinical trial was carried out in the Department of Orthopaedics and Traumatology II from the Clinical County Hospital in Tîrgu Mureș, Romania. The accept from the local ethical committee was obtained and all consecutive patients presenting to our outpatient clinic with diagnosed knee OA were screened for inclusion into this study. Radiologically, knee OA had to be Kellgren–Lawrence grade II or III and the VAS pain level on a scale of 0–100 mm had to be above 35 mm. The following criteria of exclusion were considered: pathologies other than primary idiopathic OA, any history of intra-articular injections in the last 6 months, heparin- or platelet-based anti-coagulation treatment in the last month, usage of NSAIDs one week before injection, allergy to HA injections, comorbidities that could affect the outcomes, pregnancy, lactation and infections.A total of 79 patients with primary OA were obtained. Out of those patients, 41 were excluded for matching any of the exclusion criteria . n = 35) included received two intra-articular doses of 24 mg/3 mL of HA  with a one-week interval , stiffness  and physical function . The values from each subscale are summed up in order to provide a total normalized score of the index. Every patient completed the WOMAC form before treatment, and at two and six month follow-up visits.VAS is a substantial and an accepted instrument in calculating the severity of chronic pain . The scot-test and repeated ANOVA measurements (single factor). The level of statistical significance was set at p < 0.05.VAS and WOMAC outcomes from each evaluation were compared. The demographic variables comparison was calculated using Chi-square test. The Kolmogorov–Smirnov statistical test for goodness of fit was performed and we obtained a normally distributed population. Data results from WOMAC and VAS were statistically analyzed in GraphPad (InStat) and EpiInfo v 7.1.4.0  software using The final study cohort contained 35 patients. Twenty-five (71%) subjects were females and the mean age at first injection was 63 ± 8 years old. Fourteen patients were smokers for more than one year and 27 had an education level of high school degree or more. Twenty-five individuals reported their employment status as “retired” upon registration. Regarding the body mass index (BMI), two were below 25, one was over 30 and the rest were overweight (25–30). The mean weight was 82.2 kg±16.2 SD.p < 0.0001). The baseline VAS score was 74.2 ± 11.7 before the treatment. At two-month follow-up, the pain score diminished to 69.6 ± 9.8 with no statistically significant difference from baseline. Mean VAS significantly improved from 69.6 ± 9.8 cm at two months to 57.3 ± 12.1 cm at the end of the study (p = 0.065). At 6 months, a significant improvement regarding the pain parameter was observed compared to baseline . With regard to the WOMAC stiffness subscale, there were no significant differences from baseline at two months (p = 0.819) and six months (p = 0.937). The physical function component score improved from baseline at 6 months after injections  published papers regarding HA injections is presented in The most important findings of the present study were that HymovisHymovis is a sterile, apyretic hydrogen produced by HYADD4  in buffered isotonic solution. Sodium hyaluronate hexadecylamide confers high viscosity and elasticity by reducing inflammation mediators such as prostaglandin E2, IL1 and IL6. Thus, Hymovis improves the function of lubrication and shock absorption that synovial fluid has, protecting cartilage and soft tissues from mechanical damage. These properties, together with the extended retention time in the joints, allow this product to relieve pain and improve joint function with a short-term treatment regimen .Researchers often perform comparisons between HA and other intraarticular-injected substances. Skwara compared the effectiveness of intra-articular corticosteroids (CS) (triamcinolone) with intraarticular HA by analyzing gait, maximum vertical force, muscle activity and pain . No imprIt is widely accepted that the placebo effect plays a role in pain relief. There are studies that support this theory. For example, a systematic review published by Gaendam et al., the team suggested that intra-articular saline injections are equally efficient with hyaluronic acid, corticosteroids and platelet rich plasma in the management of hip pain and functional outcomes . Contrar®) regarding pain relief in patients suffering from knee OA. Clinical results proved its ability to reduce pain and improve joint function.The WOMAC Index is widely used in assessing outcomes after knee OA therapy. The WOMAC Index has its validity and responsiveness correctly scaled when used together with VAS, making for accurate results when combined . The not


To determine whether capsular distention in the painful temporomandibular joint (TMJ) can be assessed by ultrasonography, we compared the capsular width between painful TMJs and painless TMJ. The risk factors for TMJ pain were also investigated including capsular width and other clinical factors such as TMJ sounds that may affect the occurrence and persistence of TMJ pain.TMJ ultrasonography was performed on 87 temporomandibular disorder (TMD) patients, including 47 unilateral and 29 bilateral TMJ pain patients, and 11 patients without TMJ pain.p < 0.001) and was significantly correlated with pain scores.The capsular width was greater in the 105 painful joints than in the 69 painless joints. Considering individual anatomical variations, the differences between painful and painless joints in unilateral TMJ pain patients were also analyzed, revealing a greater width in painful joints. Capsular width was a risk factor for TMJ pain with an adjusted odds ratio of 1.496 (95% confidence interval 1.312–1.706; This correlation may suggest that pain intensity is associated with widened capsular width because of joint effusion or synovitis. Further studies are required to refine and establish the protocols for standard examinations using ultrasound imaging.The online version contains supplementary material available at 10.1186/s12903-021-01853-0. The temporomandibular joint (TMJ) is a synovial joint consisting of the mandibular condyle, mandibular fossa, articular disc, and articular capsule. Temporomandibular disorder (TMD) is defined as the development of articular disc disorders, arthritis, dislocation, and masticatory disturbances owing to external and internal factors that affect the TMJ . The symUltrasonography is easily accessible and affordable, making it a viable and potent imaging modality for TMJ evaluation. Ultrasonography is a non-invasive, pain-free, economical, and real-time diagnostic modality that can be used in an outpatient setting. It has certain drawbacks, such as its limited access to deep structures or to articular discs owing to the absorption of the sound waves by the mandibular and temporal bones, as a result of which images of the internal tissue cannot be properly formed. However, by appropriately adjusting the position of the probe, images of the articular space and capsule can be captured. The articular space has been evaluated in other joints, such as knee, elbow, hip, and shoulder in cases involving inflammatory joint effusion. Koski et al. evaluated the capsular width of the hip joints in patients with chronic inflammatory disease using ultrasonography. They demonstrated that the capsular width in synovitis patients was greater than the capsular width following treatment in arthritis synovitis patients . FriedmaFurther, the use of TMJ ultrasonography has been reported in determining the presence of TMJ inflammation by measuring the capsular width . By studThe aim of the study was to determine whether capsular distention in the painful TMJ can be assessed by ultrasonography. Based on the hypothesis that there is widening in capsular width induced from the joint effusion or synovial thickening which can cause TMJ pain, we compared the capsular width by ultrasonography between painful TMJs and painless TMJs. We not only compared average capsular widths similar to in previous studies, but we also analyzed the differences between painful joints and painless joints in unilateral TMJ pain patients considering individual anatomical variations. The risk factors for TMJ pain, including capsular width and other clinical factors that could affect TMD development and the persistence of pain, were investigated to evaluate the associations.This study was approved by the Institutional Bioethics Review Board of Ewha Womans University, Mokdong Hospital (IRB No. 2019-02-036), and it complies with the most recent Helsinki Declaration revised in 2013. Inclusion criteria were patients who were diagnosed as TMD in the Department of Oral and Maxillofacial Surgery of Ewha Womans University, Mokdong Hospital, from 1 June 2017 to 31 January 2019. The diagnosis was established according to the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD) diagnostic decision tree based on patient’s history and comprehensive clinical examination . PanoramAccording to the localized TMJ pain, the 87 included patients were assigned to either the TMJ pain group (n = 76) or the painless group (n = 11). There were no patients who had pain localized in the TMJ area in the painless group. Among 11 patients in the painless group, 8 patients only had TMJ sounds without other symptoms, and 4 patients had myalgia in the neck area. The pain group consisted of 29 patients with bilateral TMJ pain and 47 patients with unilateral TMJ pain. In terms of the number of TMJs in total, 174 bilateral TMJs evaluated in 87 patients including 105 TMJs in the painful joint group and 69 TMJs in the painless joint group.Clinical characteristics such as patient sex, age, history of orthodontic treatment, TMJ sounds, pain duration, pain score, and maximum mouth opening were collected. TMJ sounds were examined by palpation on both TMJ during mouth opening and closing. Pain scores were measured using a numerical rating scale (NRS), and patients were asked to assign a score to their pain during mouth opening within the range of 0–10. The maximum mouth opening was evaluated by measuring the distance between the central incisors of the maxilla and mandible in millimeters (mm) when the patient’s mouth was maximally open. Oral conditions including tooth attrition, tongue ridging, and buccal mucosa ridging were examined. Tooth attrition was defined as 2–4 degree of wear on the incisal edges and cusp tips according to the Smith and Knight Tooth Wear Index . Based oData on psychological and behavioral factors that could affect TMD development and the persistence of pain were also collected. The psychological factors included the presence of stress, depression, and anxiety. The behavioral factors included bruxism, clenching, side sleep, unilateral chewing, chin leaning, alcohol consumption, caffeine consumption, snoring, and forward head posture. Questionnaires were used to assess psychological and behavioral factors  and a 3–12 MHz linear probe. TMJ ultrasonography was performed by a single, trained examiner blinded on clinical findings. Intraclass correlation coefficient (ICC) was estimated to evaluate intra-examiner reliability. Obtained ICC value  was 0.971 (0.661–0.991), which indicates the level of reliability was moderate to excellent . The patp < 0.05. The statistical analysis was performed using the software program, SPSS version 25.0 .The assumptions of normality and homogeneity of variance were confirmed using the Kolmogorov–Smirnov test before further statistical analyses. An independent t-test and a paired t-test were used to compare capsular widths. To identify the risk factors of TMJ pain, univariate and multivariate logistic regression analyses were used. The correlations between pain scores and capsular width and maximum mouth opening values were analyzed using Spearman correlation coefficient analysis. The statistically significant level was determined to be The clinical characteristics of the 87 patients included in this study are presented in Table p < 0.001). Concerning the anatomical variations in capsular widths, a paired comparison was performed for 47 unilateral pain patients, and the differences in capsular width were statistically significant (p < 0.001). The mean capsular width of the 47 painful joints was 2.04 ± 0.52 mm, and that of the 47 painless joints was 1.37 ± 0.36 mm. To determine the relationship between capsular width and pain duration, 105 painful joints were classified based on whether the pain was experienced for less than 3 months or for more than 3 months. The mean capsular width was not statistically different at 1.97 ± 0.45 mm for pain durations of less than 3 months and 2.15 ± 0.52 mm for pain durations of 3 months or more (p = 0.081).Table p < 0.001), indicating that the risk of TMJ pain increased 1.496 times with a 0.1 mm increase in the capsular width. The correlation coefficient between the capsular width and pain score was 0.570 (p < 0.001) (Table p = 0.002).The associations between the TMJ pain and clinical factors were evaluated using logistic regression analysis. Based on the results of the univariate logistic regression analysis, capsular width, joint sounds, tooth attrition, and stress were significant risk factors for TMJ pain Table . AdjusteIn this study, capsular distention of TMJ was assessed using ultrasonography. This study suggests that the capsular width was greater in the painful joints than painless ones. Additionally, when evaluating the associations between the TMJ pain and clinical factors, distended capsular width may be an independent risk factor for TMJ pain. Most studies on TMJ ultrasonography have focused on detecting of disc displacement, and very few works have investigated capsular width measured using ultrasonography –19. HoweManfredini et al. reported that ultrasound measurement of the capsular width could be an indirect marker for TMJ effusion . Using rIn the present study, the mean capsular width of the painful joints was 2.04 ± 0.49 mm, and that of the painless joints was 1.37 ± 0.41 mm, thereby exhibiting statistically significant differences. These results are similar to the results indicating the 2 mm capsular width threshold associated with joint effusion reported by Manfredini et al. [To determine the risk factors for TMJ pain, the associations between TMJ pain and clinical factors including psychological and behavioral factors were evaluated. On our knowledge, this study is the first study estimating risk of capsular width on TMJ pain considering other clinical factors that could play a role in the occurrence and persistence of pain. Psychological and behavioral factors have been suggested as potential causes of TMD. Psychosocial factors, including depression, stress, and anxiety, may play a role in the onset and progression of TMD . AccordiIn the present study, capsular width, joint sounds, tooth attrition, and stress were found to be significant risk factors for TMJ pain in a univariate logistic regression analysis. In a multivariate analysis, however, only capsular width was an independent risk factor for TMJ pain. Further, the correlation between the capsular width and pain score revealed that the capsular width increased significantly with increasing pain score. This correlation may suggest that pain intensity that reflects the severity of joint space inflammation is associated with widened capsular width because of joint effusion or synovitis. It may also suggest that measuring capsular width in painful TMJ may be used to measure severity of joint inflammation and follow-up on the responses to treatment by measuring width decreases. If the width were reduced, it would imply that current treatment has resolved the inflammation in the TMJ. Because ultrasonography is a simple method that can be used in an outpatient clinic, the progress of treatment can be easily monitored using TMJ ultrasonography.Johnston et al. assessed the association between TMJ inflammation as measured by ultrasound and patient disability assessed by the Steigerwald Maher TMD Disability Index (SMTDI). The authors reported that greater capsular widths were found to be significant predictors of SMTDI scores . AlthougThis study has a limitation in that ultrasonography was not compared with MRI that is considered the standard imaging modality to validate evidence of effusion or synovitis. However, the results indicating that capsular distention in painful TMJ resulting from joint effusion or synovial thickening can be detected and evaluated by a simple ultrasonography technique is valuable. TMJ ultrasonography has not yet been established as a standard modality, and the accuracy of the results mainly depends on the operator’s training . FurtherThe average capsular width of a painful TMJ was significantly greater than that of a painless TMJ. The capsular width increased significantly with increasing pain score. This correlation may suggest that pain intensity that reflects the severity of joint space inflammation is associated with widened capsular width because of joint effusion or synovitis. Further studies are required to refine and establish the protocols for standard examinations using ultrasound imaging.Additional file 1. Table S1. Questionnaire.


A 52-year-old female amateur golfer presents to the sports medicine clinic with right-sided low back pain without inciting trauma. Her intermittent pain of several years' duration became more painful and persistent after a recent round of golf. She reports that she has a “bad back” and that formal physical therapy (PT) focusing on low back strengthening, 4 weeks of oral nonsteroidal anti-inflammatory drugs (NSAIDs), and activity modification have not been helpful in the past. Lumbar spine  radiographs show degenerative changes at multiple levels without significant foraminal or spinal stenosis. Radiographs of the pelvis  show mild degenerative changes of the bilateral sacroiliac joints (SIJs). On physical examination, she had positive FABER , Gaenslen, and compression tests.1 That calculated disability number is a 54% increase from 1990 and accounts for more lost workdays than any other musculoskeletal condition in the United States.1 Low back pain, while a common complaint, can be difficult to accurately diagnose. One common etiology of low back pain is SIJ pain.2 An estimated 10% to 30% of patients with low back pain have SIJ-mediated pain.5 Given the social strain of medical expense and work productivity lost in this patient population, SIJ pain is an important pathology to understand and treat.Low back pain is the top cause of disability globally, responsible for 60.1 million years lived with disability in 2015.6 Furthermore, 39% of patients diagnosed with SIJ pain have concomitant spinal pathology.2 To differentiate between spinal and SIJ pathology, the clinician is recommended to use multiple diagnostic maneuvers  treatments to the SIJ, and the other group received HVLA treatment to the SIJ and the lumbosacral spine.4 Both groups showed significant improvements on the visual analog scale (VAS) and Oswestry Disability Index (ODI)14 at 48 hours and 1 month postmanipulation.4 However, the study lacked a control group, as sham therapy is difficult to conduct.4 Appropriate patients must be chosen to undergo manipulation, as patients with significant muscle weakness, poor endurance, or both may need to focus on stabilization through strengthening rather than repetitive mobilization.6Manipulation is usually performed by osteopathic physicians, chiropractors, and physical therapists.15 NSAIDs  should not be used long term, specifically with senior athletes because of the significant side effects.10Evidence for the use of medications to treat SIJ pain is limited. Some evidence suggests a stepwise approach, starting with over-the-counter topicals  and progressing to NSAIDs in the acute phase of SIJ pain (up to 6 weeks).16 Corticosteroid injections are often considered the next step in treatment for athletes who do not improve with conservative measures or are unable to tolerate PT.17 Injections should always be done under image guidance (ultrasound or fluoroscopy) because intra-articular needle placement is rarely (0% to 22%) accomplished with blind injections.18 Jee et al compared fluoroscopy- to ultrasound-guided steroid injections with contrast in 120 subjects with noninflammatory sacroiliac arthritis and found fluoroscopic guidance to be more accurate than ultrasound guidance (98.2% vs 87.3%).19 However, after confirming placement of the needle, the researchers injected 1 mL of 0.5% lidocaine with dexamethasone 10 mg and found that the ultrasound and fluoroscopy groups had no statistical difference in improvement of pain on the VAS and ODI at 2- and 12-week follow-up.19Injections are used both for diagnostic and therapeutic purposes in patients with SIJ pain.20 For patients without the diagnosis of spondyloarthropathy, which is likely the case for most athletes with SIJ pain, the evidence for steroid injections is less clear.20 Studies investigating the efficacy of intra-articular injections in the SIJ often have differing outcome measures and medication protocols, so they are difficult to compare.20 For instance, most studies that used a single diagnostic anesthetic injection to diagnose patients with SIJ pain found patients had an average of 76 to 94 days of relief after their therapeutic SIJ injections; however, only 19% had lasting relief, and 32% had >14 days of relief.20Kennedy et al found the effectiveness of SIJ injections to be highest in patients with ankylosing spondy-loarthropathies.21 Patients’ pain and disability were assessed on the VAS and modified Oswestry Low Back Pain Disability Questionnaire.22 Statistically significant pain reduction was observed in mean VAS scores (P<0.0001) of the 39 patients diagnosed with SIJ pain. Of these patients, 66.7% had >50% pain reduction for more than 6 weeks, and 33% responded to the injection for only approximately 1 to 6 weeks with a mean of 4.4 ± 1.8 weeks.21 Of the patients who had >50% pain reduction for more than 6 weeks (n=26), their overall mean duration of pain reduction was 36.8 ± 9.9 weeks, with a range of 12 to 60 weeks.21Comparatively, Liliang et al studied 150 patients who underwent dual SIJ block injections (2 intra-articular injections of 1 mL 0.5% bupivacaine or 0.2% lidocaine with 1 mL triamcinolone acetonide 40 mg) to diagnose and treat SIJ pain (39 patients were diagnosed).20Complications related to SIJ injections are rare, but technical issues leading to unsuccessful injections (10% to 18%), temporary sciatic palsy (4.4% to 8%), increased pain (3%), and vasovagal reaction (2.5%) have been reported, as well as one case of pyogenic sacroiliitis and one reactivation of herpes simplex.7More invasive procedures for chronic SIJ pain are outside the scope of this article, but these procedures include prolotherapy, radiofrequency denervation of the lateral branches , and sacroiliac joint stabilization and fusion surgeries.12 Image-guided diagnostic injections are a useful tool to quickly confirm the diagnosis, but the use of interventional treatments is reserved for patients who have refractory symptoms.16 The literature on the use of steroid injections to treat SIJ pain is difficult to summarize because (1) studies use single- vs dual-block diagnostic injections, (2) the types of medications and doses vary, (3) patient populations are not uniform, and (4) outcome measures differ across studies.20 Comprehensive double-blind studies are needed to understand the efficacy and appropriate use of image-guided injections to treat SIJ pain in the athlete.SIJ treatment should start with accurate diagnosis, followed by correction of biomechanical and muscle imbalances through PT.After a complete history and physical examination, the athlete was diagnosed with SIJ pain. She started a formal, regimented course of PT once a week for 4 weeks to work on her core, pelvic, and hip strength. Three weeks into PT, she was unable to progress through her PT exercises because of pain, so a fluoroscopically guided SIJ injection was performed using 1 mL of 0.2% ropivacaine and 1 mL of triamcinolone acetonide 40 mg for diagnostic and therapeutic purposes. The patient noted she was able to progress better through PT 6 days after the injection because of improved pain control. At 6-week follow-up, the patient stated that her pain was 100% improved and that she is maintaining her home exercise strengthening program. She also noted she was able to golf on back-to-back days again.


Purpose: To compare reflux, intraocular pressure (IOP) variation and pain following intravitreal (IV) injections using 30-gauge and 32-gauge needles in patients with retinal pathologies in Saudi Arabia.1) or 32-gauge (Gr2) needles. The amount of reflux of injected material, IOP before (IOP1) and five minutes after injection (IOP2) were measured. The patient-perceived pain score was assessed using a visual analogue score (VAS). Outcome variables were compared.Methods: A double-blind randomized clinical trial was conducted in 2018. Participants were randomized to receive IV injections of Ranibizumab using 30-gauge ] was significantly higher compared to Gr2 [22.1% ] (P=0.007). The median pain score was 1 in both Gr1 [interquartile range (IQR) 1.0: 3.0] and Gr2  (P=0.04). Among 56 eyes without reflux in Gr1, the IOP1 and IOP2 were 13.6±2.7 mmHg and 16.4±5.0 mmHg, respectively. Among 67 eyes without reflux in Gr2, the IOP1 and IOP2 were 13.6±2.9 mmHg and 17.0±5.2 mmHg, respectively. The change in percentage in IOP in Gr1 and Gr2 was not significantly different (Mann Whiney P=0.3).Results: The study sample was comprised of 86 eyes (86 patients) in each group. Gender (P=0.76), laterality (P=0.55) and age (P=1.0) were not different between groups. The reflux in GrConclusions: IV injection given by 30-gauge needle compared to 32-gauge needle resulted in greater patient-perceived pain and more reflux of injected material from the injection site. An increase in IOP was not associated with the gauge of the needle used for IV injection. Anti-vascular endothelial growth factor (VEGF) compounds are the initial treatment for diabetic macular edema (DME) with foveal involvement. These compounds can be used as isolated treatment or combined with photocoagulation ,2. IntraTo the best of our knowledge, studies have compared outcomes of intravitreal injections using the different gauge of needles for 27 vs 30 and 30 vs 33 gauge needles but not 30 vs 32 gauge needles in Arab patients ,12.We present the results of a double-masked randomized clinical trial (RCT) comparing the reflux, short-term IOP and the patient-perceived pain among separate groups of patients managed with 30-gauge vs 32-gauge needle for IV injection for different retinal pathologies.Patients with macular edema due to diabetic retinopathy, exudative age-related macular edema or retinal vasculopathy visiting our institution for intravitreal anti-VEGF injection comprised the study population. The institution research and ethics committee approved this study and this study adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from each participant.The field component of the study was carried out between January 2016 and December 2017. We included patients with retinal diseases mainly related to diabetes like DME and retinal vein occlusion needing IV injection. We excluded all not consenting to participate in the study.We assumed that the conjunctival reflux would occur in 11.3% of eyes that received IV injection with a 30-gauge needle whereas the reflux rate was in 1% of eyes treated with a 32-gauge needle . To achiPatients were randomly allocated to treatment with a 30-gauge needle (Gr1) or with a 32-gauge needle (Gr2). The Microsoft XL®’s random sample function was used to allocate patients in two arms of the study. The patient was not aware of the needle gauge used for intravitreal injection. The data analyzer was also masked about Gr1 and Gr2 identity.Patients with macular edema agreeing to undergo management by IV injection of anti-VEGF compounds were included in the study. Patients were excluded if they declined to participate, had received intravitreal injection previously or experienced a painful ocular condition in addition to macular edema.Demographic data were collected including patient age at presentation and gender. A retina specialist diagnosed the retinal pathology causing macular edema. The potential causes included age-related macular degeneration (AMD), DME or other retinal pathologies. The best-corrected visual acuity (BCVA) was recorded with ETDRS distance vision charts. Visual impairment was further graded as; normal functional vision (20/20 to 20/50), moderate visual impairment (<20/60 to 20/200), severe visual impairment (<20/200 to 20/400) and blind (<20/400) .The procedure for IV injection used in the present study has been previously published ,16. BrieReflux was evaluated when we inject and we notice under the magnification of the operating microscope that some fluids get out from the injection site after we removed the needle which is considered as +ve reflux. The IOP was measured before and five minutes after IV injection using applanation XL . The difference in IOP before and five minutes after injection was used to calculate the percentage proportion of IOP change.A visual analogue scale (VAS) was used to assess the patient-perceived severity of pain with a score from 1 to 10 .Data were collected using a pretested data collection form, audited and then transferred to an Excel spreadsheet . Data analysis was performed using Statistical Package for Social studies . For qualitative variable outcomes, univariate analysis with a parametric method was performed and frequencies and percentage proportions were calculated. For quantitative variables, the mean and standard deviation were reported for variables with a normal distribution. For a non-normal distribution, we estimated the median and interquartile range (IQR). To compare the pain score and IOP in two groups, we used a nonparametric method and estimated a two-sided P-value with the Mann-Whitney U test. The ordinal regression model was used to study the interaction of factors on the correlation of pain score to the gauge of the needle used for IV injection. A P-value less than 0.05 was considered statistically significant.We included 86 eyes of 86 patients in each group. The demographic and preoperative vision profile between groups was not significantly different Table .Reflux was noted in 30 [34.9% ] eyes of Gr1 and 19 [22.1% (95% CI 13.3: 30.9)] eyes of Gr2. The reflux seems to be similar in Gr1 and Gr2 (P = 0.07).Although the median of the pain score was 1 in both groups, the upper limit of IQR was more in Gr1 compared to that of Gr2. By using the nonparametric method of analysis, we noted that pain score was statistically significantly lower in Gr2 compared to Gr1 (Mann Whitney U test P =0.04).The IOP before and after IV injection is presented in Figure Data on the change in IOP and pain score in eyes without reflux were analyzed. There were 56 eyes in Gr1 and 67 eyes in Gr2 that did not have reflux after IV injection. In these eyes, the median pain score in Gr1 was 1.0 (IQR 0.25: 3.0) and 1.0 (IQR 0.0: 2.0) in Gr2. The pain score was significantly lower in Gr2 compared to Gr1 . The median IOP before and after injection changed by 20% (IQR 7 32.5) in Gr1 and 25%  in Gr2. The changes in IOP between groups were not statistically significant .Using a logistic regression model, we noted that correlation of pain score to the gauge of the needle (P = 0.05) was not influenced by gender (P = 0.3), reflux (P = 0.34), age (P = 0.64) and eye involved (P = 0.9).The reflux in eyes that underwent IV injection with a 30-gauge needle and 32-gauge needle for the treatment of retinal pathologies causing macular edema was not significantly different. The pain perceived by patients was significantly higher with a 30-gauge needle compared to a 32-gauge needle. The IOP measured five minutes after intravitreal injection using a 30-gauge needle was one in ten eyes, while it was one in eight eyes that were injected by using a 32-gauge needle. Female gender, older age, presence of reflux and underlying retinal pathology causing macular edema did not significantly influence the association of perceived pain to the gauge of the needle used for IV injection.This is perhaps the first study among Arab patients showing the outcomes of intravitreal injection using the different gauge of needles. As the use of preloaded injection cartridges for intravitreal drug delivery increases, our results support the use of smaller gauge needles and they perceive less pain as therefore more likely to be preferred by patients . AdditioReflux has been noted as less than 1% in in vitro studies . HoweverThe patient-perceived pain score in our study was on the lower scale in both groups. Proper counseling prior to IV injection could have resulted in a lower pain score. Prior counseling and female gender have been reported to influence patient-perceived pain . A studyIOP rise following 0.5 mg in 0.05 ml Ranibizumab could be due to an increase in volume or physiological alterations within the globe. This IOP rises five minutes after was marginal and not significant. Lemos et al. have reported that subconjunctival reflux contributes to lowering IOP soon after intravitreal injection . A greatThere were some limitations to our study. The volume of reflux was not quantified. All patients were treated while seated. Hence, caution is urged with generalizing our findings to patients treated while supine.With the rising population of diabetes and the trend of treating diabetic retinopathy with IV drug delivery, the selection of client-friendly but safe method is of interest to healthcare providers. The present study demonstrated that a 32-gauge needle compared to a 30-gauge needle was beneficial both for patients and service providers. The use of small-bore needles for intravitreal injection seems to reduce patient-perceived pain and maintain a lower level of side effects such as reflux and short-term rise of IOP.


How to prevent pain after the extraction of impacted teeth is a serious challenge for all patients. The purpose of this clinical trial was to investigate whether pre-emptive low dose of etoricoxib can reduce postoperative pain in patients undergoing third molars surgery.Patients were randomised to receive etoricoxib 60 mg or placebo 30 min before surgery. Post-operative pain was recorded using a visual analogue scale during 24 h within the post-operative period. The total dose of ibuprofen rescue intake was recorded. Kaplan–Meier curves and log-rank analyses were used to evaluate the proportion of patients without rescue analgesic.p < 0.05). The number of patients without analgesic rescue medication was significantly lower in the etoricoxib group than in the placebo group. The average amount of rescue medication in the etoricoxib group (0.4 ± 0.9 dose) was lower than that in the placebo group . Etoricoxib resulted in the long-term survival of patients without rescue analgesic (p < 0.001).Scores for the post-operative pain in the etoricoxib group were significantly lower than those in the placebo group during first 12 h (This study revealed that etoricoxib has a substantial pre-emptive analgesic effect, resulting in the reduced use of analgesics after third molar removal.Trial registration: Registered on ChiCTR1900024503. Date of Registration: 13/07/2019.The online version contains supplementary material available at 10.1186/s12903-021-01837-0. Acute pain caused by mandibular third molar removal is widely used to evaluate the efficacy of analgesics. Treatment of moderate or severe pain is usually given after the operation to reduce the dispersion of pain intensity measures by only including patients who need analgesics . Agents,NSAIDs contain two cyclooxygenase isoforms, namely, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) . COX-1 iEtoricoxib, as the COX-2 selective class of NSAIDs, can provide patients with effective painkillers who do not benefit adequately from first-line therapies . As the The pre-emptive analgesic of large doses of etoricoxib 120 mg) has been demonstrated to reduce pain after tooth extraction surgery . At pres20 mg hasThis study was designed as a randomized, parallel, double-blinded and placebo-controlled clinical trial from August 2019 to July 2020. Healthy patients scheduled to undergo surgical removal of an impacted horizontal mandibular third molar (Winter classification) were eligible for participation. Patients were included if they were older than 18 years old, had horizontal impacted teeth, did not take analgesics or anti-inflammatory drugs a week prior to the study. Patients were excluded if they took NSAIDs and COX-2 inhibitors; were pregnant or nursing; had other serious diseases, such as liver, kidney and cardiovascular diseases; had ulcers or bleeding in the digestive tract; had the history of GI bleeding and gastritis; had inability to express subjective discomfort symptoms; and suffered from dental caries or apical periodontitis with the adjacent teeth. The Patients were given standardised participant information sheets and signed written informed consent for their participation.All patients were informed about the study protocol and possible risks prior to any procedure. The patients were randomly divided into etoricoxib and placebo groups by Excel software. The etoricoxib group orally receive etoricoxib tablet 60 mg  or placebo group  30 min before surgery. The operator and the patients were blinded to the type of drugs administered. To prevent postoperative infection, 0.5 g dose of amoxicillin and 0.4 g dose of metronidazole tablets were taken orally, 3 times a day, for 5 days, and 1.0 g dose of azithromycin was given once a day for 5 days if allergic to amoxicillin.The patients were divided into two groups (placebo and 60 mg of etoricoxib) by Excel software to achieve randomisation. Allocation concealment was maintained using a sealed opaque envelope. The research assistant prepared the study drugs for the clinic nurses according to the randomisation list. A dedicated nurse, as non-treatment group members, gave the study drugs sealed in a similar package to the patients 30 min before the surgery.Based on the mean pain scores of previous study   were used to reduce intraoperative bleeding. Both groups received the same surgical procedure to reduce surgery-related bias. The buccal mucoperiosteal flap was elevated, the bone was removed and the tooth was sectioned. After the tooth was extracted, the alveolar tissue was scraped and rinsed with sterile saline solution. The wound was sutured with a 4–0 silk, and the suture was removed 1 week after the surgery. The operative time was calculated from flap dissection and suture after tooth extraction.An 11-point (0 to 10) visual analogue score (VAS) was used to evaluate pain . Postoperative pain was assessed and scored at 2, 4, 6, 8, 12 and 24 h after the operation. Ibuprofen (300 mg) was prescribed as the emergency analgesic only in the case of VAS > 3. The patients were asked to record their total consumption of ibuprofen (amount of tablets) within the first 24 h  and the time of the first analgesic rescue medication after the procedure was completed.p value less than 0.05 was considered statistically significant.Data were analysed with SPSS software . Independent t-test and Chi-square were used to determine significant difference between the two groups. The parametric outcomes were expressed as mean ± standard deviation (SD). The survival curves were estimated by the Kaplan–Meier method, and log-rank test was applied to compare differences between curves. Eighty patients were considered eligible Fig. . Twenty-Table Table P = 0.001). The overall survival time  in the etoricoxib group was longer than that in the placebo group (P < 0.001).The Kaplan–Meier curve in Fig. This study revealed that pre-emptive oral administration of etoricoxib (60 mg) is an effective pain management strategy compared to placebo after third molar surgery. Etoricoxib (60 mg) significantly reduced the pain scores during the first 12 postoperative hours, resulting in longer overall survival time  and reduced need of rescued analgesic consumption within 24 h after the surgery.About 60% of the patients suffered moderate pain, and 40% had severe pain, which had higher requirements for analgesia . InadequPre-emptive analgesia is a treatment initiated before the operation to prevent central sensitisation due to incision injury and other inflammatory reactions . Pre-empA low dose of etoricoxib (60 mg) showed significant analgesic effect and minimal side effects compared to placebo. In a previous study, 500 patients with osteoarthritis (OA) were administered with 60 mg of etoricoxib once a day for 4 weeks without prior medication washout. Disability and pain interference in daily activities were significantly improved . In addiIn our study, a low dose of etoricoxib (60 mg) was more effective than placebo in preventing pain at first 12 h post-surgery. Gupta et al. discovered that a low dose of etoricoxib (60 mg) was highly effective in controlling pain during fixed orthodontic appliance therapy . In an aIt should be noted that at the most pain intensity, the mean VAS measurements of treatment and placebo groups were 2.1 and 4.5 in this study. Maximum pain in this study was moderate in the placebo group. This may be related to the experience and skill of the surgeon. It is also clearly aware that the analgesic effect of low dose of etoricoxib should be specified to the mild/moderate surgery and should not be generalized for all cases at present.PGE2 was highly expressed in the peripheral tissue and central nervous system during and after the surgery; upregulated of PGE2 was associated with increased pain scores on the VAS scale . EtoricoThe total analgesic consumption at 24 h post-operation  in the etoricoxib group (0.4 ± 0.9) was less than that 1.1 ± 0.9) in the placebo group. The statistical difference between the two groups could be attributed to the analgesia, namely, etoricoxib, applied in this study. Through clinical trials, Malmstrom et al. found that patients with moderate or severe pain after removal of two or more third molars who took 120 mg of etoricoxib had reduced demand for rescue medication . Steffen.1 ± 0.9 This was a preliminary study with indispensable limitations. On the one hand, this study lacked a positive control group. This study found that low dose of etoricoxib was helpful to reduce postoperative pain after tooth extraction, but NSAID analgesics could also achieve this effect. Secondly, the postoperative follow-up time was only 24 h, and the pain assessment after 24 h was not observed. In the future study, we will extend the follow-up time and focus on the effect of etoricoxib compared with other NSAID drugs on postoperative pain after tooth extraction.This study revealed that a low dose of etoricoxib has pre-emptive analgesic effect, resulting in the reduced use of analgesics after third molar removal.Additional file 1. Trail protocol.


However, there are few reports regarding the clinical manifestations of N2O users when they present to the emergency department (ED). The purpose of this study was to describe the clinical presentations, the associated illicit substances used in combination, and the outcomes in N2O users visiting the ED. This was a retrospective observational cohort study. All N2O adult users admitted to the ED at Linkou Chang Gung Memorial Hospital between 2012 and 2020 were included. Demographic variables, clinical symptoms, and examination results were collected from medical records. Univariate comparisons were conducted between pure N2O users and combined illicit drug users. A total of 40 patients were included, 24 of which were pure N2O users. Limb weakness and numbness accounted for the majority of chief complaints. Neurologic symptoms were the most common clinical manifestations (90%). A more severe ED triage level, faster heart rate, greater agitation, and cardiovascular symptoms were significantly noted in combined illicit drug users. In ED, limb numbness/weakness should arouse physicians’ awareness of patients using N2O. Combined use of N2O and illicit drugs can cause great harm to health.Today, the concomitant abuse of nitrous oxide (N The lifetime prevalence of N2O abuse has been reported to range between 2% and 15.8% among adolescents and young adults [2O as a very common drug used in the UK and US  [2O remains problematic. For example, there has been a sharp increase in the number of patients with neurological disorders associated with recreational use of nitrous oxide (N2O) in China [2O abuse in Taiwan. However, due to increasing cases of death after N2O abuse found by autopsy, the Taiwan government had added N2O to the controlled substance list and forbidden its recreational use by law since 30 October 2020.Today, the abuse of nitrous oxide NO is evid2O is not associated with significant harm, the adverse effects of N2O abuse are well known to include neurologic sequelae such as myeloneuropathy and subacute combined degeneration, as well as psychiatric effects such as psychosis and mood changes [2O users when they present to the emergency department (ED). In the ED, physicians do not always know the kinds of substances used by patients due to self-reporting. The concomitant use of N2O with other illicit drugs has been reported in the literature [2O users present to the ED. Therefore, describing the clinical picture of N2O users and determining concomitant use of other illicit drugs may help ED physicians to provide better care to patients. Thus, the purpose of this study was to describe the clinical presentations, the associated illicit substances used in combination, and the outcomes in N2O users seeking medical help in the ED.Although the use of N changes ,6. Other changes , venous  changes , pulmona changes , and eve changes ,11. Howeterature ,13,14,152O adult users admitted to the ED at Linkou Chang Gung Memorial Hospital (LCGMH) during the study period (2012–2020) were included. LCGMH is an academic teaching hospital located in north Taiwan, with 3700 beds and approximately 14,000 monthly ED visits. The hospital ethics committee  granted approval for this study.We designed a retrospective observational cohort study. All NWe designed a standardized abstraction form to retrospectively collect all variables from electronic medical records. The following variables were collected: patient’s demographics including age and gender, vital signs at ED triage, ED triage level, patient’s reason for ED visit, positive physical examination of any neurological, psychiatric, cardiovascular, respiratory, or other symptom upon ED admission, patient’s disposition, poison severity score, and outcomes. ED triage level is based on the Taiwan Triage and Acuity Scale (TTAS), a five-level scale used for disease urgency assessment in the study, which is a modification of the Canadian Triage and Acuity Scale (CTAS). There are five levels of urgency: Level 1, resuscitation; Level 2, emergency; Level 3, urgent; Level 4, less urgent; and Level 5, non-urgent . LaboratExaminations such as magnetic resonance imaging, nerve conduction velocity tests, and evoked potentials were arranged after medical ward admission. The results of these examinations were also abstracted.2O users and concomitant illicit drug users.Since the data distribution did not meet the normality assumption, data are expressed as percentages or medians (25th–75th percentiles) unless otherwise indicated. The Mann–Whitney U-test for numerical variables and the chi-squared test for categorical variables were used in univariate comparisons between both study groups: pure N2O users with a median age of 25.5 (21.5–29) years. A total of 16 patients  were concomitant illicit drug users, with a median age of 25 (22–28) years. A total of 11 patients had self-reported N2O exposure amount. The average usage frequency of N2O was 4.9 ± 2.7 times per week. The average dose of use was 14.9 ± 8.7 bullets per week . The mean duration of N2O exposure was 25.1 ± 30.5 months. The demographic characteristics of the patients are listed in A total of 40 patients were included in the study, 24  of which were pure N2O users. On the other hand, the corresponding values were 43.7% and 6.25%, respectively, in concomitant illicit drug users. Neurologic symptoms were the most common clinical manifestations . Paresthesia and limb numbness (65%), limb weakness (47.5%), and unsteady gait (37.5%) were commonly reported.Limb weakness was reported by 29.17%, while limb numbness was reported by 20.83% of pure Np < 0.01) and faster heart rate , as well as more agitation , and cardiovascular symptoms such as palpitation  than pure N2O users. In contrast, there was no statistically significant difference in other neurologic or respiratory symptoms, as well as in poison severity score (PSS) and patient outcome, between both groups.Concomitant illicit drug users presented with a more severe ED triage level . Among the 10 patients with elevated white blood cell count, two patients had infections at the same time, and two patients had acute kidney injury and rhabdomyolysis at the same time.Laboratory investigation results are shown in n = 11), MDMA (n = 5), cathinone (n = 4), methamphetamine (n = 2), and cannabinoids (n = 1).However, eight of 21 (38%) patients initially had a low serum vitamin B12 level (<211 pg/mL). Of the 14 patients checked for serum homocysteine, 12 (85.7%) were found to have a level exceeding the upper limit of 12.42 mmol/L. However, there was no statistically significant difference in serum homocysteine level between both groups. Concomitantly used substances included ketamine  tests; 2 were normal, and the other 15 exhibited sensory motor polyneuropathy and demyelinating polyneuropathy. Five patients had their evoked potentials (EP) examined; two were normal, whereas the other three had a peripheral sensory conduction defect with sensory polyneuropathy.2O user and two concomitant illicit drug users admitted to the ICU. We observed one severe case  with severe motor nerve denervation, lower-limb muscle weakness (MRC grade 0–2), and respiratory muscle weakness, as well as subsequent aspiration pneumonia, then acute respiratory failure. The patient was managed with emergent intubation in the ED and admitted to the ICU. Upon recovering from the pneumonia, he was transferred to the rehabilitation ward for neurological sequalae, with a total of 87 days of admission. There were two concomitant illicit drug users admitted to the ICU. The first case was a 21-year-old male who had concomitant abuse of N2O, LSD, and cathinone for one day. The patient presented with visual and auditory hallucination then sudden collapse, lying on the ground for an unknown period. When the patient was brought to the ED, he was comatose with hyperthermia, tachyarrhythmia, and hypertension; the initial survey revealed rhabdomyolysis, acute kidney injury, and demanding myocardial ischemia. He ended up with emergency intubation and ICU admission. Another case was a 27-year-old male who abused N2O and cathinone in an unknown amount. The patient then had a sudden consciousness change with generalized tonic convulsion. Due to poor consciousness in the ED, he was intubated for airway protection and admitted to the ICU as well.There were one pure N2O can lead to acute intoxication and chronic neurologic or psychiatric sequelae. N2O is more water-soluble than oxygen. Once inhaled, it can rapidly diffuse and enter the bloodstream, resulting in dilution of the oxygen volume and decreased oxygen delivery. Upon acute intoxication, it may induce seizures, arrhythmia, respiratory irritation, or even respiratory or cardiac arrest. Inhaling N2O in a closed space can lead to asphyxia [2O inhalation have also been reported [2O inhalation in a short period with or without concomitant illicit drug use.Nasphyxia . Interstreported ,18. Cons2O users presented to the ED with limb weakness or numbness, regardless of whether they were pure N2O users or concomitant illicit drug users. Therefore, this parameter is important for ED physicians to identify N2O use. N2O interferes with the vitamin B12 metabolic pathway, leading to reduced recycling of homocysteine to methionine. Methionine is required for nerve myelination. Long-term N2O abuse can lead to vitamin B12 deficiency, thus causing demyelination within the central and peripheral nervous systems [2O exposure [2O intoxication can lead to severe neurological sequalae such as myeloneuropathy, subacute combined degeneration, peripheral neuropathy, and myelopathy [We found that 50% of N systems . Additioexposure . Consequelopathy . The moselopathy .2O users and concomitant illicit drug users. There has been evidence of steadily increasing N2O recreational use [To the best of our knowledge, this was the first study to describe and compare the ED clinical presentations of pure Nonal use ,22. Almoonal use . Due to 2O inhalation causes an increase in the level of the serum homocysteine. Elevated homocysteine level is an independent risk factor for cardiovascular events [2O abuse leads to ischemic stroke, myocardial infarction, and venous thrombosis in adolescents which are previously reported [2O concomitant drug abuse will cause tremendous hazard to the cardiovascular system and cause more toxic effects.Nr events . Previour events . Recreatreported ,27,28,29reported . Amphetareported . Novel preported ,33,34. AAlthough the study found no statistically significant differences in poison severity score, disposition, or admission length between both patient groups, a more severe triage level, faster initial heart rate, greater agitation, and more cardiovascular symptoms were significant in concomitant illicit drug users. We believe that, under the effect of multiple stimulants, a “fast toxidrome” was more evident in these patients. Due to apparently abnormal vital signs and a more severe triage level, we assume that ED physicians paid more attention to these patients with immediate and proper treatment. This may explain the lack of a significant difference in outcomes between both patient groups. For example, the higher white blood cell count and Hb level recorded in concomitant illicit drug users may have led ED physicians to administer more intravenous fluid to stabilize the patients.2O intoxication are not specific. Due to its short half-life and rapid clearance, it is difficult to detect N2O in screening tests. A decreased level of vitamin B12 and increased levels of methylmalonic acid and homocysteine can be found in patients with chronic N2O intoxication. Due to the poor correlation between serum and tissue levels, functional vitamin B12 deficiency can occur in the presence of a normal serum vitamin B12 level [2O users have reportedly self-treated these deficiencies with cyanocobalamin, which can also affect the lab test results [2O abusers was similar to other studies [Laboratory tests for N12 level . Some N2 results . Accordi results . In our  studies . A total studies ,39.2O exposure. The N2O inhalation amount and frequency were not recorded in most cases; hence, their relationship with the evaluated parameters was not possible. There is no formal protocol or guideline for N2O intoxication management in our hospital. Instead, examination surveys and management are currently based on the ED physicians’ clinical judgement. There is no confirmatory chemical analysis in case of urinary positive screening of drugs of abuse, which may cause false positive results. The pattern of concomitant illicit drug use may differ across countries or regions; therefore, this study’s findings  of a fast toxidrome should be interpreted cautiously. Due to the limitations mentioned above, we will consider prosecuting a prospective observational study in the future.Our study had some limitations. One of the major limitations was the low patient number. Therefore, interpreting the results, such as prevalence, was not suitable. Therefore, the finding of high prevalence of concomitant abuse in our study may be biased as well, even though our patient number was relatively bigger than or similar to the previous studies ,37,39,402O is increasing steadily, especially in adolescents and young adults. Almost half of N2O abusers are concomitant illicit drug users in the study, and this has become an obvious public health issue. In the ED, limb numbness/weakness should arouse physicians’ awareness of patients using N2O. For patients with fast toxidromes, ED physicians should also be aware of the combined use of stimulants.The recreational use of N2O intoxication can lead to severe neurological sequalae, and combined illicit drug use can cause great harm to health. ED physicians should pay additional attention to these patients with immediate and proper treatment.N


The aim of this study was to compare thoracic epidural analgesia (TEA) with transversus abdominis plane (TAP) block in post-operative pain management after laparoscopic colon surgery.One hundred thirty-six patients undergoing laparoscopic colon resection randomly received either TEA or TAP with ropivacaine only. The primary endpoint was opioid requirement up to 48 h postoperatively. Intensity of pain, time to onset of bowel function, time to mobilization, postoperative complications, length of hospital stay, and patients’ satisfaction with pain management were also assessed.p < 0.001). On the first two postoperative days (POD), the balance shifted to opioid consumption being smaller in the TAP group: on POD 1  and on POD 2 . There were no differences in postoperative nausea/vomiting or time to first postoperative bowel movement between the groups. No direct blockade-related complications were observed and the length of stay was similar between TEA and TAP groups.We observed a significant decrease in opioid consumption on the day of surgery with TEA compared with TAP block (30 mg vs 14 mg, TEA is more efficient for acute postoperative pain than TAP block on day of surgery, but not on the first two PODs. No differences in pain management-related complications were detected.The online version contains supplementary material available at 10.1007/s00464-021-08647-z. Effective pain management with minimal adverse effects is crucial for successful postoperative recovery. Recently, the standards of patient care after elective surgery worldwide have turned toward enhanced recovery after surgery (ERAS) pathways, which highlight the importance of effective but opioid-sparing methods in pain relief . EpiduraIn laparoscopic colon surgery, the benefit from epidural analgesia is even more unclear. A meta-analysis in 2013 concluded that epidural analgesia had some beneficial effects on pain relief and return of bowel function but no effect on length of stay (LOS) . FurtherTo search for new insights, many studies have been conducted on diverse analgesic techniques. In a meta-analysis, transversus abdominis plane (TAP) block was shown to reduce opioid consumption and to improve bowel function after laparoscopic colorectal surgery . In anotThe most important patient-centered outcomes after colonic surgery are return to normal life or recovery without surgical complications or prolonged hospitalization, life quality, and, in the immediate postoperative period, adequate pain management with minimal adverse effects. When pain management methods, such as epidural analgesia and TAP block, are studied, it is pertinent to concentrate on outcomes related to analgesia. As it would be unethical to let any patient to suffer from intense pain without supplementary analgesics, opioid consumption is often used as a proxy for the adequacy of analgesia.Thoracic epidural analgesia (TEA) is a technique associated with rare, but potentially serious, adverse effects. Therefore, to justify using it as a component of perioperative management of laparoscopic colon resection patients, it would have to be associated with significant benefit for pain control. In different types of acute postoperative pain, a decrease of 18–35% in opioid consumption has in most studies been considered to represent a minimal clinically important benefit . Thus, wThe aim of this study was to compare ropivacaine-based TEA with TAP block for postoperative pain management in patients undergoing elective laparoscopic colon surgery. As the adverse effects of pain management are related to size of opioid dose used , 17, opiWritten informed consent was obtained from all study patients. This trial was a prospective parallel group randomized superiority trial comparing TEA with TAP block in patients undergoing elective laparoscopic colon surgery, with a 1:1 allocation ratio. Patients were recruited from January 2018 until May 2019. The trial was registered prior to patients’ enrollment in EU Clinical Trials Register (EudraCT-nr: 2017-001714-29). The trial was performed in Helsinki University Hospital and Central Finland Central Hospital. The research plan was approved by the local ethics committee of Helsinki University Hospital and by the institutional review board at both Helsinki University Hospital and Central Finland Central Hospital. This manuscript adheres to the relevant CONSORT guidelines.All patients scheduled for elective laparoscopic colon resection were considered as candidates for inclusion. The exclusion criteria were severe renal insufficiency (GFR < 30 ml/min), severe hepatic insufficiency (TT ≤ 50%), severe COPD (FEV1 > 30%), metastatic malignancy, hematologic disease or a congenital clotting disorder, preoperative opioid use, age under 18 years, pregnancy or breast-feeding, hyper-reactivity toward ropivacaine, estimated risk for conversion to open surgery > 50%, some other contra-indication to epidural catheterization .Recruitment of patients took place between January 10, 2018 and July 1, 2019.If eligible, patients were given detailed written and verbal information on the trial. Based on this, informed written consent was obtained and patients randomly enrolled in blocks of 16 (right- and left-sided colectomies separately) for either TEA or TAP block. The randomization sequence was generated by a web-based service. The sequence was concealed in opaque numbered envelopes, which were opened in numerical order . In view of ethical issues associated with an invasive procedure and the insertion of epidural catheters for patients in the TAP group, the study was not blinded to patients or to the treating physicians or nurses. Furthermore, if placebo epidurals had been used, this would have been revealed to patients and personnel in the recovery room due to lack of any local anesthetic effect (numbness) on the truncal skin. The patients’ data were coded in CRF; therefore, outcomes assessors were blinded to the interventions.All patients were treated according to our ERAS program, optimized for elective colon surgery. Preoperative preparations were consistently performed for all enrolled patients, both at the preoperative polyclinic and at the admitting unit for elective surgery. Clear liquids were allowed up to 2 h and solids up to 6 h prior to induction of anesthesia. Two hours before anesthesia, carbohydrate drinks were given. For antibiotic prophylaxis, cefuroxime–metronidazole single dose was administered after anesthesia induction. For patients with hypersensitivity to cephalosporin, ciprofloxacin was used. If the surgery lasted longer than 3 h, another dose of cefuroxime was given. Prophylaxis against thromboembolism was accomplished with thigh-high compression stockings and enoxaparin starting 6 h after operation.All patients received paracetamol 1 g orally or intravenously at the pre-surgery unit or before induction of anesthesia. For preoperative anxiety, 5–10 mg of temazepam was given orally on request 1 h before induction of anesthesia.For anesthesia induction, propofol 1–2.5 mg/kg was given. General anesthesia was maintained with an inhalation anesthetic (sevoflurane or desflurane in oxygen and air mixture 0.8–1.2 MAC) or intravenously administered propofol. During anesthesia, 0.05–0.1 mg iv of fentanyl boluses was administered as an analgesic. Rocuronium was used as a muscle relaxant 0.3–0.5 mg/kg during induction and 10–20 mg iv boluses for muscle relaxation maintenance. At the end of surgery, relaxation was reversed by administration of neostigmine–glycopyrronium (Glycostigmin®) 1.0 ml or sugammadex 1–4 mg/kg iv. All patients received 5 mg of dexamethasone at anesthesia induction for postoperative nausea/vomiting (PONV) prophylaxis. Postoperatively, PONV medication was given on request according to the hospital guidelines. Depending on the patient's co-morbidities, non-invasive or invasive blood pressure monitoring was performed, aiming at normotension . If necessary, anesthesia-induced hypotension was treated with norepinephrine infusion.As fluid therapy, Ringer’s acetate solution 2–4 ml/kg/h infusion was administrated intravenously during surgery.Intraoperative bleeding of less than 500 ml was not replaced; for bleeding of 500–1000 ml, Ringer's acetate solution 1:1 was administered; for bleeding higher than 1000 ml, colloid solution (4% Albumin) was considered in addition to Ringer’s acetate solution. Anemia (hemoglobin below 85 g/l) was corrected by administering a red blood cell transfusion. After surgery, Ringer's solution was infused slowly (30–50 ml/h).Patients were weaned from the ventilator and extubated in the operating room. Nasogastric tubes were applied only at surgeons’ request and were removed before extubation. Urine catheters were removed on the first or second postoperative day (POD). Drains were not routinely used.For postoperative analgesia, all patients received paracetamol 0.5–1 g × 3 po/iv, starting immediately after surgery, and ibuprofen 400–800 mg × 3 po from the 1POD. NSAIDs have not been administered in cases of renal injury (postoperative oliguria or creatinine raising on the 1POD more than 50% from preoperative level). Opioids were given only on request  0–10, for pain NRS > 3 at rest or for pain NRS > 5 on exercise): oxycodone 0.05 mg/kg iv (only in the recovery room), 0.07–0.1 mg/kg im or 0.15–0.2 mg/kg po was used.In the recovery room, fluids were given orally 1–1.5 h after surgery (in the absence of nausea). The patients were mobilized in the recovery room 1.5–2 h after surgery.For patients in the TEA group, epidural catheters were placed preoperatively. Immediately after this, lidocaine and epinephrine (20 mg/ml + 5 µg/ml) solution (3 ml) was administered via epidural catheter. After 5 to 10 min, the increase in heart rate and numbness of the lower limbs were assessed in order to detect erroneous intravenous or intrathecal catheter placement.Ropivacaine 2 mg/ml infusion was started at 2–4 ml/h at anesthesia induction. At the end of surgery, the infusion rate was increased to 6–8 ml/h. Postoperatively, the infusion rate was adjusted, according to pain relief response and side effects, to 2–12 ml/h, continuing up to 48 h postoperatively.All surgeries were performed by specialized colorectal surgeons. Bilateral TAP block was administered intraoperatively at laparoscopy, directly after insufflation and insertion of the first trocar and camera. Under good visibility, an 18-gauge needle was inserted through skin until two ‘pops’ had occurred, indicating entrance into the TAP plane . The ropivacaine was infused as a bolus of 40 ml, 5 mg/ml, or 3.75 mg/ml (20 ml per side). Before incision, surgical wounds were infiltrated with ropivacaine solution 5 mg/ml, 15 ml. The maximum single dose of ropivacaine was 4 mg/kg.The primary outcome measure was opioid consumption during the first 48 h postoperatively. Secondary outcome measures included pain intensity on a numerical rating scale . In the recovery room, pain intensity was measured 30 min after arrival and then every hour until the patient was discharged to the ward. In the ward, the pain NRS score was measured for each consecutive 6-h block. Means of the first and second 6-h blocks and third and fourth blocks were calculated and used for further analysis. Additionally, the maximal daily pain NRS scores were collected. At the time of discharge, patients evaluated their satisfaction with pain management as a whole .At 2 to 4 weeks postoperatively, all patients were contacted either by phone or at the outpatient clinic during a follow-up visit and asked to complete a form with questions evaluating pain sensations, pain intensity, need for pain medication, performance of daily activities, and any limitations of these due to postoperative abdominal pain.Other secondary outcome measures included first postoperative bowel movement (gas or solid excrement) post-operatively, intraoperative fluid balance, postoperative complications (recorded by Clavien–Dindo classification), readmission rate, and LOS. Furthermore, the power of epidural analgesia was compared in pre-hoc-designed subgroups for right and left colectomies.α = 0.05 and 1 − β = 0.9, 69 patients per group  would be needed to show this difference. Taking into account the potential dropout rate of 15%, the sample size was set at 160.When this study was planned, there were no applicable direct comparison studies between epidural analgesia and TAP block in laparoscopic colon surgery available as a basis for the sample size calculation. We wanted to be able to detect a 20% decrease in opioid consumption. In a recent study, the mean PCA morphine consumption after laparoscopic colon resection was 31.3 mg (standard error (SE) 3.8) in the TAP group. Taking into account the transformation from SE to SD, conversion from morphine to oxycodone and the move from iv to im/po administration, an SD of 18.6 was chosen for the power calculation. With α of 0.05. The distribution of the patient population was tested with the Kolmogorov–Smirnov test. Accordingly, both non-parametric tests  and one-way ANOVA were used to analyze continuous variables. Categorical variables were analyzed by Pearson’s chi-squared test and Fisher’s exact test.Statistical analyses were performed using IBM SPSS Statistics 22 software. Statistical significance was set at a two-sided One hundred and sixty patients who gave written informed consent were enrolled and randomly assigned to TAP block or TEA; 24 patients dropped out of the study after enrollment for various reasons Fig. ; 136 patp < 0.001   in postoperative pain management at discharge was 2.8 (range 0–3) in both groups.p = 0.11, data not shown). In agreement, questionnaires revealed no difference in daily pain sensation (pain NRS scores) or in pain-associated disability  between groups.At 4 weeks postoperatively, median overall satisfaction scores  in pain management were similar between groups  and left colectomies (n = 70). There was no difference in overall opioid consumption (cumulative mean opioid requirement) during the first 48 h postoperatively in either group between right and left colectomies (data not shown).The power of epidural analgesia was compared in pre-hoc-designed subgroups for right (p = 0.027); cumulatively on POD 1, 47 (72%) in the TEA and 45 (63%) in the TAP groups , and for POD 2, 63 (97%) in the TEA and 69 (97%) in the TAP groups .On the day of surgery, bowel function onset (gas or solid excrement) was registered for 10 patients (15.4%) in TEA group and 3 (4.2%) in TAP group  were mobilized, either in the recovery room or in the ward. On PODs 1 and 2, all (100%) were mobilized in the TEA group and all but one (99%) in the TAP group. Reasons for unsuccessful mobilization on the day of surgery were PONV, abdominal pain, weakness of lower limbs (in TEA group), confusion, and anal hemorrhagia.On the day of surgery, 84.6% in the TEA group and 90% of patients in the TAP group .There was no difference in mean fluid intake between the TEA and TAP groups on the day of surgery  complications and re-operations was higher in the TAP than in the TEA group, although not statistically significantly. The rate of non-surgical complications did not differ between groups (Table p = 0.4). Similarly, rates of 30 days re-admissions were equal between groups  ; a continuing TEA infusion was compared with a single-shot TAP block , and the results of this study can be applied for colorectal patients.In conclusion, this is the first study to compare purely ropivacaine-based TAP block and TEA in pain management after elective laparoscopic colon surgery in the setting of an RCT and performed within an ERAS program. We report a significant reduction in opioid consumption and faster onset of bowel function on the day of surgery with TEA compared to TAP block. However, on POD 1, TAP block was not inferior to TEA in both opioid demand and bowel function. On POD 2, the opioid demand was significantly reduced with TAP block compared with TEA. Overall patient satisfaction with pain management was similar between groups and no blockade-related complications were detected.Supplementary file1 (XLSX 41 KB)Below is the link to the electronic supplementary material.