Utilizing patient-specific instrumentation during total knee arthroplasty has gained popularity in recent years with theoretical advantages in blood loss, intraoperative time, length of stay, postoperative alignment, and functional outcome, amongst others. No study has compared acute perioperative measures between patient-specific instrumentation and conventional instrumentation in the bilateral total knee arthroplasty setting. We compared patient-specific instrumentation versus conventional instrumentation in the setting of bilateral total knee arthroplasty to determine any benefits in the immediate perioperative period including surgical time, blood loss, pain medication use, length of stay, and discharge disposition. A total of 49 patients with standard instrumentation and 31 patients with patient-specific instrumentation were retrospectively reviewed in a two-year period at one facility. At baseline, the groups were comparable with respect to age, ASA, BMI, and comorbid conditions. We analyzed data on operative time, blood loss, hemoglobin change, need for transfusion, pain medication use, length of stay, and discharge disposition. There was no statistically significant difference between groups in regards to these parameters. Patient-specific instrumentation in the setting of bilateral total knee arthroplasty did not provide any immediate perioperative benefit compared to conventional instrumentation. Total knee arthroplasty (TKA) is a common orthopedic procedure used to treat osteoarthritis of the knee. Of patients undergoing TKA, approximately one-third will have bilateral joint disease . BecausePSI first became popularized as an alternative to computer-assisted TKA to allow for more predictable alignment and theoretical improvement in long-term implant survival. Computer-assisted TKA requires increased operating costs and increased surgical time due to system setup, results in difficulty registering bony landmarks and fractures from pin insertion, and requires a learning curve to appropriately understand the protocol . PSI aimThe results of unilateral TKA utilizing PSI have been mixed. While some studies show improved alignment with PSI postoperatively, the consensus appears to be that PSI does not improve the accuracy of alignment of the components in TKA compared with conventional instrumentation , 10. In There are limited data available regarding PSI in the bilateral total knee arthroplasty setting. This retrospective review aims to determine the advantages associated with PSI in the bilateral TKA setting.The medical records of patients who underwent simultaneous bilateral total knee arthroplasty at an urban teaching hospital in the Midwest between July 8, 2013, and July 8, 2015, were reviewed. Using reporting functions available in electronic medical records, charts were identified using ICD9 715.9x  and CPT 27447 . Degree of deformity was unable to be discerned due to the retrospective nature of the review.Inclusion criteria included patients with the above diagnosis and procedural codes, aged ≥ 18 or ≤89, without any previous knee arthroplasty procedures. Exclusion criteria included patients aged < 18 or >89, a diagnosis of rheumatoid arthritis, posttraumatic arthritis or inflammatory arthritis of the knee (ICD9 714.x), previous total knee arthroplasty procedure, and patients undergoing revision arthroplasty or patients undergoing unicompartmental or patellofemoral joint arthroplasty. A total of 91 bilateral knee arthroplasty procedures were performed between the studied time period. Of those, a total of 80 patients were included in the study who met the inclusion criteria and did not exhibit any exclusion criteria. The remaining 11 patients were excluded secondary to either undergoing bilateral patellofemoral arthroplasty and bilateral unicompartmental arthroplasty or had a diagnosis of rheumatoid, posttraumatic or inflammatory arthritis.Two groups were created using the above parameters. Group 1 included all patients who met the inclusion criteria while not exhibiting any exclusion criteria between the studied time period and had the procedure performed using standard instrumentation. Group 1 included a total of 49 patients. Group 2 included all patients who met the inclusion criteria while not exhibiting any exclusion criteria between the studied time period and had the procedure performed using PSI. Group 2 included a total of 31 patients.The charts were reviewed according to the following outcomes: surgical time (defined by time of incision to skin closure), tourniquet time (defined by time just prior to incision to implant placement and cement bonding), blood loss (assessed via anesthesia department by suction fluid volume during the case), change in hemoglobin up to 48 hours postoperatively, number of units of packed red blood cells transfused, morphine milligram equivalent used, length of stay, and discharge disposition. The calculation for morphine milligram equivalent used up to 24 hours post-op and from 24 to 48 hours post-op including morphine, dilaudid, demerol, oxycodone, hydrocodone, oxycontin, and tramadol is outlined by Von Korff et al. . DemograThese surgeries were performed by a cohort of five practicing attending orthopedic surgeons with high volume in total knee arthroplasty (defined by >70 procedures per year), utilizing a medial parapatellar approach with identical multimodal pain management protocols with the exception of the utilization of a periarticular injection of ropivacaine with epinephrine or liposomal bupivacaine in only 48/80 patients (31 standard and 17 PSI), solely based on surgeon preference . SurgeonPSI utilized was MRI-based cutting jigs defined from the patient's anatomy based on preoperative MRI. Implants used in these cases were from the Zimmer Persona or Natural system . Implants used in all other cases were off-the-shelf Stryker Triathlon , Zimmer Persona, or Zimmer Natural systems. Each patient received identical posterior stabilized cemented implants between the right and left sides, without the use of stems or augments. The decision to utilize Stryker or Zimmer implants in the standard instrumentation group was made by surgeon preference.t-test.The study was designed to have 80% power to detect a 0.6 standard deviation difference between the groups, resulting in 30 patients per group to achieve statistical significance at alpha 0.05, two-tailed, using an independent The comparison of demographic information and personal characteristics of the two groups was similar , includiLength of surgery from incision to closure of both incisions was similar between the two groups (99 minutes for standard and 102.2 minutes for PSI). Average tourniquet time was also similar (60.3 for standard and 62.7 for PSI).Intraoperative blood loss was slightly less for standard instrumentation, 253.8 mL, versus PSI, 275 mL. The change in hemoglobin from preoperative measurements to postoperative day 1 and then to postoperative day 2 was similar as well. These values were 3.14 and 1.31 for standard instrumentation and 3.07 and 1.14 for PSI, respectively. The need for blood transfusion was also comparable. 46.94% of the standard instrumentation group and 48.39% of the PSI group did not require a transfusion. Of those requiring a transfusion, 4.08% of the standard group and 3.23% of the PSI group required only 1 unit of PRBCs. 38.78% of the standard group and 45.16% of the PSI group required 2 units of PRBCs. Interestingly, 10.20% of the standard group required >2 units of PRBCs, while only 3.23% of the PSI group required >2 units of PRBCs. The decision to transfuse was based on a combination of clinical findings  with a hemoglobin concentration of <8.0 g/dL. No specific cutoff for hemoglobin or hematocrit was used as sole determinants to transfuse.Mean morphine milligram equivalent was nearly identical between the two groups for the periods from surgery to 24 hours after surgery, from 24 to 48 hours from surgery, and for the entire 48 hour period. The MME for the entire 48 hours postoperatively for the standard group was 68.7 mg and was 66.1 for the PSI group.The average length of stay between the two groups was 4.5 days for the standard group and 4.4 days for the PSI group. The proportion of patients discharging in less than 3 days, between 3 and 5 days, and greater than 5 days was also comparable across the board.In regards to discharge disposition, 55.1% of patients in the standard group were discharged home, while only 32.26% of the patients in the PSI group were discharged home. 28.57% of standard and 25.81% PSI were discharged to inpatient rehab. Only 16.3% of patients in the standard group required a skilled nursing facility, while 41.94% of the patients in the PSI group required a skilled nursing facility.Of note, there were no major acute perioperative complications including heart attack, stroke, periprosthetic fracture, acute wound complications, or infection, amongst others.Given the increasing number of joint replacement procedures performed, in particular, total knee arthroplasty, newer innovations have been developed with the aspiration to increase efficiency and improve outcomes. These innovations include, but are not limited to, computer-assisted navigation, patient-specific instrumentation, and patient-specific custom implants. Studies have been performed comparing these newer modalities with standard procedures, but none have been performed in the setting of bilateral total knee arthroplasty. Given the inconsistent results regarding these newer advances in technology compared to standard procedures in the unilateral arthroplasty setting, our aim was to determine the immediate perioperative benefit of patient-specific instrumentation compared to standard instrumentation.In terms of operative time, one study cited an overall surgical time average of 6.7 minutes shorter with PSI, while another cited 13 minutes shorter with PSI , 12. On Noble et al. also reported a reduction in inpatient length of stay as well as intraoperative blood loss using PSI for unilateral TKA. His findings suggest reduced blood loss and shorter length of stays for PSI . HoweverLimited data exist in regards to pain control utilizing PSI. In this study, we found no statistically significant difference amongst PSI and conventional instrumentation. Mean morphine equivalent use was essentially equivalent for both groups.While the immediate perioperative measures in this study fail to identify a definitive advantage of PSI over conventional instrumentation, there is a theoretical advantage in terms of cost analysis of utilizing PSI. However, a recent study by Barrack et al. failed to identify a cost benefit in regards to utilizing PSI over conventional instrumentation. His study identified that while the cutting guides had significantly lower total operative time and instrument processing time, the estimated $322 savings was overwhelmed by a $1,500 additional cost of the MRI and the PSI cutting guide , 24. NunOne limitation to this study is the lack of outcomes involving functionality, alignment, or patient satisfaction. While some studies show improved alignment in the unilateral setting with PSI postoperatively, the general consensus appears to be that PSI does not improve the accuracy of alignment of the components in TKA compared with conventional instrumentation , 10. In While new innovations are being developed to provide a more efficient, cost effective, and outcome driven improvement in total knee arthroplasty, this study failed to identify any advantages to PSI in the bilateral total knee setting in regards to immediate perioperative measures. Certainly, there exist theoretical advantages that are difficult to quantify, and additional studies may provide a better understanding of these.


Until now, nonivamide/nicoboxil ointment has not been tested in a randomized trial for the treatment of acute non‐specific low back pain.PI) difference between pre‐dose baseline and 8 h after the first application].This phase III randomized, double‐blind, active‐ and placebo‐controlled, multi‐centre trial investigated efficacy, safety and tolerability of topical nicoboxil 2.5%/nonivamide 0.4% for treatment of acute non‐specific low back pain [primary endpoint: pain intensity (n = 805), 18–74 years of age were treated for up to 4 days with nicoboxil 2.5%/nonivamide 0.4%, nicoboxil 2.5%, nonivamide 0.4% or placebo ointment. Pre‐dose baseline pain intensity  was reduced by 1.049 points with placebo, by 1.428 points with nicoboxil, by 2.252 points with nonivamide and by 2.410 points with nicoboxil/nonivamide after 8 h . At the end of treatment, the combination provided more pronounced PI reduction (3.540 points) compared with nicoboxil , nonivamide  and placebo . Low back mobility scores on Day 1 were better for the combination compared with all other treatments (p < 0.044); on Day 2–4, scores were better than for placebo and nicoboxil (p < 0.003). Patients assessed efficacy of the combination as greater than of the comparators (p ≤ 0.0129). All treatments were tolerated well. No treatment‐related serious adverse events were reported.Patients (Nicoboxil/nonivamide ointment is an effective, well‐tolerated medication for the treatment of acute non‐specific low back pain. Low back pain is a major health and socio‐economic problem.Clinically proven and effective treatment options are sparse.Nonivamide/nicoboxil ointment is an effective, well‐tolerated medication for the treatment of acute non‐specific low back pain.1Low back pain is a major health and socio‐economic problem in many countries. Point prevalence of up to 58%, and 1‐year prevalence of up to 82% are reported  non‐specific low back pain, clinically proven treatment options are relatively sparse. Early intervention is desirable to get patients back to their normal activities as soon as possible and to prevent chronification. Regarding pharmacotherapy, paracetamol is usually recommended as first‐line therapy and NSAIDs  as second‐line therapy when paracetamol is not sufficient. In addition, opioids, muscle relaxants, steroids, antidepressants or anticonvulsive medication are recommended by some guidelines  has been used since the 1950s to treat discomfort of the musculoskeletal system  between October 16, 2012 and April 19, 2013. The primary objective was to demonstrate superior efficacy of an ointment containing 2.5% nicoboxil and 0.4% nonivamide over placebo and ointments containing 2.5% nicoboxil alone and 0.4% nonivamide alone for the treatment of acute low back pain.2.2Prior to start of the study, the clinical trial protocol, the Patient Information leaflet, the Informed Consent Form and other locally required documents were reviewed by the Independent Ethics Committees and/or Institutional Review Boards of the participating centres and the competent authority .The trial was carried out in compliance with the clinical trial protocol, the principles of the Declaration of Helsinki, the ICH‐GCP, and with applicable regulatory requirements and Boehringer Ingelheim standard operating procedures. Prior to enrolment, patients gave their written informed consent according to German Drug Law and the ICH‐GCP.2.3Adults 18–74 years of age with acute low back pain for more than 2 days and less than 21 days, and a low back pain rating ≥5 on an 11‐point (0–10) numerical rating scale (NRS) were enrolled. Although the trial protocol stipulated the inclusion of patients up to 65 years of age, a number of older patients were also enrolled and not excluded from the analyses. Women of childbearing potential had to have a negative urine pregnancy test and be using a highly effective method of birth control.Patients were to be excluded for the following reasons: Multilocular pain or panalgesia; history of more than three low back pain episodes in the previous 6 months; patients with low back pain due to neurological causes , paresis tests in supine position upon dorsiflexion, plantar flexion, hip flexion, knee extension, bladder and/or rectum dysfunction; acute low back pain due to vertebral collapse or neoplastic, inflammatory (ankylosing spondylitis), traumatic or infective origins; any condition, disease or concomitant treatment that in the judgement of the investigator affected the patient's ability to participate in the clinical trial or that influenced the test methodology used; negative experience in the past with heat treatment for muscle complaints; history of treatment of back pain with centrally acting analgesics (e.g. opioids) and muscle relaxants; surgery due to back pain or rehabilitation due to back pain in the previous 12 months; spinal injection back pain treatment within 6 months prior to enrolment; intake of antidepressant/antipsychotic medication within 4 weeks prior to enrolment; treatment of the recent low back pain period with oral analgesics for more than four consecutive days; locally applied medication to the back within 48 h prior to enrolment; administration of other analgesics within 24 h prior to enrolment ; non‐pharmacological low back pain treatment  within 12 h prior to enrolment; participation in an investigational drug or device trial within 4 weeks prior to enrolment; hypersensitivity to nicoboxil, nonivamide or paracetamol; known hypersensitivity to any other ingredient; skin lesions  in the back region; drug dependence and/or alcohol abuse; severe hepatocellular insufficiency; patients who were pregnant or breastfeeding.2.4Patients were randomly assigned to one of the four treatment groups  in a 1:1:1:1 ratio at Visit 1. The randomization list was generated using a validated system using a pseudo‐random number generator so that the resulting treatment was both reproducible and non‐predictable. A random block size of 4 was used. Access to the treatment codes was controlled and documented.Study medication for each patient was packaged in a box containing two tubes of ointment. Patients had to administer one of the four ointments up to three times a day for a maximum of 4 days. The first 2 doses were to be applied at baseline (time point 0 at Day 1) and after 4 h on Day 1. After the second application on Day 1, patients could administer study medication on a PRN (as needed) basis but not earlier than 8 h after the first application for up to a total of 4 days. The intervals between each application of study medication had to be at least 4 h; a maximum of three applications in a 24‐h period was allowed.Two centimetres of ointment was applied to an area of about 20 cm × 20 cm on the patient's low back, where he/she felt the pain to be most pronounced. The whole application was to be completed within 3 min.Paracetamol tablets were allowed as rescue medication (up to a maximum of three times 1 g per day).2.58h). Secondary endpoints were PID between baseline (pre‐dose) and 4 h after the first application (PID4h), average PID versus baseline on the last individual treatment day (APIDLID), and patient assessment of efficacy on the last individual treatment day .Patients were to assess the intensity of their low back pain on an 11‐point NRS ranging from 0 = ‘no pain’ to 10 = ‘worst pain possible’ in a diary. Time points of assessment were pre‐dose (i.e. directly before the first application of study drug at Visit 1) and 0.5, 1, 2, 3, 4, 6, and 8 h after the first ointment application on Day 1. The pre‐dose pain intensity score was used as baseline PI. Furthermore, patients assessed the average pain intensity (API) of their low back pain on the same rating scale in the diary at the end of each treatment day. Primary endpoint was pain intensity difference (PID) between baseline (pre‐dose) and 8 h after the first application , mobility score  and number of patients taking rescue medication.2.6Adverse events (AEs) and serious adverse events (SAEs) were defined according to the International Conference for Harmonization Note for Guidance on Clinical Safety Data Management: Definitions and Standards for Expedited Reporting. Changes in vital signs and physical examination results were recorded as AEs or SAEs if they were judged clinically relevant by the investigator. Investigators recorded the intensity of AEs as mild (signs or symptoms that were easily tolerated), moderate  or severe . Investigators recorded the relatedness as possibly related or as not related to the study treatment.Tolerability was assessed by the investigators at Visit 2 (end of study) using a 4‐point VRS .2.7t‐test with α = 0.05.For the primary endpoint, PID at 8 h, a difference of 1 point on the 11‐point NRS (0–10) between the treatment groups, together with a common standard deviation of 3 was used to calculate the sample size. With a sample size of 192 per group , a power of 90% was provided assuming a two‐sided 2.82.8.1The ‘treated set’ (TS) was defined as all randomized patients who used at least one dose of study medication. The ‘full analysis set’ (FAS) included all patients of the TS who provided any post‐treatment data for the primary efficacy endpoint. The ‘per‐protocol set’ (PPS) was composed of all patients who were part of the FAS and complied with the protocol without any important protocol violations (IPVs). Efficacy endpoints were to be assessed in the FAS; safety endpoints in the TS.2.8.2For the primary endpoint, PID at 8 h, the analysis used a restricted maximum likelihood‐based repeated measures approach and included all available longitudinal pain intensity observations at each post‐baseline time point up to 8 h. The statistical model was applied to the analysis of change from baseline in pain intensity at 0.5, 1, 2, 3, 4, 6 and 8 h, and included the fixed, categorical effects of centre, treatment, time, and treatment‐by‐time interaction, the continuous covariate of baseline pain intensity and the residual error term. Centres with less than four evaluable patients for the primary analysis were pooled together with larger centres (this was the case for two centres). Within‐patient errors were modelled by unstructured covariance. The Kenward–Roger approximation was used to estimate the denominator degrees of freedom. Differences between the treatment group effects with regard to the primary endpoint of PID at 8 h were estimated by reference to the adjusted least square means and the corresponding 95% confidence intervals (CIs). Sensitivity analysis was performed on the PPS .2.8.3LID was analysed by analysis of covariance, with treatment and centre as fixed effects and baseline pain intensity as a continuous covariate. Patient assessment of efficacy on the last individual treatment day was analysed by a cumulative logit model fit to the underlying ordinal data with treatment and centre as fixed effects and baseline pain intensity as a continuous covariate. Adjusted odds ratios together with 95% CIs were used to quantify the effect of treatment and to compare the treatment groups. For the endpoint ‘time to onset of pain relief’, a Kaplan–Meier analysis was performed, and the log rank test stratifying for the variable baseline PI was used to determine the differences between the treatment groups. The time was censored at 9 h post‐dose and displayed as >8 h. The mobility score on each treatment day was analysed corresponding to the assessment of efficacy on the LID, but adding the fixed factors day, and treatment‐by‐day interaction. Safety evaluation was performed on the TS .PID at 4 h and APID on Day 1 to Day 4 were analysed with the corresponding model used for the primary endpoint. APID2.8.4Missing baseline pain intensity values were replaced by the next available post‐dose value if post‐treatment data were available within the first hour. A patient's daily overall assessment of efficacy was assigned ‘poor’ if it was missing because of discontinuation due to lack of efficacy; it was assigned ‘very good’ if the patient discontinued after the second application and had a pain intensity of 0 at 8 h post‐dose. For the primary analysis (FAS), the number of applications was recorded as 1 if missing on Day 1 in the diary, because all patients performed the first ointment application at the site. However, such patients were excluded from the PPS. No imputations or replacements were made for analyses utilizing a likelihood‐based repeated measures model as well as for other missing data.® version 9.2  and with a two‐sided alpha of 0.05.All statistical testing was performed using SAS33.1n = 194) was lack of efficacy. This was most frequent in patients treated with placebo (42.2%), accounting for 84 of 86 discontinuations in this treatment group. By contrast, premature discontinuation owing to lack of efficacy was reported for 15 (7.4%) patients treated with nicoboxil/nonivamide, 35 (17.7%) treated with nonivamide alone and 60 (29.9%) treated with nicoboxil alone. AEs led to premature discontinuation of treatment in 13 patients (6.4%) in the nicoboxil/nonivamide group, 9 (4.5%) in the nonivamide group and 1 (0.5%) in the placebo group. None of these AEs was considered serious. Ten additional patients prematurely terminated the study for the reasons ‘non‐compliant with protocol’ (one patient under nicoboxil/nonivamide), ‘refused to continue trial medication’ , ‘other’ .A total of 805 patients were enrolled and randomized; 202 were randomized to nicoboxil/nonivamide, 198 to nonivamide alone, 201 to nicoboxil alone and 204 to placebo . All patients were treated. Sex, age, race, baseline back pain and duration of back pain were similar in the four treatment groups (Table 3.2Ointment was applied only once (instead of twice) on Day 1 by one patient (0.5%) treated with nicoboxil/nonivamide, four (2.0%) treated with nonivamide alone, one (0.5%) treated with nicoboxil and four (2.0%) treated with placebo. Additionally, two patients in the placebo group applied ointment four times on several treatment days, even though the allowed maximum number of applications was three. All other patients complied with the treatment instructions. The mean weight of ointment per application was similar for the four treatment groups (data not shown).3.33.3.1p < 0.0001) and in the placebo group   and the nicoboxil/nonivamide group.At 8 h, pain intensity decreased statistically significantly more in the nicoboxil/nonivamide group  than in the nicoboxil group .3.3.2p < 0.0001) and in the placebo group . The PID at 4 h was not significantly different between the nonivamide  and the nicoboxil/nonivamide groups.Four hours after the onset of treatment, pain intensity decreased significantly more in the nicoboxil/nonivamide group  than in the nicoboxil group ; Compared with placebo, pain intensity was reduced by 1.049 points more in the combination group at this early time point.p < 0.0001 vs. placebo and nicoboxil, and p = 0.0259 vs. nonivamide) , placebo (p < 0.0001) and nonivamide (p ≥ 0.1324). Table The adjusted mean APID continuously decreased from Day 1 to Day 4 in all treatment groups and the absolute value of the APID was on all treatment days numerically highest in the nicoboxil/nonivamide group, followed by the nonivamide group, the nicoboxil group and the placebo group Fig. . On all e p ≥ 0.124. TableTime to onset of pain relief was assessed using a 7‐point VRS . Based on the distribution of patient frequencies in the different categories of time to onset of pain relief within the first 8 h, the combination of nicoboxil and nonivamide had an earlier onset of pain relief than the other three treatment groups. The median category of time to onset of pain relief was lowest for the combination of nicoboxil and nonivamide (between 1 and 2 h), followed by the nonivamide group (between 2 and 4 h), and the nicoboxil group (between 4 and 8 h), and it was highest for placebo .p < 0.01) and placebo (p < 0.0001) on all four treatment days and compared with nonivamide on Day 1  but not for nonivamide (p ≥ 0.2289).In the nicoboxil/nonivamide group, patients assessed the improvement of their mobility as better compared with nicoboxil , followed by the nonivamide group (~60%), the nicoboxil group (~43%) and the placebo group (~27%). The investigator assessment of efficacy provided comparable results (data not shown).The proportion of patients taking rescue medication was numerically highest in the placebo group (25.5%), followed by the nicoboxil group (22.4%), the nicoboxil/nonivamide group (18.3%) and the nonivamide group (17.7%).3.4A total of 66 patients experienced AEs during the study . One SAE, which was not treatment‐related, was reported in the study: a patient in the nonivamide group was hospitalized due to severe back pain. AEs reported by 38 patients were assessed as drug‐related Table .The most frequently reported drug‐related AEs on the preferred term (PT) level were feeling hot, burning sensation and erythema, which were all reported with the highest frequency in the nicoboxil/nonivamide group, followed by the nonivamide and nicoboxil groups, and did not occur in the placebo group. Pruritus was most frequently reported in the nicoboxil group. None of the drug‐related AEs was considered to be serious; all patients recovered from all drug‐related AEs.p < 0.0001) and nicoboxil (p < 0.0001) groups as better compared with the nicoboxil/nonivamide group, and for the nonivamide group (p = 0.7439) as similar compared with the combination group (Supporting Information Table S2).Across all treatment groups, patients and investigators assessed the tolerability of study medication as ‘very good’ or ‘good’ for the majority of patients (data for patients not shown). Investigators assessed the final overall tolerability for the placebo  non‐specific low back pain, clinically proven treatment options are limited. Early intervention is desirable to get patients back to their normal activities as soon as possible and to prevent chronification. A recent review of the current (inter‐) national clinical guidelines for the management of low back pain mentions early return to work (despite having low back pain) in their list of recommendations. Paracetamol is usually recommended as a first‐line therapy and NSAIDs  as second‐line therapy when paracetamol is not sufficient , the pooled effect size was 0.52, lower than the SMD for nicoboxil/nonivamide ointment . Thus, the combination in total provided more benefit, and comparable risk when compared with nonivamide alone.Limitations of this study include that superiority of the combination over nonivamide alone could not be shown concerning the primary endpoint. However, it has to be considered that ointments with the individual ingredients at these doses are not commercially available, and that the combination was shown to be superior to all other treatment arms for several clinically relevant endpoints, such as APID on the last individual treatment day, mobility score on the first treatment day and patient assessment of efficacy. The overall AE frequency in this study was low, and drug‐related AEs were consistent with the mechanism of action of hyperaemia‐inducing agents. Even most of the 18 patients in the nicoboxil/nonivamide arm who reported AEs experienced pain relief (i.e. benefited) from the treatment (data not shown). Assessment of tolerability by patients and investigators was not different for nonivamide and nicoboxil/nonivamide (One might argue that treatments inducing hyperaemia cannot be fully blinded. However, we think that the risk of unblinding was relatively low. In this parallel‐group trial, every patient experienced only one treatment, and therefore comparison with other treatments was not possible. It is known that the individual response to the local effects of nicoboxil/nonivamide products vary considerably from patient to patient. Furthermore, the application of an ointment per se can induce the perception of heat due to the mechanical stimulation of the skin, as well as effects on perspiration and thermal isolation.The maximum treatment duration of 4 days might be considered as too short compared with other studies investigating the treatment of acute low back pain, which often have duration of 7 days. However, based on the results of this study, the maximum possible effect of nicoboxil/nonivamide ointment might have been even pronounced after 7 days of treatment.In summary, this study demonstrated that nicoboxil/nonivamide ointment is an effective, tolerable, and safe treatment option for acute low back pain. Based on published data by others, the efficacy seems to be comparable or superior to that of systemic over‐the‐counter, as well as some prescription analgesics and muscle relaxants, while – as a topical treatment – has a low risk of systemic side effects, so that this combination adds a promising option for the treatment of acute low back pain.M.G. and T.S. substantially contributed to study concept, design and results interpretation; C.H., E.R., W.P.‐R., T.W. substantially contributed to study concept, design, analysis, results interpretation and drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved it.EudraCT No.: 2011‐003890‐27; Clinical Trials.gov identifier: NCT01708915Figure S1. Patient disposition. All enrolled patients were randomized, treated and provided data for the primary endpoint. FAS = full analysis set; IPV = important protocol violation; PPS = per‐protocol set. Patients may have had more than one important protocol violation. Only IPV categories with at least one IPV are presented.Click here for additional data file.Table S1. Frequency distribution, Kaplan–Meier analysis and log rank test of the time to onset of pain relief after the first application.Click here for additional data file.Table S2. Final overall investigator assessment of tolera‐bility – TS.Click here for additional data file.


The aim of this randomized-controlled clinical trial was to assess the effect of intraligamentary (PDL) injection of dexamethasone on onset and severity of post-treatment pain in patients with symptomatic irreversible pulpitis. n=20). After administration of local anesthesia and before treatment, group 1 (control) PDL injection was done with syringe containing empty cartridge, while in groups 2 and 3 the PDL injection was done with 0.2 mL of 2% lidocaine or dexamethasone (8 mg/2 mL), respectively. Immediately after endodontic treatment patients were requested to mark their level of pain on a visual analogue scale (VAS) during the next 48 h . They were also asked to mention whether analgesics were taken and its dosage. Considering the 0-170 markings on the VAS ruler, the level of pain was scored as follows: score 0 , score 1  and score 3 . The data were analyzed using the Kruskal-Wallis and the Chi-square tests and the level of significance was set at 0.05. A total number of 60 volunteers were included according to the inclusion criteria and were assigned to three groups . However, after 24 and 48 h the difference in the pain was not significant between groups 1 and 2 (P<0.6) but group 3 had lower pain levels . After 6 and 12 h, group 1 and group 3 had the highest and lowest pain values, respectively (Pretreatment PDL injection of dexamethasone can significantly reduce the post-treatment endodontic pain in patients with symptomatic irreversible pulpitis. Management of endodontic pain has a positive impact on reducing fear and anxiety of endodontic patients , 2. Endoetc. Prostaglandins which are terminal products of arachidonic acid cyclooxygenase (COX) pathway metabolism  and a pain score of ≥56 degrees (moderate to severe) on numeric visual analogue scale (VAS) indicated by the patient were necessary inclusion criteria [The inclusion criteria for patient selection were as follows: age range of 18-65 years, systemically healthy patient , pregnancy and nursing, age less than 18 and more than 65, any contraindication or sensitivity to corticosteroids, gastrointestinal disorders, hemostatic disorders or anti-coagulant therapy during the last month, consumption of opioid or non-opioid analgesics, corticosteroids, three cyclic anti-depressants and etc. during the last 12 h before treatment.Likewise the exclusion criteria included: systematic complexity  the case was condemned as failed anesthesia. For cases with unsuccessful anesthesia the injection was repeated. Volunteers who met the criteria had to sign a fully informed consent. The demographic data of patients were meticulously recorded. The endodontic treatment started with injection of 1.8 mL of 2% lidocaine containing 1:80000 epinephrine  for local anesthesia . The depth of anesthesia was checked twice with electric pulp tester in 15-min intervals. Should two negative responses were elicited n=20). In group 1 the operator pretended to perform a PDL injection with an empty cartridge using a short 20-mm 30-gauge needle set on an intra-ligamental syringe . The injection needle only touched the tissues without any penetration. In group 2, before the onset of treatment 0.2 mL of 2% lidocaine containing 1:80000 epinephrine was injected into PDL at mesiobuccal and distobuccal corners of the tooth with the needle entering the PDL with 45 degrees inclination and the piston was discarded after feeling pressure against injection with the same syringe and needle size. In group 3, PDL injection was performed using 0.2 mL of dexamethasone  with similar conditions and devices. The solutions were prepared by another blinded operator and the treatment process including all injections were done by an independent endodontist. To establish a double blinded design, neither the patient nor the practitioner were aware of the injection solution.Then the patients were randomly divided into 3 groups , score 1  and score 3 . The patients were also asked to record the type and dosage of analgesics consumption if needed to reduce their post-operative pain.After tooth isolation with rubber-dam and preparation of the access cavity, root canal treatment was done using hand K-files  with step-back technique. The least apical size was set at #30 and apical patency was maintained for all teeth. The canals were irrigated with normal saline and obturated with lateral condensation of gutta-percha and sealer . After termination of treatment the access cavity was restored with temporary restoration  and the occlusion and proximal integrity was meticulously checked to prevent future pain. Before dismissal the patients were briefed about filling of the pain questioner after 6, 12, 24 and 48 h and they were also contacted on the due time. Patients were given a non-numeric VAS ruler which had signs and a similar numerated ruler was kept by the operator who had to correlate the VAS pain signs marked by the patient to the corresponding scores from 0 to 170. The level of pain was scored as follows: The data were analyzed using the Kruskal-Wallis and the Chi-square tests. The level of significance was set at 0.05.P<0.2) (P<0.4).A total of 60 volunteers (30 in each group) met the criteria and were found eligible for this study. The patient distribution into different test groups was not significantly different regarding gender, age, the level of pretreatment pain, the type of tooth and presence/absence of acute apical periodontitis (P<0.2) . Before P<0.05). The amount of pain reduction was 65%, 48% and 25% in dexamethasone, lidocaine and placebo groups, respectively, and this reduction was statistically significant between all groups and also in two-by-two comparison (P<0.01). The highest amount of analgesic consumption was in placebo (70%), lidocaine (50%) and dexamethasone (40%) groups, respectively. The Chi-square test did not reveal a significant difference in this regard.After 6 h the highest and lowest level of post-treatment pain were found in placebo (80±44) and dexamethasone groups (dexamethasone) (35.25±17.47), respectively. The main value of pain significantly decreased in all three groups (P<0.01). Two-by-two comparison revealed that the placebo and lidocaine group and dexamethasone and placebo group were significantly different . There was no report of moderate and severe pain in dexamethasone group. The pattern of taking analgesics followed the similar manner in descending order: placebo (60%), lidocaine (25%) and dexamethasone (25%).After 12 h, similarly the lowest amount of pain level was found in dexamethasone group while the placebo group had the highest pain (P<0.6) and the two-by-two comparison did not show a significant difference between lidocaine and placebo groups, either (P<0.6).The Chi-square test showed a significant difference between the placebo and other two groups. After 24 h, although the placebo group maintained the highest level of pain perception, the difference was not significant with others (P<0.01). The analgesics consumptions were almost similar in all groups without significance.The patients in dexamethasone group maintained the significantly different pain level compared to the placebo (P<0.8). There was no report of moderate and severe pain in any groups after 24 and 48 h. There was no report of analgesic consumption after 48 h (After 48 h, the highest and lowest pain level were reported in placebo and dexamethasone groups, respectively but the difference was not significant (ter 48 h  and 3.This double-blind placebo controlled clinical trial evaluated the effect of intraligamentary injection of dexamethasone and 2% lidocaine on reduction of postoperative pain in patients with irreversible pulpitis using VAS. The VAS score data showed that intraligamentary injection of low dose of dexamethasone was more effective in reduction of post endodontic pain in comparison with lidocaine or placebo group.Many endodontic patients believe that post-treatment pain is inevitable. The occurrence of a mild postoperative pain is not a rare event even when endodontic treatment has followed all acceptable standards . AccordiPostoperative pain is usually mild and rarely lasts longer than three days. However, some patients will suffer from a moderate to severe pain that persists for several days even after appropriate endodontic treatment. The persistent pain is often attributed to the release of inflammatory mediators such as prostaglandins, leukotrienes, bradykinin and serotonin. Consequently, peripheral and central hyperalgesia are resulted from the activation and sensitization of nociceptors by these released mediators, especially prostaglandins . etc. and the second appearing in injured and inflamed tissues as an inducible enzyme [Various classes of drugs have been studied for the management of post-treatment endodontic pain including NSAID’s and acetaminophen, opioids and steroids , 17. Mane enzyme . Althouget al. [via activating the B1 and B2 receptors. The latter receptor mediates the pain in acute inflammation while the pain in chronic inflammation involves an elevation in number of B1 receptors [The results of the current study showed that PDL injection of dexamethasone significantly reduced the post-endodontic pain levels during the first 12 h postoperatively. Shantiaee et al.  demonstret al. . There aet al. . Steroidet al. . Reductiet al. . Anotheret al. , 25. Braeceptors . Reductieceptors , 25, 27.eceptors . Glucocoeceptors .et al. [per se has a major effect on reducing post endodontic pain regardless of analgesic intervention [It could therefore be assumed that glucocorticoids have greater anti-inflammatory and analgesic effects than NSAIDs where considering the fact that multiple inflammatory mediators are released or produced during pulpal inflammation . Thus syet al.  the averrvention .The present clinical study represented an effective practical way of intraligamentary injection of a very low-dose dexamethasone to control moderate to severe post-operative pain in patients suffering from symptomatic irreversible pulpitis. Considering the adverse or unwanted effects of systemic administration of NSAIDs or high doses of corticosteroids, local administration of 0.2 mL of dexamethasone may seem a safe alternative way for pain control.


Imaging results are frequently considered as hallmarks of disease by spine surgeons to plan their future treatment strategy. Numerous classification systems have been proposed to quantify or grade lumbar magnetic resonance imaging (MRI) scans and thus objectify imaging findings. The clinical impact of the measured parameters remains, however, unclear. To evaluate the pathological significance of imaging findings in patients with multisegmental degenerative findings, clinicians can perform image-guided local infiltrations to target defined areas such as the facet joints.The aim of the present retrospective study was to evaluate the correlation of MRI facet joint degeneration and spinal stenosis measurements with improvement obtained by image-guided intraarticular facet joint infiltration.Fifty MRI scans of patients with chronic lumbar back pain were graded radiologically using a wide range of classification and measurement systems. The reported effect of facet joint injections at the site was recorded, and a comparative analysis performed.τ = − 0.190 for neuroforaminal stenosis grading as suggested by Lee, to τ = 0.133 for posterior disc height as proposed by Hasegawa.When we allocated patients according to their reported pain relief, 27 showed no improvement (0–30%), 16 reported good improvement (31–75%) and 7 reported excellent improvement (> 75%). MRI features assessed in this study did, however, not show any relevant correlation with reported pain after facet joint infiltration: Values for Kendall’s tau ranged from Despite the trend in evidence-based medicine to provide medical algorithms, our findings underline the continuing need for individualised spine care that, along with imaging techniques or targeted infiltrations, includes diagnostic dimensions such as good patient history and clinical examination to formulate a diagnosis.ClinicalTrials.gov, NCT03308149, retrospectively registered October 2017The online version of this article (10.1186/s13018-017-0685-x) contains supplementary material, which is available to authorized users. Chronic lumbar back pain and sciatica are common symptoms of degenerative conditions of the spine that lead to enormous costs to the health care systems of industrialised countries –4. The dSo far, no consensus has been established about whether radiologic imaging can predict the response to diagnostic or therapeutic facet joint blocks (reviewed by Cohen and Raja (2007)) . In theiIn the present study, we aimed to systematically evaluate the quality of different measurement and classification systems for spinal stenosis and facet joint degeneration on MRI for their ability to predict reported pain relief after facet joint infiltration in patients with chronic lumbar back pain. We hypothesised that, as pathological grading increased in MRI scans, pain alleviation would also increase after bilateral facet joint infiltration.All patients who had received inpatient gradual diagnostics , 13 fromVarious measurement and grading techniques were used to evaluate facet joint degeneration, neuroforaminal stenosis or spinal canal stenosis on the MR images. All measurements were performed blinded by the same observer, who was familiar with and had practiced all tested measurement techniques.Full departmental, institutional and local ethical committee approvals were obtained before commencement of the study (project number 503/2016BO2).An analgesic (0.5 ml bupivacaine 0.25%) and a corticosteroid (0.5 ml triamcinolone 10 mg/ml) were injected intraarticularly into the facet joint under fluoroscopic guidance. Patients were then asked on the following day to report the pain relief obtained by the infiltration in terms of percentage (%) of the total pain present before infiltration.Degeneration of the facet joints was classified by using the method of Weishaupt et al. , 20, whiTo stratify stenosis of the spinal canal and the neuroforamen, we performed both qualitative and quantitative techniques. Again, the higher pathological value from both sides was used for further analyses.I.In sagittal T2 images, posterior disc height  was measII.The minimum antero-posterior diameter of the neuroforamen was measured in axial T2 images in two ways: First, it was measured in the axial plane where the root can be seen to traverse it  Fig. 1b1b. The sIII.The minimum cross-sectional area of the foraminal zone was measured on sagittal T1 images. As suggested by Sipola et al. , the keyQuantitative neuroforaminal stenosis measurements:Using sagittal T1 images, we qualitatively graded neuroforaminal stenosis, as proposed by Lee et al. , 25, wheI.Axial T2 images at the level of the intervertebral disc were used to measure the ligamentous interfacet distance . This diII.Antero-posterior constriction was measured as the mid-sagittal diameter of the dural sac at its narrowest level in axial T2 images Fig. .III.The smallest cross-sectional area of the dural sac at the infiltrated level was measured in T2 axial images –29. The Quantitative spinal canal stenosis measurements:We qualitatively graded spinal canal stenosis, as suggested by Schizas et al., in axialAll three Tesla or 1.5 Tesla MRIs were available in digital form and analysed on an Eizo RadiForce RS110 48-cm Class Colour LCD screen  with a centricity PACS Radiology RA1000 workstation .t test for independent samples and Mann-Whitney U test. To evaluate the association of reported pain relief and imaging findings, we calculated Kendall’s tau correlation coefficient. For further analyses, pain relief was additionally categorised into three groups: no (below 30%), good (30–74%) and excellent (75–100%) pain relief.Distributions of variables for all parameters were assessed as histograms. Categorical variables are described as absolute frequencies. Depending on normality, data are reported as mean (standard deviation) or median (minimum-maximum). Differences between two groups were calculated by p values have a two-tailed significance level of alpha = 0.05. No adjustment for multiple testing was performed. Graphic illustration of the results was performed by using bar diagrams, boxplots and scatterplots. Statistical analysis was conducted with IBM SPSS version 22.All reported In total, 50 patients met all inclusion criteria (30 women and 20 men). The median age was 57 (28–95) years  and those with no improvement at all , no significant difference was notable  scan –35. ThisEfforts nevertheless continue in order to improve diagnostic predictability of imaging techniques: although the supine MRI technique still predominates, upright imaging might improve the results because of the weight-bearing condition. Still, it does not provide dynamic, but only static information. Another difficulty with the correct interpretation of imaging results occurs in circumstances in which adaptational processes are difficult or even impossible to visualise. This can especially be noted when the clinical presentation of acute minor nuclear prolapses is compared with those of elderly patients with a long history of what is, in many cases, asymptomatic severe spinal stenosis. One explanation for such differences might be the triggered inflammatory processes that lead to swelling or intraarticular synovial fluid collection, which in peripheral joints is easily recognisable clinically, whereas the zygapophyseal joints do not offer such a clinical feature. In addition, fluid production in the facet joints seen on MRI is presently interpreted as a sign of instability –43 ratheIn compensation for this diagnostic imaging gap, image-guided diagnostic facet joint infiltrations have been established, for which evidence is considered strong (level II) to isolate the facet joint as a pain generator . To the Given the uncertainty surrounding both the interpretability of MRI findings and the diagnostic value of facet joint infiltrations, it is clear that future studies should first concentrate on patients with monosegmental problems. Only when a clear determination of sensitivity, specificity, validity and reliability has been obtained can multisegmental problems be addressed. In view of the given uncertainty of both modalities, the results obtained in the present study could be interpreted in two ways. First, it is possible that either of these techniques or both are completely useless. Second, the results could imply that the information that both modalities provide is complementary. There is no completely reliable gold standard with which to compare a diagnostic test (or injection) when the absence of pain is the end point . It is tAll infiltrations were guided by fluoroscopy. Nevertheless, it is possible that some of the infiltrations were not applied intraarticularly, but periarticularly. The clear difference between the effects obtained by intraarticular and periarticular infiltrations is yet to be demonstrated. A general critical feature of most studies addressing patients with chronic lumbar back pain is the mostly multisegmental underlying pathology that makes it difficult to analyse monosegmental effects. A crucial consideration for the correct interpretation of our findings is that the results described apply only to chronic conditions.Although imaging results are frequently considered as hallmarks of disease by specialists to plan their future treatment strategy, a clear correlation of symptoms and imaging results is not yet possible with current techniques. The prognostic value of facet joint infiltrations for surgical outcome has also recently been questioned. Our results show an absolute lack of correlation between imaging results with MRI and effects obtained by targeted facet joint infiltration. In view of the trend in evidence-based medicine to provide medical algorithms, our findings underline the continuing need for individualised spine medicine that, along with imaging techniques or targeted infiltrations, includes diagnostic dimensions such as good patient history and clinical examination.


Burning mouth syndrome is a poorly understood disease process with no current standard of treatment. The goal of this article is to provide an evidence-based, practical, clinical algorithm as a guideline for the treatment of burning mouth syndrome.Using available evidence and clinical experience, a multi-step management algorithm was developed. A retrospective cohort study was then performed, following STROBE statement guidelines, comparing outcomes of patients who were managed using the algorithm and those who were managed without.p=0.001). The odds ratio of not continuing care for the non-algorithm group compared to the algorithm group was 5.6 . Improvement in pain was significantly more likely in the algorithm group (p=0.001), with an odds ratio of 27.5 .Forty-seven patients were included in the study, with 21 (45%) managed using the algorithm and 26 (55%) managed without. The mean age overall was 60.4 ±16.5 years, and most patients  were female. Cohorts showed no statistical difference in age, sex, overall follow-up time, dysgeusia, geographic tongue, or psychiatric disorder; xerostomia, however, was significantly different, skewed toward the algorithm group. Significantly more non-algorithm patients did not continue care (69% vs. 29%, We present a basic clinical management algorithm for burning mouth syndrome which may increase the likelihood of pain improvement and patient follow-up. Key words:Burning mouth syndrome, burning tongue, glossodynia, oral pain, oral burning, therapy, treatment. Burning mouth syndrome (BMS), an idiopathic condition characterized by chronic oral mucosal burning and pain, afflicts between 0.7 and 7% of the population -3. OftenSymptoms of BMS are nonspecific and the diagnosis is often difficult to establish. Furthermore, there are no standard guidelines for management of BMS and physicians are left to employ whatever treatments they are comfortable and/or have experience with. Studies have not revealed any treatments that have been proven to be effective enough to be considered standard of care. Therefore, we sought to address this lack of guidance by developing and testing an algorithm incorporating the various treatment strategies utilized in studies conducted over the last 20 years . Our goaManagement Algorithm Developmentet al. Below is a summary of each step of the algorithm, which was founded on previous literature and supported by our recent systematic review , fungal infection, and other mucosal diseases .- Once primary BMS is established, start empiric B vitamins, folate, and/or antifungals ,8.Step 2: Patient Education- Educate patients on nature of BMS and provide reassurance .- Counsel relevant patients on possible relationship with menopause .- Psychiatric screening and offer psychiatric referral if pertinent.Step 3: Oral Hygiene Optimization- Encourage oral hygiene standards per current American Dental Association recommendations, including (1) brushing teeth twice daily for two minutes each time, (2) tongue brushing, (3) daily flossing, and (4) regular dental visits for professional cleaning and oral exams .- Trial non-alcoholic mouthwashes and avoid foaming agents in toothpaste such as sodium lauryl sulfate (SLS).- Prevent xerostomia by promoting adequate fluid intake; avoidance of alcohol, tobacco, overly salty foods, acidic beverages, and consumption of sugar-rich foods .Step 4: Alpha-lipoic Acid Supplementation- ALA trial regimen of 600mg/day for 3-4 months with consideration for treatment extension if improvement but relapse in symptoms after discontinuation .- If symptoms fail to improve sufficiently, gabapentin or psychotherapy may be added, as both have been shown to work synergistically with ALA .Step 5: Prescription Oral Topical Medications- Trial of daily chlorhexidine gluconate .-Increase salivary flow with over-the-counter artificial saliva  and sialagogues  .Step 6: Neuropathic Treatments- Clonazepam can be used topically using 1 mg tablets held intraorally near the sites of pain for 3 minutes without swallowing, followed by expectoration, three times a day .- Gabapentin may also be considered, starting at 300mg/day, with gradual titration up to 2400mg/day if necessary .- Consider neurology consultation for long-term use and titration due to potential adverse neurologic effects with extended use.Step 7: Psychiatric Consultation and Treatment- Patients are usually not initially inclined to obtain psychiatric consultation. It may be offered again at this time given multiple treatment failures.- Consider psychotherapy.Step 8: Systemic Clonazepam- Trial clonazepam 0.5 mg daily for 9 weeks .- Consider psychiatry consultation for long-term use.Step 9: Treatment of Refractory BMS- Consider antidepressants in patients with comorbid psychiatric disease .- Consider hormone replacement therapy (HRT) along with consultation with women’s health .- Consider less-studied and equivocal modalities such as benzydamine hydrochloride oral rinse , sucralfAnalysis of Algorithm EffectivenessA retrospective cohort study was conducted for 2013 to 2016 comparing all patients who underwent BMS management using the algorithm described above with those who did not. The STROBE Initiative statement was followed . All patp<0.05 level .The two-tailed, unequal variance, Student t-test and Fisher exact test were used where appropriate to compare groups. Means are reported as mean ±standard deviation (SD). Odds ratios (OR) and confidence intervals (CI) are reported as OR . Significance was established at the p<0.001), and significantly more non-algorithm patients did not continue care . The OR of not continuing care for the non-algorithm group compared to the algorithm group was 5.6 .A total of 47 patients were met the appropriate criteria and were diagnosed with primary BMS. Of those patients, 21 (45%) were managed using the algorithm and 26 (55%) were not. Patient characteristics are presented in p=0.001). The distribution of pain outcomes is shown in Improvement in pain was significantly more likely in the algorithm group  for every patient that is typical of non-algorithmic approaches.We found a significant difference in the rate of improvement in patients who underwent the algorithmic management (48%) from those who did not (4%). Overall, patients in our study were similar to those found in the literature, with a majority of perimenopausal females and symptom/comorbidity frequencies similar to that found in other studies . The basThere was significantly more attrition in the non-algorithm group, with 69% of patients failing to continue care compared to 29% in the algorithm group. This may be due to better patient education in the algorithm group which strengthens the patient-physician relationship and reduces “doctor shopping.” We want to emphasize that indeed, treating BMS is a time-consuming and drawn-out process, given the natural history of the disease and its progression over months to years . PatientOur study is limited by the number of total patients; however, it compares favorably to the existing literature cohorts of BMS patients. Another limitation is the number of patients who failed to continue care under our practice, a consistent finding in chronic pain patients. Prospective, clinical treatment strategies, emphasizing follow up through patient education and stepwise treatment trials are needed in this chronic pain disorder. There are intrinsic biases with retrospective studies and prospective trials with a stepwise treatment foundation would be of benefit. Acknowledging this study’s limitations, we hope this basic algorithm would serve as a practical start to the development of more comprehensive management guides. With the advent of new medications, stronger studies, and better understanding of this chronic pain disease process we propose a more algorithmic approach focusing on a stepwise treatment strategy and emphasizing proper patient education and follow-up.


These findings support the use of neuropathic pain treatment in recessive dystrophic epidermolysis bullosa.Recessive dystrophic epidermolysis bullosa is a painful condition characterised by repeated blistering of the skin. Von Bischhoffshausen  Small fibres in the skin are vulnerable to damage in metabolic or toxic conditions such as diabetes mellitus or chemotherapy resulting in small fibre neuropathy and associated neuropathic pain. Whether injury to the most distal portion of sensory small fibres due to a primary dermatological disorder can cause neuropathic pain is still unclear. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare condition in which mutations of proteins of the dermo-epidermal junction lead to cycles of blistering followed by regeneration of the skin. Damage is exclusive to the skin and mucous membranes, with no known direct compromise of the nervous system. It is increasingly recognized that most RDEB patients experience daily pain, the aetiology of which is unclear but may include inflammation (in the wounds), musculoskeletal (due to atrophy and retraction scars limiting movement) or neuropathic pain. In this study we investigated the incidence of neuropathic pain and examined the presence of nerve dysfunction in RDEB patients. Around three quarters of patients presented with pain of neuropathic characteristics, which had a length-dependent distribution. Quantitative sensory testing of the foot revealed striking impairments in thermal detection thresholds combined with an increased mechanical pain sensitivity and wind up ratio . Nerve conduction studies showed normal large fibre sensory and motor nerve conduction; however, skin biopsy showed a significant decrease in intraepidermal nerve fibre density. Autonomic nervous system testing revealed no abnormalities in heart rate and blood pressure variability however the sympathetic skin response of the foot was impaired and sweat gland innervation was reduced. We conclude that chronic cutaneous injury can lead to injury and dysfunction of the most distal part of small sensory fibres in a length-dependent distribution resulting in disabling neuropathic pain. These findings also support the use of neuropathic pain screening tools in these patients and treatment algorithms designed to target neuropathic pain. COL7A1)  . Type VIet al., 2014) such that opioids become a potentially unacceptable treatment for pain control , or musculoskeletal (due to atrophy and retractile scars) . AnecdotWe hypothesized that pain in RDEB could have a significant neuropathic component if chronic skin inflammation leads to cutaneous small fibre dysfunction. We therefore performed detailed somatosensory phenotyping in the largest cohort yet collected for this purpose including the use of: neuropathic pain screening questionnaires, quantitative sensory testing, autonomic function testing, nerve conduction studies, and morphological assessment of unmyelinated sensory afferents in the skin. Furthermore, potential associations of these outcomes with severity of the disease were determined. Here we provide evidence for the first time of functional and morphological impairment of small sensory fibres in patients with RDEB.COL7A1 gene) were asked by their physician for permission to be contacted for participation in the study. Those who accepted were asked to fill in questionnaires and to attend a single appointment during which one trained examiner performed electrodiagnostic tests, quantitative sensory testing (QST), autonomic tests, and a skin biopsy. We only included patients that were over 13 years old, because in performing QST a minimum understanding of instructions is required and in this specific cohort of patients cognition is limited by low educational level due to poor school attendance. The study was approved by the Institutional Ethics Committee of Pontificia Universidad Católica de Chile (reference number 13-317), and all participants gave informed written consent before participating. The study was conducted in accordance with the Declaration of Helsinki.Patients were recruited from DEBRA (Dystrophic Epidermolysis Bullosa Research Association) Chile. Although epidermolysis bullosa is a rare disease , DEBRA Chile cares for 64 patients with RDEB, which made this project feasible. Patients with clinical and molecular diagnosis of RDEB  score . At the cut-off of 4, DN4 has sensitivity of 80%, and specificity of 92%  (Nerve conduction studies were performed using an ADVANCE system (Neurometrix) with conventional reusable electrodes (Natus Neurology). The foot was warmed to ensure a temperature of 32°C. We recorded nerve action potential amplitudes and nerve conduction velocities from the sural nerve (sensory) and the peroneal nerve (motor). For the sural nerve the active recording electrode was placed behind the lateral malleolus with the reference electrode distal, and the stimulation point was placed at 14 cm proximal to the active electrode in the midline of the posterior lower leg. For the peroneal nerve the active electrode was placed over the midpoint of the extensor digitorum brevis muscle on the dorsum of the foot, and the reference electrode was placed slightly distal to the fifth metatarsophalangeal joint. Stimulation points were: (i) 8 cm proximal to the active electrode, slightly lateral to the tibialis anterior tendon; and (ii) slightly posterior and inferior to the fibular head.Nerve conduction studies could not be recorded from patients that presented with active wounds at a recording or stimulating site.Lying and standing blood pressure and heart rate was measured using a DINAMAP monitor (Critikon). Lying blood pressure and heart rate were measured first, after which the subject was asked to stand for 10 min to measure standing blood pressure and heart rate at 1 and 10 min. Orthostatic hypotension was determined to be present in subjects in whom either at least a 20 mm Hg reduction in systolic or a 10 mm Hg reduction in diastolic blood pressure was observed.The patient was connected to an electrocardiograph monitor. The test was performed with the patient lying quietly and breathing deeply at six breaths per minute (inspiratory and expiratory cycles of 10 s), during five successive breathing cycles. The maximum–minimum heart rate during each breathing cycle was measured and the mean of the differences was calculated.Subjects were asked to perform a forced expiration (40 mmHg) during 15 s. The ratio of the maximal heart rate generated during the Valsalva manoeuvre divided by the lowest heart rate following the manoeuver was calculated.Sympathetic skin responses were recorded using EMG equipment (Cadwell Sierra Wave). The differential surface electrodes were fixed at the sole of the right foot with the reference electrode fixed on the dorsum of the foot. Responses were recorded in a quiet dimly lit room at 22–24°C, with the subject supine and relaxed, with the skin temperature at 32–36°C. Responses were elicited by asking the subject to do deep breathing. The recording time was 10 s, the lower frequency limit was 0.1 Hz, and the upper limit 200 Hz. Amplitude of the sympathetic skin response was analysed determining the peak-to-peak distance.TM X-100 and secondary antibody was incubated overnight at 4°C . On the third day, sections were washed and mounted for analysis. We used immunofluorescence instead of bright field microscopy because we have more experience with the former technique, and both have shown to have comparable diagnostic efficiency (http://imagej.nih.gov) and IENFD was expressed as fibres per mm epidermis. The investigator performing this technique (M.C.) trained at a well-established skin biopsy laboratory (Prof David Bennett at Oxford University). To calculate z-scores we used normative data on IENFD done with immunofluorescence , following published guidelines , and DAPI following the protocol described above. Images were taken at the same exposure conditions in a confocal microscope (Nikon SPECTRAL ECLIPSE C2) using a 60× objective. Dermal innervation was quantified measuring immunofluoresence intensity in ImageJ. Sweat glands were identified by their tubular structure seen by DAPI, and their innervation was quantified by measuring PGP9.5 immunostaining signal over them. Labelling endothelial cells with CD31 identified blood vessels, and their innervation was quantified by measuring PGP9.5 immunostaining signal over them. For each analysis we examined three randomly chosen sections per subject .t-tests or Mann-Whitney U-tests as appropriate. Pearson’s correlation analyses were performed to explore associations between QST findings, IENFD and severity of the disease (BEBS).SPSS Statistics Version 23 (IBM) was used for statistical analysis. Data were tested for normality with the Kolmogorov-Smirnov test. Mean values and standard error of the mean (SEM) are reported for normally distributed data. QST z-scores, results from nerve conduction studies, autonomic tests, and skin biopsies were compared with independent samples P = 0.13). There were more females in the RDEB group than in the control group but this was not statistically significant (P = 0.3). Demographic data are shown in COL7A1 gene. The severity of RDEB can vary between patients, so we used the BEBS score , and four declined to participate in the study. An age and gender matched cohort of 27 healthy volunteers without any dermatological, neurological or systemic medical conditions were recruited from the general population in Santiago. The mean age of patients was 22.3 ± 12.1 years [standard deviation (SD)] and of controls was 26.5 ± 7.9 years (SD), with no significant difference between both groups (Most RDEB patients (92.8%) interviewed said they have pain every day, with a mean rating of 4.2 ± 0.52 in the numerical rating scale (0–10). Pain starts in early life, as blistering develops at birth or very shortly after birth. Acute pain occurs localized to areas of active skin blistering and resolves following healing. However, in addition patients also describe persistent pain arising from uninjured areas of skin and especially localized to the feet. We asked for the duration of this pain that was unrelated to active wounds, and found that it varied significantly ranging from 1 to 25 years with a mean duration of 4.7 years (SD: 5.1 years).Only a minority of RDEB patients took regular analgesic medications, although all of them complained of chronic pain. These included paracetamol (20%), ibuprofen (3.4%), tramadol (10%), pregabalin (3.4%) and amitriptyline (3.4%). Some patients were prescribed medication for other conditions such as depression, anxiety disorders, and epilepsy . Of the control subjects, four subjects took antidepressants .We assessed the presence of specific descriptors of pain by using two complementary questionnaires to understand if the pain reported by RDEB patients had neuropathic characteristics. We used the DN4 as a screening tool for neuropathic pain and found that 75.9% of RBED patients had a score of 4 or higher, which is highly suggestive of neuropathic pain . In a minority of cases (16%) thermal sensitivity was also impaired in the hands .P < 0.0001, P = 0.02), which is indicative of loss of low threshold mechanosensation mediated by β fibres. No patient presented with loss or gain in vibration detection thresholds (P = 0.13) (QST over the dorsum of the foot (S1 dermatome), revealed that patients with RDEB had significantly reduced cold and elevated warm detection thresholds (i.e. reduced sensitivity to warm and cool stimuli) as well as increased thermal sensory limen compared to control participants  A.FigureP = 0.02), increased mechanical pain sensitivity (P < 0.001), and increased wind up ratio (P = 0.02) (P = 0.53), mechanical pain thresholds (P = 0.86), and pressure pain thresholds (P = 0.14) were found between both groups  B. No difh groups B. We looPressure pain thresholds could not be measured in eight patients because of concern regarding exacerbation of blistering and wounding of the skin. One-third of RDEB patients presented with abnormal paradoxical heat sensations (a sensation of warmth on skin cooling) and 17.2% of them demonstrated dynamic mechanical allodynia phenomena not observed in controls. Overall, the somatosensory phenotype of RDEB patients reflects hypoaesthesia in small fibre mediated domains but in addition, a number of examples of hypersensitivity including mechanical and thermal hyperalgesia and brush evoked allodynia.P = 0.16). For the tests that demonstrated a gain-of-function in RDEB patients  we found no correlation with the RDEB severity scores  and the different QST parameters in which we found significant loss- or gain-of-function in patients with RDEB . We founy scores E and F.The BEBS score consists of eight items: area of damaged skin, involvement of nails, involvement of mucous membrane, scarring of hands, skin cancer, chronic wounds, alopecia and nutritional compromise. We investigated the correlation of the different items of the BEBS with the different measurements of the QST that correlated with BEBS (note that skin cancer was excluded as no patients had developed skin cancer). We found that scarring of the hands correlates very well and consistently with loss-of-function on thermal tests . Scarring of the hands gets worse with the repetitive cycles of blistering and regeneration and therefore reflects active and long-lasting disease affecting the hands (and probably the lower limbs as well) .Therefore, small sensory afferents (C and Aδ fibres) seem to be the most affected by the level of damage produced in the skin by the disease.Nerve conduction studies were done in 21 volunteers and 21 RDEB patients. Neurophysiology could not be undertaken in some RDEB patients where the location of active wounds made it impossible to perform the tests or the investigation was declined. Sensory and motor conduction examined in the sural and peroneal nerves revealed no difference in any parameters comparing patients with RDEB and controls .Table 2P < 0.0001, P = 0.04, P = 0.3, Skin biopsies to quantify intraepidermal nerve fibre density in the distal leg were performed in 18 volunteers and 18 RDEB patients and were only taken from sites in which there was no active blistering. There was a striking reduction in IENFD in RDEB patients [mean (SD) fibres per mm: 2.6 (1.2)] compared to our controls recruited in Chile [14.1 (0.6), We also assessed autonomic nervous system function. Tests that assess blood pressure responses to orthostatic testing are in a large part a reflection of sympathetic activity. Conversely, changes in heart rate during orthostatic testing and Valsalva manoeuvre, as well as during deep breathing, reflect parasympathetic modulation . We asseP = 0.02). Moreover, sympathetic skin response was absent in two patients with RDEB and was present in all control subjects  and as such are less exposed to the damage and healing processes within the skin, are not affected. These results suggest that neuropathy is caused by repeated episodes of blistering and skin regeneration and emphasize the need for adopting treatment algorithms for neuropathic pain in these patients.Chronic pain in RDEB patients is a common and debilitating problem and in accordance with previous literature we found that in our cohort, over 90% of patients have daily moderate-to-severe pain . It is iThe DN4 questionnaire was developed as a screening tool to discriminate between neuropathic and non-neuropathic pain. A score of 4 or higher suggests neuropathic pain . We also found reduced innervation of sweat glands in the dermis. These findings are consistent with selective injury to cutaneous small fibres with no evidence of generalized autonomic dysfunction.COL7A1 gene, which encodes the alpha-1 chain of type VII collagen a protein restricted to the basement zone beneath stratified squamous epithelia . Animals lacking COL7A1 do not develop any abnormalities of the nervous system (Mutations in our cohort of patients are all located at the The exact mechanism of the injury and its length dependence is interesting and as yet not fully established. It may be direct physical severing of axons at the dermo-epidermal border. Or may be due to changes in local environment as the loss of type VII collagen can change the bioavailability of soluble proteins; an increase in TGF-β and a decrease in MMP2 have been reported (Neuropathic pain is defined as pain caused by a disease or a lesion of the somatosensory nervous system (Innervation in the skin consists of myelinated and unmyelinated fibres in the dermal plexus, and only unmyelinated fibres that cross the dermo-epidermal border reaching the epidermis. Dermatological conditions in theory could affect epidermal innervation, increasing or decreasing its density , photodaWe conclude that abnormalities in the dermo-epidermal boundary in patients with RDEB lead to injury to the distal terminals of small fibres with a particular vulnerability of the longest axons. This results in small fibre dysfunction and a high incidence of neuropathic pain. Assessment and targeted treatment of neuropathic pain in this population should be instituted in order to ameliorate their disabling pain.Supplementary DataClick here for additional data file.


Introduction. The primary objectives of this study were to assess patients' description of their acute pain intensity; patients' attitude towards their pain management during hospitalization; and their overall satisfaction with pain treatment. Methodology. A cross-sectional questionnaire-based study was conducted between October 2014 and March 2015 in three medical centers in Lebanon. All participants' responses were reported using descriptive statistics. The association between categorical variables was evaluated using Pearson χ2 test or Fisher's exact test where the expected cell count was < 5. Results. A total of 119 women on the maternity services and 177 patients on the orthopedic services were surveyed. Around 50% of obstetric and 37% of orthopedic patients reported pain to be severe at its highest intensity. In maternity and orthopedic patients, respectively, unfavorable practices included pain not being assessed prior to pain medication administration (19.3% and 30.5%), having to wait for ≥30 minutes before getting the pain medication (14.2% and 11.3%), and pain score not being documented on medical chart (95% and 93.2%). Surprisingly, 94.1% of the maternity and 89.2% of orthopedic patients were satisfied to strongly satisfied with their pain management. Conclusion. Pre- and postoperative pain remain a prevalent problem that requires a consensus and joint efforts for improvement. Pain-related position statements and published clinical guidelines consider pain as the “fifth vital sign” that requires a holistic management approach –5. Pain Pain management is a major concern for patients. Patients' perception of pain care became a vital criterion and a relevant outcome measure for healthcare institutions . FurtherSuboptimal pain control has been frequently reported in acute care settings and documented to negatively impact patients' health, delay recovery, increase postoperative morbidity, and reduce patient satisfaction , 13, 14.Reports on pain management approaches and outcomes in cancer palliative care patients in Lebanon and the Middle East have been published –26. HoweAccordingly, the primary objectives of this study were to assess (1) patients' description/rating of their acute pain intensity before and after surgical procedures; (2) patients' attitude and perception towards their pain management during hospitalization; and (3) their overall satisfaction with pain treatment. Secondary objectives were (1) to identify predictive factors that affect patients' satisfaction with pain management and (2) to evaluate the agreement between patients' overall satisfaction with their pain management and that of their healthcare providers.A prospective, cross-sectional study was conducted between October 2014 and March 2015 in three academic medical centers in Beirut, Lebanon. The study targeted two different in-patient adult populations who are most likely to experience acute noncancer pain: orthopedic surgery and obstetric postdelivery patients.Two sets of questionnaires, one for the orthopedic surgery and another for the obstetric postdelivery patients, were developed by the investigators in English and then translated to Arabic by a licensed translator for use with patients. Questionnaires were developed in congruence with the American Pain Society Patient Outcome Questionnaire (APS-POQ) and modified to align with the study objectives . The queA brief cover letter was provided to participants, detailing the purpose of the questionnaire and reassuring confidentiality. Participating patients were asked to voluntarily and anonymously fill out the questionnaires that included the following sections: (1) demographics, (2) pain characteristics including intensity, (3) attitude towards pain management including patient expectations and preferences, and (4) patient satisfaction with pain management.Demographic information included gender, age, marital status, educational and occupational status, type of healthcare coverage, and other demographics as applicable to the study population. Pain intensity was measured with the items “least” and “most” severe based on numerical rating scales (NRS) with answer options ranging from 0 to 10, where 0 reflects no pain and 10 worst pain possible. Pain severity was further categorized, as described by the patient, into the following categories: no pain (NRS score of 0), mild (NRS score of 1–3), moderate (NRS score of 4–6), severe but tolerable (NRS score of 7–9), and excruciating (NRS score of 10). Pain intensity was assessed right before and right after the procedure for both populations studied. For the purpose of this study, “right before” was defined as the day of the procedure, while “right after” was defined as day 1 after procedure. Similar to the APS-POQ, the questionnaire targeting the orthopedic surgery population assessed pain interference with activities and sleep, with answer options from 0 to 10, where a higher number indicates more interference . The actAttitude towards pain management section included questions related to (1) patients' barriers to receiving pain medications ; (2) pain assessment by a healthcare provider prior to delivery of intervention; (3) patient education by a healthcare provider regarding pain treatment; and (4) timely delivery of intervention. Patient satisfaction was measured using a 4-point Likert scale including strongly dissatisfied, dissatisfied, satisfied, and strongly satisfied.Third-professional-year pharmacy students from the Lebanese American University School of Pharmacy were properly trained by their clinical preceptor to approach patients asking for their willingness to fill out the questionnaire and to assist them in collecting the required data. Patients were eligible for inclusion if they were alert and have been hospitalized for at least 24 hours on the orthopedic surgery and obstetric postdelivery patient care services. Data were collected on day 1 after delivery or surgery. Upon completion of the questionnaire, students place the collected data forms in a sealed envelope that was then submitted to the primary investigator at the end of each week. The investigators did not have any control over the pain management delivery to the patients.Data collection for the outcomes involving the healthcare providers (HCPs: physicians or nurses) was completed through the input of the healthcare providers who were in direct charge of patient care. This included a personal communication with the HCPs in charge to assess (1) their rating of patients' pain after the procedure, (2) their documentation of the patients' pain intensity in the medical chart, and (3) their overall satisfaction with the result of the pain management they provided.No participants' identifiable information (name or contact information) was collected and all obtained information was processed confidentially. The study was approved by the Lebanese American University Institutional Review Board and the applicable executives of the three involved hospitals. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.χ2 test or Fisher's exact test where the expected cell count was less than 5. p values below 0.05 were considered to be statistically significant.Completed questionnaires were entered in an excel form throughout the study duration using a coding system, and then data were analyzed using the SPSS version 21 software. Data from each unit were entered separately on different excel sheet to maintain accuracy of records of each unit thus avoiding mixing of data entry and analysis. Demographic data, information about pain intensity, and attitudes towards pain management were summarized using descriptive statistics. The association between categorical variables was evaluated using Pearson A total of 119 women on the maternity services and 177 patients on the orthopedic services were surveyed on day 1 after surgery. The majority of surveyed patients were married (100% and 76.3%) and completed high-school (33.6% and 31.6%) or university education (48.7% and 33.3%); were employed (64.7% and 49.7%); and were covered by private insurances (30.3% and 31.1%) or national social security fund (37.8% and 42.9%) in the maternity and orthopedic patient populations, respectively. Patients' sociodemographic characteristics are listed in The majority of obstetric patients described their pain as mild to moderate at its least intensity . When at its highest, the pain was mostly reported as moderate to severe . Pain experienced right before delivery was generally severe (31%) or excruciating (37%) in this patient population. Right after delivering the baby, patients were still experiencing moderate (42%), severe (30.3%), and excruciating pain (13.4%) .Orthopedic patients varied in their description of pain at its least severity and reported pain of different intensities: mild (22.0%), moderate (36.7%), severe (21.55%), and excruciating (19.8%). When at its highest, the pain intensity was again broadly reported as moderate (18.1%), severe (36.7%), and excruciating (18.1%). Right before the surgical procedure, pain intensity in orthopedic patients was variable as follows: mild (20.9%), moderate (25.4%), severe (26%), and excruciating (27.1%). After the surgical procedure, patients still experienced variable pain severity with more of them reporting moderate (28.9%) and severe pain intensity (29.9%). After surgery, pain was moderately interfering with activities in bed such as turning and repositioning (44.6%) and activities out of bed such as walking or sitting in a chair or standing (46.9%) .Healthcare providers (HCPs) were asked to rate the patients' pain intensity right after the procedures. For both studied populations, HCPs mostly reported the pain as moderate in intensity: 19.3% for obstetric patients and 27.7% for orthopedic patients. Moreover, it is worth noting that pain scores were documented in obstetric and orthopedic patients' charts in 5% and 6.8% of the cases only, respectively .Sixty percent of obstetric patients and 74.6% of orthopedic patients mentioned that they would like to be treated when in pain, while some of them preferred not to be treated (22.7% of obstetric patients versus 10.7% of orthopedic patients). Barriers to pain management identified by patients included fear of adverse reactions as the main barrier listed by both obstetric and orthopedic patients (52.1% and 49.2% resp.), followed by the fear of addiction potential (11.8% and 18.1%), tolerance (16% and 13%), and additional cost (12.4% and 13.6%) .Several unfavorable management practices related to pain assessment and management were reported in the obstetric and orthopedic services . These iWhen asked about satisfaction with the overall pain management, the majority of patients in obstetric and orthopedic services reported to be satisfied  to strongly satisfied . Generally, 5.8% of the obstetric patients and 10.7% of the orthopedic patients were dissatisfied (dissatisfied and strongly dissatisfied) with the overall pain management they received .p = 0.041), not having Ministry of Health coverage , and not receiving first class services were associated with higher patients dissatisfaction (Results detailing the sociodemographic factors and their association with patients' satisfaction with pain management for the combined populations of obstetric and orthopedic patients are presented in sfaction .p = 0.030). Patients who were not asked about their previously used pain medication , those who were not questioned about their pain severity prior to medication administration , and those who did not receive timely medication administration (<30 minutes)  were dissatisfied with the delivered care. In addition, failing to educate the patient about the importance of pain management and the need to report uncontrolled pain was identified as a predictive factor   .This study addressed patients' perception of pain management in two patient populations experiencing postoperative acute noncancer pain. Our results showed that pain was prevalent and consistently experienced by obstetric and orthopedic patients before and after surgical procedures in varying intensities. In fact, at least 50% of patients in each of the studied populations experienced severe to excruciating pain right before the procedure. Similarly, at least 40% of patients in each of the surveyed populations reported being in severe to excruciating pain right after the procedure. Such findings suggest that the problem of postoperative pain remains substantial despite the availability of treatment options and published guidelines for pain management. This is in line with published studies in obstetric patients showing that acute postdelivery pain was commonly reported , 31. In When asked about their pain intensity, our studied populations demonstrated a widespread subjectivity in reporting pain intensity that encompassed all pain intensity levels during the different assessment time points. This is in congruence with the definition of pain by the International Association for the Study of Pain whereby pain is referred to as an emotional experience . This emPain intensity is the most relevant clinical dimension of the patients' pain experience , 37. ValAn intervention-necessitating finding in our current study is that documentation of pain intensity was not completed for more than 90% of surveyed patients according to their HCPs. Although 80% of obstetric patients and 69.5% of orthopedic patients confirmed that their pain was assessed prior to pain medication administration, documentation of that pain assessment was only completed in 5% of obstetric patients and 6.8% of orthopedic patients. Similarly, multiple studies on pain management have shown that documentation of pain assessment was not consistently done for the majority of patients –45. DespBarriers to effective pain management reported in this study and based on the surveyed patients' perspective included fear of adverse effects followed by addiction, tolerance, and fear of cost. This lack of patients' knowledge regarding pain issues was also identified by the First National Pain Medicine Summit as one of the top three barriers to receiving adequate patient care along with lack of competent pain providers and lack of knowledge by peers and/or patients regarding the field of pain medicine. The Summit further details patients' barriers to include (1) belief that pain is inevitable; (2) reluctance in reporting pain and in taking prescribed medications; (3) concern about addiction and the adverse effects of medications; (4) inaccessibility of pain management professionals; and (5) cost of pain medications and lack of insurance coverage for pain management .This study provided optimistic data suggesting that communication between patients in pain and HCPs was being implemented. Patients were engaged in the care process as 76.5% and 80.8% of obstetric and orthopedic patients, respectively, were asked about previously used medications for pain management. In addition, 63% and 67.2% of obstetric and orthopedic patients, respectively, were asked to report when in pain. Moreover, 80.7% and 74% of obstetric and orthopedic patients were informed when pain medications were administered. Accordingly, such favorable practices involving communication and patient engagement in the care process could explain our positive findings of patient satisfaction with the delivered care despite the substantial pain that was still being experienced. In fact, 94.1% of obstetric patients and 89.2% of orthopedic patients were satisfied to strongly satisfied with the pain management they received.Similarly, Bourdillon et al. assessed patient perception of pain management in an effort to determine the factors related to patient satisfaction . In theiA secondary study objective identifying predictive factors for patient satisfaction with pain management further supports the importance of patient engagement in the care process to ensure satisfaction. The practices in pain management were found to be statistically correlated with patient dissatisfaction in this study mostly centered on patients' engagement in their care. Dissatisfied patients were those who did not have their pain assessed prior to pain medication administration, those who were not asked about previous medications used for pain management, and those who were not informed to report it when in pain. In addition to involving patients in their own care, our study reported that the timely delivery of pain medications to the patients was another factor affecting patient satisfaction. These results are in congruence with the previously referenced literature on patient engagement and satisfaction with care which can be explained by the notion that both ideas stem from trust and communication between HCPs and patients .Interestingly, an incongruity was noted among the HCPs' and the survey populations' satisfaction. In fact, HCPs' satisfaction was independent of patients' satisfaction levels. Such a disagreement in satisfaction with pain management was reported in the literature and related to various reasons. The latter include subjectivity of pain experience and the difficulty of accurately quantifying it; differing interpretations of patient pain intensity and treatment response between patients and HCPs; and a general perception that patients exaggerate their pain experience , 52, 53.To our knowledge, no studies in Lebanon report on the pain intensity and attitude towards pain management in the postoperative setting from patients' perspective. This study addressed a current and essential clinical problem that remains suboptimally managed. The method is strongly elaborated and includes two large patient populations with different conditions, which strengthens our findings. A limitation in our study is that interviewed participants could have recall bias. Another limitation, in our secondary endpoints, was the missing information from the patients' charts and the relatively low number of healthcare providers that we were able to interview. Yet, this study was able to identify the urgent need to have HCPs document pain intensity scores in patients' charts and the importance of engaging patients to ensure their satisfaction with pain management. Our findings will be shared with the concerned institutions to better understand their patient population needs, contemplate the implementation of acute pain management services, and improve on pain assessment, management, and patient education.Patients presenting with acute pain expect and deserve utmost treatment. High quality pain management should include appropriate assessment; collaborative care planning comprising patient involvement; and efficacious treatment resulting in overall patient satisfaction. Pre- and postoperative pain remain a prevalent and severe problem that requires a consensus and joint efforts for improvement. Identified patient barriers that hamper pain management must be overcome. Active patient participation in their care might be an effective way to improve pain management.