Rates of chronic pain are rising sharply in the United States and worldwide. Presently, there is evidence of racial disparities in pain treatment and treatment outcomes in the United States but few interventions designed to address these disparities. There is growing consensus that chronic musculoskeletal pain is best addressed by a biopsychosocial approach that acknowledges the role of psychological and environmental factors, some of which differ by race.The primary aim of this randomized controlled trial is to test the effectiveness of a non-pharmacological, self-regulatory intervention, administered proactively by telephone, at improving pain outcomes and increasing walking among African American patients with hip, back and knee pain. Participants assigned to the intervention will receive a telephone counselor delivered pedometer-mediated walking intervention that incorporates action planning and motivational interviewing. The intervention will consist of 6 telephone counseling sessions over an 8–10 week period. Participants randomly assigned to Usual Care will receive an informational brochure and a pedometer. The primary outcome is chronic pain-related physical functioning, assessed at 6 months, by the revised Roland and Morris Disability Questionnaire, a measure recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). We will also examine whether the intervention improves other IMMPACT-recommended domains . Secondary objectives include examining whether the intervention reduces health care service utilization and use of opioid analgesics and whether key contributors to racial/ethnic disparities targeted by the intervention mediate improvement in chronic pain outcomes Measures will be assessed by mail and phone surveys at baseline, three months, and six months. Data analysis of primary aims will follow intent-to-treat methodology.We will tailor our intervention to address key contributors to racial pain disparities and examine the effects of the intervention on important pain treatment outcomes for African Americans with chronic musculoskeletal pain.NCT01983228. Registered 6 November 2013.ClinicalTrials.gov:  Approximately 100 million adults in the United States (US) suffer from chronic pain, and musculoskeletal pain is the most common type of chronic pain [pain to be a type of health disparity, defined as a difference in health status that systematically and negatively impacts racial/ethnic minority groups [pain treatment, using the definition of health care disparities from the Institute of Medicine report, Unequal Treatment, as “differences in the quality of health care that are not due to access-related factors or clinical needs, preferences or appropriateness of intervention” [Presently, there is evidence of racial and ethnic disparities in pain in the United States but few interventions designed to address these disparities –3. We coy groups . We defivention” . Importavention” .healthcare system. African American patients in the United States are more likely to experience barriers to accessing and utilizing healthcare. African American patients are more likely than whites to have unmet medical needs due to myriad factors, including lack of insurance and underinsurance [racial disparities in pain treatment. They are more likely than whites to have their pain discounted and underestimated, are less likely to be screened for pain, and more likely to be undertreated and to receive less or no analgesia [poor quality communication with their providers, which adversely affects the quality of pain treatment [A number of contributors to racial disparities in pain occur at the level of the nsurance , experiensurance , 7. Afrinalgesia , 8–10. Areatment .Environmental factors may also contribute to racial disparities in pain, through multiple pathways. There is growing evidence that experiences of racial discrimination, experienced within and outside healthcare, are associated with greater pain, although the mechanisms by which this occurs are not fully understood [derstood –18. Afriderstood , 20.Psychological factors may also contribute to disparities in pain, by reducing the use of effective self-management strategies [rategies –10. Thisrategies , 22.There is growing consensus that chronic musculoskeletal pain is best addressed by a biopsychosocial approach that acknowledges the role of psychological and environmental contributors to pain –28, someThe intervention was based on several lines of research evidence. First, physical activity can reduce chronic musculoskeletal pain and improve function –18. SecoGiven the psychological and environmental contributors to racial disparities in chronic pain treatment, we developed an intervention that addresses the multiple contributors to chronic pain that disproportionately affect African American patients . This approach to developing engagement materials was successfully used by Fu and colleagues in a prior study with Veterans .Intervention participants will be asked to complete six telephone counseling sessions over a 10 week period (with a 12 week absolute cut off time point) using a patient workbook  , 16 withThe action planning component of this intervention was based on a protocol and structured curriculum developed by French and colleagues. This program was found to be effective at increasing walking in several trials in a non-clinical population  –30. It aThe pedometer component of this intervention was based on the work of French and colleagues , and KreCounselors have at least a Master’s degree in a counseling-related field  and receive at least 15 h of training by an expert to prepare them to deliver the intervention using a structured training manual. Training involves reviewing the treatment manual, role playing, attending a Motivational Interviewing course and review of audio-taped sessions with feedback. Session tapes are reviewed to assess fidelity to the protocol and to provide feedback to counselors. Counselors will participate in case consultation throughout the course of the intervention to prevent “drift” from the manualized treatment. An expert in counselor training will meet with the study counselors about every week to provide corrective feedback and ongoing support. In order to ensure treatment integrity, all treatment sessions will be audiotaped and 10% will be randomly selected and reviewed by trained coders to assess both the use of treatment concordant strategies and the absence of commonly used treatment strategies not included in the manualized treatment.Participants randomized to the Usual Care (UC) control condition will receive pedometers and an informational brochure about the benefits of walking. They will be instructed  to wear the pedometer and to record their pedometer readings on logs over 7 days at the baseline assessment, three months and six months follow-up time points. They will report these step counts during the surveys, a procedure which has been used successfully in previous studies with similar populations  (BurgessP = 0.105) than in the UC group and 0.6 point lower (P = 0.007) than in the health education (HE) group. The mean visual analog scale pain score in the intervention group was 1.1 points lower (P < 0.001) than in the UC group and 1.0 point lower  than in the HE group [Our research team has conducted several studies that address acceptability, feasibility, and potency of key components of intervention. The “Self-Management of OsteoArthritis in Veterans” (SeMOA) study  was a seHE group , 10.The “Tailoring Coping Skills Training (CST) for African Americans with Osteoarthritis” pilot study involved focus groups and a pilot trial to 1) assess the cultural appropriateness of an intervention using specific CBT techniques to improve coping skills and improve pain outcomes among black veterans with OA, 2) tailor the intervention and modify it for telephone, and 3) perform a pilot trial of the intervention. These CBT techniques are part of the proposed intervention . Focus groups showed that black Veterans viewed the intervention as culturally appropriate. Tailoring involved lowering literacy levels of patient materials. The pilot trial of CST demonstrated individual improvements on the AIMS-2 .P = 0.01) as well as lower pain scores , and greater average step counts [Pedometer-Mediated Walking program to reduce pain among chronic musculoskeletal pain patients. In the “Veterans Walk to Beat Back Pain” study, 229 Veterans with back pain were randomly assigned to a pedometer-mediated walking intervention, administered over the internet, or Usual Care . Potentially eligible participants were identified both through provider referrals and by using VA electronic medical record data. Findings from this study showed that > 90% of patients in both groups completed 6-month assessments, with intervention patients reporting significantly less back pain-related disability compared to controls  techniques and exercise for chronic MSK pain. Dr. Heapy and Dr. Robert Kerns have reported a number of studies that demonstrate the feasibility and acceptability of conducting CBT trials with Veterans with chronic pain , as well as formative research that provided information about the types of coping skills most preferred by patients with chronic pain (which included exercise). These studies include: 1) an evaluation of the effect of a tailored cognitive-behavioral approach to the management of chronic back pain on promoting adherence to therapist recommendations for pain coping skill practice; 2) a randomized controlled trial of cognitive-behavior therapy for painful diabetic peripheral neuropathic pain; and 3) a study testing the efficacy of interactive voice response, for delivering CBT for chronic low back pain –40.The goal of this randomized controlled trial is to investigate the effectiveness of the intervention in improving the pain-related function of African American patients with chronic musculoskeletal pain through a proactive coaching program designed to increase walking. Data collection will occur at baseline (randomization) and at three and six months post-randomization.The specific study aims are:improve pain-related physical functioning (primary outcome),improve emotional functioning, pain intensity, and ratings of overall improvement (first secondary outcome)increase walking as measured by step counts (second secondary outcome).Primary Aims: To test the hypothesis that compared to UC, a proactively delivered walking intervention targeted to African American VA patients with chronic musculoskeletal pain will:investigate whether key contributors to racial disparities targeted by the intervention mediate improvement in chronic pain outcomes and increases in walking,test the effectiveness of the intervention on non-African American patients and explore whether effectiveness differs between African American and non-African American patients, andexamine whether the intervention reduces the use of opioid analgesics.Secondary Aims are to:This study is approved by the Institutional Review Boards (IRBs) at the Minneapolis VAMC and VA Central Office IRB in Washington, DC. ACTION is also reviewed and approved annually by the granting institution, the VA Health Services Research & Development (HSR&D) Service.Study participants will be recruited from the Atlanta VAMC, which we chose because it has a high percentage of African American patients. The main facility and satellite clinics have about 9,294 patients who meet our initial eligibility criteria. These criteria include having 1 hip, back or knee diagnosis code in the past year, a second hip, back or knee diagnosis code 18 months from the first one, and the Atlanta VA is identified as their preferred care location. From this cohort, we will randomly select patients (African Americans and non-African Americans) for recruitment. We will include non-African Americans in our sample for comparison purpose. Administrative race data will be verified on the brief screening survey.Recruitment will be conducted via an introductory letter, which describes the study for potential participants and provides an option to opt out if they are not interested in participating in the study. Further, qualifying criteria will be determined through the administration of a telephone screening questionnaire. Eligible patients must have pain duration of ≥ 6 months, moderate-severe pain severity and interference with function (defined as a brief pain intensity and interference (PEG) score of ≥ 5), self-reported ability to walk at least 1 block, and be able to communicate effectively by telephone. The PEG  is an ultra-brief (three items) assessment tool for pain, which is valid, reliable and responsive to change –44. The Recruitment and telephone counseling will be conducted by staff at the Center for Chronic Disease Outcomes Research (CCDOR) at the Minneapolis VAMC. Telephone counseling will be conducted separately from recruitment by separate staff.The primary analyses will use the sample of African American patients, and the study was intentionally designed to be adequately powered to detect effects in this core group. Additional analyses will be conducted in the non-African American sample and the overall sample. Because our primary aims focus on the sample of African American patients, the methods outlined ensure the study is sufficiently powered for this sample see Fig. .Fig. 2StBased on our previous experience conducting interventions with African American veteran patients with chronic pain , we antiParticipants will be randomized to either study intervention or UC (1:1) at the time that the baseline surveys are listed as complete in the study tracking application. At receipt of a completed baseline, participants will be randomized and sent letters describing whether they are in the intervention or UC group. The randomization list will be concealed from the research team within the tracking application, so team members will not know the next study assignment. In order to ensure that treatment is equally balanced on race the randomization is stratified on participant self-identified African American or non-African American status and balance in assignment over time is achieved using permuted block randomization with block sizes of 4, 6 or 8.Data collection will be conducted by mail at baseline, and a combination of mail and telephone at three and six months post-randomization. At pre-screen, potential participants will receive a pre-notice letter. About a week later, research staff will call to assess patients’ interest, answer questions, conduct an eligibility screener, go over the information sheet (in place of an informed consent form), and obtain oral consent. Participants will then be mailed a baseline survey and pedometer.Fourteen days prior to the three and six month follow-up dates, all participants will be mailed a postcard reminding them to wear their pedometers in preparation for filling in the 7 day walking journal on the upcoming survey. A week prior to the three and six month dates, follow-up surveys will be mailed to all participants. Over the course of two weeks after surveys are mailed, non-responders will be called to ensure receipt of the survey, answer questions, and do the survey over the phone (instead of the mailed version) if the participant is willing. After 3 completed reminder calls, non-responders will be mailed another postcard reminding them to return the paper survey. In addition, at 6 months non-responders will receive a second copy of the survey in the mail along with an especially engaging cover letter. (See Tables The primary outcome of a pain-specific measure of functioning will be assessed at six months using the revised version of the Roland and Morris Disability Questionnaire (RMD), which is widely used in studies of chronic musculoskeletal pain and included in the IMMPACT recommendations. The RMD at three months will also be assessed as a secondary outcome. Although the original version of the RMD focused on low back pain [We will assess the following core chronic pain outcome domains and measures recommended by IMMPACT:  1) The pack pain , the revack pain . The scaack pain . 2) Emotack pain  and the ack pain . 3) Painack pain , 42. 4) Walking will be measured as the number of average daily steps using pedometer readings recorded in walking logs at three and six months, based on seven consecutive days of data. We are using the Omron HJ-321 pedometer, which can be worn in a pocket, around the neck, or on a belt clip (orientation does not matter) and has been shown to be highly accurate, including in obese populations . PatientPain-related fear avoidance will be measured by the fear-avoidance beliefs about physical activity subscale  of the Fear-Avoidance Beliefs Questionnaire (FABQ) . Self-efSocial support for exercise will be assessed using the Marcus Social Support questions , and relThese factors will include perceived discrimination in healthcare , which will be assessed using the Perceived Discrimination in Healthcare Scale , and theIn order to further assess use of opioid analgesics, we will obtain prescription information from electronic medical records. We will include survey questions to assess the use of opioids and non-opioid treatments for pain.Participants will be asked to provide information about whether they use a walking aid and information  used to calculate their Body Mass Index. We also will assess basic socio-demographic information such as education level, income, employment status, and disability status .Our sample size calculation uses the RMD score as the primary outcome at six months. For our primary analysis we will use a responder analysis, in which we define clinically significant changes as a 30% reduction in pain disability from baseline, using the RMD, and have powered the study to be able to detect this change. This is the accepted threshold for clinically significant improvement in clinical trials and recommended by the IMMPACT guidelines , 58. PreWe factored in that up to 50% of the study sample might be non-African American. Since we want to have power to detect meaningful effects in the subgroup that only includes African American patients (~100/50% = 200), and to allow for up to 20% attrition, we will need to randomize 250 patients for each arm of the study, for a total of 500 patients recruited with at least 200 African American patients with complete data for the final analyses. For the purposes of this study, we are not forcing balance between African American and non-African American participants, and are instead allowing for the potential that more than half of the participants are African American, since assessing efficacy of the intervention in a population of African American pain patients is the primary target.The primary aims are to test the hypothesis that the intervention will improve chronic pain-specific physical functioning—the primary outcome (H1a), improve emotional functioning, pain severity and ratings of overall improvement (H1b), and increase walking (H1c), compared to UC for African American patients with chronic hip, back, and knee pain.After assessing data for normality and evidence of balance of baseline factors across intervention groups, generalized linear regression models will be used to estimate the main effects of the intervention for all participants (African Americans and non-African Americans).To compare the effects of the intervention to UC on the IMMPACT measures of pain outcomes, the primary outcome measure is the RMD score assessed at 6 months (i.e. primarily a 30% reduction from baseline and secondarily mean change from baseline) (aim 1a). The secondary outcome measures are pain severity, the PHQ-8 and GAD-7, and the global rating of change scale (aim 1b). For all of these outcomes we will use generalized linear regression fit using appropriate distribution and link functions. Each participant will be modeled as a random intercept to allow within-patient correlation of the repeated measures. The use of a mixed-effects model will allow us to use data from participants who may be missing either baseline or the 6-month data while giving an unbiased estimate of the outcome comparisons as long as missing data is approximately random.To compare the effects of the intervention to UC on increasing walking behavior (aim 1c), walking will be measured by step counts, which are reported based on readings from the Omron HJ-321 pedometer. The effect of the intervention on step counts will be assessed by comparing average daily step counts measured over 7 days. We will use a mixed-effects model with the average daily step counts during the last week of the three month and six month measurement points as the dependent variables, with a similar analytic plan as described for Aim 1a.Our secondary aim is to investigate whether key contributors to racial/ethnic disparities targeted by the intervention  mediate improvement in chronic pain outcomes.The key measures for this aim include the Fear-Avoidance Beliefs Questionnaire (FABQ) , the ExeOur secondary aim 2 is to explore whether the intervention reduces use of opioid analgesics. Using similar analytical methods as described for the Primary Aims, we will use generalized linear models to explore whether use of opioid analgesics are reduced in the intervention group compared to the UC group, using survey responses and pharmacy data. We will compare the proportion of participants who, at baseline, report taking opioids at baseline at the 6-month follow-up report that they no longer take opioids, using the question, “Do you take an opioid medication for pain? .” We will also examine opioid daily dose reduction of 50% from baseline to 6 months, based on VA pharmacy dispensing data that has been converted to morphine equivalent doses.Our secondary aim 3 is to determine if the intervention is effective for non-African American VA patients and other subgroups of patients who may experience barriers to effective pain treatment. We will also explore whether there are differences in effectiveness between African American and non-African American patients. We will conduct the same analyses as for the Primary Aims and Secondary Aims 1–2 on the sample of non-African American patients (most of whom are expected to be white) and subgroups based on key demographic factors  and psychological, environmental and utilization factors, measured at the baseline survey that we included because they are expected to constitute barriers to effective pain treatment, based on our theoretical framework. We will also explore whether treatment effects will be moderated by common psychiatric conditions (anxiety and depression) and receipt of other forms of pain treatment.UC patients will receive some intervention elements . Nevertheless, we believe that the design represents the optimal compromise between scientific rigor and real-world practicality. Further, we expect that neither the pedometer nor the extra education will have a substantial influence on our primary outcome. If they do have any impact, the effect would be to reduce the likelihood of finding treatment differences between the control and intervention groups. Thus, the design for this study will provide rigorous evidence about the effectiveness of the proposed intervention.Another limitation inherent to this design is that, if the program is effective, we will not be able to determine the specific intervention element responsible for the success of the program. We decided to test a multi-component intervention, rather than test different components of the intervention separately, in order to target key factors that we believe are necessary to increase walking in this population, and to ensure that the intervention was potent enough to affect change.Presently, there is evidence of racial disparities in pain and pain treatment in the US but few interventions designed to specifically work well in populations most impacted by these disparities. This project adds to the evidence base on how to best improve pain treatment for African American patients with musculoskeletal pain, as well as other individuals who experience similar contributors to pain, and on the specific mechanisms that contribute to this reduction.One innovative aspect of this study is that it uses proactive telephone outreach to increase physical activity among patients with musculoskeletal pain. In proactive telephone outreach, counselors reach out to patients, offering them treatment, as compared to “reactive care,” in which the individual patient must initiate treatment. Proactive outreach can address barriers that members of negatively stereotyped groups (such as minority patients and chronic pain patients) are likely to experience. For example, such patients may experience poor quality communication with providers, and discrimination within and outside the healthcare system, which is associated with avoiding and delaying healthcare  –15, 32. At the present time when we are in the midst of a public health crisis caused by increased prescription of opioids , with li


Local infiltration analgesia (LIA) is commonly used for postoperative pain management following total hip arthroplasty (THA). However, the long-term effects of the component drugs are unclear. The aim of our study was to investigate functional outcome, quality of life, chronic post-surgical pain, and adverse events in patients within 2 years of undergoing THA.The study was a secondary analysis of data from a previous larger study. Eighty patients were randomized to receive either intrathecal morphine (Group ITM) or local infiltration analgesia (Group LIA) for pain management in a double-blind study. The parameters measured were patient-assessed functional outcome [using the Hip dysfunction and Osteo-arthritis Outcome Score (HOOS) questionnaire], health-related quality of life [using the European Quality of Life–5 dimensions (EQ-5D) questionnaire and the 36-Item Short Form Health Survey (SF-36) score], and pain using the numeric rating score (NRS), with persistent post-surgical pain having a NRS of > 3 or a HOOS pain sub-score of > 30. All complications and adverse events were investigated during the first 2 years after primary surgery.Pain intensity and rescue analgesic consumption were similar between the groups after hospital discharge. No differences were found in HOOS or SF-36 score between the groups up to 6 months after surgery. A significant group × time interaction was seen in the EQ 5D form in favor of the LIA group. No between-group difference in persistent post-surgical pain was found at 3 or 6 months, or in adverse events up to 2 years after surgery.Analysis of functional outcome, quality of life, and post-discharge surgical pain did not reveal significant differences between patients receiving LIA and those receiving ITM. LIA was found to be a safe technique for THA during the long-term follow-up. However, it should be noted that these conclusions are based on a limited number of patients. Total hip arthroplasty (THA) is a common and standardized surgical procedure. Postoperative mortality after hip joint replacement is low, but a number of complications remain, including persistent post-surgical pain (PPSP) , hip disThe use of NSAIDs administered orally or systemically during orthopedic surgery has been controversial due to the risk of delayed healing from the inhibition of osteoclast and osteoblast formation , specifiApproval for this study was obtained from the Regional Ethics committee in Uppsala as well as from the Swedish agency on drugs prior to patient recruitment for the initial larger study. The initial larger study was registered in Clinicaltrials.gov (Identification number: NCT01281891) and monitored by an independent organization based in the hospital for quality control; it was conducted in accordance with Good Clinical Practice. Patients were recruited from the Department of Orthopedic Surgery, University Hospital, Örebro, Sweden between 2011 and 2012. The study reported here is a secondary analysis of the data from the initial study on post-discharge events, including hip function and quality of life. These data are therefore part of the larger study but have never been published; in contrast, the primary data on early postoperative recovery and postoperative pain management have been published previously .A total of 80 patients in the age group 50–85 years, with ASA physical status I–II, who were undergoing elective THA were randomized in this prospective, double blind, parallel group, longitudinal study. Written and verbal informed consent was obtained from all patients prior to inclusion. The exclusion criteria were chronic pain requiring opioid medication, known allergy to local anesthetics, contraindications for using NSAIDs or receiving regional anesthesia, and inability to follow verbal or written instructions. Patients were allocated to one of two groups, namely, Group ITM  and Group LIA, according to a computer-generated randomization sequence by the hospital pharmacy. Thus, double-blinded syringes were sent to the operating room with the drugs/placebo according to the randomization sequence.Detailed information was provided to all patients on the surgery, anesthesia, postoperative pain management, and physiotherapy and all patients were asked to complete several questionnaires relating to hip function, pain and health-related quality of life  or an equal volume of saline (Group LIA). In Group LIA, 151.5 ml of a mixture consisting of a long-acting local anesthetic (ropivacaine 2 mg/ml = 150 ml), a NSAID (ketorolac 30 mg/ml = 1 ml), and epinephrine (1 mg/ml = 0.5 ml) was injected into the periarticular tissues in a systematic way as described previously; in Group ITM, an equivalent amount of saline was injected. Propofol was administered intravenously during surgery for sedation, if needed. At the end of surgery, a multi-hole catheter was tunneled about 8–10 cm from the skin incision and placed intra-articularly and connected to a bacterial filter under sterile conditions. After 24 h, 22 ml of active drugs  was injected in Group LIA patients via the catheter, and an equal amount of saline was injected into Group ITM patients, after which the catheter was withdrawn. Tramadol and paracetamol were administered as needed as rescue medication following surgery and home discharge. Cloxacillin 1 g was given intravenously before surgery and at 8, 16, and 24 h postoperatively.Pain (NRS). Pain now and average pain over the previous week was evaluated at then end of postoperative weeks 1, 2, 3, and 4 using a questionnaire. At 3 and 6 months pain intensity was recorded as pain on movement  when performing activities of daily living and was determined by a telephone call.Analgesic consumption. Analgesic consumption (paracetamol and tramadol) after discharge home was recorded each week for 1 month.Side effects and complications. All side effects and post-discharge complications were recorded. Any re-admission to the hospital following home discharge and the reason for admission was recorded up to 2 years postoperatively.Surgical outcomes. Patients were followed-up for a period of 2 years following THA to assess any complications, such as delayed wound healing, surgical site infection, persistent post-surgical pain (PPSP), hip dislocation, re-operation, or readmission to the hospital. Any deaths were recorded.Patient-assessed outcomes. Health-related quality of life (HRQoL) was determined preoperatively and after 7 days and 3 and 6 months following surgery using the European Quality of Life–5 Dimensions (EQ-5D) questionnaire and the 36-Item Short Form Health Survey (SF36) preoperatively and after 3 and 6 months postoperatively. Additionally, hip function was assessed using a standardized and validated questionnaire, the Hip dysfunction and Osteoarthritis Outcome Score (HOOS) preoperatively and after 14 days and 3 and 6 months following surgery.The EQ-5D questionnaire is a descriptive system of HRQoL states consisting of five dimensions , each of which can elicit one of three responses. A weighted average is constructed that varies from 1.0  to 0 (dead). The Swedish version is derived from the original British version.The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically based physical [physical component score (PCS)] and mental [mental component score (MCS)] health summary measures and a preference-based health utility index. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.The HOOS evaluates symptoms and functional limitations related to the hip. It consists of 39 items, assessing five separate patient-relevant dimensions: pain (P) (nine items); symptoms (S), including stiffness and range of motion (five items); activity limitations-daily living (A) (17 items); sport and recreation function (SP) (four items); hip-related quality of life (Q) (four items). To answer each question, five Likert-boxes are used . All items are scored from zero to four, and each of the five subscales is calculated as the sum of the items included. To enhance the interpretation, HOOS is transformed into a 0–100 (best to worst) scale.U test. HOOS markers were non-normally distributed and therefore evaluated after logarithmic transformations. P values of < 0.05 were considered to be statistically significant. All statistical analyses were performed using SPSS version 22  or STATA release 11 .Continuous variables were summarized using the mean ± standard deviation or the median with range, and categorical variables as percentages. The chi-squared test, or Fisher exact test when appropriate, was used to compare study groups for categorical data, with measures of association being the odds ratio with 95% confidence intervals. In view of the study setting with repeated measurements on subjects, we applied a mixed model with unstructured correlation structure to evaluate outcome variables EQ-5D, SF-36 (PCS and MCS), and different HOOS scores. Study group, time, and statistical interaction (group × time) were independent variables in the model as well as preoperative measurement of the outcome, the latter to adjust for mean differences in outcome between study groups at baseline. All independent variables were evaluated on a categorical scale, with the exception of preoperative outcome measurement, which was evaluated on a continuous scale. A statistically significant interaction indicates different mean differences of an outcome between study groups at different postoperative time-points. Analgesic consumption during the period 8–14 days following surgery and NRS pain scores were analyzed using the Mann–Whitney A total of 80 patients were randomized, but two patients were subsequently excluded from the analysis, one in each group: one patient decided not to continue the study after randomization (Group ITM) and the other patient left the study because the spinal anesthetic did not achieve adequate surgical analgesia (Group LIA) . Three additional patients were excluded from the analysis of the post-discharge follow-up: two patients in Group ITM (one with suspected postoperative infection and the other patient did not wish to continue with the study) and one patient in Group LIA (postoperative re-operation due to loosening of the cup) Fig. . The ageNo statistical differences were found in the NRS (pain now and average pain during the preceding week) between the groups during postoperative weeks 1–4 Fig. a, b. In p = 0.417); tramadol: 250 (0–2100) mg vs. 0 (0–2100) mg, respectively (p = 0.314)]. The incidence of persistent post-surgical pain (NRS > 3 or HOOS > 30) in the two groups is shown in Table p = 0.115). Two patients (6%) in group ITM had pain (NRS > 0) during walking at 6 months following surgery.No significant differences were found in rescue analgesic consumption between Group ITM and Group LIA during postoperative days 8–14 [median (range); paracetamol: 15 (range 0–34) vs. 14 (0–28) g, respectively , with a significant interaction (group × time) (p = 0.036); the latter indicated somewhat higher scores  in Group LIA (Table p < 0.001)  p = 0.06; the la) p = 0.06; the lap < 0.001), with the exception of the sport and recreation function (Table p = 0.004), with somewhat lower HOOS-Pain in Group ITM, specifically at 3 months, but there was no statistical difference between the groups.A significant improvement was found over time in all components of HOOS   in patients undergoing THA . The low–38% in pLocal anaesthetics have been used for the management of postoperative pain and have been injected in different tissue planes with good effect . AlthougWe used two different questionnaires to assess HRQoL. The EQ-5D is a standardized method to assess quality of life in five dimensions. The questionnaire is well validated, but it is non-specific and can therefore be used in different situations . The aveThis study was a follow-up of post-discharge data collected from a larger study performed to investigate the LIA technique for postoperative pain management. Therefore, power calculations were done on the basis of postoperative pain and not post-discharge events or quality of life. The study is consequently underpowered to detect uncommon hip complications following THA. For example, assuming that the incidence of hip dislocation requiring revision arthroplasties is 10%, it would require about 400 patients to see a doubling of the incidence in the LIA group. On the other hand, in our series of 80 patients, and assuming an overall incidence of 10%, we should have seen at least eight patients with major complications, which we did not. Additionally, if hip complications requiring re-operation were common when using NSAID in the LIA technique, we would have detected these over the last 10 years since we started using the technique because > 1000 patients have today been exposed to LIA during total hip and knee arthroplasties at our hospital. Therefore, and despite the small number of patients recruited into this study, we believe that the risk for worsened hip function, persistent pain, or delayed-healing appears to be minor and that the use of LIA did not appear to worsen these outcomes.Functional recovery after THA did not differ between patients receiving LIA and those receiving ITM at 6 months following surgery. Post-discharge pain, analgesic consumption, and PPSP were similar between the groups. HRQoL at 6 months and the incidence of adverse events up to 2 years following the surgery were also similar between the groups. LIA would appear to be a good alternative to ITM for postoperative pain management following THA and to be associated with mild post-discharge pain, satisfactory functional recovery, a good HRQoL, a low risk for PPSP at 6 months and a low incidence of adverse events up to 2 years after surgery.


State-related brain structural alterations in patients with episodic tension-type headache (ETTH) are unclear. We aimed to conduct a longitudinal study to explore dynamic gray matter (GM) changes between the pain and pain-free phases in ETTH.We recruited 40 treatment-naïve ETTH patients and 40 healthy controls. All participants underwent brain structural scans on a 3.0-T MRI system. ETTH patients were scanned in and out of pain phases. Voxel-based morphometry analysis was used to determine the differences in regional gray matter density (GMD) between groups. Additional regression analysis was used to identify any associations between regional GMD and clinical symptoms.ETTH patients exhibited reduced GMD in the bilateral primary somatosensory cortex, and increased GMD in the bilateral anterior cingulate cortex (ACC) and anterior insula for the in pain phase compared with the out of pain phase. The out of pain phase of ETTH patients exhibited no regions with higher or lower GMD compared with healthy controls. GMD in the left ACC and left anterior insula was negatively correlated with headache days. GMD in the left ACC was negatively correlated with anxiety and depressive symptoms in ETTH patients.This is the first study to demonstrate dynamic and reversible GMD changes between the pain and pain-free phases in ETTH patients. However, this balance might be disrupted by increased headache days and progressive anxiety and depressive symptoms. Tension-type headache (TTH) is the most prevalent and the most neglected form of primary headache worldwide , 2. EpidETTH is characterized by a recurrence of pain and pain-free states. Recent neuroimaging studies from other cyclical recurrence of pain conditions, including episodic migraine, episodic cluster headache, and menstrual pain, demonstrated dynamic brain structural changes depending on the states of diseases. These findings suggest that this neural plasticity may be an important pathophysiological mechanism underlying these disorders , 9–13. IVoxel-based morphometry (VBM) is a powerful analytical tool based on structural MRI data  that hasThe purpose of this study was to use whole-brain VBM analysis to longitudinally explore whether dynamic GM changes existed between pain and pain-free phases and to delineate possible relationships between GM changes and clinical variables in patients with ETTH. We hypothesized that ETTH exhibited state-related GM changes and that these regions might be involved in pain processing.An ETTH diagnosis was established according to the third edition (beta version) of the International Classification of Headache Disorders (ICHD) for ETTH . Most of2; matrix size = 256 × 256; in-plane resolution = 0.47 × 0.47 mm2; and number of slices = 156. A T2-weighted axial scan and a coronal fluid-attenuated inversion recovery (FLAIR) scan were also acquired to exclude brain lesions in patients and controls.High-resolution T1-weighted images, using a 3D-spoiled gradient echo sequence were obtained on a 3.0-Tesla MRI scanner  with a standard head coil for all participants. The scanning sequences were as follows: repetition time (TR) = 8.5 ms; echo time (TE) = 3.93 ms; flip angle = 12°; slice thickness = 1 mm; field of view (FOV) = 240 × 240 mmwww.fil.ion.ucl.ac.uk/spm) using the VBM toolbox with Diffeomorphic Anatomic Registration Through Exponentiated Lie Algebra (DARTEL) on the Matlab 10.0 platform . Images were initially assessed for scanner artifacts and gross anatomical abnormalities for each subject. Then, the anterior commissure was set as the origin of spatial coordinates along the reoriented anterior–posterior commissure line. All imaging analyses were conducted as suggested by the VBM Tutorial (http://www.fil.ion.ucl.ac.uk/~john/misc/VBMclass10.pdf). The process is briefly summarized as follows: (1) The T1-weighted images were segmented into GM, white matter (WM) and non-brain voxels  using the ‘new-segment’ routine implemented in SPM8 [For cross-sectional data, image pre-processing was performed with Statistical Parametric Mapping version 8 (SPM8) ( in SPM8 . (2) Pop in SPM8 , 26. (3)http://www.neuro.uni-jena.de/cat12/CAT12-Manual.pdf). Image pre-processing used the default settings involving intra-subject realignment, bias correction, segmentation, and normalization. A flexible factorial model was applied for the statistical analysis in one group with 2 time points.For longitudinal imaging data (pain ETTH vs. pain-free ETTH), we conducted the VBM analysis using the Computational Anatomy Toolbox (CAT12)  was used for statistical evaluation. Continuous variables were examined using 2-tailed paired or 2-sample p < 0.05, corrected by AlphaSim (per-voxel p < 0.001 with cluster size greater than 33 contiguous voxels). We performed further analyses to explore the correlation between regional GMD over the entire brain and clinical features  in ETTH patients with age and TIV as covariates. A p value less than 0.05 after correction for multiple comparisons was considered significant.For cross-sectional GM density (GMD) analysis, a general linear model in SPM8 was applied within and between groups  to assess the possible morphological changes with covariation for the age, the interval time between scans, total intracranial volume (TIV), and SAS and SDS scores. For longitudinal GMD analysis (pain ETTH vs. pain-free ETTH), a flexible factorial model was used. The statistical significance level was set at p > 0.05). The interval time between scans in ETTH patients was 6.56 (2.72) days. Compared with healthy controls, ETTH patients had significantly higher scores on the SAS and SDS for both in pain and out of pain phases . The SAS and SDS scores in ETTH patients were significantly increased during the pain phase compared with the pain-free phase (both p < 0.05).All participants completed the study. Table r = −0.782, p = 0.002 and r = −0.646, p = 0.007, respectively). In addition, GMD in the left ACC was negatively correlated with the SAS score  and the SDS score  in ETTH patients during the pain phase. No correlation was identified between regional GMD and disease duration or regional GMD and the VAS score in ETTH patients.No significant differences were identified between patients and controls for the total volume of GM, WM, or TIV. As demonstrated in Table To the best of our knowledge, this is the first longitudinal study that primarily investigated whether treatment-naïve ETTH patients have dynamic changes of brain GMD in different pain states. Our results demonstrated a lower GMD in the bilateral S1 and a higher GMD in the bilateral ACC and anterior insula in ETTH patients during the pain phase compared with the pain-free phase. In contrast, no GMD changes were observed in ETTH patients during the pain-free period. Our study exhibited a dynamic cortical plasticity in patients with ETTH. Furthermore, the correlation analyses indicated that these GMD changes could be affected by the headache days per month and anxiety and depressive symptoms.Convergent evidence from anatomical, imaging, and lesion data reveals that the S1, the ACC, and the anterior insula are key regions implicated in complex nociceptive processing , 28. TheOf note, the structural abnormalities were not observed in the pain-free period in ETTH patients. This structural reorganization and dynamic change may be ascribed to the transmission of sensory input and pain perception . AlthougHowever, this adaptation or balance might be disrupted as the headache days increased and anxiety and depressive symptoms progressed. Our correlation analyses demonstrated that ETTH patients with longer headache days per month had lower GMD in the ACC and anterior insula in our study. Increased headache days may contribute to the progression from episodic to chronic TTH, which leads to the central sensitization with GM reductions in multiple cerebral regions, such as the ACC and the anterior insula . This coSome limitations should be mentioned when interpreting the findings of our study. First, VBM has inherent limitations. For example, VBM detects only linear, spatially limited differences . Second,This is the first study to demonstrate dynamic and reversible GMD changes in the S1, ACC, and anterior insula between pain and pain-free phases in ETTH patients, which suggests cerebral adaptation to pain stimuli with a balance of pain modulatory circuits. However, this balance might be disrupted by increased headache days and progressive anxiety and depressive symptoms. Future studies are warranted to determine whether this structural plasticity is a characteristic of ETTH.


Haematuria and pelvic pain are recognized and documented adverse reactions related to Cabazitaxel use. To date there has not been any documentation of imaging findings in patients with this presentation.We report a case series of five patients who experienced these symptoms while on Cabazitaxel and were all found to have very similar urothelial changes on CT. The patients were noted to have ureteric and renal pelvic dilatation along with urothelial enhancement (in those who had post contrast imaging). All of these changes were noted to be reversible in those who had follow up imaging after cessation of Cabazitaxel and initiation of a short course of steroids.This case series helps demonstrate the pathological reversible urothelial inflammatory changes that may be occurring in patients experiencing haematuria and pelvic pain on Cabazitaxel therapy. These changes may relate to direct toxic effect of drug metabolites, a radiation recall type phenomenon or a combination of both. Cabazitaxel is an antineoplastic agent currently indicated for the treatment of adult patients with hormone refractory metastatic prostate cancer, who have previously been treated with a Docetaxel containing regime. It works primarily through disruption of the microtubular network in cells which in turn inhibits mitotic and interphase cellular functions. Once administered intravenously Cabazitaxel is primarily metabolized in the liver (>95%) by mainly CYP3A isoenzyme (up to 90%). The majority of excretion is in faeces as numerous metabolites with less than 4% of the dose excreted by the kidneys .The incidence of haematuria and pelvic pain with Cabazitaxel therapy is estimated to be 16.7% and 1.9% respectively [We report a series of five cases of Cabazitaxel induced pelvic pain and microscopic haematuria with characteristic pattern of urothelial inflammatory changes on CT at the time of symptoms. All patients had a history of prior pelvic radiotherapy, uncomplicated treatment with Docetaxel and exclusion of urinary tract infections at the time of presentation.All patients in our series tolerated at least 5 cycles of Cabazitaxel prior to onset of symptoms, which included a varying description of pelvic pain with microscopic haematuria. Table Four of the patients in the series cases 1–4) had whole pelvis radiotherapy and one patient case 5) had radiotherapy only to the right hemi-pelvis . Corresponding to this, cases 1–4  were able to be restarted on Cabazitaxel therapy without recurrence of significant symptoms.Follow up imaging was conducted on two of the patients (cases 3 and 4) after resolution of pelvic pain and haematuria. These scans revealed significant improvement in the urothelial inflammatory changes supporting the reversible nature of these effects both clinically and radiologically.Through this case series we are providing imaging based evidence of reversible urothelial inflammatory changes occurring in patients experiencing pelvic pain and haematuria while on Cabazitaxel therapy.While reversible side effects such as pelvic pain and haematuria have been documented related to the use of Cabazitaxel , to our We hypothesise these changes to be due to either direct toxic effect of Cabazitaxel (or its metabolites) on the urothelium or the provocation of radiation recall syndrome or a combination of both.The reversibility of inflammatory changes following Cabazitaxel cessation is compatible with both drug toxicity and radiation recall syndrome . Very liWe feel that the unilateral nature of urothelial inflammatory changes in case 5 (corresponding to the side of hemi-pelvic radiation) also further supports the possibility of a radiation recall syndrome rather than drug toxicity .Although the timing of symptom onset to beyond 5 cycles of treatment and involvement of the entire urothelium rather than just the radiated pelvic regions is atypical for radiation recall syndrome, it is still possible for such a presentation to occur , 3, 6. CThere is at least one case series we are aware of that has histologically shown urothelial inflammation from Cabazitaxel induced radiation recall syndrome . Whilst It must be noted that if this is indeed a radiation recall syndrome while successful re-initiation is possible (as in our case series), there is also the possibility of severe symptom recurrence at re-initiation  and cautWe hope our observations will help to improve assessment and management of patients experiencing pelvic pain and haematuria while on Cabazitaxel treatment.


Radiofrequency-targeted vertebral augmentation (RF-TVA) is a recognized treatment for painful compression fractures. RF-TVA in a patient with multiple compression fractures due to type I osteogenesis imperfecta (OI) has not been previously reported. A 54-year-old patient with type I OI is presented with a segmental thoracic hyperkyphosis and 7 recent vertebral compression fractures. Because of persistent severe thoracolumbar back pain despite conservative therapy, RF-TVA was indicated. Nocturnal back pain was almost completely relieved at all postoperative time points evaluated. However, overall pain relief dropped only slightly from 7 to 5 on the numerical rating scale (NRS) at the 6-week follow-up, and there was only a small decrease in the Oswestry Disability Index (ODI) from 72% to 63%. An MRI at the 3-month follow-up revealed hyperintensity at levels T11 and T12, indicating slight recollapsing. At the 6-month follow-up, the ODI improved to 55%, although overall pain had worsened to 6 on the NRS. Pain at rest remained at a very low level. Despite the remaining lumbago, RF-TVA may be a good option for patients with OI who have multiple fractures. However, fractures at multiple levels and segmental thoracic hyperkyphosis may increase the risk for recollapsing and ongoing pain.  Vertebral compression factures are common and painful in patients with osteoporosis and osteogenesis imperfecta (OI). Adequate treatment is required to relieve serious back pain, restore activities of everyday life, and maintain spine alignment in the sagittal profile. Conservative treatment frequently provides only short-term pain relief , 2, in wWe extended the indication of RF-TVA to a 54-year-old woman with multiple compression fractures of Th8–12, L1, and L3, along with diminished osseous stability owing to type I osteogenesis imperfecta and osteoporosis. To our knowledge, this is the first case report describing treatment of a multilevel-fractured spine with RF-TVA.T-Score of −3.3 at the lumbar spine), and at the time untreated Crohn's disease presented at the orthopedic institution with serious thoracolumbar back pain over the previous 5 months and lower back pain over the previous 4 months, without preceding trauma. Several applications of cortisone  over the previous 15 years were used for treating her Crohn's disease.A 54-year-old woman with type I OI, osteoporosis . When lying, the pain worsened to 10/10. The Oswestry Disability Index (ODI) was 72%, constituting a crippling condition. The ODI was determined in German .Radiographs showed multiple compression fractures in the thoracic and lumbar regions, and high signal on the STIR sequence of an MRI was observed at levels Th8–12, L1, and L3 see also . An addiRegarding the sagittal profile, X-ray of the whole vertebrae showed a thoracic hyperkyphosis of 70 degrees and a C7 offset of 4.3 cm.The patient was placed in a prone position on a radiolucent operating table. The compression fractures were localized fluoroscopically using a conventional C-arm device (Endura/Philips/Netherlands). Under fluoroscopic guidance, an introducer was inserted through a small skin incision into either the right or the left pedicle at levels T8–T12 and L3. Access was bipedicular only at level L1. The navigational MidLine Osteotome (DFINE) was inserted through the introducer and guided fluoroscopically. After creating a three-dimensional cavity in the center of the fractured vertebrae, the radiofrequency-activated cohesive ultrahigh-viscosity PMMA cement was delivered at a controlled rate into the cavity under continuous pressure from the hydraulic assembly. The cement volume per vertebral body ranged from 2.2 to 4.3 mL. The intent was to restore and strengthen the vertebrae by injecting the cement primarily into the anterior part of each vertebral body. The total time from incision to suturing was 100 minutes. The patient tolerated the intervention well without pulmonary or neurological complications.The procedure was conducted during a brief in-hospital stay. Immediately after the treatment, the patient's NRS back pain rating decreased from 7 to 5, allowing some activities of her daily life to be restored. Pain reduction in the lying position was more evident, with a decrease in the NRS rating from 10 to 2. Immediately after surgery, the patient reported being able to sleep at night without pain interruptions. At the 6-week follow-up, the ODI had decreased from 72% to 63%.Because of ongoing pain 3 months after surgery, we performed another MRI of the lumbar spine. The MRI revealed small hyperintense signals at levels T11 and T12, indicating the possibility of slight recollapsing see also . At the T-Score of −3.3) associated with OI and osteoporosis secondary to long-lasting cortisone treatment for Crohn's disease.The patient in this study had type I osteogenesis imperfecta, which is the most benign form of a group of connective tissue disorders that cause skeletal abnormalities such as bone fragility and deformity . VertebrCorporal disability and severe lumbago unresponsive to conservative therapy indicated that surgical intervention was appropriate for the patient. Several operative procedures were available for treatment, but the large number of fractures and very low bone quality limited the practical options. Standard approaches would have required extensive instrumentation, with high risks of screw loosening, establishing bone union, and perioperative complications. Under these circumstances, we considered vertebroplasty and kyphoplasty as possible alternatives before selecting RF-TVA. This treatment had several novel characteristics and improvements over standard therapy. In particular, the operating time in RF-TVA was shortened because the unipedicular approach is often sufficient to achieve adequate cement distribution , 7, 12. Similar to balloon kyphoplasty, RF-TVA is associated with some common adverse events. However, both procedures are considered safe and the rates of PMMA extravasation are low , 7. It iAlthough the patient reported noticeable pain relief, she remained disabled because of ongoing severe lumbago and was consequently not able to work. Nevertheless, the patient appreciated the pain relief, which enabled her to sleep continuously and improved her quality of life. Her stagnating improvement at the 6-month follow-up may have been related to the disease severity and the presence of fractures across 7 vertebral levels. Most published studies have evaluated patients with only up to 3-level fractures. The patient did not have an adjacent segment fracture, though she had a segmental thoracic hyperkyphosis, which might be a risk factor for new fractures at adjacent levels . AdjacenAnother reason for ongoing pain may have been the application of an insufficient cement volume in some of the vertebrae. This could have resulted in the enhanced signals seen on the postoperative magnetic resonance image 3 months after surgery, indicating a process of recollapsing without significant secondary loss of height restoration. There is no recommendation in the literature for a specific amount of cement to achieve optimal results, although a biomechanical study by Liebschner et al. suggests that 3.5 mL in L1 is necessary to adequately restore stiffness . HoweverRT-TVA should be considered as a potential treatment for patients with OI who have numerous vertebral fractures and for whom conservative treatment has been ineffective. We believe that it is probably the most suitable surgical procedure in such cases, even though the pain relief observed in this study was not comparable to what may be expected for patients with 1-level or 2-level fractures. The patient reported that the initial pain relief at night immediately after RF-TVA was of sufficient value that in hindsight she would elect to undergo the treatment again.RF-TVA is a minimally invasive therapeutic procedure offering an alternative to standard treatments for multiple vertebral fractures in patients with type I osteogenesis imperfecta and pain that is unresponsive to conservative treatment. In this case report, the patient improved only slightly in overall ODI and pain level, but this may have been because of the multilevel fractures or segmental kyphosis. The patient did, however, experience immediate and significant pain relief at night, which led her to report that the procedure was worthwhile.


The main clinical application of electromyography is to detect abnormalities in muscle function, to assess muscle activity for purposes of recruitment, and in the biomechanics of movement.To analyze electromyography (EMG) findings for masticatory muscles during chewing following surgical extraction of lower third molars, and to determine any correlation between pain, inflammation, trismus, and the EMG data registered.This prospective study included 31 patients. Surface EMG was used to study masseter and temporalis muscle function before lower third molar extraction and 72 hours and seven days after surgery. Clinical variables, pain, inflammation, and trismus were registered before and after surgery.Studying the area and size of the masticatory muscles, higher values were found for temporalis than masseter muscles, regardless of the surgical side, which points to the greater involvement of the temporalis muscle in mastication. Comparing the side where surgery had been performed with the non-surgical side, a sharp and statistically significant reduction in amplitude and area were noted on the surgical side reflecting major functional affectation. One week after surgery, amplitude and area had almost returned to base-line values, indicating almost complete recovery. While pain decreased progressively after surgery, inflammation peaked at 72 hours, while mouth opening reached a minimum at this time, returning to normality within the week.Surgical extraction of lower third molars produces changes to electromyography activity that are more evident during the first hours after surgery and closely related to the intensity of pain suffered and the patient’s inflammatory responses, although they are not related to mouth opening capacity. Key words:Third molar surgery, electromyography, pain, inflammation, trismus, masticatory muscles. Third molar extraction is the most common type of maxillofacial and oral surgery. Impacted third molars, and their attempts to erupt, trigger a variety of pathological conditions in some 75% of cases, calling for their surgical extraction .Complications related to third molar extraction have been well documented. Major complications following extraction are defined as those requiring treatment, which sometimes causes irreversible damage. Among these are abscesses, cases of uncontrollable bleeding, neurological damage, and mandibular fracture . Minor cFollowing third molar extraction, many patients report restricted mouth opening, in other words, trismus. Many methods are used to assess patient discomfort and mouth opening capacity after surgery, such as visual analogue scales, quality of life questionnaires, and measurement of inter-incisal distance. But these techniques show little objectivity and do not determine muscle function .Electromyography (EMG) is a technique that allows the registration of electrical activity generated by muscle cells when these are stimulated electrically or neurologically. The signals emitted are measured on the skin surface as the sum of electrical activity of muscle fiber bundles ,6.The main clinical application of EMG is to detect abnormalities in muscle function, to assess muscle activity for purposes of recruitment, and in the biomechanics of movement. In dentistry, EMG has mainly been used for analyzing masticatory function, but few studies have evaluated masticatory muscle activity after third molar extraction and any correlation between EMG muscle activity and the minor complications derived from surgery .The objective of this study was to evaluate EMG activity of the masticatory/mouth closing muscles after third molar extraction surgery and to correlate the findings with the presence of minor complications. This prospective study performed baseline EMG before third molar extraction surgery, and at 72 hours and 7 days after surgery, measuring temporalis and masseter muscle activity with surface electrodes. Pain, inflammation and trismus parameters were also evaluated in order to identify any correlation between these and the EMG parameters registered.-Study design This is a longitudinal prospective study approved on December 5, 2015, by the Institutional Ethical Committee of the Complutense University of Madrid, under protocol number CEIC-09/2015. Free and informed consent was obteined from participants in writing prior to conducting the research. The recommendations from Strengthening the Reporting of Observacional Studies in Epidemiology (STROBE) were followed for the study´s design and development .A patient sample was selected according to pre-established criteria; patients underwent an EMG study before and after surgical extraction of impacted lower third molars, in order to evaluate mouth closing muscle function while chewing following an evaluation chronogram: baseline, 72 hours after extraction surgery, and 7 days after surgery.-PatientsThe study included 38 patients (25 women and 13 men with a mean age of 22.26 years), who attended the Department of Medicine and oral surgery, Faculty of Medicine and Dentistry, the Complutense University of Madrid (Spain) from January to June 2016; EMG was performed at the Department’s EMG Unit.Of the initial 38 patients, seven were excluded as they had taken analgesics during the study period. Before the study began, each patient gave his/her informed consent to undergo third molar extraction, and to take part in the EMG study. The dentist, who performed all clinical procedures, recorded the patients’ clinical histories and performed a radiographic study from orthopantomographs, a usual procedure in this type of surgery.Inclusion criteria were: patients classified as ASA I or II according to the American Society of Anesthesiologists classification , patientExclusion criteria were: patients presenting temporomandibular disorders, patients with multiple missing teeth, facial asymmetries, or patients classified as ASA III or IV. Patients who requested oral analgesic administration during the post-operative period were excluded, as only local measures were applied: chlorhexidine mouthwash and a soft cold food diet.-Study variablesThe study’s predictive variable was muscle function registered during chewing before and after lower third molar extraction surgery. The outcome variables evaluated were the amplitude and area of the masseter and temporalis muscles. The term muscle amplitude refers to muscular contraction, so that the greater the amplitude, the greater the contraction. The term area refers to the muscle’s attempts to recruit more motor units and so achieve a correct function. Other variables registered included patient age and gender, post-operative pain, inflammation, and mouth opening/trismus.-Electromyography (EMG)EMG was performed to evaluate muscular function on the surgical and collateral sides during chewing (the food masticated was fried potatoes) following the following evaluation chronogram: pre-operative baseline EMG, 72 hours after surgery, and 7 days after surgery. EMG was performed with surface electrodes placed on the patient’s skin over the masseter and temporalis muscles to quantify the amplitude and area in ?v over a period of 250 ms. Two surface electrodes were applied to each muscle in order to register the difference in voltage between the two independent electrodes.-Lower third molar extraction surgery In all cases, surgery was performed by the same surgeon, following the same procedure under local anesthesia blocking the inferior alveolar nerve, lingual nerve, and afterwards the buccal nerve. A scalloped incision was made from the first molar with distal release directed posteriorly towards the ramus, followed by mucoperiosteal detachment, osteotomy using a handpiece with micromotor and a round carbide tungsten bur, extraction, bone regularization, and 5-0 silk sutures. Patients received no oral drug treatment in order to avoid data bias.-Data collectionEvaluation of inflammation and mouth opening/trismus parameters were performed at the same study times as the EMG evaluations. For pain measurement, baseline registration was not pre-surgical but rather the pain experienced on the same day as surgery was measured, and therafter at 72 hours and one week after surgery. Pain was evaluated using a visual analogue scale (VAS), whereby the patient scored pain intensity on a scale from 0 to 10, 0 indicating absence of pain and 10 maximum pain. Inflammation was evaluated following the method proposed by Amin and Laskin , before -Statistical data analysisData were entered in a Microsoft Excel spreadsheet  and processed using SPSS software . Pearson’s test was used to study correlations between two means and ANOVA F for more than two means, compared pairwise by the Bonferoni test.-Descriptive study of variables analyzed Mean patient age was 22.26 ± 2.59. The ratio of men/women was 2.5/0.6.The pain suffered by patients registered by VAS was found to diminish gradually and progressively from each study time to the next. It should be noted that over 90% of the patients did not experience any pain at the 7-day mark. In the initial evaluation following surgery, patients reported pain levels 4 and 5 in 3.2% cases, level 3 in 9.8%, and levels 2,1 and 0 in 29%, 25.8% and 29% respectively. At 72 hours, the number of patients not experiencing any pain increased substantially to 58.1%, with cases reporting level 1, representing 22.6%, and level 2 19.4%; no patient reported pain intensity at higher levels. The final evaluation at 7 days made it clear that the majority of patients (90.3% of the sample) felt no pain by this time; one patient (3.2%) reported level 1 pain and two patients (6.5%) level 2 , but a clear tendency for both muscles to recover was observed on both sides . No correlation was found between patient age and pain or inflammation. As for gender, women (mean=1.64) reported greater pain than men (mean=0.5), with statistically significant difference at the first evaluation time on the day of surgery (p=0.049), but without significant difference at 72 hours or seven days after surgery. No correlation was found between patient gender and intercisal distance at any of the study times. However, inflammation was significantly higher in men than women at all three study times (Statistical analysis identified some significant correlations between the study variables. Regarding age, younger patients recovered more slowly than older patients (Pearson dy times .A statistically significant correlation was found between pain and muscle amplitude and area reduction at the first two study times. Seven days after surgery, there was no significant correlation, as pain had mostly disappeared and muscular function had been restored, presenting similar amplitude and area values to baseline.Following the same pattern, after 72 hours a positive correlation was found between the degree of inflammation and muscle amplitude and area; the greater the inflammation, the less the muscle amplitude and area. After 7 days, muscle amplitude and area values had been re-established in accord with the reduction in inflammation, indicating the recovery of muscle function.No statistically significant results were registered to correlate muscle function during chewing with changes to intercisal distance, from which it may be concluded that functional disorders of the masseter and temporalis muscles do not determine mouth-opening capacity.The literature includes numerous articles on the signs and symptoms arising from third molar impaction, indications for its extraction, and post-operative complications deriving from extraction, which together have generated some controversy. There is a wide range of opinion as to the frequency, order of appearance and duration of impacted third molars, but all researchers agree on a trio of symptoms that derive from extraction: pain, trismus, and inflammation. The value of the present study lies in its EMG evaluation of masticatory muscle behavior in relation to pain, mouth opening/trismus, and inflammation.Complications related to the masticatory muscles, such as trismus and inflammation are subjective parameters, and so difficult to quantify objectively . ElectroMotor units contribute to signals passed to surface EMG, which are, as the name suggests, on the surface. Any decrease in EMG activity is due to a reduction in surface muscle fiber activity . But theet al. (EMG data for amplitude and area of masseter and temporalis muscles showed significantly different values between the surgical and non-surgical sides 7 days after surgery, with lower values on the surgical side than the non-surgical side. But some researchers such as Moraes MB et al. , who conet al. . The recet al. ; if thisThe present results show a positive correlation between the presence of pain and a reduction in electromyography activity in the masticatory muscles with pain subsiding by the 7-day study time, when the correlation was reversed. And so it may be concluded – as other authors have done – that pain experienced on the extraction side leads to a reduction in muscle activity as a defense mechanism; the reduced activity, and therefore function, is considered an innate analgesic mechanism exercised to avoid pain .The possible correlation between post-operative inflammation and EMG activity in the masseter and temporalis muscles was also investigated. Inflammation peaked at 72 hours, coinciding with a significant decrease in amplitude and area. The release of inflammation mediators causes pain and oedema, which limit jaw movements . In addiTo sum up, lower third molar extraction alters post-operative EMG variables in the mouth closing/masticatory muscles. Seven days after surgery, statistically significant differences were found between amplitude and area values in favor of the non-surgical side, which points to greater functional recovery of the muscles on the antagonist side. The EMG alterations observed would appear to be transitory as there was a significant improvement in amplitude and area values from the 72-hour to the 7-day study time, regardless of the side intervened. Although the reliability of EMG readings has been a topic of some controversy, it may be considered an objective method for evaluating muscle function. This method can be used to assess reduced masticatory function of the masseter and temporalis muscles after third molar surgery, as well as the trio of symptoms correlated to these variables – pain, inflammation, and trismus.As in many studies, the findings were subject to a possibility of bias. One potential source of bias is the fact that the capacity of surface electromyography may be influenced by the individual patient’s skin type and surface grease. This is a factor that is difficult to homogenize although, according to the authors’ criteria, the phenotypic characteristics of the study population were very similar.Surgical extraction of lower third molars produces changes to electromyography activity that are more evident during the first hours after surgery and closely related to the intensity of pain suffered and the patient’s inflammatory responses, although they are not related to mouth opening capacity.


The aim of this study was to evaluate the palliative efficacy of localized external radiotherapy (RT) combined with systemic radionuclide (RN) therapy in patients who had multiple painful osseous metastases of different primary origins.Thirty-three patients initially local external radiotherapy was delivered to the most symptomatic region in all patients. Then they received either Re 186 HEDP or Sm 153 EDTMP. The performance status was assessed according to ECOG scale. Before treatment, at the end of the radiotherapy and after the four weeks of systemic radionuclide therapy, analgesic intake and pain status were recorded by the RTOG scoring system, and EORTC QLQ C30 (Version 3.0 Turkish) questionnaire was performed to evaluate the quality of life.Improved performances of 33.3% for post radiation therapy and 50% for post radionuclide therapy in the ECOG scale were observed. Statistically significant correlations were found between the primary origins and decreased pain and analgesic intake (p < 0.05), but no differences were observed on the self assessment quality of life questionnaire.Both Re 186 HEDP, Sm 153 EDTMP are effective and safe in bone pain palliation as an adjuvant to local field radiation therapy of breast and prostate cancer patients, who also continued to receive chemotherapy and/or hormontherapy. Bone metastasis is a common, challenging problem in patients with advanced cancer. Although they are often clinically silent, they may lead to serious complications such as pain, fractures and hypercalcemia, which result in reduce performance status and decrease the quality of life. The life expectancy of the patients with bone metastases varies widely, depending on tumor types . ManagemRadiation therapy and surgery are used for the treatment of localized bone metastases. The goal of localized irradiation is to relieve symptoms, restore function and prevent the sequelae of disease progression in the area treated -6. DespiThe aim of this study was to evaluate the palliative efficacy of localized external radiotherapy (RT) combined with systemic radionuclide (RN) therapy in patients with multiple painful osseous metastases of different primary carcinoma.Thirty-three patients who had multiple transient pains because of multiple skeletal metastases from different primary origins were eligible for this trial. The primary histology proved that malignancy was breast cancer in eight patients, prostate cancer in six, lung cancer in ten, gastro-intestinal system (GIS) cancer in three and various other types of cancer in six. A 99m Tc-methylenediphosphonate (MDP) bone scan was obtained in all patients before the radiotherapy and one week after systemic radionuclide therapy. The performance status was recorded according to the Eastern Cooperative Oncology Group (ECOG) scale. All patients were required to have a mandatory pain and narcotic evaluation using a scoring system validated through the Radiation Therapy and Oncology Group (RTOG) before treatment, at the end of radiotherapy and four weeks after radionuclide therapy. Pain and narcotic scores were obtained by multiplying severity and frequency. Pain severity was classified as: 0 (none), 1 (mild), 2 (moderate), or 3 (severe). Pain frequency was classified as: 0 (none), 1 , 2 (intermittent = at least once daily), or 3 (constant). Drug severity was classified as 0: (not administered), 1 , 2 (mild narcotic), or 3 (strong narcotic). Drug frequency was classified as: 0 (not administered), 1 (less than once per day), 2 (once per day), or 3 (twice or more per day). The patients’ characteristics are shown in table1.All patients received external local radiotherapy to a maximum of two sites. The local field size was chosen to include the most painful site and an appropriate margin. The patients were given three different doses; 30 Gy in 10 daily fractions, or 20 Gy in five fractions, or 8 Gy in one fraction. At the end of, or one week after, the radiotherapy, the patients received Re 186 HEDP = Rhenium 186 hidroxyethylydene disphosphonate (n = 11) or Sm 153 EDTMP = Samarium 153 ethylene diamine tetramethylene phosphate (n = 22). Each patient received 1,221 MBq Re 186 HEDP or 37 MBq/kg Sm153 EDTMP. To confirm RN treatment, bone scans were taken after 72 hours for Re 186 HEDP and 24 - 48 hours for Sm 153 EDTMP. All patients had received chemotherapy and/or hormontherapy and biphosphanate according to the therapeutic protocol.The patients were issued with an EORTC QLQ-C30 (version 3.0 Turkish) questionnaire before the radiotherapy, at the end of the radiotherapy and four weeks after the radionuclide therapy.As a second end point, overall survival (OS) and progression free survival (PFS) was reported. OS was calculated from the date of diagnosis of bone metastasis to the date of the last follow up. PFS was calculated from the date of radiation therapy to the date of physician-reported progression.A response was defined as an improvement of the ECOG performance status by at least one level and symptomatic response reduction of the prescribed daily dose of analgesics and pain level compared with the pretreatment situation.t-tests. For statistical analysis P values less than 0.05 were considered significant.All data was transferred to the SPSS version 10.1 for statistical analysis. Differences between pre-treatment and post-treatment ECOG, pain and analgesic scores were analyzed by Wilcoxon Signed Ranks. Survival and the duration of pain palliation were assessed by Kaplan-Meier curves. The differences in Kaplan Meier curves with respect to the primary tumors were evaluated by log rank tests. Differences of quality of life questionnaire variables were evaluated by Fourteen patients with disseminated bone metastasis had breast (n = 8) or prostate cancer (n = 6), and 19 patients were affected from other cancers. Patients received the systemic radionuclide treatment on an outpatient basis whereas the radiation therapy was given on either an out- or in-patient basis .In all patients the response rate was 33.3% at the end of RT and this increased to 50% four weeks after RN. The response rate in comparing the post radiation therapy to the initial evaluation after post RN was observed to be 50%. The response rates are shown in Baseline quality of life questionnaires were assessable in 33 patients. At the end of RT and post RN, QLQ forms were available for 23 patients. However, no differences were observed on the self assessment quality of life questionnaire following the treatment. The differences in the global quality of life scale before RT after RN therapy and before and after RN therapy were found to be statistically significant (p = 0.001 and p = 0.003 respectively)Four patients (12%) experienced a flare reaction (defined by a transient increase in pain intensity after tracer administration). It occurred in the first week after the injection and disappeared spontaneously. No patient showed any appreciable change in vital signs or any clinically evident acute adverse effect. Bone marrow suppression was generally mild, reversible. There was no significant correlation between hematological toxicity and chemotherapy cycles and/or RT.The overall survival (OS) for all patients was 17 months . ProgresMetastatic disease represents roughly 40-50% of oncology practice. Over 70% of patients with metastatic disease exhibit uncontrolled pain . Pain maet al reported that both Re 186 HEDP and Sm 153 EDTMP, showed similar pain palliation effects in patients suffering from breast and prostate cancer [In our study, the overall clinical response with RT and with RN (Re 186 HEDP and Sm 153 EDTMP) were reported respectively as 33.3% and 50%. Patients with non breast and non prostate cancer might have negatively influenced our results. Our breast and prostate cancer patients showed better progression free survival and pain relief than the other cancer types. Theoretically, pain palliation in non prostate cancer could show peculiar features, as the pathologic microenviroments of bone metastases are quite different, with prostate cancer having a prevalently osteoblastic structure and the other cancers lytic or mixed patterns; especially breast cancer shows mixed features. The lytic pattern may result in a less suitable target for RN treatment. Liepe e cancer . In 21 se cancer . Some ine cancer .This maye cancer . Due to e cancer . In thiset al found a 60% response in breast cancer patients using a pain assessment through daily documentation of the visual analogue scale [et al found an overall response rate of 67.5% with different types of cancer  using Re 186 HEDP [et al reported that data on the radiation absorbed dose of Re 188 HEDP showed comparable results to with other bone-seeking radionuclides with lower energies than 188Re-HEDP for 186Re- HEDP, 153Sm-EDTMP [et al have reported similar results with breast cancer patients who had been treated with Re 186 HEDP [Palliation of pain, or pain relief, is a very subjective response and has always been a difficult subject for research. The rate of response may also depend upon the pretreatment condition of the patient, the etiology of the bone metastases, the extent of the disease, and previous or concurrent local or systemic therapy given. Although there are standard ways of measuring pain using a pain scale, investigators often cannot calculate pain relief. The Visual Analogue Scale is probably the most accurate method to measure pain intensity and variations but, it is difficult to use in the elderly and in patients with poor compliance who represent the majority in the palliative care setting. Most studies have described only pain assessment, without adjustment for medication index and daily activities. Pain relief can be observed as a result of the increased use of analgesic. Any simultaneous change in the use of analgesics must be considered in the final response evaluation. Our experience with response evaluation is supported with changing pain, analgesic, and ECOG performance scales. Palmedo ue scale . They al186 HEDP . The pai186 HEDP . This pa186 HEDP . Liepe eSm-EDTMP . Our ownSm-EDTMP . Palmedo186 HEDP . However186 HEDP . Patient186 HEDP .To our knowledge, there are few studies about RN treatment as an adjuvant to external beam radiation for multiple painful osseous metastases in the literature. Hauswirth found a response rate of 59% and concluded that Re 186 HEDP can be used in conjunction with analgesic and external beam irradiation . Porter In conclusion, the results of this study demonstrate that both Re 186 HEDP and Sm 153 EDTMP are effective and safe in bone pain palliation as an adjuvant to local field radiation therapy of breast and prostate cancer. Re 186 HEDP and Sm 153 EDTMP show similar response rates, hematological toxicity is not clinically relevant, and chemotherapy is not impaired by RN treatment.