The current standard for pain control following liver surgery is intravenous, patient-controlled analgesia (IV PCA) or epidural analgesia. We have developed a modification of a regional technique called medial open transversus abdominis plane (MOTAP) catheter analgesia. The MOTAP technique involves surgically placed catheters through the open surgical site into a plane between the internal oblique muscle and the transverse abdominis muscle superiorly. The objective of this trial is to assess the efficacy of this technique.This protocol describes a multicentre, prospective, blinded, randomized controlled trial. One hundred and twenty patients scheduled for open liver resection through a subcostal incision will be enrolled. All patients will have two MOTAP catheters placed at the conclusion of surgery. Patients will be randomized to one of two parallel groups: experimental  or placebo . Both groups will also receive IV PCA. The primary endpoint is mean cumulative postoperative opioid consumption over the first 2 postoperative days (48 hours). Secondary outcomes include pain intensity, patient functional outcomes, and the incidence of complications.This trial has been approved by the ethics boards at participating centres and is currently enrolling patients. Data collection will be completed by the end of 2014 with analysis mid-2015 and publication by the end of 2015.http://clinicaltrials.gov The study is registered with Liver resection is the optimal treatment for patients with primary or metastatic liver malignancies, benign liver tumours, and some biliary diseases-5. In CaDue to the location of the liver and the propensity for bleeding during resection, surgery is typically performed through a large right subcostal incision. The subcostal incision, however, is associated with significant postoperative pain and distress which may result in respiratory complications, delayed mobilization and physiotherapy, and prolonged hospital stay. InadequConventional techniques of postoperative analgesia include epidural catheters, intravenous opioid patient-controlled analgesia, and peripheral nerve blocks-17. PeriEpidural analgesia remains the gold standard for pain control following an abdominal surgical procedure. HoweverDespite the variety of pain-relieving modalities available, postoperative pain following liver surgery is significant and remains a challenge to manage. Opioid analgesia, while effective at rest, fails to provide adequate pain relief associated with movement such as breathing, coughing, ambulation, and gastrointestinal motility,31. MoreMovement-evoked incisional pain accounts for the majority of pain experienced, and the nerves responsible arise from thoracic levels T6 to T10. These n3/kg 0.125%) at the end of surgery and this regimen was repeated every 12 hours until postoperative day 3. We compared postoperative pain scores and opioid use to historical controls and found a significant (P < 0.05) difference in cumulative postoperative opioid (hydromorphone) consumption at 48 hours ).We have recently developed a modification of the TAP technique for regional analgesia following subcostal incisions termed MOTAP catheter placement. This technique involves surgical placement of the catheter under direct vision. During subcostal incision these muscular planes are clearly visible, allowing more confident insertion of a catheter directly into the correct plane. In a piTo assess the impact of MOTAP catheters plus intravenous, patient-controlled analgesia (IV PCA) compared to the standard of care  on opioid consumption in patients undergoing hepatic resection requiring a subcostal incision.To assess the effect of MOTAP catheters on:1. Postoperative pain intensity.2. Opioid-related adverse effects, including nausea, vomiting, pruritus, sedation, and postoperative ileus.3. Time to ambulation, duration of hospital stay and reduced postoperative pain disability.4. Post-surgical complications .5. Incidence and intensity of chronic postsurgical pain.This is a multicentre, prospective, blinded, randomized controlled trial comparing MOTAP catheters plus IV PCA to standard care  in patients undergoing subcostal incision for liver resection. Full inclusion and exclusion criteria for the trial are summarized in Table Patients meeting the eligibility criteria will be recruited at the preoperative surgical consent visit or the anaesthesia pre-assessment clinic. Information pamphlets will be provided and written informed consent will be obtained. At the time of enrolment, patients will complete baseline questionnaires: the ‘Preoperative Current Pain and Pain History Questionnaire’, Numeric Rating Scale (NRS) for PainPatients will be randomized to one of two parallel groups: experimental  or placebo . Each research pharmacy will have a concealed randomization list and the appropriate syringes will be dispensed by the pharmacy. The code will be retained centrally and only revealed to the investigators once recruitment and data collection is completed. Randomization will be stratified by centre. A brief schema and study outline of this trial is summarized in Figure All patients will undergo routine preoperative testing at the preadmission clinic to confirm fitness for surgery . No additional tests are required beyond standard-of-care for patients undergoing liver resection.Patients will undergo routine anaesthesia and liver surgery with no additional requirements for this study. No preoperative oral analgesics are permitted, including non-steroidal anti-inflammatory drugs, gabapentin, and acetaminophen. Epidural catheters, intravenous lidocaine, and ketamine are not permitted. Surgery will be performed through a right subcostal incision. An upper midline extension or limited left subcostal extension is permitted. All aspects of the liver resection will be left to the surgeon’s discretion. Local anaesthetic may not be infiltrated into the surgical wound.Following liver resection, the operating surgeon will insert two catheters. The following muscles will be identified: rectus abdominis, transversus abdominis, internal oblique, and external oblique. The surgeon will dissect between the internal oblique and transversus abdominis fascia superiorly to open the TAP. A plane will also be developed between the rectus muscle and the posterior sheath. The first catheter will be placed subcostally in the anterior axillary line, between the transversus and internal abdominal muscles. The second catheter will be sited at the lateral border of the right rectus abdominis muscle, between the posterior rectus sheath and the rectus abdominis muscle. Approximately 10 cm of catheter will be left in each plane, and tunnelled to skin sites distal to insertion. The catheters will be secured under occlusive sterile dressing, and covered with tape. The skin will be closed using either staples or suture at the surgeon’s discretion. The catheter will be fastened to the skin using steri-strips and an occlusive sterile dressing. For the TAP catheter we will use the 001159-20D InfiltraLong 600 T  and we will use a standard three-orifice catheter for the rectus space.The study lead at each site will be responsible for ensuring that all participating surgeons adhere to this technique of MOTAP insertion. Prior to enrolling a patient, each participating surgeon must perform at least one MOTAP insertion with the site’s lead present to become credentialed in the technique. We will audit the insertion technique of each surgeon at least every five cases to ensure consistency.At the conclusion of surgery, both catheters will be bolused with 20 ml ropivacaine 0.2% followed by a continuous infusion through each catheter of ropivacaine 0.2% 5 ml per hour.At the conclusion of surgery, patients in the control group will have 0.9% normal saline 20 ml bolused then a 5 ml/hour infusion into each catheter.Patients in both groups will be prescribed celecoxib 200 mg orally twice daily (if baseline serum creatinine is less than 90 μmol/l), and IV PCA hydromorphone 0.2 mg bolus with a lockout time of 5 minutes and no background infusion. If patients have inadequate analgesia with this regimen the bolus dose will be increased to 0.2 to 0.4 mg bolus and the TAP catheter infusions will be increased to 7.5 ml/hour in each catheter. If pain is still inadequately controlled, patients will be started on a continuous intravenous infusion of hydromorphone 0.2 mg/hour in addition to the bolus PCA dosing. If pain is still inadequately controlled, the study coordinator will be contacted and the patient assessed by the study site lead.Patients may receive additional opioid boluses to control acute intractable pain while the IV PCA dose is being adjusted, at the discretion of the acute pain service clinician or the post-anaesthesia care unit nurse caring for the patient. These doses will be recorded and included in the measurement of total opioid consumption.Serum creatinine will be monitored daily in the postoperative period and, if it increases above 90 μmol/l, the celecoxib will be discontinued; however, patients will remain in the trial.The MOTAP catheters will be removed on the morning of postoperative day 3 in all patients.This will be a blinded, placebo-controlled study. All patients, clinicians, and data collectors will be unaware of the group allocation. A pharmacist not involved in patient care will dispense the study medications according to the computer-generated randomization list.The primary endpoint is mean cumulative postoperative opioid consumption over the first 2 postoperative days (48 hours). Both IV PCA opioids and oral opioids will be recorded from the patient’s medical records daily, converted to morphine equivalents, and compared between the two groups.The following information will be collected at regular intervals as a measure of the primary endpoints: cumulative IV PCA opioid consumption every 12 hours for 72 hours as well as total opioid consumption for the entire hospital stay.We will collect the following secondary patient-reported outcome scores:1. NRS scores f2. Preoperative Current Pain and Pain History Questionnaire, NRS for Pain Intensity and Pain Unpleasantness, PCS, SF-MPQ-3. NRS patient satisfaction scores regarding pain control  TID for the first 48 hours and then daily until discharge.4. NRS for Pain Intensity and Pain Unpleasantness, PCS, SF-MPQ-5. Long-term pain Follow-Up Pain Questionnaire, PDI,37, PCS6. In-hospital opioid-related side effects - presence of nausea, vomiting, pruritus, and dizziness .7. Sedation scores, measured TID for the first 48 hours, then daily until discharge using a standard sedation scale , 2 = moderate , 3 = severe , S = normal sleep, easy to arouse).8. Duration of hospital stay.9. Time to first bowel movement.10. Time to ambulation.11. Incidence of in-hospital complications, graded using the Clavien classification.If, at any time, the patient is found to be ineligible for the protocol as designated in the section on eligibility the patient will be removed from the study. Patients who are not extubated within 4 hours from the end of the operation or who are reintubated within 48 hours from the end of the operation (including a return to the operating room) will also be excluded from the primary analysis, although we will continue to follow them while in hospital. Patients who wish to withdraw from the study at any point in time will be able to do so.P < 0.05.All statistical analyses will be performed using SAS software version 9.2 . All tests will be two-sided and significance will be considered at t-test.Mean cumulative postoperative opioid consumption during the first postoperative 48 hours will be reported for the two groups as mean ± standard deviation. The two groups will be compared using a two sided t-test or the Wilcoxon rank-sum test as appropriate. Time-to-event outcomes will be defined from the completion of surgery until the time of event. Patients who do not have the event at last follow-up will be censored. The number of censored events is expected to be low as both events (ambulation and bowel movements) are requirements prior to the patient’s discharge from hospital. Time to event outcomes will be analyzed using the Kaplan-Meier method and survival curves will be compared between the two groups using the log-rank test.Sample size calculationOutcomes will be reported for the two groups as mean ± standard deviation for normally distributed variables and the median and interquartile range for nonparametric variables. The two groups will be compared using chi-square tests, two sample Student’s Our pilot data consisted of 111 patients that had undergone liver resection surgery between April 2004 and January 2009 prior to the use of MOTAP catheters when postoperative pain relief was provided by IV PCA hydromorphone alone. Cumulative hydromorphone consumption over the first 48 hours after surgery was 39.09 ± 25.07 mg. Based on our experience with the use of MOTAP catheters following adult liver donation surgery, we have found a reduction of 47% in mean cumulative opioid consumption over the first 2 postoperative days (48 hours). Patients receiving MOTAP catheters consumed a mean ± SD of 20.81 ± 15.8 mg of hydromorphone. The difference of approximately 18 mg over 48 hours is clinically significant and represents a reduction of almost 50%.To be conservative, we will estimate a relative reduction in mean cumulative opioid consumption of 40%. Assuming a baseline opioid consumption of 39.09 mg with a standard deviation of 25.07, a sample size of 58 patients per group will achieve 90% power at a significance level  of 0.05. We will round up to 120 patients in total (60 patients in each group).Data from this study will help us optimize postoperative pain management in patients undergoing liver resection. It will assist us in developing a standardized protocol for pain management for these operations. Based on the results of this work, we hope to further test the efficacy of these catheters in other surgical cohorts in which upper abdominal incisions are used and where central neuraxial blocks are either contraindicated or refused by the patient. Better control of pain will help improve patient’s pain experience, mobilization and physiotherapy following surgery, reduce pain disability and possibly decrease the incidence and intensity of CPSP.This trial has been approved by the ethics boards at participating centres and is currently enrolling patients. Data collection will be completed by the end of 2014 with analysis mid-2015 and publication by the end of 2015.Toronto Academic Health Sciences Network Research Ethics Boards from Sunnybrook Health Sciences Centre and from the University Health Network.CPSP: chronic postsurgical pain; HADS: Hospital Anxiety and Depression Scale; IV PCA: intravenous, patient-controlled analgesia; MOTAP: medial open transversus abdominis plane; NRS: Numeric Rating Scale; PCA: patient-controlled analgesia; PCS: Pain Catastrophizing Scale; PDI: Pain Disability Index; SF-MPQ-2: McGill Pain Questionnaire - Short Form-2; TAP: transversus abdominis plane; TID: three times daily.The authors declare that they have no competing interests.PK conceived the study, participated in the design, coordination, and data collection of the study, and wrote the first draft of the manuscript. SC and PM participated in the design, coordination, and data collection of the study, and revised the manuscript. SM, JS, SL, CL, AW, NC, RK, JKa, SC, and JLM participated in the design and data collection of the study, and revised the manuscript. AK participated in the design and statistical analysis of the study, and revised the manuscript. JKh participated in the design of the study, and revised the manuscript. HC conceived the study, participated in the design, coordination, and data collection of the study, and revised the manuscript. All authors read and approved of the final version of the manuscript.


Pain and anxiety occurring from cardiovascular disease are associated with long-term health risks. Integrative medicine (IM) therapies reduce pain and anxiety in small samples of hospitalized cardiovascular patients within randomized controlled trials; however, practice-based effectiveness research has been limited. The goal of the study is to evaluate the effectiveness of IM interventions  on pain and anxiety measures across a cardiovascular population.Retrospective data obtained from medical records identified patients with a cardiovascular ICD-9 code admitted to a large Midwestern hospital between 7/1/2009 and 12/31/2012. Outcomes were changes in patient-reported pain and anxiety, rated before and after IM treatments based on a numeric scale (0-10).Of 57,295 hospital cardiovascular admissions, 6,589 (11.5%) included IM. After receiving IM therapy, patients averaged a 46.5%  decrease in pain and a 54.8%  decrease in anxiety. There was no difference between treatment modalities on pain reduction; however, mind-body and energy therapies , traditional Chinese medicine , and combination therapies  were more effective at reducing anxiety than bodywork therapies. Each additional year of age reduced the odds of receiving any IM therapy by two percent  and females had 96%  higher odds of receiving any IM therapy compared to males.Cardiovascular inpatients reported statistically significant decreases in pain and anxiety following care with adjunctive IM interventions. This study underscores the potential for future practice-based research to investigate the best approach for incorporating these therapies into an acute care setting such that IM therapies are most appropriately provided to patient populations. Pain and anxiety occurring from acute care for cardiovascular disease (CVD) are associated with long-term health risks. Specifically, preoperative anxiety and acute postoperative non-anginal pain in cardiac patients have been found to predict persistent postoperative pain up to 24 months after surgery . FurtherPharmacological symptom management among cardiovascular patients, while often appropriate and necessary, presents challenges such as side effects, limited effectiveness, and risk of adverse events . In 2005Several systematic reviews report on efficacy of IM for CVD-related outcomes and risk factors including blood pressure –9, bloodFor inpatients with cardiovascular diagnoses, randomized controlled trials specifically focused on the use of IM therapies for symptom management have reported improvements in pain and anxiety, among other outcomes –17. TriaIn 2010, our research group reported a 55.8% average reduction in pain with IM use across 1,837 inpatients at Abbott Northwestern Hospital (ANW), based on a retrospective medical record review; however, results for cardiovascular patients were not separately analyzed at that time . In the This retrospective, practice-based research study of cardiovascular inpatients was conducted at ANW, a 630-bed teaching and specialty hospital in Minneapolis, MN. The Penny George Institute for Health and Healing (PGIHH) at ANW was founded in 2003 and offers hospitalized patients, through electronic physician and nurse referrals, a wide-array of integrative health services at no charge to patients . All IM All cardiovascular inpatients age 18 years or older at ANW, who were admitted between July 1, 2009 and December 31, 2012, were included in the study population. Patients seen as outpatients, in the emergency room, and who were in the hospital solely for observation were excluded. Medical record data were obtained on all eligible inpatients and cardiovascular patients were retrospectively identified. All patients whose medical record data were obtained gave written permission upon hospital admission to use their records for research purposes.th Revision, Clinical Modification diagnosis codes (390-459). Any admission that had at least one of these ICD-9 codes as the admission’s primary or secondary diagnosis or any hospital encounter-level diagnosis was eligible for the study.The study population included those with diseases of the circulatory system, identified using the International Classification of Diseases (ICD), 9We created non-mutually exclusive indicators pertaining to five circulatory system diseases: diseases of arteries, arterioles and capillaries (440-448); cerebrovascular disease (430-438); hypertensive disease (401-405); ischemic heart disease (410-414); and diseases of pulmonary circulation (415-417). Patients of all other circulatory system diseases were grouped into an ‘other’ category.The study was approved by the Institutional Review Board of Allina Health with a waiver of informed consent.Data extracted from medical records included patient age at time of admission, sex, race, marital status, and health insurance status. The data included the All Patient Refined Diagnostic Related Groups (APR-DRG)  severityIM practitioners used their clinical judgment to provide therapies, within their scope of practice, they deemed necessary and therapeutic for each patient, after consulting with the patient. Many patients received IM therapy numerous times throughout their hospital admission. The term ‘session’ is used to define each unique administration of IM therapy, distinguished by time of procedure, within a hospital admission. For the present analyses, IM therapies were placed into one of three broad categories: bodywork (BW), which included craniosacral therapy, medical massage, and reflexology; mind-body and energy therapies (MBE), which was divided into separate mind-body and energy subcategories; and traditional Chinese medicine (TCM), which included acupressure, acupuncture, and Korean hand therapy. Importantly, patients could receive therapy from more than one category during each session, which has been defined as combination therapies. The presence or absence of each of these IM therapies was coded at each session such that BW, MBE, TCM, and any combination of these therapies were mutually exclusive.IM practitioners collected patients’ self-reported pain and anxiety scores directly prior to and after each IM session. Practitioners requested patients to provide a single number to indicate the level of pain they were currently experiencing on an 11-point numeric rating scale where 0 was defined as ‘no pain’ and 10 was defined as ‘worst pain imaginable’. Similarly, practitioners recorded anxiety scores using the same methodology, where 0 was ‘no anxiety’ and 10 was ‘worst anxiety imaginable’. The primary endpoints were changes in pain and anxiety scores, calculated by subtracting the pre-score from the post-score. Zero to 10 numeric rating scales for pain have been found valid and reliable , 26.A total of 57,444 cardiology-related hospital admissions were identified from medical records. During data cleaning, 149 hospital admissions were removed due to missing demographic data (51 admissions) or inability to determine severity of illness (98 admissions), resulting in 57,295 cardiology admissions from 37,259 unique patients. Of the 57,295 admissions, 6,589 (11.5%) had 16,344 IM therapy sessions (average of 2.48 per admission). In many cases, practitioners were unable to collect pre- or post-pain and anxiety scores or patients reported no pain or anxiety. Only patients who reported pre- and post-pain scores and/or pre- and post-anxiety scores, and pre-pain/pre-anxiety scores greater than zero, were included in the subsequent analyses examining changes in pain and anxiety after receiving IM therapy.Because IM therapies were observed at the hospital admission level, but pain and anxiety scores were assessed at the IM session level, one session was randomly selected from each remaining hospital admission in order to keep the level of analysis consistent between the selection and score change equations (see below). Thus, we dropped all hospital admissions with only missing scores or pre-pain or -anxiety scores equal to zero. This method produced a sample of 54,163 hospital admissions for the pain model, of which 3,457 (6%) had IM therapy, and 52,572 admissions for the anxiety model, of which 1,866 (4%) had IM therapy.Logistic regression was used to predict the probability of receiving any IM therapy during a hospital admission as a function of patient demographics, circulatory system disease diagnosis, severity, and health insurance status, and odds ratios for each covariate are presented. A p-value of less than 0.05 was used to signify statistical significance. We used a random sample of 25,000 observations to test the goodness-of-fit for our model using the Hosmer-Lemeshow test . We did First, to determine if IM therapies were associated with reductions in pain and anxiety, paired t-tests were conducted using the null hypothesis that the pre- and post-pain or anxiety scores were equal.Next, multivariate regression was used to estimate reductions in pain and anxiety during IM sessions. Because patients receiving IM therapy may systematically differ from the general sample of cardiovascular patients, an ordinary least squares model could produce bias parameters when generalizing results. To address this bias, a Heckman selection model  was usedTo correctly identify the parameters that affect pain and anxiety, at least one variable in the selection-equation (i.e. utilization of IM therapy) should be specified which predicts IM therapy use, but does not affect changes in pain or anxiety. Since marital status and health insurance status were expected to fit this criterion, our model predicted selection into the sample of IM sessions using all patient demographic, circulatory system disease diagnosis, severity, and health insurance variables (the same set of covariates as our logistic regression predicting IM therapy use). Changes in pain and anxiety scores were estimated using diagnosis, age, sex, race, severity, and the inverse Mills ratio calculated from the selection-equation to control for selection. Additionally, we estimated a second model, which included IM therapy categories, to determine if differential effects between the categories existed.All analyses were conducted in Stata Version 13 .Of the 57,295 hospital admissions over the study period, 6,589 11.5%) included IM therapy  in the predicted probability of receiving IM therapy between the IM hospital admissions group (predicted probability = 0.16) and the non-IM hospital admissions group (predicted probability = 0.11).Sessions with IM therapy resulted in, on average, a 46.5%  decrease in pain score , mean inverse Mills ratio 2.05), and the modal value of all categorical variables , IM therapy was associated with a 1.81  point reduction in pain  point decrease Table  or a 41.This practice-based research study, using routinely-collected electronic medical record data, assessed the effectiveness of adjunctive IM therapy on pain and anxiety among cardiovascular inpatients. Of 57,295 hospital admissions over the study period, 6,589 (11.5%) included IM therapy. Older patients had reduced odds of receiving any IM therapy and females had 96% higher odds of receiving any IM therapy compared to males. After receiving IM therapy, patients averaged a 46.5% reduction in pain and a 54.8% reduction in anxiety. For acute pain measured by a 0-10 numeric rating scale, a clinically significant reduction in pain is 20% for minimal noticeable improvement by patients, and between 35% and 44% reduction for a more substantial improvement  ; therefoHospital-based IM is an emerging field encompassing a wide range of practice models and arrays of services offered, and both RCTs and observational studies comprise a relatively small portion of the evidence base in the IM field . The preThe present study is unique for its practice-based observational design and large sample of cardiovascular inpatients. Prior investigations have been randomized trials with smaller sample sizes and more limited scope –17, 32. This study is not without limitations. First, the present results reflect only short-term changes in pain and anxiety. Because clinical relevance may be limited with a focus on short-term changes, further investigation into the long-term effects of IM on pain and anxiety should be considered. Second, the IM practitioner who delivered the IM therapy was also responsible for collection of the pre- and post-IM therapy pain and anxiety scores. As a result, the potential exists for social desirability or other response or reporting bias. However, provider-collected scores are reflective of how pain and other symptoms are assessed in a real-world acute care setting. Physicians, nurses, and other care providers regularly ask patients to self-report their rating of symptoms, and commonly used measures such as the numeric rating scale have been reported on , 26. It This study provided a unique opportunity to describe and investigate the effectiveness of delivering IM therapy to cardiovascular inpatients. Our results suggest that after receiving adjunctive IM therapies, cardiovascular inpatients reported statistically significant decreases in pain and anxiety. This study lays preliminary groundwork for future practice-based research to investigate the best approach for incorporating these therapies into an acute care setting such that IM therapies are most appropriately provided to patient populations.


Objectives. To evaluate substance P (SP) and the effect of ketoprofen administration, a nonsteroidal anti-inflammatory drug (NSAID), on SP in the pulp of upper third molars with experimentally induced pulpal lesion. Materials and Methods. A sample of 20 young systemically healthy adults of both sexes, nonsmokers, with a healthy upper third molar to extract for orthodontic purposes, was selected. Prior to the procedure, an inflammatory process was generated by mechanical exposure of the pulp. After 15 minutes, the pulp was collected using a sterile barbed broach. SP levels were determined by using a commercially available enzyme immunoassay (ELISA) kit. The subjects were randomly divided into two groups: group 1 received a dose of ketoprofen 30 minutes prior to the experimental procedure. The subjects of group 2 did not receive any kind of drug administration. The patients were asked to complete a diary on the postoperative pain. Results. No statistically significant difference could be detected in SP expression between the two groups. In group 1, pain manifestation was significantly delayed in comparison with group 2. Conclusions. Preventive administration of ketoprofen did not significantly affect the pulpal levels of SP but resulted in a significantly postponed manifestation of pain after extraction. Almost all pathological conditions that affect the oral tissues, as well as dental care or orthodontic procedures, increase the production and release of substance P (SP), a neuropeptide produced in a subset of capsaicin-sensitive sensory peripheral neuron cell bodies localized in the dorsal root and trigeminal ganglia . This neA sample of 20 young (19–30 years old) systemically healthy adults of both sexes, nonsmokers, was selected among the patients of the Department of Orthodontics of the University of Insubria, Varese, Italy. Inclusion criteria comprehended the presence of a healthy upper third molar programmed for extraction for orthodontic purposes. Written informed consent was obtained from each patient. The study was performed according to the recommendations regarding ethical issues in research with human tissues of the University of Insubria of Varese, Italy, and was conducted in accordance with the Declaration of Helsinki.Prior to extraction, the teeth were anaesthetized (1.8 mL of 4% articaine with 1 : 100.000 epinephrine by infiltration injection) and isolated with a rubber dam. Shortly after a pulpal inflammatory process was generated by mechanical exposure of the pulp using a No. 1 round carbide bur mounted on a high-speed handpiece, the bur was used on the tooth without irrigation inducing also a thermal trauma in the underlying pulpal tissue. After a period of 15 minutes, the pulp was extracted using a sterile barbed broach. All pulp samples were placed into test tubes and kept frozen at −20°C until the SP expression determination.The subjects were randomly divided into two groups: group 1 received a single dose of 80 mg ketoprofen lysine salt  in the form of sachet to dissolve in water, 30 minutes prior to the experimental procedure. The subjects of group 2 did not receive any kind of drug administration. After the extraction of the third molar, the wound was sutured and the patient was asked to complete a diary on the postoperative pain until the control appointment seven days after, in which time of appearance and recurrence of pain, necessity of use ketoprofen, and efficacy of the drug in controlling pain were analysed.A verbal pain intensity scale was used, where pain intensity was indicated as follows: no pain, slight, moderate, intense, and severe . Before For SP determination, pulp samples were weighed and 0.5 mL of acetic acid 0.5 N, containing a protease inhibitor cocktail , was added to all samples that were then boiled for 10 minutes. Samples were homogenized and centrifuged at 10000 ×g for 10 minutes at 4°C. Supernatants were collected, dried with a Speed Vacuum Concentrator, and resuspended in 0.3 mL of assay buffer. SP levels were determined by using a commercially available enzyme immunoassay (ELISA) kit according to the manufacturer's instructions . Sensitivity of the kit was 15 pg/mL.U test was applied to assess differences in the SP levels and to analyse differences in pain duration.Nonparametric Mann-Whitney The experimental procedure was completed with some complications, rubber dam resulted in being quite difficult to position in 6 patients  and it was possible to fix it only with composite resin. Two pulp samples in group 1 (7 and 10) resulted in being difficult to analyse because of the exiguous quantity of pulp tissue collected. These two samples were not comprehended in the statistical analysis.U test) was present between the two groups. In Tables SP concentrations, expressed as pg/mg of pulp tissue, of each patient are reported in Tables p = 0.0002 Mann-Whitney U test). Generally, the patients experienced only slight to moderate pain; one patient described pain as intense. Only half of the patients in group 1 felt the necessity to take a second ketoprofen dose after tooth extraction, while in group 2 all the patients decided to take the drug at the appearance of pain after the surgical procedure.In group 1, pain appearance was significantly delayed (6.2 ± 0.13 hours) in comparison to patients who did not receive ketoprofen before the experimental procedure (3.95 ± 0.2 hours) . This diThis study investigated the expression of substance P (SP) and the effect of ketoprofen administration, a commonly used nonsteroidal anti-inflammatory drug (NSAID), on the quantity of SP in the pulp of upper third molars with experimentally induced pulpal lesion. The approach of investigating SP levels in pulps with induced lesion could represent a possibility to standardize the experimental procedure in order to evaluate the effect of the NASID tested in presence of lesions with similar features and similar time outline. In the patients of group 1, a single dose of ketoprofen lysine salt  was administered 30 minutes prior to the experimentally induced pulpal lesion and the extraction of the third molar while in group 2 no drug was administered before the procedure. No statistically significant difference in SP expression could be detected between the two groups; only a higher variability was observed in the ketoprofen group.Several studies have reported an increase in SP levels in inflamed pulps. Sattari and coworkers  reportedThe presence of increased SP levels may open new directions for treating pulpal inflammation and pain but no studies have yet been performed to evaluate the effect of common used NSAIDs on this parameter and, as far as we know, the present is the first study to address this aspect. Pain after extraction occurred significantly later in the group in which the NSAID was administered before the experimental procedure; the overall experience of pain in this group was described as better and only half of the patients decided to use painkillers after the extraction, while all the patients of the group with no drug administration prior to extraction reported intake 3–5 hours after the experimental procedure. Still, these data are not sufficient to configure a recommendation regarding the opportunity of ketoprofen administration before tooth extraction procedures.In this preliminary study, considering the limited number of patients, ketoprofen does not seem to interfere significantly in the SP expression in the pulp with induced lesion. Considering the efficacy of this molecule in the modulation of pain and inflammation in third molar surgery previously reported , this reThe study reported an increase in SP expression in the pulp of third molars with experimentally induced lesion, correlating with the data of previous studies. The presence of increased SP levels may represent a possibility for treating pulpal inflammation and pain. Pain after extraction occurred significantly later in the group in which ketoprofen was administered before the experimental procedure; still preventive administration of the drug did not significantly affect the pulpal levels of SP. More studies with other molecules and performed on larger samples are necessary to evaluate the effect of NSAIDs on SP expression.


Researchers in clinical trials in rheumatoid arthritis (RA) and osteoarthritis (OA) often measure pain levels with a visual analogue scale (VAS). Of interest to clinical practice and future clinical trial design are associations of change from baseline (CFB) between time points with predictive ability of earlier response for long-term treatment benefit. We assessed the association and predictive ability of CFB in VAS pain between 2, 6 and 12 weeks in randomised controlled trials (RCTs) of non-steroidal anti-inflammatory drugs (NSAIDs).Aggregated VAS pain data at baseline and CFB at 2, 6 and 12 weeks were collected from a systematic literature review of 176 RCTs in OA and RA. The predictive ability of earlier assessments for longer-term pain reduction was estimated using correlation and regression analyses. Analysis was performed using the R software package for statistical programming, version 3.1.1.Appropriate data were available from 50 RCTs . Correlations between time points were high . CFB at 6 weeks was highly predictive and close to CFB at 12 weeks . CFB at 2 weeks was significantly associated with CFB at 12  and 6 weeks .The results showed that early analgesic response measured by VAS for pain beyond 2 weeks of treatment with a particular NSAID is likely to be predictive of response at 12 weeks. Failure to achieve desired pain relief in OA and RA after 2 weeks should trigger reassessment of dosage and/or analgesic.The online version of this article (doi:10.1186/s13075-016-0972-7) contains supplementary material, which is available to authorized users. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the most common arthritic conditions in adults . They leNon-steroidal anti-inflammatory drugs (NSAIDs), both traditional and cyclooxygenase 2 inhibitors (COXIBs), are commonly prescribed to relieve pain and inflammation  and are Recent clinical trials have follow-up periods of 12 weeks, which has become a regulatory requirement for registration of symptom-modifying drugs in OA . Change While many clinicians may recognise the link between early and late pain response and non-response in their everyday practice, this tends not to be reflected in guidance. For example, if early non-response predicted that there would be no later response, guidance might well suggest early switching of therapy in the face of non-response after 2, 4 or 6 weeks. This does not happen, and, as a consequence, perhaps pain is frequently poorly treated: over half of patients still had moderate or severe pain despite being on treatment .This study builds on a large, recent systematic review and network meta-analysis of traditional NSAIDs and COXIBs in patients with OA or RA in which researchers examined relative benefits and risks . The datIn the present study, we therefore set out to assess the association and predictive ability of CFB in VAS pain scores between the time points of 2, 6 and 12 weeks in randomised controlled trials (RCTs) including traditional NSAIDs, COXIBs and placebo. The predictive ability of earlier pain measurements for long-term treatment benefit is of interest to clinical practice and future clinical trial design, and would add substantially to the currently available literature in arthritis.The evidence base for this analysis was obtained from a recently published systematic literature review that included 176 RCTs with a total of 146,524 patients with OA and RA . This reTo assess the association between mean CFB in VAS pain scores, a linear regression model was fitted for all the possible pairs of subsequent measurements, with the later time point as an outcome and the earlier time point as the predictor. Thus, three models were fitted to the respective available data: model 1, predicting mean CFB at 6 weeks based on mean CFB at 2 weeks; model 2, predicting mean CFB at 12 weeks based on mean CFB at 2 weeks; and model 3, predicting mean CFB at 12 weeks based on mean CFB at 6 weeks.Each treatment arm was treated as a data point, while random intercept models were fitted to account for clustering within studies.As the number of patients analysed in each of the included studies varied considerably, the weight of each data point should be taken into consideration proportionally. Thus, two weighting options were tested for these models: (1) weighting by the sample size used at the later measurement and (2) weighting by the precision of the later measurement, implying the outcome variable of each model. The Akaike information criterion (AIC) was used for selecting the model option that best fit the data. Models with a smaller AIC are better supported by the data. R software for statistical programming , versionr) are presented with the weighting method used. This is a measure of the linear correlation between two variables, x and y, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation and −1 is total negative correlation.Correlation coefficients  in whicOverall, 33 RCTs  reported VAS pain scores at 2 and 6 weeks (model 1), 21 RCTs  at 2 and 12 weeks (model 2) and 26 RCTs  at 6 and 12 weeks (model 3). Descriptive statistics on CFB in VAS pain scores at weeks 2, 6 and 12 are shown in Table r values are 0.84 between 2 and 6 weeks, 0.79 between 2 and 12 weeks, and 0.96 between 6 and 12 weeks. This indicates a very strong positive association between outcomes at the evaluated time points, and that for most patients early and later response or non-response will be much the same, with few experiencing a different late response compared with the early response. Clinical effect (decrease in VAS pain score) observed at the earlier time points  of treatment is associated with the effect (decrease in VAS pain score) at the later time points . Thus, clinical effect (decrease in VAS pain score) observed at the earlier time points  of treatment is predictive of the effect at the later time points .Sample size weighted correlation coefficients between the three time points are presented in Table The (average) intercept and slope, together with the 95 % confidence interval (CI) and AIC for each model, are reported in Table CFB in VAS pain score at 2 weeks was significantly associated with CFB in VAS pain score at 6 weeks ; intercept −4.6, 95 % CI −6.9, −2.4). A scatterplot of observed data per arm at both time points, along with predicted regression lines N-weighted and precision-weighted, is presented in Fig. CFB in VAS pain score at 2 weeks was significantly associated with CFB in VAS pain score at 12 weeks . Similarly, CFB in VAS pain score at 6 weeks was found to be highly predictive and very close to CFB in VAS pain score at 12 weeks . Scatterplots of observed CFB in VAS pain data per arm at 2 and 12 weeks and 6 and 12 weeks, along with the predicted regression lines, are presented in Figs. In this study, we assessed the association and predictive ability of CFB in VAS pain score between the time points of 2, 6 and 12 weeks in RCTs of OA and RA. The analysis was based on data derived from a systematic literature review of published RCTs comparing diclofenac, ibuprofen, naproxen, celecoxib or etoricoxib with each other or with placebo . That reThe results suggest that average CFB in VAS pain scores at all time points are highly associated. CFB in VAS pain score at 2 weeks was predictive of response at both 6 and 12 weeks. CFB in VAS pain score at 6 weeks is also predictive and almost identical to CFB in VAS pain score at 12 weeks. This is in accordance with individual patient-level responder analysis of etoricoxib, celecoxib, naproxen and ibuprofen over 2–12 weeks, where the proportion of patients achieving various levels of response was consistent at 2, 4, 8 and 12 weeks .Earlier, Bingham and colleagues demonstrated a similar predictive effect of early response to NSAIDs in predicting later response in a pooled analysis of two identical 26-week studies testing etoricoxib, celecoxib and placebo in patients with OA of the hip and knee. With active treatment, around 75 % of patients who were responders at 2 weeks were also responders at 12 weeks . This isThe finding that early response is predictive of later response is important in a number of ways. In clinical practice, for example, it can be used to consider ‘stopping rules’, whereby the failure to achieve a certain level of pain relief by 2 or 6 weeks with one NSAID would mean that the therapy is reviewed, the dose is escalated or a switch is made to another analgesic. Together with the knowledge that analgesics provide good pain relief in only a portion of patients , this caThese ideas can also inform appropriate treatment duration in designing a clinical trial (with consideration of both tolerability and efficacy). For example, studies of efficacy could be shorter, perhaps 6 instead of 12 weeks. But studies of harm, which are typically longer and often larger, might be considered unethical if they included a large proportion of patients who were at risk but had no benefit; studies of harm might have to have quite different designs, perhaps based on cohorts of only those patients who actually benefit. However, the actual design can build in aspects of this knowledge, either in pragmatic trials of switching therapy in the face of non-response, designs for which have been proposed , or in tLimitations of this study should be borne in mind when interpreting the results. The limitations related to availability of data and the potential for within-study bias and publication bias have been extensively discussed elsewhere . Our anaThe predictive ability of the models was assessed by examining the discrepancies between observed and predicted values and the standardised residuals. In Additional file For patients with OA and RA, early analgesic response measured by VAS for pain beyond 2 weeks of treatment with a particular NSAID is likely to be predictive of response at 12 weeks. Failure to achieve desired pain relief after 2 weeks of treatment should trigger reassessment of dosage and/or choice of analgesic.


Adolescent idiopathic scoliosis (AIS) is a four dimensional deformity of the spine arising in otherwise healthy children during puberty. The fourth dimension is time. This dimension is the characteristic of our database created in 1998 with systematic reconvening of our patients at regular intervals which increases the level of scientific evidence , 3. LongTo measure the effectiveness of a brace two main factors can be involved: 1. the immediate in-brace reduction depending how to get the three-dimensional correction and its reproducibility; 2. the patient’s adherence which depends on aesthetics and tolerance , 8. DiffHistorically, in the early twentieth century, in the United States, Sayre  was the In France, the Lyon brace, created in 1947 by Pierre Stagnara, was the first 3D adjustable contention brace used after a plaster cast. With the Lyon brace, elongation occurs between the pelvic and shoulder girdle with equal distribution of forces on the right and on the left. The elongation requires precise adjustment of the brace during the growth of the child . Other TThe segmental derotation is difficult to achieve because it is done through the ribs and could lead to an increase in a flat back. It is impossible to achieve derotation when the rib hump is angular. The mathematical basis of the twisted column is the circled helicoid with horizontal generating circle. The overall untwisting occurs between the axillary and pelvic clamps and the thoracolumbar horizontal plane Fig. .Fig. 2FrCotrel added a fundamental component: the flexion in the frontal plane , 15. TheMany previous studies support the positive results associated with the casting and Lyon braces , 16, 17 Even if the old Lyon brace in polymethacrylate was very rigid, the credit for HIGH RIGIDITY goes to the Italian team of ISICO with the Sforzesco brace, which has proven to be effective by avoiding plaster casts for scoliosis over 45° . The acrSince May 2013, all patients of JCdM were treated with the ARTbrace instead of a plaster cast which showed good initial results. Indeed, the first immediate results of the ARTbrace have demonstrated that the in-brace correction of the Cobb angle in the first 225 cohort of patients was 70 %, a correction which is 40 % higher than with the former Lyon brace or historical Lyon brace. The value of this correction was even higher than for other braces published in the literature, including retrospective studies , 23, 24.Like the historical Lyon brace, the ARTbrace is ADJUSTABLE. Both axillary and pelvic clamps are adjustable with a precise wrench and a bolt system and an anterior ratcheting buckle.Like the historical Lyon brace, the SAGITTAL PLANE is fixed by the posterior bar. But the sagittal plane is determined by the segmental mould and the superposition of the mouldings. In additional it is the lack of support at the sterno-clavicular level and at the abdominal level that avoids lumbar delordosis and thoracic flat back.In this study, early results of 148 first consecutive scoliosis treated with the ART-brace after 1-year are reported in correlation with a matched pair control of the last 100 patients treated with the old Lyon Brace.We performed a prospective case series of 148 scoliosis with short time results after 1 year compared with a historical retrospective case series of 100 scoliosis. Consecutive cases are recruited in both groups. Randomization was not possible due to the administrative impossibility to perform plaster casts after May 2013. All lumbar scoliosis Lenke 5 were eliminated in the two groups as they continue to be treated by the GTB short brace .Since May 2013, we treated more than 400 patients at the “Clinique du Parc – Lyon” with the new Lyon brace (ARTbrace) instead of the classical EDF plaster cast followed by the historical Lyon brace. The initial aim was to avoid a plaster cast, but very quickly, the ARTbrace appeared to be a much more effective solution compared to the former plaster casts and it was even better tolerated. Following the early successes the whole treatment was continued with the same brace. In this prospective study, only the first 148 of all patients, 17 % of males and 83 % of females with an average age of 13.37, with a follow-up at 1 year, have been included. The patients of this main group presented 35 thoracic primary curves and 28 lumbar or thoraco-lumbar primary curves and 37 double major curves with a Cobb angle ranging from 20° to 53° (average 29.23° and Standard Deviation: 8.14°). These 148 patients are group A. The second matched pair control group consisted of a consecutive series of 100 patients  and an average age of 13.6, treated with a plaster cast and the historical Lyon brace, and controlled 1-year after brace fitting, with 41 thoracic primary curves, 23 primary lumbar or thoraco-lumbar curves and 36 double major curves with a Cobb angle ranging from 20° to 52° (average angle Cobb 30.4° and Standard Deviation: 9.61°). These 100 patients are group B.All treatment parameters like indications, physiotherapy, full or part-time bracing were identical for both groups, according to the experience of Lyon management , 16, 17.The study of dropouts is fundamental and we expected a high rate because the realization of the plaster cast was a barrier that only 2/3 of children were crossing. Lyon bracing management has always been considered as an elitist treatment. After 1 year the number of dropouts is 14 (162-148) about 10 %. Some patients referred by colleagues from other countries and controlled by them are not considered as dropouts.All patients were evaluated radiologically before treatment (T0), in-brace (T1), at 6 months without brace (T2) and at 1 year without brace (T3) during treatment. Clinical evaluation at T1 is performed at the end of full time wearing. The clinical parameters were identical for both groups and consisted of measure rib hump in millimetres, and Bunnel ATR by Adam’s posture.The radiological examination of ARTbrace group A was performed with an EOS micro dose radiological System, an ultra-low dose radiation imaging system that provides simultaneous AP and Lateral views in the standing position with 25 times less radiation than traditional X-ray, equivalent to one week of natural Earth radiation –28. The An automated management system control facilitates regularity in follow up meetings. A 3D sterEOS study was carried out every time we had the EOS radiography at T0.The radiological follow-up of control group B patients was performed without a sagittal view due to radiation saving habits with traditional radiology and probably also because the correction in the sagittal plane was not perfect. The problem of radiation in scoliosis was discussed in the consensus session of the SOSORT 2011 meeting . In factAll the data are recorded immediately into a database and a serial number is automatically assigned at T1 about 3 days after bracing. All other statistical tests are done with the package SPSS v20. The first step is to confirm the normality of distribution (Kolmogorov-Smirnov & Shapiro-Wilk) and then use an independent-samples T test to compare Cobb angles T0 (before brace), T1 (in-brace),T2 (at 6 months) and T3 (at 1 year). A p value of less than 0.05 was considered to be significant. A copy of the Excel database can be downloaded to allow any comparisons  and Bunnel’s ATR (Bu) are shown in Table p = 0.929.There was not a significant difference in the score of Thoracic rib hump before brace for control group with the old Lyon brace  and the ARTbrace group  = 0.089, p = 0.193.There was not a significant difference in the score of Thoracic Bunnel ATR before brace for control group with the old Lyon brace  and the ARTbrace group  = 1.307, p = 0.541.There was not also a significant difference in the score of Lumbar rib hump before brace for control group with the old Lyon brace  and the ARTbrace group  = -0.612, p = 0.943.There was not also a significant difference in the score of Lumbar Bunnel ATR before brace for control group with the old Lyon brace  and the ARTbrace group  = -0.072, There was a significant difference in the scores for thoracic rib hump and Bunnel ATR and for lumbar rib hump and Bunnel ATR, at 6 months between the two groups.p = 0.00Thoracic rib hump: t(176) = 5.651, p = 0.00Thoracic Bunnel ATR: t(176) = 5.104, p = 0.00Lumbar rib hump: t(155) = 5.459, p = 0.00Lumbar Bunnel ATR: t(155) = 5.304, Group A (ARTbrace)At the thoracic level the percentage improvement is: 57 % for rib hump and 51 % for ATRAt the lumbar level the percentage improvement is: 79 % for rib hump and 86 % for ATRGroup B At the thoracic level the percentage improvement is: 27 % for rib hump and 25 % for ATRAt the lumbar level the percentage improvement is: 53 % for rib hump and 49 % for ATRThe percentage improvement between the old and the new Lyon brace is near 30 % for both rib hump and ATR. It is better for the lumbar area compared with the thoracic one.The main group A of 148 patients (ARTbrace) had 195 primary curves from 20° to 55°: 63 curve Thoracic, 42 curve lumbar with 45 double major curves. Only primary curves were selected.The control group B of 100 patients  had 136 curves from 20° to 50°: 41 Thoracic curves 23 lumbar curves with 36 double major curves. Only primary curves were selected /average T0 and so on for T2 and T3 /percentage B for T1, T2 and T3 Table .Table 4DThe results were reported for the thoracic and lumbar curves. We find that the extra in-brace correction obtained persists at 6 months with even a tendency to improve after 1 year Fig. .Fig. 5EvWith SPSS we can confirm with two tests: Shapiro-Wilk, and Kolmogorov-Smirnov, that the data comes from a normal distribution  and the ARTbrace group  = 0.834, p = 0.378.There was not also a significant difference in the score of Lumbar Cobb before brace for control group with the old Lyon brace  and the ARTbrace group  = -0.884, There was a significant difference in the scores for thoracic and lumbar curves: in brace, at 6 months and after 1 year.p = 0.00Thoracic in-brace: t(182) = 4.254, p = 0.00Lumbar in-brace: t(144) = 3.993, p = 0.023Thoracic at 6 months: t(182) = 2.284, p = 0.035Lumbar at 6 months: t(144) = 2.131, p = 0.02Thoracic at 1 year: t(182) = 3.205, p = 0.015Lumbar at 1 year: t(134) = 2.463, The distribution of improvements at the 1 year follow-up was first studied with standardized SRS criteria  with a wThe radiological follow-up of control group patients was performed without lateral X-ray and therefore it is not possible to make a statistical comparison. But thanks to the use of the micro dose EOS system a systematic sagittal analysis was possible for the main group of patients (ARTbrace).In a previous study, we showed that the average thoracic kyphosis angle with the upper limit T4 was 37° . For thi73/148 patients (i.e. 49.4 %) had initial thoracic kyphosis below 30° In-brace angulation  improvement in ARTbrace is 8.84°, significant (p = 0.000)The in-brace improvement rate is 50 % and very significant (p = 0.000), and without brace at the last follow up, the improvement rate is 46 % (p = 0.000). There was no statistical difference between the in-brace group and 1 year after when not wearing a brace (p = 0.289). The in-brace improvement is therefore maintained at the 1 year follow up when the brace is off.38 % of patients showed an improvement of 10° or more, 36 % of patients showed an improvement between 5° and 9°, 26 % of cases with stability, no back flat worsening.50 patients were monitored with sagittal EOS without brace at the 1 year follow-up . For this specific group: initial kyphosis , in-brace kyphosis  and last follow-up without brace  were analysed  takes place to the detriment of the lumbar lordosis and the thoracic kyphosis. In ARTbrace, the sagittal plane is determined by the posterior metal bar and ahead, expansions at both ends allow active 4D correction Fig. .Fig. 8CoIn this case n° 389, the improvement in the sagittal plane is important and harmonious. The spine follows the curve imposed by the posterior metallic bar  is a structural three-dimensional deformity of the spine arising in otherwise normal children during puberty. The use of brace in the conservative treatment for AIS  plays anMany previous studies support the positive results with the casting and Lyon braces , 16, 17.Segmental moulding with individual correction of the frontal and sagittal plane,Individual shape superpositionFixed sagittal plane with simultaneous correction of flat back or hyperkyphosisNight and day overcorrecting braceAxilla baby lift conceptCoupled movement with biomechanical helicoidally detorsion of spine,High rigidity asymmetric polycarbonate with “mayonnaise tube” elongation effectSoft contact to increase tolerance and compliance4D action with breathing toward the lateral expansionsFor ethical reasons, comparative studies of braces are exceptional. The originality of this study is the instantaneous transition from the old to the new Lyon brace in one step, for administrative reasons. Since May 2013 all patients (450) of JCdM at the ‘Clinique du Parc – Lyon’ were treated with the new Lyon brace (ARTbrace) instead of the classical EDF plaster cast. In fact from the first patient being treated with the new brace, the ARTbrace appeared to be a much more effective solution compared to the former plaster cast and it was even better tolerated. JCdM  has repoOne limit of this study was to only value the results of the immediate in-brace reduction of scoliotic curves by the ARTbrace, so in a limited time frame (3 day follow-up). In our study, instead, we report the early clinical and radiological results of group A (of 148 patients) with a follow-up after 1 year, so over a longer period of time, in correlation with a matched-pair control old Lyon brace group B.T1 initial in-brace correctionFor thoracic curves, the percentage improvement between the two groups was 37 %, confirming the initial results.T2 at 6 monthsX-rays at 6 months are conducted without the brace. In both groups we observe an angular recurrence linked to the elasticity of the scoliotic curvature with and without brace, which is normal. Overall, this elasticity is statistically lower for group A, as if a better in-brace correction decreased elasticity of scoliosis i.e. the difference between in-brace angulation without brace. These results confirm the BRAIST study that retains the importance of in-brace correction brace as a fundamental criterion of the final outcome treatment. If we compare the two groups, the percentage of improvement is even slightly higher.T3 after 1 yearMany authors consider the results at 6 months as an excellent point in time to predict the final outcome , 21, 35.In frontal radiological outcomes of this study, significant differences in the scores for Thoracic and Lumbar curves at T0, T1, T2, T3 are reported.Certainly angular reduction after 1 year is not the final treatment outcome (2 years after weaning of brace), but we can identify some trends.In the sagittal plane, this is the first brace to significantly improve the flat back and delordosis tendency.This improvement with the ARTbrace can be related to segmental moulding with fixed sagittal correction but above all to the unscrewing or untwisting effect of the spine with translation of the vertebral bodies near the midline. In the literature, studies on improvement to the sagittal plane due to brace effect do not exist. Instead, many authors report accentuating brace effect on the flat back, probably related to axial stretching due to the overcorrection in the frontal plane , 37. AnaIn the horizontal plane, this is the first time we no longer speak of segmental derotation but overall untwisting of scoliosis measured automatically by SterEOS .As scoliosis is a structural three-dimensional deformity, the development of the EOS-system has allowed us to study better transverse plane analysis. It is a concept initiated by  his “torThe former Lyon brace requires the use of Lenke classification adapted to bracing. The segmental moulding of the new Lyon brace is much simpler and requires only two classes: C and S shaped scoliosis. The overall alignment is provided by the first moulding. For C shaped scoliosis, the thoracic and lumbar shifts will be realized in the same direction, while it will be carried out in opposite directions for the S curves. The lumbar oblique tilt and high curvatures are also much easier to manage.The interest of overcorrection is not obvious especially for a specialist symmetrical brace such as the historical Lyon brace. However, we were using the night overcorrection for small thoracolumbar curves with good results. The Chêneau brace experience also goes in the direction of overcorrection. The ability to manually perform that overcorrection directly on the child is an advantage. Toru Maruyama showed us the interest of the shift in the scoliosis correction , 42 and The indications are the same with wear time in the day depending on the initial angulation.The management is the same during treatment with adaptation of wearing time according to the elasticity of the scoliosis (X-ray without brace compared to in-brace X-Ray). Indeed, we believe that the spine is not made to grow properly under a rigid brace, and a very effective brace worn for a shorter period during the day is better than a less effective brace worn 23h/24. Although the consequences of the brace on bone mass is not obvious, the precautionary principle is required .Physiotherapy has remained the same, but the brace asymmetry and preparation for segmental moulding are closer to asymmetric methods and probably the current protocol will change in the future.The continuation of sports during treatment is a characteristic of the Lyon bracing treatment because the plaster cast causes a realignment of tension along the spine. The results with the historical Lyon brace were better when the children were practicing at least 5 h of sport each week. The initial full time wearing has the same creep effect. There is also another advantage with increase of skin tolerance (watch effect of Manuel Rigo). However, tolerance is worse in part time wearing.So far we have not changed the overall management of the Lyon bracing treatment following the guidelines set by the SOSORT in 2011 .The indiCompliance is a key element of the final results of the treatment with immediate in-brace reduction. Compliance depends on the child and the family, but also on the brace which should be light, aesthetics and the allowance of normal breathing by expansions. The low dropout rate may also be due to changes in the brace.This study demonstrates not only good results of the ARTbrace about immediate in-brace reducibility of scoliosis described in previous studies published by the same author, but this trend is maintained further at 6 months and at 1 year. So the new concepts and first results of ARTbrace, defined as a modified or “new” Lyon brace, confirm that it can completely replace the casting and old Lyon brace process.Finally, angular reduction at 1 year is not certainly the final treatment outcome (2 years after weaning of brace) even if some authors are using the reduction at this point in time as a predictive criterion. So, future studies could confirm if this criterion is valid and consequently the effectiveness of the ARTbrace.The data set supporting the results and all SPSS statistics results are included within the article.All patients were informed and have given their consent for this work. This monocentric study was the object of a declaration to the CNIL under the number 1831534 in France and the procedure accepted.


This study aimed to evaluate the effect of the full-length carbon fiber (FCF) insole on the lower leg muscle activity and the GRF during walking in patients with unilateral midfoot arthritis.Fifteen patients with midfoot arthritis aged between 20 and 60 years participated in the study. Foot function index (FFI) was assessed to evaluate pain before and after the walking activity. Lower leg muscle activity, GRF and gait cycle time during walking were measured under two conditions: “shoe only”, and “shoe with FCF insole”. Electromyography (EMG) activities of the tibialis anterior (TA), gastrocnemius medialis (GCM) and soleus muscles in the involved leg were assessed by multi-channel telemetry EMG. Simultaneously, the GRF was measured under both conditions. The gait cycle was divided into four different phases including loading response (LR), mid-stance (MS), terminal stance (TS), and pre-swing (PS).With reference to the pain subscale of the FFI, we divided the patients into “reported pain reduction” and “reported no pain reduction” groups. While walking under the shoe with FCF insole condition, significant reductions of the TA muscle activity were observed in the LR phase only in the group that reported pain reduction (p = 0.028). Contrastingly, in the group that reported no pain reduction, the TA muscle activity showed no difference between both conditions (p = 0.237). As for the measurement of the GCM muscle activity, under the shoe with FCF insole condition, a significant reduction was observed in the TS and PS phases only in the group that reported pain reduction (p = 0.046 and p = 0.046). However, in the group that reported no pain reduction, there was no significant reduction of GCM muscle activity in any of the gait phases under either the shoe with FCF insole condition or the shoe only condition (p > 0.05). Neither group reported any statistically significant reduction in the GRF or gait cycle time (p > 0.05).Symptomatic improvement in patients with midfoot arthritis during walking with the FCF insole was accompanied by reduced TA muscle activity in the LR phase along with reduced GCM muscle activity in the TS and PS phases. However, walking with the FCF insole was not effective in reducing the GRF or gait cycle time. From a clinical perspective, these findings suggest that prescription of the FCF insole can be a viable alternative to other non-operative treatments in patients with midfoot arthritis.


Subacromial shoulder pain is a common complaint. Radial Extracorporeal Shock Wave Therapy (rESWT) has being increasingly used to treat calcific and non-calcific tendinosis, although there is no evidence of the effectiveness of rESWT in non-calcific tendinosis of the rotator cuff. A randomised single blind study showed that the short-term effect of supervised exercises (SE) was significantly better than rESWT on subacromial shoulder pain, but both groups improved. In a clinical trial on achilles tendinopathy rESWT improved the effectiveness of treatment with eccentric loading. The objective of this present study is to evaluate if rESWT in addition to SE is more effective in improving shoulder pain and function compared with sham rESWT and SE in patients with subacromial shoulder pain.This is a double blind, randomised sham-controlled trial which is performed at the shoulder clinic at the Department of Physical Medicine and Rehabilitation in Oslo University Hospital, Norway. One-hundred-forty-four patients with subacromial shoulder pain lasting at least 3 months, age from 25 to 70 years old are included in the trial. Patients are randomly allocated in 1:1 ratio to receive either rESWT or sham rESWT once a week in addition to SE once a week for the initial 4 weeks. Subsequently SE are provided twice a week for 8 weeks. The primary outcome measure is a change in the Shoulder Pain and Disability Index (SPADI) at 24 weeks follow-up. Secondary outcomes include return to work, pain at rest and on activity, function, and health related quality of life. The patients, the physiotherapist providing the exercise regimen and the outcome assessor are blinded to group assignment. The physiotherapist providing the rESWT is not blinded.Because of the extensive use of rESWT in the treatment of subacromial shoulder pain the results of this trial will be of importance and have impact on clinical practice.NCT01441830ClinicalTrials.gov  Shoulder pain is a common complaint, and in Norway about half of the population reports to have at least one episode of shoulder pain annually . The mosThe patients with subacromial shoulder pain are treated by physicians with different specialities, including general practioners, rheumatologists, doctors in physical medicine and rehabilitation, orthopedic surgeons, and physiotherapists. Many patients with subacromial shoulder pain undergo surgery, even though supervised exercises (SE) have been shown to be as effective as surgery in both short and long term, and better than placebo , 8. The Extracorporeal Shock Wave Therapy (ESWT) is another treatment option for patients with subacromial shoulder pain. The proposed mechanisms for the effect of ESWT include pain relief, tissue regeneration and destruction of calcification . A systeIn recent years, a new method of shock wave treatment has been developed: radial Extracorporeal Shock Wave Therapy (rESWT), also called radial pulse therapy (RPT). In contrast to regular focused shock wave therapy (ESWT), rESWT creates a diverging pressure field, which reaches a maximal pressure already at the source, and therefore has a more superficial, but broader, effect than ESWT . This trMusculoskeletal ultrasound might be an important supplement to the clinical examination . UltrasoPhysiotherapy treatment for subacromial shoulder pain often is a combination of rESWT and exercise therapy. In a recent randomised single blind study the short-term effect of supervised exercises was significantly better than the effect of rESWT on subacromial shoulder pain, but both groups improved . A cliniAdditionally, previous studies have reported that the prognosis of subacromial shoulder pain is affected by education, work status, polymedication and high baseline pain and disability , 19, 20.To evaluate whether rESWT in addition to supervised exercises is more effective in improving pain and function (SPADI) compared with supervised exercises and sham rESWT in patients with subacromial shoulder pain at 24 weeks follow-up.To evaluate the influence of demographic and clinical factors on the clinical course of SPADI and sick leave in patients with subacromial shoulder pain during 1-year follow-up.This study is a double blind, randomised, sham-controlled trial. All the patients are recruited from the shoulder clinic at the Department of Physical Medicine and Rehabilitation at Oslo University Hospital, Norway.This study has received approval from the Regional Committee for Medical and Health Research Ethics (2011/255).Patients aged 25–70 years, with subacromial shoulder pain lasting at least 3 months, are eligible for inclusion.The inclusion criteria are: dysfunction or pain on abduction, normal passive glenohumeral range of motion, pain on at least one of two isometric tests  and a positive Hawkins impingement sign . PatientThe exclusion criteria are: previous surgery on the affected shoulder, instability, rheumatoid arthritis, full thickness tear of the rotator cuff, cervical radiculopathy, infection, patients considered not being able to fill out questionnaires or follow the treatment, contraindications for shock waves therapy , previous experience with shock wave therapy, injection of cortisone in the affected shoulder in the last 6 weeks and SPADI score below 20.The patients who fulfil the inclusion criteria and give their informed consent after having received oral and written information are randomised to one of the two treatment groups: supervised exercises and rESWT, or supervised exercises and sham rESWT. Computer-based block-randomisation with 20 in each block in a 1:1 ratio will be performed. A research assistant not involved in the further management of the patients opens the sealed envelopes and assignes the patients to their respective treatment group. The rESWT and the sham rESWT are subsequently performed by a physiotherapist not involved in any further management of the patients.The patients, the researchers collecting and analysing the data, the authors and the physiotherapists providing the exercise regimen are all blinded for rESWT/sham rESWT. The blinding will not be revealed until the results are analysed and the interpretation is discussed and written down in two versions, one assuming that treatment A is rESWT, and one assuming that treatment A is sham rESWT.To evaluate the blinding, all the patients are asked at the 24-week follow up whether they think they have received real rESWT or sham rESWT.Patients from both intervention groups receive a supervised exercise regimen by experienced physiotherapists. During the initial 4 weeks, they conduct supervised exercises once a week. The last 8 weeks, they perform supervised exercises twice a week. Each supervised exercise session lasts 40 min. In addition, the patients are instructed to conduct home exercises daily.The patient’s history and functional diagnosis are used as individual guidelines for treatment in the first phase. The main goals of the supervised exercise regimen used in this study are to unload mechanical stress and to normalise dysfunctional neuromuscular movement patterns. Postural exercises, optimal scapular positioning and centralisation of caput humeri are of importance when perfoming the exercises. The physiotherapist supervises and ensures that the patients perform the movements correctly. Then eccentric training, exercises with gradually increasing resistance, and plyometric exercises to improve muscle strength and endurance are performed . Newer rThe first 4 weeks, the patients receive rESWT or sham once a week in addition to the exercises. The rESWT or sham treatment (SwissDolorClast/EMS) is given by one of two physiotherapists who both went through an application course and training before the study started. The rESWT/sham is given on one to three tendons , depending on which tendons are painful at isometric tests. Two thousand impulses of shock waves are applied to each painful tendon, with a pressure between 1,5 and 3 bar (depending on what the patient tolerates). We use a power handpiece, which provides an energy of 0,01 – 0,35 mJ/mm2. This handpiece was chosen after advice from the producer (Enimed/SwissDolorClast), physiotherapists with experience in rESWT, and a previous systematic review concluding that future research on rotator cuff tendinosis should focus on high-energy shock wave .The sham rESWT is administered in the exact same way as the rESWT. The sham handpiece is similar to the real handpiece in design, shape and sound, and vibrates exactly like the real handpiece, but no real shock waves are conducted.Compliance to the treatment is recorded.The patients eligible for inclusion are referred to a physician (EK), who examines all the patients at baseline according to a structured protocol including active and passive range of motion, isometric tests, Hawkins sign, examination of the AC joint and biceps tendon. Ultrasound examination of the affected shoulder is performed the same day. The patients also complete a comprehensive standardised questionnaire including primary and secondary outcome measures, the prognostic demographic and clinical factors including sex, age, duration of symptoms, education, drug use, sick leave status and emotional distress. If an MRI has not been performed within the last 3 months, the patients are also referred for an MRI of the affected shoulder.Self-reported primary and secondary outcome measures are filled in at each follow-up. At 6 weeks after starting the treatment, the patients fill in a short questionnaire. At 12- and 24 weeks and at 1 year they come to follow-up visits where they have an additional clinical examination, all done by the same blinded physician (EK) Fig The primary outcome measure is the Shoulder Pain and Disability Index (SPADI). The SPADI is a self-assessed, validated shoulder score that consists of 13 questions in two subscales, five about pain and eight about function. We use the original version, with each question scoring previous week’s symptoms on a visual analogue scale (VAS). The total SPADI is calculated from averaging the two subscales, and the total score ranges from 0 to 100 with higher score indicating worse pain and disability .Secondary outcomes are return to work, pain at rest and activity measured on an 11-point Likert type scale, function (ability to take something down from a shelf or to carry a 5-kg shoppingbag) measured on an 11-point Likert type scale, and health related quality of life on EuroQol.EuroQol (EQ-5D and EQ-VAS) is a standardised generic instrument for describing and valuing health related quality of life. The EQ-5D comprises five domains that define health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain has three response categories; no problem, some or moderate problems, extreme problems. The resulting health state can therefore be defined as a five-digit number by using the response (1–3) from each dimension. Potentially 243 health states can be defined. The five-digit number is then transformed into a number between -0.56 and 1 with 1 representing the best imaginable health state. The EQ-VAS is a self rating of health status on a vertical VAS from 100  at the top to 0  at the bottom .The patients are instructed not to attend to any other treatment in the study period. We will register on each follow-up visit if they have received any other treatment since the last visit. The use of analgesics is recorded on baseline and on each follow-up visit.A previous study indicates an expected standard deviation (SD) of 20 points . To deteDescriptive statistics will be used to describe baseline characteristics of the treatment groups. The comparison of between group difference in both primary and secondary outcome variables will be performed according to the intention to treat principle.Analysis of variance will be applied to evaluate the difference between groups in the change of primary outcome measure (SPADI) between the baseline and 24 weeks follow-up, adjusting for demographic and medical factors such as age, sex, education, sick leave, duration of symptoms, calcification in the rotator cuff, dominant arm affected, bilateral shoulder pain, drug use, emotional distress and compliance to the rESWT treatment. Secondary outcome measures will be assessed with the same approach in separate models. Cox regression will be used to analyse the secondary outcome of return to work at 1 year follow-up.Finally, mixed model will be applied to explore the variations of the mean SPADI from baseline through the 1-year follow-up within and between patients (between the intervention groups) simultaneously. The effects of demographic and clinical factors on the change of SPADI will also be explored. Number needed to treat will be calculated according to Guyatt et al . BonferrTo deal with missing values of the important analytic variables multiple imputation will be carried out. Estimations from the imputed data will be compared with the estimation from the data with complete values.Placebo means to please (from latin placere). It is proposed that placebo and opioid analgesics share a neuronal network . The powRadial ESWT is being increasingly used for musculoskeletal complaints including subacromial shoulder pain, with and without calcification. Current evidence suggests that rESWT may have an effect on calcific tendinopathy of the shoulder, but there is no evidence so far to support the use of rESWT in subacromial shoulder pain without calcification , 17, 27.In the present study we have included sham treatment to make sure that any difference in results between the groups is due to the rESWT treatment, and not the placebo effect. All the patients get supervised exercises in addition to rESWT or sham, because this is the way most therapists use rESWT today. Exercise therapy is an evidence based treatment option for subacomial sholder pain, both in short- and long term , 37.Because of the abundant use of rESWT, the results of this study will be of major interest. A positive result will support current practice, while no difference between the groups indicates that the use of rESWT for subacromial shoulder pain should not be recommended.


Primary care pharmacological management of new musculoskeletal conditions is not consistent, despite guidelines which recommend prescribing basic analgesics before higher potency medications such as opioids or non-steroidal inflammatory drugs (NSAIDs).The objective was to describe pharmacological management of new musculoskeletal conditions and determine patient characteristics associated with type of medication prescribed.The study was set within a UK general practice database, the Consultations in Primary Care Archive (CiPCA). Patients aged 15 plus who had consulted for a musculoskeletal condition in 2006 but without a musculoskeletal consultation or analgesic prescription in the previous 12 months were identified from 12 general practices. Analgesic prescriptions within two weeks of first consultation were identified. The association of socio-demographic and clinical factors with receiving any analgesic prescription, and with strength of analgesic, were evaluated.3236 patients consulted for a new musculoskeletal problem. 42% received a prescribed pain medication at that time. Of these, 47% were prescribed an NSAID, 24% basic analgesics, 18% moderate strength analgesics, and 11% strong analgesics. Increasing age was associated with an analgesic prescription but reduced likelihood of a prescription of NSAIDs or strong analgesics. Those in less deprived areas were less likely than those in the most deprived areas to be prescribed analgesics . Those without comorbidity were more likely to be prescribed NSAIDs (relative risk ratios (RRR) compared to basic analgesics 1.89; 95% CI 0.96, 3.73). Prescribing of stronger analgesics was related to prior history of analgesic medication .Over half of patients were not prescribed analgesia for a new episode of a musculoskeletal condition, but those that were often received NSAIDs. Analgesic choice appears multifactorial, but associations with age, comorbidity, and prior medication history suggest partial use of guidelines.The online version of this article (doi:10.1186/1471-2474-15-418) contains supplementary material, which is available to authorized users. Guidelines for the management of painful musculoskeletal conditions advocate a holistic approach incorporating education, psychological, physical, and surgical interventions administered in a step-wise fashion , 2. ThisIn 2003, the World Health Organisation (WHO) offered health care professionals guidance on the use of analgesia in low back pain that is equally applicable to musculoskeletal conditions in general . This adDespite guidance advocating similar approaches for neck and low back pain, their management strategies have been shown to be different in terms of the analgesics prescribed and other therapies . Whilst The primary objectives of this study were therefore, to describe the analgesics that primary care clinicians prescribe when a patient consults with a new episode of a musculoskeletal condition, and to determine socio-demographic and clinical factors associated with being prescribed medication and type of medication.This was a retrospective study based in the Consultations in Primary Care Archive (CiPCA). CiPCA is a high quality primary care database, giving comparable musculoskeletal consultation prevalence to national primary care databases , 9. ApprPatients aged 15 and over were included if they consulted for a musculoskeletal condition in 2006, with no musculoskeletal consultation and no prescribed analgesic medication for the 12 months preceding their 2006 consultation. Musculoskeletal conditions were defined using Read Codes based on a previously derived set of codes . Read coIn the United Kingdom (UK) there are over 300 prescribable analgesic formulations available to general practitioners (GPs) . Bedson . Pain medication was deemed as being related to a musculoskeletal consultation if it was prescribed on the same day as the consultation, or within 14 days of that consultation. This was to allow for patients to take up a ‘delayed’ prescription for analgesics that the GP offered should the condition not improve.For this study, due to the low prevalence of prescription of very strong opioids  and to aFactors evaluated for their association with pain medication prescription on first consultation included the patient’s age, gender, co-morbidity, region of pain, previous consultation for musculoskeletal conditions, analgesic medication history, neighbourhood deprivation, registered practice, and staff consulted. The age of the patient was calculated as of 1st July 2006 and grouped into the following categories: 15–29, 30–44, 45–59, 60–74, and 75+. Neighbourhood deprivation was based on the Index of Multiple Deprivation 2007. This is linked to the postcodes of patient addresses . The depThe area of pain was categorised as back, knee, hip, neck, foot and ankle, arm , shoulder, and other or unspecified. The specified areas are the most common locations of musculoskeletal pain . IdentifCo-morbidity was defined as the presence of one or more specified disorders or diseases in the period 0–24 months before the baseline musculoskeletal consultation. The specific comorbidities were diabetes, chronic obstructive pulmonary disease (COPD), depression, cardiovascular disease, chronic kidney disease, gastro-intestinal, and neoplasm. These are long term comorbidities which clinicians take into consideration when deciding which type of analgesia to prescribe .Multilevel logistic regression was used to evaluate the associations of being prescribed any pain medication on first consultation with patient and practice characteristics. Levels within the multilevel model were patient (level 1) within practice (level 2). Results are presented as odds ratios (OR) with 95% confidence intervals. Both adjusted and unadjusted odds ratios for the patient characteristics are reported.A second analysis was then performed on only those receiving a pain medication. A multilevel multinomial logistic regression model with the analgesic group as the dependent variable was used to assess associations of patient and practice characteristics with type of analgesic received. The reference category was group 1 . Results are reported as relative risk ratios (RRR) with 95% confidence intervals. All models were evaluated using a 5% statistical significance level with no adjustment for multiple testing using the statistical package Stata.In 2006, there were 83,875 patients aged 15 and over registered at the 12 practices. 3236  patients were identified as having a new consultation for a musculoskeletal problem in 2006. The mean age of these 3236 patients was 43.1 years (SD 15.8), and 1916 (59%) were male , followed by the knee 11%). Least commonly affected was the hip (6%), with other or unspecified regions accounting for 26% (Table 1%. Least1344 42%) patients received prescribed pain medication within 14 days of their new musculoskeletal consultation  but higher in those aged 45 to 59 , 60 to 74 , and those aged over 75 . Those in the least deprived areas were least likely to receive a pain medication prescription . Pain medication was most likely to be prescribed for those with pain in the back; however, no difference was apparent between those with shoulder and back problems. Those who had received prescribed analgesics in the past were more likely to be prescribed pain medication at this new consultation .There were no significant relationships with comorbidity, gender or whether the patient saw a GP or other medical staff.In the 1344 patients prescribed analgesics, there was wide variation between practices in type of analgesic prescribed. Variation between practices accounted for 27% of all remaining variation in type of medication prescribed in the multivariable model.Table Those with back pain were more likely to be prescribed weak-moderate analgesics, strong analgesics and NSAIDs than basic analgesics compared to those presenting with musculoskeletal problems in other regions. Those who were seen by GPs were more likely to be prescribed strong analgesics than basic analgesics .This study has shown that more than half the patients consulting for a new episode of a musculoskeletal condition were not prescribed pain medication. Of those who were, most commonly NSAIDs were prescribed, with basic analgesics being the second most common analgesic. There appears to be restricted early use of stronger medication with strong opioids being prescribed for only one in ten new musculoskeletal patients prescribed pain medication. Patient age, deprivation, body region of pain, comorbidity and previous analgesic prescriptions were associated with prescribing behaviour and there was extensive practice variation.Our study found less than half of new consulters for musculoskeletal pain received an analgesic. A previous study of those aged over 50 consulting in primary care for musculoskeletal pain, and who had not consulted in the previous 30 days, also reported that less than half were prescribed analgesics  and thisThe WHO advice relating to managing low back pain, one of the commonest forms of musculoskeletal pain treated in primary care , suggestClinicians appear to consider patient age when choosing to prescribe a pain medication or not, and what level of analgesic potency to prescribe. In our study, those aged over 75 were twice as likely to receive pain medication as younger age groups, but were less likely to be prescribed NSAIDs. This finding is in keeping with current advice on NSAID use in older patients who might be considered more likely to experience adverse effects such as renal toxicity , 22 and Younger adults (15–29) were more likely to be prescribed basic analgesics, perhaps reflecting the less severe nature of pain in younger people with musculoskeletal problems . Female Patients from the most deprived areas were more likely to be prescribed pain medication than patients from medium and least deprived areas and be prescribed stronger analgesics. Social characteristics such as neighbourhood level of deprivation have an additional effect on pain , 34. ThePatients presenting with back problems were most likely to receive pain medication and to receive stronger analgesics. Back pain limits the functional reach of limbs and the ability to rotate the trunk repetitively which is essential for mobility, and results in restrictions on individuals’ social and physical activities and a substantial impact on their life style . CliniciThe findings of this study are limited by the fact that it was based in a regional dataset and therefore might not be reflective of analgesic prescribing in other areas of the United Kingdom. However, the data used in the study is drawn from a data set, CiPCA, which gave comparable consultation figures for musculoskeletal conditions as the larger national databases . We did This study highlights that age, deprivation, body region of pain, comorbidity and previous analgesic prescriptions are associated with analgesic prescribing in primary care when treating patients with a new consulting episode of a musculoskeletal condition. There appears to be a clinically sensible use of these painkillers, in as much as analgesics such as NSAIDs and opioids are less likely to be used in groups that may be more vulnerable to potential side effects. Prescribing also varies depending upon the region of pain being treated. The prescribing characteristics may follow the WHO analgesic ladder of prescribing since there is a restricted use of stronger analgesics at first consultation. However, further research into the pharmacological management of musculoskeletal pain is required to determine if these patterns of prescribing represent the optimum management pathways when managing musculoskeletal conditions.