The second part of the trial, investigating TDF in patients with rheumatoid arthritis (RA) is reported separately.This study was designed to evaluate the utility of transdermal fentanyl  and improvements in functioning (p < 0.001) and physical (p < 0.001) and mental (p < 0.05) health. Scores for 'pain right now' decreased significantly within 24 hours of starting TDF treatment. TDF was assessed favourably and 84% of patients would recommend it for OA-related pain. Nausea and vomiting were the most common adverse events (reported by 32% and 26% of patients respectively), despite prophylaxis with metoclopramide, which showed limited efficacy in this setting.TDF significantly increased pain control, and improved functioning and quality of life. Metoclopramide appeared to be of limited value in preventing nausea and vomiting; more effective anti-emetic treatment may enable more people to benefit from strong opioids such as TDF. This study suggests that four weeks is a reasonable period to test the benefit of adding TDF to improve pain control in OA patients and that discontinuing therapy in cases of limited benefit creates no major obstacles. Osteoarthritis (OA) is a slowly developing articular disease, characterized mainly by cartilage degeneration, which is reflected clinically by a gradual development of joint pain, stiffness, and loss of full range of movement. OA is the most common disease to affect synovial joints, being a major cause of musculoskeletal pain, reduced quality of life and disability. About 40–60% of patients with radiological osteoarthritic changes suffer from clinical symptoms of pain, stiffness and loss of mobility , and aroCurrent treatments for OA include a wide range of non-pharmacological, pharmacological and surgical options, although evidence to support their effectiveness is variable and there are no curative treatments. Therapies focus on reducing symptoms such as pain and stiffness, and minimalizing functional limitation and disability . HoweverTransdermal fentanyl (TDF), providing systemic delivery of fentanyl at a constant rate for 72 hours , has beeThe present study was undertaken to evaluate the utility and safety of TDF for the treatment of pain associated with RA or with OA of the knee or hip, which was not adequately controlled by NSAIDs, Cox-2 inhibitors, paracetamol or weak opioids at optimal doses. As it was an open-label study, it was not designed to prove efficacy of the treatment but to investigate practical aspects of opioid therapy, such as the usefulness of a test-period or concomitant use of antiemetic therapy and to serve as a pilot for a double-blind trial in this patient population. A test period for evaluation of a patient's response to opioid treatment is recommended  and in tAll participants were outpatients requiring supplementary analgesia because of moderate or severe pain, which was not adequately controlled with paracetamol, NSAIDs, Cox-2 inhibitors or weak opioids (e.g. tramadol or codeine). Because non-opioid analgesia is not always taken at sufficient doses to achieve pain control  the triaPatients were excluded from the study if they had received regular treatment with a strong opioid (e.g. morphine) or had received more than the maximum recommended dose of weak opioids or other analgesics in the four weeks before the study. Strong opioids other than fentanyl, supplementary weak opioids or other treatments that might alter the degree or nature of pain could not be started during the study. Patients were excluded if they had continuous pain of non-arthritis origin, or had undergone surgery/arthroscopy within 3 months, intra/peri articular injections for arthritis pain (e.g. steroid injection) within 6 weeks, or arthrocentesis within 4 weeks of the study start.Screened patients satisfying the selection criteria each gave written informed consent before inclusion in this international, open, prospective trial. The study was carried out in accordance with the latest revision of the Declaration of Helsinki and Good Clinical Practice and was approved by independent local ethics committees.®) at a dose of 25 μg/h. Patches were replaced every 72 hours (3 days). Previous non-opioid analgesia was continued and kept stable, but weak opioids were discontinued. The dose of TDF could be increased in steps of 25 μg/h every 72 hours  if required (no maximum dose specified) until adequate pain control was achieved. After 28 days or if necessary for other reasons, e.g. if side effects occurred or the treatment was not effective, a similar downward titration regimen was employed. Paracetamol 500 mg tablets were provided for supplementary analgesia and could be used in doses of up to 4 g/day. With the exception of paracetamol, other non-opioid analgesics were kept stable and no short acting opioids were added during down titration.During the one-week run-in period, non-opioid analgesic treatment was increased to the maximum tolerated or maximum recommended dose, while weak opioids were kept stable. All patients with pain control rated as poor or very poor on a 5-point scale at the end of the run-in period started treatment for 28 days with transdermal fentanyl , at baseline (day 0), on days 7, 14  and on day 28 , on other days if dose adjustment was necessary, and at the end of a one or two week tapering-off period.The primary efficacy variable was pain control, evaluated weekly on a five-point assessment scale ranging from very poor to excellent. For this assessment, the investigator presented the question "would you rate your pain control today as being excellent, good, moderate, poor or very poor?" Patients also completed a pain assessment questionnaire (shortened version of the Wisconsin Brief Pain Inventory (WBPI) )  and treated at least once with trial medication, was also performed .The ANCOVA model was used to analyse the change from baseline to endpoint, and the influence of baseline values. The ANCOVA model was also used to determine differences by centre. The Wilcoxon signed-rank test was used to compare intragroup results and results at each time point or endpoint with baseline, where applicable. Statistical tests were interpreted at the 5% significance level (two-sided).A total of 159 patients, 102 with OA of the knee and 57 of the hip, were recruited into the study from 47 centres in 11 countries and started treatment with TDF. Patient characteristics are shown in Table Concomitant medication with possible analgesic effects during the treatment phase included paracetamol (69%), NSAIDs (45%), weak opioids (33%), Cox-2 inhibitors (13%), other analgesics (8%), steroids (6%), immunomodulating drugs (1%), and strong opioids (1%). Of those taking weak opioids, most took them on the first day of treatment only. Only two patients used opioid rescue medication and had to be considered as protocol violators. There was a reduction in the use of NSAIDs (from 45% to 18%) and Cox-2 inhibitors (9%) and paracetamol (15%) after the first 24 hours of treatment. Rescue medication was required by 59% of participants, of whom almost all used non-opioids, particularly paracetamol. Most patients suffered from concomitant diseases: 59% of the patients had currently active cardiovascular diseases, 50% musculo-skeletal, 48% genito-urinary, 47% endocrine, and 19% gastrointestinal disease. The most frequently used non-analgesic concomitant therapies during treatment were metoclopramide 49% and omeprazole 12%.Of the 159 participants recruited, 25% withdrew from the trial during the treatment phase. Reasons for withdrawal were adverse events (35), insufficent response (1) and other reasons (4). Around half of the drop-outs  occurred in the first week of TDF treatment  of all patients used 25 μg/h as a maximum dose during the study .Adequate pain control was defined as a score of 'moderate', 'good' or 'excellent' on the 5-point pain control assessment scale. The proportion of patients with adequate pain control increased during the one-week run-in period  from 4% to 27%. These patients continued in the study and accounted for the majority of protocol violators. At baseline, 25% of patients reported very poor pain control, 48% poor and 25% moderate pain control, and there was no notable difference between those with OA knee and OA hip . This gives a mean pain control score at baseline of 2.03 , rising to 3.33  at endpoint and a mean change from baseline of 1.3 (SD ± 1.14). This gives an absolute effect size of 1.14.Patients reported a significant reduction in pain from baseline to endpoint for each WBPI item at every time point (p < 0.001). The mean reduction in 'pain at its worst' was 1.8 points (from 8.1 to 6.3), 'pain at its least' was 1.6 points (from 4.4 to 2.8), and 'pain on average' was 2.0 points (from 6.4 to 4.4). The amount of trouble or bother the pain was causing also decreased by 2.7 points on average (from 7.2 to 4.5). The mean reduction in 'pain right now' was 2.6 points (from 6.1 to 3.5) from baseline to endpoint. A significant reduction in 'pain right now' was reported as early as 24 hours after baseline .From patients' diaries, the mean score for degree of pain was significantly decreased at each time point, and from severe pain (score 3) to moderate pain (score 2) from the run-in period to endpoint (p < 0.001). Results were similar for the patients' highest score for their degree of pain. Thus, while at baseline 58% (79/137) reported severe/extreme pain, 4% (5) mild, and only two patients were without pain, by endpoint 41% (56/138) reported moderate pain, 30% (41) mild and 7% (9) no pain. There was little difference between the OA knee and OA hip group.In their assessment of treatment , 63% of patients rated TDF positively with respect to pain control and 84% would recommend TDF for their type of pain. Most patients were satisfied with its convenience of use , and 53% considered side effects were not an issue. In general, there was a difference of less than 10% between the OA knee and OA hip groups. In assessing how they had felt over the past week, the percentage of all patients who answered good or very good increased during the study from 7% (10/142) during the run-in period to 32% (31/97) in week 4, and their scores at all time points were significantly better than before treatment (p < 0.001). By the end of the study, help with basic activities was required by only 28% of patients, with 49% relying less on their helper.For the 122 patients who completed the SF-36 quality of life questionnaire, there were statistically significant improvements in all domains from baseline to endpoint, including overall physical health (p < 0.001) and mental health (p < 0.05)  improved significantly from baseline to endpoint for all groups   from baseline to endpoint Table . In addiAdverse events occurring during the treatment phase and tapering off phase were those associated with strong opioid treatment Table . AdverseThe study was intended to evaluate the utility of TDF under routine conditions and to investigate different practical issues, such as the usefulness of a test-period and use of concomitant antiemetic treatment during the first weeks. It was not designed as a primary efficacy study, since the efficacy of TDF in providing pain relief has already been demonstrated -18. For A one-month test period  is suffiA few patients started treatment with TDF, despite adequate pain control during the run-in phase. These patients were considered to be protocol violators. However, their inclusion provided the opportunity to determine whether TDF could give additional benefits to these patients above those already gained by their current medications. About half of these patients achieved further pain reduction while treated with TDF.Over the treatment period, the numbers of all patients using other analgesics, especially NSAIDs decreased substantially (from 45% to 19%). This may be beneficial in reducing side effects such as gastrointestinal bleeding. Nearly all patients taking weak opioids took them on the first day of treatment only when serum levels of fentanyl had not yet achieved steady state. Paracetamol may be useful for breakthrough pain in some patients but need for rescue medication should be evaluated on an individual basis. Metoclopramide did not appear to prevent nausea or vomiting.Treatment was considered favourable in terms of efficacy, side effects and convenience. A preference for treatment with TDF over sustained release morphine has previously been shown by patients with chronic non-cancer pain .The general health measure, SF-36, indicated that control of pain significantly improved both physical and mental components of quality of life. The improvement in mental health may be related to improved functioning which permits greater social activity. In spite of similar pain control, patients with OA of the hip appeared to have slightly more difficulty with stiffness and general mobility than those with OA of the knee, such as getting in/out of the bath or bed, probably due to the location and function of these joints.WOMAC is a reliable, valid and responsive multidimensional, self-administrated outcome measure designed specifically to evaluate patients with OA of the knee or hip . OverallOverall, the spectrum of reported side effects was consistent with those commonly associated with opioid therapy and with previous experience with TDF. Constipation was not a problem for this patient population as with other patients receiving TDF for non-cancer pain or cancer pain ,29,30, aAs might be expected in an elderly population, many patients had co-existing diseases. For example, 59% had cardiovascular disease on entry, which is of particular interest given the concern about the cardiovascular safety of some Cox-2 inhibitors which, since this trial was undertaken, has led to the withdrawal of rofecoxib.This trial demonstrates that patients with OA of the knee or hip continue to experience pain even at optimal doses of their non-opioid treatment, providing a major reason why patients and clinicians alike are often dissatisfied with current therapies. The study also shows that patients with OA benefit from additional pain control provided by TDF . CliniciDr Richarz is an employee of Janssen-Cilag and the other authors have both received research funding from Janssen-Cilag, which funded this study.UR designed the study and coordinated it. XLL and KP recruited patients to the study and contributed to the interpretation of the findings. All authors contributed to developing the manuscript for publication.The pre-publication history for this paper can be accessed here:


The Spanish National Health Service is a universal and free health care system. Non-specific low back pain (LBP) is a prevalent disorder, generating large health and social costs. The objectives of this study were to describe its management in primary care, to assess patient characteristics that influence physicians' decisions, and to describe clinical outcome at 2 months.A cross-sectional sample of 648 patients with non-specific low back pain was recruited by 75 physicians (out of 361 – 20.8%) working in 40 primary care centers in 10 of the 17 administrative regions in Spain, covering 693,026 out of the 40,499,792 inhabitants. Patients were assessed on the day they were recruited, and prospectively followed-up 14 and 60 days later. The principal patient characteristics that were analyzed were: sex, duration of the episode, history of LBP, working status, severity of LBP, leg pain and disability, and results of straight leg raising test. Descriptors of management were: performance of the straight leg raising test, ordering of diagnostic procedures, prescription of drug treatment, referral to physical therapy, rehabilitation or surgery, and granting of sick leave. Regression analysis was used to analyze the relationship between patients' baseline characteristics and physicians' management decisions. Only workers were included in the models on sick leave.Mean age (SD) of included patients was 46.5 (15.5) years, 367 (56.6%) were workers, and 338 (52.5%) were females. Median (25th–75th interquartile range) duration of pain when entering the study was 4 (2–10) days and only 28 patients (4.3%) had chronic low back pain. Diagnostic studies included plain radiographs in 43.1% of patients and CT or MRI scans in 18.8%. Drug medication was prescribed to 91.7% of patients, 19.1% were sent to physical therapy or rehabilitation, and 9.6% were referred to surgery. The main determinants of the clinical management were duration of the episode and, to a lesser extent, the intensity of the pain , a positive straight leg raising test, and degree of disability. The main determinant of sick leave was the degree of disability, followed by the characteristics of the labor contract and the intensity of leg pain (but not low back pain). After at least 2 months of treatment, 37% of patients were still in pain and approximately 10% of patients had not improved or had worsened.Although the use of X-Rays is high, determinants of physicians' management of LBP in primary care made clinical sense and were consistent with patterns suggested by evidence-based recommendations. However, after 2 months of treatment more than one third of patients continued to have back pain and about 10% had worsened. Non-specific or common low back pain is defined as pain between the costal margins and the inferior gluteal folds, usually accompanied by painful limitation of movement, often influenced by physical activities and posture, and which may be associated with referred pain in the leg. Diagnosing common low back pain implies that the pain is not related to conditions such as fractures, spondylitis, direct trauma, or neoplastic, infectious, vascular, metabolic, or endocrine-related processes ,2. Low bA considerable number of clinical guidelines have been developed for the management of acute and subacute patients ,10. The There is considerable variation in LBP related clinical practice -17. MostThe Spanish National Health Service is a public organization in which all health care services are provided free to every citizen. Physicians are free to prescribe, apply or refer their patients to any diagnostic procedure or treatment that they consider appropriate. That treatment will be provided to the patient for free as long as it is within the list of National Health Service accepted procedures. That is the case for virtually all commercially available drugs, diagnostic procedures, and non-pharmacological treatment, except for cosmetic surgery and some dental procedures. Primary care physicians receive no incentive to prescribe any diagnostic test or treatment, or to refer patients to any specialist. Actually, the primary care physician acts as a "gatekeeper" of access to specialized medical care and is responsible for deciding whether or not sick leave is granted. However, the patient may challenge the physician's decision, so that the decision is usually taken by consensus between the patient and the physician.Identifying the clinical variables on which physicians base their decisions is as important as describing usual clinical practice and its variability. Additionally, the clinical course of subjects with low back pain treated in the Spanish National Health Service is actually unknown. Therefore, the objectives of this study were to describe the management of LBP in primary care in the Spanish National Health Service, to assess those patient characteristics that influence physicians' decisions, and to describe clinical outcome at 2 months.The directors of 40 Primary Care Centers of the Spanish National Health Service were sent a letter inviting them to join the study. Those Centers were those in which there was at least one physician having expressed or stated an interest at any time on any kind of research on back pain. The Centers were located in 10 of the 17 Spanish administrative regions and they covered a total population of 693,206 subjects, out of a total Spanish population of 40,499, 792 inhabitants . The DirPrimary care physicians were asked to recruit all subjects who visited them because of low back pain, with or without leg pain, 18 years of age or older. Exclusion criteria were functional illiteracy , illnesses affecting the central nervous system, and "red flags" for surgical referral , or for possible specific spinal pathology . The stuThis being an observational study, there was no intervention per se. Physicians were given no instructions, but encouraged to treat their patients as they usually do, and no attempt was made to homogenize their practice. They were told that the objective of the study was to contribute to the knowledge of low back pain. Management of non-specific low back pain in the primary care setting of the Spanish National Health Service is based on clinical history, physical examination, recommendation of diagnostic tests, medical counseling, drug treatment, physical therapy, rehabilitation, or referral to specialists. All visits of patients and all the diagnostic procedures, treatments, and referrals that were prescribed by the primary care physicians were registered in structured questionnaires.The clinical condition of each patient was assessed at the primary care center by his/her general practitioner on the day of inclusion in the study  and 15 and 60 days later. Besides these three obligatory follow-up assessments, all visits requested by the patient during the study period because of low back pain were considered additional voluntary visits and data on patients' clinical evolution and on physicians' management of the patients were recorded.At baseline, the following variables were recorded: age (date of birth); sex; educational level ; duration of pain , chronicity of pain when entering the study  ,24; prevAt each assessment, including the first one, the following variables were recorded: current pregnancy (yes/no); work status , sick leave , reason for sick leave , severity of low back and leg pain   in which"Key descriptors" of the essential aspects of clinical practice in low back pain were defined, and this information was collected in each of the assessments. Performing the SLR test at any moment between the first and third assessments  was conThe prescription of medication in the first visit  or referral  at any moment during follow-up were considered descriptive of treatment. Physician's counsel was not included as descriptive of treatment because it was understood to be inherent to all medical practice, and because no validated system to classify its content was found .The granting of sick leave by the general practitioner at any moment between the first and third assessments was considered descriptive of sick leave.Data recording and transference to the database were as follows: questionnaires on pain, disability and quality of life were self-administered and completed by the patient on his/her own in the absence of the treating physician, other health care staff, family members, or accompanying persons. Completed self-reported instruments were then given to the auxiliary staff of the primary care center who stapled scales and questionnaires to the patient's data collection form. At the end of the working day, ratings of the scales were transcribed to the data collection form by the treating physician. At each Primary Care Center, concordance of scores in the data collection form and ratings of self-administered instruments were verified by the study coordinator in the Center. Structured data collection forms with information on patients' clinical management were then sent along with patients' self-reported instruments to the central coordination office, where data were entered in a database by two administrative assistants who double-checked data entry. They also double checked that scores on pain, disability and quality of life scales coincided with actual patients' ratings of the VAS, Roland-Morris and EuroQol questionnaires. All throughout the process, patients' answers on the self-administered questionnaires were considered the gold standard, but no inconsistencies were actually found.p < 0.05 to eliminate variables from the model.The analysis was done by a team of biostatisticians who had no connection with the primary care physicians involved in this study. Frequencies were calculated for categorical variables. For continuous ones, means and standard deviations were calculated for those with a normal distribution, and median and interquartile ranges for the rest. Logistic regression models were developed to explore the influence of different factors on the key descriptors of clinical management of non-specific low back pain. In each model the descriptor was used as a dependent variable. Colinearity of the maximal models was evaluated with the criteria proposed by Belsley . A backwThe following variables were introduced in all maximal models: sex, previous number of episodes of low back pain when entering the study (recoded as "less than three" and "three or more"), intensity of lumbar and leg pain at the first assessment, degree of disability at the first control, and chronicity of pain when entering the study  ,25. The During an 18-month period, 653 patients were recruited, of which 5 were excluded at the first assessment . At the second assessment two patients were excluded (one because of a systemic disease and the other due to a house move), and at the third assessment another two . Thus, a total of 648 patients fulfilled the inclusion criteria at the first assessment and were included in the study, and 374 (57.7%) completed all assessments.The mean  number of patients recruited by each physician was 8.65 (8.5). Table A total of 495 patients came for the second visit and 374 came for the third, and there were no differences in baseline data between patients who attended and those who did not attend those assessments (data not shown). Table In comparison with baseline data, Roland Morris disability scores improved by 5.0 points at 14 days and by 6.6 points at 60 days. However, they remained the same in 8,7% of patients at 14 days, and in 4.3% at 60 days, and worsened in 10.5% of patients at 14 days and in 7.3% at 60.Throughout the study, physicians performed the SLR on 439 patients (67.7%), requested imaging tests for 279 43.1%) and neurophysiologic tests for 21 (3.2%), prescribed medication at the first visit for 594 (91.7%) -mostly non-steroidal anti-inflammatory drugs, analgesics and muscle relaxants-, referred 124 (19.1%) to physical therapy or rehabilitation, and 62 (9.6%) to orthopedic surgery or neurosurgery  patients in a potentially active work situation went on sick leave Table .In addition to the planned visits, 22.8% of patients requested medical attention in primary care during the first two weeks, 8.7% visited other health services, and 3.2% went to the emergency room. Between 2 weeks and 2 months, 21.7% of the patients requested additional health care in primary care, 13.4% visited other specialists, and 2.4% went to the emergency room. Between 2 and 6 months, only 23 (6.1%) patients requested health care in primary care, and 8 of them visited a specialist (orthopedic surgeon or neurosurgeon).vs. females). The prescription of medication was associated with greater limitation in the SLR and shorter duration of pain. The referral to rehabilitation or physical therapy was associated with longer duration of pain, greater intensity of low back pain, more than 2 previous episodes of low back pain, and greater limitation in the SLR. Referral to a surgeon (orthopedic or neurosurgeon) was associated with a greater intensity of leg pain, greater level of disability, longer duration of pain, and being male rather than female (OR = 1.9). Sick leave was associated with greater severity of leg pain, being employed by another (as opposed to self-employed) and especially with the level of functional disability , and limitation in the SLR are greater. The same variables influence the prescription of MRI studies, except that this is not influenced by the number of previous episodes and that the probability of prescription is also greater for men than for women. This is in accordance with what has been described in other settings,  and mighThe probability of prescribing medication increases with a positive (<60°) SLR test and with having acute (vs. chronic) pain Table . This laIn addition to a longer duration of the episode, the probability of referral to physical therapy or rehabilitation is also greater when low back pain is more intense, when there is greater limitation in the SLR, and when the patient has had previous episodes of low back pain. Factors associated with a greater probability of referral to surgery are being male, having a greater severity of leg pain, having a greater level of disability and, especially, that the episode is chronic Table .The apparent relationship between the granting of sick leave and being employed by another (vs. self-employed) is not surprising since in the Spanish Social Security System only self-employed workers have an economic incentive to continue working. However, it is important to point out that the level of disability and the intensity of leg pain (but not low back pain) are more closely related to the granting of a sick leave, which suggests that physicians do not consider sick leave a treatment for low back pain, and only grant it when the level of disability requires it.The main common recommendations from the different currently available evidence based practice guidelines for acute non-specific low back pain are: avoiding bed rest and trying to stay active , prescribing drug treatment  only for limited periods when the pain exacerbates, and restricting imaging procedures and referral to surgery to a subset of patients -13. In tHowever, although factors associated with X-ray prescription make clinical sense, the rate of prescription was 43.1%, which is higher than recommended -13. MostAlthough the design and objective of the study were not to compare clinical practice in different regions, and the study population was too small for that purpose, in general the criteria for management by family physicians were consistent throughout the different Spanish regions (data not shown). The main difference between regions was in the use of muscle relaxants, a subject on which scientific evidence is partial . In factThe mean evolution of pain and disability was favorable, as was to be expected in acute patients due to regression toward the mean, to the natural course of the condition or to the effect of treatment. However, 64.4% of patients assessed at two months continued to have pain or disability, and in approximately 10% of them those variables had not improved at all, or had even worsened. Even if all the patients who did not comply with the follow-up assessments had been totally asymptomatic, patients with pain or disability at two months represent 37% of those seen initially. This is consistent with the results of other studies -43, and The degree of disability and the intensity and duration of low back pain have proved to be the main determinants of quality of life in Spanish patients with non-specific low back pain ,25,45. TThere are other limitations to this study. Fear-avoidance beliefs (FAB) on low back pain were not recorded, since there were no validated instruments in Spanish for that purpose when it was performed. However, contrary to what has been shown in Northern Europe and Anglo-Saxon countries, the influence of FAB on disability and quality of life is virtually irrelevant in Spanish patients . TherefoOnly 20.8% of the primary care physicians invited to participate in the study did so. It is possible that they were the physicians most interested in low back pain and possibly the most up-to-date on the management of this condition. If that were so, the overall management of low back pain in the Spanish National Health Service could be more inconsistent with evidence-based recommendations. However, physicians working in the Spanish National Health Service do not have any incentive to participate in studies during their work time, including this one, and only do so because of their own scientific interest. Their rate of participation in this study is similar to that found in other reports. AdditioBecause the recruitment for this study was cross-sectional, patients with acute, subacute, and chronic low back pain could have been included. However, only 28 patients had chronic low back pain (4.3% of the sample). Since it was anticipated that the duration of pain may influence clinical management, patients' chronicity when entering the study was included in all the regression models. In fact, the results of this study show that the ordering of X-ray, CT scans or MRI studies, the prescription of medication, and the referral to rehabilitation, physical therapy, and surgery, are different for acute, subacute and chronic patients.Only 374 patients (57.7% of those included) were seen at all assessments. The Spanish National Health Service is universal and free, and patients with non-specific low back pain tend to visit their physician when they feel pain. However, once they are asymptomatic they stop their visits, as has been shown in previous studies on low back pain performed in Spain, in which recall mechanisms were used . This maThis study shows that the main variables affecting physicians' management of non-specific low back pain in the primary care setting of the Spanish National Health Service were duration of the episode and, to a lesser extent, intensity of low back pain, especially of leg pain, limitation in the SLR, and degree of disability. Although the rate of use of X-ray examinations was high, the criteria for management of non-specific low back pain were consistent with evidence-based recommendations. However, 2 months after treatment, more than one third of patients continued to have pain and in about 10%, the outcome was poor.CI: confidence intervalCT: computed tomographyMRI: magnetic resonance imagingOR: odds ratioSLR: straight leg raising testVAS: visual analogue scaleThis study was funded by the Kovacs Foundation and Fondo de Investigación Sanitaria (grant number 98/1264), Madrid, Spain.The author(s) declare that they have no competing interests.Francisco M. Kovacs is the principal investigator, participated in the conception, design and development of the study, writing of the article, and editorial decisions.Carmen Fernández participated in the development of the study and in data collection.Alfonso Muriel participated in data analysis and in the writing of the article.Luis González-Luján participated in the development of the study and in data collection.María Teresa Gil del Real participated in the design, development of the study and writing of the article.Other members of the Spanish Back Pain Research Network participated in the development of the study, data collection, data analysis, and the writing of the article.a Luz Besteiro, Centro de Salud de Guayaba, Madrid; C. Tourné and L. V. Marín, Centro de Salud de Abanilla, Murcia; E. Thomás, M. J. Nadal, and A. Sánchez and G. Rodríguez, Centro de Salud de Jazmín; J.C. Vergara, F. Gordillo, and L. C. Morales, Centro de Salud de Pintores, Madrid; E. Arranz and A. B. Bellón, Centro de Salud de Isabel II, Madrid; A. Martín, D. Giménez, and N. Herranz, Centro de Salud de Eras del Bosque, Palencia; C. Rubio, Centro de Salud de Plaza Argel, Cáceres; R. Elena Duro, S. Ribot, J. Coll, V. Reyes, and M. Arrate Olivera, Centro de Salud de de Coll d'en Rebassa, Palma de Mallorca; R.A. Escribá, H. Moreno, and J. Rubio, Centro de Salud de Palomares, Madrid; J. Gili, Centro de Salud de Santa Catalina, Palma de Mallorca; J. Martín, M. J. Santero, and L. Cossio, Centro de Salud de Aranjuez II, Madrid; A. de Torres, Centro de Salud de Pinto, Madrid; J. C. García and D. Jiménez, Centro de Salud de Alcolea del Pinar, Guadalajara; R. Martín, Centro de Salud de los Cármenes, Madrid; V. Portuguéz, Centro de Salud de UB de Jesús, Ibiza; E. Fernández, I. Gil, J. Moreno, A. Aura, R. Vercher, G. Albert, and G. Díaz, Centro de Salud de Salvador Allende, Valencia; P. Pascual, M. Llinás, and J. Ripoll, Centro de Salud de Valldargent, Palma de Mallorca; E. Rodríguez, J. González, and C. Nicolau, Centro de S'Escorxador, Palma de Mallorca; M. A. Castillo, Centro de Salud de Puerta Bonita, Madrid; R. Llidó, Centro de Salud Santa Eulalia, Ibiza; S. Luna, B. Leal, and J. Nieto, Centro de Salud de Alburquerque, Badajoz; C. Santos, Centro de Salud de C'n Misses, Ibiza; L. M. Rubiera, I. Aguilar, M. D. San Román, C. Sánchez, and U. López, Centro de Salud de Guzmán el Bueno, Madrid; and J. Llobera, Unidad de Investigación, Gerencia de Atención Primaria, Ib-Salut, Palma de Mallorca, Spain.Other members of the Spanish Back Pain Research Network who participated in the study are: V. Abraira and J. Zamora, Hospital Ramón y Cajal, Madrid; M. Gestoso, N. Mufraggi, M. Martín, and S, Santos, Fundación Kovacs, Palma de Mallorca; V. González, L. Palacios, J. Mardones, J. A. Estévez, and E. Marzo, Centro de Salud de Albia, Bilbao; A. Fajardo and I. Barrio, Centro de Salud de Cadalso, Madrid; P. González and B. Navalón, Centro de Salud de Los Castillos, Madrid; M.A. Usero, M. Arnalte, and M. Rojo, Centro de Salud de Perales del Río, Madrid; C. Isanta and N. Giménez, Centro de Salud de Perpetuo Socorro, Huesca; P. Puente, Centro de Salud de San Agustín, Burgos; A. Careaga, B. Amutxategui, M. Fernández, and J. M. Gendive, Centro de Salud de Casco Viejo, Bilbao; R. Ruiz and M. Chaparro, Centro de Salud de Barconcillo, Guadalajara; S. Borregón, J.E. Villares, and A. Ruiz, Centro de Salud de las Ciudades, Madrid; M. Gómez, L. Perelló, J. Ramón, J. Ripoll, and C. Mateu, Centro de Salud de Son Serra/La Vileta, Palma de Mallorca; P. Ibáñez and A. Jover, Centro de Salud de Arquitecto Bennassar, Palma de Mallorca; S. Segura, E. Viñuelas, I. Sanz, and M. Delgado, Centro de Salud de Carrascosa del Campo, Cuenca; M. C. Vargas and MThe pre-publication history for this paper can be accessed here:


Inadequate management of postoperative pain is common, and postoperative pain is a risk factor for prolonged pain. In addition to medical and technical factors, psychological factors may also influence the experience of postoperative pain.Pain was measured postoperatively at 24, 48, and 72 hr in hospital and after 3 months at home in 140 patients undergoing radical prostatectomy (RP). Patients answered questionnaires about anxiety and depression  and health-related quality of life (SF-36) at baseline and 3 months after surgery.In the first 3 postoperative days, mild pain was reported by 45 patients (32%), moderate pain by 64 (45%), and severe pain by 31 (22%) on one or more days. High postoperative pain scores were correlated with length of hospital stay and with high pain scores at home. Forty patients (29%) reported moderate (n = 35) or severe (n = 5) pain after discharge from hospital. Patients who experienced anxiety and depression preoperatively had higher postoperative pain scores and remained anxious and depressed 3 months after surgery. The scores for the physical domains in the SF-36 were decreased, while the mental health scores were increased at 3 months. Anxiety and depression were negatively correlated with all domains of the SF-36.There is a need for nurses to be aware of the psychological status of RP patients and its impact upon patients' experience of postoperative pain and recovery. The ability to identify patients with psychological distress and to target interventions is an important goal for future research. Radical prostatectomy (RP) is a procedure that has been performed with increasing frequency in patients with localized prostate cancer. Although the morbidity associated with this procedure is quite low , inadequSeveral techniques for postoperative pain management are available for patients undergoing RP: Continuous epidural analgesia (EDA) is a safe and effective method that is frequently used ,12, althIn addition to medical and technical factors, psychological factors may also influence the experience of postoperative pain. Studies exploring the relationship between emotional variables and postoperative pain have highlighted the influence of anxiety and depression . AccordiOne way to improve our understanding of the consequences of postoperative pain and functioning after hospital discharge is to measure health-related quality of life (HRQOL) . There aThe study was a prospective, longitudinal descriptive study conducted from December 2002 to June 2004. After approval was obtained from the Ethical Committee of Sahlgrenska University Hospital, Sweden, patients undergoing RP were recruited from two hospitals: a University hospital with two surgical units and a community hospital. Three weeks before surgery, patients on the waiting-list for RP, received a letter with written information about the study. Patients willing to participate signed and returned a consent form. The patients answered baseline questionnaires preoperatively and reported their postoperative pain experience. At 3 months after the operation, patients were given a second questionnaire to answer.The demographic form contained questions about age, marital stage, education, employment, and time on the waiting list. Data related to physical status classification according to the American Society of Anaesthesiologists (ASA score), pain treatment, and length of hospital stay (LoS) were collected from the patients' records. Three months after surgery, the patients answered a questionnaire about their worst and mean pain experience, the anatomical location of the pain, and their pain medication  at home.Pain was measured with a visual analogue scale , on which the patients' pain intensity was represented by a point between the extremes of "no pain at all" and "worst pain imaginable." The simplicity, reliability, and validity of this instrument have made the VAS a good tool for describing pain severity or intensity .Pain scores were divided into three broad categories based on pain intensity, as suggested by Bodian et al. . Pain grThe HAD scale  has beenThe SF-36 measures perceived health status by assessing eight health components:physical functioning – limitations in physical activity, including self-care activities; 2) role-physical – work and activity limitations due to physical problems; 3) bodily pain – limitations due to pain; 4) general health – overall self-rated health; 5) vitality – energy versus fatigue; 6) social functioning – limitations in social activities due to emotional problems; 7) role emotional – work and activity limitations due to emotional problems; and 8) mental health – emotional symptoms . Standardized scores range from 0 (poor functioning) to 100 (good functioning). In addition, a single item addresses the health transition over the past year. The reliability for the Swedish version of the SF-36 is > 0.70 [1) s > 0.70 .Three weeks before surgery, consecutive patients on the waiting list for RP received a letter with written information about the study. Patients willing to participate signed and returned a consent form. At the same time the patients answered the form about demographics and the SF-36 questionnaire. The HAD scale was answered the day before surgery. The patients' postoperative pain experience was determined at 24, 48, and 72 hr by asking about "worst pain" during the last 24 hr at rest or when moving. Three months after the operation the patients were mailed the SF-36 and the HAD questionnaires and a form asking about pain at home, together with a stamped return envelope.Initially, EDA was the routine treatment for postoperative pain in these RP patients; about a year after the beginning of the study, the method for postoperative analgesia was shifted to ITA. Study patients who were deemed unsuitable for either EDA or ITA received systemic opioids for pain relief.SPSS (version 12.0) for data analysis was used to analyze the data. Continuous variables are presented as means and standard deviation, and categorical data are presented as number and percent. To measure the differences before and after surgery, the paired sample t-test was used. For correlations between variables, we used Pearson's product moment correlation and Spearman's rank order correlation . All tesOf the 183 consecutive patients who were invited to participate, 155 patients (85%) gave informed consent to participate. At 3 months after the operation, the patients were mailed the follow-up questionnaires, which were answered and returned by 140 patients (90%) . Most of the subjects (91%) were married, and about a third had an elementary education. Half of the patients were retired. After being diagnosed with prostate cancer, 41% of the patients had to wait >3 months for their operation  patients had received EDA, 48 (34%) ITA, and 14 (10%) systemic opioids for their postoperative pain relief. There were more patients in the EDA group than in the other two groups who experienced severe pain, both in hospital and at home  reported mild, 64 (45%) moderate and 31 (22%) severe pain for one or more days (Table % reporteForty patients 29%) reported moderate (n = 35) or severe (n = 5) pain during the 3 months at home (Table 9% reportThe HAD questionnaire was answered before and at 3 months after surgery by 123 patients (88%). Prior to surgery, 28 men (23%) suffered from possible or probable anxiety (Table The number of patients reporting depression decreased from 13 (11%) preoperatively to 11 (9%) at 3 months. Preoperative depression was correlated with "worst pain" in the hospital  and "worst pain" at home . Patients with the highest pain scores after discharge from the hospital were also the most depressed at 3 months , and patients with preoperative depression were the most depressed at 3 months .At 3 months after surgery, 84 patients (60%) had reached baseline in all HRQOL components except vitality. The physical functioning and role-physical components had significantly decreased (p < 0.001) when compared to baseline, while mental health had increased (p < 0.001)  reporting moderate pain. This finding is consistent with previous reports concerning RP patients . The devper se, since the patients remained anxious and depressed beyond the surgery.Psychological well-being is of great significance with regard to the experience of pain after surgery, and psychological preparation of patients undergoing surgery has been shown to shorten hospital stays and reduce the need for postoperative analgesics ,15. In tA good nurse-patient relationship allows patients to discuss their anxiety and depression. Preoperative nursing interventions have been found to have a positive effect on preoperative anxiety, postoperative pain, and start-out-of-bed activities ,28. As aBecause this study was not designed to evaluate urological problems after RP, the prostate-specific SF-36 was not employed. As compared to baseline, the results for the physical dimensions of the SF-36 had significantly decreased by 3 months after RP in our study. However, the mental health scores were significantly higher postoperatively, in agreement with previous results . DemograThe patients in our study population were treated with one of three different pain management techniques. After we determined  that EDAIn the present study, we found that men with the highest pain scores in the hospital after RP also experienced the most pain during the 3 months immediately after discharge. Patients who experience anxiety and depression preoperatively seemed to have higher postoperative pain scores and remained anxious and depressed 3 months after surgery. Physical functioning had decreased, and mental health had increased at 3 months when compared to baseline. Anxiety and depression at 3 months correlated negatively with all components of HRQOL.The results of this study indicate that there is a need for further education about the psychological consequences of RP and its impact upon patients' experiences of postoperative pain and recovery. Thus, the ability of health professionals to identify patients with psychological distress and to target interventions are highly desirable goals. There is also a need for interventions to be developed to prepare this group of patients for the physical and mental complications most likely to be experienced after surgery.The author(s) declare that they have no competing interests.KWE and FGJ were responsible for the study design. KWE performed the data collection. All authors contributed to data interpretation, helped revise the manuscript, and approved the final version.The pre-publication history for this paper can be accessed here:


To evaluate the short-term symptomatic efficacy of rofecoxib and diclofenac versus placebo in acute episodes of shoulder pain.Randomized controlled trial of 7 days.Rheumatologists and/or general practitioners totaling 47.Acute shoulder pain.Rofecoxib 50 mg once daily, diclofenac 50 mg three times daily, and placebo.Pain, functional impairment, patient's global assessment of his/her disease activity, and local steroid injection requirement for persistent pain. The primary variable was the Kaplan-Meier estimates of the percentage of patients at day 7 fulfilling the definition of success .n = 88, placebo n = 94, and diclofenac n = 89). At day 7, the Kaplan-Meier estimates of successful patients was higher in the treatment groups than in the placebo . During the 7 days of the study, there was a statistically significant difference between placebo and both active arms (rofecoxib and diclofenac) in all the evaluated outcome measures A local steroid injection had to be performed in 33 (35%) and 19 (22%) patients in the placebo and rofecoxib group respectively. Number needed to treat to avoid such rescue therapy was 7 patients .There was no difference in the baseline characteristics between the three groups , supplemented with steroid injections (which are often reserved for the treatment of severe or persistent pain). One NSAID, diclofenac, is used frequently for this condition, but other NSAIDs might also be effective. A subgroup of NSAIDs called the Cox-2 selective inhibitors specifically inhibit one particular enzyme  which is involved in inflammation and pain. These drugs are thought to be less likely to cause stomach irritation than other NSAIDs. Therefore the researchers in this study carried out a short-term, three-way clinical trial comparing diclofenac with one particular Cox-2 inhibitor, rofecoxib, and placebo in patients with acute shoulder pain. However, rofecoxib was withdrawn from the market in September 2004 because of evidence that use of the drug was associated with an increased risk of heart attacks and strokes, and controversy remains regarding the risk of such events among users of other Cox-2 inhibitors.What this trial shows: The main aim of this trial was to compare the level of pain relief over seven days of treatment with either diclofenac or rofecoxib, as compared to placebo. The primary outcome measure used in the trial was the proportion of patients achieving a 50% or greater decrease in pain levels over the course of the study, measured using a numerical rating scale. A total of 273 participants were recruited into the trial and at day 7 the proportion achieving a 30% decrease in pain was 38% in the placebo arm, 54% in the diclofenac arm, and 56% in the rofecoxib arm. The differences in this outcome measure between diclofenac and placebo and between rofecoxib and placebo were statistically significant; however, the researchers did not carry out a direct comparison between diclofenac and rofecoxib. The rates of adverse events were roughly comparable between all three arms of the trial, although the study was not originally planned to be large enough to detect differences in the rates of such events, so it is not possible to conclude whether there was any true difference.Strengths and limitations: The randomization procedures used in the study minimize the possibility of bias in assigning patients to treatment arms. Bias in assessment of outcomes was also minimized by ensuring that steps were taken to prevent investigators and patients from knowing which drugs a particular patient received until the end of the trial. A key limitation of the study is the short follow-up, only seven days, and it is therefore unclear whether efficacy and safety of these drugs would continue for the much longer periods of time (weeks or even months) for which these patients might need pain relief. Finally, patients randomized to the placebo arm received no treatment for the seven days of the study other than acetaminophen or steroid injections . This design does not limit interpretation of the data but could be criticized because of concern over whether the patients receiving placebo received adequate pain relief.Contribution to the evidence: This study provides some data on the efficacy of diclofenac and rofecoxib, as compared to placebo in treatment of this condition. Given that rofecoxib is now withdrawn, the efficacy of this drug is no longer relevant. However, the information from this trial should help in designing future studies of NSAIDs in shoulder pain, for example to define appropriate trial outcomes, sample size, and other aspects of study design. Shoulder pain is the third most common musculoskeletal symptom encountered in medical practice after back and neck pain ,2. A widGiven the invasiveness of injections, many practitioners prefer an initial trial of oral NSAIDs with injections reserved for patients with persistent pain or severe pain at the time of initial presentation . DespiteThese findings prompted us to conduct a seven-day clinical trial evaluating the short-term symptomatic efficacy of rofecoxib in acute, painful episodes of rotator-cuff syndrome using both potentially negative (placebo) and active (diclofenac) control groups. A secondary but clinically relevant end point was the requirement for local steroid injections. Although one of the study drugs (rofecoxib) was withdrawn from the market in October 2004, the data are being reported now for the sake of completeness and transparency.The inclusion criteria were selected to optimize the probability of recruiting patients suffering from an acute painful episode of tendonitis of the rotator cuff. For this purpose, the following criteria were chosen: patients less than 60 years of age, suffering from an acute (less than 7 d), painful , episode occurring in the shoulder area with the following findings at physical examination: no limitation of the glenohumeral external rotation and a painful Job test ,20. A scAny NSAID intake other than the study drug was prohibited during the study. In case of previous intake, the NSAIDs had to be discontinued at least 3 d before enrollment. During the baseline visit, the following information was also collected: lateralization (right- or left-handedness) and history of progression of the symptoms with the a priori defined following four categories: (i) no history of chronic pain before this episode; (ii) history of chronic pain before this first acute episode; (iii) history of similar acute episodes without any history of chronic pain between episodes; and (iv) history of similar acute episodes with history of chronic pain between episodes. Therefore, the date of onset of shoulder disease was not always that of the current episode.The study was a double-blind, 7-d randomized controlled trial comparing placebo, rofecoxib 50 mg, and diclofenac 150 mg using a double-dummy technique. The design of the study was approved by the ethics committee of Cochin Hospital . All patients gave their written informed consent before entering the trial. The study was conducted in 47 centers from 15 April 2003 to 16 March 16 2004.After confirmation of patient eligibility and after written informed consent was obtained, patients were randomly assigned to receive placebo, diclofenac 50 mg three times daily, or rofecoxib 50 mg once daily. All the patients took four capsules per day  during the seven days of the trial, regardless of the level of symptoms and the randomization group. Capsules and packages were identical in appearance.Compliance was evaluated by pill count at the final visit.Acetaminophen  was used as analgesic treatment during the study when needed. Since acetaminophen was supplied as part of the study, a pill count of acetaminophen was performed at final visit.In cases of persistent intolerable pain, a local injection of steroids was performed. This injection was defined as treatment failure, resulting in the withdrawal of the patient from the trial.The objective of this trial was to demonstrate the superiority of NSAIDs over placebo in acute shoulder pain over a 7-d treatment period.Changes in pain were considered as the primary outcome measure. The original trial protocol was referring to a “clinically relevant” definition of the primary outcome . While the recruitment of patients was still ongoing and based on discussion concerning the potential loss of statistical power by using a dichotomous variable instead of a continuous variable, an amendment was proposed and accepted by the ethical committee to redefine the primary variable as the mean changes in pain during the study. Since both techniques resulted in similar findings, we are presenting here the results according to the original trial protocol. For this purpose, a diary was provided to the patient in order to collect twice a day (in the morning and in the evening) his/her pain intensity over the 12 previous hours  using a 0–10 NRS.Functional impairment and patient's global assessment were considered as secondary symptomatic outcome measures. Clinical assessment was performed at baseline and after 7 d by the same investigator, and functional impairment and patient's global assessment were collected. Functional impairment was evaluated using the function subscale of Neer's index . This scPatients' global assessments were evaluated using three different techniques. In one, at the baseline and the final visits, patient's global assessment of disease activity was collected by the following question “considering all the ways your shoulder disease affects you, mark an (X) in the appropriate box for how well you are doing” and the following potential answers 0, very well; 1, well; 2, fair; 3, poor; and 4, very poor. For the analysis, this variable was considered as a continuous one and normalized from 0 = best condition to 100 = worst condition.In a second technique, at the final visit, patient's global assessment on her/his relative condition was collected by the following question: “compared to when you started the study, how have you been during the last 48 hours?” and the following potential 15 answers from −7, very great deal worse to +7, very great deal better. For the analysis, we considered this variable as a dichotomous one .In a third technique, at the final visit, acceptable symptom state was assessed by the following question: “considering your current level of pain and functional impairment, if you were to remain for the next following months as you were during the last 48 hours would this be acceptable or unacceptable to you?” and the potential following answers 0, acceptable; 1, not acceptable.Moreover, the requirement for rescue therapies  was also considered as a secondary outcome measure of efficacy.At baseline and final visit, blood pressure and body weight were systematically collected and at final visit, the investigators checked for tolerability.The sample size needed in order to demonstrate a statistically significant difference between NSAID and placebo using the pain intensity  was calculated. A success was a priori defined by a sustained improvement of at least 50% and an absolute level of pain 30 or less . The analysis was conducted using the Kaplan-Meier technique in which the event was defined by the time the patient fulfilled the above definition of improvement in pain with such an improvement sustained until the end of the study. Based on information on changes in pain in previously reported trials , the KapA computer-generated randomization sequence assigned participants in a 1:1:1 ratio to receive rofecoxib, diclofenac, or placebo using a block size of six. For each individual patient recruited in the trial, a coded package for the drugs was used.The randomization code was available only to the statistician who did not participate in any way for patient recruitment. The code was revealed to the researchers once recruitment, data collection, and statistical analysis were complete. Because of the double-dummy technique used with matching placebo, allocation was concealed from both investigators and patients.After checking that screened patients fulfilled the inclusion/exclusion criteria of the study and after written informed consent was obtained, the investigator assigned the patient on an individual basis to an allocated number. The patient remained on the same allocation throughout the study. The investigators responsible for seeing the patients allocated them to the next available number into the trial , and provided the treatment corresponding to the allocated number of the patients.This was a double-blind trial. Both the patients and the physicians providing care were blinded of the study drug allocation. For this purpose, a coded package for the drugs was used. The active drugs and their corresponding placebos were identical in appearance, color, and taste. The blinding process remained complete until the database  was completed and was locked.The efficacy analysis was conducted on the modified intention to treat population, defined as all patients randomized in the study and receiving at least one dose of study drug with the last observation carried forward technique. For patients who withdrew without assessment, the baseline value was reported as the final value. All patients were analyzed in the group to which they were randomized.The primary efficacy variable (success of treatment was defined by a decrease in pain of at least 50% and an absolute level ≤30) was evaluated using life table analysis (Kaplan-Meier technique) in which the event was defined by the time to reach a sustained definition of success until the end of the study. The results are expressed as Kaplan-Meier estimates of the percentage of success per treatment group at day 7. The primary analysis consisted in the comparison between rofecoxib and placebo groups using the log-rank test. As a secondary analysis, diclofenac was also compared to placebo according to the same definition of success.Exploratory analyses were also performed using the same approach  but with different definitions of event (success): time to reach an improvement of 50%; time to reach an improvement of 50% and such an improvement is maintained during the remaining days of the study; time to reach an absolute level of pain ≤ 30; and time to reach an absolute level of pain ≤ 30 and such a good condition is maintained during the remaining days of the study.The continuous secondary variables are also expressed in normalized units using a 0–100 scale in which 0 = best condition and 100 = worst condition. Absolute changes between day 0 and day 7 of “nocturnal pain,” diurnal pain,” “number of pills of acetaminophen,” “functional impairment,” and “patient's global assessment” were compared with a nonparametric Mann-Whitney test. The dichotomous secondary variables  were compared using the Chi-square test.In order to estimate the clinical relevance of the observed treatment effect on the requirement for local steroid injection, the number needed to treat and its 95% confidence interval were calculated.http://www.sas.com).Statistical analysis was performed using SAS version 8.2 p = 0.025). The percentage of patients achieving the definition of success over time during the trial by treatment group is summarized in The mean changes in the different continuous variables by treatment groups are summarized in At the end of the trial, the percentage of patients considering their condition as substantially improved or as acceptable was more important in the two active groups than in the placebo group see . MoreoveThirty-nine patients (13 patients in each group) experienced at least one adverse event  during the study. Gastrointestinal disorders  occurred in 12 (12.8%), 11 (12.4%), and 9 (10.2%) in the placebo, diclofenac, and rofecoxib groups, respectively.In the rofecoxib group, one patient had to be hospitalized 2 d after the end of the study because of an ulcer perforation; outcome was favorable after surgery. There was no death and no cardiovascular event. During the study, eight patients had to discontinue the study drug mainly because of gastro-intestinal discomforts. The most frequent adverse events observed during the trial are summarized in This study confirms the short term symptomatic efficacy of NSAIDs  in acute shoulder pain. The observed treatment effect in the a priori selected outcome variable  reached statistical significance and was also close to the a priori expected treatment effect . The interpretation of results is made difficult by the fact that there is no clear consensus on the primary outcome variable which should be chosen in this type of study. However, the positive and statistically significant results in favor of NSAIDs in the secondary outcome variables, especially the requirement for steroid injections, support the primary analysis. Finally, the interpretation of the results should also take into account issues related to both the eligibility criteria, the outcome measures, and the choice of the study drugs (in particular the placebo).There is no current, formal recommendation for conducting clinical trials in shoulder pain syndrome, at least to our knowledge. The design of the currently reported trial was based on knowledge of the disease and of the commonly used outcome variables in musculoskeletal disorders. Concerning the disease, reviews on diagnostic criteria for shoulder pain conclude that current diagnostic tools are not evidence based . The maiWhile designing the trial, concerning the choice of the outcome measures used in this trial, we considered three key aspects: Which domain? Which instrument? Which analysis? The ultimate goal of any therapeutic intervention for shoulder pain is the restoration of pain-free function . Based oThe report results also anticipated considering that presentation at an individual level is probably more relevant than presentation at a group level –30. TherThe choice of the threshold of 30/100 in degree of severity of pain below which the patient considers her/his status as acceptable was arbitrarily chosen but was close to other patient-acceptable symptom state thresholds recently reported .Because of the huge variability of symptoms in most painful musculoskeletal disorders, a placebo arm is usually encouraged in order to facilitate the interpretation of the results. Such a placebo arm seems acceptable from an ethical point of view if the patient has the opportunity to obtain an optimal rescue therapy. This was the case in this trial during which a persistent painful condition was treated by use of acetaminophen and if necessary by local injections of steroids.Despite the fact that we did not perform formal comparative statistical testing, data obtained in this trial are in favor of a similar treatment effect for rofecoxib and diclofenac. However, we have to re-emphasize the fact that because of cardiovascular safety concerns, rofecoxib has been withdrawn from the market. This study, conducted during a very short period of time without further follow-up of patients, cannot contribute toward the assessment of safety.Based on this study, it is hard to generalize the obtained results with regard to both the study drugs and clinical condition being evaluated. In particular, such a study does not allow a conclusion that any NSAID at any dose might be beneficial in such conditions. Also, such a study does not allow conclusions to be made that positive clinical benefit may be identical in another musculoskeletal condition (such as epicondylitis or achilleus tendinitis).A Cochrane review on therapeutic interventions for acute shoulder pain currently does not include an estimate of the treatment effect of NSAIDs for this particular condition . A recenFinally, other studies are needed in order to evaluate the best dose regimen and the best therapeutical strategy, in particular whether it might be more clinically relevant to perform as the first step an NSAID/coxib intake and thereafter (in case of failure) a local injection of steroids  versus a local injection of steroids without oral drugs as the first step versus the combination of oral drug and local injection of steroids.CONSORT ChecklistClick here for additional data file.(50 KB DOC)Trial Protocol Click here for additional data file.(413 KB DOC)Trial Protocol (Amendment)Click here for additional data file.(384 KB DOC)


Despite the large amount of time and money which has been devoted to low back pain research, successful management remains an elusive goal and low back pain continues to place a large burden on the primary care setting. One reason for this may be that the priorities for research are often developed by researchers and funding bodies, with little consideration of the needs of primary care practitioners. This study aimed to determine the research priorities of primary care practitioners who manage low back pain on a day-to-day basis.A modified-Delphi survey of primary care practitioners was conducted, consisting of three rounds of questionnaires. In the first round, 70 practitioners who treat low back pain were each asked to provide up to five questions which they would like answered with respect to low back pain in primary care. The results were collated into a second round questionnaire consisting of 39 priorities, which were rated for importance by each practitioner on a likert-scale. The third round consisted of asking the practitioners to rank the top ten priorities in order of importance.Response rates for the modified-Delphi remained above 70% throughout the three rounds. The ten highest ranked priorities included the identification of sub-groups of patients that respond optimally to different treatments, evaluation of different exercise approaches in the management of low back pain, self-management of low back pain, and comparison of different treatment approaches by primary care professions treating low back pain.Practitioners identified a need for more information on a variety of topics, including diagnosis, the effectiveness of treatments, and identification of patient characteristics which affect treatment and recovery. Low back pain imposes an enormous social and economic burden on society, and can be seriously disabling. International guidelines for the management of low back pain generally agree that the condition should principally be managed in primary care . Back coThe burden of low back pain on society continues to rise despite the vast amount of research and time devoted to its resolution. Many aspects of low back pain remain poorly understood, including risk factors for developing acute low back pain and attributing the cause of low back pain to a specific pathology . DespiteOne potential explanation for the continued poor outcomes of low back pain, despite the attention it has received, is that research priorities are typically developed by government and industry authorities, funding agencies, and researchers ,6 who caIn Australia, the community primary care setting consists of a number of health care professions who provide health services to patients without the need for a prior referral. Low back pain is managed in primary care by three main professions in Australia, namely general practitioners, physiotherapists, and chiropractors. We identified practitioners in these three professions from clinics recruiting patients to a cohort study evaluating the prognosis of acute low back pain. All practitioners involved in the prognosis study were invited to participate. The study region was within the Sydney metropolitan area and was specifically chosen to cover a range of socio-economic values. Practitioners were provided with an information sheet regarding the modified-Delphi study and the first round questionnaire. If they consented to participate, they were asked to complete and return the questionnaire. All practitioners were experienced in managing patients with acute and chronic low back pain, and demonstrated continuing professional interest in improving the management of low back pain.The Delphi technique is best-known as a survey method used to gain consensus among a group of respondents ,8. ThereThere were three rounds to this survey with a two week interval between each of the three rounds. In round 1, participating practitioners were asked to list up to five of the most important questions about the management of low back pain in primary care that if addressed by researchers would improve their management of low back pain. Two authors collated the results and similar responses were collapsed to enable the development of the round 2 questionnaire. The intention was to maintain the subtlety and specific nature of as many of the responses as possible. Any discrepancies were resolved via consensus. In round 2 the participants were asked to rate the importance of the collated research priorities on a Likert scale from 0 to 5, with 0 meaning not at all important, and 5 meaning very important. In this way, practitioners are able to reconsider their responses while receiving feedback as to the responses of the rest of the practitioners. Round 3 consisted of the ten most important priorities, determined by median importance ratings, being returned to the practitioners in order. Where the median importance of the priorities was the same, the mode and then the mean was used to identify the top ten priorities. Each practitioner then ranked the ten priorities from 1 (highest) to 10 (lowest). In the second and third rounds of the Delphi, participants were asked to rate the importance of the priorities in general, not just the importance of those relevant to their practice.The responses for round 3 were analysed using descriptive statistics, and ordered by the median rank. Where the median was equal between two priorities, the mode score was used to determine the higher rank. Inter-quartile ranges were inspected to determine the consistency of results within the sample. All statistical analyses were performed using SPSS v.12.0.1 .Eighty-five primary care practitioners were invited to participate, of which 70  agreed to participate and completed the first round questionnaire. The practitioners were mostly male (56%) and had a mean (SD) of 14.8 (± 9.5) years of clinical experience. In total, 141 research priorities were identified by the 70 practitioners.The 141 research priorities were collapsed to 39 discrete research priority topics for the second round questionnaire. The response rate for the second round was 74.2% . The mean importance scores were calculated for each topic, and the top ten priorities are presented in Table These ten priorities were then sent back to the practitioners for the final ranking process. The response rate for round three was 71.4% . The median and mode rank after the third round can be seen in Table Table This study is the first to assess the low back pain research priorities of primary care practitioners. The top ten priorities identified in this study demonstrate that the primary care practitioners view low back pain within its broad clinical and social context, and suggest that research should be aimed towards developing more effective clinical tools , and changing knowledge and behaviour of patients (self management and the importance of primary care). For primary care practitioners to successfully manage low back pain and for progress to be made in reducing the burden of the condition, they need answers to these questions.Generally, clinical guidelines for the management of acute low back pain around the world provide similar recommendations for diagnosis and treatment . Many alA number of similarities can be observed when a comparison is made between the research agenda in the Australian guidelines and the research priorities identified in this study by the primary care practitioners Table . The ideFive out of the top ten priorities identified by the practitioners in this study were not represented in the research agenda of the current Australian guidelines. In our view, the inclusion of these five priorities in research agendas is important to further the understanding and management of low back pain. By developing effective strategies for patients to self-manage their low back pain (priority 4) and gain further understanding of the role of the primary care setting (priority 7) and the professions involved priority 10), the burden of low back pain on practitioners may be reduced. The presence of these issues within the top ten priorities of the practitioners, but not in the research agenda of the guideline seems anomalous given that guidelines generally recommend that low back pain should be managed in primary care [0, the buPrevious authors ,6 have sThe choice of primary care practitioners for this study was based the need for an informed study population who would be able to provide research priorities using their knowledge of current low back pain research. Different priorities may have been raised by other primary care practitioners; however it was thought that any differences between them and the guidelines may simply reflect a lack of awareness of current research. Nevertheless, some of the priorities identified in this study have received a lot of research attention in the past, such as identifying a cause for low back pain. The inclusion of this priority, among others, may be influenced by the lack of consensus among the research community and the demands of patients in the primary care setting.Our results suggest that there are a number of similarities between the research questions that practitioners need answered and those promoted in clinical practice guidelines, but there are also important differences. Primary care practitioners identified a range of topics in need of further information including diagnosis, reducing the burden on primary care, and effectiveness of treatments. This study provides important information to researchers, and highlights the importance of including primary care practitioners in the development of a research agenda.NH, CGM, KMR, and JHM contributed to the design of the study. NH, AD, and JHM collected data and contributed to the analysis of the study. NH drafted the manuscript with input from the other authors. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Chronic neck pain is highly prevalent in Western societies, with about 15% of females and 10% of males suffering with it at any time. The course of untreated chronic neck pain patients in clinical trials has not been well-defined and the placebo effect has not been clarified.A systematic review of RCT's of conservative treatments for chronic mechanical neck pain was conducted. Studies were excluded if they did not include a control group, if they involved subjects with whiplash injuries, a predominance of headache or arm pain associated with chronic neck pain and if only one treatment was reported. Only studies scoring 3–5 out of 5 on the Jadad Scale for quality were included in the final analysis. Data on change in pain scores of subjects in both placebo (PL) as well as no-treatment (NT) control groups were analyzed. Mean changes in pain scores as well as effect sizes were calculated, summarized and compared between these groups.Twenty (20) studies, 5 in the NT group and 15 in the PL group, with outcome intervals ranging from 1–52 weeks were included in the final analysis. The mean [95% CI] effect size of change in pain ratings in the no-treatment control studies at outcome points up to 10 weeks was 0.18  and for outcomes from 12–52 weeks it was 0.4 . In the placebo control groups it was 0.50  at up to 10 weeks and 0.33.  at 12–24 weeks. None of the comparisons between the no-treatment and placebo groups were statistically significant.It appears that the changes in pain scores in subjects with chronic neck pain not due to whiplash who are enrolled in no-treatment and placebo control groups were similarly small and not significantly different. As well, they do not appear to increase over longer-term follow-up. Neck pain is a very common problem, second only to low back pain in its frequency in the general population -3 and inClinical researchers are interested in the following question as it relates to chronic neck pain: "in a clinical trial, what is the expected outcome of chronic mechanical neck pain patients who are assigned to control groups?" Specifically, it would be useful to know the average magnitudes of change in various clinically important parameters such as pain and disability status at, for example, one, three, six and twelve months, in order to track the course of the condition in the absence of any formal treatment. Surprisingly, this question has received little attention in the literature.As noted above, numerous studies exist which provide information on the prevalence of chronic neck pain in general and specific  populations and typically report these as one-week, one-month, six-month, annual or lifetime occurrences -11. Howe"...within six months, approximately 50% of patients had less pain and a general improvement of 50%, with a mean reduction of pain and use of analgesics of about 30%" .We have used Borghouts et al.'s study as a foundation for an expanded review of the issue of the response of chronic mechanical neck pain patients in clinical trials who do not receive any formal treatment. It is recognized that data obtained from controlled clinical trial reports would not be truly observational, in that subjects in control groups are highly selected for inclusion. As well, they may benefit from the mere fact that they participated in a clinical trial; however, at least this effect would not be confounded by any formal intervention .Two types of control groups exist for this purpose: no-treatment (NT) controls and placebo (PL) controls. Each of these groups has advantages and disadvantages with respect to a determination of clinical outcome or course. For no-treatment controls, a so-called "trial effect" (non-specific effect) would exist resulting from the basic fact of selection for and participation in a clinical trial; however, since subjects would be aware of their status as "not receiving treatment", the positive "trial effect" might be counteracted (nocebo effect), making their outcomes an approximation of the "natural history" of chronic neck pain over the duration of the study and any follow-up intervals. In Borghouts' et al. review of 17 RCT's, 3 trials had no-treatment control groups -22; howeThe outcomes of placebo control groups would not constitute the "natural history" of the chronic neck pain, as, in these circumstances, subjects are lead to believe that they are receiving a true treatment ,24. DataCurrent experimental theory ,24 wouldA comprehensive literature search was performed in MEDLINE, CINHAHL, AMED, MANTIS, Index to Chiropractic Literature, Alt HealthWatch, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Registry, and several EBSCO Information Services databases  using the strategy outlined in Table Citation searches were also conducted manually. The limitation to English was based on the inability to translate any non-English studies.Inclusion: the study design was a randomized clinical trial of conservative or complementary therapies for chronic neck pain. As several studies employed time frames for pain duration less than the conventional interval of 12 weeks, and as we sought the largest sample possible, we defined "chronic neck pain" as neck pain of longer than eight weeks in duration  mm; the mean (95%CI) relative change in VAS mm was -10.3% ; the mean [95%CI] effect size of these changes was 0.18 .The 12–52 week outcomes are summarized as follows: the mean absolute change in VAS mm was -11.9 ; the mean relative change in VAS mm was -25.7% ; the mean [95% CI] effect size of these changes was 0.4 .One study provided data on self-rated improvement (% of subjects who rated full improvement). Taimela et al. , reporteTable The majority of these comparisons were made at between 2–6 weeks post-baseline. Four (4) studies measured outcomes past 10 weeks ,51,59,61Four (4) studies ,51,59,61Lewith and Machin  reportedThe baseline pain scores in the PL group were statistically significantly greater than those in the NT group  = -3.29, p = .005).Comparisons of the change scores between the two groups (PL vs NT) at 0–10 weeks and at greater than 10 weeks for absolute (mm) or relative (%) change showed no significant differences in any of the four comparisons.There are several ways to interpret the results of this analysis. The average effect size, from those studies in which this could be calculated, is in the small -to – medium range ,37, althThe baseline pain scores for both types of study group were in the mild-moderately severe range (3–5 out of 10). The range of average absolute changes in 100 mm pain VAS ratings is -5.7 to -11.9 mm over all outcome intervals. All but two of the studies ,61 reporBased on these summaries, and with due regard to the large confidence intervals for the mean effect sizes, and with due regard to the small sample in some of the sub-groups of this study, it appears that the change scores for chronic neck pain patients not receiving formal therapy increase relatively little over 4–10 weeks at which point their increase appears to plateau for up to 12 months. As well, it appears that the "placebo effect" is not significantly different from the effect obtained in unblinded no-treatment control groups.Our findings do not appear to bear out the hypothesis that the changes obtained in the PL groups would be greater than those in NT control groups. The statistical comparisons for all four outcomes  were not significant. As noted in the introduction, the basis for this hypothesis is that the "placebo effect" is postulated to be stronger than the effect obtained from mere "trial participation". This expected difference hinges on the issue of blinding: subjects assigned to no-treatment control groups become, in short order, aware of this status; this awareness is then thought to have a diminishing effect on their treatment expectations. This, along with the absence of putatively stronger "placebogenic" effects, is thought to result in the lowest expected treatment outcome.On the other hand, subjects assigned to a placebo group are, ideally, not aware of this status; their higher treatment expectations are then thought to contribute to the more positive placebo "effect"; i.e., a short-term, self-referential state of improvement which, we had proposed, would be larger than that obtained in un-blinded, no-treatment control subjects.The fact that our findings did not support this expected effect is, thus, surprising. This is especially so since the mean PL group baseline pain score was higher than that of the non-treatment group. One explanation may be that subjects in the no-treatment control groups, once they recognize this status, conclude that they will not, or at least may not, obtain the optimum benefit from their participation in the study. They may then decide to drop out. If they remain in the study, they may then decide to seek additional forms of relief not sanctioned by the study. These self-relief measures may include increasing the frequency of low-level over-the-counter (OTC) medications , increasing the use of higher strength OTC medications, increasing the use of heat or cold applications, herbal products or other proprietary procedures, increasing the use of non-professional "treatments" such as casual massage and increasing their use of exercises, both at home and in one of the many facilities which have lately sprung up to offer rather sophisticated exercise protocols .The use of these sorts of self-treatment measures is by no means a new phenomenon in the conduct of clinical trials. Trial teams may take a variety of measures to deal with it, including, explicit attempts to limit it, attempts to measure it and attempts to incorporate it into their analytic models. It is likely that trial designers would expect that such self-help behaviors (self-directed co-interventions) would "wash-out" across all study groups. Our findings suggest that, at least for chronic neck pain subjects, this may not be so, with the difference possibly arising from the effect that un-blinded assignment to no-treatment control status has on the pain management decisions the subjects so assigned may make during their participation in the study.As we did not intend to identify the causal explanation for the outcomes we obtained, it should be noted that, as Borghouts et al.  and otheOur results are very consistent with two other recent systematic reviews of placebo-controlled trials ,24. HrobOur findings are in agreement with those of Borghouts et al. . The sumOur findings are also in good accord with Farrar et al.  who repoWhile we attempted to obtain the largest possible sample of high quality studies, it is possible that some English-language studies were missed. As well, since non-English studies were not included, it is possible that such studies may provide different findings. However, the findings from the studies in our sample were all relatively consistent; it would be surprising to find a separate sample with greatly different findings.The findings of our study can be of use to clinical trial planners by providing a general benchmark of minimum group mean change scores on pain measures for chronic mechanical neck pain patients. These findings may also be of use in the development of clinical guidelines, in that they provide a benchmark against which the results of studies of various treatments can be compared. This does not, however, replace using control groups in future trials, especially in the early stages of research into a specific modality of treatment. Where a body of studies does exist, and where there are no or few well-controlled trials, these findings may provide a proxy measure for guideline developers in evaluating the benefit of various treatments.Our initial question, "what is the expected outcome of chronic mechanical neck pain patients who are assigned to control groups?", has been addressed by analyzing two sets of RCT's providing data on chronic neck pain subjects in either no-treatment or placebo control groups. It appears that the changes in pain scores in subjects with chronic neck pain not due to whiplash who are enrolled in no-treatment and placebo control groups were similarly small and not significantly different. As well, they do not appear to increase over longer-term follow-up.The author(s) declare that they have no competing interests.HV was involved in planning and designing this study, retrieving, organizing, evaluating and selecting the article to be reviewed, abstracting the relevant data and writing all aspects of the manuscript.KH was involved in planning and designing this study and in evaluating the articles to be included in this review. He also assisted in the writing of all aspects of the manuscript.CH was involved in planning and designing this study and in evaluating the articles to be included in this review. She also assisted in the writing of all aspects of the manuscript.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here: