This open, multicentre, observational survey investigated how physicians diagnose neuropathic pain (NeP) by applying the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, and how neuropathic pain conditions are managed in daily practice in Belgium.Physicians were asked to complete the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale for diagnosing NeP, and to fill out a questionnaire regarding the management of NeP, together with a questionnaire evaluating the impact of pain on sleep and daily life. Data on 2,480 pain patients were obtained. A LANSS score ≥ 12 (meaning NeP is most probably present) was reported for 1,163 patients. Pathologies typically associated with NeP scored above 12 on the LANSS scale, contrary to pathologies generally considered as being of non-neuropathic origin.Over 90% of the patients with a LANSS score ≥ 12 reported that the pain impaired sleep. A high impact on social, family and professional life was also recorded. Additional examinations were performed in 89% of these patients. Most patients were taking multiple drugs, mainly paracetamol and non-steroidal anti-inflammatory drugs, indicating that physicians generally tend to follow treatment guidelines of chronic nociceptive pain, rather than the specific ones for NeP. Specific neuropathic guidelines rather recommend the use of anti-epileptic drugs, tricyclic antidepressants or weak opioids as first-line treatment.In our survey, application of the LANSS scale lead to pronounced treatment simplification with fewer drug combinations. Awareness about NeP as well as its specific treatment recommendations should be raised among healthcare providers. We concluded that the LANSS screening scale is an interesting tool to assist physicians in detecting NeP patients in routine clinical care. Neuropathic pain (NeP) has been defined by the International Association for the Study of Pain (IASP) as pain that is initiated or caused by a primary lesion or dysfunction in the nervous system . NeP oftCommon causes of NeP include diabetes mellitus, cancer, herpes zoster, trigeminal neuralgia, complex regional pain syndrome (CRPS), alcohol abuse, multiple sclerosis (MS) and other . NeP is However, a major hurdle in establishing a correct diagnosis and hence to provide the patient with the appropriate therapy is the lack of unambiguous diagnostic criteria for distinguishing NeP from NocP. Physicians often rely on the clinical diagnosis that may be complemented with exams such as radiological examinations , electromyography (EMG), or a somatosensory evoked potential test. Recently, the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS) pain scale was developed and validated to provide clinicians with a practical instrument for discriminating NeP from NocP in daily practice . The LANThe objective of this survey was to increase awareness of NeP among Belgian physicians and to determine whether a screening scale would be helpful in making the correct diagnosis. Furthermore, we aimed to assess how NeP is managed in Belgium, and how this condition affects the quality of sleep and daily life in the patients. To our knowledge, this is the first study to report on the use of a pain scale in the diagnosis of NeP on a large scale in real-life clinical practice.all patients before their inclusion in the study.One hundred and seventy seven general practitioners (GP) and 97 specialists  participated in this study. In Belgium (pain) patients can directly consult any specialist of their choice, without prior referral by their GP. Because GP's in Belgium often do not act as frontline physicians for pain conditions – with pain patients immediately contacting the specialists they consider appropriate for solving their problem – we believe that there is no major difference in patient population nor pain characteristics in the specialists' reception from those in GPs'. The study was approved by the local ethics committee of the Antwerp University Hospital (UZA). Written informed consent was obtained from consecutive patients presenting with symptoms of sub-acute (between 3 and 6 months of duration) and chronic (> 6 months) pain in their practice, irrespective of the type of pain (nociceptive or neuropathic). Pregnant and breastfeeding women, and women who were planning to become pregnant in the near future, were excluded from the study. Age, gender, and duration of pain of all patients were recorded. The possible underlying cause of the pain was also documented by the physician.Participating physicians were instructed to document 15 The physicians were asked to fill out the LANSS questionnaire (characterization of the pain true 5 questions), as well as to perform the two included items for sensory testing: (1) allodynia and (2) altered pin-prick threshold. Allodynia was judged to be present when pain was elicited by gently stroking a piece of cotton wool over the painful area and when normal sensation was experienced in the control site. Hyperalgesia was judged to be present when pin-prick testing elicited an exaggerated painful response at the painful site compared with the control site. Validation of a Dutch and French version of the original (English) LANSS-scale was performed before the start of the study, in accordance to how this validation was performed for other languages ,18. Tranall patients would have completed this additional questionnaire, due to practical reasons (work load of participating physicians) it was opted by the investigators not to obtain this additional information in patients with LANSS-scores < 12. Sleep was assessed in a quantitative way by using a visual analogue scale for sleep quality (VAS) offering a score between 0 (no sleep disturbance) to 10  for sleep disturbance during the past 24 h. In addition, sleep was assessed qualitatively by asking the patients which specific aspects of sleep were disturbed . Finally, patients were asked if their pain had an impact on following aspects of daily life: family life, social activities, professional life and leisure.For the patients who had a LANSS scale pain score ≥ 12 (meaning NeP is most probably present) the physicians filled out an additional questionnaire providing more detailed information on (1) previously performed and future planned treatment options for the pain condition, (2) any additional tests that were performed for confirming the diagnosis and (3) the impact of the pain symptoms on sleep and activities of daily living. Although useful information regarding treatment and functional status could have been generated if Data analyses were based on descriptive statistics, including percentages, medians, means, ranges and standard deviations. Percentages were calculated based on all values for that particular question (missing excluded). Analyses were performed on the total patient group as well as the LANSS pain score subgroups . Comparison of parameters  between LANSS pain score subgroups was carried out using t-test statistics. Fisher's exact test was employed for assessing differences in gender and type of pain. All statistical tests were interpreted at the 5% significance level (two-tailed). In addition, odds ratios, together with 95% confidence intervals, were calculated for the patients with only one underlying cause of pain to investigate the influence of the underlying pathology on the LANSS pain scores. Patients reporting multiple underlying causes of pain were excluded from the odds ratio analysis to avoid confounding effects of the various pathologies on the LANSS score.In total 2,480 pain patients were enrolled in the study by 177 general practitioners (GPs) and 97 specialists. The total number of patients that could have been expected was not reached since 63 physicians  failed to fulfil the inclusion target, and a number of questionnaires (n = 493) had to be discarded due to incompleteness of the data. Reasons for these failures are probably the work load and the strict time schedule of this protocol. Around two thirds of the patients  were treated by a GP, while 831 patients (34%) were being treated by a specialist. More than half of the participating pain patients (59.6%) were women. The mean age of the patients was 58.2 years . The average duration of the pain amounted to 3.0 years (SD = 4.4), with a range from less than three months to 60 years (diabetic neuropathy). Almost one third of the patients (28%) reported their pain having lasted from six months to three years.Data on the underlying pathology were obtained for 2,436 out of 2,480 pain patients (98%). A total of 65.2% of the patients had one underlying cause of pain, while in 25.4% of patients two underlying disorders could be identified. Three or more pathologies were reported by 9.4% of the patients. The most prevalent causes of pain consisted of lumbar pain (32.1% of patients), followed by osteoarthritis (OA) (24.2%), post-traumatic lesions (13.4%), diabetes mellitus (10.4%), post-surgical lesions (9.5%), osteoporosis (7.6%), complex regional pain syndrome (CRPS) (7.3%), and post-herpetic neuralgia (6.7%) , while 37.8% reported spontaneous pain as their only symptom. Finally, 0.7% of patients reported only provoked pain symptoms. Spontaneous pain was mainly described in terms of throbbing pain (61.3%), a burning sensation (47.9%), or abnormal and disagreeable (painful) sensations (dysaesthesia) (47.8%). Less frequent manifestations of spontaneous pain comprised cutting-lacerating pain (31.8% of patients), electric shock sensation (22.8%), stab sensation (18.8%), and abnormal but not disagreeable sensation (paraesthesia) (17.3%). The majority of the patients with spontaneous pain symptoms (57.7%) identified two or three terms to describe their symptoms. The combination of a burning sensation, throbbing pain and dysaesthesia was the most frequently reported combination (6.4% of the patients with spontaneous pain), followed by a burning sensation together with dysaesthesia (4.5%), throbbing pain with dysaesthesia (4.3%), and throbbing pain in combination with cutting-lacerating pain symptoms (4.0%).Evoked pain was mostly present as allodynia (40.3%), hyperalgesic symptomatology only (10.3%), or mixed allodynic/hyperalgesic symptoms (47.0%). Touch-evoked allodynia was most common . These allodynic symptoms were induced by several triggers, such as contact with clothes (38.8%), or allodynia in the shower or in bath (15.2%), followed by painful symptoms resulting from wind blowing against the face (12.5%) and during shaving (5.4%). Pin-prick hyperalgesia was found to be the most common form of hyperalgesia, being present in more than half (52.5%) of all patients suffering from hyperalgesic symptoms. Other forms of hyperalgesia were reported in 2.5% of the patients. Once more, as observed previously with spontaneous pain, a majority of patients (61.6%) reported more than one subtype of provoked pain. The most frequently reported combinations of provoked pain symptoms were touch-evoked allodynia combined with pin-prick hyperalgesia (12.5% of the patients with provoked pain symptoms), followed in second place by touch-evoked allodynia combined with allodynia induced by clothing and pin-prick induced hyperalgesia (11.7%).Of the total number of patients enrolled in this survey for whom a LANSS pain score was recorded , 1,163 patients (47.2%) presented with a LANSS score of 12 or more (LANSS ≥ 12 group), which strongly suggests the presence of a pain component of neuropathic origin . DemograDiseases that are known to be associated with NeP such as diabetes mellitus (mean LANSS score = 14.4), syringomyelia (17.5), thalamic syndrome (18.1), post-herpetic neuralgia 17.2), and CRPS type 2 (16.6) yielded higher mean LANSS scores than pathologies that are generally considered to be associated with NocP, e.g. OA (mean LANSS score = 8.7) or osteoporosis (9.2). Further support for the efficacy of the LANSS scale in detecting NeP can be found in the results of the odds ratio (OR) analysis, in which 1,580 patients reporting only one underlying cause of pain were included. Indeed, the OR of having a LANSS score ≥ 12 for patients suffering from a typical nociceptive pathology, such as OA or osteoporosis, amounted to only 0.1 and 0.2 respectively, while the OR for NeP conditions such as diabetic neuropathy, multiple sclerosis, post-herpetic neuralgia and CRPS were 3.0, 6.9, 5.4, and 3.1 respectively  25/133 of diabetic patients, 20/137 PHN patients, 6/42 patients suffering from thalamic syndrome, 9/59 patients with carpal canal syndromes, 9/75 CRPS patients, and 3/26 MS patients . This amounts to a total number of failures of 72/472 . In nociceptive syndromes, the LANSS Pain Scale produced high scores (≥ 12) in 26/169 OA patients, 68/316 patients suffering from lumbar pain, and 7/26 osteoporotic patients. In these three non-neuropathic conditions, 101/511 received false high LANSS scores . When considering the above mentioned NeP and NocP syndromes, the LANSS Pain Scale was able to correctly identify 82,4% (810/983) of patients with one pain complaint, representing 84,7% sensitivity and 80,2% specificity.p < 0.001). Most conditions of allodynia were also significantly more prevalent among patients from the LANSS ≥ 12 group than among those from the LANSS < 12 group . In addition, the various manifestations of spontaneous and provoked pain syndromes were described in different terms by the patients belonging to the different subgroups. Pain types indicative of NeP occurred much more frequently in patients with LANSS ≥ 12 than in those with a score of < 12  on a scale from 0 to 10, with 10 indicating a maximal sleep disturbance during the past 24 h. It is important to mention that only 8.2% of all patients completing the queries about their sleep quality failed to report any negative impact of the pain symptoms on their quality of sleep. Lumbar pain in combination with post-surgical lesions was identified as the medical condition that caused the most sleep disturbance with an average VAS score of 6.0 . The lowest mean VAS score was found in the group of multiple sclerosis patients . Patients with combined complaints of spontaneous and provoked pain had a mean VAS score of 5.3 , whereas patients with only spontaneous complaints had a mean VAS score of 4.8 . Hyperalgesia and allodynia caused similar degrees of sleep disturbance . When considering the type of sleep interference, the large majority of patients reported difficulties falling asleep (60.4%), interruption of sleep (72.1%), premature awakening (60.4%) and non-restorative sleep (66.7%). In addition, 93.6% of patients reported an impact on their activities of daily living. Most of the patients reported an influence on family life (77.5%), social activities (79.8%), spare time (81.8%) and professional activities (66.1%). It should be noted that 41.4% even reported influence of their pain on all of these aspects.On top of the clinical examination, the large majority of patients in the LANSS ≥ 12 group received complementary technical investigations to obtain final confirmation of the diagnosis of NeP. Data were available for 1,125 of the patients in the LANSS ≥ 12 group, and revealed that 1,002 of these (89.1%) were subject to one of more supplementary examinations . The most commonly performed technical investigations were electromyography (68.9% of patients), followed by radiography (59.2%), CT/MRI scan (56.2%), lab tests (51.4%), bone scan (31.4%), and a sensory evoked potential test (8.5%). Of all patients subject to additional testing, 77.8% received more than one test. Based on the results of this study, post-herpetic neuralgia is apparently perceived as the most straight-forward clinical diagnosis since only less than half of these patients (44.9%) received additional tests. In all other disorders a large majority of patients was subject to additional exams. Interestingly, our study results clearly indicate that the actual number of additional tests that were carried out is highly dependent on the underlying pathology. Most patients with carpal canal syndrome  and almost half of those suffering from diabetes  received only one additional test, while the majority of those with another underlying pathology received two or more exams  in the LANSS ≥ 12 group had received pharmacological treatment prior to enrolment in this survey. In almost all patients this (previous) treatment consisted of prescription drugs (88.5% of the patients) or a combination of prescription and over-the-counter (OTC) drugs (9.8%). Paracetamol was the most commonly prescribed drug (67.1% of the patients) followed by drugs belonging to the non-selective non-steroidal anti-inflammatory drugs (NSAID)/cyclo-oxygenase-2 specific (COX-2) inhibitors (61.4%). On the third place came the antidepressant agents (41.4%). Less common were opioids , anti-epileptic drugs (AED) in 18.0% of the patients, and finally acetylic salicylic acid (4.2%). Similar treatment patterns were found in patients consulting a GP or a specialist. However, patients treated by specialists received more treatments using AED than when treated by primary care physicians . In contrast, the use of antidepressant drugs was more common in patients seeking help of primary care physicians than specialists (44.7% vs. 34.4%).Only 24.1% of the patients had previously received one drug, while 38.2% had been prescribed a combination of two drugs, and 23.1% had even received three different drugs  in 87.6% of the patients from the LANSS ≥ 12 group . Interestingly enough, physicians stated that respectively 36.6% and 17.6% of the patients would be referred for physiotherapy and for psychosocial support.Compared to previous treatment regimens, physicians indicated that future treatment would consist of less drugs being prescribed concomitantly Fig. : whereasProgress in the further understanding of neuropathic pain (NeP) in the general population has been seriously hindered by a lack of epidemiologic research. One reason for the lack of population-based epidemiologic data has been the lack of a good case identification instrument for use in surveys. In this study the Leeds Assessment of Neuropathic Symptoms and Signs score (LANSS) was applied to investigate the management of neuropathic pain in Belgium. The LANSS scale was developed as a clinic based instrument for identifying patients whose pain is dominated by neuropathic mechanisms . AlthougThe average age of the participating patients was 58 years, and the majority were women. This is congruent with literature data showing that female gender and higher age constitute major risk factors for chronic pain -22.all participating patients would have significantly increased the physicians' work load, perhaps further diminishing their preparedness to include sufficient number of patients.It is generally conceived that about 25% of all chronic pain patients suffer NeP . In our Bennett  reportedIt should be noted that distribution of patient populations and pain characteristics did not differ significantly between GP's and specialists. This should perhaps be considered a somewhat typical Belgian finding, since general practitioners have no major gate-keeping role in the referral of patients to specialist care. In other countries (e.g. The Netherlands) GP's tend to be much more in control of this referral process, which probably leads to significantly different patient populations and pain characteristics in specialists' reception compared to those in GPs'. In addition, no significant differences were observed in the obtained LANSS-scores, which proves that this scale can be used by a diverse group of physicians.Post-herpetic neuralgia and diabetic neuropathy were the most common underlying diagnoses in patients with LANSS score ≥ 12 for whom one cause of pain was diagnosed. This is in line with data from other investigators ,5,20, anConsidering the observation that almost 90% of the patients with a LANSS score suggestive for the possible presence of a neuropathic pain syndrome, still received additional technical investigations, a more widespread use of these types of screening scales may perhaps decrease the need of additional medical exams and speed up the implementation of neuropathic-specific treatment regimens . It is of importance that NeP should be treated promptly, because the longer the delay in appropriate therapy, the lower the proportion of patients in whom the NeP is relieved . Fewer aThe negative impact of chronic pain including NeP on Quality of Life (QoL) is well documented. Chronic pain adversely affects overall health, daily activities and productivity at work, and is an important predisposing factor for depression ,24-26. DRecent recommendations for the treatment of NeP suggest the use of AED , tramadol, the 5% lidocaine patch or antidepressants as a first-line therapy for NeP -10. It sThe data obtained in our study shows that in Belgium NeP is still mainly managed with conventional analgesics such as paracetamol and NSAIDs, instead of the more effective anti-neuropathic drugs. A widespread use of conventional analgesics in the treatment of NeP has been reported by others ,5,20. GiIn conclusion, our study results confirm previous reports that NeP is under-recognised and often not treated adequately in daily practice, and that it has a considerably negative impact on QoL. NeP patients are treated mainly with combinations of conventional analgesics rather than the more effective antineuropathic drugs, indicating that physicians often do not follow the guidelines for NeP. Clearly, awareness among physicians about NeP and the availability of diagnostic tools should be augmented, and the importance of applying appropriate treatment regimens tailored to the individual patient's needs should be more strongly emphasised. The results of this study indicate that the LANSS-scale is a useful tool to discriminate patients with a neuropathic pain component and to assist in modifying the analgesic approach to these critical pain syndromes.The author(s) declare that they have no competing interests.GH participated in the design of the study, served as a principal investigator and drafted the manuscript. EM participated in the design of the study and served as principal investigator in this study. PDC conceived the study, coordinated the practical aspects of this study project and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The purpose of this prospective randomised study is to evaluate the efficacy, safety and the appropriate dose of the ropivacaine in the control of post-knee arthroscopy pain.We randomised 60 patients in two groups to receive 10 ml/7.5 mg/ml ropivacaine (Group B) or 20 ml/7.5 mg/ml (Group A) at the end of a routine knee arthroscopy. We monitored the patient's blood pressure, heart rate, allergic reactions, headache, nausea, we assessed the pain using the visual analogue score at intervals of 1,2,3,4 and 6 hours after the operation. and we recorded the need for extra analgesia.The intraarticular use of the ropivacaine provided excellent control of pain after knee arthroscopy. At two hours post-operatively there wasn't any difference between the two groups. Afterwards, the Group A showed increased pain and need for supplementary medication.We believe that intraarticular use of ropivacaine is effective to reduce post-operative pain minimising the use of systematic analgesia. Arthroscopic knee surgery is one of the most common surgical procedures done in an outpatient setting. Post operative pain undoubtedly, it has a negative impact on the patient's psychology causing discomfort and prohibiting early mobilisation.Administration of oral opioids and non-steroid antinflammatory drugs are combined with sufficient relief of pain in the immediate postoperative period . HoweverAlthough the pain has been reported slight to moderate and of short duration, a review of 20 studies showed evidence for reduction in postoperative pain after intra-articular local anaesthesia following arthroscopic knee surgery . No adve+ channels. It has the similar pharmacokinetic properties as bupivacaine but different pharmacodynamic such as their vasodilatory property and the toxicity. Furthermore, ropivacaine has a lower molecular weight than bupivacaine (Ropi 262 vs Bupi 288) The chance to use this drug in high concentrations provides higher clinical efficacy [Ropivacaine is a new local amino-amide anesthetic that blocks peripheral afferents from acting on voltage-dependent Naefficacy . The purAfter the approval of local scientific committee and signed informed consent, 60 patients  with mean age of 33 years (range 19–50 years) and ASA I-II(American Society of Anesthesiologists) physical status, were scheduled for a routine elective knee arthroscopy. Patients with a history of sensitivity to local anaesthetics or preoperative administration of opioids or any other analgesics in the preceding 48 h were excluded from the study. Surgical interventions were diagnostic arthroscopies, meniscal excision or repair, removal of loose bodies and arthroscopic debridement. Cases of extensive arthroscopic synovectomy, ligament reconstruction and articular cartilage procedures were excluded.All the arthroscopies were performed under tourniquet application and by the same surgeon. Two standard portals  were used and the mean duration of the whole procedure was 45 min (range 35 to 60 min).Standardised general anaesthesia was selected in all the cases. Muscle relaxants and short-acting opioids (fentanyl) were used at the beginning of the operation. No nonsteroidal anti-inflammatory drugs or additional pain medications were administered.Patients were divided in two groups of 30 patients in each group using randomly sealed envelopes. Group B patients received ropivacaine 10 ml of 7,5 mg/ml and Group A patients received ropivacaine 20 ml of 7.5 mg/ml at the end of surgery.At the postoperative period we record the heart rate, blood pressure, allergic reactions, nausea and headache for the first 6 hours. Visual Analogue Score (VAS) for pain scores was recorded at intervals of 1, 2, 3, 4 and 6 h after the intra-articular injection.In case of need of supplementary analgesics, 1 g paracetamole plus codeine phosphate 60 mg was administered. In the event that there was no pain relief, 75 mg i.m diclophenac was injected. The time to the first request for analgesia and the total analgesic requirements were recorded.The data were analysed using T-test for VAS and Chi-square test for analgesic consumption.No statistical difference regarding the VAS at the first 2 hours was detected between the two groups. At 3 hours post-operatively there was statistically lower VAS in Group A than in Group B fig . After tAs mentioned above none of the patients required extra analgesia until 3 hours post-operatively. Afterwards, Group B used significantly more analgesics than Group A. .No adverse reaction has been recorded between the groups.Many modes of postoperative analgesia have been reported for patients undergoing knee arthroscopy . The useRopivacaine is a commonly used local anaesthetic and it is related structurally to bupivacaine and mepivacaine. It is a less lipid soluble than bupivacaine, but its pharmacokinetic disposition is similar. Ropivacaine seemed to provide similar and effective post-arthroscopy analgesia  comparedPlasma concentrations of ropivacaine has been studied by Convery et al  and theyThe acute and most serious adverse effects of local anesthetics involve the CNS and the cardiovascular system. They usually occur either because of accidental intravascular or intrathecal injections, or a pronounced overdose. CNS symptoms of local anesthetic toxicity occur before cardiovascular symptoms and signs, and include numbness of the tongue, light-headedness, visual disturbances, and muscular twitching; more serious signs include seizures, coma, respiratory arrest, and cardiovascular depression. Extremely high concentrations depress spontaneous pacemaker activity in the sinus node and result in sinus bradycardia and sinus arrest. In our study none of the patients developed any adverse reactions therefore we assume that intraarticular dose of ropivacaine up to 150 mg is safe.Our results revealed that there is no difference in pain between 10 ml and 20 ml of 7,5 mg/ml, at 2 hours postoperatively. At 3 hours there was a statistical difference in VAS and this was also confirmed by the use of supplementary analgesia.After arthroscopy, acute inflammation is induced by the release of mediators from damaged cells. Martin et al noted that cryotherapy works in the acute inflammatory response decreasing the narcotic consumption, pain and knee swelling . AlthougAs a conclusion, intraarticular injections of local anaesthetics seems to provide an alternative and effective solution in pain control after knee arthroscopy.


Being able to estimate the likelihood of poor recovery from episodes of back pain is important for care. Studies of psychosocial factors in inception cohorts in general practice and occupational populations have begun to make inroads to these problems. However, no studies have yet investigated this in chiropractic patients.A prospective inception cohort study of patients presenting to a UK chiropractic practice for new episodes of non-specific low back pain (LBP) was conducted. Baseline questionnaires asked about age, gender, occupation, work status, duration of current episode, chronicity, aggravating features and bothersomeness using Deyo's 'Core Set'. Psychological factors  and LBP bothersomeness (ES 1.37). Although most patients began with moderate-high back pain bothersomeness scores, few had high psychometric ones. Co-morbidity was a risk for high-moderate interference with normal work at 6 weeks . An episode duration of >4 weeks was associated with moderate to high bothersomeness at 6 weeks  and negative outlook (inevitability) with moderate to high interference with normal work .Patients attending a private UK chiropractic clinic for new episodes of non-specific LBP exhibited few psychosocial predictors of poor outcome, unlike other patient populations that have been studied. Despite considerable bothersomeness at baseline, scores were low at follow-up. In this independent health sector back pain population, general health and duration of episode before consulting appeared more important to outcome than psychosocial factors. Recovery from persistent low back pain is determined not solely by clinical factors but also by the individual's psychological state . Such psFailure to improve as expected leads to disappointment and sometimes to unexpectedly protracted treatment. As well as the distress this may cause the patient, it could engender criticism of the practitioners and their profession. Indeed, the chiropractic profession has been noted for seeming over-treatment of patients . TraditiPain is defined as an unpleasant sensory and emotional experience . It is hAcute pain gives rise to anxiety about its aetiology and prognosis , whereasBetter care strategies for patients at risk of poor outcome require that they first be recognised as being at risk. The literature suggests that the main psychosocial risk factors relate predominantly to depression, distress and role issues, especially with regard to work ,14-17. WResearch has identified risk factors with predictive value for chronicity in various public sector settings , notablyOver a one-year period, 200 consecutive new patients contacting a chiropractic clinic in the market town of Salisbury in the UK for an appointment were asked by the clinic receptionists to confirm if their primary complaint was a new episode of pain in the lower back. If it was, they were informed about the study and that, if eligible and willing, their participation would involve the completion of two questionnaires prior to treatment on first attendance at the clinic, followed by one further, short (6 questions) questionnaire six weeks after initial presentation. This follow-up questionnaire was administered via the telephone. Two years on from initial presentation, all patients who had completed the 6-week follow-up were contacted to see if they would be willing to complete the 6-item questionnaire one more time.If the patient was willing in principle to participate, the receptionist was required to ask four questions to determine eligibility. To be eligible, patients had to be aged between 18 and 65 years, to have not undergone previous back surgery, not be pregnant and to not have pain below the knee.If the patient remained eligible and willing to join the study, s/he was asked to attend the clinic 20 minutes prior to their scheduled appointment with the chiropractor. Upon arrival, the patient was given a consent form to read and sign. The receptionist was only allowed to answer clarifying questions if asked. The patient was also given an information sheet that they could take away with them detailing the study. A contact number for the senior researcher was provided on this form in case the patient had any queries or concerns. On completion of the questionnaires, the patient was then examined by the chiropractor who confirmed their final eligibility as having non-specific back pain. Reasons for non-eligibility were recorded.When the receptionist received back the patient notes and eligibility form, the details of those patients for whom it was appropriate to join the study were entered onto a patient log. This recorded patient contact details, date of recruitment, the granting of consent and the completion date of the first questionnaires. Completed questionnaires, signed consent and eligibility forms and the patient logs were retrieved from the clinic on a weekly basis. A date for a 4 and 6-week follow-up for each participating patient was calculated. The purpose of the 4-week follow-up was to check that the original diagnosis of non-specific (simple) back pain had not changed. This was done by review of the patient's clinical notes at the practice. The results of this re-examination of the patient's notes were also recorded in the log.The baseline questionnaire requested information about age, gender, occupation, work status . Duration of current episode and chronicity  were detWhen the date for the 6 week follow-up was known, the patient was sent a reminder card showing the date and time for its completion. The time of day was determined by the patient's stated preference on the consent form as being the most convenient time for them to be contacted by telephone. This was also the case regarding where they were to be contacted, i.e. at home, work or on their mobile telephone. The patient was asked to keep the reminder somewhere prominent and to contact the investigators if the scheduled appointment was not convenient. An alternative appointment could be made for a period of up to 5 days from the original due date. On the agreed date and time, the patient was contacted by telephone and the questionnaire administered. The due date for completion of the 6 week follow-up was noted on the patient log, as was the date it was actually completed.At 2 years, the number of attendances after the first 6-weeks from presentation was recorded from a note search. In addition, patients were contacted by telephone and asked to complete Deyo's core set  again, bDescriptive analysis of the baseline characteristics of participating patients was initially performed, followed by correlation analysis between selected baseline and follow-up variables. Baseline and 6 week outcomes  were compared and effect sizes  were calOf the 200 patients initially approached to participate in the study, 158 were eligible to participate and completed the baseline questionnaires. (Ineligibility was mainly by reason of having pain below the knee.) Of these, 130 (82%) completed the 6 week follow-up. However, 29 patients failed to provide full details at this stage, thus reducing the number of participants to 101 (64%). At 2 years, only 55 (54%) of these 101 subjects were available for further follow-up.Fifty-seven percent of the sample was female and the mean age was 43 years (SD:10.39). The majority (n = 34) had experienced their current episode of low back pain for 1–4 weeks and 26 for >12 weeks. The remainder reported durations of 1–6 days (n = 24) and 5–12 weeks (n = 17). The current episode was the first ever experience of LBP in 24% of subjects, while over half (55%) had been troubled by episode(s) of LBP for ≥ 50% of the past year. Eighty-six percent were either employed or self-employed and virtually all (99%) enjoyed their work. Nearly two-thirds (n = 10) of the 16 patients who reported currently being off work had been off for more than 1 week and 38% of the participants also had other conditions.Baseline outcome scores are summarised in Table The range and mean baseline psychometric scores are shown in Table At 2 years, the high attrition rate rendered further analysis to identify predictors of poor outcome unfeasible. However, 15% (n = 8) reported moderate-extreme LBP bothersomeness, while 9% (n = 5) were experiencing similar levels of interference with their normal work due to LBP. Sixteen percent (n = 9) had reduced normal activities over the preceding 4 weeks (mean = 1 day) and 4% (n = 2) had needed to take time off work due to their LBP (mean = 0.5 days).One factor which may partly explain our inability to identify any psychosocial predictors of poor outcome in LBP patients may be the relatively low number of participants. It is also possible that this inability relates to the practice being in the independent sector. Studies  from theThe Deyo 'Core Set' of outcome measures proposed for low back pain research  was usedDunn and Croft (2005)  found thThe proportion in our sample with work absence, however, may be untypical. Sorensen et al 2006) , conduct006 , conDespite relatively high baseline bothersomeness scores, almost all patients in this study had resolution or near-resolution 6 weeks from presentation. Only co-morbidity and complaint duration of >4 weeks prior to consultation significantly predicted low back pain bothersomeness at 6 weeks. Although in this study higher inevitability scores were a significant psychological risk factor, no others were found. Studies that seek psychosocial predictors of poor long-term outcome in private chiropractic patients from measures used in this study may not find them. Future work could helpfully address whether locus of control and self-efficacy differs between patients in the public and independent healthcare sectors and whether there is a relationship between this and outcomes.The author(s) declare that they have no competing interests.Both authors collaborated on the rationale and design of the study and liaised with the practice for the collection of data. AB carried out the note searches for co-morbidity and numbers of treatment sessions. JL carried out all data entry. Both authors participated in the analysis of data. JL wrote the first draft of the manuscript. Both authors read and approved the final manuscript.


Minimally invasive procedures such as percutaneous cementoplasty can provide immediate pain relief and can restore mechanical stability for patients with bone metastases who are not candidates for surgery or who show resistance to radiotherapy or analgesic treatment. Here, we examine a case of percutaneous cementoplasty to treat a lytic lesion of the acetabulum from breast cancer. Good filling was observed, and no complications occurred. A research assistant recorded the patient’s scores on the Karnofsky Performance Scale, Townsend Functional Assessment Scale, and Brief Pain Inventory before surgery and at days 1, 2, and 4 and weeks 1, 2, and 4 post-procedure. Improvement in pain and walking ability was demonstrated within the first 48 hours of treatment, and that improvement remained constant throughout follow-up. These findings echo the literature, in that percutaneous cementoplasty provides immediate and long-term pain relief with few complications. We recommend that percutaneous cementoplasty be used as an additional tool for palliative treatment of patients with bone metastases. Bone metastases are a frequent complication in oncologic patients, often affecting the acetabulum and producing significant pain and disabilityAn 80-year-old woman was treated with a modified radical mastectomy for stage I breast cancer in 1979. She developed chest wall recurrences in 1994 and was treated with surgical resection and postoperative locoregional radiotherapy at that time. In 2002, the patient was treated for benign anterior vertebral body compression at T12 with percutaneous vertebroplasty.ct) images of the lumbar spine and pelvis , Stouffville, ON] was advanced into the left acetabular lesion through the anterior superior iliac spine . Cement bpi)bpi is a patient-based assessment tool that evaluates worst, average, and current pain intensity on a scale of 0–10, with “no pain” and “worst possible pain” as descriptive anchors. Pain interference with functionality is measured in seven categories—general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life—on a scale of 0–10 where 0 is no interference and 10 is complete interference. Functional status was measured using the Karnofsky Performance Scale (kps) and the Townsend Functional Assessment Scale (tfas). The kps is widely used to assess functional status, level of ambulation, and ability to perform self-care in cancer patientstfas classifies patients into categories according to their functional capabilitiesThe patient was evaluated before and after the procedure for pain, functional status, and analgesic intake. The patient rated pain intensity and functional interference according to the Brief Pain Inventory . The patient was taking ibuprofen 6 times daily as needed for her osteoarthritic back pain.Pre-procedure, the patient had a kps, worst pain score, and functional interference remained unchanged; however, she claimed to feel dramatically better. Her tfas rating improved to a 2, because she was not relying on a cane to ambulate. At day 2, her tfas rating improved to a 1, and she reported a worst pain score of 2, with a score of 0 for the seven functional interference measures. These improved scores remained constant through the four subsequent follow-ups. No change in analgesic consumption was reported.Immediately post-procedure and at day 1, the patient’s Deformation of the bone because of cancer may result in stress on the periosteum, causing painet al. reported 18 patients with acetabular metastases treated with percutaneous cementoplastyet al. recorded improvement in pain in 83% of their 12 acetabular osteolytic lesion casesWeill et al. followed patients for an average of 9.4 months (range: 2–48 months) with only two incidences of pain recurrence (one at 6 months and one at 39 months), both in keeping with local tumour progressionet al.et al.These immediate improvements in pain and walking from percutaneous cementoplasty are also long lasting. Weill Our findings are consistent with the cases mentioned above. The patient experienced pain relief very quickly (within 48 hours) and remained steady for the remainder of the follow-up. Functional status and interference also improved, probably as a direct result of reduced pain and improved walking ability.et al.n = 5) and 22% (n = 4) of patients respectively. However, only 2 patients (11%) were symptomatic: one from each case of complications. Kelekis et al.et al.et al.et al.Although pain relief and stabilization of the bone are the most important objectives of percutaneous cementoplasty, it is also important that complications do not arise, because they could potentially be hazardous or result in additional pain. Weill patients % were syOsseous metastases that are resistant to traditional conservative treatment modalities such as radiation or medication (or both) present a significant problem in the management of oncology patients. Surgical procedures can be dangerous for certain subsets of patients, and the undesirable effects may outweigh the clinical benefits for those with a short life expectancyOur case echoes the literature, in that percutaneous cementoplasty of painful metastasis in the acetabulum provides immediate and long-term pain relief with few complications. We recommend that this procedure be used as an additional tool for palliative treatment of patients with bone metastases.


Prompt diagnosis of an acute coronary syndrome is very important and urgent referral to a hospital is imperative because fast treatment can be life-saving and increase the patient's life expectancy and quality of life. The aim of our study was to identify GPs' reasons for referring or not referring patients presenting with chest pain.In a semi-structured interview, 21 GPs were asked to describe why they do or do not refer a patient presenting with chest pain. Interviews were taped, transcribed and qualitatively analysed.Histories of 21 patients were studied. Six were not referred, seven were referred to a cardiologist and eight to the emergency department. GPs' reasons for referral were background knowledge about the patient, patient's age and cost-benefit estimation, the perception of a negative attitude from the medical rescue team, recent patient contact with a cardiologist without detection of a coronary disease and the actual presentation of signs and symptoms, gut feeling, clinical examination and ECG results.This study suggests that GPs believe they do not exclusively use the 'classical' signs and symptoms in their decision-making process for patients presenting with chest pain. Background knowledge about the patient, GPs' personal ideas and gut feeling are also important. Chest pain can be a sign of an ischemic or non-ischemic cardiac disease, a gastro-oesophageal or pulmonary disease, a musculoskeletal disorder or psychiatric illnesses, all of which require specific treatment -14. For Severe prolonged chest pain of acute onset accompanied by other specific symptoms is rarely a decision-making problem. Attacks of chest pain that are experienced by patients as not very severe and prolonged, but distressing enough for them to contact a general practitioner, present a more difficult problem in diagnosis and management .In a diagnostic meta-analysis, we were not able to define an important role for individual signs and symptoms in the diagnosis of acute myocardial infarction or acute coronary syndrome (ACS), except chest wall tenderness on palpation, which largely rules out those diseases in low-prevalence settings .This is confirmed by Abu Hani et al. who found that GPs use criteria not present in classical textbooks when diagnosing acute coronary syndrome (ACS), such as person-specific discrepancies between previous and actual consultations.Pauker and Kassirer defined a threshold as the disease probability at which no action changes into action , based on the balance between risks and benefits of acting versus not acting. Similarly, in patients with chest pain, the GP has to decide on referral of the patient rather than making a specific diagnosis of ACS ,17. In fHowever, little is known about the grounds on which GPs decide to refer a patient with chest pain. The aim of our study was therefore to identify GPs' reasons for referring or not referring patients presenting with chest pain.We invited 85 GPs in the first author's region  by invitation during a local CME meeting, by personal letter two months later, and by phone-call after another two months as a reminder, to participate in an interview-based study exploring why some patients presenting with chest pain were referred and others were not. To increase the number of participants, we also sent an email to 320 GPs in the region between Brussels and Antwerp. The GPs were asked to call us immediately after seeing a patient presenting with chest pain, regardless of their initial diagnosis and regardless as to whether or not the patient was referred. Cases were not limited to patients with an acute coronary syndrome, but the GPs were actively encouraged to include any patient consulting with chest pain.All interviews were carried out within at most two days after the contact, usually at the GP's office. The semi-structured interview consisted of three main questions: how does the GP act in general when seeing a patient with chest pain and what is considered important when referring or not referring a patient; how would the GP describe this specific patient and what actions were or were not undertaken for which reasons; and how does the GP cope when confronted when making an incorrect decision concerning a patient with chest pain. A more detailed list is given in Table The study was approved by the Medical Ethics Committee/Clinical Research of the Catholic University of Leuven. (ML 2378)Saturation was reached after 21 interviews with 21 GPs; GP characteristics are described in Table Fourteen of these patients were female (mean age 52). Six were not referred, seven were referred to a cardiologist (one of them refused) and eight were referred to the emergency department (one of them refused). Of those seven who accepted referral to the emergency department, three were transported by relatives, two by their GP and two by ambulance.Table All the GPs interviewed gave very personal accounts of their reasoning. All the GPs stated the importance of history taking.-And then I've actually already got an idea of what it is, before I investigate further, I'm 95% certain what it is. (GP17)The decision reasons mentioned by GPs could be divided into three general categories:the GP's background knowledge about the patient, independent of the current episode; the current clinical presentation; and the GP's personal ideas.[specific ACS] Previous coronary events and coronary risk factors were always considered important factors in the referral decision. However, two GPs mentioned that the presence of risk factors is not necessarily indicate ACS.-and given the medical history, i.e. two bypass operations, diabetes and high blood pressure, I had reason enough to think that there was something wrong with his heart again. (GP5)-..I've had patients like that in my office, people who have no risk factors at all and then have a heart attack. But that's extremely bad luck, unlike an obese diabetic who hasn't looked after himself for 20 years, who is a very high risk..(GP17)[not specific ACS] Discrepancies between previous and actual consultations were often stated as a trigger for the diagnosis of heart disease and a reason for referring.-She's normally an active woman, her house is always well cared for but that day she hadn't done a thing the whole day! So that influenced my decision. (GP2)[not specific ACS] The belief that the patient tends to play down the seriousness of his complaints was also an important factor in the decision-making process. It made the GP more suspicious about the possibility of a serious disease needing referral.-a complainer, but if there's really something physically wrong, she's so good at pretending there isn't a problem. (GP8)[specific ACS] Pain on exertion, radiating pain, oppression-like pain were of major importance for the decision. Retrosternal pain was the key for referral. Other localizations were less important.-I almost always ask if it feels tight and then I demonstrate it with my hand, like the tightening of a screwdriver, or pressure of the foot on the ribcage because I usually find that specific enough. (GP5)-I think that if the pain is not retrosternal, for example if it is lateral, there's a lot less chance of heart problems. (GP15)[specific ACS] The start, frequency and duration of the pain are used to decide on referral. Pain of longer duration, constant or very frequent pain dissuaded GPs from referring.-If it lasts longer, one hour or longer or even half a day, then I find that less alarming; it's more likely to be the result of stress or something...if it is only 5 minutes, then I'm much more likely to suspect angina than if it lasts two hours. (GP20)-Something that occurs very frequently, several times a day without being too much of a problem, means it's a lot less acute in my book. (GP7)[specific and not specific ACS] In general, GPs perform the clinical examination to rule in some diseases such as rhythm disorders, lung diseases and gastro-intestinal diseases. Chest wall tenderness is mentioned to rule in musculoskeletal diseases. But in the end, the clinical examination is not considered very influential as regards the referral decision.-Just blood pressure, and doing an auscultation as well to exclude heart arrhythmias, because you never know. A palpation of the abdomen. An auscultation of the lungs, it's rare to get thoracic pain of the lungs, so it would have to be pneumonia that causes the pain. (GP5)[specific ACS] When a GP decides to perform an ECG, it is mainly used to rule in acute coronary syndrome. In cases of an abnormal result, this was an important reason to refer. Sometimes, the combination of a normal ECG, the absence of risk factors and the presence of pain of longer duration was used to rule out ACS.-At that moment I was pretty sure that it was not an acute heart attack because I had an ECG of someone at rest, who had been complaining for a few days; I would have seen something at that moment if it had really been a heart attack. (GP5)[specific ACS] This picture was used in a positive and a negative way. If the picture was positive, urgent referral by ambulance was performed.-It actually depends a little on how the patient looks. If they are pale and sweaty, and really don't look well, then I will always call the medical rescue team. (GP2)-A young man with pain in the left hemithorax, frequent and daily shooting pain when at rest, not sharp, just a few seconds. He's not able to move during those moments and he is anxious. The clinical examination was completely normal. No ECG was taken; it's probably something musculoskeletal or perhaps nothing, just anxiety. (GP18)[not specific ACS] Without the 'typical coronary heart disease patient' picture, the appearance of the patient – their looks – was often stated as very important in the decision-making process. It is more than the combination of the signs and symptoms: it is more like a 'gut feeling'.-She came in and she was different from usual: she looked drawn. It was really striking: her countenance was so sharp. (GP2)-Basically, if it looks fishy, I refer them immediately. (GP1)[not specific ACS] Uncertainty as well as explicit certainty about an acute coronary syndrome were reasons for referring the patient.-If I'm not sure and anxious about it, then I refer. (GP4)-But I think that if I'm reasonably sure it's a heart attack, I will always call for the medical rescue team. (GP4)[not specific ACS] Younger patients were referred more readily to the emergency department than older ones. Older people were sometimes not referred because the expected benefit of the referral was considered to be limited.-For the whole of society too; why should society pay so much money if you know that the prognosis is very limited. Incidentally she died a few days later. (GP17)[not specific ACS] Some GPs objected to the attitude of these personnel, which made it more difficult to refer.-The whole scene; the sirens and waking up all the neighbours, and those men, my room is too small for them with their 5 cases and oxygen and you stand there...And when they remember to think of it, they ask if you've given the patient anything. (GP18)[specific ACS] If the patient has been given the all-clear by a cardiologist, can give the GP a false feeling of certainty about the absence of an acute coronary syndrome and influence his referral attitude.-I have to say that I hesitated a little, especially because he had been to the cardiologist a few days before and had been told everything was alright. (GP14)[specific and not specific ACS] Ten GPs mentioned an error relating to chest pain patients in the past. The reasons for the error were not recognizing ACS because of resemblance to gastric problems or chest wall tenderness on palpation; or because of the patient's behavior, e.g. the patient is always consulting with minor complaints or always complaining; and for GP-related reasons, e.g. the GP waited too long before making a home visit and the patient was transported by ambulance without the assistance of a medical rescue team. This error created various feelings such as regret and the realisation of the huge responsibility. Talking to the family is reported as being important, but the memory of the error keeps some GPs awake at night. Some GPs mentioned that an error influences subsequent decisions, in that they are more careful and their threshold for action is lower.-Then I can't go straight to sleep when I come home. I continue to think about it for a long time. (GP10)-You feel bad in a way because you made a wrong diagnosis, but I don't lie awake at night; this sort of thing happens, and then it's a case of not justifying yourself to these people, but instead having a chat with them about it. (GP21)-I have to be honest, it sometimes makes me a little over cautious as well. Then I may be too quick to refer a patient so as to be sure nothing is missed. (GP17)Background knowledge on the patient – coronary risk factors, differences in behavior, playing down the seriousness – was an important factor in the decision-making process about whether or not to refer. For those factors, knowing the patient is essential.This study suggests that the background knowledge on the patient, the patient's current clinical presentation and the GP's personal opinions are used by GPs when deciding on whether or not to refer a patient with chest pain. current clinical presentation: clinical examination in particular is used to rule in diseases other than acute coronary syndrome which need no referral. An ECG was used to confirm the presence of an acute coronary syndrome and refer the patient. A normal ECG was a reason for not referring, but only in combination with a long duration of pain and the absence of risk factors. A gut feeling is sometimes more important than the presence of individual signs and symptoms.The GP's personal ideas – the patient's age, perception of a negative attitude from the medical rescue team, recent patient contact with a cardiologist, past errors – were factors in the decision-making process. Sometimes, uncertainty about the diagnosis causes an unnecessary referral. Referring older people has a higher threshold than referring younger people because of the expected smaller benefit.The The interviews were taken very shortly after the GPs had seen a patient with chest pain. This is important, as the GPs may reinterpret their diagnostic reasoning in the light of information from a cardiologist or based on the evolution of the patient's condition.All the interviews were carried out by the principal researcher, himself a GP experienced in medical research and qualitative studies. Being a 'man of the field' and knowing the reality of the situation, certainly had an impact on the interviews, the participants and the analysis. The data were analysed by the principal researcher, who developed the initial codebook, and independently by a second researcher. The second researcher was a sociologist, who introduced a broader, non-medical perspective to the study topic.The recruitment of GPs who were willing to participate in the interviews was a difficult process. The prospect of being judged and facing possible criticism may have been a reason for non-collaboration.Loss of time – without financial compensation – could be another reason. More reminders may have been necessary. Although e-mail is an easy way to recruit GPs, the response is limited. On the other hand, the quality of the interviews of the GPs recruited by e-mail was very high.Compared to the general population of GPs in Flanders, the participating GPs were similar in age and practice organization – single-handed or group practice – but not in gender: female GPs are underrepresented in our sample. Our data did not reveal any difference in reasoning between the three females and the three trainees, and the male group of participants. Of course, gender bias is always possible. The same applies – although in reverse – for the patient population: women are overrepresented here. But female patients with chest pain may present a more diagnostic and decision-related dilemma, in which the selection of the sample does not necessarily threaten the validity of the results. In addition, in qualitative studies, the goal is not to recruit a representative sample of participants to quantify opinions, but rather to elicit all possible opinions and views on a specific subject. In our data, saturation was reached, which suggests that all important criteria were identified.In spite of the recruitment difficulties, all the interviews were conducted with highly motivated GPs. The GPs responded honestly and voluntarily to the interviewer. Although what doctors say they do is not the same as what they actually do, we believe the quality of the interviews was high . The latAbu Hani et al. identified the importance of differences in pain characteristics and the 'typical coronary heart disease patient', the patient's behaviour, the presence of standard cardiovascular risk factors and a tendency to play down the seriousness of the complaints by the patient . They weOthers have found that the 'typical' symptoms of myocardial ischemia are well known by patients . This 'tThe importance of 'certainty' and 'gut feeling' for GPs when referring patients with chest pain has already been demonstrated by Buntinx et al. ,13.We have shown in another quantitative study that, in the case of diagnostic uncertainty, 26% of the patients presenting with chest pain were urgently referred to the emergency department and 53% were not urgently referred to the specialist . In thisThe importance of the GP's gut feeling was also described by Van den Bruel et al. in her GP-based study on diagnosing serious infections in children .Our criterion that the 'perception of a negative attitude from the medical rescue team' increases the referral threshold is in line with Tod's finding, when it was demonstrated that the referral threshold decreases when the consultant was easily approachable and communicated well with the patients and the GPs .The new reasons for referral mentioned in our study should now be further evaluated for their effect in a subsequent quantitative study, in a synthesis of qualitative studies or both. Hopefully, these studies will further enhance our understanding of the referral decisions made by GPs for patients with chest pain.This study suggests that GPs believe they do not exclusively use the 'classical' signs and symptoms in their decision-making process for patients presenting with chest pain. Background knowledge about the patients, GPs' personal ideas and gut feeling are also important. What is already known on this subject- In general practice the low prevalence, the early and often diffuse stages of coronary heart disease are factors making this diagnosis difficult.- Discrepancies between previous and actual consultations alert the GPs to coronary heart diseases.- Based on the threshold theory of Pauker and Kassirer, the GP has to decide whether or not to refer a patient consulting with chest pain.What this study addsReasons for referral of patients presenting with chest pain were the GP's background knowledge on the patient, the patient's clinical presentation and the GP's personal opinions and ideas. In particular, a change in behaviour, typical presentation, a GP's gut feeling, and the perception of a negative attitude from the medical rescue team influence a GP's referral decision. Clinical examination is used to exclude and an ECG to include the possibility of an acute coronary syndrome.The authors declare that they have no competing interests.RB, AV, FB and BA designed the study. RB conducted the interviews. RB and EA analyzed the data. RB wrote the first draft of the article. AV, FB, KH and BA provided substantial subsequent contributions. BA supervised the study design and analysis. All authors read and approved the final manuscript. RB is guarantor.The pre-publication history for this paper can be accessed here:


Sparse literature documenting the location of pain at the onset of migraine attacks and during established headaches is available.A prospective study (2003–05) on 800 adult migraine patients , 2:1.1, 1.2.1 and 1.6.1) was conducted to document (a) sites of onset of pain and (b) location of pain during established attacks (in >50% occasions) through semistructured interviews.N = 800; M:F = 144:656 (1:4.56); age, 16–42 years ; duration of migraine, 1–18 years . 87% of the subjects were ethnic Bengalis from the eastern Indian state of West Bengal, Calcutta being the capital city.(on the basis of >50% headache spells): N = 800; 1.1:668 (83.5%); 1.2.1:18 (2.25%); 1.6.1:114 (14.25%).Unilateral onset was present in 41.38% of the patients; of these, 53.17% had eye pain; 8.16%, frontal pain and 38.67%, temporal pain. In 32.25% of the patients, bilateral/central location of pain, mostly bitemporal or at vertex was noted. Cervico-occipital pain onset was noted in 26.43% patients .In 47.4% of the patients, with unilateral ocular or temporal onset, pain remained at the same site. Pain became hemicranial in 32.9%. In most patients, unilateral frontal onset pain (55.5%) became bilateral or holocranial. Most bilateral ocular (69.4%) and temporal onset (69.7%) pains remained at the same location. However, most bifrontal (55.6%) and vertex onset (56.9%) pains subsequently became holocranial. Most occipital pains at onset became holocranial (45.3%), but cervical pains subsequently became either hemicranial (38.3%) or holocranial (36.2%).This study documents location of pain at the onset and during established headaches in migraine patients largely from a specific ethnic group. Migraine with aura appears to be rare among ethnic Bengalis in eastern India. More than half had onset pain bilaterally/centrally and in the cervico-occipital regions. Only 40.5% experienced only unilateral pain. Cervico-occipital migraine pain appears to be common in ethnic Bengalis. This notion has perpetuated through centuries, and a unilateral location of pain has been included in the diagnostic criteria of migraine  by the International Headache Society (IHS) according to the International Classifications of Headache Disorders (ICHD-1 and ICHD-2) conducted in 1988 and 2004, respectively.14 Experieut aura).6 These aut aura). These obThe present study was carried out between September 2003 and December 2005 at the neurology outpatients department (tertiary care center) of a large general hospital (550 beds) in Calcutta in eastern India, which is largely dominated by ethnic Bengali population. We assessed a total of 1172 adult patients (>15 years of age) by using a semi-structured questionnaire; these patients were diagnosed with episodic migraine attacks and experienced at least 2 attacks of acute migraine every month during the preceding 6 months of enrollment and were not on any form of prophylactic medication for the same period. Diagnoses of migraine and migraine subtypes were made according to the ICHD-2 criteria available on the web in 2003 and later published in February 2004. The assessment was made through several stages.At the first visit, each patient was evaluated by one of the three participating consultants (authors) to confirm the diagnosis of migraine, identification of subtype and arranging relevant investigations to exclude secondary headaches as and when required (imaging performed in 162 patients and showed positive result in only two patients).During the second visit, one week (on average) later, each patient was evaluated using a semi-structured questionnaire by a trainee physician specifically assessing the site of location of the onset pain and its subsequent location during established attacks in the majority (>50%) of headache spells in the preceding six months. The patients were requested to place their hands at the sites of onset pain, indicate with their hands the subsequent spread of the pain (if possible) and finally the location of pain during the established phase of the headache. Descriptions of the terminologies associated with anatomical sites are presented at the end of this section.During a third visit, usually a month later, each patient was asked the same question regarding the location of pain by one of the authors (consultants) and the responses compared to those given in the interview by the trainees. In subjects in whom some discrepancies were noted between the two responses, the patients were offered the first responses and given the choice to be really specific. At this stage, patients (n = 102) providing grossly discrepant and vague responses  were excluded from the study. Moreover, patients who failed to turn up for the second or third stage of interview (even after reminder) were excluded at this stage.Finally, all response sheets were carefully evaluated by the corresponding author and only the first 800 subjects providing consistent (or near consistent) responses to questions associated with pain localization both at the onset and during the established phase of headache, were included for analysis.The study includes only patients with episodic migraine and not those presenting with chronic migraine (ICHD-2 criteria). Pain in most of these patients was found to be rather poorly localized at the onset and during the ongoing headache phase.Description of terms used for anatomical sites for the location of pain:1.Ocular:Eye/Orbit2.Frontal:Unilateral – one side of forehead Bifrontal – whole of forehead3.Temporal:Unilateral/Bilateral temporal region4.Hemicranial:Unilateral temporal and parietal regions; may involve ipsilateral frontal/orbital regions and occasionally ipsilateral occipital area5.Vertex/Central:Center of the cranium6.Occipital:Back of head above hairline – generally both sided7.Cervical:Back of neck below hairline – generally both sided8.Holocranial:Whole forehead, temporal and parietal as well as central cranial area and occipital regionIt may be noted that, while noting the location of pain, especially at the onset, the area mostly affected was taken into account. For example, pain involving one side of forehead but extending slightly into the temporal region, had been designated as frontal onset and similarly vice versa. Indeed, this may be somewhat artificial, but this was necessary for simplifying the final analysis a little but maintaining its significance.The demographic and ethnic characteristics of the subjects are described in Our main observations were the following: migraine with aura is uncommon in Indian patients, especially amongst ethnic Bengalis in eastern India . ApproxThe present study was carried out among adult migrain patients attending the neurology outpatient department of a general teaching institution and comprised largely (87%) of subjects belonging to a specific ethnic origin . It appears that apparently no previous study on clinical aspects of migraine has taken into account the ethnicity of the subjects.Apart from Kelman's recent report, no otherThere are two important observations that deserve special attention. In Indian patients with migraine , only unilateral headache occurred in only 40.5% patients and true hemicranial headache  occurred in only one-fifth of all the subjects on most (>50%) occasions of migraine attacks. These f10et al,[The location of migraine pain at the onset in the cervico-occipital region (noted in over a quarter of subjects in the present series) is noteworthy, especially the occurrence of predominantly cervical location in over 10% of subjects. This had not been adequately addressed to in the western literature, although Kelman did note this in a recent communication. Indeed, et al, but the Most migraine pains noted in the present series appeared to have an ‘anterior’ location, as noted in nearly all studies conducted in the West. This would be consistent with the generally agreed pathophysiology of migraine with trigeminovascular activation involving the first division of the trigeminal nerve. Kelman suggesteIt is expected that similar clinical studies associated with the location of migraine pain would be carried out in different geographic regions and in different ethnic groups to highlight global variability in the phenotypic expression of this common disorder.


Previous meta-analysis suggested that transdermal fentanyl was not inferior to sustained-release oral morphine in treating moderate-severe cancer pain with less adverse effects. Now, we updated the data and performed a systematic review.Updated cohort studies on transdermal fentanyl and oral morphine in the treatment of cancer pain were searched in electronic databases including CBMdisc, CNKI, VIP, Medline, EMBASE and Cochrane Library. Primary end points assessed by meta-analysis were remission rate of pain and incidence of adverse effects. Quality of life was assessed by systematic review, which was the second end point.32 cohort studies, which included 2651 patients, were included in present study. The remission rate in transdermal fentanyl group and sustained-release oral morphine group were 86.60% and 88.31% respectively, there was no significant difference . Compared with oral morphine group, there were less adverse effects in terms of constipation , nausea/vomiting , and vertigo/somnolence  in transdermal fentanyl group. Six of selected trials supported either transdermal fentanyl or sustained-release oral morphine improved QOL of cancer patients and one of them showed more patients got better QOL after sustained-release oral morphine transferred to transdermal fentanyl.Our study showed again that both transdermal fentanyl and oral morphine had the same efficacy in the treatment of moderate-severe cancer pain in Chinese population, but the former might have less adverse effects and better quality of life. For patients with cancer, up to 70% suffered from pain caused by their disease or its treatment . For patSince the 1980s, treatment of cancer pain was based on the WHO analgesic ladder. Strong opioids were classified at the highest step of the analgesic ladder. But studies of cancer pain control consistently revealed that up to half of patients received inadequate analgesia and 30% did not receive appropriate drugs for their pain . More details were shown in Table Data on main adverse effects was summarized in the additional file Six of selected trials were included to systematic review of QOL ,17,32-34In the funnel plot, the selected trials were plotted by the RR of the endpoints for meta-analysis and SE (logRR) as abscissa and ordinate. Small sample studies scattered widely at the bottom of the graph, while the spread narrowed for larger sample studies. Funnel plot was symmetrically distributed, and there was no influence of publication bias in our study Figure .Sensitivity analysis should be used to analyze stability of data when heterogeneity existed among selected trials. A single study involved in the present meta-analysis was deleted each time to reflect the influence of the individual data-set to the pooled RRs of constipation and nausea/vomiting, and the corresponding pooled RRs were not materially altered (data not shown).Opioids were main drugs for managing pain according to WHO analgesic ladder. Oral morphine is generally accepted to be the drug of choice for maintenance therapy of moderate-severe cancer pain. But transdermal fentanyl is challenging the position because of its convenience, relative lower incidence of constipation and higher compliance of patients reported in clinical trials -44. ClarIn our meta-analysis, transdermal fentanyl and oral morphine were effective in controlling moderate-severe cancer pain. 86.60% patients with cancer pain would experience 50% or greater pain reduction by transdermal fentanyl, in contrast, 88.31% for oral morphine, but it didn't reach significant difference . The result supported NCCN guideline (adult cancer pain-V.1.2009) that transdermal fentanyl and oral morphine were alterative drugs for maintenance therapy of stable moderate-severe cancer pain. In other words, both drugs were also effective in treating moderate-severe cancer pain in Chinese population, which might suggest both of opioids have no race choose.P < 0.05). Constipation caused by opioids was irreversible and even severely influenced QOL, but other adverse effects were reversible after 1-2 weeks use of opioids. Therefore, constipation is a common reason for patients refusing to continue to use opioid analgesics. Because of the less adverse effects, especially for constipation, transdermal fentanyl might be easier to improve QOL. In present study, 6 trials reported data on QOL and showed either transdermal fentanyl or sustained-release oral morphine improved QOL of cancer patients [Adverse effect and QOL might be more important indications for choosing drug when the therapeutic effect was similar between two drugs. In our meta-analysis, transdermal fentanyl caused less adverse effect compared with oral morphine, which the risk reduced 65% in constipation, 43% in nausea/vomiting and 41% in vertigo/somnolence. All reached significant difference . In general, an IPD-based meta-analysis would give a more robust estimation for the association; therefore, we should interpret the results with care, especially for a positive result. Clearly, further investigations using IPD should be conducted to examine the main end points. Second, all selected trials were cohort studies, which is not most suitable clinical trial to explore the difference of two drugs. Third, heterogeneity existed among the trials when pooled analysis of adverse effects (constipation and nausea/vomiting), fortunately, the data was not materially changed in sensitivity analysis. Fourth, side effects seemed to be lower in our selected trials compared with clinical practice. We thought that these results might be explained in two aspects of small sample in single trial and better tolerance in Chinese population. At last, transdermal fentanyl takes 12-24 hours for serum levels to stabilize after starting the patch and dose increment was trouble in clinic practice, so it is less flexible and needs to be used with caution in patients with unstable pain.In summary, the present study supported that transdermal fentanyl and sustained-release oral morphine were effective for maintenance therapy of moderate-severe cancer pain in Chinese population, and the former might have less adverse effects. Our results were similar with European and American data, which might suggest that both of opioids have no race choose. In addition, our data suggested transdermal fentanyl might improve QOL more easily. Well-designed randomised control trials should be further conducted in this area.CBMdisc: Chinese Biomedical Literature Analysis and Retrieval System; CNKI: China National Knowledge Infrastructure; VIP: Chongqi VIP Information; QOL: quality of life; RR: risk ratio; SE: standard error; WHO: World Health Organization; NCCN: National Comprehensive Cancer Network; IPD: individual patient data.The authors declare that they have no competing interests.DRX and QY contributed to the conception and design of the study; QY, DRX, and ZMJ contributed to collection and assembly of data; DRX, QY, ZMJ, WM, YDZ, ZFB, and DLC contributed to data analysis and interpretation; QY and DRX contributed to manuscript writing. All authors have read and approved the final manuscript.Characteristic of Eligible Cohort Studies.Click here for fileForest plots.Click here for file


Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis.We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM) and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS) for spasticity, pain and ease of care.A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options.RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial. Cerebral palsy (CP) is a central nervous system deficit resulting from a non-progressive lesion in the developing brain. Although these brain lesions are static, the movement disorders that arise are not unchanging and are characterised by atypical muscle tone, posture and movement . The spaAn alternative for the SDR is a radiofrequency lesion of the dorsal root ganglion (RF-DRG), which has been used to treat chronic pain for over 30 years . The RF-We thus hypothesized that an RF-DRG may alleviate spasticity and pain in CP patients, and we tested this hypothesis in a pilot study of 17 patients.Children with spasticity from CP were seen by a multi-disciplinary spasticity management team  in the Maastricht University Medical Centre. Individual treatment goals were determined after a careful assessment of the aetiology, functional ability and associated impairments as a result of the spasticity. The RF-DRG treatment was considered in children with severe hip flexor/adductor spasms accompanied by pain or care giving difficulties. The procedure was approved by the Institutional Review Board of the Maastricht University Medical Centre, according to Dutch governmental regulations and informed consent from the caregivers was obtained for each patient.A total of 17 children were treated with RF-DRG tables . The sevSix children (group A) were systematically evaluated at baseline, and 1 month and 6 months after treatment table . In thisThe following 11 children (group B) were evaluated at 6 weeks and 3 months using a Visual Analogue Scale (VAS), which was used to measure the severity of the individually formulated problems. We changed the evaluation methods, as we were not able to detect the kind of change that the caregivers unanimously did notice. Furthermore, we learned from literature that the MAS and the GMFM are not indicated to measure changes in these severely handicapped children -29. InstAll patients were treated in our outpatient clinic, and RF-DRG was performed as described ,13,35. UThe procedure was performed in tunnel vision, a technique for entering the electrode in the direct vision of the X-rays. Therefore, the C-arm (Ziehm electronics) was adjusted in such a way that the X-rays ran parallel to the end plates of the relevant level. Thereafter, the C-arm was rotated until the processus spinosus projected over the contralateral facet column. With the C-arm in this projection, the injection point was found by projecting a metal ruler over the lateral part of the foramen intervertebrale.A 10-cm long, 22-G needle SMK-5 mm tip was inserted locally in the direction of the X-rays. Thereafter, the direction was corrected in such a way that the needle was being projected as a point on the screen. The direction of the radiation beam was now modified to a profile  view, and the needle was inserted until the point was located in the craniodorsal part of the foramen intervertebrale Figure .In an AP view, the course of a small amount of contrast agent was followed with "real-time imaging"; it should spread out laterocaudally along the spinal nerve Figure . The styA total of 19 RF-DRG treatments were performed in 17 patients. One patient received three interventions, as the effects gradually wore off. A summary of the clinical data, including treated levels and outcome measures, are given in table In the first six systematically evaluated children table  an improUsing the GMFM no improvement was observed after RF-DRG treatment. At baseline a mean total score including all 5 domains of 17.2% +/- 6 was found. After 4 weeks the score was 17.3% +/- 7 and after 6 months the score was 16.2% +/- 6.Using the caregiver's questionnaire, an improvement in ease and quality of care and pain was detected. Although statistically not significant, in four patients pain in the lower extremities decreased, at both 4 weeks and 6 months. In one patient there was no change in pain and in another patient pain increased at 4 weeks but decreased at 6 months when compared to the baseline.Because of the abovementioned results we switched to a VAS to evaluate the initiated treatment in the subsequent patients. This score was available in 8 out of the 11 patients. The missing values are due to the fact that some caregivers did not feel comfortable judging their own child in a numerical way. During outpatient follow up, the evaluation of the VAS scores showed improvement in most of the defined goals in most children table . Most paIn one patient (no. 9), the VAS score showed no change after the third procedure. Her flexor spasms were then successfully treated with Botulinum Toxin-A injections in the iliopsoas and adductor muscles .To test our hypothesis that RF-DRG may be a serious treatment option for severe spasticity in children with CP, we undertook a pilot study in 17 patients. Our primary treatment goal was improvement of well-being and ease of care of CP patients with severe hip flexor/adductor spasms and pain. Our first 6 consecutively treated patients (Group A) were evaluated at baseline, 1 month after treatment and 6 months after treatment with the GMFM and the MAS. We found a small improvement in muscle tone by the MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG  and pulsed radiofrequency current [The exact mechanism of action of an RF-DRG lesion remains unknown. We recently reported an increase of proliferation inside the dorsal root ganglion after RF-DRG adjacent to the ganglion without signs of neural tissue damage (e.g. necrosis) inside the ganglion . For yea current . In one  current . ReductiOur pilot study on RF-DRG in 17 CP patients with severe hip flexor/adductor spasms and pain shows that it may improve spasticity, pain, and ease of care, with a duration of up to 9 months. As the amount of improvement is in the same range as in conventional treatments, RF-DRG is thus a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial. The main advantages are the less invasive character of RF-DRG compared to the SDR with the potential benefit of a shorter hospitalisation period, and its clear pain-reducing effect.The authors declare that they have no competing interests.JV originated the idea, is a member of the multi-disciplinary working group and together with LR and HS selected the patients. HS and LR are also members of the multi-disciplinary working group and together with GV they scored hip classification (inter-observer agreement with each other). MK and JZ performed the procedure. DS is the supervisor of the multi-disciplinary working group and provided the date for GV which he analysed together with AL. GV wrote the article under supervision of AL, WW and JV. MK en JV participated in writing the methods-sections of the article. AL, HS, KG and WW have revised the manuscript critically for important intellectual content. JV is the final supervisor of the study and manuscript.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/10/52/prepub


Duloxetine hydrochloride is a reuptake inhibitor of 5-hydroxytryptamine and norepinephrine used to treat depression, generalized anxiety disorder, neuropathic pain, and stress incontinence in women. We investigated the efficacy of duloxetine in painful diabetic neuropathy and fibromyalgia to allow comparison with other antidepressants.We searched PubMed, EMBASE (via Ovid), and Cochrane CENTRAL up to June 2008 for randomised controlled trials using duloxetine to treat neuropathic pain.We identified six trials with 1,696 patients: 1,510 were treated with duloxetine and 706 with placebo. All patients had established baseline pain of at least moderate severity. Trial duration was 12 to 13 weeks. Three trials enrolled patients with painful diabetic neuropathy (PDN) and three enrolled patients with fibromyalgia. The number needed to treat (NNT) for at least 50% pain relief at 12 to 13 weeks with duloxetine 60 mg versus placebo  was 5.8 (95% CI 4.5 to 8.4), and for duloxetine 120 mg  was 5.7 (4.5 to 5.7). There was no difference in NNTs between PDN and fibromyalgia. With all doses of duloxetine combined (20/60/120 mg) there were fewer withdrawals for lack of efficacy than with placebo ), but more withdrawals due to adverse events (number needed to harm (NNH) 15 (11 to 25)). Nausea, somnolence, constipation, and reduced appetite were all more common with duloxetine than placebo . The results for duloxetine are compared with published data for other antidepressants in neuropathic pain.Duloxetine is equally effective for the treatment of PDN and fibromyalgia, judged by the outcome of at least 50% pain relief over 12 weeks, and is well tolerated. The NNT of 6 for 50% pain relief suggests that this is likely to be a useful drug in these difficult-to-treat conditions, where typically only a minority of patients respond. Comparing duloxetine with antidepressants for pain relief in DPN shows inadequacies in the evidence for efficacy of antidepressants, which are currently recommended in PDN care pathways. Neuropathic pain is the consequence of damage to the central nervous system  or peripheral nervous system (e.g. painful diabetic neuropathy (PDN), postherpetic neuralgia (PHN), surgery). It has a significant negative impact on quality of life . Some paThe incidence of PHN and trigeminal neuralgia and PDN together is almost 0.1% per year in the UK . The incThe most common pharmacological approaches to the management of neuropathic pain include antidepressants , antiepileptics , opioids, other analgesics, topical lidocaine patch, and topical capsaicin. The evidence for these has been reviewed extensively ,8-16.5-hydroxytryptamine (5HT) and norepinephrine (NE) are involved in the modulation of endogenous analgesic mechanisms via descending inhibitory pain pathways in the brain and spinal cord . DisinhiDuloxetine hydrochloride is a serotonin-norepinephrine reuptake inhibitor used to treat depression, generalized anxiety disorder, neuropathic pain, and stress incontinence in women. We investigated the efficacy of duloxetine in the management of PDN and fibromyalgia as duloxetine had not been included in the most recent systematic reviews, including one of antidepressants . DuloxetWe searched PubMed, EMBASE (via Ovid), and Cochrane CENTRAL up to June 2008 for randomised controlled trials using duloxetine to treat neuropathic pain. The detailed search strategy included use of the drug name "duloxetine" anywhere in an article, together with "randomized controlled trial" as subject heading, publication type or text word; this was modified appropriately for different databases. Reference lists of retrieved articles and reviews were also searched for relevant trials. We contacted Boehringer Ingelheim Limited as a UK distributor for duloxetine in neuropathic pain to enquire about relevant published or unpublished studies, and examined an on-line register .Included trials had to be randomised, double blind, placebo controlled, and use duloxetine to treat adult patients with painful neuropathies of any cause. Trials had to have a minimum of 10 patients per treatment arm, and a planned duration of at least four weeks.The abstracts were read, and potentially useful reports retrieved in full. No information was taken from posters or abstracts. Decisions on inclusion or exclusion of trials, assessment of trial quality and validity and all data extraction were made independently by three reviewers, with discrepancies resolved by consensus.Methodological quality of included studies was assessed using a validated 5-point scale  utilisinData were abstracted into a standard form. Information extracted from the trials included details of the patients , duloxetine dose, and permitted rescue analgesia. The primary outcome sought was 50% pain relief. Other measures of pain relief were abstracted where reported. Secondary outcomes were withdrawals  and adverse events .Guidelines for quality of reporting of meta-analyses were followed where appropriate . The pri• When significantly more beneficial outcomes occurred with duloxetine than placebo, we used the term number needed to treat (NNT).• When significantly fewer adverse events occurred with duloxetine than placebo we used the term the number-needed-to-treat to prevent one adverse event (NNTp).• When significantly more adverse events occurred with duloxetine than placebo we used the term the number-needed-to-harm to cause one adverse event (NNH).Statistical significance of any difference between NNT for different doses was assumed if there was no overlap of the confidence intervals, and additionally tested using the z statistic . RevMan We identified six trials satisfying the inclusion criteria -35. DetaTrial duration was 12 to 13 weeks. One trial  had a 13Trials were of good methodological quality, with three scoring 5/5, two scoring 4/5, and one scoring 3/5 on the Oxford Quality Score . Two scoAll six trials reported the outcome of at least 50% pain relief over baseline in the 24-hour average pain score by the end of the trial, and results are summarised in Figure Five of the trials used 60 mg, and all six used 120 mg; only 66 patients (in two treatment arms) received the 20 mg dose. The dose of duloxetine made little difference to the result . The proportion of patients with this outcome was slightly lower for both placebo and duloxetine groups in the fibromyalgia trials Table , with siFive of the trials -35 recorWithdrawals for any cause occurred in slightly more patients with duloxetine (30%) than placebo (28%); the NNTp for all cause withdrawal with duloxetine rather than placebo was 26 13 to 426)  than placebo (8%). The NNH was 15 (11 to 25) (Table 5% than pThe "at least one adverse event" criterion was met in significantly more patients taking duloxetine (82%) than placebo (67%) in the four trials that reported this outcome. The NNH was 6.7 5.0 to 10)  than with placebo (24%) over 12 weeks. The outcome of 50% pain represents substantial clinical pain relief, and an NNT of 6 suggests that this is likely to be a useful drug in these difficult-to-treat conditions, where typically only a minority of patients respond. There was no dose response between 60 mg and 120 mg, nor was there any significant difference in the duloxetine response between PDN or fibromyalgia. There was a similar lack of dose response in this range for use of duloxetine in major depressive disorder .Duloxetine was well tolerated in the trials, with fewer withdrawals due to adverse events with 60 mg than with 120 mg. Most adverse events were reported to be mild or moderate, with nausea, somnolence, constipation, decreased appetite and dry mouth frequently mentioned. In stress incontinence duloxetine affects the resting tone and contraction of the urethral striated sphincter muscle. It might be expected to cause symptoms of urinary hesitancy in patients without incontinence, but urinary problems were not reported in any of these trials, or in trials of duloxetine in depression .This review has some limitations. Firstly, pain intensity measurements used to calculate our primary outcome of at least 50% pain relief were derived from average pain intensity scores during the previous 24 hours. Secondly, the trials were 12 to 13 weeks in duration, and although they demonstrated a sustained response and good tolerability over this period, they provided no information for longer-term efficacy or safety. Russell et al  includedDuloxetine has been widely trialled in other conditions, in particular depression and stress-induced incontinence in women, and the many trials have been subject to systematic review in those therapeutic areas. An evaluation of cardiovascular safety in 42 placebo controlled trials involving 8,500 patients concluded that duloxetine did not appear to be associated with significant cardiovascular risks .Finally, the studies in fibromyalgia included some patients with depression. Although only a minority were depressed (Additional file The quantity and quality of randomised trial data in neuropathic pain is limited. Table Several evidence-based recommendations for the treatment of neuropathic pain place use of antidepressants early in any care pathway ,9,50. CoDuloxetine is equally effective for the treatment of PDN and fibromyalgia, judged by the outcome of at least 50% pain relief over 12 to 13 weeks, and is well tolerated. The NNT of 6 for this outcome suggests that this is likely to be a useful drug in these difficult-to-treat conditions, where typically only a minority of patients respond. Doses higher than 60 mg do not provide additional pain relief, but do cause slightly more withdrawals due to adverse events. Comparing duloxetine with other antidepressants for pain relief in PDN shows inadequacies in the evidence for efficacy of antidepressants, which are currently recommended in PDN care pathways.RAM, and SD have received research support from charities, government and industry sources at various times, and HG from government, but no such support was received for this work. No author has any direct stock holding in any pharmaceutical company.AS, SD and HG carried out searches, selected studies and carried out data extraction. AS, SD and AM were involved with analysis. All authors were involved with writing, and all authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Included studies. Details of the design and outcomes of the included studies.Click here for file