The efficxacy of triptans for acute migraine has been well established in clinical trials but not in primary care, where they are most commonly prescribed. The aim of this open-label study was to evaluate the effectiveness of eletriptan 40 mg in primary care, using a patient-weighted satisfaction scale.Eligible patients met International Headache Society criteria for migraine, with 1–6 attacks per month. Patients completed questionnaires at screening and following a single eletriptan-treated attack. Treatment satisfaction was evaluated using a six-item Medication Satisfaction Questionnaire (MSQ). MSQ item scores were weighted, based on the important score ratings, to yield individualised satisfaction scores. The primary end-point was the difference in weighted satisfaction scores between the patient's previous treatment and eletriptan 40 mg. Secondary end-points assessed quality of life (QOL), functioning and efficacy of treatment.Of 590 patients screened, 437 completed the study. Degree (95.2%), time (88.8%) and duration (83.8%) of headache pain relief were rated as most important by patients. The mean (±SD) total satisfaction score on the MSQ was higher for eletriptan than previous therapy . The high level of satisfaction with eletriptan vs. previous treatment reflects the improvements in QOL and functioning observed, and the high headache and pain-free response rates.Patient-weighted satisfaction with eletriptan 40 mg was higher than with previous treatment for all items. The use of patient-weighted importance ratings of satisfaction is a promising approach for establishing effectiveness of treatment in primary care. Previous studies have highlighted the treatment outcomes that are most important to migraine sufferers . Asking patients to rate their treatment in terms of the treatment outcomes that are most important to them has been suggested as a useful way of assessing the effectiveness of a treatment in primary care.The efficacy of triptans  in treating acute migraine attacks has been established from the results of approximately 100 double-blind, randomised, parallel-group trials , improvement in migraine-associated symptoms , and risk of side effects. This method for rating the importance to the patient of each clinical outcome has been proposed –10, but The aim of this open-label study was to investigate the utility of patient-weighted outcomes for evaluating the effectiveness of eletriptan in the acute treatment of migraine, in a primary care setting.Men and women aged 18–65 years were eligible for inclusion in the study if they met International Headache Society criteria for migraine with or without aura , with anKey exclusion criteria were: (i) the presence of migraine with prolonged aura, familial hemiplegic migraine or migrainous infarction; (ii) any acute or unstable medical condition, clinically significant laboratory test or electrocardiography (ECG) abnormality, or presence of any illness or treatment known to be a contraindication to the safe use of eletriptan as summarised in the US prescribing information label; (iii) the misuse or abuse of alcohol or other substances, based on the Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria; and misuse of analgesics  or ergotamine (defined as use on > 2 days per week).This open-label, single-attack, outpatient study was conducted at 185 primary care practices in the USA between August 2003 and May 2004.At the screening visit, patients with a history of disabling headaches completed the three-item ID Migraine™  questionnaire, a validated self-administered instrument that assesses the presence of nausea, photophobia and headache-related disability . Those wTo assess their perceptions of previous treatments used, patients were asked to complete three baseline questionnaires at the screening visit: (i) Migraine Relief Questionnaire (MRQ), (ii) Medication Satisfaction Questionnaire (MSQ) and (iii) Migraine Quality of Life Questionnaire (MQOLQ). The MRQ and MSQ are shown in A medical evaluation consisting of a physical examination, measurement of vital signs, a 12-lead ECG and urine pregnancy testing (as appropriate) was also conducted at screening.Enrolled patients were provided with two tablets of eletriptan 40 mg and a headache diary. Patients were instructed to treat a single migraine attack in the following 12 weeks with eletriptan 40 mg, taking it as soon as they were certain they were experiencing a migraine, after the aura phase (if present) had ended and the headache phase had begun . If migraine symptoms recurred within 24 h postdose, a second dose of eletriptan 40 mg was allowed, provided at least 2 h had elapsed after taking the first dose. Rescue medication was also permitted if subjective headache relief was inadequate.Patients recorded the date and time of onset of their eletriptan-treated migraine immediately postattack, and completed two questionnaires: (i) the MQOLQ, to assess QOL associated with eletriptan use 24 h after first dose and (ii) the Functional Assessment in Migraine, Activities and Participation Scale (FAIM-A&P), a validated scale derived from the World Health Organization's International Classification of Impairments, Disability and Handicaps (ICIDU-2) , which aPatients were instructed to return to the study centre within 2 weeks of their eletriptan-treated attack to complete two further questionnaires: (i) the MSQ, to assess treatment satisfaction with eletriptan 40 mg and (ii) a migraine treatment preference questionnaire, which asked patients about their overall migraine medication preferences.At study conclusion investigators rated, on a seven-point scale (where one = very dissatisfied and seven = very satisfied), their satisfaction with ID Migraine™ as a tool to: (i) identify migraine sufferers, (ii) help patients to clearly and effectively communicate their symptoms and (iii) improve patient–physician dialogue related to headache diagnosis.The primary end-point was the difference in satisfaction between a patient's previous migraine treatment and eletriptan 40 mg, as measured on the six weighted items of the MSQ. The secondary efficacy end-points were: (i) the MQOLQ; (ii) the FAIM-A&P; (iii) 2-h headache response, defined as improvement in headache intensity to mild or no pain from a pretreatment level of moderate or severe, rated on a four-point global intensity scale ; (iv) 2-h pain-free response, defined as improvement to no pain at 2 h postdose following a pretreatment pain level of moderate or severe, on the four-point scale; (v) sustained headache response at 48 h postdose, defined as response within 2 h of the first dose of study medication, no headache recurrence, no use of rescue medication and no second dose of eletriptan within the remainder of a 48-h period; (vi) sustained pain-free response at 48 h defined as pain-free response within 2 h of the first dose of study medication, no headache recurrence, no rescue medication use and no second dose of eletriptan within the remainder of a 48-h period; (vii) patient drug preference, as indicated by the migraine treatment preference questionnaire; and (viii) investigator satisfaction with the ID Migraine™ screener. Tolerability was also assessed.As this was an open-label, single-attack study, descriptive statistics were calculated, but no significance testing was performed.The averaged MSQ scores were weighted based on the importance values assigned to specific treatment attributes at the screening visit using the three-point MRQ. The MSQ item scores were multiplied by one if the patient rated the outcome item as ‘not so important’, two if the patient rated the item as ‘important’ or three if the patient rated the item as ‘very important’. To aid in the interpretation of the satisfaction score, the MSQ scores were re-coded from a one to five rating to a −6 to +6 rating, where the lowest number corresponded to a rating of ‘very poor’ and the highest number corresponded to a rating of ‘excellent’. Descriptive statistics (mean and standard deviation [SD]) for the weighted scores and the weighted difference scores were calculated.t-test was used to assess the change from baseline to 24 h postdose.Descriptive statistics were performed on the MQOLQ individual and the total domain scores, and a paired t-test was performed to test the change from baseline to 2 and 4 h postdose.A standard score was calculated for each patient from the FAIM-A&P scale as follows: (i) the rating scale was reversed  and (ii) the score on each item was summed to obtain a raw total score. The raw total score was subsequently transformed to a standardised score of 0–100, with a higher value indicating improved functioning. A paired The study was conducted according to the Declaration of Helsinki (1996 revision) and is consistent with the International Conference on Harmonization Good Clinical Practice guidelines . The pron = 437).Five hundred and ninety patients were screened, of whom 582 met eligibility criteria and were entered into the study. The safety sample consisted of 481 patients who took study medication, while the intent-to-treat sample consisted of all patients who took study medication and completed the MSQ postdose , followed by time of pain relief (88.8%) and duration of pain relief (83.8%) . ResultsTreatment with eletriptan 40 mg vs. usual previous treatment was associated with higher weighted satisfaction scores overall and on the six individual items of the primary outcome measure, the MSQ .For the total sample, the proportion of patients reporting treatment satisfaction as ‘good-to-excellent’ was significantly higher on eletriptan compared with usual previous treatment on the first five MSQ treatment satisfaction items  FAIM-A&P score was 23.2 ± 23.3, a score consistent with clinically significant migraine-related impairment in functioning. At 2 h postdose, the mean FAIM-A&P score had increased by 31.5 points to 54.7 ± 34.5, thus functional impairment was significantly reduced (p ≤ 0.001). At 4 h, the score showed a further increase to 67.7 ± 36.4.n = 437), 62% [95% confidence interval (CI): 51–60%] of patients experienced 2-h headache response and 36% (95% CI: 31–40.3%) experienced 2-h pain-free response. Headache response was sustained over 48 h in 33% (95% CI: 25–46%) of patients, and a pain-free response was sustained in 23% (95% CI: 14–31%).For the total sample  preferred eletriptan 40 mg to all previous acute migraine treatments they had used.One hundred and forty-three investigators rated their satisfaction with the ID Migraine™ screener at study conclusion. Satisfaction was extremely high on all items assessed. One hundred and twenty-nine investigators (90%) were ‘satisfied’ or ‘very satisfied’ with the assistance provided by ID Migraine™ in identifying migraine sufferers, 126 (88%) were ‘satisfied’ or ‘very satisfied’ with how ID Migraine™ helped their patients to clearly and effectively communicate their symptoms, and 129 (90%) were ‘satisfied’ or ‘very satisfied’ that ID Migraine™ improved patient–physician dialogue related to headache diagnosis.Only one adverse event, nausea (2.1%), occurred with an incidence ≥ 2%. Overall, 10.8% of patients on eletriptan reported having at least one adverse event. Five patients (1.0%) rated their adverse events as ‘severe’. There was one serious adverse event, which was not treatment related (a patient was involved in a motor vehicle accident 3 days after taking eletriptan). No patients discontinued treatment because of an adverse event. There were no clinically significant changes in laboratory tests, vital signs or ECG during the study.a priori end-point.We report here the results of an open-label, single-attack study that used patient-centred ratings of treatment satisfaction as the primary outcome. To our knowledge, no previous trial has utilised weighted satisfaction to assess the primary, The MRQ indicates that the three most important treatment outcomes for patients were degree of pain relief 95%), time of pain relief (89%) and duration of relief (84%). These results reflect those reported by Lipton and Stewart %, time o. TherefoOur study found treatment with eletriptan 40 mg was associated with high levels of satisfaction in approximately two-thirds of patients for degree of pain relief, time of pain relief, duration of relief, time to return to usual activities and relief of associated symptoms. In contrast, only 49% of patients reported high levels of satisfaction with previous treatment for degree of pain relief, and only one-third of patients reported high levels of satisfaction for the other outcomes.The high satisfaction reported with eletriptan 40 mg most likely reflects the high 2-h and sustained (48-h) headache response, and pain-free response rates recorded. We would expect presence/absence of a 2-h headache/pain-free response to influence satisfaction with time of pain relief and time to return to usual activities, presence/absence of pain-free response (at 2 and 48 h) to influence satisfaction with degree of headache pain relief, and presence/absence of sustained headache/pain-free response to influence satisfaction with duration of relief. Indeed, the 2-h headache response rate (62%) and the proportion of patients reporting satisfaction as ‘good-to-excellent’ for time to headache pain relief (63%) are approximately equal. The high levels of satisfaction reported by patients treated with eletriptan also reflect improvements in both QOL, as measured by the MQOLQ, and in functioning, as measured by the FAIM-A&P scale. In particular, improved QOL and functioning would impact on satisfaction with time to return to usual activities, which was rated as ‘good-to-excellent’ in 66% of study participants.Eletriptan was also effective in achieving high levels of satisfaction in patients reporting low satisfaction with previous migraine therapy and in patients who experienced poor tolerability. Thus, switching a patient from a suboptimally effective triptan to eletriptan can be a useful treatment strategy, a finding consistent with those of previous switch studies ,20.The study was limited by the following important factors: (i) the study was not double blind, and had no parallel-group active comparator or placebo control; rather it was an open-label study specifically focusing on satisfaction with eletriptan 40 mg. Open-label studies may be affected by patients’ views about the study medication, whether positive or negative. The fact that eletriptan is a new treatment may also affect the way it is perceived relative to longer established therapies, (ii) patient perceptions of eletriptan treatment were based on only one treated attack, which may or may not have been ‘typical’ for that patient, (iii) patient ratings of their previous migraine treatment were retrospective, which may have introduced recall bias, (iv) furthermore, although patients were asked to rate their ‘usual’ therapy, their response may have been influenced by their experience of a number of treatments, not just their most commonly utilised therapy. Thus the results of the baseline MSQ may reflect general impressions with previous treatments used and (v) we did not evaluate whether patients on different previous treatments reported different satisfaction results with eletriptan. A patient's prior experience with treatment may affect their rating of a new therapy. For example, patients previously receiving migraine-specific drugs such as triptans or ergotamine may have had higher expectations of eletriptan than patients previously treated with general analgesics.Despite these limitations, our study demonstrates the utility of patient-weighted satisfaction scores in assessing migraine treatment effectiveness. It also shows that eletriptan 40 mg produces higher levels of satisfaction than previous migraine therapy on the items identified as important to patients. The preference weighting methodology used in the current study is a promising approach for measuring patient-rated outcomes, as it customises standard efficacy assessments based on individualised patient inputs. Consequently, the real-world effectiveness of treatment can be assessed on an individual patient basis in terms of the factors that are most important to them.


Patient's expectations are variably reported to influence self-rated outcome and satisfaction after medical treatment; this prospective study examined which of the following was the most important unique determinant of global outcome/satisfaction after total knee arthroplasty (TKA): baseline expectations; fulfilment of expectations; or current symptoms and function.One hundred and twelve patients with osteoarthritis of the knee  completed a questionnaire about their expectations regarding months until full recovery, pain, and limitations in everyday activities after TKA surgery. Two years postoperatively, they were asked what the reality was for each of these domains, and rated the global outcome and satisfaction with surgery. Multivariable regression analyses using forward conditional selection of variables  identified the most significant determinants of outcome.P = 0.005). They were also overly optimistic about the likelihood of being pain-free  and of not being limited in usual activities . Global outcomes were 46.2% excellent, 41.3% good, 10.6% fair and 1.9% poor. In multivariable regression, expectations did not make a significant unique contribution to explaining the variance in outcome/satisfaction; together with other joint problems, knee pain and function at 2 years postoperation predicted global outcome, and knee pain at 2 years predicted satisfaction.Patients significantly underestimated the time for full recovery (expected 4.7 ± 2.8 months, recalled actual time, 6.1 ± 3.7 months; In this group, preoperative expectations of TKA surgery were overly optimistic. The routine analysis of patient-orientated outcomes in practice should assist the surgeon to convey more realistic expectations to the patient during the preoperative consultation. In multivariable regression, expectations did not predict global outcome/satisfaction; the most important determinants were other joint problems and the patient's pain and functional status 2 years postoperatively. Patieoutcomes ,7, perhaoutcomes  or a soroutcomes ,10.Only few studies have examined the relationship between expectations and outcome/satisfaction in relation to total joint replacement surgery, and even fewer specifically in relation to the knee joint. Engel and colleagues examined the influence of baseline expectations regarding improvement in the condition and regarding change in quality of life on outcome , as measMahomed and colleagues examined the importance of expectations  in predicting outcomes after total joint arthroplasty . In multdid examine the notion of expectations being met in relation to the outcome of total joint replacement (hip) [Burton and colleagues nt (hip) , and notnt (hip) . Unfortunt (hip) .Moran and colleagues  quantifiIn summary, previous investigations in the field of joint replacement have delivered inconclusive findings, in part due to the retrospective nature of the investigations or failure to use multivariable models to identify the relative importance of putative predictors.The present study seeks to expand our knowledge of the relationship between expectations and outcome, measured as satisfaction with surgery and the global outcome of surgery, in patients undergoing joint replacement for osteoarthritis of the knee. Specifically, in multiple regression analysis we tested, when controlling for potential confounding variables, which (if any) of the following variables made a unique significant contribution to explaining the variance in satisfaction and in global outcome 2 years after TKA: baseline expectations, the actual knee status (pain and function) at 2-year follow-up, and expectations being fulfilled .The patients described in the present investigation were participating in a large-scale prospective study examining subjective and objective aspects of locomotor function before and after TKA (results on objective changes in function to be reported elsewhere). The participants completed questionnaires before total joint replacement surgery and again 2 years later. The study group comprised those with questionnaire data from both baseline and follow-up assessments (n = 112/146 (77%); for details on drop-outs, see later).The patients received an oral and written explanation of what would be required of them, and signed an informed consent form confirming their agreement to participate. The study was approved by the local University Ethics Committee.All patients who were scheduled for a primary knee arthroplasty (TKA) at the authors' hospital in the year of study were invited to participate; approximately 55% volunteered. The only inclusion criteria were a willingness to comply with the test battery and complete the follow-up assessments, and a good understanding of written German. No patients were excluded on the basis of their age or activity level.reasons for choosing knee replacement surgery ; the importance of decreasing pain and increasing function; and expectations of surgery in relation to expected time until full recovery , expected pain after recovery from surgery , and expected limitations in everyday activities after recovery from surgery .Approximately 2 weeks before the operation, during a visit to the hospital for the accompanying functional tests (reported elsewhere), the patients completed the Total Arthroplasty Outcome Evaluation Questionnaire Baseline and History Forms of Katz and colleagues  (modifieThe History Form enquired (amongst other things) about various sociodemographic characteristics, pain in the left and right knees , and extent of limitation in usual activities .The form also enquired about the involvement of other joints by asking 'Other than your knee, what areas are very painful?' . The answer was then dichotomised as yes if any of the joints given in the option list (or feet as other) were indicated, and as no if the answer was none or any other areas of the body, with the rationale that these other joints might affect overall mobility/locomotor function.The American Society of Anesthesiologists Physical Status Classification System was used to assess the patient's overall physical health , since it was considered that this may have influenced the patient's function or postoperative outcome.current status in relation to the domains that had been enquired about in the preoperative expectations questionnaire . They also completed the Post-operative Form, which asked them to rate the global outcome/result of surgery  and their satisfaction with surgery  - these two measures were to serve as the dependent variables in the multiple regression analyses - and to state whether they would choose to undergo the procedure again if they found themselves in the same situation, knowing what they now know about the outcome .Two years after surgery, when the patients attended for their follow-up assessment, they completed the same items from the History Form to assess expectations were measured at baseline, and current pain and function were measured prospectively (each preoperatively and at 2 years), also yielding a measure of the change in pain and function. In each expectations domain , the difference between the preoperative expected score and the follow-up actual score yielded a measure of the extent to which expectations had been fulfilled.In summary, Descriptive data are presented as the mean and standard deviations unless otherwise stated. Contingency analyses were used to examine associations between categorical variables. Bivariate analyses  were used to examine the zero-order correlations between global outcome (or satisfaction) and the potential predictors.Multiple linear regression analyses were carried out to identify the variables that made a significant unique contribution to explaining the variance in outcome, using firstly global treatment outcome and then satisfaction with treatment as the dependent variable to be predicted. Age, gender, and presence of other joint problems were entered into the model as a first step, to control for these potential confounding variables. After this, the following variables were entered using a forward conditional selection criterion (with a probability-of-F-to-enter ≤ 0.05): the two expectations items ; pain and function at 2 years; the change in pain and the change in function ; and the fulfilment of expectations  scores for each of the three domains.Collinearity was assessed by examining the tolerance values and variance inflation values for the independent variables in the final regression models; values < 0.1 and > 5, respectively, were considered to suggest problematic collinearity   and SPSS version 16.0 for Apple Macintosh .P < 0.05 level and no corrections were made for multiple testing [Statistical significance was accepted at the  testing .P = 0.07), but showed no significant differences from those with 2-year data regarding gender distribution (P = 0.70), body weight (P = 0.99), height (P = 0.56), baseline pain (P = 0.86) and baseline functional limitations (P = 0.36). The reasons for dropping out were that seven patients had died, one patient had moved abroad, four patients had undergone revision and did not want to continue, five patients had other operations or physical problems, one patient did not go on to operation (heart problem), and 16 simply did not want to continue with the study. Of the 34 drop-outs, 17 patients had actually returned for a clinical check-up with the physician at 2 years: review of the medical notes indicated that 13 of these patients had no pain, two patients had pain, and two patients had no specific information on pain; 11 patients were satisfied with the results of the operation, one patient was dissatisfied, and five patients had no specific information; and 13 patients had good function, one patient had poor function, and three patients had no specific information on function.The baseline sociodemographic and pain/function data for the group of 112 patients with questionnaire data at baseline and at 2-year follow-up are presented in Table P = 0.003) and satisfaction grades (P = 0.012) than the rest of the group - since these revisions could not have been anticipated at baseline, yet they may have had an influence on the overall outcome rating at 2 years, the data from this group were not included in the multivariable analyses of predictors of outcome.Thirteen out of the 112 patients with baseline data and 2-year follow-up data had undergone some sort of further surgery on the same knee, between 1 month and 21 months after the index surgery . As expected, this group recorded significantly worse 2-year global outcomes , was 'I can't stand the pain any longer; something has to be done'. This was followed by 'I want to walk without a limp, and/or without using a cane/crutch' (17.2%), 'I want to increase my walking endurance' (14.1%), and 'doctor's recommendation' (6.1%). The other six options were each chosen by 1 to 3% patients (13 patients were not able to answer the question).The distribution of answers (n = 111) to the question 'In deciding to have knee replacement surgery, how important was it for you to decrease your pain' was as follows: 44.1% extremely important, 51.4% very important, 3.6% moderately important, and just 0.9% slightly important. The same question in relation to 'increasing your ability to do normal activities' returned the following answer distribution (n = 112): 48.2% extremely important, 47.3% very important, and 4.5% moderately important.The expected mean time until recovery was 4.7 ± 2.8 months; in reality, by the 2-year follow-up only 80% of the patients actually considered themselves fully recovered from the operation, and they recalled that it had taken them, on average, 6.1 ± 3.7 months to do so. Figure The preoperative expectations for pain and function compared with the actual outcome at 2 years follow-up are presented in Table Consistent with the most common reason for deciding to undergo surgery, the majority of patients  declared that they expected no knee pain and the remainder  declared expectation of only slight knee pain after surgery. In reality, only 43% of the group reported being pain-free at 2 years post operation. The patients were similarly overly optimistic about function, with the majority of the group expecting no limitations  or only slight limitations  after surgery, but with only 20% and 30% patients, respectively, achieving such a status.On an individual basis, expectations regarding pain were met or exceeded in 47% patients; for function, just 30% achieved their expected function or better Table .The ratings of the global outcome of the knee replacement 24 months after surgery (n = 112) were as follows: 46.4% excellent, 42.0% good, 9.8% fair, and 1.8% poor .The ratings for satisfaction with the results of the knee replacement (n = 112) were similarly distributed, although with somewhat more patients in the highest category: 58.6% very satisfied, 31.5% satisfied, 8.1% somewhat dissatisfied, and 1.8% dissatisfied .In response to the question 'Now that you have learned a lot about knee replacement surgery, if you could go back in time and make the decision again, would you choose to have the surgery?', 73.9% patients said 'yes, definitely', 18.9% said 'yes, probably', 6.3% said 'no, probably not', and 0.9% said 'no, definitely not'.Table P = 0.034); the variable having other joint problems made a unique significant contribution, also in the final model (P = 0.046). At the second step, knee pain at the 2-year follow-up was selected for entry, with a significant 20.5% increase in the step change in R2 (P < 0.0001). At the third step, functional limitations at the 2-year follow-up explained a further significant 4.4% variance (P = 0.022). In the final model, the variables that made a significant unique contribution were other joint problems, knee pain at 2 years, and knee functional limitations at 2 years - with higher values for each being associated with a poorer global outcome.The results of the final step of the multiple regression analyses are presented in Tables P = 0.042) and knee pain at 2 years (P < 0.0001) were unique significant predictors . This was most probably the result of the high correlations between pain/functional limitations at the 2-year follow-up and the fulfilment of expectations in these domains . Interestingly, and in contrast to some previous studies ,5,20, thThe patients' expectations of surgery declared in the present investigation were quite high, and were overly optimistic compared with the actual results achieved. The vast majority 85%) of patients expected to be pain free, yet only 43% were; and 52% expected to have no functional limitations, yet just 20% achieved this. This overestimation of the probable improvement after TKA ,13 and o5% of patThe negative influence of other joint problems on the probable outcome of TKA may need to be emphasised to a greater extent in the preoperative informed consent process. As banal as it may seem, it is important that patients with co-morbidity in terms of other joint problems  are made aware that the operation is being carried out for the specific knee joint disease identified, and that it will not necessarily serve as a general panacea for other ongoing medical problems. Indeed, ongoing pain and functional limitations in connection with other joint problems will probably persist after the surgery, and influence general functioning and the quality of life accordingly. If this is not explicitly discussed with the patient prior to surgery, then inappropriate expectations may go unchecked, ultimately leading to disappointment with the result.The salient features of the present study include its prospective nature, its relatively large sample size, its examination of different domains for which the patient may hold expectations, and its multivariable approach to the analysis. Further, the overall proportion of successful outcomes (88.5% excellent and good) was similar to the figures presented in previous studies , provThe questionnaire used to assess the (preoperative) expectations of improvement and the (postoperative) achievement of improvement and overall outcome has not been validated for use in the knee; it was originally developed and validated for use in the hip . Many ofThe Total Arthroplasty Outcome Evaluation Questionnaire was chosen for use in the present investigation because, when the study was first designed, this instrument appeared to offer one of the most comprehensive, but simple and efficient, means of assessing the many domains/constructs of interest in arthroplasty patients. Most of the individual scales in the questionnaire are single-item measures  with adjectival or Likert scales; although a number of studies have shown that these can be just as valid and representative of a domain as multi-item scales ,27, it wIn relation to the statistical analyses used in the present study, the regression models examined the main effects of level of expectations, regardless of whether these were met, and of fulfilled expectations, independent of their preoperative level. However, perhaps the interaction of both should be considered, for example to investigate whether expectations that are met lead to a good outcome only when expectations are high. This particular analysis could not be carried out in the present study, because, for the given sample size, the power using moderated hierarchical regression analysis would have been too low  and becaIn the patient group examined, patient expectations of surgery were generally overly optimistic. This highlights the importance of routinely assessing patient-orientated outcome and the various factors influencing it, such that realistic expectations for different outcome domains can be discussed with the individual patient prior to surgery. Although in bivariate analyses expectations being met were significantly associated with outcome, in the final multivariable model only the presence of other joint problems and the degree of improvement in symptoms and function were unique significant determinants of a good global outcome and of satisfaction with the procedure.TKA: total knee arthroplasty.The authors declare that they have no competing interests.IK-dQ and UM were responsible for the conception and design of the main study, of which this substudy is part, and acquired funding for the project; they also coordinated all of the practical work and acquisition of data. AFM performed the statistical analysis, interpreted the data and drafted the manuscript. SK organised and prepared the data for analysis, and assisted with some of the statistical analyses and with the writing of the manuscript. All authors read and approved the final manuscript.


Major shoulder surgery often results in severe post-operative pain and a variety of interventions have been developed in an attempt to address this. The continuous slow infusion of a local anaesthetic directly into the operative site has recently gained popularity but it is expensive and as yet there is little conclusive evidence that it provides additional benefits over other methods of post-operative pain management.This will be a randomised, placebo-controlled trial involving 158 participants. Following diagnostic arthroscopy, all participants will undergo arthroscopic subacromial decompression with or without rotator cuff repair, all operations performed by a single surgeon. Participants, the surgeon, nurses caring for the patients and outcome assessors will be blinded to treatment allocation. All participants will receive a pre-incision bolus injection of 20 mls of ropivacaine 1% into the shoulder and an intra-operative intravenous bolus of parecoxib 40 mg. Using concealed allocation participants will be randomly assigned to active treatment  or placebo  administered continuously into the subacromial space by an elastomeric pump at 5 mls per hour post-operatively. Patient controlled opioid analgesia and oral analgesics will be available for breakthrough pain. Outcome assessment will be at 15, 30 and 60 minutes, 2, 4, 8, 12, 18 and 24 hours, and 2 or 4 months for decompression or decompression plus repair respectively.The primary end point will be average pain at rest over the first 12-hour post-operative period on a verbal analogue pain score. Secondary end points will be average pain at rest over the second 12-hour post-operative period, maximal pain at rest over the first and second 12-hour periods, amount of rescue medication used, length of inpatient stay and incidence of post-operative adhesive capsulitis.The results of this trial will contribute to evidence-based recommendations for the effectiveness of pain management modalities following arthroscopic rotator cuff surgery. If the local anaesthetic pain-buster provides no additional benefits over placebo then valuable resources can be put to better use in other ways.Australian Clinical Trials Register Number ACTR12606000195550 Surgical options for rotator cuff disease that has failed to improve with conservative treatments include open or arthroscopic subacromial decompression (ASD)  with or Post-operative pain is often a problem following major shoulder surgery and may delay mobilisation of the shoulder . It has A variety of strategies may be used to manage post-operative pain including low dose continuous intravenous opioids with or without patient managed bolus doses using patient controlled analgesia (PCA) pumps , intra-aUse of a pre-emptive (before incision) bolus dose of local anaesthetic  injected into either the glenohumeral joint and/or subacromial space is gaining wide acceptance as an alternative method for pain management following shoulder surgery. Pre-emptive analgesia is purported to induce prophylactic neural blockade thus blocking nociceptive input and reducing post-operative pain . The effAdministration of local anaesthetic has been performed by direct infiltration, intermittent lavage, continuous infusion with PCA bolus or PCA alone and some of the trials have also included pre-emptive or intra-operative analgesia and/or NSAIDS. Shoulder operations have included open as well as arthroscopic surgery, and surgery to the capsule and ligaments as well as to the rotator cuff. Seven previous randomised placebo-controlled trials of differing methodological quality have assessed the efficacy of local anaesthetic  continuously infused into the operative site following various types of major shoulder surgery -19. WhilWhile ropivacaine is now considered the local anaesthetic of choice despite its greater cost, earlier trials used either the shorter acting lignocaine or bupivacaine. Bupivacaine has been shown to cause greater dose related central nervous system and cardiac toxicity than ropivacaine . RopivacIn our setting, post-operative pain management has traditionally consisted of pre-emptive local anaesthetic (ropivacaine) and post-operative PCA opioids. Recently and concurrently, both intra-operative intravenous parecoxib a selective COX-II inhibitor, and direct operative ropivacaine infusion pumps were introduced as standard practice although evidence for their added benefits is limited. The disposable pump with single or dual catheters and ropivacaine costs $AUD300–600 and $155 respectively (at time of publication), while a single pre-emptive bolus of 20 mls 1% ropivacaine costs $20 and an IV bolus of parecoxib (40 mg) costs only $25. Reported adverse effects of infusion pumps include difficulty in removal of the catheter, too rapid delivery of the drug, leakage with local contamination, and breakage of the catheter tip leaving a remnant in the joint ,23. To wThe aim of this randomised placebo controlled trial is to determine the efficacy and safety of a continuous infusion of ropivacaine 0.75% (Naropin – AstraZeneca) delivered by a single catheter 'Painbuster' pain management system when used following elective arthroscopic rotator cuff surgery. Our hypothesis is that continuous infusion of local anaesthetic following rotator cuff surgery would be equivalent to pain relief provided by a placebo in the setting of pre-emptive ropivacaine, intra-operative parecoxib and post-operative intravenous morphine and oral dextropropoxyphene hydrochloride/paracetamol available on demand.This will be a randomised placebo-controlled trial Figure . ParticiParticipants will be recruited from the private community-based practice of a single orthopaedic shoulder surgeon in Melbourne, Australia. The decision to include only one surgeon will eliminate any potential confounding of results due to differences in surgical skill, technique and care across treatment arms. One of two elective operations will be performed based upon diagnostic arthroscopy at the time of operation: ASD or ASD plus RCR. All rotator cuff surgery will be performed at either the Mercy Private Hospital or Linacre Private Hospital in Melbourne, Australia.All consecutive, eligible patients who fulfil selection criteria will be offered study participation. Inclusion criteria will be adults aged 18 years or over in whom elective subacromial decompression or rotator cuff repair is planned. Exclusion criteria will be: (i) patients with massive or irreparable rotator cuff tears; (ii) patients requiring grafts to fill the defect; (iii) previous injury or surgery to the shoulder i.e. fracture or revision surgery; (iv) previous mastectomy on the affected side; (v) peripheral neuropathy affecting the upper limbs; (vi) chronic opioid use; (vii) morbid obesity (body mass index greater than 35 kg per metre squared); (viii) Parkinson's disease; (ix) pregnancy; (x) contraindication to parecoxib including aspirin sensitive asthma, history of recent gastric or duodenal bleeding, severe renal impairment or sulphonamide allergy; (xi) inability to understand written and/or spoken English.The Monash University and Mercy Aged and Health Care Ethics Committees have approved the study and all participants will provide written informed consent.Once eligibility has been assessed following diagnostic arthroscopy, participants will be randomly assigned in random permuted blocks of differing sizes to either active treatment (ropivacaine) or placebo , stratified by type of operation (ASD or ASD plus RCR) Figure . The ranThe surgeon's standard surgical protocol for rotator cuff surgery will be adhered to as follows: Participants will be asked to cease all NSAIDs two weeks prior to commencement of the study but will be allowed codeine, paracetamol or dextropropoxyphene. All operations will be performed under general anaesthesia using a standardised method consisting of propofol 2–2.5 mg/kg and fentanyl 1–2 mcg/kg as induction agents, nitrous oxide/oxygen 2:1, +/- isoflurane, morphine as required to maintain heart rate, blood pressure, respiratory rate within normal limits, and spontaneous ventilation on a laryngeal mask unless contra-indicated.All patients will receive a total of 20 mls of 1% ropivacaine injected as a pre-emptive bolus dose into both the glenohumeral joint and the subacromial space fifteen minutes prior to insertion of the arthroscope. During the operation all patients will receive an intravenous bolus of 40 mg of parecoxib. At the conclusion of the surgery, all patients will have insertion of a 'Pain buster' catheter into the subacromial space with the position verified by direct or arthroscopic vision. According to blinded randomised treatment allocation the 'Pain buster' elastomeric pump will contain 180 mls of either 0.75% ropivacaine or an identical placebo of normal saline administered at 5 mls per hour.All patients will have access to alternative analgesia for break through pain including both a PCA pump of intravenous morphine available on demand with a lock out period and dextropropoxyphene hydrochloride/paracetamol. All medications will be recorded.All assessors collecting and assessing outcome will be blinded to treatment allocation. One assessor will perform all baseline, and 2 or 4 month (JC) assessments. Post operative assessment of pain, analgesia and duration of hospital stay will be recorded by nursing staff.Baseline data will include gender, age at operation, dominance, side of operation, height, weight, history of diabetes, employment, duration of symptoms and compensation status. As a verbal analogue pain scale (VAPS) will be used to measure pain postoperatively, participants will be taught to use the scale at the time of pre-operative baseline assessment to measure current level of pain at rest. The VAPS is an 11-point scale where 0 = no pain and 10 = worst pain imaginable.Outcomes will be assessed post operatively at 15, 30 and 60 minutes, 2, 4, 8, 12, 18 and 24 hours, and 2 or 4 months for ASD or ASD and RCR respectively. Average pain at rest and maximal pain over the first and second 12 hour post-operative periods, will be computed using the VAPS. The amount of rescue medication used over the first and second 12 hour post-operative periods will be computed as intravenous opioid intake in mgs and oral analgesic intake as a tablet count.Range of movement of the shoulder will be measured at baseline and at 2 or 4 months for ASD or ASD plus RCR respectively. Active shoulder movements will be measured according to a standardised and reliable protocol : Total sLength of hospital stay will be measured in days from time of surgery and all adverse effects will be recorded.The primary end point will be the average pain at rest over the first 12 hour post-operative period. Secondary end points will be the average pain at rest over the second 12-hour post-operative period, the maximal pain over the first and second 12-hour periods, the amount of rescue medication used, late discharge (>1 bed day) from hospital following ASD, early or late discharge (< or > 2 bed days) following ASD plus RCR, and the incidence of post-operative adhesive capsulitis up to 2 or 4 months following ASD or ASD plus RCR respectively.Sample size is based upon clinical equivalence being deemed as a difference in mean pain scores of +/-1 point on a 10 point scale. That is, any difference between groups of 1 point or less will be regarded as equivalent for practical purposes. Statistically, equivalence will be declared if the 90% CI for the difference in mean pain scores between the groups lies entirely within the interval -1 to +1. To have 80% probability that this equivalence will occur when the two infusion therapies are actually exactly equivalent requires 70 patients per arm, assuming a standard deviation of 2 points within each arm (obtained from pilot work). This sample size will also be able to detect a difference of 0.95 points with 80% power and a two-sided 5% significance level. Allowing for 10% dropout, the sample size is inflated to 78 patients per group.The principal analyses will involve the comparison of average scores of pain at rest in the first 12 hours post-operation between the ropivacaine pump infusion and placebo patients using an intention-to-treat analysis. This will be performed by multiple regression adjusting for infusion type and type of operation. Similar analyses will compare maximal pain at rest in the first 12 hours and average and maximal pain at rest in the second 12-hour post-operative period. Sensitivity analyses to assess dependence upon potential baseline imbalance in prognostic factors will also be performed. Other secondary outcome analyses will include amount of morphine administered, the incidence of complications, late discharge from hospital (>1 bed day) following ASD, early or late discharge (< or > 2 bed days) following RCR, and the incidence of post-operative adhesive capsulitis up to 2 or 4 months following ASD or ASD plus RCR respectively. Further analyses will assess differences between arms in maximum and average pain scores at rest adjusted for amount of opioid used.The results of this trial will contribute to evidence-based recommendations for the effectiveness of pain management modalities following arthroscopic rotator cuff surgery. If we can show that the pain-buster is equivalent to current treatment and adds nothing to current pain management then this will reduce the costs of the surgical procedure and hospitalisation. Strengths of our trial include blinding of all personnel involved in participant care including the surgeon; assurance of homogeneity of study population by pre-randomisation identification of the surgical procedure required; use of a realistic placebo infusion; use of a single surgeon and single post operative regime limiting confounding; and statistical power to detect small differences of importance.The author(s) declares that they have no competing interests.JC, RB, AF and SB conceived and designed the trial protocol. AF designed the statistical analysis. JC, RB and AF drafted the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The potentially serious nature of herpes zoster (HZ) and the long-term complication post-herpetic neuralgia (PHN) are often underestimated. One in four people will contract herpes zoster in their lifetime, with this risk rising markedly after the age of 50 years, and affecting one in two in elderly individuals. Pain is the predominant symptom in all phases of HZ disease, being reported by up to 90% of patients. In the acute phase, pain is usually moderate or severe, with patients ranking HZ pain as more intense than post-surgical or labour pains. Up to 20% of patients with HZ develop PHN, which is moderate-to-severe chronic pain persisting for months or years after the acute phase. We review the available data on the effect of HZ and PHN on patients' quality-of-life.Findings show that HZ, and particularly PHN, have a major impact on patients' lives across all four health domains - physical, psychological, functional and social. There is a clear correlation between increasing severity of pain and greater interference with daily activities. Non-pain complications such as HZ ophthalmicus can increase the risk of permanent physical impairment. Some elderly individuals may experience a permanent loss of independence after an acute episode of HZ. Current challenges in the management of HZ and PHN are highlighted, including the difficulty in administering antiviral agents before pain becomes established and the limited efficacy of pain treatments in many patients. We discuss the clinical rationale for the HZ vaccine and evidence demonstrating that the vaccine reduces the burden of the disease. The Shingles Prevention Study, conducted among >38,000 people aged ≥60 years old, showed that the HZ vaccine significantly reduces the burden of illness and the incidence of both HZ and PHN. In the entire study population, zoster vaccination reduced the severity of interference of HZ and PHN with activities of daily living by two-thirds, as measured by two questionnaires specific to HZ.A vaccination scheme may positively impact the incidence and course of HZ disease, thereby improving patients' quality-of-life. Herpes zoster (HZ) is a common, painful and debilitating condition caused by a reactivation of the varicella-zoster virus (VZV) from a latent infection of sensory ganglia -3. The dPost-herpetic neuralgia (PHN) is the most common complication of HZ. A standard definition for PHN is lacking, but it is often defined as pain that persists for ≥90 days after the onset of HZ rash . The chrThe lifetime risk of contracting HZ is one in four, but this risk increases markedly after 50 years of age due to an age-related decline in VZV-specific cell-mediated immunity ,14,15. PHZ is incorrectly perceived by many clinicians to be a mild and readily treatable disease. In fact, treatment options remain inadequate -- particularly for PHN -- and the disease can have devastating effects on patients' quality-of-life (QoL) in the acute and chronic phases ,18,19. TThis contribution discusses the available data on the impact of HZ and PHN on the QoL and functional status of patients and highlights the current challenges in their management. An increased awareness of the substantial burden of HZ and PHN on QoL is essential and may lead to an improvement in prevention and management strategies.The World Health Organization defines health as 'a state of complete physical, mental and social wellbeing, and not merely the absence of disease or infirmity' . The terClinical studies should assess all aspects of the life and health of a patient in order to establish how a disease or treatment affects their QoL . Health-In patients with HZ and PHN, the QoL analyses rely on subjective self-reporting using generic, standardized and validated health-status questionnaires such as EuroQoL and Short form (SF)-12 . These gTwo questionnaires have been specifically developed to assess how the pain and discomfort associated with HZ and PHN diminish functional capacity: the Zoster Brief Pain Inventory (ZBPI) ,26 and tPain is usually the predominant symptom in all phases of HZ disease, being reported by up to 90% of patients . The intMost patients with acute HZ experience moderate or severe dermatomal pain in the skin innervated by the afflicted ganglion . Acute-pPain in the acute phase can be constant or intermittent and may show varied symptoms, such as burning or stabbing sensations, itching, tingling or numbness, angina-like aching or squeezing sensations and a deep aching or 'pulled muscle' sensation . Many paThe substantial impact of acute-phase pain on QoL is being increasingly recognized, with QoL studies showing effects on patients' lives across all four health domains Table  18,19,2,26,36-38Different components of acute-phase pain impact on different health domains. This has been demonstrated by multivariate analyses, controlling for patients' demographic and clinical variables . Data shSome elderly individuals may experience a permanent loss of independence, never fully regaining their lifestyles, interests and levels of activity after an acute episode of HZ .PHN is characterized by constant and/or intermittent paroxysmal pain persisting for ≥90 days after the onset of HZ rash ,10. For Most patients categorise the intensity of PHN as moderate-to-severe  despite receiving analgesic agents . The perReduced QoL is a particular problem in patients whose pain persists as PHN. The impact of PHN on patients' lives is substantial and apparent across all domains of QoL Table  13,19,3,38,40-42PHN causes a loss of physical function, with patients experiencing fatigue, anorexia, weight loss, reduced mobility, physical inactivity, sleep disturbance  and reductions in overall health ,13. PHN PHN may also affect patients' psychological wellbeing ,34. PsycSeveral typical symptoms of HZ can be debilitating for patients, even among those who do not experience clinically meaningful pain . The maiHZ can also give rise to non-pain complications, many of which can increase the risk of permanent or long-standing physical impairment . ComplicComplications associated with HZ and PHN place a heavy burden on individuals, who may suffer a permanent reduction in QoL even if the original HZ symptoms fully resolve .et al. was designed to capture the full course of HZ episodes from rash onset to pain resolution. The findings demonstrate the major and wide-ranging impact that HZ, and in particular PHN, have on patients' QoL . Du. Du38]. Treatment of patients with HZ aims to accelerate rash healing, relieve pain and reduce complications . CurrentDespite the development of treatment guidelines by the International Herpes Management Forum , HZ manaTo be effective, antiviral agents must be administered within 72 h of acute-symptom onset , which mA recent Canadian study of patients with HZ rash or pain showed that pain resolution is associated with recovery of QoL to a pre-morbid state . Data showed that the median duration of pain was equal to the median duration of QoL impairment. Once established, the pain associated with HZ or PHN is difficult to treat . PHN remAs patients with PHN may find it difficult to tolerate pain therapies, drug doses are often titrated. This may result in several weeks of suboptimal treatment, during which it is unclear if (or when) the drugs will become effective . Therapeet al. [Treatment dissatisfaction is high in patients with PHN. In one study, only 14% of patients aged >65 years were satisfied with pain medication for PHN . In the et al. , patientCurrent treatment strategies for HZ and PHN are only partially effective, so reducing the burden of HZ disease remains an area of considerable need . A solutThe clinical rationale for the development of an HZ vaccine has centred on reducing the severity of HZ and PHN. Studies have shown that the live attenuated Oka/Merck VZV vaccine ('zoster vaccine') also reduced the incidence of HZ and PHN in addition to burden of illness . Evidence that the zoster vaccine reduces HZ burden in an ageing population is derived from the Shingles Prevention Study . The ShiIn an adverse event substudy of the Shingles Prevention Study, rates of serious adverse events were higher in the vaccine group (1.9%) than in the placebo group (1.3%) . InjectiThe impact of vaccination on QoL was assessed in the entire study population of the Shingles Prevention Study using ZBPI and ZIQ questionnaires. Mean ZBPI and ZIQ scores, which rated the 'interference' of HZ and PHN with ADL, were used to calculate a 'severity of interference score'. For the entire study population, zoster vaccination reduced the ZBPI severity of interference by 66%  and the ZIQ severity of interference by 68% . In individuals who developed HZ, vaccination reduced the ZBPI severity of interference by 31%  and the ZIQ severity of interference by 35% . Zoster vaccination therefore reduced the burden of HZ-related interference with ADL by about two-thirds in a population of older adults and by about one-third in vaccine recipients who developed disease . Much ofHZ is a common disease that can substantially reduce patients' QoL and functional status. HZ is rare in young individuals, but there is a marked increase in risk after 50 years of age. The consequences of HZ are a particular problem in older individuals. In part, this may be due to slow healing of nerve damage and inflammatory scarring in an ageing nervous system. The number of cases of HZ and PHN is expected to increase in coming decades due to the steady rise in the mean age of the population.Pain is the major symptom that affects the QoL and ADL of patients and is usually present across all phases of HZ disease. In patients whose pain persists for months or years as PHN, the effects on patients' lives can be devastating. The negative effects of HZ and PHN on physical, social, functional and psychological health are as substantial as the effects described by patients with other chronic health conditions. Non-pain-related complications of HZ may also contribute to a reduced QoL. HZ and PHN can also have significant consequences for patients' partners, relatives and social circle.To be effective, antiviral medication needs to be started within 72 h of the onset of acute symptoms. Antiviral agents show limited efficacy if administered within 72 h of acute-symptom onset. Treatment within this time is often not achievable and patients may present with pain that is established and difficult to treat. Current treatments for PHN are largely suboptimal and often accompanied by intolerable side-effects. Awareness of these challenges and the substantial burden of HZ and PHN on patients' QoL may lead to improved prevention and management strategies.Zoster vaccine has been demonstrated to attenuate the severity of HZ disease and significantly reduce the incidence of HZ and PHN. The introduction of a prophylactic vaccination scheme may achieve a significant positive impact on the incidence and course of HZ disease, thereby improving patients' QoL.ADL: activities of daily living; CI: confidence interval; HZ: herpes zoster; PHN: post-herpetic neuralgia; QoL: quality-of-life; VZV: varicella-zoster virus; ZBPI: Zoster Brief Pain Inventory; ZIQ: Zoster Impact Questionnaire.RWJ received honoraria as consultant and/or lecturer for Merck, Sanofi Pasteur MSD, Novartis, Astellas, GSK and Merck Frosst. DB received support from Sanofi Pasteur MSD, Sanofi Aventis, Pfizer, Boehringer Ingelheim, Eli Lilly. GK received an honoraria and support to attend scientific meetings from Sanofi Pasteur MSD, GSK, Novartis, AstraZeneca, Sanofi Aventis, Pfizer and Roche. AL was a consultant for Sanofi Pasteur MSD. KES received a grant support from Merck and Wyeth and was a consultant for Merck and GSK. TW received honoraria as a consultant and/or lecturer for GSK, Novartis Vaccines and Sanofi Pasteur MSD.All authors contributed to the content of this manuscript and have read and approved the final draft.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/8/37/prepub


Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain. Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology.Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic  LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity  and specificity . The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs.We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment. Pain, although unpleasant, is essential for survival. Whenever the body is damaged, nerve cells detecting the injury send an electrical message via the spinal cord to the brain and, as a result, action is taken to prevent further damage. Usually pain is short-lived, but sometimes it continues for weeks, months, or years. Long-lasting (chronic) pain can be caused by an ongoing, often inflammatory condition  or by damage to the nervous system itself—experts call this “neuropathic” pain. Damage to the brain or spinal cord causes central neuropathic pain; damage to the nerves that convey information from distant parts of the body to the spinal cord causes peripheral neuropathic pain. One example of peripheral neuropathic pain is “radicular” low back pain . This is pain that radiates from the back into the legs. By contrast, axial back pain (the most common type of low back pain) is confined to the lower back and is non-neuropathic.Chronic pain is very common—nearly 10% of American adults have frequent back pain, for example—and there are many treatments for it, including rest, regulated exercise , pain-killing drugs , and surgery. However, the best treatment for any individual depends on the exact nature of their pain, so it is important to assess their pain carefully before starting treatment. This is usually done by scoring overall pain intensity, but this assessment does not reflect the characteristics of the pain  or the complex biological processes involved in pain generation. An assessment designed to take such factors into account might improve treatment outcomes and could be useful in the development of new therapies. In this study, the researchers develop and test a new, standardized tool for the assessment of chronic pain that, by examining many symptoms and signs, aims to distinguish between pain subtypes.One hundred thirty patients with several types of peripheral neuropathic pain and 57 patients with non-neuropathic  low back pain completed a structured interview of 16 questions and a standardized bedside examination of 23 tests. Patients were asked, for example, to choose words that described their pain from a list provided by the researchers and to grade the intensity of particular aspects of their pain from zero (no pain) to ten (the maximum imaginable pain). Bedside tests included measurements of responses to light touch, pinprick, and vibration—chronic pain often alters responses to harmless stimuli. Using “hierarchical cluster analysis,” the researchers identified six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain based on the patterns of symptoms and signs revealed by the interviews and physical tests. They then used “classification tree analysis” to identify the six questions and ten physical tests that discriminated best between pain subtypes and combined these items into a tool for a Standardized Evaluation of Pain (StEP). Finally, the researchers asked whether StEP, which took 10–15 minutes, could identify patients with radicular back pain and discriminate them from those with axial back pain in an independent group of 137 patients with chronic low back pain. StEP, they report, accurately diagnosed these two conditions and was well accepted by the patients.These findings indicate that a standardized assessment of pain-related signs and symptoms can provide a simple, quick diagnostic procedure that distinguishes between radicular (neuropathic) and axial (non-neuropathic) low back pain. This distinction is crucial because these types of back pain are best treated in different ways. In addition, the findings suggest that it might be possible to identify additional pain subtypes using StEP. Because these subtypes may represent conditions in which different pain mechanisms are acting, classifying patients in this way might eventually enable physicians to tailor treatments for chronic pain to the specific needs of individual patients rather than, as at present, largely guessing which of the available treatments is likely to work best.http://dx.doi.org/10.1371/journal.pmed.1000047.Please access these Web sites via the online version of this summary at PLoS MedicinePerspective by Giorgio Cruccu and and Andrea TruiniThis study is further discussed in a pain in English and SpanishThe US National Institute of Neurological Disorders and Stroke provides a primer on 2006 report on the health status of the US, the National Center for Health Statistics provides a special feature on the epidemiology of pain, including back painIn its Pain Treatment Topics Web site is a resource, sponsored partly by associations and manufacturers, that provides information on all aspects of pain and its treatment for health care professionals and their patientsThe pain and of back pain and links to further information on both topics (in English and Spanish)Medline Plus provides a brief description of low back pain (in English and Spanish)The MedlinePlus Medical Encyclopedia also has a page on  Conventional measures of chronic pain either rely on global scores to assess pain intensity and determine treatment success, or they employ surrogate markers of improvement such as gain of function and quality of life Clinical pain is generally classified as acute or chronic and is divided into two major categories: inflammatory and neuropathic pain. Combinations of inflammatory and neuropathic pain do occur, for example, in postsurgical A global pain intensity score obliterates differences in pain-related symptoms or signs that might indicate the relative contribution of particular mechanisms to a patient's pain. A clinically more useful pain assessment would associate particular symptoms and signs that constitute the pain phenotype of a patient with the underlying mechanisms and in this way reveal potential targets for pharmacological intervention. Such an assessment would provide a specific measure of treatment success or failure. It would also allow tailoring analgesic therapy to the needs of the individual patient by selecting and combining drugs with proven efficacy against operating mechanisms. However, it is currently not possible to determine pain mechanisms in patients directly We hypothesize that pain mechanisms are reflected and therefore recognizable by the specific patterns of pain-related symptoms and clinical signs they elicit We conducted the study in two parts. In Part 1, we prospectively evaluated a comprehensive range of pain-related symptoms and signs in order to develop a standardized clinical tool for the differentiation of pain subtypes. We performed this part of the study at the Massachusetts General Hospital Center for Pain Medicine in Boston, Massachusetts, United States, from March 2002 until October 2004. Part 2 of the study, in which we validated the pain assessment tool, was carried out between January 2006 and November 2007 at the Back Pain Triage Clinic and the Neurosurgical Outpatient Clinic of Addenbrooke's Hospital, Cambridge, United Kingdom. The study was conducted according to the principles expressed in the Declaration of Helsinki. The study protocols were approved by the Human Research Committee of Massachusetts General Hospital (2001-P-000872) and the National Health Service Research Ethics Committee in Cambridge (05/Q0108/477). All patients gave written informed consent.We recruited patients with painful diabetic polyneuropathy (DN), postherpetic neuralgia (PHN), or chronic low back pain (LBP) through physician referrals and advertisements. Patients with DN had clinically documented diabetes mellitus, reported distal abnormal sensations such as numbness and tingling in their feet and lower legs, and exhibited symmetric sensory deficits and absent ankle jerk reflexes upon examination. If available, records of impaired nerve conduction were used to supplement the clinical diagnosis of a neuropathy, but electrophysiological evaluation was not an inclusion criterion. Patients with PHN had persistent pain in an area previously affected by an eruption of herpes zoster; altered sensation, scarring, and changes in skin pigmentation were considered additional signs supporting the diagnosis of PHN. We divided patients with chronic LBP in two groups: with (radicular LBP) and without  clinical signs of nerve root involvement, including sensory or motor deficits in the leg and a diminution or loss of tendon reflexes. In taking the history of patients with LBP, we asked about the primary location of the pain and whether it radiated into the leg. We also explored whether body positions such as sitting or activities such as weight-bearing or walking elicited or enhanced the pain. If available, we considered results from spinal imaging and further investigations such as electromyography for the diagnostic decision.We included patients who met all of the following criteria: pain duration ≥3 mo, average global pain intensity in the week prior to enrollment ≥6 on a numerical rating scale (NRS) from 0 to 10, age ≥18 y, and ability to give written informed consent. Patients with a severe medical or psychiatric illness, another painful disorder or neurological disease that might have interfered with the pain assessment, or a local infection were excluded. The patients were allowed to continue their previously prescribed analgesic treatment.We evaluated pain-related symptoms and signs and somatosensory function through a structured interview followed by a standardized physical examination. The interview consisted of 16 questions exploring 46 items; the physical examination included 23 bedside tests that provided information about 39 items see .In the interview, we explored the location and temporal characteristics of the pain and its dependence on external stimulation. To determine the sensory quality of the pain, we first asked the patients to characterize the pain in their own words. We then offered a choice of one or more descriptions from the following list: throbbing, pounding, pulsating, shooting, radiating, cramping, squeezing, stabbing, sharp, aching, dull, painful pins and needles, stinging, burning, or hot. We also asked the patients to report unpleasant nonpainful sensations (dysesthesia) and describe the characteristics of these sensations. The patients indicated the intensity of each specific aspect of their pain using an 11-point NRS from 0 (no pain) to 10 (maximum imaginable pain) see .The physical examination was designed to involve tests that would be readily available for a bedside assessment, without the need for advanced or expensive technical equipment. We looked for cutaneous changes indicative of an autonomic nervous system disorder. Two von Frey filaments  were employed to examine the response to punctate tactile stimulation: a filament of low strength (2 g) applied a force above the detection threshold for touch on intact skin; a filament of high strength (26 g) elicited a prickly, but normally painless sensation Investigators graded a decreased response to stimulation following standardized guidelines. For example, a reduced response to punctate tactile stimulation was considered mild if the patient failed to notice stimulation with the low-strength von Frey filament but detected the high-strength filament. If pain was provoked by a test stimulus, we asked the patient to rate the intensity of this particular pain using an NRS. All tests were carried out in the affected (painful) body area. We compared the results with the response to stimulation in an adjacent or contralateral area that was free of pain or any other sensory disorder such as numbness or dysesthesia. For diabetic patients with neuropathic symptoms and signs below the knee, we chose the thigh as reference. For patients with PHN, we examined the contralateral dermatome. For patients with LBP, we examined a reference area in the midline of the back above the painful area , and if the patient had leg pain, the corresponding dermatome of the opposite leg.All investigators involved in the study were experienced clinicians. Training sessions were held before patients were recruited to ensure that each investigator was performing the assessment of pain-related symptoms and signs in the same way and that the interpretation of patient responses was consistent between investigators.http://www.r-project.org/), we calculated a distance matrix based on Gower's general dissimilarity coefficient Groups of patients with similar responses in the interview and the physical examination were identified by hierarchical cluster analysis. Using the function DAISY of R  and a test set (the remaining third), with each diagnosis represented at the same proportion in both sets as in the overall group of patients. For classification with the patient clusters as outcome variable, all patients were used to train the tree with 10-fold cross-validation. Here, we intended to determine the minimum number of interview questions and physical tests that allowed correct assignment of the patients to the clusters. We named this shorter version of the initial assessment tool Standardized Evaluation of Pain (StEP).In Part 2 of the study, we applied StEP to an independent group of patients with chronic LBP to validate the assessment tool for the distinction between radicular and axial back pain . The patStEP consists of a brief structured interview including six questions and ten standardized physical tests see . To ensuWe used the clinical diagnosis as the reference standard to determine the sensitivity and specificity of StEP and its positive and negative predictive values for the distinction between radicular and axial back pain. A patient's back pain was classified as radicular or axial by an interdisciplinary team of at least two experienced physicians—usually a rheumatologist and a neurosurgeon—and a spinal physiotherapist, who were not involved in the study. Typically, the physicians and the physiotherapist based their diagnosis on a detailed history and a comprehensive neurological and rheumatological examination that included testing for radicular sensory or motor deficits, reduced tendon reflexes, neurogenic claudication, and an evaluation of back mobility and muscle spasm. Further investigations such as electromyography, spinal magnetic resonance imaging (MRI), or computed tomography, with or without myelography, were carried out if deemed necessary. The study investigators who applied StEP were blind to the clinical classification of back pain and the results of additional investigations.Douleur Neuropathique en 4 Questions (DN4) screening tool for neuropathic pain We compared StEP with the Spinal MRI is a widely used noninvasive method to assess degenerative changes of the spine and intervertebral disk pathology leading to nerve root compression. We analyzed the MR images of those patients who were referred for the procedure as part of their diagnostic evaluation. The decision to refer a patient for spinal MRI was made independently of the study by the attending physicians. MRI of the lumbar spine was performed with a 1.5-T scanner  and a dedicated receive-only spine coil. The imaging protocol included the following sequences: sagittal T2-weighted fast spin echo , sagittal T1-weighted spin echo , and axial T2-weighted fast spin echo . MR images of the lumbar spine at the L3/L4, L4/L5, and L5/S1 segmental levels were read by an experienced specialist in neuroradiology who was blind to the clinical diagnosis and the result of the pain assessment. Nerve root impairment was graded depending on contact between intervertebral disks and nerve roots, nerve root deviation, and compression After completion of the pain assessment, we asked the patients to evaluate StEP on a standardized self-administered form. Using an NRS from 1 to 5, the patients graded the accuracy and comprehensiveness of the pain assessment, and how difficult it was for them to respond to the interview questions and comply with the physical tests. The patients also rated their willingness to repeat the pain assessment during a future visit.Not considering pain intensity ratings and the question about current pain, the 16 interview questions and physical tests of StEP contain 45 binary predictors. For the purpose of calculating statistical power, we constructed a composite score consisting of a linear combination of these predictors and estimated the sensitivity and specificity of StEP in distinguishing between radicular and axial back pain. We generated a receiver operating characteristic (ROC) curve for the score based on the results that we obtained in the previous part of our study. The estimated area under the ROC curve was 0.97. Assuming that the area under the curve (AUC) in the validation study would be 0.90, we calculated that a sample size of 65 patients per diagnostic group would provide 80% power to determine in a two-sided test at the 0.05 significance level whether the AUC is ≥0.80.We employed the software SAS  for the statistical analysis of our validation study. Only complete patient data sets were included in the analysis.U-statistics Using the LOGISTIC procedure of SAS, we performed a logistic regression analysis to examine the relationship between StEP items and the clinical diagnosis of radicular and axial LBP. We fitted a linear logistic regression model for binary response data by the method of maximum likelihood. Based on the regression coefficients of StEP items, we created numerical scores that reflect the size of the contribution of these variables to the outcome. Potential cutoff values for the total StEP score were evaluated based on the number of correctly classified patients and the balance between sensitivity and specificity to identify patients with radicular LBP. We generated an ROC curve for the fitted model and calculated its AUC using the trapezoid rule. An ROC curve is a graphical representation of the test results with the AUC being measured in a range of 0 to 1. Values close to 1 indicate a higher power of discrimination between a positive (radicular LBP) and a negative  test outcome. We also constructed ROC curves for the ten-item and seven-item versions of the DN4 screening tool and for the radiological assessment of nerve root impairment by spinal MRI. To compare the AUCs of ROC curves, we generated an estimated covariance matrix based on a nonparametric approach using the theory on generalized Sensitivity, specificity, and positive and negative predictive values for identifying patients with radicular back pain and the corresponding two-sided 95% confidence intervals (CIs) are provided for each diagnostic method. Areas under the ROC curves are given as mean±standard error.We assessed 219 patients in Part 1 of the study and 155 patients in Part 2 for eligibility. Thirty-two patients in Part 1 and 11 patients in the Part 2 were excluded because the duration or average global intensity of their pain did not meet the inclusion criteria, or because they suffered from other painful disorders, or neurological or psychiatric diseases that would have compromised the evaluation of their pain. Another six patients with LBP were excluded from the validation study, because there was no unanimous decision between the attending physicians on the clinical classification of their pain as radicular or axial. One patient in the validation study was lost to follow-up because his records were incomplete. We used a hierarchical cluster analysis to examine associations between pain-related symptoms and signs in the 187 patients that were included in Part 1 of our study and identified eight subgroups of patients (patient clusters) with distinct constellations of symptoms and signs (pain subtypes) . The cluPatients with DN, PHN, and radicular LBP were distributed across clusters C1 through C6, demonstrating that the symptoms and signs of neuropathic pain that are produced by these diseases overlap considerably . Only thThe physical examination was essential for the distinction of pain subtypes. A cluster analysis based only on physical test results separated clearly between patients with neuropathic and non-neuropathic pain . The resIn contrast, differentiation of patient subgroups based only on symptoms described in the interview was weak and did not discriminate between patients with neuropathic and non-neuropathic pain . The mosPinprick was the most sensitive  and most specific  single test to distinguish between neuropathic and non-neuropathic pain. The response to pinprick was decreased or hyperalgesic in 123 of 130 patients with DN, PHN, or radicular LBP, as opposed to four out of 57 patients with axial LBP. The pinprick test must evaluate a decrease in the detection threshold; pinprick hyperalgesia alone is not a specific indicator of neuropathic pain Elements of the physical examination were also dominant among those variables that were identified in a classification tree analysis as key determinants of the assignment of patients into clusters: response to pinprick and cold temperature, presence of trophic skin changes, and performance in the proprioceptive tests . Pain quOf 112 patients who described numb skin areas in the interview, 89 had a decreased response to at least one tactile or thermal test stimulus in the physical examination; 73 patients had decreased responses in both tactile and thermal tests. However, the physical examination revealed sensory deficits with higher sensitivity (in 130 patients) than the interview. In some patients skin patches with sensory loss were adjacent to areas of stimulus-evoked pain, a mixture of negative and positive signs that is a well-known feature of neuropathic pain Based on the symptoms and signs that differentiated between the eight patient subgroups, we created a short form of the initial pain assessment tool that we named Standardized Evaluation of Pain (StEP). StEP comprises six interview questions and ten physical tests see  that capOur findings indicated two possible applications for StEP, a differentiation of pain subtypes and the dichotomous distinction between neuropathic and non-neuropathic pain. Both applications are clinically valuable, yet reference standards for pain subtypes do not exist, so we decided to validate StEP for the separation between LBP with (radicular) and without  involvement of the nervous system. This distinction, which has immediate consequences for therapeutic decisions We used a logistic regression analysis to determine the size of the contribution of interview questions and physical tests included in StEP to the separation between radicular and axial LBP. The results confirmed our initial observation that physical tests have more discriminatory power than interview items. A positive straight-leg-raising test and abnormal responses to cold stimulation and pinprick were key indicators of radicular LBP . Decreasp<0.001 for either version of the DN4) or not .We compared StEP with a screening tool for neuropathic pain, the DN4 A large number of patients with radicular and axial LBP were included in Part 1 of the study. For an independent evaluation of the logistic regression model that we used to derive the scoring system for StEP, we applied the scores retrospectively to equivalent items of the initial pain assessment tool and determined how back pain would have been classified in these patients. We found that 89% of the patients would have been diagnosed correctly as having radicular or axial LBP, and that the sensitivity and specificity in discriminating between the two groups of patients would have been 79% (95% CI 63%–90%) and 98% (95% CI 89%–100%), respectively. These numbers underline the diagnostic utility of the scoring system. Its reduced sensitivity when applied retrospectively is likely explained by differences between StEP and the assessment tool that we employed to evaluate pain-related symptoms and signs in Part 1 of our study. This initial tool contained more interview questions and physical tests, and there were also minor differences in the wording of questions and test instructions.Fifty-one patients with radicular LBP and 22 patients with axial LBP were examined by spinal MRI. The severity of vertebral endplate abnormalities, intervertebral disk degeneration, and facet joint arthrosis was similar in patients with radicular LBP and patients with axial LBP see .Although the primary aim of the validation was to determine the sensitivity and specificity of StEP in distinguishing radicular from axial LBP, we sought to identify patients with those subtypes of LBP that we had characterized in Part 1 of our study. Based on the criteria specified in the previous classification tree analysis , we foun1 = 4; upper quartile, Q3 = 5) on a numerical scale of 1 (many important aspects of the pain were missed) to 5 (very good representation of the pain). The ease of answering the interview questions was rated 5  on a scale of 1 (very difficult) to 5 (very easy). The ease of compliance with the physical examination also scored as 5 . The willingness to complete the assessment again as a measure of change after treatment was 5  on an NRS from 1 to 5, indicating high acceptance of the assessment tool. We used a two-tailed Wilcoxon rank sum test to compare how patients with radicular LBP and those with axial LBP evaluated StEP and found no significant difference in their assessment of StEP's comprehensiveness (p = 0.96), the ease of answering the interview questions (p = 0.69), or ease of compliance with the physical tests (p = 0.56). Patients in both groups indicated that they would be willing to complete StEP again (p = 0.17).StEP was evaluated by 134 patients. These patients regarded StEP as a suitable and appropriate tool for the assessment of their pain. StEP's comprehensiveness was rated 5  is more likely to result from an increase in the excitability of dorsal horn neurons Patients with neuropathic pain are usually classified based on disease diagnosis. However, we did not find a unique correlation of neuropathic pain-related symptoms and signs with disease except for one pain subtype associated with a subgroup of patients with DN. Disease itself does not predict the occurrence or natural course of neuropathic pain, nor do the etiological factors and pathological changes that define a neurological disease necessarily correlate with mechanisms responsible for the manifestation of spontaneous pain, hyperalgesia, or allodynia, all common features of neuropathic pain We show that a standardized evaluation of pain-related symptoms and signs helps separate patients with neuropathic pain including radicular LBP from those with non-neuropathic  back pain. Distinguishing between radicular and axial LBP is often difficult: nerve root involvement may manifest with a minor sensory or motor deficit, and patients with LBP originating in the facet joints or other structures of the spine may experience pain lateral to the midline, which can be confused with radicular pain. In addition, degenerative changes of the spine are likely to contribute also to back pain in patients with nerve root involvement We validated StEP for its ability to distinguish radicular from axial LBP and found that StEP identifies patients with radicular LBP with high diagnostic accuracy. Based on the results of our validation study, we propose a scoring system that can be implemented in the analysis of StEP to detect radicular back pain. The most discriminatory indicators for radicular pain were a positive straight-leg-raising sign, a deficit in the detection of cold, and a reduced response to pinprick. This is not too surprising: the straight-leg-raising test is routinely performed in the examination of patients with back pain The DN4 screening tool for neuropathic pain was developed in a study not involving patients with radicular LBP Further studies are needed to determine the accuracy of StEP for the distinction of neuropathic and non-neuropathic pain in conditions other than LBP. The discriminatory value of single variables will certainly vary depending on each condition. However, we believe that the interview questions and physical tests included in StEP will be sufficient, because StEP was still highly sensitive and specific in discriminating between radicular and axial LBP after excluding the straight-leg-raising sign, which has utility only for the diagnosis of radicular LBP. Future studies will also have to address important issues such as test-retest and intra- and inter-rater reliability, which we did not investigate here. Whether successful analgesic treatment modifies the presence or intensity of specific painful symptoms or signsremains to be investigated, but the reliability of StEP is likely to be affected by the response to treatment. It is therefore possible that we would have observed different constellations of symptoms and signs in untreated patients, of whom only a few were included in the present study .Spinal imaging is recommended for the evaluation of patients who have LBP that persists beyond 4 weeks, exhibit severe or progressive neurologic deficits, or are suspected of having a serious underlying condition such as vertebral infection or cancer We demonstrate that a standardized assessment of pain-related symptoms and signs provides a simple diagnostic procedure for the distinction between radicular and axial LBP. This distinction is crucial because back pain is a diagnostic label for a heterogeneous group of patients and it is often difficult to decide which patients will benefit from treatment strategies that target neuropathic pain. However, the potential therapeutic implications of a standardized method to identify pain subtypes go beyond the dichotomous separation between neuropathic and non-neuropathic pain. First-line medications recommended for neuropathic pain include anticonvulsants, tricyclic antidepressants, and opioids Figure S1ROC curves reflecting the sensitivity and specificity of the DN4 screening tool for neuropathic pain in distinguishing radicular and axial LBP.(0.52 MB EPS)Click here for additional data file.Figure S2Spinal MRI in patients with LBP. (A) An axial T2-weighted fast spin echo image through the vertebrae L5 and S1 shows a central disk protrusion (arrow) compressing the left S1 nerve root (arrowhead). (B) Marked stenosis (3/3) of the right lateral recess in an axial T2-weighted fast spin echo image through the facet joints of the L4 and L5 vertebrae. (C) An axial T2-weighted fast spin echo image through the L4 and L5 vertebrae indicates bilateral severe (grade 3) arthrosis of the facet joints.(1.00 MB EPS)Click here for additional data file.Table S1Structure of the initial pain assessment that was used to develop StEP.(0.07 MB DOC)Click here for additional data file.Table S2Radiological assessment of nerve root involvement and degenerative changes of spinal structures.(0.07 MB DOC)Click here for additional data file.Text S1Standardized evaluation of pain (StEP).(0.10 MB PDF)Click here for additional data file.Text S2StEP score sheet for the distinction between radicular and axial low back pain.(0.07 MB PDF)Click here for additional data file.