To investigate the effect of surgical decompression on painful diabetic peripheral neuropathy (DPN) patients and discuss the role which pain distribution and characterization play in the management of painful DPN as well as the underlying mechanism involved.A total of 306 patients with painful diabetic lower-extremity neuropathy were treated with Dellon surgical nerve decompression in our department. Clinical evaluation including Visual analogue scale (VAS), Brief Pain Inventory Short Form for diabetic peripheral neuropathy (BPI-DPN) questionnaire, two-point discrimination (2-PD), nerve conduction velocity (NCV) and high-resolution ultrasonography  were performed in all cases preoperatively, and at 6 month intervals for 2 years post-decompression. The patients who underwent surgery were retrospectively assigned into two subgroups  according to the distribution of the diabetic neuropathic pain. The control group included 92 painful DPN patients without surgery.P<0.05). More improvement of VAS, scores in BPI-DPN and CSA was observed in focal pain group than that in diffuse group (P<0.05).The levels of VAS, scores in BPI-DPN, 2-PD, NCV results and CSA were all improved in surgical group when compared to the control group (Efficacy of decompression of multiple lower-extremity peripheral nerves in patients with painful diabetic neuropathy was confirmed in this study. While both focal and diffuse group could benefit from surgical decompression, pain relief and morphological restoration could be better achieved in focal group. There are over 250 million people in the world with type 1 and 2 diabetes mellitus. The management of neuropathic pain in diabetes still remains challenging mainly due to its various clinical features, wide spectrum severity and different distribution involved. Descriptions of pain can be burning, prickling, lancinating, shooting, cramping, aching, and also contact hypersensitivity  and “dead feeling” (numbness) in their legs. Aside from traditional management including glucose control, lifestyle modification and pharmacological treatment, surgical decompression is recommended for pain relief in the recent reports This study is approved by the Xinhua Hospital Ethics Review Board and the forms of consent were obtained from all patients involved in this study.A consecutive series of 306 patients  with painful diabetic lower-extremity neuropathy, who underwent Dellon surgical nerve decompression Inclusion criteria include (1) history of pain in the distribution of the posterior tibial , common and superficial peroneal , or deep peroneal nerves , (2) positive Tinel sign presented at a known site of nerve entrapment including the fibular tunnel at the lateral side of the knee, for the common peroneal nerve, the tarsal tunnel at the ankle for the tibial nerve, and the junction between the first and second metatarsals and the cuneiforms for the deep peroneal nerve, (3) Decreased two-point discrimination: the big toe pulp two-point discrimination was greater than 9 mm Exclusion criteria include (1) presence of defined risk factors such as alcohol, nutrition, uremia and peripheral vascular disease, as demonstrated by absence of a palpable pulse, (2) previous history of cervical and lumbar spondylosis, (3) radiculopathy, (4) pedal edema.The decompression surgery adopting Dellon triple procedures A 3 cm-long incision was made below the fibular head and the skin, superficial and deep fascia was cut. After excision of fascia above the common peroneal nerve and the peroneus longus muscle tendon, the common peroneal nerve trunk was exposed and decompressed.A 6 cm-long curved incision was made along the medial malleolus and the skin, superficial and deep fascia was cut. After excision of the flexor retinaculum, the posterior tibial artery and veins and the tibal nerve were indentified and decompressed. Following this, the abductor halluces brevis was cut and spread to expose and divide the roof of the medial and of the lateral plantar tunnels. The medial calcaneal tunnel was then identified and decompressed. Epineurium decompression was performed if there was evidence of epineurial thickening.A 2 cm-long incision was made longitudinally between the first and second metatarsal heads and the skin, superficial and deep fascia were cut to expose the tendon of the extensor hallucis brevis muscle. This tendon was then excised to decompress the deep peroneal nerve.During the perioperative period, blood glucose was controlled at 6.2–8.0 mmol/L. After the patients were discharged, they were required to monitor their fasting plasma glucose every week and control their blood glucose levels to <8.0 mmol/L.Careful history taking and peripheral neurological/vascular examination were completed in all patients at admission. Aside from pain as a chief complaint, some of them simultaneously presented with other sensory symptoms including numbness, tingling and so forth. Patients were additionally inquired about their functional status, normal activities, ability to work, walking distance, family history of diabetes and the use of medications.Assessment of pain including visual analogue scale (VAS) and Brief Pain Inventory Short Form for diabetic peripheral neuropathy (BPI-DPN), of sensation including plantar big toe and small toe two-point discrimination (2-PD), of morphological changes of nerves employing high-resolution ultrasound, of electrophysiological changes performing nerve conduction velocity (NCV) on admission prior to surgery and then at 6 months intervals for two years after surgery. The follow-up was conducted mainly on an outpatient basis.Pre and post operative evaluations were performed by two clinical residents , one sonographer  and one technician of electrophysiology (performing the NCV tests).The visual analogue scale (VAS) Neurosensory examination mainly included percussion over a distribution of the affected peripheral nerve (Tinel sign) and two-point discrimination (2-PD) using the Disk-Criminator at the big and small toes for medial and lateral plantar nerves, respectively. A positive Tinel sign was taken to be a positive response that indicated either a tingling or radiating electriclike perception either into the heel, the arch, or the toes (the most common responses), or proximally up the inside of the ankle (the least common response) Nerve conduction velocity was detected with the employment of a Denmark Medtronic EMG (DK 1 2740). The testing was performed under a quiet indoor environment with a room temperature of 25°C and skin temperature of 30°C, using surface electrodes for stimulation and recording. Bilateral motor NCVs of tibial nerve and sensory NCVs of the common peroneal nerve and superficial peroneal nerve were recorded in all patients.High-resolution ultrasound of peripheral nerves was performed employing a Sequoia 512 ultrasound device (Siemens) with a 8–14 MHz transducer. Multislice, longitudinal, and transverse scans were made through the common peroneal nerve and the posterior tibial nerve to observe the continuity and echogeneity of the nerves. The anteroposterior diameter (Da) and transverse diameter (Dt) of the nerves were measured at the cross-section of 1.5 cm below the distal tip of fibular head  and distal tip of medial malleolus . And then cross-sectional area (CSA) was calculated by the formula of S = π(Da*Dt/4) 2 test and student's t-test were used with the employment of SPSS 18.0. A P value <0.05 was considered statistically significant.Analysis was performed separately for patients comparing the change from preoperative levels to that of last visit . Data were expressed as the mean ± standard deviation. Pearson’s χP>0.05). The average courses of diabetes mellitus were longer than the average courses of pain symptom in all groups. In some individuals, however, the onset of pain symptom came before the diagnosis of diabetes, some may even lead to the diagnosis of diabetes, in which situation other potential diseases had been excluded before the diagnosis of diabetic neuropathy. There is no statistically significant difference between surgical and control groups and, also no statistically significant difference among the three groups  after dividing the surgical group into two subgroups regarding to the initial VAS level, 2-PD, scores in BPI-DPN, NCV and CSA (P>0.05).Twenty-five patients in surgical groups and six patients in control group were lost during the follow-up. The differences of age, sex, course of diabetes and pain symptom between the two groups were not statistically significant (P<0.01). The average pain level remained between 2 and 1 for the remainder of the study. The mean VAS pain level of patients with diffuse pain was 8.32 and decreased to 3.43 (P<0.01) 6 months after surgery, higher than that of patients with focal pain (P<0.05). The mean pain level of diffuse pain group remained between 4 and 2 with fluctuation for the remainder of the study. The average VAS of patients in control group was 8.03 at first visit and remained around 8.0 during the two-year follow-up (P>0.05). There was a statistically significant difference as to VAS level between surgical and control groups after surgery (P<0.01). The results show pain relief can be achieved through surgical decompression, especially in the patients with focal pain.The VAS levels in different time points were recorded and comparison was made among the three groups to assess the outcome of surgery.  In focalP<0.05) comparing to those before surgery . Analogously, markedly improvement can also be observed when comparison was made between preoperative  and postoperative  big toe and small toe 2-PD in diffuse pain group (P<0.05). There is no statistically significant difference between two groups with regard to both big toe 2-PD (P = 0.73) and small 2-PD (P = 0.77) after decompression. In control group, no statistically significant difference could be seen between preoperative and postoperative 2-PD of big toe  and small toe . A statistically significant improvement in both small toe and big toe 2-PD could be observed between surgical and control groups (P<0.05)  average big toe 2-PD (6.43±1.46 mm) and small toe 2-PD (6.24±1.72 mm) showed a statistically significant improvement ((P<0.05)  A, B.P<0.05). There is also an observable decline  in “Mean severity” two years after surgery in the diffuse pain group (P<0.05). Initial “Mean interference” of focal and diffuse pain group is 4.75±0.86 and 4.73±0.82, which decreased to 1.88±1.15 (P<0.05) and 2.00±1.07 (P<0.05) respectively. Statistically significant difference existed between the two groups regarding both postoperative “Mean severity” (P<0.05) and “Mean interference” (P<0.05). As respect to “Mean severity”  and “Mean interference” , there was almost no changes in control group.The scores of all items in BPI-DPN were recorded, and the “Mean severity” as well as the “Mean interference” was compared in this study.  C, D In P<0.05) while NCVs of patients in control group remained almost unchanged. Statistically significant difference could be observed between the surgical and control groups (P<0.05) while no statistically significant difference existed between the focal and diffuse pain group (P = 0.84) two years after surgery . (P<0.05) and diffuse (P<0.05) pain group after surgery .  The CSA  surgery .All patients underwent surgical decompression recovered well except that three patients suffered from surgical complications. Wound dehiscence in two patients healed within 2 months after strict blood glucose control, antibiotics administration and daily dressing change. One patient with extensive lower-leg subcutaneous hemorrhage was treated by surgical incision and drainage. In the control group, ten patients developed superficial ulcers in the lower-limb and two underwent surgical amputation during this period. None of the operated patients had developed new ulcer, ulcer progression or amputation in two-year follow-up.Diabetic neuropathy has traditionally been considered as an irreversible condition and the treatments are mostly symptomatic aiming to prevent the development of complications rather than to target the underlying pathologic mechanisms. Painful DPN can be divided into two varieties: acute and chronic painful DPN. Here we mainly focus on chronic painful DPN due to its highly prevalence and the facts that acute painful DPN is relatively rare and the acute symptoms may resolve within a year. The answer to the question of “what is the pathophysiology behind the distinct reaction to the decompression between patients with focal or diffuse painful DPN” should be started with the mechanisms of neuropathic pain in diabetes. Although the exact pathophysiological mechanisms of neuropathic pain in diabetes remain enigmatic, several mechanisms including peripheral and central mechanisms have been postulated based on the result of experiments in animal model of neuropathic pain. Diabetes causes deposition of collagen in the small arteries that supply the peripheral nerves, hypothetically resulting in a length-dependent sensorimotor neuropathy. Increased aldose reductase activity in diabetes converts glucose to sorbitol, which is hydrophilic and draws water into the nerve, rendering the peripheral nerve susceptible to mechanical compression and decreasing the slow axoplasmic transport in the diabetic nerve. As a consequence, proteins for structural repairs could not be transported to the impaired site within the diabetic nerve. Given all that above, in the early stage of some cases, nerve thickening is suggested to play a fundamental role in the pathophysiology of painful diabetic neuropathy, with a manifestation of focal pain. As such, it is conceivable that entrapment of affected nerves at sites of anatomic narrowness may occur, which could be treated through surgical decompression. As the compression continues, however, neuroplastic changes in central nervous system happen after reorganization of structures participating in the processing of noxious information, which may present with diffuse pain in certain patients. The management is rather complicated. Aside from the current medical therapies including tricyclic antidepressants, the serotonin and noradrenaline re-uptake inhibitor and anti-convulsants, and so forth, an unmet need still exists for pharmacological agents targeting the underlying mechanisms due to the ineffectiveness and the side effects of the available drugs. In this study, the severity of pain, two-point discrimination, NCV results and morphological changes (SCA) of compressed nerve were all improved in surgical group when compared to the control group. Furthermore, there is no significant difference between the focal and diffuse pain groups regarding the results of two-point discrimination and NCV testing, which was increased by 15–20% after nerve decompression.  ThereforThe limitations in our study include: (1) although being queried on admission, non-surgical treatment such as pharmacotherapy of neuropathic pain was not precisely measured among all the patients due to the retrospective nature of this study. For this reason, preoperative evaluation including pain levels was performed with both VAS and BPI-DPN and no significant difference was observed. (2) The specific definition of the focal and diffuse pain. Although extent of pain in most patients is relatively invariable, parts of patients would experience both focal and diffuse pain during the course of painful DPN. The phenotype of pain was decided on admission prior to surgery. Further prospective, randomized and controlled trial with blinded study executers and observers is needed to verify the role of peripheral nerve decompression in patients with painful DPN and further elucidate the role which pain distribution and characterization play in managing painful diabetic neuropathy as well as the underlying mechanism involved.Allowing for the mixed results reported and the continuing controversy among researchers as to the effectiveness of nerve decompression surgery on DPN, The results of this study continue to support the efficacy of decompression of multiple lower-extremity peripheral nerves in patients with painful diabetic neuropathy who presented with a positive Tinel sign. Favorable outcomes could be achieved in treating focal painful DPN through surgical decompression, which would also be helpful and should not be abandoned in diffuse painful DPN in the presence of Tinel sign.


Single-photon emission computed tomography-computed tomography (SPECT-CT) is a highly sensitive tool for detecting bone metabolism. We determined whether subchondral bone metabolism, as indicated by SPECT-CT in the patellofemoral (PF) joint, predicts response to conservative management in middle-aged patients with chronic anterior knee pain (AKP), and whether SPECT-CT results correlate with arthroscopic assessments of chondral lesions in the PF joint.The study group comprised 74 middle-aged patients with chronic AKP. All of the patients underwent SPECT-CT, and the results were graded along a scale of 0 to 3°. After 8 weeks of conservative management, they were grouped as responders (n = 40) or non-responders (n = 34) according to symptom improvement. We compared the median scintigraphic uptake of the PF joint between the two groups, and evaluated the positive predictive value (PPV) of uptake for treatment response in each patient. In non-responders, cartilage condition was assessed during arthroscopy, and the correlation of scintigraphic uptake with severity of the chondral lesion was assessed.vs. 1). Among patients with higher patella uptake (grade 2 or 3), the PPV for non-response to conservative therapy was 62–67 %, whereas it was 24–25 % in patients with lower uptake (grade 0 or 1). Patella uptake corresponded strongly with arthroscopic assessment of patellar chondral lesions; the correlation was less strong for the femoral trochlea.The median scintigraphic uptake in the patella was higher in non-responders than in responders (2 Increased subchondral bone metabolism in the patella is associated with responsiveness to conservative therapy. SPECT-CT can benefit clinicians by predicting the treatment response from conservative management. Anterior knee pain, or anterior knee pain syndrome, is one of the most common orthopedic disorders –4. This Functional images generated by the administration of radioactive tracers, which map metabolic changes, can also assess a variety of orthopedic problems –17. In pWe retrospectively reviewed a prospectively collected database of 151 patients with anterior knee pain who presented at our outpatient clinic from August 2009 to December 2011. All of the patients provided informed consent regarding the use of their medical records. Patients were selected based on the following criteria: age between 40 and 65 years, lack of traumatic cause of knee pain, and pain lasting at least 8 weeks. Patients presenting with a chief complaint of anterior knee pain were evaluated by radiography including a standing anteroposterior (AP) knee radiograph, a standing 45° flexion posteroanterior radiograph (Rosenberg view), 30° lateral knee radiographs, a Merchant PF radiograph, and a standing full-limb radiograph. The radiographic presence and degree of radiographic knee osteoarthritis (OA), as well as the presence of tibiofemoral (TF) and PF joint malalignments were assessed; sulcus angle, congruence angle, and Insall-Salvati ratio were also measured. In addition, patients underwent routine blood tests including uric acid, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) to exclude the possibility of inflammatory knee arthritis. A single investigator (SBK) also took a detailed history and performed a comprehensive physical examination to determine the presence of previous trauma or other predisposing factors for anterior knee pain, as well as the presence of ligament injuries and/or meniscal injuries.2 . The average sulcus angle was 129.7° , the average congruence angle was −4.4° , the Insall-Salvati ratio was 0.97 , and the average Q angle was 9.9 ° . All of the study protocols were approved by the institutional review board of our hospital .Of the 151 patients, 77 patients were excluded for the following reasons: (1) radiographic evaluation yielding Kellgren-Lawrence OA grade ≥ 2 in the PF and/or TF joints (n = 31); (2) history of knee, spine, or hip surgery (n = 17); (3) pain in the affected leg other than anterior knee pain, such as radiating pain (n = 5); (4) any form of knee instability on physical examination, a positive McMurray test, or a limited range of motion (n = 10); (5) any evidence of inflammatory knee arthritis such as gout or rheumatoid arthritis (n = 4); (6) evidence of habitual or recurrent patellar instability on physical examination, such as the apprehension test, passive patella translation test, J-sign test, and patella tilt test (n = 10). In total, 74 middle-aged patients remained with unilateral, atraumatic, and isolated anterior knee pain. The study population included 51 female and 23 male patients with a mean age of 54 years  and a mean body mass index (BMI) of 26.3 kg/mAll of the 74 patients underwent SPECT-CT using the Infinia™ Hawkeye® 4 device , which incorporates bone scintigraphy and a CT scan in a one-step procedure. Patients were injected with 1110 MBq (30 mCi) Tc-99 m hydroxymethylene diphosphonate (HDP), and images were taken 3 h post-injection. Multiplanar two-dimensional SPECT images were reconstructed in three phases . Multi-slice CT images  of the entire lower extremity with multi-planar reconstruction  were also constructed. Scintigraphic uptake was graded on the following scale: grade 0, no uptake ; grade 1, higher uptake than normal cancellous bone, but lower than articular surface; grade 2, same uptake as the articular surface; grade 3, higher uptake than the articular surface , quadriceps strengthening exercises , and nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were re-evaluated at 4 weeks to determine compliance, and at 8 weeks to determine treatment response. They were classified into two groups: (1) responders (n = 40), whose knee condition improved by 8 weeks ; and (2) non-responders (n = 34), whose knee condition did not improve (knee pain rated as 3 or more on the VAS)  for both the patella and femoral trochlea. Fisher’s exact test was used to compare the number of non-responders in each uptake group. To examine the correlation of scintigraphic uptake and arthroscopically assessed focal chondral lesion severity in the PF joint among non-responders, we assessed agreement between the two values using Goodman and Kruskal’s gamma (γ) statistics. Gamma statistics were rated by the following criteria: γ > 0.81, very good agreement; 0.8 ≥ γ > 0.61, good agreement; 0.6 ≥ γ >0.41, moderate agreement; 0.4 ≥ γ >0.21, fair agreement; γ < 0.2, poor agreement.All of the statistical analyses were performed using the statistical package SPSS® 19.0.1 for Windows® ; vs. 1). However, median scintigraphic uptake in the femoral trochlea did not differ between non-responders and responders (2 vs. 2) . The PPV of non-response for grade 2 or 3 patella uptake was 62 to 67 %. In contrast, only 24–25 % of patients with grade 0 or 1 patella uptake did not respond to treatment. However, the proportion of non-responders did not differ between patients with high and low uptake in the femoral trochlea (Table No differences in mean age, gender distribution, BMI, or any radiological measurements were evident between responders and non-responders Table . Scintigsponders  vs. 2 (FAmong the 33 non-responders whose patellae were arthroscopically assessed, scintigraphic uptake correlated with the pathological grade of chondral lesions Fig. . BesidesThe most important finding of our study is that a higher degree of subchondral metabolism in the PF joint in patients with chronic anterior knee pain, particularly the patella, is predictive of a poorer response to conservative management. To date, this is the first study to show a relationship between SPECT-CT uptake and treatment response for chronic anterior knee pain.Increased subchondral metabolism detected has been consistently observed by scintigraphy in anterior knee pain patients. Naslund et al.  found diSPECT-CT is increasingly recognized by the orthopedic field for its ability to identify changes in subchondral bone at a high spatial resolution , 16, 20.Interestingly, patellar metabolic tracer uptake, and not trochlear uptake, was predictive of benefit from conservative management. We speculate that the higher shear stress in patellar cartilage than in the femoral trochlea during activity underlies this result . IncreasArthroscopic assessment of the 33 non-responders yielded a stronger correlation between scintigraphic uptake and pathological grade of chondral lesions in the patella. Our findings provide additional information on this issue: a more severe chondral lesion is more likely to lead to metabolic changes, which may be associated with a poorer prognosis. Although there is no widely accepted definition of early OA, altered subchondral bone metabolism with a higher grade chondral lesion and accompanying pain is a key feature of early stage OA , 24. TakSeveral limitations of the present study require consideration. First, because this study included only middle-aged patients, our findings may not be generalizable to patients in other age groups. However, we confined the study to middle-aged patients, because this patient group presents a significant diagnostic challenge in clinical practice. Second, because the optimal treatment method for chronic anterior knee pain is controversial, it may be debatable whether our conservative management was adequate. However, we applied an 8-week program of comprehensive conservative management, including activity modification, muscle strengthening exercise, and use of NSAIDs; in addition, we determined compliance with management at four weeks. Thus, we believe that this program is adequate to determine responsiveness to conservative management of chronic anterior knee pain. Third, the present study did not involve a control group for investigation of correlation between metabolic tracer uptake and arthroscopic grades, as we did not evaluate the knees of responders arthroscopically. However, because such an invasive procedure is unethical in the absence of a clinical problem, results from this group would be less meaningful in practice. Fourth, outcomes after arthroscopic surgery were not presented. Although our preliminary results reveal the effectiveness of arthroscopic procedures in non-responders, we believe that inclusion of clinical results after surgery is beyond the goals of this study and might create redundancy. We hope to address this issue in the future by assessing longer term follow-up results. Fifth, we did not conduct predictive modeling; future studies are required to confirm the potential of SPECT-CT for predicting the clinical response to conservative therapy. Sixth, we did not use absolute VAS values, rather dichotomizing responder and non-responders using a VAS pain score cutoff of 3. Although the use of absolute VAS scores would have yielded more information, we found that VAS pain scores varied widely over time. Thus, we considered that use of a cutoff average VAS score for each patient would allow us to more reliably distinguish responders from non-responders.Patients with greater metabolic tracer uptake in the PF joint on SPECT-CT, particularly in the patella, are less likely to respond to conservative management; furthermore, patella uptake correlates with arthroscopically assessed grading of patellar chondral lesions. These findings suggest that SPECT-CT can aid clinicians in predicting treatment response from conservative management in middle-aged patients with isolated atraumatic unilateral anterior knee pain. In addition, the findings suggest that more aggressive treatment should be considered for patients with high patellar uptake on SPECT-CT.


Pain and function improve dramatically in the first three months after hip and knee arthroplasty but the trajectory after three months is less well described. It is also unclear how pre-operative pain and function influence short- and long-term recovery. We explored the trajectory of change in function and pain until and beyond 3-months post-operatively and the influence of pre-operative self-reported symptoms.The study was a prospective cohort study of 164 patients undergoing primary hip (n = 80) or knee (n = 84) arthroplasty in the United Kingdom. Self-reported measures of pain and function using the Western Ontario and McMaster Universities Osteoarthritis index were collected pre-operatively and at 3 and 12 months post-operatively. Hip and knee arthroplasties were analysed separately, and patients were split into two groups: those with high or low symptoms pre-operatively. Multilevel regression models were used for each outcome (pain and function), and the trajectories of change were charted (0–3 months and 3–12 months).Hip: Most improvement occurred within the first 3 months following hip surgery and patients with worse pre-operative scores had greater changes. The mean changes observed between 3 and twelve months were statistically insignificant. One year after surgery, patients with worse pre-operative scores had post-operative outcomes similar to those observed among patients with less severe pre-operative symptoms. Knee: Most improvement occurred in the first 3 months following knee surgery with no significant change thereafter. Despite greater mean change during the first three months, patients with worse pre-operative scores had not ‘caught-up’ with those with less severe pre-operative symptoms 12 months after their surgery.Most symptomatic improvement occurred within the first 3 months after surgery with no significant change between 3–12 months. Further investigations are now required to determine if patients with severe symptoms at the time of their knee arthroplasty have a different pre-surgical history than those with less severe symptoms and if they could benefit from earlier surgical intervention and tailored rehabilitation to achieve better post-operative patient-reported outcomes. Joint replacement is a common elective surgical procedure, with more than 158,000 primary hip and knee arthroplasties performed during 2013 in England, Wales and Northern Ireland .Many studies have reported important improvement in patient-reported outcomes by comparing scores completed at baseline and at one single post-operative assessment usually 6 or twelve months after the arthroplasty. FindingKnown determinants of post-operative outcome following hip and knee arthroplasties include patients’ expectations, mental health status, co-morbidities and the severity of pre-operative pain and function –25. PatiFrom the data available it is difficult for a surgeon to make an accurate prediction of how an individual patient is likely to recover post-operatively  and it iThe aims of our study were to use information obtained from a cohort study to describe the trajectory of change after primary hip and knee arthroplasty, and to determine the effects of pre-operative pain and function on these trajectories and on outcomes one year after surgery.th December 2009 by the Southwest 4 Research Ethics Committee (09/H0102/72) and all patients provided informed, written consent.ADAPT is a single-centre UK prospective cohort study including people undergoing hip and knee arthroplasties. The study is registered on the NIHR Clinical Research Network Portfolio (UKCRN ID 8311). Its main purpose is to assess ways in which function can be assessed. The study was approved on 24Detailed information on study design, patient recruitment, inclusion-exclusion criteria, and assessment methods are provided in the published study protocol . BrieflyAssessments were conducted prior to surgery  and then at 3 and 12 months after surgery. At each post-operative assessment time, participants completed a postal questionnaire. Pain and functional ability were assessed by self-report using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) function and pain sub-scales . The WOMTo ensure we had a sufficient number of patients to perform meaningful data analysis, we aimed to recruit approximately 250 patients for the main ADAPT study. However, the trajectory of recovery was expected to differ between patients listed for primary surgery and those listed for revision surgery. The latter participants were not considered in this research and analyses reported here focus on the group of ADAPT participants who underwent a primary arthroplasty. Analyses were conducted separately for patients undergoing hip and knee surgery. To investigate the influence of pre-operative function on the post-operative recovery pattern, patients were split into two groups: those with high or low pre-operative function using the median pre-operative WOMAC-function score as a cut-point. The median was chosen as a cut-point to prevent major imbalance by creating groups of equal size. A similar strategy was used for pain. Two participants undergoing hip surgery and one undergoing knee surgery who participated in the post-operative follow-up had missing pre-operative pain and function WOMAC scores. Their pre-operative high/low profiles were determined with a single imputation technique using regression models and the longitudinal measures of WOMAC-pain and function as independent factors.We used univariate linear multi-level regression analysis, one for each outcome (WOMAC-pain and WOMAC-function) to model longitudinal trajectories (group changes) and conduct between-group comparisons of the change pattern. This approach accounts for repeated and unequal number of measurements per participant while producing estimations valid under the missing at random assumption . FunctioChange was modelled as two linear splines (a line between two points): one spline for the “short-term change” occurring between the pre-operative assessment and the second assessment (3 months post-operative) and another spline for the “long-term change” occurring between the two post-operative assessments (3 and 12 months). These changes were normally distributed  allowing us to use the models presented above. The regression models were stratified by high/low pre-operative status. They were adjusted for the above two time splines, and random effects on the intercepts and slopes were modelled. Differences in the short-term or long-term changes between groups were tested using appropriate linear contrasts. Contrary to the changes between measurement points, outcome scores at each post-operative measurement occasion (3 months or 12 months) were non-normally distributed. Group comparisons of time-specific post-operative observed scores were therefore conducted with Mann-Whitney tests. A p-value of <0.05 was considered statistically significant. All models were fitted using Stata SE 13.1 and MLwiN v2.31 using Stata runmlwin command .Overall, 1451 eligible patients listed for hip or knee arthroplasty were approached about the ADAPT study and 264 agreed to take part (recruitment rates of 20% for patients waiting for hip surgery and 17% for those waiting for knee surgery). Of those who gave informed consent to participate, we excluded three people who did not subsequently undergo surgery and 12 people in whom all pre-operative data were unavailable. Patients who underwent a revision surgery (n = 85) were not considered for this study. Of those included in the final analysis, 80 had a primary total hip arthroplasty and 84 had knee arthroplasty .At 12 months post-operative, 89% of the participants who underwent primary hip surgery and 86% of those who underwent primary knee surgery had complete WOMAC-pain and function scores. These rates were comparable by pre-operative high/low pain or function status using Fisher’s exact test: hip: pain p = 0.73, function p = 0.15; knee: pain p = 0.54, function p = 0.76. For hip surgery, three patients withdrew after their surgery, one after the three months assessment and five were lost to follow-up. For knee surgery, six patients withdrew after their surgery, two after the three months assessment and four were lost to follow-up.2  for hip participants and 31 kg/m2  for knee participants.The demographics and clinical characteristics of the cohort are shown in The distributions of participants by high or low pre-operative WOMAC-function and pain scores are presented in Self-report functional ability and pain both improved after surgery, as shown in Improvements in function and pain mainly occurred within the first 3 months. Patients with low pre-operative function experienced short-term functional improvements that were larger than those reported by patients with high pre-operative function, between-group difference in monthly mean change in WOMAC-function standardised score 0.39 (95% CI 0.30, 0.48; p<0.001, Short-term pain improvements were also larger for those with high pre-operative pain, between-group difference in monthly mean change in WOMAC-pain standardised score 0.42 (95%CI 0.34, 0.51, Patients experienced an improvement in self-reported function and pain after their knee surgery, with this improvement occurring primarily in the first three months, as shown in Patients with low pre-operative function reported short-term functional improvements that were larger than those reported by patients with high pre-operative function, between-group difference in monthly mean change in WOMAC-function standardised score 0.14 (95%CI 0.04, 0.25; p <0.01, Short-term pain improvements in pain were also larger for participants with high pre-operative pain compared to those with low pre-operative pain, between-group difference in monthly mean change in WOMAC-pain standardised score 0.17 (95%CI 0.03, 0.30; p = 0.014, The majority of the symptomatic gain made after both hip and knee arthroplasty was achieved within the first three months after surgery. No significant mean change beyond three months was observed in our sample. Patients with worse pain and functional limitations prior to surgery had the greatest capacity to benefit from arthroplasty. They had larger improvements during the first three months of their surgery than those with better pre-operative scores; beyond this period, the mean changes in pain and function were not related to pre-operative scores. One year after surgery, the levels of pain and function achieved by those who underwent a primary total hip arthroplasty were not dependent on pre-operative pain and function. In contrast, patients who had the most severe pain and functional impairment prior to knee arthroplasty never achieved as good an outcome as those with less severe pre-operative pain and functional limitations.Our results on improvements in function and pain after surgery are in agreement with previous studies which show that most of the recovery as measured by self-reported outcomes occurs in the first few months after arthroplasty , 16, 39.We have found that the associations between pre-operative pain and function scores and the course of recovery differ between patients undergoing hip and knee arthroplasty. Our findings showing that the level of pre-operative pain/function influences the course of recovery and level of score reached at 12 months after knee surgery is consistent with previous research , 28, 40.The absence of an association between the pre-operative score and post-operative pain and function outcomes following hip arthroplasty is in disagreement with several studies , 28, 40 The absence of significant improvements observed after three months may be a consequence, at least in part, from the ceiling effect inherent in patient reported outcome measures used in arthroplasty research –46. PatiThe strengths of the study include the use of robust and validated outcome measures, good follow-up rates, more than one follow-up point, and a reasonable sample size for this type of investigation. The use of linear mixed regression models allowed the modelling of the repeated measures of pain and function and facilitated the use of all available observations including those of patients who did not participate in all follow-ups while providing estimations valid under the missing at random assumption.The apparent limitation of a relatively low participation rate is not, in our view, a major problem because this was not a trial, the overall demographics of those taking part are similar to those found in other studies, and we achieved the wide variation in disease severity at baseline which we were aiming for. Participation rates are explained by the high burden of attending additional research appointments in the ADAPT study. It is possible that those who agreed to take part differed from those who declined with regard to important determinants of the outcome of arthroplasty, such as mental health. Furthermore, this cohort is a single centre study limiting its external validity as context and culture may influence outcomes .The modest sample size limited our ability to adjust for factors known to be associated with post-operative outcomes such as age, gender, mental health and co-morbidities , 50, 51.We analysed results of patients who underwent unicompartmental and total knee arthroplasty together to keep a large enough study group. Evidence suggests that following unicompartmental knee surgery there is a faster recovery and lower rates of adverse events , 53. OthMeasuring outcomes only at 3 and 12 months is another limitation of the study, as inclusion of additional assessment points would have allowed more detailed investigation of recovery trajectories. We considered that additional assessment points would be too much of a burden for participants with a probability of increased levels of attrition.Losina and Katz  discusseMost of the improvement following hip and knee arthroplasty occurs within the first three post-operative months with no subsequent statistically significant improvement. Patients with worse pre-operative function or pain report poorer outcome at 12 months after knee arthroplasty, but not hip arthroplasty. Further investigations are now required to determine if patients with severe symptoms at the time of their knee arthroplasty have a different pre-surgical history than those with less severe symptoms and if they could beneficiate from earlier surgical intervention, when symptoms are less severe, and/or tailored pre- and post-operative rehabilitation to achieve better post-operative patient-reported outcomes.


Diabetic peripheral neuropathy (DPN) is a common, symptomatic, long-term complication of diabetes mellitus. Many of the agents used to treat DN have not been compared with each other. This study was, therefore, undertaken to compare the efficacy and safety of carbamazepine, pregabalin and alpha-lipoic acid in diabetic neuropathy patients.This was a prospective, observational study. The patients were categorized into three groups, Group I included those patients who were prescribed carbamazepine while group II included those on pregabalin and group III patients received alpha-lipoic acid. Each patient was followed up at every month for total duration of 6 months. Demographic details, presenting symptoms, history of diabetes, laboratory values pertaining to diabetes  were recorded. Intensity of pain, using a visual analogue scale (VAS), diabetic neuropathy symptom (DNS) score and diabetic neuropathy examination (DNE) score were assessed at baseline and then at each monthly follow-up. Nerve conduction velocity (NCV) was also measured at baseline and then at the end of 3 and 6 months.A total of 101 patients were enrolled out of them 96 completed the study. Regarding VAS, the number of patients having pain was reduced substantially however, the speed and the quantum of this reduction were best in group II . Regarding DNS, also group II showed the best response in terms of number of patients as well as the speed of improvement. The results also imply that the relief from diabetic neuropathy (as per DNE score) is superior with pregabalin administration. However, no improvement in NCV was evident in any group.Results of this study suggest that treatment with pregabalin gives faster and better improvement in diabetic neuropathy. Diabetic peripheral neuropathy (DPN) is a common, symptomatic, long-term complication of type 1 and 2 diabetes mellitus. At the initial diagnosis, 10% of the patients already experience pain, and about 50% are afflicted with this complication after 25 years of the disease . It leadA large number of randomized clinical trials have been conducted to assess the efficacy of various therapeutic agents but the results have been disappointing, most probably due to the complexity of mechanisms involved in its pathogenesis ,6. ThereThis was a prospective, observational study conducted at the Diabetic outpatient department, of a tertiary care, teaching hospital. The study was carried out over a period of 21 months from October 2010 to June 2012. Approval from The Institutional Ethics Committee  was obtained. The enrolled patients were followed up monthly for 6 months. They were categorized into three groups according to treatment prescribed by the physician. Group I included those patients of diabetic neuropathy (DN) who were prescribed carbamazepine while group II included those on pregabalin and group III patients received alpha-lipoic acid. Demographic details, presenting symptoms, history of diabetes, laboratory values pertaining to diabetes  were recorded. Several tests were conducted to assess the severity of DN and its amelioration in response to the treatment given. Intensity of pain, using a visual analogue scale (VAS), diabetic neuropathy symptom score (DNS) and diabetic neuropathy examination score (DNE) were assessed at baseline and then at each monthly follow-up. Nerve conduction velocity (NCV) was measured at baseline and then at the end of 3 and 6 months.The VAS used for measuring the pain intensity was a 10-cm horizontal line that ranged from no pain (0) to worst pain (10) imaginable with mild, moderate, severe and very severe grades . DNE scoThe value of each test was compared with baseline and between groups using Fisher’s exact test andone way analysis of variance (ANOVA). Adverse drug reactions were recorded and analysed.p < 0.05) reduction in number of patients having polyuria  and polydypsia  was observed in each group at the end of the study. At baseline the most common presenting symptom of diabetic neuropathy (DN) was burning/aching pain in one or both lower limbs reported by all patients. Pricking sensation in one or both lower limbs was the next common symptom reported by majority of the patients in all three groups . Improvement in symptoms of DN was noticeable in all three groups but it was relatively faster and better in patients of group II  starting from first follow up itself. In all the groups, a significant (p < 0.05) improvement in FBS, PPBS and HbA1c was also seen in with effect from first or second follow up and was maintained until the end of study.A total of 101 patients were enrolled for the study. Out of them 96 completed the study  whereas 5 patients were lost to follow up due to non compliance. The mean age of patients in group I (carbamazepine) was 54.5 ± 8.3 years, 54.8 ± 7.2 years in group II  and 57.3 ± 8 years in group III . The average duration of diabetes was 10.43 ± 3.42 years . There were 51 patients taking oral hypoglycemic drugs, 12 patients received insulin while 33 patients were receiving both. Hypertension was the most common concomitant disease (n = 47). At baseline, the most common symptom of diabetes was polyuria  followed by polydypsia . A significant (p < 0.05) number of patients had ‘no pain’ with effect from 3rd follow up in group I, 1st follow up in group II and 2nd follow up in group III. A further analysis of patients having ‘no pain’ revealed that group II had significantly (p < 0.05) higher rate of improvement as compared to other groups up to fourth follow up, while there was no significant difference between groups I and III. It is apparent that while the number of patients having mild, moderate, severe and very severe pain was reduced substantially by the end of the study (as compared to baseline), the speed and the quantum of this reduction was best in group II .Severity of pain (as assessed by VAS) was classified into six categories, 0 = no pain, 1–2 = mild, 3–4 = moderate, 5–6 = severe, 7–8 = very severe and 9–10 = worst pain. A detailed classification of patients in each category is given in Table p < 0.05)  was also calculated at every follow up. An approximately similar number of patients were observed to be having zero score by the end of this study. However, group II showed the best response in terms of number of patients as well as the speed of improvement as compared to group I and III. The difference in improvement between group II and group I and III was statistically significant  Figure .p < 0.05) improvement was evident only in group II at fifth and sixth follow ups (6 and 8 patients out of 32 respectively). It was observed that the number of patients with absence of DN (score less than 3) was significantly more in group II than group I and III. The difference noted between group I and III was statistically insignificant  and parameters of DN  was studied. Only group I showed a significant (p < 0.05) correlation between FBS and VAS (correlation coefficient (r) was 0.35, confidence interval (95%) 0.01 to 0.6 and coefficient of determination (r ) 0.12). Regarding safety, the drug therapy was well tolerated in all groups. Only three (3) adverse drug reactions were reported during the study period. Two patients developed rashes with carbamazepine while one had somnolence with pregabalin. These ADRs were non-serious in nature and the patients recovered completely.p < 0.05) improvement in burning/aching pain and pricking sensation was found in all the treatment groups at various follow ups. However, patients treated with pregabalin showed the best response in terms of rate (100%) and speed of improvement. While a similar results for early and sustained improvement with pregabalin have been reported [Diabetic neuropathy is a common long term complication of diabetes mellitus affecting nearly 50% of the patients . The meareported , a meta-reported .p < 0.05) in all the groups. However, the reduction in mean VAS scores and in number of patients having ‘no pain’ was relatively better with pregabalin. It is difficult to explain a superior response to pregabalin. It, however, appears that a unique mechanism action of pregabalin may be responsible for this. Pregabalin blocks alpha 2 delta protein, an auxillary subunit of voltage gated calcium channel. It also reduces the synaptic release of several neurotransmitters apparently by the same mechanism which possibly results in the reduction of neuronal excitability and ultimately the pain [We conducted several specialized tests to evaluate the status of pain , other symptoms (diabetic neuropathy symptom score) and signs (diabetic neuropathy examination) of diabetic neuropathy as well as the peripheral nerve physiology (nerve conduction velocity). As known, pain and sensation abnormality are the classical symptoms of DN. We evaluated them by using visual analogue scale (VAS) and neuropathy symptoms score (DNS) respectively. VAS is a reliable, valid and widely used test to assess the pain intensity. According to VAS score six categories can be classified ranging from no pain (0) to worst possible pain (9–10) . Our resthe pain . On the the pain . It compthe pain . Number Another special test conducted during this study was diabetic neuropathy examination (DNE) score. This is a sensitive and well-recognized scoring system that is fast and easy to perform in clinical practice. Its predictive value is high both for screening and prognosis of diabetic neuropathy . It consWe also conducted the tests on nerve conduction velocity in patients of DN in this study. Nerve conduction velocity (NCV) is the most sensitive and specific method for detection of DN. The use of NCV is recommended for early diagnosis as well as follow-up in DN . Comparip < 0.05) improvement in various tests of diabetic neuropathy  and glycemic control (FBS) was observed separately with all three treatments. It gives an impression that the improvement in DN may have been due to the improved glycemic control with anti-diabetic drug therapy. On further analysis, however, it was observed that a significant correlation between FBS and the parameters of DN did not exist in any of the groups. A small exception was the correlation between FBS and improved VAS score in patient treated with carbamazepine. It is therefore opined that the improvement in DN in any of the groups was not due to a better glycemic control but it rather appears to be due to the specific treatment  received by the patients. It is also concluded that the medication received by the patients in our study was very well tolerated as very few adverse drug reactions of mild variety were reported during this period.A strong correlation between improvement in glycemic control and diabetic neuropathy has been reported in various trials . In presResults of this study suggest that treatment with pregabalin is associated with faster and better improvement in diabetic neuropathy. Effectiveness of alpha lipoic acid appears to be equivalent to pregabalin. However, carbamazepine appeared to be inferior to the other two drugs. Use of pregabalin as first line therapy in diabetic neuropathy is, therefore, justified and recommended.There is no competing interest of the author.NM carried out the study, PP, VM and RKD carried out the initial designing of study, reviewing and final drafting activities. All authors read and approved the final manuscript.


Objective. To develop and evaluate process indicators relevant to biopsychosocial history taking in patients with chronic back and neck pain. Methods. The SCEBS method, covering the Somatic, Psychological , and Social dimensions of chronic pain, was used to evaluate biopsychosocial history taking by manual physical therapists (MPTs). In Phase I, process indicators were developed while in Phase II indicators were tested in practice. Results. Literature-based recommendations were transformed into 51 process indicators. Twenty MTPs contributed 108 patient audio recordings. History taking was excellent (98.3%) for the Somatic dimension, very inadequate for Cognition (43.1%) and Behavior (38.3%), weak (27.8%) for Emotion, and low (18.2%) for the Social dimension. MTPs estimated their coverage of the Somatic dimension as excellent (100%), as adequate for Cognition, Emotion, and Behavior (60.1%), and as very inadequate for the Social dimension (39.8%). Conclusion. MTPs perform screening for musculoskeletal pain mainly through the use of somatic dimension of (chronic) pain. Psychological and social dimensions of chronic pain were inadequately covered by MPTs. Furthermore, a substantial discrepancy between actual and self-estimated use of biopsychosocial history taking was noted. We strongly recommend full implementation of the SCEBS method in educational programs in manual physical therapy. Since the introduction of the biopsychosocial disease model by Engel , there hTogether with contributions from many other similar papers, a publication by Waddell in 1987 in particular catalyzed the worldwide introduction of the biopsychosocial model for patients with spinal disorders . The lasThe process of clinical reasoning consists of a diagnostic phase , a treatment phase (treatment plan and treatment), and an evaluation phase . The “history taking” is the first step in the diagnostic phase and is crucial to the orientation on the health problem of patients with (chronic) musculoskeletal pain in terms of (impairments in) body functions and structures, activity (limitations), participation (restrictions), and personal and environmental factors. The SCEBS method, developed in 1995 by Van Spaendonck and Bleijenberg , is designed as a diagnostic frame work for general practitioners who are less familiar with the biopsychosocial history taking in patients with (chronic) pain. –9. This The transparency of the SCEBS method-based process of history taking, using measurable elements such as Quality Indicators (QIs), is seen as one of the cornerstones of the quality of care, particularly the quality of manual physical therapy in patients with (chronic) musculoskeletal pain. QIs have been defined as “measurable elements of practice performance for which there is evidence or consensus that they can be used to assess the quality, and thus change the quality, of care provided” , 13. QIsThe present study focused on the development and evaluation of process indicators in patients with chronic musculoskeletal pain, with an emphasis on nonspecific back and neck pain. The two primary goals of this study were (1) to develop a set of process indicators relevant to biopsychosocial history taking in patients with nonspecific back and neck pain and (2) to subject this set to a pilot practice test to determine its value in assessing the actual extent of implementation of biopsychosocial history taking in Dutch manual physical therapy practice.The study consisted of two phases: (i) indicator development and (ii) indicator testing through a pilot practice test. The QI development included three steps: (i) extraction of recommendations from original description of the SCEBS method and related literature, (ii) transformation of recommendations into process indicators, and (iii) classification of process indicators according to the SCEBS method. For the pilot practice test, we used an observational prospective cross-sectional design to test the integration of biopsychosocial history taking in manual physical therapy practice.The Medical Ethics Committee of Radboud University Medical Centre Nijmegen in the Netherlands stated in writing that ethical approval was not necessary. Each practice formally consented to participate in the study and all patients were informed about the study and gave permission for anonymous use of data.Recommendations were identified using the original SCEBS method literature, systematic reviews of the screening, assessment and management of patients with nonspecific back or neck pain, and core ICF sets for musculoskeletal disorders. These recommendations were extracted by two members of the research team (Rob A. B. Oostendorp and William Duquet) and, where necessary, differences were discussed with a third member (Peter Vaes) until consensus was reached. Based on these recommendations, a set of questions was formulated for each dimension ; Cognition: what are your expectations of treatment?).The questions were transformed into process indicators by treating them as percentages of patients who were asked a certain question .The process indicators were classified into the three dimensions of the SCEBS method with eight subdimensions of the Psychological dimension (appendix).An invitation to participate in the pilot practice test was sent to 112 physiotherapy practices in the south of the Netherlands, of which 68 (60.7%) indicated interest .From the 68 practices, MTPs from 49 practices (72.1%) participated in a regional information session that outlined the purpose and content of the study and the expected contribution. Of the 49 practices, 27 (55.1%) enrolled 21 MTPs. These MTPs were asked to collect data on at least five new patients with nonspecific back or neck pain, preferably on the first new patient each week meeting the criteria. Based on the number of participating MTPs, the number of patients expected to be included in the study was about 100. Patients had to meet the following inclusion criteria: age from 18 to 70 years, pain and/or stiffness in the back or neck for at least six weeks, back or neck complaints reproducible during active or passive examination, and written informed consent. Nonspecific back or neck pain was defined as pain with no specific cause, such as systemic disease, fracture, or other organic disorder. Patients with a history of additional complaints, such as nonradicular pain, were included only if the back or neck pain was dominant. Patients whose history, signs, and symptoms suggested a potential nonbenign cause (including previous surgery of the back or neck) or who showed evidence of a specific pathologic condition, such as malignancy, neurologic disease, fracture, herniated disc, or systemic rheumatic disease, were excluded.Data were collected over a period of six months. The history taking during the first appointment took place in the MTP's practice and was recorded using digital audio recording equipment. The audio recordings were transcribed by four students supervised and checked by Rob A. B. Oostendorp and William Duquet. The questions posed by the MTPs and the patients' answers were counted. The patients' demographic and clinical characteristics were also recorded. The age, gender, clinical experience, and additional educational attainment of the MTPs were noted. To evaluate the extent of self-estimated use of biopsychosocial history taking, the MTPs were subsequently asked if all dimensions of the SCEBS method were dealt with.The transcripts were read several times by each of the students and supervisors, in order to achieve familiarity with the contents of the questions and answers during history taking. Significant phrases were identified that characterized a specific question and answer of a (sub)dimension of the SCEBS method of history taking. One point was scored for each question that adhered to (sub)dimensions of the SCEBS method.Process indicators were scored as percentages , with the number of times an indicator was met as the numerator and the number of patients assessed as the denominator. To allow for easy interpretation, percentage scores of process indicators were categorized as negligible (0–15%), low (16–25%), weak (26–35%), very inadequate (36–45%), inadequate (46–55%), adequate (56–65%), substantial (66–75%), good (76–85%), very good (86–95%), and excellent (96–100%). The cut-off point for acceptable coverage for every dimension was set at 60%.The estimated extent of the use of biopsychosocial history taking by the MTPs themselves was expressed as percentages using the same categorization as above.Sixty-eight literature-based recommendations were extracted for biopsychosocial history taking in patients with nonspecific back or neck pain. After critical evaluation and checking for duplication and overlap by two members of the project group (Rob A. B. Oostendorp and William Duquet), the number of preselected recommendations was reduced to 51 items.The recommendations were transformed into 51 process indicators: for instance, “the percentage of patients who were asked about their own influence on their complaints,” “the percentage of patients who were asked about the reaction of their social environment to their complaints,” or “the percentage of patients who were asked about fear related to certain physical activities” (see appendix).n = 10), Psychological dimension , and Social dimension (n = 10).The process indicators were classified into the dimensions of the SCEGS method: Somatic dimension  submitted data to the pilot practice test . One hunn = 20) was 40.7 years (SD = 8.5), of whom 45.0% (n = 9) were female. All participants had postgraduate level education in manual therapy (Stichting Opleiding Manuele Therapie (SOMT) , Amersfoort, Netherlands). The range of practice experience was eight to 22 years. The average age of the patients (n = 108) was 42.3 years (SD = 14.1) of whom 60 (55.6%) were female. Of the 108 patients, 68 (62.9%) had back pain and 40 (37.0%) had neck pain.The mean age of the MTPs  pain were inadequately covered during history taking in these patients. Although we could not find a comparable study in the literature, these data are consistent with studies of physical therapy care that showed poorer quality in the implementation of biopsychosocial management of musculoskeletal disorders than in the implementation of biomedical management for back and neck pain . These rMTPs should be familiar not only with biopsychosocial context of pain but also with modern insights from pain neuroscience concerning reconceptualization of pain . A sustaDespite the development of many  implementation strategies and activities in the field of manual physical therapy , 26, proThis study describes the development of QIs to measure the use of biopsychosocial history taking as a first step in clinical practice guidelines associated with (chronic) musculoskeletal pain in patients with back or neck pain. Additional evidence indicates that many interfering factors in relation to pain can only be identified by careful history taking . The SCEAlthough no formal external validation of the set of QIs has taken place, the systematic approach and the composition of the research group underline the content validity of the QIs set derived from the SCEBS method. External validity depends on the heterogeneity of the expert panel, which consists of patient representatives, psychologists, general physicians, MTPs, and teachers. There is a pressing need for further research in the aforementioned area that includes larger groups of both experts and patients. While in this case the response rate of participating practices was acceptable (55.1%), the relatively small self-selected sample of participating MTPs might limit the external validity of the practice test. The MTPs were comparable to national profiles for this group  and patiIn addition to the years of clinical experience, the majority of participating MTPs were also educated in the biomedical model of pain. Unsurprisingly, the use of Somatic history taking was “excellent” in this study. By contrast, the use of the Psychological and Social dimension was “very inadequate” to “low.” Unlike recent graduate MTPs, it might have been expected that a group of MTPs with long clinical experience would have integrated the biopsychosocial approach into their first contacts with patients. In a qualitative study, Agledahl et al.  found thA large number of published studies and (systematic) review articles in various journals  advocate a broader view of (chronic) musculoskeletal pain , 40–42. In summary, our results indicate that MTPs perform screening for musculoskeletal pain mainly through the use of the Somatic or biomedical dimension of (chronic) pain according to the SCEBS method in patients with back or neck pain. Psychological and Social dimensions of chronic pain were inadequately covered by MPTs. There is a substantial discrepancy between the actual and self-estimated use of biopsychosocial history taking. Further work should focus on the role of education of MTPs in promoting complete biopsychosocial history taking and follow-through within the diagnostic, therapeutic, and evaluative phases of the clinical reasoning process.


Low back pain (LBP) is a common health problem and a substantial part of LBP is presumed to be attributable to degeneration of the intervertebral disc. For patients suffering from intractable discogenic LBP, there are few evidence-based effective interventional treatment options available. In 2010, the results of a randomized controlled trial (RCT) were published concerning “intradiscal methylene blue injection” (IMBI), in which this intervention appeared to be very successful in relieving discogenic pain. Therefore, we decided to repeat this study to investigate whether we could replicate the published results. The results of our preliminary feasibility study gave reason to set up an RCT. The aim of this RCT is to evaluate if IMBI is a more effective treatment of discogenic low back pain as an intradiscal placebo intervention, and furthermore, to assess the cost-effectiveness of this intervention.Consecutive discogenic low back pain patients referred to four specialized pain treatment facilities are being screened for eligibility. After a positive standardized provocation discography and informed consent, patients are randomized into two groups. The treatment group receives an intradiscal injection with methylene blue, lidocaine, and contrast, and the control group receives intradiscal isotonic saline with lidocaine and contrast.Main outcome measures are pain at the 6-month follow-up, patient’s global impression of change, cost-effectiveness, quality of life, disability, and analgesic intake.The importance of this study is emphasized by the fact that for intractable discogenic low back pain patients, evidence-based effective pain treatments are rare. If this study establishes clinical success and cost-effectiveness, IMBI could become the “pain treatment of choice” for a selected group of patients with chronic discogenic low back pain for whom noninvasive treatment options have failed.NTR2547National Trial register Registered at 29 September 2010 and 31 March 2014. Low back pain (LBP) is a common health problem; more than 70 % of the population in industrialized countries will experience low back pain at least once in their life . In mostThe treatment of discogenic chronic low back pain remains controversial. Patients who do not respond to conservative therapy may undergo various treatments, varying from interventional chronic pain treatment to fusion surgery, generally with variable and unpredictable results .In 2010, results of a randomized placebo-controlled trial concerning intradiscal methylene blue injection (IMBI) were published . It showThe rationale for this treatment is that methylene blue (MB) is neurolytic. Intradermal MB injection has shown by electron microscopy to be able to destroy dermal nerve endings . By injeIn 2011, the Departments of Anesthesiology and Pain Medicine of Maastricht and Arnhem in the Netherlands started a pilot study to acquire information about effect size, recruitment strategies, acceptability of intervention, study burden, and safety of IMBI. The pilot indicates that IMBI could be effective (40 % responded to the treatment) in a well-selected group of patients suffering discogenic pain.The proposed placebo controlled randomized clinical trial (RCT) was designed to investigate whether the results of the aforementioned RCT on IMBI can be replicated and additionally, to assess the cost effectiveness of this intervention.A double-blind placebo controlled randomized clinical trial (RCT) will be conducted in four interventional pain centers in the Netherlands by certified pain specialists. The RCT is approved by European Union Drug Regulating Authorities Clinical Trials (EudraCT) and the medical ethics committee (METC) of the Maastricht University Medical Centre; registration number NL325 11.068.10 and 10-2-055, respectively. Informed consent will be obtained from all participants.This study is sponsored by ‘The Netherlands Organisation for Health Research and Development’ (ZonMw), registration number 836011026.Clinical trials registration number is NTR2547.Consecutive patients with chronic lumbar axial pain referred to the specialized pain centers are assessed for eligibility. Eligibility criteria are a history consistent with lumbar discogenic pain ; low back pain for at least 6 months, and in at least the last 6 weeks a poor response to treatment that is, analgesics, physiotherapy, facet blockade and radiofrequency therapy; age between 18 and 66 years; neurological exam without motor deficit; pain intensity of at least 5 measured with the Numeric Rating Scale (NRS) 1 to 10 .2)) of ≥ 35, pregnancy, coagulopathy or oral anticoagulant therapy  in conditions that do not allow for a temporary discontinuation, and infection. Patients who are incapable of following verbal or written instructions or with psychiatric problems potentially interfering with cooperation in the study will be excluded as well.Exclusion criteria are discogenic pain confirmed on more than two levels; extruded or sequestered herniated nucleus pulposus; previous lumbar surgery or invasive intradiscal procedures on suspected levels; symptomatic lumbar spinal stenosis; grade 1-2 spondylolisthesis. Further exclusions include BMI (Body Mass Index (kg/mMagnetic Resonance Imaging (MRI) must have been performed in the last 12 months before inclusion to rule out severe disc degeneration as evidenced by a > 50 % disc height loss at the affected level . PatientPatients who fulfil the eligibility criteria for this study are asked to participate in the study.After written informed consent, patients will be randomized 1:1 for the treatment or control group Fig. Intradiscal methylene blue injection (IMBI) treatment consists of intradiscal injection with 1 ml of methylene blue, 0.5 ml of lidocaine hydrochloride 2 %, and 0.5 ml contrast dye (Iohexol-Omnipaque 300). The placebo treatment consists of 1 ml isotonic saline, 0.5 ml contrast dye, and 0.5 ml of lidocaine hydrochloride 2 %. This solution will be injected in the affected disc(s) under control of pressure (maximum of 100 PSI), velocity (0.02 ml/s), and volume using a CDS. During this procedure, the patient remains blind for the study-fluid. After the treatment, the patient has bed rest for at least 2 hours and during that time will be held in observation at the daycare surgery unit. Data will be collected at 6 weeks and at 3, 6, 12, and 24 months after the intervention, and patients will be seen by a physician or research nurse at each time-point to monitor patients’ adherence to the protocol.Both patients and post-intervention observers, such as pain managing nurses and physicians, are to remain blinded to the treatment or control intervention for at least 6 months. Therefore, during the intervention the interventional pain specialist takes care that the patient does not see the injected fluid. By asking the patient half an hour after the procedure what medication they think they received - either 1) methylene blue, 2) placebo or, 3) “I really don’t know” - the efficacy of the blinding procedure shall be checked. Furthermore, the same question will be repeated in the online patient questionnaire at 6, 12, and 24 weeks. Six-months post-intervention, at the patient’s request, patients from the control group who still suffer pain can receive the IMBI treatment.Patients are assessed at baseline, at 6 weeks, 3 months, and at the primary end-point of 6 months, and furthermore, at the follow-up of 12, and 24 months.Primary outcome measures is average pain at 6 months, measured by a pain diary with numeric rating scales (NRS) three times a day for 4 consecutive days. Success of the intervention is defined as pain reduction of at least 30 % at 6 months.Other study variables include the Patients Global Impression of Change (PGIC) measured by a 7-point Likert Scale and number of adverse and serious adverse events . SocietaWith the exception of the pain and medication diary, and the health-related quality of life EuroQol (EQ-5D) questionnaire, which are presented to the patient in a booklet, all data will be collected by web-based questionnaires software, SelectSurvey. (NETv4.075.011© Copyright 2008 ClassApps.com) and MACRO .The randomization of study patients in either the treatment or the control group will be done with software for randomization of clinical trials ALEA (version 2.2 CTCM/ALEA). The stratification factors, that are used in the randomization procedure to assure that potential confounders are equally distributed between the two randomized groups, are study center; gender; dichotomized disc levels (1) L3/L4 to L4/L5 and (2) L5/S1; and dichotomized Modified Dallas criteria (1) 1 to 2 and (2) 3 to 4. The software automatically sends an e-mail with the randomization results to the un-blinded physician who will perform the IMBI treatment.The sample size of the RCT is determined on the basis of success rates in the previous RCT  and our Given the invasive character of the IMBI procedure, we consider that the treatment group should be at least 30 % more successful than the control group to reach minimally clinical relevance. Furthermore, we assume 10 % drop out per group.For a power of 80 % and a level of statistical significance of 5 %, the minimum sample size is under these assumptions estimated to be 80 patients, that is, 40 per randomized group .Given the invasive character of IMBI and the burden for the patients, an interim analysis is pre-planned to test whether we can stop the study preliminarily assuming that the experimental group has a higher success rate than the control group and to monitor planned sample size assumptions. The sample size calculation for the interim analysis is based on the assumption that a success rate of 20 % in the placebo group is probably too high. Therefore, we assume a success rate of 10 % at 6 months in the placebo group, instead of 20 % success. If we detect a difference in success rate of 40 % between the two groups, the sample size is estimated to be 50 patients, that is, 25 per randomized group with a power of 90 % and a level of statistical significance of 2.5 % (one-sided).Differences in success rate between the groups will be tested with a Chi square test (univariate). Success is defined as at least 30 % pain reduction at 6 months. To account for cluster effects, a linear multivariate mixed model will be used to determine differences in pain score changes over time. A logistic regression model will explore possible predictors for success or failure of the procedure. The changes after 6 months of the outcome variables of the two groups will be compared with a Student’s t-test.A trial-based economic evaluation will be performed, based on empirical data obtained in the RCT. The base-case economic evaluation will be performed from the societal perspective, including costs inside and outside the healthcare sector and will follow the, in 2012 published, international guidelines . The timThe major task of the DMC is safety monitoring. Any serious adverse event or suspected unexpected serious adverse reaction, which might be life threatening or liable to produce disability or deformity, is an indication to set up a DMC meeting. Another important task for the DMC is monitoring the efficacy for futility and monitoring the planned sample size assumptions, whether criteria for early stopping are met. The statistician of the DMC will be the only one during the trial who has access to the un-blinded data. He performs the (interim) analyses. Members of the DMC are (1) head of the department of orthopedic surgery and (2) statistician and internal medical specialist of Maastricht University Medical Centre (MUMC) the Netherlands. Each member has no conflicts of interest with the study or the study members. The advice(s) of the DMC will be notified upon receipt by the research committee to the METC that approved the protocol. With this notification a statement will be included indicating whether the advice will be followed.This RCT will be audited and monitored by the Clinical Trial Centre Maastricht (CTCM); this organization is independent from the investigators and sponsor.Methylene blue (10 mg methylthioninium) is an off-label medicine, usually used as a dye for therapeutic and diagnostic applications. To establish presumed efficacy and cost-effectiveness of IMBI for discogenic LBP, a grant was obtained from “The Netherlands Organisation for Health Research and Development” (ZonMw).Preceding this RCT, a pilot study with 15 discogenic LBP patients was performed, to acquire information about efficacy, safety, feasibility, and acceptability of this intervention . InformaThe use of invasive placebos for pain treatment interventions is currently under debate and questions are raised about whether it is justified to expose control group patients to risks of serious harm , 33. SinIt is debatable if the use of the term ‘placebo’ treatment is correct for lidocaine shall be injected in the control group as well as in the treatment group. Local anesthetics are originally known for their inhibitory function on sodium channels, but they also have important anti-inflammatory effects , 39. HowProviding evidence for cost-effectiveness of low back pain interventions is a stipulated condition from the Ministry of Health in the Netherlands. Without this evidence, the Dutch Public Health Insurance System will not reimburse low back pain interventions. Overall, there is lack of cost-effectiveness studies for interventional pain medicine; therefore, an important part of this study concerns a cost-effectiveness assessment.This study will generate information for health care providers, patients, and health insurance companies, and results can be used in future guidelines and clinical practice algorithms.Intradiscal methylene blue injection could potentially be a new treatment in specialized interventional pain centers for patients with discogenic LBP who do not respond favorably to conservative treatments. For these intractable discogenic low back pain suffering patients, there is currently no recommended pain treatment available; therefore, this intervention could become a “pain treatment of last resort.”This is the protocol of an ongoing trial; patient recruitment is not completed at the time of submission.


The most common complaint of patients attending the emergency department (ED) is pain, caused by different diseases. Yet the treatment of pain at the ED is suboptimal, and oligoanalgesia remains common. The objective of this study is to determine whether the administration of analgesia at the ED increases by implementation of revised guidelines in pain management.We conducted a prospective pre-post intervention cohort study with implementation of a revised guideline for pain management at our ED, in which nurses are allowed to administer analgesia (including low-dosage piritramid (opioid) intravenous) without doctor intervention. Numeric Rating Scales (NRS) were measured, and administration of medication (main outcome) was documented. We included every adult patient presenting with pain (NRS 4–10) at the ED.p < 0.001).A total of 2107 patients (1089 pre-implementation phase and 1018 post-implementation phase) were included in our study. During pre-implementation, 25.4 % of the patients with NRS between 4 and 10 received analgesia. After implementation, 32.0 % of these patients received analgesia . The most common complaint of patients attending the emergency department (ED) is pain, caused by different diseases. The pain prevalence in EDs, throughout the world, ranges from 52 to 79 % . Yet, thThus, improvement of knowledge (among nurses and doctors) and revision of guidelines may increase the administration of analgesia.Therefore, the objective of the present study is to determine whether the administration of analgesia at the ED increases by implementation of revised guidelines in pain management. Secondly, we will investigate which factors are contributing to pain management at the ED.This was a prospective pre-post intervention cohort study with implementation of a revised guideline for pain management to increase the administration of analgesia. The study was divided into two periods (both 1 month) of data collection, before and after implementation of the revised guideline separated by a 1-month interval. During this interval, the revised guideline, developed by the emergency department (emergency physician and nurse) in cooperation with the anaesthesiology and consented by the specialties surgery and internal medicine, was implemented.The study took place in the ED of a level 1 teaching (inner city) hospital and trauma centre with ±50.000 ED visits per year . The study was conducted between September 2012 and January 2013. Our study was approved by the review board of the Medical Centre Haaglanden and by the Dutch Association of Medical Research Ethics Committee.We included every adult patient (16 years and older) presenting with pain (NRS 4–10) at the ED. As patients entered the ED, nurses assessed patients’ NRS and entered the values into the patients’ charts. Patients with life-threatening diseases/injuries requiring immediate transfer to the operating room or intensive care unit, altered mental status  and language barrier were excluded.A clinical committee was formed, in which hospital staff from the emergency, anaesthesiology and surgical departments were represented. They reviewed the literature and revised the existing guideline for pain management according to the current standard . In compThe guideline was written in Dutch and distributed to all ED staff and nurses. The ED staff was informed by email. In addition, the ED nurses were also educated face-to-face. Pocket-sized versions Fig.  of the gDemographics, pain assessment (NRS) at entrance and leave of the ED, administration of analgesia during ED visit, triage category, medical specialty and usage of analgesia before entering the ED (by patients at home or by EMS personnel) were retrieved from the medical records. Triage levels were assigned according to the five-level Manchester Triage System (MTS) : 1 immedThe main outcome was administration of analgesia in general during ED visit. Secondly, we investigated patient and visit factors that influenced analgesic administration.χ2 test. Continuous data were analysed with a t test. A p value <0.05 was considered to be significant. The difference in analgesia administration before and after implementation was analysed by multivariate logistic regression analysis, adjusting for the following variables: triage category, usage of analgesia pre-hospital, ethnicity (Dutch versus other ethnicity), gender and age. According to the literature, all these factors are possible confounders in analysing the administration of pain medication [Categorical data were expressed as number (%) and compared using the dication –18. We aA total of 2107 patients (1089 resp. 1018) were included in our study . After implementation, there were less patients in the high-NRS group. However, median NRS at admission was comparable between the two time periods. There were differences with regard to the use of analgesia pre-hospital and medical specialty: after implementation, significantly more patients were referred to surgical specialty, and furthermore, the use of analgesia pre-hospital was significantly lower Table .Table 1Pp = 0.001). The odds to receive analgesia after implementation was 1.35 higher than that before implementation (Table χ2 < 0.001). After implementation the administration of analgesia was significantly increased in both NRS groups (NRS 4–6: OR 1.41 (1.09–1.83); NRS 7–10: OR 1.43 (1.04–1.96)). There was a significant difference in type of drugs administered after implementation: more acetaminophen was used and combinations of drugs were used more frequently during the post-implementation phase. The route of administration also changed significantly: after implementation, more patients received medication p.o. (comparable with the difference in the administered acetaminophen). There was no difference in the medication given intravenously . Secondly, patients treated by a surgical specialty received more frequent analgesia than patients treated by a non-surgical specialty  (Table n = 973).In a certain number of patients in both groups (before and after implementation), the pain NRS at entrance to the ED was missing, either because it was not established or the patient was unable to answer Fig. . Among tThis study has several limitations. First, it was a large prospective observational study. Therefore, we can only show associations and no causality. We could not abstract from the charts whether the analgesic administration was protocol driven or by treating physicians. We did not use a blind design because we aimed to modify clinical practice of the ED staff by implementing the revised guidelines. During this period, there were no other changes in pain management , so the effect observed in this pre-post study was likely to be caused by the intervention.Second, there is a percentage of patients (in both groups) whose pain NRS at entrance to the ED was not measured. Compared to the research group, this group was triaged as less urgent and they received fewer analgesics. We assume that this group was treated during triage and left the ED before being asked the pain NRS. Since the group was triaged as low urgency, the NRS scores are expected to be low , and therefore, it is possible that a large amount of this group would have been excluded (NRS <4). Thus, we assume the effect of our intervention would not change if we had measured the NRS in this group. There are also high urgency patients in this group. An explanation for the missing NRS in this subgroup could be that their injuries/diseases were of such urgency that they had to be transferred to the operation room or intensive care unit immediately. If we had been able to measure the NRS in this high urgency (with expected high NRS scores) category, one could expect the effect of our intervention to be the same or even larger, because analgesic administration is significantly associated with increasing severity of pain , 20.Third, the Hawthorne effect (change of behaviour of nurses and physicians induced by the study itself) is difficult to avoid. Yet, the effect would have been present in both study phases.Fourth, the use of analgesia pre-hospital was higher before implementation than after implementation. To avoid overdoses, one could expect that less analgesia was administered in the pre-implementation group or more analgesia was administered in the post-implementation group. However, we adjusted the analysis for the use of pre-hospital analgesia and still the difference between the administration of analgesia between pre- and post-implementation was significant.Fifth, we were not able to measure ethnicity properly, rather than dividing patients into Dutch and not-Dutch based on country of birth of the patient and his or her parents. This may have caused biased information.Sixth, at baseline, there were differences between the two groups in triage category. Yet, this difference is not explained by more pain, because the median NRS is comparable in the two groups. Although the nurses are obligated to register the administration of medication, it was possible to administer the medication but forget to register this in the patient chart. Thus, the effect size is possibly underestimated.Finally, the pre- and post-groups differed with respect to specialty and triage category. Therefore, the finding that patients with surgical problems received more often analgesia may have been biased. Still, patients admitted to the ED with a non-surgical problem received less often pain medication than the patients treated by one of the surgical specialties, independent of triage category. Since the education on pain management for all emergency department staff did not differ, this could not explain the found difference. One hypothesis that would explain the difference in specialty in the administration of analgesia would be that tangible proof  influences physician/nurse practice more than patients’ reports of pain.In this study, we demonstrated that after implementation of the revised guideline in pain management at the ED, the administration of pain medication increases significantly. Nevertheless, the percentage of patients in pain receiving analgesia remain low (32 % after implementation). In line with this main outcome, Decosterd et al.  showed tIn our study, inadequate pain management is evident. Several other studies show that around 40 % of patients in pain at the ED do not receive pain medication , 22. ThiTo address the differences in pain medication administration, this study found that age was not correlated to the administration of analgesics. Previous research is contradictory: according to Jones et al. , elderlyAccording to our study, male and female patients had similar chance of being treated with pain medication. Raftery et al. , on the In the future, we would like to test the hypothesis that tangible proof causes differences in the management of pain. There is a high variability in pain management frameworks and protocols among EDs worldwide . The useIn summary, we found that after implementation of the revised guidelines in pain management at the ED, the administration of pain medication increased significantly. Nevertheless, the percentage of patients in pain which receive analgesia remain low (32 % after implementation). We also found that triage category and surgical specialty were influencing the administration of pain medication.