We aimed to examine the association between pain, stiffness and fatigue in newly diagnosed polymyalgia rheumatica (PMR) patients using baseline data from a prospective cohort study. Fatigue is a known, but often ignored symptom of PMR. Newly diagnosed PMR patients were recruited from general practice and mailed a baseline questionnaire. This included a numerical rating scale for pain and stiffness severity, manikins identifying locations of pain and stiffness and the FACIT-Fatigue questionnaire. A total of 652 PMR patients responded (88.5%). The mean age of responders was 72.6 years (SD 9.0) and the majority were female (62.0%). Manikin data demonstrated that bilateral shoulder and hip pain and stiffness were common. The mean fatigue score (FACIT) was 33.9 (SD 12.4). Adjusted regression analysis demonstrated that a higher number of pain sites (23–44 sites) and higher pain and stiffness severity were associated with greater levels of fatigue. In newly diagnosed PMR patients, fatigue was associated with PMR symptom severity. Polymyalgia rheumatica (PMR) is an inflammatory condition characterised by bilateral pain and stiffness in the shoulder and hip girdles. In the UK, PMR is the most prevalent inflammatory rheumatic disease in adults aged 50 years and over, peaking in incidence in those aged 70–79 years (22.9 per 10 000 person-years) .et al., Anatomical location of pain and stiffness were elicited using body manikins, up to a maximum of 44 body areas   reporting a mean score of 40.1 (SD 10.4)  Cella, . A minimet al., et al., Other survey outcome measures recorded sleep problems (insomnia severity index (ISI) Morin, , anxietyet al., The characteristics of the study sample were initially summarised using descriptive statistics. The mean age (SD) and gender were reported, and self-report BMI was categorised into four groups  and IMD was categorised into three groups . The total number of pain/stiffness sites for each participant was reported in quartiles . The manikin data were also used to dichotomise participants into those who had experienced bilateral pain/stiffness in the shoulder/hips using relevant manikin locations   were generated for the FACIT-Fatigue questionnaire. Scoring of the ISI creates four severity categories: 0–7, no clinically significant insomnia; 8–14, sub-threshold insomnia; 15–21, clinical insomnia (moderate severity) and 22–28, clinical insomnia (severe). GAD-7 scores were categorised into those with no anxiety (0–4 points), mild (5–9), moderate (10–14) and severe anxiety (15–21) and PHQ-8 scores into no depression (0–4), mild (5–9), moderate (10–14), moderately severe (15–19) and severe depression (20–24) using already existing scoring thresholds . The mean age of responders was 72.6 years (SD 9.0) and the majority were female (62.0%). As previously described, responders were similar to non-responders in terms of age and gender, although non-responders were more likely to be more deprived (Muller The mean FACIT-Fatigue score was 33.9 (SD 12.4), and did not significantly vary by age or deprivation tertile. However, levels of fatigue were greater in women and in those with higher BMI, and higher levels of anxiety and depression . BilaterMean fatigue scores were lower (ie more fatigue) in those reporting a pain severity of ⩾8 on the 0–10 NRS compared to those reporting a score of ⩽7 [regression coefficient (95% CI): –3.76 (−5.8 to –1.7)]. After adjustment for age, gender, deprivation status, BMI, anxiety, depression and insomnia the association was reduced, but still statistically significant [−1.66 (−3.1 to –0.2)] .Unadjusted analysis demonstrated an association between a higher number of pain sites and greater fatigue. However, after adjustment only the participants with the highest quartile of pain sites (23–44 sites) remained significantly different [−3.45 (−5.3 to –1.6)] from the group with the lowest number of pain sites (0–9 sites). No association was demonstrated between fatigue and reporting either bilateral shoulder [−1.02 (−3.2 to 1.1)] or hip pain [−1.44 (−2.9 to −0.0)].In the unadjusted analysis, higher stiffness severity (⩾8) was associated with experiencing significantly greater fatigue [−3.55 (−5.5 to –1.6)]. Though attenuated, this remained a statistically significant association after adjustment [−1.48 (−2.9 to –0.1)] and was the only stiffness characteristic to be associated with fatigue after adjustment.Pain and stiffness were common in this primary care cohort of newly diagnosed PMR patients. Those reporting higher levels of pain and stiffness had significantly greater levels of fatigue than those with a lower symptom severity. Furthermore, those reporting pain at a higher number of anatomical sites, rather than just isolated to the classical shoulder and hip regions reported the greatest experience of fatigue.n=164, mean 38.6, SD 10.8) ] was lower than that of a similarly aged sample (65 years or older) from the US general population  Cella, , demonstet al., et al., et al., Compared to other inflammatory conditions, our cohort reported more fatigue than US patients with newly diagnosed ulcerative colitis [mean FACIT-Fatigue score 39.4 (SD) (10.6)] and psoriatic arthritis [35.8 (SD 12.4)] (Chandran et al., Apart from those patients with PMR reporting the highest stiffness ratings, fatigue was not associated with the general number of stiff sites or stiffness at specific locations. Though stiffness is clearly a common symptom in PMR and will cause difficulties in multiple aspects of daily living and functioning (Mackie et al. found that pain, stiffness, sleep quality and fatigue all significantly improved in RA patients prescribed a 12-week home-based exercise intervention (Durcan, Wilson, and Cunnane, Individuals newly diagnosed with PMR who report fatigue as a significant problem may benefit from modified pain treatment or management that directly addresses these issues. A randomised controlled trial conducted by Durcan et al., This prospective cohort is the first study of patients newly diagnosed with PMR in primary care. Such a sample is representative of patients with PMR, as the majority are managed in primary care (Dasgupta In conclusion, severe pain was predominantly associated with fatigue in newly diagnosed PMR patients, but it is those patients who have pain in a high number of body sites who experience fatigue that is clinically meaningful. Fatigue is of concern to patients’ with PMR, but often under-represented in research and not prioritised by clinicians. Future studies should characterise the experience of fatigue over-time in patients’ with PMR and determine how this relates to reported pain and stiffness. This may highlight those who warrant earlier or more specific interventions.Guarantor of overall study integrity: S.M. and C.D.M. Study concept and design: S.M., B.D., K.B., T.H., S.H., S.L., C.D.M. Data collection and interpretation: J.A.P., S.M., S.L. and C.D.M. Statistical analysis: J.A.P. and S.M. Manuscript preparation: J.A.P., S.M., T.H., S.H., S.L., K.B., B.D. and C.D.M. Final approval of manuscript: J.A.P., S.M., T.H., S.H., S.L., K.B., B.D. and C.D.M.


In postherpetic neuralgia (PHN) different types of patients can be distinguished regarding their predominant peripheral nociceptor function.The aim was to examine somatosensory profiles in the course of disease with special regard to the different subtypes existing in PHN.Twenty patients with PHN  were examined at baseline (disease duration 18.1 ± 26 months) and follow-up (31.6 ± 23.8 months later) with quantitative sensory testing (protocol of the German Research Network on Neuropathic Pain).P = n.s.) at follow-up. Impaired PHN improved in thermal and mechanical detection thresholds as well as allodynia independent from change in pain intensity. By contrast, pPHN showed an increase in mechanical pain sensitivity  and a trend towards a stronger loss of detection  on follow-up.Fourteen (70%) PHN patients presented with impaired (iPHN) and 6 (30%) with preserved (pPHN) C-fiber function. Groups did not differ regarding age, disease duration, or pain intensity at baseline. Both groups did not differ regarding change in pain intensity (−0.5 ± 2.3 vs −1.7 ± 2.6 numerical rating scale, Results demonstrate that patients with preserved C-fiber function are more predisposed to develop signs of central sensitization as demonstrated by an increased mechanical pain sensitivity. Impaired C-fiber function is able to improve even in chronic cases, but a functional loss is unlikely to play a role here. The knowledge of development of somatosensory profiles in the course of the disease offers possibilities to optimize a mechanism-based treatment. Pain and somatosensory abnormalities of PHN patients with preserved or even sensitized nociceptors might be due to an abnormal sensitization of unmyelinated cutaneous nociceptors (irritable nociceptors7). To date, it is unclear why some patients have the impaired and others the preserved clinical phenotype. However, the assessment of these specific sensory symptoms and signs enables to identify the underlying mechanism that can help to understand pathophysiology and improve treatment in the concept of a mechanism-based therapy.28 Because it has been shown that a specific symptom may be generated by several different mechanisms, it became clear that a specific somatosensory constellation might be more suitable to mirror the mechanisms instead of a single sign.16 Standardized quantitative sensory testing (QST) enables to investigate different afferent nerve fiber functions or their central pathways and create an individual somatosensory profile.9 The presence of different somatosensory signs and their constellation are suggested to be linked to underlying mechanisms.1Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection.31; however, investigations regarding changes of somatosensory signs and symptoms in the course of PHN are rare. The aim of our study was therefore to examine somatosensory signs and symptoms in the course of disease with special regard to the different subtypes existing in PHN.Several studies have investigated somatosensory function of patients with PHN9) on the affected and corresponding contralateral body side. Patients with any neurological comorbidity that could otherwise influence testing results such as polyneuropathy, diabetes, vascular disease, etc., as well as patients with skin lesions or dermatological disorders in the areas to be tested or with difficulties in German language skills were excluded from the study. The study was in accordance with the Declaration of Helsinki and approved by the institutional review board of the Faculty of Medicine at Christian-Albrechts-University of Kiel. All patients gave written informed consent to take part in the study.Twenty patients with PHN  were examined at baseline  and follow-up visit (31.6 ± 23.8 months later). Recruitment consisted of all patients with PHN who had been included into the database of the German Research Network on Neuropathic Pain in Kiel, Germany, between 2004 and 2007 who agreed to participate in a follow-up examination. Postherpetic neuralgia was present in trigeminal innervation territory (n = 5), cervical (n = 1), thoracic (n = 11), as well as lumbar (n = 3) dermatomes. The initial visit's (baseline) data set was provided by the database of the German Research Network on Neuropathic Pain. The examination of both baseline and follow-up visit followed an identical algorithm and included medical history  and QST  and vibration detection threshold representing the function of large myelinated fibers or central pathways, cold detection threshold (CDT), cold pain threshold, warm detection threshold (WDT), thermal sensory limen (TSL), heat pain threshold (HPT), presence of paradoxical heat sensations, mechanical pain threshold, mechanical pain sensitivity (MPS), and pressure pain threshold representing small fiber function or central pathways. In addition, the presence of dynamic mechanical allodynia (DMA) and temporal summation of pain (wind-up ratio) are assessed. Parameters were tested as described previously.11 Patients were tested bilateral on the affected and corresponding contralateral body side. Testing always started on the unaffected, ie, corresponding contralateral side before the affected area of maximal pain (test area) was tested.Current and mean pain intensity during the week before examination was measured with a numerical rating scale . For assessment of somatosensory function, the QST protocol of the German Research Network on Neuropathic Pain was used.29 and compared with a reference database of healthy controls.20 To make the patients' data comparable with the values of healthy controls, individual patient data were normalized to the respective sex, age group, and tested area of the healthy controls using z-values . Resulting Z scores above “0” indicate hyperfunction, ie, patients are more sensitive to the tested parameter compared with controls (lower thresholds), whereas Z scores below “0” indicate hypofunction and therefore a loss of or lower sensitivity of the patient compared with controls (higher thresholds). Because PHN is a unilateral disease, both z-values out of the 95% confidence interval  in the affected area and a difference of more than 2 SDs in the z scores between affected and corresponding contralateral area  were considered as abnormal values. The Wilcoxon test was used for intragroup comparison, ie, analysis between affected and contralateral side as well as between baseline and follow-up within the groups. Linear relationships were assessed by Pearson correlation coefficient. Frequencies of abnormal QST values were analyzed with the χ2 test. P < 0.05 was considered statistically significant.Quantitative sensory testing results were analyzed according to published guidelinesP < 0.001; warm detection: n = 14, P < 0.001) and mechanical detection  as well as heat pain  in the affected area compared with the reference values of healthy controls. Mechanical pain sensitivity to pinprick stimuli was either increased  or decreased , whereas pain sensitivity to blunt pressure was increased  compared with healthy controls. Dynamic mechanical allodynia and paradoxical heat sensitivity were present in 40% and 20%, respectively. None of the QST parameters at baseline correlated with pain intensity or disease duration, but z-values for thermal thresholds were lower, the older the patients were .On baseline, patients had higher frequencies for loss of thermal  PHN patients presented with impaired C-fiber function, ie, loss of warm detection. Six (30%) patients had preserved C-fiber function, ie, no abnormalities in warm detection or HPTs, whereas one patient additionally demonstrated sensitized C-fiber function, ie, no abnormalities in warm detection, but increased heat pain sensitivity. Patients with impaired C-fiber function did not differ from patients with preserved C-fiber function regarding age, disease duration, or pain intensity at baseline  and mechanical (MDT and vibration detection threshold) detection as well as decreased sensitivity to thermal pain (cold pain threshold and HPT), but increased sensitivity to blunt pressure and DMA on the affected side compared with the contralateral side Table . All patBy contrast, patients with preserved C-fiber function did not differ between the affected and contralateral side regarding gain or loss of thermal or mechanical detection or pain thresholds Table . The onlPatients with impaired C-fiber function had a stronger loss of detection for thermal  and mechanical (MDT) detection and painful heat on the affected side compared to patients with preserved C-fiber function Table .P = not significant [n.s.]) nor with preserved C-fiber function . Only 4/14 patients (28%) improved in pain intensity from baseline to follow-up in the subgroup with impaired and 3/6 (50%) patients with preserved C-fiber function (P = n.s.). Between baseline and follow-up, pain medication was unchanged in 2 patients , whereas the number of coanalgesics was reduced in 7  and increased in 11 patients . Interestingly, change in pain intensity did not differ between those patients where the number of pain medication was increased or decreased .Mean pain intensity did not change between baseline and follow-up measurement, neither in patients with impaired  detection as well as an increase in cold and heat pain sensitivity in the follow-up examination Fig. A. ChangeChanges in the frequencies of abnormal values are shown in Figure stronger loss of mechanical detection on baseline  as well as mechanical detection  and TSL  on follow-up testing compared to those with a high pain intensity . No differences of QST parameters at baseline or follow-up were observed between those with and without a reduction of pain intensity between baseline and follow-up examination.No differences were observed between patients with short or long disease duration. Interestingly, patients with a lower pain intensity  had a In contrast to patients with impaired C-fiber function, patients showed an increase in MPS on follow-up Fig. A. FurtheNo differences were observed between patients with short or long disease duration or between those with higher  or lower (n = 2) pain intensity within the group of patients with preserved C-fiber function.P = n.s.), pain intensity at follow-up examination , time in between the 2 examinations , or disease duration  at follow-up. Patients with impaired C-fiber function improved in thermal and MDTs as well as DMA compared to those with preserved C-fiber function  pain reduction is independent from the subtype of PHN and (2) patients with impaired and preserved C-fiber function differ regarding change of somatosensory function: Although patients with impaired C-fiber function at baseline improve in loss of thermal and mechanical detection independent from the improvement in pain intensity and even after a long duration of disease, ie, show a shift towards a normalization of the somatosensory profile, patients with preserved/sensitized C-fiber function are more predisposed to develop signs of central sensitization, ie, an increase in MPS. Results therefore suggest that C-fiber function is able to improve even after a long time, as the disease duration at baseline measurement was already more than 1 year after disease onset and follow-up examination about 3 years later. This is in line with the observation of another follow-up examination of patients with herpes zoster that demonstrated an improvement of sensory thresholds 3.9 to 7.7 years after herpes zoster, despite the presence of somatosensory abnormalities and partly missing reinnervation of herpes zoster affected on skin biopsy.8 plays a major role because pain intensity did not change in this subgroup, change in somatosensory profiles was independent from improvement in pain intensity and patients with a lower pain intensity demonstrated a stronger loss on QST.It is unlikely that a functional loss, ie, pain-induced hypoaesthesia2 In addition, in this group, there was a trend towards a development of a mechanical and thermal loss of detection. Of course, it has to be kept in mind that this subgroup of patients within the study was small; however, with regards to the increasing central sensitization, this progressive loss could be secondary to nociceptive stimulation8 rather than due to degeneration of peripheral nerve fibers. Although the change in somatosensory profiles was independent from improvement in pain intensity, central sensitization of the nociceptive system was clearly visible on the somatosensory profile. Processes underlying central sensitization  sensitization of the nociceptive system in the preserved/sensitized subtype of PHN are in line with current concepts of pain chronification demonstrating that central sensitization can develop as a result of ongoing C-fiber activity of intact C fibers.33 as well as painful events and treatment.35 Regarding the idea of a mechanism-based treatment in neuropathic pain32 based on the somatosensory phenotype,1 a change of the somatosensory phenotype within the course of a disease would have major influence on treatment. For example, patients with a strong loss of detection due to degeneration might respond better to treatment with anticonvulsants or topical agents when regeneration occurs.22 On the other hand, in the sensitized/preserved phenotype, it might be more important to prevent further mechanisms of pain chronification, ie, by a more aggressive analgesic treatment.23Results of the change of the somatosensory phenotype within the course of PHN further support the view that the pain profile is dynamic, ie, can change within the same individual as a consequence of individual characteristics such as age, sex, genetic phenotype, prior medical history including primary and secondary psychological factors,One limitation of this study is of course the small study number, especially in the preserved/sensitized subtype of PHN. Thus, the conclusions that can be drawn from this subgroup are limited. In addition, treatment was not stable in the patients; however, because mean pain intensity did not change between baseline and follow-up and change in pain intensity did not differ between those patients where the number of pain medication was increased or decreased, this should not have major influence on our results.In conclusion, our results suggest a dynamic of the somatosensory profile and that follow-up examinations of the somatosensory phenotype to assess underlying mechanisms are important to optimize treatment.J. Gierthmühlen has received speaker fees and travel support from Pfizer, Grünenthal, Sanofi Pasteur MSD GmbH, TAD Pharma and consultancy fees from Glenmark. A. Binder received honoraria from Astellas, Pfizer, Allergan, Grünenthal, Boehringer Ingelheim, Bayer, and advisory from Grünenthal, Genzyme, Pfizer, Boehringer Ingelheim, and Bayer. S. Rehm reports travel support from Grünenthal and speaker fees from Bayer Vital. R. Baron has received grants/research support from Pfizer, Genzyme, Grünenthal, and Mundipharma. He is a member of the EU Project No 633491: DOLORisk. A member of the IMI “Europain” collaboration and industry members of this are: AstraZeneca, Pfizer, Esteve, UCBPharma, Sanofi Aventis, Grünenthal, Eli Lilly, and Boehringer Ingelheim. German Federal Ministry of Education and Research (BMBF): Member of the ERANET NEURON/IM-PAIN Project. German Research Network on Neuropathic Pain, NoPain system biology, and German Research Foundation (DFG). He has received speaking fees from Pfizer, Genzyme, Grünenthal, Mundipharma, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Desitin, Teva Pharma, Bayer-Schering, MSD, and bioCSL. He has been a consultant for Pfizer, Genzyme, Grünenthal, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Novartis, Bristol-Myers-Squibb, Biogenidec, AstraZeneca, Merck, Abbvie, Daiichi Sankyo, Glenmark Pharmaceuticals, Genentech, and bioCSL. The remaining authors have no conflict of interest to declare.This work was supported by Pfizer Germany. The sponsor was not involved in design and conduct of the study, in collection, management, analysis, interpretation, and preparation of the data, and in review or approval of the manuscript.


The aim of this study was to evaluate patients’ pain levels during four different debonding procedures. The null hypothesis was that the pain perception of the patients undergoing four different debonding applications was not statistically significant different.One hundred and twenty orthodontic patients who underwent orthodontic debonding were included in this study. The patients were randomly divided into 4 groups according to technique used in the patients. Debonding groups were as follows: Group 1) Conventional debonding group, Group 2) Medication group (acetaminophen was given 1 hour before debonding), Group 3) Soft bite wax group, and Group 4) Soft acrylic bite wafer group. The patients’ levels of anxiety and fear of pain were evaluated before debonding, and Numerical Rating Scale (NRS) was applied to evaluate their pain perception during debonding. Mann-Whitney U and Kruskal–Wallis tests were used to evaluate non-normally distributed data. Categorical data analysis were carried by chi-square and McNemar tests. The significance level was set at p<0.05.Anxiety scores of the patients were not statistically significant between both genders and debonding groups. In the quadrants in which the patients were perceived, the highest pain level was in the left side of the mandible. The teeth in which the highest pain level was perceived were the lower left and upper right lateral incisors. Although there was no statistically significant difference among the pain scores of the patients in each group, quadrant scores of female patients showed significant differences, being the lowest scores in the soft bite wax group.Majority of the patients had no fear of pain before debonding. Pain levels of the patients in the conventional debonding group were not significantly different from those of the other groups, except quadrant scores of females in the soft bite wax group. The null hypothesis was accepted. The calculation was made based on a significance level of 0.05 and a power of 90% to detect a clinically meaningful difference of 1 cm in NRS. For acute and traumatic pains, minimum mean change of 13 mm (median of 11 mm) was accepted as clinically significant level in visual analog pain scale.Patients arriving at debonding appointment were enrolled to 4 different groups (n=30) determined by debonding method. The first 30 patients whose active orthodontic treatments terminated were enrolled to Group 1, the second 30 patients to Group 2, and so on, without considering the age, gender, malocclusion type, and treatment duration.The debonding procedures applied to each group were as follows:Group 1) Conventional debonding group: Debonding was performed with a Weingart plier. Teeth were not in contact with their counterparts during the operation. In other words, debonding was performed with an open mouth position .Group 2) Medication group: A single dose of acetaminophen  was given to the patient 1 hour before debonding, and debonding was done as explained in Group I.Group 3) Soft bite wax group: The patient was requested to bite on an occlusal wax , and then debonding was performed with a Weingart plier .Group 4) Soft acrylic bite wafer group: The patient was asked to bite on a soft plastic bite wafer , and then debonding was performed with a Weingart plier .in situ during debonding.All the debondings were performed with the same Weingart pliers, beginning from the upper and lower left sides of the jaws, respectively. The Weingart plier was applied to the bracket base and squeezed the base in a mesiodistal direction. The archwires were All the procedures mentioned above were managed by the same author (G.S).Before debonding, a two-part questionnaire was applied to the patients. The dichotomous questions about the presence of anxiety and/or fear of pain were asked, and the patients answered these questions as yes or no. After debonding, numerical rating scale (NRS) was applied to evaluate the patients’ pain perception.Statistical analysis was performed with statistical software IBM SPSS Statistics . Normality of the data was evaluated with Shapiro–Wilk test. Mann-Whitney U and Kruskal-Wallis tests were used to evaluate non-normally distributed data. The analysis of categorical data was performed with chi-square test. The results were presented as median (minimum-maximum) values and interquartile ranges. The significance level was set at p<0.05.Distribution of the patients’ anxiety scores before debonding and their between-groups comparisons and the comparisons between the genders are shown in The quadrants and teeth in which the patients perceived the highest pain during debonding and their frequencies and percentages are presented in The results of As can be seen from ,,-Bond strength is important for maintaining orthodontic treatment efficiency, but easy debonding of the brackets is preferred at the end of the treatment. Many kinds of debonding methods have been suggested to lessen the patient discomfort. These debonding methods include ultrasonic instrumentation, laser irradiation and electrothermal heating, using special pliers. In addition to these methods, modified adhesive resins containing thermoexpandable microcapsules have been used to lessen the pain and discomfort.,Pain is an inherently subjective symptom, and thus no objective method exists for its assessment. Visual analog scale (VAS), numerical rating scale (NRS), and verbal rating scale (VRS) are commonly used measurement instruments to quantify pain intensity of the patients. The comparative studies regarding these instruments showed no statistically significant difference among them.Debonding procedures should be harmless, painless and quick.,,,,Pain perception has been reported in different phases of the orthodontic treatment. For debonding, not pain perception but different effects of debonding procedure generally has been investigated in literature.Williams and Bishara,,, Mangnall, et al.It has been known that intrusive forces in debonding are tolerable force types.,per unit area in the lower anterior region than in the posterior, and thus greatest pain was perceived in the lower anterior teeth (39%) followed by the upper right posterior teeth (18%). The authors also stated that debonding was started from the upper right side, and thus the first debonded quadrant was remembered as more painful.The location of the tooth has an impact on the degree of pain,Pre-debonding anxiety may induce pain during debonding. Pre-debonding anxiety levels of the male and female patients in each group were determined, and no significant difference between genders was observed. Between-groups, anxiety scores were also not statistically significant in both females (p=0.292) and males (p=0.658). This finding is consistent with the study by Williams and Bishara,A statistically significant difference was observed in the quadrant scores of female patients. Soft bite wax group showed lower debonding pain levels than the other groups and no significant differences among the other groups was observed. The subjectivity of pain perception shown in this study was similar to that in the previous reports.It might be thought that this study had some limitations. For example, there may have been a bias in patient recruitment into the different groups because this study is a controlled clinical trial. Again, adding the patients with ceramic brackets could enhance the scientific value of the study.The results of this study can be summarized as follows:Pre-anxiety scores of the patients showed no difference between genders and groups.The quadrants and teeth in which the patients perceived the highest pain level was the left side of mandible and lower left and the upper right lateral incisors, respectively.No significant difference among the four different debonding techniques was found. The pain level perceived in conventional debonding technique was not statitically different from the others.


To establish the recovery priorities of individuals suffering with degenerative cervical myelopathy (DCM).A cross-sectional, observational study.Patients from across the world with a diagnosis of DCM accessed the survey over an 18-month period on Myelopathy.org, an international myelopathy charity.481 individuals suffering from DCM completed the online survey fully.p<0.05.Functional recovery domains were established through qualitative interviews and a consensus process. Individuals were asked about their disease characteristics, including limb pain  and functional disability (patient-derived version of the modified Japanese Orthopaedic Association score). Individuals ranked recovery domains  in order of priority. Priorities were analysed as the modal first priority and mean ranking. The influence of demographics on selection was analysed, with significance p<0.005) who prioritised walking, even among patients with lower pain scores.Of 659 survey responses obtained, 481 were complete. Overall, pain was the most popular recovery priority (39.9%) of respondents, followed by walking (20.2%), sensation (11.9%) and arm and hand function (11.5%). Sexual function (5.7%), bladder and bowel (3.7%) and trunk function (3.5%) were chosen less frequently. When considering the average ranking of symptoms, while pain remained the priority (2.6±2.0), this was closely followed by walking (2.9±1.7) and arm/hand function (3.0±1.4). Sensation ranked lower (4.3±2.1). With respect to disease characteristics, overall pain remained the recovery priority, with the exception of patients with greater walking impairment (This is the first study investigating patient priorities in DCM. The patient priorities reported provide an important framework for future research and will help to ensure that it is aligned with patient needs. This is the largest study of patient perspective in degenerative cervical myelopathy (DCM) to date and the first to consider patient recovery priorities.This study is unique in reporting on both surgical and non-surgical DCM patients.This study includes a broad demographic representation of patients from across the globe and includes subgroup analysis.This is an open-access, internet-based survey, a methodology which can lead to a sampling bias.Efforts to mitigate against sampling bias, alongside reassuring subgroup analysis suggest this risk is low.Degenerative cervical myelopathy (DCM) has been coined as an umbrella term for degenerative and congenital or acquired conditions of the cervical spine, such as spondylosis or ossification of the posterior longitudinal ligament, which lead to symptomatic cord compression.The cervical spinal cord acts as a processor and conduit of information between the brain and the periphery. Its injury can, therefore, give rise to a range of possible symptoms.At present, decompressive surgery is the only evidence-based treatment for DCM.Lancet series, Chalmers et al estimated that as much as 85% of the US$240 billion expended on health research in 2010 was wasted and an important contributing factor was the misalignment of patient and clinician research objectives.Medical research is primarily designed by healthcare professionals. This bears the risk of not taking into account actual patient needs. The concept of ‘research wastage’ has emerged to depict healthcare research that does not yield actual or potential clinical benefit. In the 2014 A recent systematic review of DCM research demonstrated a heavy focus on surgical technique.In this study, we sought to establish the recovery needs and priorities of individuals suffering from DCM. This will help to determine the outcome assessments that should be included in clinical research and to better direct future research.Reporting adheres to the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network Strengthening the Reporting of Observational Studies in Epidemiologychecklist.et al, who conducted a survey among patients with traumatic spinal cord injury asking them to rank seven domains of spinal cord function in order of priority for recovery.Individuals with DCM and their caregivers were invited to attend the Myelopathy.org PPI day, hosted at the University of Cambridge and captured by Cambridge TV in their documentary.These questions were embedded into an existing electronic survey initiative, developed using Survey Monkey  and following the Checklist for Reporting Results of Internet E-Surveys,Respondents were asked to rank recovery domains in order of priority and provide details about their DCM. DCM characteristics included age, gender, history of surgery, best daily limb pain score , duration of symptoms and disease severity as measured using the self-reported, patient-derived, modified Japanese Orthopaedic Association (P-mJOA).The survey was accessed via a landing page on Myelopathy.org, allowing assessment of response rates using Google Analytics . Individuals with DCM were recruited over an 18-month period. The recruitment process has been described in detail previously2 test. For continuous variables, the Shapiro-Wilk test was used to assess for parametric distribution of data sets. The Mann-Whitney U test was then used to compare the means of non-parametric distributions while a two-tailed t-test used to compare the means of parametric distributions. Pearson’s correlations were performed to assess between-group differences in characteristics, which could have influenced subgroup analysis. Significance was set at p<0.05.Research priorities are presented using summary statistics, including average ranking and overall proportion of patients per domain. Domains that were not ranked by a respondent were omitted from these scores. For subgroup analysis, variables were dichotomised and thresholds were chosen based on the graphical distribution of responses and sample sizes. Categorical variables were compared using the χPatients were involved in the design, development, recruitment and conduct of this study. At a PPI day hosted at the University of Cambridge, a focus group of DCM patients evaluated and confirmed the recovery domains in DCM. DCM patients were used to pilot the subsequent survey, including optimising its design to reduce the time taken to complete and clarify questions. The online survey for the study was hosted on Myelopathy.org, an international DCM charity run largely by DCM patients. Patients were, therefore, active in disseminating the survey via online DCM support groups, including Myelopathy Support, led by IS, patient and coauthor. Patients who were involved in preparation of the manuscript are among the authors. In addition, all patients who participated in the research are recognised in the acknowledgement statement. DCM patients are involved in plans to disseminate this research to the patient community, including blog articles on Myelopathy.org, posts in online patient support groups and presence at spinal conferences in the UK.p=0.04), otherwise there was no statistical difference within variables of interest . A total of 481 responses contained complete data (completion rate 73%). A missing data analysis was conducted comparing incomplete and complete responses. Patients who completed the survey in full were more likely to have undergone surgery (rest see . Only co10.1136/bmjopen-2019-031486.supp1Supplementary datap=0.07) and have worse myelopathy . They were also more likely to suffer greater pain . Average pain scores were 3.1 (±2.4) for patients suffering with the disease for less than a year, rising to 4.5 (±3.0) for patients suffering for at least 10 years. There was no relationship between severity of myelopathy and pain scores . Between-group differences are summarised in On average, respondents were more likely to be female  and suffer with moderate myelopathy (11.9±3.0) for between 3 and 10 years . Around half of patients  had undergone surgery. Overall respondent demographics are summarised in 10.1136/bmjopen-2019-031486.supp2Supplementary dataOverall, pain was the most popular number one ranked recovery domain, chosen by 39.9% of respondents. This was followed by walking (20.2%), sensation (11.9%) and arm and hand function (11.5%). Sexual function (5.7%), bladder and bowel (3.7%) or trunk function (3.5%) were chosen less frequently. When considering the average ranking of symptoms, while pain remained the priority (2.6±2.0), this was closely followed by walking (2.9±1.7) and arm/hand function (3.0±1.4) . Sensatip<0.005) and trunk function (p=0.03), whereas patients who had not yet undergone surgery were more likely to prioritise upper limb function (p<0.05) (p<0.005) and walking (p<0.005), respectively (p<0.005), even among patients with lower pain scores  . Patientectively . Overalln scores .When considering the average rankings pain, arm/hand function and walking remained the top three recovery priorities . However10.1136/bmjopen-2019-031486.supp3Supplementary dataWhen overall P-mJOA scores were considered to evaluate mild, moderate and severe patients,This is the first study to systematically survey functional domains relevant to DCM and to ask patients to rank them in order of importance to their quality of life. The established priorities are likely to reflect symptom prevalence and their impact on day-to-day life.These findings are surprising: functional disability  has been and continues to be a focus for researchers, typically in response to surgery,et al,The priorities established in the present study differ from those of individuals suffering from spinal cord injury. Although pain is among the most prevalent symptoms of traumatic spinal cord injury,In DCM, the symptom burden is less well-describedFollowing recommendation by the James Lind Alliance, which was founded to support priority setting in research,The survey questions were not randomly sorted and therefore each respondent answered identical surveys with spinal cord function domains presented in the same order. The last domain assessed was sensation. In keeping with it being the most prevalent DCM symptom,et al, the pain domain was kept non-specific, asking patients to rank ‘elimination of pain’ as a recovery priority (see Following the qualitative development work and the previous experience of Anderson rity see . In cont10.1136/bmjopen-2019-031486.supp4Supplementary dataThe priorities reported in the present study identify functional domains that are relevant to the quality of life of DCM patients. They provide an important framework for future research and will serve as a valuable reference for the development of a core outcome set relevant to studies in DCM.


There is increasing interest in the role of pro-inflammatory cytokines in the pathogenesis of sciatica and whether these could be potential targets for treatment. We sought to investigate serum biomarker levels in patients with low back-related leg pain, including sciatica.n = 119) had samples taken for biomarker analysis. Participants were classified having: a) clinically confirmed sciatica or referred leg pain, and then subdivided into those with (or without) MRI confirmed nerve root compression due to disc prolapse. Seventeen key cytokines, chemokines and matrix metalloproteinases (MMPs) implicated in sciatica pathogenesis including TNFα and IL-6, were assayed in duplicate using commercial multiplex detection kits and measured using a Luminex suspension array system. Median biomarker levels were compared between the groups using a Mann Whitney U test. Multivariate logistic regression analysis was used to investigate the association between clinical measures and biomarker levels adjusted for possible confounders such as age, sex, and symptom duration.Primary care consulters aged > 18 with low back-related leg pain were recruited to a cohort study (ATLAS). Participants underwent a standardised clinical assessment, lumbar spine MRI and a subsample (n = 93) or without (n = 26) clinically confirmed sciatica, nor between those with (n = 44) or without (n = 49) sciatica and MRI confirmed nerve root compression.No difference was found in the serum level of any of the 17 biomarkers tested in patients with (In this cohort, no significant differences in serum levels of TNFα, IL-6 or any other biomarkers were seen between patients with sciatica and those with back pain with referred leg pain. These results suggest that in patients with low back-related leg pain, serum markers associated with inflammation do not discriminate between patients with or without clinically confirmed sciatica or between those with or without evidence of nerve root compression on MRI. Lumbar spinal radicular pain (with or without radiculopathy) or sciatica, represents one distinct presentation of low back-related leg pain, which is often characterised by pain radiating to below the knee and into the foot. Patients with sciatica suffer more severe pain and disability and take longer to recover than those with low back pain (LBP) alone . AlthougInterest on possible inflammatory aetiologies for sciatica initially focused on the cytokine TNFα, including randomised trials of anti-TNF inhibitors infliximab  and adalOther pro-inflammatory cytokines investigated include IL-6- with studies showing high levels of IL-6 in disc samples from patients undergoing surgery . A studyTherefore, the aim of this study was to examine serum levels of key biomarkers in patients presenting in primary care with symptoms of low back-related leg pain including sciatica, and to see whether levels were different in patients with clinically diagnosed sciatica with or without or evidence of nerve root compression on MRI.Primary care consulters aged > 18 with low back-related leg pain were recruited as part of a longitudinal study (the ATLAS study) investigating the overall prognosis of low back-related leg pain and sciatica in primary care. The ATLAS study procedures have been described in detail elsewhere , here weFor the purposes of this nested study , patients consenting to the main study at this site, were also invited to take part in the biomarker sub study. Consenting patients had serum samples taken for biomarker analysis in addition to the standardised clinical assessment.Participants were classified as having nerve root involvement due to suspected disc prolapse on the basis of the clinical assessment .For the purposes of analysis, we first examined levels of serum biomarkers between patients with clinically diagnosed disc-related sciatica and with referred leg pain, and secondly we examined levels of serum biomarkers between patients with clinically diagnosed disc-related nerve root involvement and evidence of concordant MRI findings, and those patients without evidence of concordant MRI findings.All patients provided written informed consent. The biomarker study was approved by the North West- Greater Manchester South Research Ethics Committee (REC reference number: 12/NW/0173).o C until required. Key cytokines, chemokines and matrix metalloproteinases (MMPs) implicated in sciatica pathogenesis including TNFα, IL-1, IL-6, MMP1,3,8, aggregan and monocyte chemoattractant protein-1 (MCP-1/CCL-2) were measured in duplicate on a Bio-Plex™ 200 suspension array system using commercially available multiplex detection kits for cytokines  kits, Millipore (UK) Ltd., Walford, Hertfordshire, UK), or Fluorokine MAP kits for MMPs . Further details on the kits used are available in the Sera were separated from bloods collected in plain BD Vacutainer® tubes at study entry. All sera were stored at -70All data were tested for normality and the appropriate parametric or non-parametric test was selected for analysis. Initial univariable analysis was carried out using the Mann Whitney U test to compare median cytokine levels between groups. A multivariate variable selection procedure using the algorithm of McHenry  was usedp value of 0.05.Statistical analyses were carried out using Number Cruncher Statistical Software package for Windows . The significance level was set at a Data for the main ATLAS cohort are published elsewhere . One hunn = 44) and those without (n = 49). Serum IL-6 levels were low or below the level of detection, and no difference was seen in the levels of IL-6 or TNFα or any of the other biomarkers between the groups  and the health and societal level . Studies have suggested a possible inflammatory aetiology in the development or persistence of sciatic pain, and given the availability of cytokine inhibitors for treatment of inflammatory arthritis, this has prompted research to determine whether these agents could be effective for sciatica. Previous studies have confirmed the presence of key cytokines such as TNFα and IL-6 in surgical disc samples, and recent data have suggested that serum levels of these cytokines may be elevated in patients with sciatica symptoms –10, althIn this study of patients with low back-related leg pain seeking primary healthcare, no difference was found in the levels of TNFα or IL-6 between those with or without either clinically defined sciatica or clinically defined sciatica with concordant MRI findings. The results of this study are in contrast to those of Wang  who founThere are a number of strengths and weaknesses that need to be considered when interpreting the results of this study. A key strength is that the cohort represents an unselected population of primary care consulters with low back-related leg pain and sciatica rather than being recruited from spinal surgical clinics and as such the results are likely to be highly generalizable. Furthermore, patients underwent a standardised clinical assessment and MRI scan , providiOne of the weaknesses is that biomarker measurements were made at a single time point only, so we are not able to determine whether there were fluctuations in the levels of biomarkers over time  or that the groups were not sufficiently different to detect differences. Since there are currently no internationally agreed standard benchmark serum levels for any of these biomarkers, comparisons across studies is not possible . SecondlIn summary, in our primary care cohort of patients with low back-related leg pain including sciatica, serum markers associated with inflammation, angiogenesis or extracellular matrix remodelling do not discriminate between patients with and without sciatica, or between those with sciatica with and without obvious evidence of nerve root compression on MRI. Larger longitudinal studies are required to determine whether any serum biomarker levels are associated with persistence of sciatica symptoms or whether other biomarkers could be important in the pathogenesis and persistence of sciatica.


The aim of this pilot study was to describe vulnerability and resilience and possible subgroups in patients with chronic work related musculoskeletal pain in occupational healthcare. A second aim was to evaluate a patient-centered approach. This study was based on consecutive patients with chronic pain, seen by the same physician and sick-listed full or part time three months or longer. They were included during a period of three months. Patient reported outcome measures (PROM) were administered at baseline and at follow-up after 8 months. A patient-centered approach was applied where the patient's whole situation was taken into account.p=0.01), pain interference (p=0.001), life control (p=0.01), affective distress (p=0.02), and dysfunction (p=0.001) on the multidimensional pain inventory (MPI) and fewer patients were sick-listed full time at follow-up (13 patients versus 21). By means of multivariate data analyses this change in MPI was confirmed and was also correlated with a significant increase in health related quality of life (HRQoL). Moreover subgroups with different outcome at follow-up were identified according to attachment pattern and subgroups on MPI. A dominance of an insecure dismissing attachment pattern and a subnormal sense of coherence (SOC) was reported both at baseline and at follow-up. The patients (n=38) reported significant improvement of pain severity ( A patient-centered approach may be of value for patients with chronic pain in occupational healthcare, improving pain and dysfunction. Patients with chronic pain are a heterogeneous group where outcome of treatment might be influenced by individual resilience and/or vulnerability. Chronic pain is defined as pain lasting for more than three months . In a suDuring a period of three months all consecutive patients sick-listed for ≥3 months due to chronic musculoskeletal pain were included. Exclusion criteria were insufficient knowledge of the Swedish language and not being able to independently complete the questionnaires. A biopsychosocial approach was used and the patient's whole situation was taken into account in the treatment with a focus on empowerment as described by Malterud and Hunskaar . The patThe questionnaires were administered in the clinical setting as a rule at baseline and after 8 months of treatment. However, at follow-up the questionnaires were mailed to a few patients (after a telephone contact).The Relationship Scales Questionnaire (RSQ) is a self-assessment instrument for the assessment of attachment patterns according to Bowlby's Attachment theory developed by Griffin and Bartholomew . A four-The SOC used in this study contains 29 items. The concept sense of coherence was developed by Antonovsky to describe health promoting resources based on three components of this concept: comprehensibility, manageability, and meaningfulness . Higher The MPI is a self-assessment instrument measuring psychosocial, cognitive, and behavioural effects of chronic pain developed by Turk and Rudy , 27. TheThe BAI measures the severity of anxiety during the past week with a 21-item self-report inventory using a four-point scale ranging from 0 (no symptoms present) to 3 (severe symptoms). The standard cut-offs are as follows: 0-7 indicates minimal anxiety, 8-15 indicates mild anxiety, 16-25 indicates moderate anxiety, and 26-63 indicates severe anxiety . It has The BDI is a widely used questionnaire for assessing the severity of depression and is sensitive to changes over time . The staThe Pines' Burnout Measure assesses three components of burnout: physical exhaustion, mental exhaustion, and emotional exhaustion. It consists of a 21-item scale. Of the 21 items, 17 are negative and four are positive. All items are responded to on a 7-point scale ranging from1 to 7. The score is determined as the mean response to all items with positive items reversed. The cut-off value for burnout is >4.0 , 35. TheThe Short Form 36 (SF-36) evaluates physical and psychological aspects of health related quality of life (HRQoL). The items are grouped into eight subscale scores: physical functioning (PF), role limitations caused by physical problems (RP), bodily pain (BP), general health (GH), energy/vitality (VT), social functioning (SF), role limitations caused by emotional problems (RE), and mental health (MH). The subscales range from 0 to 100, where a higher value indicates a better HRQoL –39.For comparison within the group over time the Wilcoxon signed rank test was used in SPSS 12.0.1. All statistical tests were two-tailed and conducted at a 5% significance level.In a next step Multivariate data analyses (MVDA) using Principal Component Analysis (PCA)  and Two-p= 0.01).During the inclusion period 45 patients were identified, and, of those, 35 women and 7 men agreed to participate in the study. Three patients were not eligible due to insufficient Swedish language competency, hence not being able to independently complete the questionnaires. In the remaining group (n=42) , 50% werp=0.01) (p=0.35), indicating a minimal impairment of the mean value of SOC both at baseline and at follow-up (p=0.01), pain interference (p=0.001), life control (p=0.01), affective distress (p=0.02), and dysfunction (p= 0.001) (As shown in p=0.01) . SOC at ollow-up . At baseollow-up . No signollow-up . The pat= 0.001) . Subgrou= 0.001) . In SF-3= 0.001) .2X=0.40) with a cross-validated prediction, Q2X=0.17 . Component p1 and p3 modeled items in MPI, RSQ, SOC, BAI, BDI, burnout, and HRQoL . AC correlated inversely with the loadings of a Dys subgroup (Cluster 2) with another Dys subgroup was distinguished inversely correlated with the loadings of an ID subgroup. The patients in this Dys subgroup were older. They had good support from significant others and reported a higher HRQoL and a strong SOC but also had a positive correlation with dysfunction and pain in MPI.In the PCA three significant principal components (p1-3) explained 40% of the variation of the data,  and one orthogonal component (po1). The explained variance R.34 Fig. . The cha.34 Fig. . The loaCluster 3) with high levels of dysfunction, affective distress, and interpersonal distress in MPI, anxiety, depression, burnout, and fearful attachment at baseline and follow-up. These patients also had a significant lower SOC and mental health, physical function, social function, and vitality in SF-36 at baseline and follow-up and a lower mean age. This model also implied an opposite interpretation where a subgroup of older patients with higher scores of items in SF-36, SOC, and support from significant others at baseline and follow-up also had lower scores of pain severity and dysfunction in MPI and lower scores of burnout and depression at baseline and follow-up. Thus this orthogonal model represents a third cluster of patients comprising adaptive and a mixture of very dysfunctional or interpersonally distressed patients, all with a low potential of change.Significant variations in the orthogonal component po1  comprisecorr in the third predictive component of the O2PLS, working percent at follow-up had a correlation of 0.43 with high scores in SF-36 and interpersonal distress and low scores in MPI for pain and dysfunction both at baseline and at follow-up , especially regarding the heterogeneity of the group, short follow-up time, and the lack of a control group. In order to compensate for relatively few observations and many variables multivariate data analyses (MVDA) were performed. The multivariate projection discards noise and the latent factors  become stabilized by inclusion of relevant variables. By introducing many variables at the same time multiple collinearity can be created. Most datasets in the present area provide a few underlying phenomena that describe the system. In recent years this method has been used increasingly to investigate both very small and large populations of patients with chronic pain according to systemic differences in serum and liquor metabolomics . The samThe nonresponse at follow-up was 4 patients. These patients did not diverge from the group mean values at baseline but for a significant lower mean value of dysfunction and pain interference. The heterogeneity in groups of patients with chronic pain also makes it difficult to assess the effects of treatment as all patients do not benefit from the same treatment . Using MA patient-centered approach may be of value for patients with chronic pain in occupational healthcare, improving pain and dysfunction. Patients with chronic pain are a heterogeneous group where outcome of treatment might be influenced by individual resilience and/or vulnerability.


Methods. Between 2015 and 2016, 94 patients who received both nonimage- and fluoroscopy-guided L-ESIs were analyzed retrospectively. The changes of the numeric rating scale (NRS) in pain intensity and functional outcome and the differences in the number of complications between blind and fluoroscopy-guided L-ESIs in the same individuals were evaluated by a matched paired analysis.  Although fluoroscopic guidance is recommended highly for more accurate lumbar interlaminar epidural steroid injection (L-ESI), many physicians still use a nonimage-guided approach for L-ESIs. However, because of its associated risk of radiation and increased medical expense, the cost-effectiveness and safety of fluoroscopy-guided ESI have been called into question. The goal of this retrospective matched paired analysis in the same individuals was to assess the effectiveness and prevalence of complications of nonimage-guided L-ESI compared to those of fluoroscopy-guided L-ESIp=0.16). More subjective functional improvement was observed in fluoroscopy-guided L-ESI  than in nonimage-guided L-ESI  without statistical significance (p=0.16). Nine (9.6%) patients in the nonimage-guided group experienced complications related to the procedure overall compared to 4 (4.3%) in the fluoroscopy-guided group (p=0.27).  Of the 94 patients, the differences in NRS before and after the procedure were 1.29  = 0.94–1.65) for the nonimage-guided group and 1.64 (95% CI = 1.28–2.01) for the fluoroscopy-guided group ( In this study, both blind and image-guided L-ESI techniques included similar extents of postprocedural outcomes and complications. Physicians should consider the risks associated with the two different techniques overall and develop ways to individualize the procedure to decrease the risk of complications and improve the positive outcomes of lumbar epidural steroid injections. Traditionally, lumbar interlaminar epidural steroid injections (L-ESIs) have been performed without radiographic guidance. Over the past two decades, image-guided fluoroscopy has been adopted in practice and rapidly has become available to achieve more accurate procedures . Most ofBecause of the radiation hazard and increased medical expense, the cost-effectiveness and safety of fluoroscopy-guided L-ESIs have been called into question. Both patients and operators are at significantly increased radiation risk because of the widespread use of fluoroscopy-guided interventional procedures , 5. AlthBecause of the discrepancy between the technically ideal approach and the approach used more frequently, this retrospective analysis was undertaken to assess data on the effectiveness, rate of failure, and prevalence of iatrogenic complications of nonimage-guided, blind L-ESI compared to those of fluoroscopy-guided L-ESI with a focus on lower back pain in the same patients. The retrospective review of the patients who went through both fluoroscopy-guided and nonimage-guided L-ESI were analyzed. This study was the first to compare the efficacy of both blind and image-guided ESI technique in the same patients. Comparing the two different procedures in the same patients provided us with extremely helpful information because they were performed under exactly the same anatomical conditions.This retrospective study was performed at the Pain Clinic in Asan Medical Center, and the protocol was approved by its institutional review board . We searched our institution's Information Technology of Service Management (ITSM) system between January 2015 and December 2016 using the procedure name, “lumbar epidural steroid injection.” Regardless of whether the procedure was performed with fluoroscopy, both were included in the study if they met the following criteria: (1) patients were at least 20 years of age; (2) patients had chronic lumbar pain that did not respond to conservative therapy, including medical or physical therapy; and (3) patients had undergone both fluoroscopy and nonimage-guided L-ESI. Patients with the following conditions were excluded from the study: (1) uncontrolled psychiatric or medical conditions; (2) experience with fluoroscopy- or nonimage-guided L-ESI alone; (3) lost follow-up from our pain clinic; (4) allergic to local anesthetics, contrast dye, or steroids; and (5) coagulopathy.According to the retrospective review, reasons to go through the blind technique included (1) nonavailability to use the fluoroscopy on patients visiting days and (2) refusal to go into the OR room or to wait for days to get the procedure. On the other hand, reasons to go through the fluoroscopy-guided technique included the following: (1) patients have enough time to wait until the scheduled operation and (2) patients readily available fluoroscopy on the patients' visiting days.All procedures were performed on an outpatient basis. Nonimage-guided L-ESIs were performed at the outpatient clinic, and fluoroscopy-guided L-ESIs were performed in the operating room. The level of pathology was determined by clinical symptoms and signs, and sensory deficits were correlated with the imaging tests. For the blind L-ESIs, operators used the line connecting the superior iliac crests to estimate the level of the L4 vertebra or the L5-S1 intervertebral space as an anatomical landmark to locate the intervertebral level desired. These anatomical landmarks were corrected and confirmed by simple lumbar spine radiography obtained previously. The patient was placed in the lateral decubitus position with flexion of the knee and hip before the nonimage-guided L-ESI was performed. After sterile skin preparation, infiltration of 1% lidocaine into the skin and subcutaneous tissue was performed in an aseptic fashion. At the interspace closest to the clinical level of pathology, a 20-gauge Tuohy needle  was placed and the loss of resistance technique was used to guide the needle tip to the epidural space accurately. After confirming no aspiration of blood and/or cerebrospinal fluid, 6 mL of a mixture of 1% lidocaine, 5 mg of dexamethasone, and 1500 IU of hyaluronidase was administered.In the case of the fluoroscopy-guided L-ESIs, a fluoroscope was used to visualize the needle during the procedure. To monitor incidental neural damage and allow the patients to cooperate during the procedure, medications or sedatives were not used prior to the procedure. The patient was placed on the table in a prone position with a pillow under the abdomen to minimize lumbar lordosis. After sterile preparation of skin and anesthetization of skin and soft tissue with 1% lidocaine, a 20-gauge Tuohy needle was inserted into the target intervertebral space. An epidurogram of the target vertebral level was obtained using a contrast medium , and 6 mL of a mixture of 1% lidocaine, 5 mg of dexamethasone, and 1500 IU of hyaluronidase was injected into the fluoroscopy-confirmed epidural space.In cases of accidental dural puncture, intrathecal needle insertion, motor weakness, sudden hypotension during the procedure, and intravascular drug injection, the needle was removed immediately and the events were noted in the electrical medical records. The epidural injection was attempted at either one intervertebral space above or below the initial attempt when accidental dural puncture occurred.The outcome evaluation was performed at baseline and at the next follow up visit after the procedure. For the outcome assessment, the numeric rating scale (NRS) of pain intensity and improvement in physical functional status were reviewed from each patient's medical record. Patients were considered to have better functional outcomes if they said “better” after the procedure. If they expressed “no change or worse” or did not mention the functional change after procedure, the patients were considered no change or worse functional outcomes.Baseline characteristics, including age, gender, body mass index, underlying diseases, duration of pain, pain intensity, etiology of lumbar pain, and formal reading of diagnostic imaging tests, including magnetic resonance imaging (MRI), lumbar X-rays, and lumbar computer tomographic (CT) tests, were obtained for analysis. We reviewed the lumbar MRIs to determine the principal pathology of lumbar pain and divided our findings into 5 groups: (1) herniated intervertebral disc; (2) foraminal spinal stenosis; (3) central spinal stenosis; (4) failed back surgery syndrome, and (5) facet joint syndrome. Complications associated with the procedure with respect to postdural puncture headache, intrathecal needle insertion, motor weakness, hypotension, and intravascular drug injection also were reviewed in the analysis.t-test or Wilcoxon rank sum test to assess differences between the nonimage guided and fluoroscopy-guided L-ESI groups, as appropriate. Categorical data were compared with a McNemar's test to assess differences between the two groups. The data were analyzed using SPSS v. 21.0 .Continuous variables were expressed as means and 95% confidence intervals (CI), and categorical variables were expressed as frequencies or percentages. Continuous variables were compared using a paired n=12); transforaminal approach to the epidural space (n=14); caudal approach to the epidural space (n=9), and ESIs performed at the intervertebral space between the 12th thoracic and 1st lumbar vertebra (n=2). Ultimately, data from 94 ESIs were analyzed. Of these, patient demographics and diagnosis of lumbar pain are shown in A total of 131 charts were reviewed. Of these, 37 were excluded for the following reasons: follow up loss (p=0.160). The changes in functional outcome after the procedure were compared similarly and are shown in p=0.16). Nine (9.6%) patients who experienced complications related to the procedure overall were in the blind L-ESI group and four (4.3%) patients were in the fluoroscopy-guided L-ESI group (p=0.27), as shown in The initial and postprocedure pain intensity between the blind and fluoroscopy-guided interlaminar epidural steroid injections in the same individuals are shown in This study was the first to review and compare outcomes and complications of blind and image-guided L-ESI techniques performed in the same individuals. Studying the effects of both procedures in the same patients gave us reliable information with which to compare postoperative efficacy, as the procedures were performed in exactly the same anatomical situation. Most previous studies have used heterogeneous patient groups with different diseases and variable anatomical conditions. Various cases of chronic low back pain could provide us with confounding data in comparisons of the postprocedural efficacy of both blind and image-guided L-ESIs , 9.For patients with chronic low back pain in which imaging tests support that the etiology of the pain is the lumbar spine, L-ESI is one of the best treatment choices according to reliable evidence , 11. HowHowever, data suggest that the occupational exposure to radiation ultimately could cause irreversible tissue damage , 14, 15.Furthermore, although image-guided L-ESI is used more widely and commonly, it is still much more expensive than is blind L-ESI . ArrangeThe limitations in this study included the following: (1) small sample size; (2) observer bias in reviewing the retrospective data; (3) heterogeneity of diagnoses, and (4) heterogeneity of various pain physicians who performed the procedures. In view of the widespread use of fluoroscopy, despite the fact that it provides more reliable data, the radiation risk and medical expense lead pain physicians to favor the older blind technique often. Larger sample sizes and more homogenous data are vital in future studies to clarify the remaining uncertainties about this subject.In this study, we reached the conclusion that both blind and image-guided L-ESI techniques have similar efficacy with respect to postprocedural pain relief, functional improvement, and complication risk. Physicians should consider the advantages and disadvantages of the two techniques carefully and determine ways to individualize the procedures to decrease the risk of complications and improve positive outcomes after lumbar interlaminar epidural steroid injections.


The aim of the study was to analyze the effect of local infiltration analgesia (LIA), peripheral nerve blocks, general and spinal anesthesia on early functional recovery and pain control in primary unicompartmental knee arthroplasty (UKA).n = 38) or epidural catheter  in combination with general anesthesia or spinal anesthesia, respectively, and LIA combined with general anesthesia  or spinal anesthesia . Outcome parameters focused on the evaluation of pain (NRS scores), mobilization, muscle strength and range of motion up to 7 days postoperatively. The cumulative consumption of (rescue) pain medication was analyzed.Between January 2016 until August 2016, 134 patients underwent primary UKA and were subdivided into four groups according to their concomitant pain and anesthetic procedure with catheter-based techniques of femoral and sciatic nerve block  mean NRS scores (at rest) compared to the catheter-based groups at the day of surgery. In the early postoperative period, the dose of hydromorphone as rescue pain medication was significantly lower (up to 68%) in patients with SP&EPI compared to all other groups. No significant differences could be detected with regard to grade of mobilization, muscle strength and range of motion. However, there seemed to be a trend towards improved mobilization and muscle strength with general anesthesia and LIA, whereof general anesthesia generally tended to ameliorate mobilization.Except for a significant lower NRS score at rest in the LIA groups at day of surgery, pain relief was comparable in all groups without clinically relevant differences, while the use of opioids was significantly lower in patients with SP&EPI. A clear clinically relevant benefit for LIA in UKA cannot be stated. However, LIA offers a safe and effective treatment option comparable to the well-established conventional procedures. Anteromedial knee osteoarthritis is a distinct clinicopathological entity which often leads to disabling pain and limitation of range of motion . If consAlong with UKA, minimally invasive surgery became more and more popular in the early 1990s . BesidesAs an alternative method for multimodal, postoperative pain management, local infiltration analgesia (LIA) around the soft tissues of the knee joint gained increasing interest in recent years with excellent pain relief and absent muscle weakness . This leIn literature, there are only a few trials, which described the LIA technique in UKA. In preliminary trials, Beard et al.  and ReilIn literature, there is no study analyzing the effect of LIA,  catheter-based techniques and their combination with general or spinal anesthesia on pain control, mobilization, muscle strength and range of motion for up to 7 days postoperatively in one patient collective of UKA. Therefore, the aim of the study was to analyze the effect of these different peri- and postoperative anesthetic therapies on early functional recovery and pain control in primary UKA.One hundred thirty four patients were treated for medial knee osteoarthritis with UKA between January and August 2016 and were included for this retrospective analysis. The inclusion criterion was primary medial knee osteoarthritis. Patients were excluded if they had significant patellofemoral or lateral osteoarthritis, secondary arthritis due to rheumatoid arthritis or trauma, osteonecrosis or revision surgery. Patient demographics and clinical data are shown in Table This study was performed in conformity with the Declaration of Helsinki and was approved by the Ethics Committee of the Bavarian State Chamber of Physicians (ID: 2017–109).After induction of general anesthesia, patients allocated to group GA&FNB had a FNB catheter inserted with real-time monitored ultrasound imaging. A total of 20 ml of 0.1% ropivacaine was injected around the femoral nerve; additionally ultrasound-guided sciatic nerve block with 20 ml of 0.1% ropivacaine was established as single shot block. Postoperatively, 0.2% ropivacaine was continuously infused at the rate of 3 ml/h for 3 days through the femoral catheter.In group SP&EPI, a catheter was preoperatively sited at the cranial lumbar vertebrae.combined with a spinal anesthesia (1 ml of 0.5% bupivacaine and 10 μg sufentanil in the subarachnoid space) in a single needle technique. After recovery from spinal anesthesia under the level L3, an initial 10 ml bolus containing 0.5% bupivacaine, 0.6 μg/ml sufentanil and saline was introduced. Thereafter, patients were self-medicated with a bolus of 4 ml via a patient-controlled epidural anesthesia (PCEA) system with a lockout of 20 min. PCEA was discontinued three days after surgery.In the LIA groups, 100 ml of 0.2% ropivacaine without any additional components were intraoperatively administered by the surgeon periarticularly in the soft tissues according to the injection technique popularized by Kerr and Kohan . During ® Partial Knee System  was used. Implants were fixated cementless, hybrid cemented  or fully cemented depending on bone stock and age  for infection prophylaxis was given to all patients. The surgeries were performed with a standard minimal invasive midline vertical incision and medial parapatellar approach; the patella was removed laterally but not dislocated or everted. A tourniquet was inflated to 250 mmHg at the beginning of the surgery and deflated after removal of the surgical dressings. In all cases, the OxfordPostoperative management was identical in all groups. After surgery, every patient was given a peripheral pain medicament  for about 2 weeks to relieve pain and low molecular weight heparins subcutaneously for about 2 weeks to prevent deep vein thrombosis. The cumulative doses of rescue analgesia (hydromorphone p.o. or piritramide i.v.) were also registered.Postoperative physiotherapy was started immediately after surgery in a progressive manner and all patients received physiotherapy daily. A specially trained pain service regularly visited all patients twice a day for the first four postoperative days.Self-reported pain scores in terms of numeric rating scores (NRS) at rest and with activity  from day of surgery until postoperative day 4 were collected and analyzed. For evaluation of functional outcomes, grade of mobilization ranging from values of 1 to 6 according to our institutional grading system of mobilization was analyzed: 1 = bedridden, 2 = sitting, 3 = standing, 4 = walking in room, 5 = walking on the floor, 6 = walking stairs. Furthermore, muscle strength according to the British medical research council (M0/5-M5/5) and passive range of motion (degrees of extension and flexion) were examined. Functional outcomes of mobilization, muscle strength and range of motion were documented daily from pre-operative day until postoperative day 7, respectively. The patients’ medical files were also studied for potential analgesic technique-related and surgery-related complications within the first 7 days, such as rates of neurologic events, cardiovascular events, falls, knee joint infections, prosthesis loosening, or revision surgery. All data were collected from the patients´ medical records and nurses´ observational charts.Statistical analysis was performed with SPSS statistical software 20.0 . Descriptive statistics were calculated for all variables of interest. Continuous measures such as age were summarized using means and standard deviations whereas categorical measures were summarized using counts and percentages.The Kruskal-Wallis test was used for analysis of one nominal variable and one ranked variable. In a further detailed analysis, post-hoc comparisons of factor-level combinations were conducted by use of Mann-Whitney-U test, depending on previous  significance testing. In this explorative study, no adjustment of the alpha-error level was conducted.Baseline characteristics of patients were comparable among all groups Table . No patin = 1), secondary application of a FNB (n = 1) and to general anesthesia (n = 1). In GA&LIA, 4 patients (8.7%) were changed to FNB (n = 3) and PCIA (n = 1). These patients were excluded from analysis. In SP&LIA, a modification of anesthetic regime was not necessary for any patient. No analgesic technique-related and surgery-related complication was encountered in any group within the first postoperative 7 days. At the day of surgery, the demand for piritramide was significantly higher  in groups with general anesthesia compared to spinal anesthesia. All LIA patients received 100 ml of the LIA mixture with 15.4 mg ± 3.1 (GA&LIA) and 16.6 mg ± 2.1 (SP&LIA) dexamethasone, respectively.Pain exacerbation after surgery due to insufficient pain relief (NRS > 7) with the current anesthetic technique led to another analgesic technique. In GA&FNB, one patient received a patient-controlled intravenous analgesia (PCIA) with an initial bolus of 4 mg piritramide followed by an optional bolus of 2 mg piritramide with a lockout of 10 min. In SP&EPI, 3 patients (15.0%) were converted to PCIA (p < 0.05) . The values of the LIA groups slightly increased at day 1 while the catheter-based groups showed almost constant pain values at the day of surgery and day 1. Afterwards, a gradual reduction of pain values was detectable.At the day of surgery, the NRS scores at rest of the LIA groups were statistically significant lower  compared to the catheter-based groups  Fig. . In compp < 0.05)  lower values  and reached full standing as recently as on postoperative day 1. From day 2 on, all patients were able to walk in the room or even on the floor  and the slight differences in mobilization among the groups were diminished. Overall, GA&LIA still tended to achieve a slightly accelerated and earlier mobilization compared to all other groups, particularly at the day of surgery with on average 21% higher grade of mobilization while at later time points this trend diminished to about 6% (p > 0.05).Upon analyzing the grade of mobilization, no significant differences among the groups at any time point were observed Fig. . All patp > 0.05) among the groups with respect to muscle strength (M0/5-M5/5) .There were no significant differences (/5) Fig. . At the The mean range of motion (flexion and extension of the knee joint) was similar within the groups Fig. . At the In recent years, several studies described the benefit of LIA as an alternative analgesic procedure in TKA , 23, 24;At the day of surgery, the LIA technique revealed about 50% lower mean NRS values at rest (0.9 ± 0.1) compared to the catheter-based groups (1.8 ± 0.1). However, even when being statistically significant these findings are not clinically relevant because the differences are too marginal to reach a clinical impact. At postoperative day 1, pain values of NRS scores with activity in LIA with general or spinal anesthesia, respectively, nearly doubled to decrease again at day 2 indicating a pain exacerbation at day 1. A slight increase of the dose of hydromorphone was also visible at day 1. However, the results of the significant differences in the dose of hydromorphone in patients with SP&EPI within the early postoperative days may be very well of clinical relevance; alone by the not negligible side effects including nausea, dizziness and constipation , which cInterestingly, we did not find any significant differences in terms of mobilization, muscle strength or range of motion. It is well known, that UKA resulted in improved and faster postoperative knee function compared to TKA –5. The eFinally, it is up to the treating surgeon to choose a procedure, which is individually and thoroughly adapted to the patient. It is important to obtain a detailed medical history and clinical examination upon meeting the patient including analysis of the individual sense of pain and knee function. It has to be considered individually whether the advantage of spinal anesthesia and epidural catheter in terms of comparably lower dose of opioids predominantly exceeds the slightly poorer function. Patients with good preoperative knee function and muscle strength may physically and mentally benefit from decreased pain postoperatively by use of spinal anesthesia; while patients who predominantly suffer from functional restrictions rather than chronic knee pain might be more satisfied with LIA.Originally, Kerr and Kohan described the LIA mixture as a combination of ropivacaine 2 mg/ml, ketorolac 30 mg and adrenaline 10 mg/ml that is infiltrated in different layers of the joint in volumes of 150–170 ml for TKA . HoweverIn the present study, we only used 100 ml of 0.2% ropivacaine for infiltration for several reasons. In knee arthroplasty, chondrolysis due to injected local anesthetics is mainly of concern after UKA, since there is still healthy cartilage remaining in the joint. With numerous studies demonstrating chondrotoxicity of local anesthetics in human and animal joints, it is very important to understand the molecular mechanisms and clinical effects of these medications on chondrocytes including decreased cell metabolism, increased apoptosis, necrosis and morphologic tissue degeneration and thereby, the risk for early osteoarthritis –36.The chondrotoxic effects occur dose- and time-dependent –39. In lFurthermore, a direct linear relationship of increasing cell death with increasing duration of exposure has been described in prior studies , 44, 45.There are some limitations that pertain to that study. Due to its retrospective design, the study was not blinded or randomized, which may have introduced reporting bias. Furthermore, the choice of anesthesia by the patient might have induced some selection bias, although the group characteristics appeared to be identical among the four groups. Although it was a retrospective investigation, the strengths of the study include a large number of patients managed according to clear inclusion and exclusion criteria. The surgical and anesthetic procedures followed a consistent standard-treatment protocol in the same hospital by the same surgeons with extensive surgical experience in the treatment of UKA and its concomitant analgesic procedures.In conclusion, the findings from this study suggest a slight but clinically not relevant advantage of the LIA groups in the early postoperative period in terms of mobilization, muscle strength and range of motion. In general, pain relief was similar in all groups, with exception of a significant lower NRS score at rest in the LIA groups at day of surgery. The use of rescue pain medication was significantly lower in patients with SP&EPI. A clear clinically relevant benefit for LIA in UKA can not be stated. Preoperative information including knee function and pain status should be considered for each patient individually before choosing a multimodal perioperative analgesia protocol. In UKA, infiltration of a local anesthetic offers a safe and effective treatment option comparable to the well-established conventional procedures.