The aim of this study was to evaluate the outcome of patients with patellar tendinopathy treated with platelet-rich plasma injections (PRP). Additionally, this study examined whether certain characteristics, such as activity level or previous treatment affected the results.n = 36) were asked to fill in the Victorian Institute of Sports Assessment – Patellar questionnaire (VISA-P) and visual analogue scales (VAS), assessing pain in activities of daily life (ADL), during work and sports, before and after treatment with PRP. Of these patients, 14 had been treated before with cortisone, ethoxysclerol, and/or surgical treatment (group 1), while the remaining patients had not been treated before (group 2).Patients (p < .0.05). However, group 2 also improved on VISA-P (p = .0.003), while group 1 showed less healing potential (p = 0.060). Although the difference between group 1 and group 2 at follow-up was not considered clinically meaningful, over time both groups showed a clinically significant improvement.Overall, group 1 and group 2 improved significantly on the VAS scales (After PRP treatment, patients with patellar tendinopathy showed a statistically significant improvement. In addition, these improvements can also be considered clinically meaningful. However, patients who were not treated before with ethoxysclerol, cortisone, and/or surgical treatment showed the improvement. Like tendinopathy of the elbow, rotator cuff and Achilles tendon, tendinopathy of the patellar tendon (jumpers’ knee) is caused by degenerative tearing of collagen fibres rather than an acute inflammatory condition . The undN = 36) before and after treatment with PRP. Of these patients, 14 had been treated with cortisone, ethoxysclerol and/or surgical treatment before PRP injection (group 1), while the other 22 patients had not received an injection or surgical treatment before (group 2). All patients had visited a physiotherapist and eccentric exercises had been performed exhaustively before being treated with PRP. The diagnosis of patellar tendinopathy was made on clinical grounds (pain on resisted extension of the knee located at the inferior pole of the patella). An additional MRI was performed in 21 (58.3 %) cases, showing oedema at the origin of the patellar tendon at the apex patellae in all cases. The mean follow-up period (in months) after being treated with PRP was 18.4 (SD = 4.9). The study was performed between March 2008 and June 2009 at the Medinova Hospital in Rotterdam (The Netherlands). The study protocol was approved by the Medical Ethics Committee.This prospective cohort study measured pain and sporting ability in patients with chronic patellar tendinopathy . This device uses a desktop-size centrifuge with disposable cylinders to isolate the platelet- and leukocyte-rich fraction from a small volume of the patient’s anticoagulated blood drawn at the time of the procedure. A 27-ml sample of whole blood was collected from the uninvolved arm into a 30-ml syringe that contained 3 ml of sodium citrate. The platelet-rich fraction was prepared according to the instructions for the use for the Recover System. Approximately 3 ml of PRP was obtained for each patient. The PRP was then buffered to physiological pH using 8.4 % sodium bicarbonate and Bupivacaine HCL 0.5 % with epinephrine (1:200000) was added. No activating agent was used. The total time from blood aspiration to injection in the patients was about 30 minutes. No specialised equipment, other than the centrifuge to process the Recover disposable, was required. All procedures were performed in the same office setting by an independent person certified for blood management.Approximately 1 ml of PRP with Bupivacaine HCL 0.5 % and epinephrine (1:200000) was injected directly into the area of maximum tenderness. Then the remaining PRP with Bupivacaine HCL 0.5 % with epinephrine  was injected by the investigator using a 22-g needle into the patellar tendon origin on the patella with a peppering technique. This technique involved a single skin portal and then five penetrations of the tendon.Immediately after the injection, the patient was rested in a supine position without moving the leg for 15 minutes. Patients were sent home with instructions to rest the leg for approximately 24 hours. If necessary, patients were allowed to use aminocetaphen, but the use of nonsteroidal anti-inflammatory medication was prohibited. After 24 hours, patients were given a standardised stretching protocol to follow for two weeks under the supervision of a physiotherapist. A formal eccentric muscle and tendon-strengthening program was initiated after this stretching. At four weeks after the procedure, patients were allowed to proceed with normal sporting or recreational activities as tolerated. The procedure for L-PRP preparation, injection technique and post-procedure protocol were identical to the procedure described for the lateral epicondylitis randomised controlled trial published previously, except for the standardised stretching protocol .Patients were asked to fill in the Victorian Institute of Sports Assessment – Patellar questionnaire (VISA-P) and visual analogue scales (VAS) before and after treatment with PRP.The VISA-P consists of eight questions , 14. ThiA VAS is an instrument to quantify the amount of pain reported by the patient. Scores can range from 0 (no pain) to 10 (severest pain). Patients were asked to fill in the level of pain during activities of daily life (ADL), work activities, and sport activities.P < 0.05. All statistical analyses were performed using the Statistical Package for the Social Sciences .Descriptive statistics  were used to present the available sociodemographic and clinical data at baseline. The groups (treated before or not treated before) were compared with Student t-tests or the Mann–Whitney U test and chi-square test. The paired-samples test was used to compare the VISA-P scores at follow-up with results assessed at baseline . The Wilcoxon signed-ranks test was used to compare the VAS scores and VISA-P scores at follow-up with the results assessed at baseline . In addition, effect sizes  were calculated. An effect size (ES) between 0.1 and 0.3 is small, 0.3–0.5 is moderate, and an ES greater than 0.5 is considered as large . A 15-pon = 22; 61.1 %). Group 1 received different treatment combinations: one patient received cortisone, ethoxysclerol and surgical treatment (2.8 %), four patients received cortisone and ethoxysclerol (11.1 %), four patients received cortisone and surgical treatment (11.1 %), four patients received only cortisone (11.1 %), and one patient received ethoxysclerol (2.8 %). Table Table Before treatment with PRP, only two patients (5.6 %) indicated that when they had no pain during sports, they were able to perform up to 40 minutes without any pain. After treatment with PRP, eight patients (22.2 %) were able to exercise without pain. These patients were able to play for at least 90 minutes without any pain, except for one patient who was able to play 40–60 minutes without pain. Before treatment, 13 patients (36.1 %) had pain, but were able to continue performing (score range: 60 minutes or more). After treatment, these numbers increased to 24 patients . Initially, 11 patients (30.5 %) had such pain that they were not able to finish the training (score range: 30 minutes or more). However, after PRP treatment only four patients (11.1 %) had to quit during a training session (score range: 30 minutes or more).p < 0.0001, and ES = 0.56. VAS ADL decreased from 5.9 to 2.7 , VAS work decreased from 6.3 to 3.2 , and VAS sport decreased from 8.50 to 4.61 .The total group significantly improved after being treated with PRP. That is, mean scores on VISA-P improved from 40.1 (SD = 15.6) to 57.7 (SD = 25.4), with t(35) = −3.986, p < 0.003, and ES = 0.59. Group 1 did not show significant improvement on VISA-P . However, VAS ADL scores, VAS sport scores, and VAS work scores significantly improved in both groups (see Table Mean scores on VISA-P significantly improved in group 2 from 39.1 (SD = 16.6) to 58.6 (SD = 25.4), with t(21) = −3.339, PRP treatment results in statistically significant improvement in patients with chronic patellar tendinopathy compared with the pre-injections status. Furthermore, these improvements can be considered clinically meaningful. Those patients who were not treated before with ethoxysclerol, corticosteroid, and/or surgical treatment before entering this prospective study, showed the largest improvement and thus showed the largest healing potential.The use of platelet-rich plasma as a treatment for chronic patellar tendinopathy reflects its use in other tendons and ligaments. There is increasing interest in sports medicine and orthopaedics in endogenous growth factors to relieve symptoms of degeneration of tendons and to counteract the failed healing response, which is characteristic of these injuries, to potentiate a faster return to sports and daily life activities. Despite this interest, and apparent widespread use, there is a lack of high-level evidence from randomised clinical trials assessing the efficacy of PRP in treating ligament and tendon injuries. Basic science and animal studies and small case series reports on PRP injections for ligament or tendon injuries, but few randomised controlled clinical trials have assessed the efficacy of PRP injections and none have demonstrated scientific evidence of efficacy. Scientific studies should be performed to assess clinical indications, efficacy, and safety of PRP, and this will require appropriately powered randomised controlled trials with adequate and validated clinical and functional outcome measures and sound statistical analysis. Other aspects of PRP use that need to be determined are (1) volume of injection/application, (2) most effective preparation, (3) buffering/activation, (4) injection technique (1 depot vs. multiple depots), (5) timing of injection to injury, (6) single application versus series of injections, and (7) the most effective rehabilitation protocol to use after PRP injection .This small series is not randomised, although the data were prospectively collected, and therefore the positive effect of PRP series does not represent the highest level of evidence. On the other hand, it is the largest series of patients with a chronic patellar tendinopathy treated with PRP. Other reports –20 in liThere was a significant difference between those that had chronic tendinopathy without previous failing therapies and those with chronic tendinopathy of the same duration but with previously failing treatments. In this study we measured large effect sizes in VAS for pain in daily life, sports and work after the injection of PRP, thus a large change in pain when PRP is injected, which is independent of whether patients were treated before or treated for the first time. The effect size for the VISA-P was in a different range, indicating less effect of the injection of PRP following previously failed treatments such as injection of steroids, ethoxysclerol or surgery. It is important to realize is that the duration of complaints in months was not statistically different between these two groups: the previously treated patients did not have a longer history of symptoms. The well-known negative effects of repeated steroid injections were recently emphasised by Coombs et al.  The effeIt was also noted that the pain with sports decreased significantly but most patients were still not pain free. This is illustrated by the improvement in VAS, but not by the improvement in VISA-P—the VISA-P scores the ability to perform specific sporting activities without pain whereas the VAS scores the level of pain during daily activities (ADL), work activities, and sport activities. Although the athletes were satisfied with this result it remains a point of interest. In search for complete recovery a second procedure was considered, but not attempted because of the experimental nature of this treatment. Repeated injections might be beneficial in patients who had suboptimal results after the initial injection, although no evidence for a beneficial effect of more than one injection exists. On theoretical grounds, by studying the inflammation cascade in tendon repair, a reinjection after three to four weeks seems logical since at this stage the cell proliferation and matrix deposition activity will have peaked and can be expected to subsequently decline. However, at this time no true indication of what the result of a second injection would be can be determined.Comparing our results with operative treatment in literature, we believe that these results may justify the implementation of a PRP injection before considering surgical treatment of patellar tendinopathy. Surgical treatment has been recommended when nonoperative treatment fails. Open tenotomy and debridement proved to be a safe and effective technique with 59 % excellent and 35 % good results . These pSeveral other limitations should be acknowledged. The needling/fenestration of tendinopathic tissue has a positive effect itself on tendon healing. This study was not aiming to show the difference between dry needling and the injection of L-PRP, but showed a poorer healing potential in those who had been previously treated, irrespective of the duration of the symptoms that were classified as chronic in all cases. In this study we used the multiple-penetration-of-the-tendon-technique. The reason for choosing this technique is, in our opinion, not scientifically supported, but was made on an empirical basis   and to cIn this study, we used the clinically minimal difference of the VISA-P to compare not only the treatment groups, but also to determine whether such a difference is present over time. However, no study has been performed to show whether this clinically meaningful difference could be used over time.Another limitation of this study, apart from the fact that it is a non-randomised and non-controlled study, is that although this manuscript presents one of the largest samples of patients with patellar tendinopathy treated with PRP, it is too small to analyse the effect of the different treatment combinations on the outcome. We were not able to show the logically existing relation between multiple previous treatments and a less optimal outcome, although the results were not as good as those patients who had previous failed injections with steroids or sclerosants. Both groups improved in VAS for pain in daily life, sports and work, but VISA-P shows no significant improvement in those who had been treated before compared to those who only received PRP. Whether this proves the lesser ability of PRP to jump-start the healing mechanism, which was stopped by ethoxysclerol, steroid or surgery, or just proves the worsening effect of those treatment methods, remains to be seen. Yet, the results suggest that there may be a relationship between prior treatments and efficacy of PRP therapy for chronic patellar tendinopathy. This relationship needs further studies powered to detect such a difference.


Several recent studies report the presence of a specific EEG pattern named Thalamocortical Dysrhythmia (TCD) in patients with severe chronic neurogenic pain. This is of major interest since so far no neuroscientific indicator of chronic pain could be identified. We investigated whether a TCD-like pattern could be found in patients with moderate chronic back pain, and we compared patients with neuropathic and non-neuropathic pain components. We furthermore assessed the presence of psychopathology and the degree of psychological functioning and examined whether the strength of the TCD-related EEG markers is correlated with psychological symptoms and pain ratings.Controlled clinical trial with age and sex matched healthy controls.Spontaneous EEG was recorded in 37 back pain patients and 37 healthy controls.We were not able to observe a statistically significant TCD effect in the EEG data of the whole patient group, but a subsample of patients with evidence for root damage showed a trend in this direction. Pain patients showed markedly increased psychopathology. In addition, patients' ratings of pain intensity within the last 1 to 12 months showed strong correlations with EEG power, while psychopathology was correlated to the peak frequency.Out of several possible interpretations the most likely conclusion is that only patients with severe pain as well as root lesions with consecutive thalamic deafferentation develop the typical TCD pattern. Our primary method of defining ‘neuropathic pain’ could not reliably determine if such a deafferentation was present. Nevertheless the analysis of a specific subsample as well as correlations between pain ratings, psychopathology and EEG power and peak frequency give some support to the TCD concept.NCT00744575ClinicalTrials.gov  Chronic pain is one of the most frequent chronic diseases. The largest subgroup of chronic pain conditions is lower back pain which is often considered as the one condition causing the largest financial damage to the economy in terms of treatment and work days lost Considerable information on the central neural mechanisms of chronic severe neurogenic (or neuropathic) pain has been obtained from studies on specific thalamocortical patterns In order to describe the specific EEG pattern of this TCD Sarnthein et al. Based on these findings it can be assumed that the presence of TCD can be detected in the surface EEG and that this pattern  may be a marker of severe chronic neuropathic pain. Since TCD seems to be related to the perpetuation and chronification of pain we wondered if this specific EEG pattern could also be found in a wider population of chronic pain patients.We were furthermore interested in psychological correlates of chronic back pain and whether these correlates were also related to the EEG patterns under consideration. It is well known that chronic pain and especially chronic back pain is associated with psychological distress In the current investigation we replicated the study of Sarnthein et al. We performed a controlled clinical trial with age and sex matched healthy persons as controls. The EEG spectral density as well as a set of questionnaires assessing psychological symptoms and psychological functioning of a sample of 37 patients with chronic back pain was compared with a sample of 37 healthy sex and age matched controls. Data within the patient group were split into patient with neuropathic pain vs. non neuropathic pain and compared to each other. The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Inclusion criteria for our study were (1) chronic back pain of least 1 year, (2) daily complaints about back pain, (3) an average rating of at least 5 for the average pain of the last 12 months on a VAS ranging from 0 = no pain at all to 10 = worst pain possible (4) age 18 to 70 years and (5) command of German language. Exclusion criteria were (1) the presence of psychiatric conditions including substance dependence, (2) immune suppressive treatment, (3) life threatening diseases, (4) participation in other clinical trials. Patients were recruited between July 2008 and December 2008 by public announcements and via pain specialists, neurologists and orthopaedists as well as through the Interdisciplinary Pain Unit of the University Medical Center. Patients underwent telephone screening before being invited to an intake interview to the Department of Environmental Health Sciences were all measurements took place. They were examined by an MD to determine inclusion and exclusion criteria before being included in the trial. Patients were offered participation in a behavioural intervention free of costs after EEG measurement.Healthy controls were recruited via public announcements. They had to be healthy and were not allowed to suffer from any pain. Controls were remunerated with 20 Euros for their participation in the EEG recording.www.clinicaltrials.gov NCT00744575. All patients and controls gave written informed consent.The trial was approved by the University Medical Center ethic's committee (please see Supporting Information for full letter) and was registered before start of recruitment at The sample of chronic pain patients was furthermore divided into two sub-samples. This was done by an MD with special training in chronic pain management. Patients were classified as either having pain of neuropathic origin (or not). Assessment took place according to the definition published by Treede et al. Sample size was determined on the basis of the predecessor study, which found significant results with N = 15 patients. Since we wanted to split our sample in two subsamples we recruited with N = 37 more than twice as many patients in order to arrive at least at the same statistical power for each subsample than in the original study.QuestionnairesPatient filled in the following questionnaires:EuroQol Quality of Life Questionnaire EQ-5DBrief Symptom Inventory BSIHospital Anxiety and Depression Scale HADSPain Perception Scale PPSChronic Pain Grade CPGQuestions on Life Satisfaction QLSgeneral intake form of the Interdisciplinary Pain Unit. This is an 18 page intake questionnaire especially designed for pain patients which collects information on sociodemographics, medication, pain localisation and prior treatments.The Healthy control participants had only to fill in BSI, EQ-5D, QLS, and HADS.EEG was recorded  with 72 channel amplifier  according to the international 10/20 system, from 60 electrode sites distributed throughout the whole head of the participants. The ActiCap System , that includes a cap with active electrodes was used. Diagonal EOG was recorded bipolarly from above and below the right eye to exclude trials contaminated with eye movements from further analysis. The ground electrode was placed in the left mastoid and the output EEG data was average referenced.Electrode impedances were kept under 5 kΩ. All measurements took place between 8 and 12 am in order to avoid sleepiness. All participants had to abstain from caffeine on the day of measurement since caffeine is known to influence theta activity replication and CSD analysis. In both cases, topographic distribution of power spectral density (PSD) was obtained by averaging across all 100 epochs. Given that PSD from all channels were similar, we averaged the log-transformed spectra across all channels for each participant. Grand-average power spectral density was then computed across subjects for comparing different sub-groups .All data analyes were performed with the commercial software Brain Vision Analyser 2.0  and custom scripts in MatLab . Artefacts due to ocular movement were first eliminated applying the Gratton & Coles algorithm, as implemented in Brain Vision Analyzer. Remaining EEG segments contaminated with eye movements, EMG or other artefacts of technical origin were rejected off-line by visual inspection. EEG channels with residual artefacts  were excluded from further analysis. Data were filtered with a bandpass filter  and segmented into 4 seconds epochs (with 2 s overlapping), allowing for a frequency resolution of 0.25 Hz. For each participant, 100 free-of artefact segments were included in further analyses. At this point two different analyses were conducted in parallel: In the first one, a discrete 4000 sample Fast Fourier Transformation (FFT) was computed for each segment  and the log-transformed PSD values at this frequency (peak power) was determined for each participant, in order to assess differences between the subgroups. Since for some participants the power spectral density did not show only one clearly dominating peak but looked broadly distributed within the frequency range of interest (4–12 Hz), we defined two other indices to grasp the overall EEG activity and its dominant frequency within this frequency range. First, the mean peak frequency and according standard deviation were computed across all participants. Next the lower and upper limits of a frequency-based ROI were defined by ± two standard deviations of the mean peak frequency. This resulted in two ROIs of 7.34 to 12.43 Hz for the replication and 7.07 to 12.43 Hz for the CSD analysis respectively. Additionally for each participant and type of analysis, the overall power was computed as the log-transformed sum of all PSD values within the empirically defined ROIs. In addition, we calculated for each ROI its centre of gravity CoG, which is the frequency at which the whole EEG power is split into two equal parts. This CoG splits the ROI into two parts with the same overall power. By this procedure we arrived at four different indices  which were then passed on to the subsequent statistical analysis.Similar to the study of Sarntheim et al. Cohen's d was applied All statistics were calculated with SPSS for Windows 15.0 . We tested all variables comparing between patients and controls for normal distribution by the Kolmogorv Smirnoff Test. If they proved to be normally distributed we applied the t-test for independent samples otherwise we used the non parametric Mann-Whitney U-Test. For the correlation of questionnaire and pain rating data with EEG parameters we applied the non parametric Spearman's rho. As an effect sizes measure for group differences On the basis of telephone screenings 38 patients were invited for intake examination and were included as well as and 40 healthy controls of same age (±3 yrs) and sex. Eighteen patients were classified as having neuropathic pain and 19 as non neuropathic. One patient and 3 control persons had to be excluded from the analysis . We assessed pain ratings by VAS (0 to 10) and pain perception by the Pain Perception Scale. As can be seen in Methods section two different frequency indices, i.e. Peak Frequency and Center of Gravity (CoG). Furthermore we assessed the specific power at the peak frequency (Peak Power) as well as within the defined ROI . Analyses of EEG spectral data were based on surface EEG values  showed differences in the expected direction but none of these differences reached significance, p-values ranged from p = .23 to .69). The according effect sized for these differences ranged from d = 0.15 to 0.47.In order to find out whether our failure to replicate the findings by Sarnthein was due to the extension of our sample to patients with moderate chronic pain we selected a subsample with severe pain from all patients. Fourteen patients reporting a pain intensity ≥7 were included in this sub-sample, 8 out of them with neuropathic and 6 with non neuropathic pain. In this subsample six of the eight indices  assessed patients' records for the following criteria: (a) ICD diagnosis either M51.2  or M54.4 (Lumbago with sciatica), and (b) irradiation of the pain and/or somatosensory deficits in the lower extremity. The goal was here to ascertain more tightly the presence of neuropathic pain mechanisms, i.e. of a root damage as the source of thalamic deafferentation. Eight patients fulfilled these criteria and were compared to their respective controls in an exploratory post-hoc analysis. None of the eight EEG indicators yielded a significant difference , but contrary to the whole sample, patients in this subsample had higher power values than their respective controls. The effect sizes for the four power indices were in the range from d = 0.20 to d = 0.44. The findings for the frequency parameters were inconsistent with two times patients having lower frequencies and two times controls. These 8 patients tended, however, to cluster in the top left part of In order to see whether there is a relationship between subjective questionnaire data and EEG parameters we calculated the respective correlation coefficients see . We repoAll significant correlations found between EEG parameters and psychological variables were only with frequency indices. All significant correlations were in the same direction associating larger psychopathology with lower frequency values or better psychological functioning with higher frequency respectively. On the other hand all significant correlations between pain ratings and EEG were only with power indices. Here higher pain ratings correlated consistently positive with EEG power values. Highest correlations were found for averaged pain ratings of the last four weeks, three months and 12 months but not for pain at the moment of EEG recording.In our comparison of subjective and objective data of chronic back pain patients with sex and age matched controls we see most clearly strong differences in psychopathology and psychological functioning between the two groups. Patients scored significantly worse regarding psychological symptoms in general  as well as on seven of the nine specific subscales with the other two approaching significance. Effect sizes ranged from 0.41 to 0.98 and are all medium or large in size. In the HADS questionnaire, a screening tool for depression and anxiety, the effect sizes were even higher with 1.17 (anxiety) and 1.42 (depression). This finding was supported by the more generic measures of HrQoL and life satisfaction. Here the differences were still larger with the topmost value being close to two standard deviations . It is evident form our findings that the continuous back pain present in these patients is accompanied by a severe reduction in quality of life, life satisfaction as well as increased psychopathology compared to a healthy control group. This is in line with findings of other investigators, e.g. for psychological distress measured by the SCL 90-R  in relation to chronic back pain Regarding their pain intensity patients reported medium to strong values. The inclusion criteria requested an average pain rating during the last months of at least 5 on a VAS from 0 to 10. On the day of the measurement patients showed a rather moderate rating with a mean of 4.5. Average pain ratings during the last four weeks, last three months and last twelve months were all between 5 and 6. We split our sample into the two subgroups of 18 pain patients with neuropathic origin and 19 patients with non-neuropathic origin. These subgroups showed no differences regarding their pain intensity but differences regarding their pain perception. Neuropathic patients reported more intense pain perceptions in the sensory and in the affective domain. This makes sense on the background that neuropathic pain can also be diagnosed on the basis of pain sensations which are markedly different on several sensory dimensions Regarding the EEG results we were not able to replicate the findings by How can these only slight effects be explained? There are several possibilities we can think of.peak frequency and peak height 87% of all participants could be correctly classified as patients or controls. The fact that the power spectra of patients and controls showed clear differences can also be seen from the graphical display in Sarnthein et al.  mechanisms elicited by increased nociceptor activation in peripheral tissues. This is indeed the opposite of a neuropathic dynamic induced by reduced thalamic activation (or deafferentation) and causing the EEG pattern described as TCD. This study provides an important negative result: pain syndromes due to nociceptive mechanisms do not give rise to TCD, or possibly only to thalamocortical overactivities too discrete to show up with the applied techniques.SD = 1.18, median = 6.5, no time interval reported) compared to 5.7  in our study. This difference may be even a bit masked due to the pain medications many patients took in both studies. In the Sarnthein study 10 out of 15 patients (67%) took either benzodiazepines, antiepileptics, antidepressants, opiates or a combination of them; in our study the rate for the same medications was only 43%. To test for this hypothesis we drew a subsample of 14 patients with a pain rating of ≥7 (average over the last four weeks). We still did not find any significant differences compared to healthy controls but now the direction of the effect changed for 6 out of 8 EEG variables into the hypothesized direction with small to medium effect sizes. This is at least a hint pointing into the direction of a TCD pattern.Another difference in comparison to the forerunner study was that patients in the Sarnthein et al. study had much stronger pain, which lead them to surgical treatment. Mean pain intensity was rated 6.9  which was not true for the full sample. In addition, these patients tended to cluster in the top left part of According to the last three interpretations, it can be assumed that a majority of the patients in our study had either not severe enough and/or non-neuropathic pain components. Because of this, they could not elicit as a group a statistically significant TCD pattern.We found medium size but highly significant correlations between the individual pain rating and the EEG parameters as well as between the subjective variables and the EEG patterns. Regarding pain intensity we only found significant correlations with power indices but not with frequency indices. In contrast questionnaire data correlated only significantly with frequency indices but not with power related variables.r = .39–.50 demonstrate that 15% to 25% of the variance in EEG power is due to pain experience in the last year. This finding indicates that severe chronic pain in a group of patients having predominantly nociceptive and/or psychogenic components results in larger EEG power. To explain this finding, we have evidence The correlations with pain intensity were strongest for average pain intensity during the last 1 to 12 months but were weaker and mostly not significant with pain intensity during the day of measurement. This finding clearly indicates that there is a relationship with continued pain experience and EEG power. Since the correlation was smallest for the pain present during the measurement it can be assumed that the increase in power is not due to actual pain experience but due to a chronification process due to persistent pain as this is hypothesized in TCD. The correlation coefficients of α = .05, four EEG indices, 17 subscales) while we find seven. Here it is also interesting that we do find correlations mainly for life satisfaction (QLZ) but not for strength of psychopathological symptoms as e.g. reflected by GSI. Additionally there is a significant correlation with affective pain perception. In order to assess if these results could also be explained by the fact that chronic pain is correlated with poorer life satisfaction and larger psychopathology as reflected in Interestingly and in the same direction, the shift of the peak frequency was correlated with some of the self-reported data. Here all significant correlations also pointed into the expected direction showing a shift towards smaller frequency with an increase in psychopathology or a reduction in life satisfaction. These findings are quite likely not due to chance. For the whole set of EEG frequency variables correlated with subjective indices we can expect by chance 3.4 significant correlations Click here for additional data file.Protocol S1Trial Protocol.(PDF)Click here for additional data file.Table S1Clinical description of all patients.(DOC)Click here for additional data file.


Objective. To evaluate the effect of acupuncture on endemic skeletal fluorosis (ESF) through the randomized controlled trial. Methods. Ninety-nine cases were divided into the treatment group (68 cases) and the control group (31 cases) randomly. Normal acupuncture combined with electroacupuncture was used in treatment group, while Caltrate with vitamin D tablets were applied in control group. After 2 courses, the VAS, urinary fluoride, serum calcium, and serum phosphate were evaluated before and after treatment. Results. Both of these two methods could relieve pain effectively and the effect of acupuncture was better (P < 0.05). In treatment group, the content of urinary fluoride after treatment was higher than before (P < 0.05), while the content of serum calcium and phosphate was lower (P < 0.05). Conclusion. The effect of acupuncture on relieving pain and promoting discharge of urinary fluoride is better than that of western medicine. Acupuncture can reduce the content of serum calcium and phosphate. Endemic fluorosis, known as endemic skeletal fluorosis (ESF), is a kind of chronic poisoning disease caused by excessive intake of fluorine for a long time during people's lives. It usually includes dental and skeletal fluorosis. The disease, endemic skeletal fluorosis in drink-water type, is caused by high content of fluorine in drinking water in prevalent areas. At present, the pandemic disease has affected 35 countries and regions.The pathogenesis of skeletal fluorosis is unclear, so the method of descending fluorine though water improvement is the only effective one , 2, but This study applies acupuncture therapy to treat skeletal fluorosis, which promotes qi circulation, regulates meridians, dredges collaterals to relieve pain, and improves the joint motion. The mechanism of acupuncture analgesia has been studied profoundly and gets a positive effect. The dysfunction of joints actually belongs to a fibrous ankylosis, a reversible change, which results from low tensity of muscle, tendon, and ligament, around the affected joint after pain relief . The calThe study is designed as a randomized controlled trial and obeys the scientific research principle of random, blindness, control, and so forth, also follows the TCM treating principle of promoting blood circulation to remove blood stasis, dispelling wind to eliminate dampness, and dredging collaterals to resolve pain, and aims to evaluate the acupuncture treatment on skeletal fluorosis for 99 patients by means of clinical outcomes as pain alleviation, urinary fluoride, serum phosphate, and serum calcium.From May 2009 to June 2010, the study enrolled 99 patients suffering from skeletal fluorosis diagnosed by WS 192–2008 health industry standard of China. All of them lived in Caosi village, Qing country, Cangzhou, Hebei province (the fluorine content in water from 2.67 to 7 mg/L).age from 30 to ~75 years old (including 30 and 75 years old);the syndrome which is blood stasis and phlegm and dampness blockage (the detailed syndrome differentiation can be referred in the addendum);life history with long-time consuming water of high-content fluorine;in accordance with WS 192-2008 health industry standard of China;patients who signed the informed consent volunteer.Inclusive criteria are as follows:the etiology that was due to burning the coal with high fluoride or drink the brick-tea water with high fluoride content;the disease that is at the severe stage, and also patients suffers from bedridden status, paralysis, or cannot live without others;complications of severe diseases from primary cardiocerebral vascular, hepatic, nephritic, hemopoietic, and nervous systems, drug addicts, or psychopaths;patients suffering from hepatitis B, tuberculosis, and malignancy;women with pregnancy or lactation;trauma of bone or joints within 2 months, without fully recovery;continuous intake of medicine for tonifying kidney or calcium supplement 3 months before treatment;intake of purified or cleaned water with normal content of fluoride;severe adverse reaction to acupuncture, Chinese herbal medicine, and western medicine of the study .Exclusive criteria are as follows:The randomized controlled method was conducted, and the stratification method was also employed with severity of disease as the layering factor. The ratio of patients assigned to the treatment and control group was 2 : 1, and the sequence number was generated and kept in the randomized center. Finally, the treatment group consisted of 27 male patients and 42 female patients (3 patients dropped off), with age 54.76 ± 10.22 years old; the control group consisted of 12 male patients and 19 female patients (5 patients dropped off), with average age of 60.03 ± 9.44 years old.The treatment group (acupuncture group) based on the TCM treating principle of promoting blood circulation to remove blood stasis, dispelling wind and eliminating dampness, as well as dredging collaterals to resolve pain, employed the acupuncture treatment with electroacupuncture. The basic points group was combined with local points group.The Basic Points. The basic points are Dazhui (Du 17), Geshu (BL 17), Quchi (LI 11), Hegu (LI 4), Xuehai (SP 12), Yinlingquan (SP 10), Sanyinjiao (SP 6), and Fenglong (ST 40).Local Points. Local point is added in the case of pain in the local part (shoulder: Jianyu (LI 15); elbow: Chize (LU 5), wrist: Yangchi (SJ 4); neck: Tianzhu (BL 10); waist: Yaoyangguan (DU 3); hip: Huantiao (GB 30) or Juliao (GB 29); knee: Dubi (ST 35); ankle: Jiexi (ST 41)). And a local Ashi point was also combined.Points Applied with Electroacupuncture. The basic points are Quchi (LI 11) and Hegu (LI 4) in the same side, Quchi (LI 11) and Hegu (LI 4) in the same side, and local points in both sides. The dilatational wave was applied.The Frequency of Treatment. Once every other day, 30 min for each time, and points without electroacupuncture were applied with lifting and thrusting and rotating manipulation by hand for 1 min every 15 min, with reducing method. The treatment was applied 3 times a week, 1 course lasted for 1 month, and 2 courses in total.The control group  based on rectifying the disorder of calcium-phosphorus metabolism and enhancing the fluoride dispelling applied Caltrate with Vitamin D tablets  to patients. The oral intake method was 600 mg one time, twice a day, one in morning, and the other in the evening. One course lasted for 1 month and 2 courses in total. The study was approved by the Ethics Committee of the Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, and written informed consent was obtained from all the patients.Visual Analogue Scale (VAS) measured the pain intensity with a 10 cm scale ruler. One end was marked with no pain, and the other end with worst pain. A moving ruler slid from 0 to ~10 in the front, and 0~10 scale numbers just corresponded in the back. Patients were asked to slide the ruler to the position that symbolized the pain intensity for themselves, and the observer got the corresponding scale number in the behind to be the pain score. In front of the ruler, there was no mark, the left end was no pain, and the right end was the worst pain .Urinary fluoride was measured by electrode method using the Urinary Fluoride Tester (HACH-F523) in the laboratory department of Caosi Center Hospital of Hebei Province. The analysis and calculation was based on the standard curve method . Urinary fluoride was measured before and after treatment in both groups.Serum Calcium. Methyl thyme phenol blue colorimetric method (MTB): the adult: 2.03~2.54 mmol/L; children: 2.25~2.67 mmol/L.Serum Phosphorus. Molybdenum acid salt method: the adult: 0.97~1.45 mmol/L, children: 1.45~2.1 mmol/L. Both of them were measured in the laboratory department of Caosi Center Hospital of Hebei Province.t test would be employed then; if the measurement data was not in accordance with normal distribution, parametric test would be employed after data altered to normal change. If the data was not in accordance with normal distribution, rank sum test was adopted. The rank sum test was also adopted for the ranked data. P < 0.05  meant comparison between groups had statistical significance.SPSS 17.0 was adopted to analyze data. According to the clinical data and certain statistical principle, the baseline, therapeutic effect, and safety were analyzed and expressed by mean ± standard deviation for measurement data. Measurement data was dealt by normality test, and if it was in accordance with normal distribution, P > 0.05)  (P < 0.01) (The VAS after treatment in two groups both decreased than those before treatment (both  < 0.01) . The eff < 0.01) .P < 0.05) (The urinary fluoride after treatment was higher than that before in treatment group . The uri < 0.05) . P < 0.05).The serum calcium after treatment was lower than that before in both groups . The serThough there are lots of western therapy and medicine for treating skeletal fluorosis, the effect of chemical elements preparation , vitamin, and amino acid , antioxiSkeletal fluorosis is a disease manifested as injuries in skeletons and soft tissue caused by excessive intake of fluoride for a long time and high content of fluorine in environment . Main syAt present, the mechanism study on acupuncture's analgesia effect on skeletal fluorosis has been very deep, and main research directions are as follows. The first is the effect of acupuncture on peripheral nerves. Experiments indicate that acupuncture or electroacupuncture on nerves conducting pain can block the conduction of pain fibers in these nerves. The second is the effect of acupuncture on nervous centralis. Acupuncture can stop new and old spinothalamic tract to conduct pain into central nervous system and then transmit relieved pain and acupuncture stimulation into different levels of central nervous system though new and old spinothalamic tract. Pain changes through the integration of neurohumor and pain modulatory system, and then the sensation and reaction caused by pain is stopped. This is the process of analgesia effect . The lasAcupuncture's effect on improving range of motion of joints is related to its analgesia effect. Studies on joint injury of skeletal fluorosis indicate that the joint dysfunction of skeletal fluorosis is caused by fibrous ankylosis actually, and this change is reversible. When pain relieves or disappears obviously, the joint dysfunction relieves or disappears too. This is the result that the tension of muscle, tendon, ligament, and so forth around joints gets lower after pain relieving .Besides relieving pain of joints, the treatment group can also increase urinary fluoride, while the effect in control group is not significant statistically. This indicates that acupunctures' effect on skeletal fluorosis may be related to fluorine's excretion through urine. The level of serum calcium and phosphorus in treatment group also reduced obviously, while only the level of serum calcium in control group reduced. Calcium and phosphorus, normal elements in bone, form calcium-phosphorus metabolic pathway with effects of PTH, CT, vitamin D, and so forth, and calcium-phosphorus metabolism is closed related to osteolysis and osteogenesis . Based oFollowup was not applied in this study due to the time limitation, but followups in 6 months, 1 year, and 3 years are suggested strongly because of the slow developing course and recurrent episodes of this disease.Considering of the therapeutic effects and side effect, we suggest acupuncture as the first choise for the endemic skeletal fluorosis, especially for relieving the pain caused by it.Both acupuncture and western medicine can relieve the pain of skeletal fluorosis patients, and the effect of acupuncture is better than that of western medicine.The urinary fluoride of skeletal fluorosis patients increases after acupuncture treatment, while that does not change after taking western medicine.Both acupuncture and western medicine can decrease the serum calcium of skeletal fluorosis patients, and acupuncture can decrease the serum phosphorus also.


Back pain is one of the UK's costliest and least understood health problems, whose prevalence still seems to be increasing. Educational interventions for general practitioners on back pain appear to have had little impact on practice, but these did not include quality improvement learning, involve patients in the learning, record costs or document practice activities as well as patient outcomes.We assessed the outcome of providing information about quality improvement techniques and evidence-based practice for back pain using the Clinical Value Compass. This included clinical outcomes (Roland and Morris Disability Questionnaire), functional outcomes, costs of care and patient satisfaction. We provided workshops which used an action learning approach and collected before and after data on routine practice activity from practice electronic databases. In parallel, we studied outcomes in a separate cohort of patients with acute and sub-acute non-specific back pain recruited from the same practices over the same time period. Patient data were analysed as a prospective, split-cohort study with assessments at baseline and eight weeks following the first consultation.Data for 1014 patients were recorded in the practice database study, and 101 patients in the prospective cohort study. We found that practice activities, costs and patient outcomes changed little after the intervention. However, the intervention was associated with a small, but statistically significant reduction in disability in female patients. Additionally, baseline disability, downheartedness, self-rated health and leg pain had small but statistically significant effects (p < 0.05) on follow-up disability scores in some subgroups.GP education for back pain that both includes health improvement methodologies and involves patients may yield additional benefits for some patients without large changes in patterns of practice activity. The effects in this study were small and limited and the reasons for them remain obscure. However, such is the impact of back pain and its frequency of consultation in general practice that this kind of improvement methodology deserves further consideration.ISRCTN30420389ISRCTN:  Back pain is one of the UK's costliest and least understood health problems, whose prevalence still seems to be increasing . GeneralQualitative studies into general practitioner (GP) attitudes to back pain have suggested that including education and feedback could be promising -11, HoweTwo occupational studies of physician education showed slightly more positive results. A Norwegian randomised controlled trial of the implementation of 'Active Sick Leave' (ASL - a scheme to facilitate the use of return to work with modified activities), used educational workshops and literature to help promote general practitioner adoption for patients who were off work with back pain . This trSo far there have been no UK studies of GP educational interventions to improve the management of back pain, although one randomized trial of a posted information package reported a positive shift in beliefs and behaviours in chiropractors, osteopaths and musculoskeletal physiotherapists .Researching care improvement benefits from the documentation of current care and prognostic factors, as well as the effects of interventions. One systematic review of randomised trials that examined both of these for back pain found inadequate data to describe the care given and a lack of studies that assessed the role of prognostic factors . It was One ethnographic study in the UK found that in the presence of organisational demands and constraints, iterative negotiations and informal networking may be a promising approach  and a meIn order to test the effects of such a combined inter-professional approach, this study used facilitated 'action-learning' to promote evidence-based back pain management, along with practical knowledge of health care quality improvement . Action-In the present study, 9 practice teams, each with a patient, attended a series of 8 half-day workshops over 9 months. For our outcomes evaluation we used the Clinical Value Compass whose components are: clinical outcomes, functional health status, satisfaction against need and total costs . This toWe also recorded GP interventions, referrals and their costs in a parallel study of the same practices over the same time period. The purpose of this study was twofold:1. to assess changes in patient outcomes following a practice improvement intervention that included patients in the improvement learning, taking account of prognostic factors and 2. to identify any changes in practice care patterns for back pain after such an intervention.Nine practices from two Primary Care Trust localities in the South of England recruited two cohorts of patients who attended for back pain. The first cohort was recruited in the 12 months before practice teams had attended 8 half-day workshops over nine months starting in March 2008. The second cohort was recruited over the 15 months following the workshops. Patients were recruited by the general practitioners, who explained the study, obtained consent to pass their contact details to a co-ordinator and gave consenting patients an information sheet.Inclusion criteria were: age 18-65, low back pain, with or without leg pain, back pain of less then 12 weeks duration and no previous spinal surgery. Patients were not eligible if they had serious spinal pathology, traumatic onset of their pain, were pregnant, had severe depression, had constant pain lasting more than 6 months or had compensation or litigation proceedings pending.Each team had up to 6 members, each comprising up to three doctors, plus various combinations of people involved with the practice, including physiotherapists, receptionists, practice nurses, practice managers and patients. All practice teams included at least one patient. A bursary was provided for each practice team to offset costs such as provision of locum cover.Concurrent with the collection of questionnaires from patients, a second study was conducted of practice activity for back pain patients as recorded in practice computer databases. For this, the computer databases  of all practices were extended to include a range of new variables to be recorded if the Read Code N142 'low back pain' was entered. Doctors then logged their consultation activities for all back pain patients at each visit, including sickness certification, referrals and their own interventions. Prescribing of oral medications was not included. All 9 practices, populated by 40 doctors, participated in this data collection process. Costs were attributed to each chargeable activity from national and local NHS tariffs for 2008-9. This constituted the fourth Clinical Value Compass component. Medication costs were not included.During the workshops, both the principles of quality improvement and the latest evidence for back pain management, based on the European Acute Back Pain Guidelines , were inhttp://www.limbic.org.uk) which posted information and commentaries by the project team and other participants. It was central to communication about specific project activity; improvement projects and the sharing of ideas. A Quality Improvement Facilitator also visited practices to help with problems and answer queries. This Facilitator played a key role in supporting practices with the development of their improvement projects, the sharing of ideas with other practices, and the use of the Wiki to provide access to improvement tools.Each practice team also identified its own individual priorities for improving care and generated at least one improvement project of its own, using a plan, do, study, act (PDSA) methodology. Practices were also supported by a project Wiki. This was a private section of the LIMBIC website , and was registered on the Current Controlled Trials database (ISRCTN30420389).In the back pain patient study, patient outcomes were assessed with the cohort split into before and after workshop groups Figure . The patDemographic and prognostic variables for each Cohort were analysed descriptively. Significance of differences of change scores for interval or categorical data between cohorts was determined using 2-sided Mann-Whitney and Fisher Exact tests. Significance for all tests was set at the 5% level.We combined data from both cohorts and used multiple linear regression analysis to model the RMDQ score at follow-up, always including as predictors age, sex, the baseline RMDQ score and a dummy variable that identified whether the patient was seen before or after the series of workshops. The regression coefficient for the last term measured the effectiveness of the workshop. Other variables that might influence the follow-up RMDQ score were introduced in a forwards stepwise manner - the most significant variable from the remaining set being introduced at each stage until the introduction of a new variable was not statistically significant at the 5% level.Differences in the proportions of patients improved were also calculated. These were determined using ROC curve analyses to determine the RMDQ cut-off scores for an improvement of at least 2 out of 10 on the global improvement question from the follow-up questionnaire and, alternatively, as the same reduction of severity on the visual analogue pain scales between baseline and follow-up .Ten questions from the Patient Satisfaction Scale were grouped under the subsets of; Information, Caring and Effectiveness . An addiData were transferred from practice databases into Microsoft Excel (2003 Version) and SPSS (V17.0) files for analysis. Items were tallied by practice for the pre and post intervention cohorts and analysed by cohort. The rates of the various practice activities per patient were calculated by dividing the number of times the activity was used by the number of patients in the cohort. The average cost of each activity per patient was calculated by multiplying its relevant NHS tariff for 2008-9 by the rate for that activity. The average total cost of an episode was estimated by summing these costs. Differences in the proportions of patients who received the most frequent care activities were compared using the Fisher Exact test.Seventy-five patients were recruited for the pre-intervention phase Cohort 1) and 65 to the post-intervention phase (Cohort 2)  and significantly fewer who said they enjoyed their jobs .  There were no other significant differences between Cohorts.Multiple regression analysis of the pooled data revealed that baseline (RMDQ) score, downheartedness, self-rated health and leg pain had small but statistically significant effects on follow-up RMDQ scores in various groups Table . When thA higher proportion of patients who attended the practices after the workshops improved (0.64 vs 0.51) in terms of the global scale, but not the pain scale (0.69 vs 0.70). Neither was statistically significant, although such small changes observed at a population level could be very important to individual patients.Change scores for functional outcomes are shown in Table There was no statistically significant difference in post-treatment satisfaction scores between patients who consulted before and after the workshops Table .Data for 1024 patients were entered in practice databases; 648 before 366 after the workshops. The mean number of GP consultations for back pain before (1.65 [SD 1.342]) and after (1.81 [SD 1.350]) the learning workshops were very similar , p = 0.437 [2-way unpaired t-test]). The activity rates and attendant costs per patient can be seen in Table The main activities recorded as taking place within practices before the workshops were the provision of sickness certification (26.3%) and self-help literature (11.6%). Referrals were spread over 19 different community practitioner groups and 19 consultant groups in secondary care. Changes in rates of referral for X-ray, MRI and hospital admissions, although important, represented only small proportions of patients.Fifty-three different activities were used, ranging from advice given by doctors, to referrals for investigations or treatments, sickness certifications and hospital admissions recorded. Overall, there was a significant reduction in the number of individual activities used (30/53) after compared to before (48/53) the workshops (p = 0.0001 Fisher exact test). However, the rates for the most prominent activities (rates >0.050) of giving literature, referral to a physiotherapist, chiropractor or osteopath, sickness certification and consultant referral did not change significantly after the workshops (p > 0.05 Fisher Exact test). There were significantly fewer referrals to an osteopath and less use of epidurals after the workshops (p < 0.05 Fisher exact test), but these represented less than 5% of patients and the latter was largely attributable to just one practice.The highest costs (i.e. over £5 per patient) were for referrals to physiotherapy, orthopaedics and rheumatology, where referral rates (and therefore costs) did not change significantly. The total cost of all activities for a patient episode of care before the learning workshops was £104.78 and £103.70 afterwards.A significant strength of this project was the extent to which it engaged both practice staff and patients in the intervention, where the feelings and preferences of both had a significant role in the intervention. Conversely, greater application of the evidence in management;  might have been sacrificed to this.All that was actually done to individual patients could not be recorded by busy GPs and entries in practice databases were not independently validated. Therefore, some evidence-based interventions may have been used, but not recorded. This is a limitation of the study. It is also important to bear in mind that the patient study sampling operated inclusion and exclusion criteria, whereas the practice database study recorded visits by patients with all manner of complaints, of which back pain may have been only one.The Clinical Value Compass was a helpful tool to frame the outcomes selected, representing a balanced set of outcomes. Although overall functional status and disability were no different after the intervention, as was also found by Cherkin et al, adding inter-professional improvement learning and networking that included patients to learning about evidence-care for back pain had some positive effect on disability scores in female patients when prognostic factors were controlled for . The mosGeneral practitioners recorded the use of a large number of services to investigate and treat patients with low back pain. Some of these would have been aimed at co-morbidities that accompanied the complaint. It is reasonable to expect that these could not always be disaggregated in the back pain consultation. Additionally, practices were asked to record data for all patients with back pain, including all three triage categories of non-specific back pain, nerve root pain and back pain arising from serious pathology. Thus, and as mentioned above, many patients would not have attended for back pain alone, as reflected in the variety of specialist health personnel they were directed to.Like previous studies by Engers et al  and CherBarnett et al have suggested that guideline recommendations are less likely to be adopted if patient management techniques or referral routes need to be developed . A similPrevious studies have not found GP educational interventions for back pain to be useful. However, these did not include quality improvement learning and the inclusion of patients with the practice teams. Furthermore, practice activity and referral patterns have not been monitored concurrently and important prognostic factors have not always been adequately controlled for when measuring patient outcomes. Importantly, outcome measures need to embrace a multidimensional perspective which reflects the impact of back pain on the sufferer. For this, the Clinical Value Compass offers a useful tool.In the present study, when downheartedness and leg pain were controlled for, there was a small, but clinically important and statistically significant reduction in post-intervention disability in female patients. For males, all effects were either small or statistically insignificant except that a higher baseline disability score predicted slightly higher disability at follow-up. This apparent gender effect is unexplained and merits further investigation.The small, positive effects found in this study occurred without any tangible change in practice activity or patient referral patterns. However, so large is the economic impact of back pain that with general practice being the most frequent provider of care, GP education that combines evidence-based practice with health improvement methodologies and involves the patients themselves, may yet yield worthwhile additional benefits without additional costs.The authors declare that they have no competing interests.All authors participated in the preparation of the manuscript and read and approved the final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/28/prepubAnnexe. Content of LIMBIC WorkshopsClick here for file


The objective of this double-blinded, randomized controlled trial was to evaluate whether CO2 insufflation does decrease pain and bloating during and after colonoscopy compared to room air. Methods. 219 consecutive patients undergoing colonoscopy were randomized to either CO2 or air insufflation. Propofol was used in all patients for sedation. Transcutaneous CO2 was continuously measured with a capnograph as a safety parameter. Pain, bloating, and overall satisfaction were assessed at regular intervals before and after the procedure. Results(data are mean ±SD). 110 patients were randomized to CO2 and 109 to room air. The baseline characteristics were similar in both groups. The mean propofol dose was not different between the treatments, as were the time to reach the ileum and the withdrawal time. pCO2 at the end of the procedure was 35.2 ± 4.3 mmHg (CO2 group) versus 35.6 ± 6.0 mmHg in the room air group (P > .05). No relevant complication occurred in either group. There was significantly less bloating for the CO2 group during the postprocedural recovery period (P < .001) and over the 24-hour period (P < .001). Also, patients with CO2 insufflation experienced significantly less pain (P = .014). Finally, a higher overall satisfaction (P = .04) was found in the CO2 group. Conclusions. This trial provides compelling evidence that CO2 insufflation significantly reduces bloating and pain after routine colonoscopy in propofol-sedated patients. The procedure is safe with no significant differences in CO2 between the two groups.Many patients experience pain and discomfort after colonoscopy. Carbon dioxide (CO Conversely, room air insufflation has remained the standard of care in most endoscopy centres [2) may reduce periprocedural pain. CO2 was first recommended 1953 to avoid gas combustion in the colon during electrocoagulation [2 in the colon and minimal interference with colonic circulation were described, therefore minimizing the risk of bowel ischemia [2 is absorbed about 150 times faster compared to nitrogen and is rapidly eliminated through the lungs [2, the gas has disappeared, whereas patients with standard room air insufflation still have a significant distension of both small bowel and colon [2 use: Sumanac et al. [2 or room air insufflation and showed that 45% of the patients examined with room air had pain one hour after examination compared with only 9% in the CO2 insufflation group. Six hours after colonoscopy, the fraction of patients with pain was 31% in the room air group versus 7% in patients with CO2 insufflation. Conventional X-rays revealed colonic distension of more than 6 cm in diameter in 71% of patients assigned to room air compared with only 4% in the CO2 group [2, with the latter group experiencing less postprocedural pain. With recent new developments that facilitate the use of CO2, more data have become available supporting the observation that insufflation with CO2 causes less pain [Many patients experience pain and discomfort after colonoscopy. An explanation for this observation is the retention of gas in the colon, as several liters of air are insufflated during colonoscopy. For decades, CO centres . Prelimihe lungs . Interesc et al.  examinedess pain –10. The ess pain .A large, population-based survey based on 7,370 colonoscopies performed in Norwegian endoscopy centers revealed that up to 24% of patients experience severe pain during colonoscopy . Accordi2 use is that no gas aspiration is necessary during withdrawal due to the fast gas absorption. Better colonic insufflation may be associated with a better diagnostic yield and especially a higher polyp detection rate. Comfort during and after colonoscopy represents a major issue for patient tolerance and acceptance. It is imperative that the nowadays recommended longer withdrawal times, and consecutively longer insufflations, do not compromise patient comfort. It would be wrong to shorten the withdrawal time during colonoscopy to make concessions with respect to patient comfort. In addition to better periprocedural pain control, another potential benefit of CO2 insufflation versus standard room air.The objective of the present randomized controlled double-blinded trial was to assess patient satisfaction, pain, and bloating between patients undergoing colonoscopy with CO2 versus room air insufflation. This randomized trial was double blinded, as neither the patients nor the gastroenterologist were aware of the intervention. The randomisation was done with a dice for each patient. If the number was even, the patient underwent colonoscopy with CO2, if the number was uneven, colonoscopy with room air. The study nurse, without any involvement of the investigator, did the selection. The ethical committee approved the trial, and written patient consent was obtained for each patient for colonoscopy and for the study receiving patient study information including an informed consent section on a visit prior to the scheduled colonoscopy. In this randomized controlled trial, 219 consecutive patients undergoing colonoscopy in a private Swiss gastroenterology practice were enrolled between April 2008 to June 2008 (only one patient did not participate in this time period). Patients were randomly assigned to colonoscopy with either CO2 insufflation, the medical licensed and approved CO2-Efficent Insufflator device  was used. This insufflator is connected to a 10 L CO2 bottle. The CO2 is then supplied over a tubing set connected with a branch connection to the water bottle tube directly connected to the endoscope. The flow rate  can be controlled on demand over the standard air valve. Air supply with the Pentax processor or CO2 insufflation with the CO2 Efficent Insufflator cannot be acoustically discriminated. The valves for the endoscope using CO2 are identical with the standard valves. Moreover, the switch for the pump of the CO2 processor was hidden as was the switch for the insufflator. The front line of the processor and the CO2 insufflator were covered to mask the operational status. The setup was done by the assisting nurse prior to the start of the colonoscopy without knowledge of the examiner. Therefore, this was a truly double-blinded trial. All patients were sedated with propofol using standard procedures previously described [All patients that seemed medically fit for an ambulatory colonoscopy were enrolled in this study. No particular exclusion criteria were used to maximize the generalizability  of this study. All colonoscopies were done by the first author and carried out with standard Pentax endoscopes (EC-3885K and EC-380FKp) with a standard processor EPK 1000. For COescribed . A levelThe primary endpoint of the present investigation was overall pain scores. Secondary endpoints were bloating as well as overall satisfaction assessed on a 10-point visual analogue scale (VAS) before and after the examination at 1, 3, 6, and 24 hours. The grading of the VAS were as follows: for pain: 0 = no pain at all, 10 = worst possible pain; for bloating: 0 = no bloating at all, 10 = terrible bloating; for satisfaction: 0 = not at all satisfied, 10 = perfectly satisfied.As quality indicators and characteristics of the performed colonoscopy time to reach the ileum, withdrawal time, length of intervention, procedural length, and the number and the size  of removed polyps and their histology were assessed. Finally, periprocedural complications were registered as well as time to discharge, propofol dosage, oxygen supply, and other medication given. We also continuously measured transcutaneous carbon dioxide with a Sentec Capnograph device  for respiratory monitoring.The patients were motivated at discharge to fill out the postprocedure survey regarding pain, bloating, and satisfaction. We purposefully and a priori decided not to call any patients who did not mail in the survey, as this would have potentially led to imprecise results from patients retrospectively filling out the survey. P < .05. To compare dichotomous (yes/no) and categorical outcomes, the Chi Square test was used. For comparisons of continuous outcomes, unpaired t-tests were used.Statistical analyses were performed using SPSS Version 11.0, and the level of statistical significance was set at 2 group versus 6 in the room air group). With a power of 80% (beta error of 20%), type I error of 5%, and standard deviation of 5, the resulting sample size was 200 patients.The sample size computations were based on a difference for overall pain scores (the primary endpoint) with an effect size of 2  and IBS patients in the CO2 group . Withdrawal times were 13.6 ± 6.0 minutes in the CO2 group and 13.3 ± 6.1 minutes in the room air group (P > .05). Outcomes are listed in 2 group, relevant polyps were removed  or by high grade dysplasia). In the air group, the corresponding percentage was 7.3%. Additional adenomas  were found in 34.5% versus 33.9%, respectively (P > .05).The duration to reach the ileum was 7.7 ± 4.7 minutes in the COFor the data collection in the office, data was complete for all patients. Seventy-five percent of group 1 and 82% of group 2 returned the completed questionnaire. 2 group compared to the room air group , three hours (P < .001), and six hours after the procedure (P = .04). Also, patients randomized to CO2 experienced significantly less pain at one hour (P < .001) and three hours (P < .001) after the procedure. Overall pain summary scores for 24 hours were significantly lower in the CO2 group compared to the patients assigned to room air . Similarly, overall pain scores were significantly lower in patients randomized to CO2 versus room air . The percentage of patients, who did not experience any pain, was significantly higher in the group examined with CO2 up to 3 hours . At all time points, the VAS scores for bloating and pain were lower in the CO Figures  and 2: p 3 hours . Bloatin2 group, the overall satisfaction score was 9.6 ± 0.7 versus 9.3 ± 1.0 on a 10-point visual analogue scale.The overall acceptance of the colonoscopy was excellent in both groups. In the CO2 was continuously measured. There was no significant difference with respect to transcutaneous CO2 levels between the CO2 and room air groups . Second, it is one of the few  studies  studies . Thereaf studies  showed a2 was not associated with a prolonged preparation time to set up or perform the procedure, and there were no side effects and no complications. Finally, the use of CO2 insufflation, as commonly used for establishing pneumoperitoneum during laparoscopic surgery, has already been proposed and introduced in different fields of endoscopy [2 use was demonstrated in patients undergoing ERCP as well as ESD with respect to periprocedural pain [2 use for balloon enteroscopy was not only less painful for patients, but also associated with a significantly deeper intubation length of the small intestine. Another advantage is that CO2 is less combustible in presence of stool or sub-optimal bowel preparation and, therefore, potentially safer when diathermy is being used. Moreover, it has advantages in longer procedures to avoid overdistention of the colon. However, the number of studies investigating the use of CO2 is limited and safety concerns with respect to respiratory side effects have been raised. This issue was assessed in three studies. The first including nonsedated patients undergoing colonoscopy showed a slight, however, clinically irrelevant  increase in end-tidal pCO2 with CO2 insufflation compared to room air use [2 was reported in the study of Yamano et al. [2. The authors concluded that CO2 insufflation was safe [2. Here, we show the safety of CO2 insufflation in a large sample of sedated patients. Abdominal pain after colonoscopy is common and distressing for some patients and can cause even sick leave . It is dndoscopy –19. Thisral pain , 18. In  air use . No diffo et al.  in nonsewas safe . However2 appears to be important to reach this goal with less bloating, less pain, and higher patient satisfaction. The lack of awareness [2 insufflation.It is well known and intuitive that the success of any screening strategy is critically dependent on population acceptance of the screening methods; efforts to minimize discomfort associated with colonoscopy may positively influence compliance. With the prospect of widespread colonoscopy screening for colorectal cancer in asymptomatic populations, it is imperative to optimize patient comfort and convenience as well as the quality of the examination itself. Based on the findings of the present double-blinded, randomized controlled trial, COwareness  of this 2 and room air group with respect to gender and IBS. In fact, the CO2 group contained more female and IBS patients. However, it is well known that IBS and female patients usually have more pain and bloating after colonoscopy [2 colonoscopy may be even more important. Second, the randomization was done with a dice for each patient, and thus is theoretically prone to bias. However, a study nurse did the randomization without any involvement of the investigators, and therefore, the risk of bias is minimal. We would like to acknowledge the limitations of this study. First, despite the randomized controlled study design, there were some imbalances between the COonoscopy , 23. The2 in sedated patients with continuous CO2 monitoring. Third, there were no exclusion criteria in this study, and therefore, the generalizability  is high. Most importantly, the present trial addresses a very relevant and novel research questions and hopefully will help changing practice patterns.There are several strengths of this study: first, this investigation was done in a double-blinded randomized, controlled fashion. Second, this is a large randomized patient sample; more important, there are only few reports that have investigated the benefit of CO2 insufflation is associated with significantly less bloating and pain during and after routine colonoscopy. Colonoscopy with CO2 insufflation is safe as no significant differences in CO2 measurements were observed. Based on these data, the routine use of CO2 insufflation for colonoscopy is encouraged.This study provides compelling evidence that CO


The diagnosis “lumbar facet syndrome” is common and often indicates severe lumbar spine surgery procedures. It is doubtful whether a painful facet joint (FJ) can be identified by a single FJ block. The aim of this study was to clarify the validity of a single and placebo controlled bilateral FJ blocks using local anesthetics. A prospective single blinded triple cross-over study was performed. 60 patients ) with chronic low back pain  admitted to a local orthopaedic department for surgical or conservative therapy of chronic LBP, were included in the study. Effect on pain reduction  was measured. The 60 subjects were divided into six groups with three defined sequences of fluoroscopically guided bilateral monosegmental lumbar FJ test injections in “oblique needle” technique: verum-, placebo-(sodium chloride-) and sham-injection. Carry-over and periodic effects were evaluated and a descriptive and statistical analysis regarding the effectiveness, difference and equality of the FJ injections and the different responses was performed. The results show a high rate of non-response, which documents the lack of reliable and valid predictors for a positive response towards FJ blocks. There was a high rate of placebo reactions noted, including subjects who previously or later reacted positively to verum injections. Equivalence was shown among verum vs. placebo and partly vs. sham also. With regard to test validity criteria, a single intraarticular FJ block with local anesthetics is not useful to detect the pain-responsible FJ and therefore is no valid and reliable diagostic tool to specify indication of lumbar spine surgery. Comparative FJ blocks with local anesthetics and placebo-controls have to be interpretated carefully also, because they solely give no proper diagnosis on FJ being main pain generator. In 1911, Goldthwait As the intervertebral discs are compressed in the upright position, the facet joints are subject to compression under (hyper-) extension of the spine. The amount of force was calculated at 16% (3–25%) of the entire compression force of the lumbar spine Autonomous nerves in FJ have been proven to explain the role of the FJ in LBP Schleifer et al. Because of unspecific and inconsistent clinical symptoms  In literature The prevalence of a disease defines the importance of correct test results. Therefore, diagnostic tests in a population with high prevalence of a specific pathology are more important than in populations with a lesser frequency of the same pathology. Some investigators, with limited evidence and no gold standard, suggest that the prevalence of FJ involvement in LBP seems to be 15–40%, with LBP caused solely by the FJ as low as 7% The FJI as diagnostic tool for FJS is a widely accepted instrument in spine surgery for preoperative diagnostic. The results are often used in decision making for FJ denervation, segmental dynamic or rigid stabilization The property clinicians expect most from a diagnostic test is a good predictive value, which is a function of the specifity, sensitivity, and validity of the test applied, as well as safety (low rate of complications) and reliability (reproducibility). It is considered impossible to accurately determine specificity and sensitivity in spine related issues There are numerous reports on diagnostic lumbar FJB Randomized studies have been published in which either placebo or verum was injected A prospective, clinical, randomized, closed, single-blinded, triple cross-over study with six parallel groups was performed. Verum agent and placebo were applied as intraarticular FJI in all patients. According to study protocol, each patient received three bilateral injections: verum (V: 1.5 ml 1% Mepivacaine), placebo (P: 1.5 ml 0.9% isotonic sodium chloride solution) and sham injection  after a period between 8 and 12 hours (wash out period). If the patient was still reporting a benefit from the previous injection, the following injection was also performed, however, the current pain level was taken as base for the following injection. For the injections, gauge 22–23 needles with a length of 5–15 cm (3.5–5 in.) were used. In order to avoid additional irritation, local anesthesia of the skin or contrast medium application were avoided.The order of injections ( = sequence) was randomized according to a protocol created by the local Department of Biometrics and Medical Documentation leading to 6 evenly split sequence-groups .60 consecutive patients admitted to the local orthopaedic department for surgical or conservative therapy of chronic LBP were included in the study. These patients had undergone adequate conservative outpatient treatment for chronic LBP for at least 6 months without success. The mean age  was 53.2 years (22–73).Exclusion criteria were age under 18 and over 75 years, intermittent LBP triggered solely by stress, pain during the night or mainly ischialgia with positive Valsalva or Lasègue test. Patients with radicular pain referable to the same segments of FJ degeneration were not accepted. Patients with maximum local pain in the thoracolumbar region, sacroiliac pain or with a history of major surgical procedures of the lumbar spine , osteonecrosis, tumor or severe anatomical deformities, local or systemic infection, tendency towards bleeding, severe osteoporosis, metabolic bone disease, kidney failure, obesity (Broca index >30), pregnancy, allergy to any of the agents applied, or poor compliance were also excluded from the study.Patients fulfilling these criteria had their medical history taken and underwent a physical examination including evaluation of radiological imaging  according to the criteria introduced by Helbig If a degenerative FJS was present, the patients were informed about the content and course of the study and written informed consent was obtained with approval of the local ethics committee  and in accordance to the Declaration of Helsinki. The patients were admitted to the study according to the randomization plan when the current pain was adequate (VAS>4) and no analgesics were taken 24 hours prior to the first scheduled FJI.All patients had local lumbar back pain, 44 patients (73.3%) had pseudoradicular pain additionally. Another 11 (16.7%) patients had intermitted radicular pain, which could be referred to spinal segments above the indentified segments of FJ degeneration . Pain had been present for an average of 31 months, with a range from 6 months to >10 years. In only 2 cases (3.3%) the level L3/4 was injected, otherwise FJI was done in segments L4/5 (46.7%) or L5/S1 (50%).In order to optimize fluoroscopy of lumbar FJ, we used the “oblique needle technique“ : the patFor the exact diagnosis of pain syndromes relating to FJ, it is considered as a crucial factor, that the injected agent is not be allowed to diffuse into adjacent structures. Therefore, the joint capacity must not be exceeded and the tip of the needle has to be positioned intraarticularly In 60% of cases, the injection sequence was done within 2 days, and 30% within 3 days. In 6 subjects (10%), the testing period included a weekend which led to an extension of the testing period to 4 days. During the study, no patient withdrew from the testing.In this triple cross-over design, the interesting factor was the effect of the injection. The subjects were blinded toward the applied injection sequence. Target value was the pain level and the change of pain intensity after FJI. The pain level was recorded using a 10-point visual analogue scale (VAS: 0–10) before the injection (time t0) and at definite time t1 (30 min), t2 (60 min), t3 (2–3 h) and t4 (6–8 h) after the injection. If degenerative FJS were present in 2 or 3 segments, the segment which was clinically or radiologically most likely affected was chosen. If a clear identification was not possible, the statistically most likely affected segment L4/5 was tested Evaluation included description of the collective, dropouts and comparison of sequences and descriptive statistical evaluation. To gerneralize the effect of triple cross-over injection test design the data results were evaluated using a linear mixed model. For time t1–t4 a special model was calculated (variance-component-model). Target value was the difference of the score value before the treatment (t0) minus the score value after an injection, separate for t1, t2, t3 and t4. Cause variables were the sequence of injections and pain level before injection. Disturbance variable was the time between injections.The test injection was considered positive if the difference of the pain scores 2 pts (VAS) in minimum. In case of pain difference below 2 pts or an increase of pain compared to the pain level before FJI the test injection was regarded as negative. In other words; a responder reacts to an injection  with a relevant reduction of pain of at least 2 pts (Δ≥2), a pain relief of less than 2 pts after injection (Δ<2) is defined as non-response.With regard to the cross-over design, we checked for the presence of a sequence (periodic) or carry-over effect. In this model, the subject was considered incidental and, therefore, the combined structure of the data was taken into consideration. All calculated models were viewed as an explorative data analysis 0). With regard to the periodic effect the following hypothesis was constructed: the physiological effect to the verum is not influenced by the time of injection (H0).With regard to the carry-over effect, the tests for difference and equivalence were based on the following hypothesis: the physiological effect to the verum is not influenced by previous injections (H0) were constructed: the 3 injections are not equivalent, therefore at least one comparison of effects of two injections would result in a difference more or less than Δ = 2.For implementation of the testing on equivalence 0 is correct, this means that the diagnostic FJI with verum is a sufficiently specific method for differential diagnostic testing of a degenerative lumbar FJS.In order to enable comparison regarding the equivalence of interventions, the differences of the estimated median values  were calculated with the 90% confidence intervals. If all 3 confidence intervals were within the clinical relevant equivalence interval  with a significance of p = 0.05 and when reaction to sham injection is not positive (ΔS≤0). A false positive reaction of a verum responder is given, when reaction to verum is less than 2 pts better than to placebo (ΔP - ΔV≥−1) or when reaction is positive to sham injection (ΔS>0). Placebo effect or sham injection gives better pain relief than verum, when difference is positive compared to verum .The results were descriptively analyzed and evaluated using the following differentiation : A totalTests on difference regarding the change of pain level (10 pts-VAS) between the 3 injection forms  at the different times after FJI and between the 3 severity groups of FJS  a carry over effect could be demonstrated which means, that no injection type had any influence on the subsequent injection , Fig. 3 The distribution of the pain reduction caused by the injections in relation to the pain level before the injection is shown in Responder rates regarding verum, placebo und sham-FJI are depicted in The estimated model based mean values of the target value with regard to the different injection types are depicted in There is no significant difference of pain reduction between verum- and placebo-injection at any time after FJI . BetweenIn 3 of the 4 patients with prior nucleotomy a positive pain relief is seen after verum and placebo at time 1 and 2 after injection, 1 patient showed no response to all injections. In 2 patients pain relief is measured after sham injection at time 1 and 2 also. Due to the small number of 4 patients statistical analysis on difference to patients without prior operative intervention was not possible.Early studies of FJI with steroids and anesthetic agents for diagnosis and therapy were encouraging; short-term pain relief from 59% up to 94% and long-term pain relief from 27% to 65% after a single injection were reported We were able to confirm these results with a controlled triple cross-over design. At time point 2 the periodic effect and thus the test for difference became significant . This reThe lack of reliable clinical predictors with regard to FJ pain on the lumbar spine was confirmed by our relatively high rate of non-responders of 33%. The rate for positive tests (true verum responder) was only 16.5% . Moran eIn our sample, classification of clinical and radiological findings in FJS severity scores like suggested by The large volumes injected in the early investigations almost certainly resulted in capsular rupture with extravasations of local anesthetic and steroids. In many reports the volume of the injected LA exceeded the capacity of the FJ by far, thus increasing the probability that the effect of FJB was due to other, extraarticular mechanisms Lynch and Taylor We performed intraarticular test injections with local anesthetics and contrast medium  in 8 patients which were not part of the study group applying the same technique and found extravasations in half of the patients (4) even though the needle was placed correctly .LFJ syndrome is a known possible consequence after nucleotomy, due to mechanical pathological load resulting from loss of intervertebral distance According to our results a single intraarticular FJI does not confirm the diagnosis of a FJS. We found a low specificity  and a low sensitivity (high rate of positive sham reactions in patients with negative verum reaction). Other investigators suggest the reproducibility of the single (uncontrolled) injection is not high, and the specificity may be about 65%. Schwarzer et al. Jackson et al. In cases of (sub-) chronic LBP we can assume that a greater rate of patients already suffer from somatic pain disorders, which would explain a certain influence of placebo reactions on verum injections caused by psychosomatic factors. Temporary “diagnostic” nerve blocks may be nonspecific in localizing pathology which generates or maintains an ongoing chronic pain problem In literature, periarticular sicca sham injections in lumbar FJ is not discussed or compared to volume injections till now. At time 2 and 4 after FJI the sham injection partly shows relevant difference to verum and/or placebo. Relevant relief of pain level was set as Δ>1, This is very low; with a level of significance of Δ>2, the injection types  would have been equal at any time after FJI. Equality of extraarticular sham injection without volume to the intraarticular volume injection was significant in most but not all cases in our sample. But tendency of lower placebo effects of sham injection compared to placebo injection could be shown. Further inverstigations should confirm the hypothesis, that intraarticular volume application in lumbar FJ influences pain perception resp. placebo effects more than perifocal simple sham therapeutic procedure.It is essential to have a gold standard with which to compare the accuracy of a given diagnostic test. Numerous studies have described the technique and clinical results of diagnostic blocks for chronic LBP . Saal desingle local FJB via LA as diagnostic tool for FJS has to be abandoned. Therefore, the assessment of the severity of the clinical relevant degenerative FJS and of the success of the therapy lies in the optimization of the specificity of the diagnostic tool. Leclaire et al. Despite these known neurophysiologic limitations, the known problems with validity and specificity, the FJI are commonly used for the diagnosis of suspected pathology in the FJ. But due to the discussed reasons, the With regard to test validity criteria, a single intraarticular facet block with local anesthetics is not useful to prove a FJS and has to be abandoned from preoperative testing and indication finding. Although several studies have been performed in the last decades, evaluation of FJI remains difficult due to lack of reliable clinical and radiological predictors. Comparative FJ blocks with local anesthetics and placebo-controls give no proper diagnosis on FJ being main pain generator. But they they are the only standard we have till now.