This study aimed to quantify the effect of spinal manipulative treatment (SMT) from an analysis of baroreflex, systolic blood pressure and heart rate variability (HRV) on patients with acute back pain. It was hypothesized that SMT would increase the parasympathetic cardiovascular autonomic control.Twenty-two patients with acute back pain were randomly divided into two groups: one receiving sham treatment (Sham) and the other receiving SMT. Recordings were completed during the first day and the seventh day, immediately before and after treatment on both days. ECG and systolic blood pressure were continuously recorded to compute cardiovascular variability and baroreflex sensitivity components. The perceived level of pain was measured with the numeric pain scale (NPS) 48 h before, just before and just after each treatment. The NPS ranged from 0 to 100% (peak of pain before treatment). ECG and systolic blood pressure recordings were analyzed in time frequency domain using the Smoothed pseudo Wigner-Ville distribution.p < 0.01), whereas no differences were observed with the other heart rate variability components. Also, no differences were observed with the systolic blood pressure components. Although the estimated pain scale values decreased over time, no difference was observed between the SMT and Sham groups.Root mean square of the successive differences, high frequency power of the heart rate variability, and high frequency baroreflex sensitivity differences between post and pre tests were higher in the SMT group than in the Sham group (This seems to be the first study to assess the effect of SMT on both heart rate variability and baroreflex sensitivity in patients with acute back pain. SMT can be seen to provoke an increase in parasympathetic control known to relate to a person’s healthy state. Thus, cardiovascular variability analysis may be a useful tool for clinicians to quantify and objectify the beneficial effects of spinal manipulation treatment. Low bac. [. . Low bac. [. . Spinal . [. . SMT is . [. . In the . [. [. , 8. To o. [. [. [. [. [The HRV and baroreflex sensitivity can be analyzed in such a way as to provide several indices of cardiovascular autonomic control . Signal . . In a nu. [. , whereas. [. [. . Further[. [. [. , hyperte[. [. [. , and oth[. [. [. , 13.To quantify these short term modulations of BP and HR, spectral analysis has been used , 15 prov. [. [. [. [. [Linked to pathological states, it has been shown that pain has an effect on cardiovascular control through an increase in heart rate. –21, show. [. . Moreove. [. [. . In addi[. [. [. . Other s[. [. [. .. [. [. [Conversely, chiropractic care. , cervica. [. , SMT and. [. [.  have bee. [. [Although some studies on the effect of manipulative treatments on HRV have been published. , 8, the . [. . HoweverTherefore, the objective of the present study was to quantify the effect of SMT by comparing the results of SMT and sham treatment on (i) the baroreflex sensitivity, (ii) the systolic blood pressure variability, and (iii) the HRV in subjects with acute back pain. In addition, we compared the level of self-reported pain in the two study groups.Twenty-two male volunteers with acute mechanical back pain were enrolled in the study. The patients were randomly divided into two groups: one receiving sham treatment and the other receiving SMT treatment. All patients received exactly the same type and amount of interventions based on the intensity and area of pain. All volunteers were patients attending the Osteopathy Higher School Clinic in Paris and had received manual therapy within the preceding 6 months. The subjects were recruited through personal contact.Only male patients were included in order to avoid the possibility of menstrual hormone interferences. All were free of cardiac or pulmonary disease, any analgesic treatment, and had not ingested any caffeine or alcohol for 72 h prior to each experimental session. All patients had suffered acute pain for less than 3 months, with a numeric pain scale greater than 5/10 in the last 48 h. The 22 patients were split randomly into two groups by drawing lots. The treating clinician and the person doing the assessment were not involved in the treatment allocation.This study was carried out in a double blind fashion  and carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki). Before measurements were taken, participants were familiarized with the experimental procedure and informed of the risks associated with the protocol. Ethics committee approval  and written informed consent of the participants was obtained, including the authorization to publish their data.Each patient underwent a clinical examination of the thoraco-lumbar spine  by an osteopath to confirm the lumbar origin of the symptoms and to determine the vertebral level at the origin of the pain in sitting position. In addition, lumbar and pelvic muscles were palpated in search of associated myofascial pain. The palpation in search of painful reproduction has been recommended to locate the treatment site in manual therapy .The HVLA classical manipulation : the patLumbar mobilization: the patient was positioned in a side-lying position or on the stomach depending on the least painful position. The therapist contacted the lumbar vertebral segment in the symptomatic area with one or two hands and applied a rhythmic oscillation without impulse. The mobilization was applied 3 times during 30 s, with a one-minute pause between each application.Muscular manipulations: the patient was positioned in a ventral position, Myofascial pain in the lumbar and gluteal region was treated with ischemic pressure , deep trThe treatment could consist of various techniques of vertebral manipulation  vertebral manipulations or passive mobilization) and muscular manipulations, depending on the tolerance of the patient, as follows:. and referenced in the Glossary of Osteopathic Terminology. [The SMT intervention lasted 45 min and the subjects received exactly the same type and amount of vertebral manipulation by the same person. The protocol was standardized, and was performed by techniques taught at the Higher School of Osteopathyinology. .. [The Sham intervention simulated these techniques, but with improper patient positioning, deliberately misdirected movements, and diminished treatment provider force. . The theThe study took place over 7 days. On day 1 (D1) and day 7 (D7), two recording phases were performed: one before and one after the SMT or Sham interventions, respectively  were continuously recorded during in total of 35 min. The protocol included four recording phases of 7 min each. The patient’s breathing frequency was paced at 0.25 Hz, imposed by an audio recording feedback. Recordings began 15 min after patients were placed supine in a quiet room at a constant temperature (22 °C) in order to ensure that heart rate level was accommodated to the participant’s posture.ECG data were recorded and digitized using a PowerLab device  at a sampling frequency of 1000 Hz.. [A Finometer device  recorded blood pressure, using a cuff placed on the middle finger. The blood pressure signal was displayed by the Finometer device, which had been experimentally validated during previous laboratory tests. , 33. The. [The perceived level of pain was measured with the numeric pain scale (NPS). The NPS is a 100 mm line on which the patient places a single “X” to record the amount of pain perceived. , 35. TheBeat to beat (RR) intervals were extracted from ECG, and systolic BP from blood pressure signals . Before using the smoothed pseudo Wigner-Ville distribution (SPWVD) processing, occasional ectopic beats  were identified, visually and manually, and replaced with interpolated adjacent RR and BP interval values using control Excel with macros.The root mean square differences of successive RR intervals (RMSSD) were calculated as following:Where N = number of R-R interval terms.All RR series were then re-sampled at 4 Hz, using a cubic spline function.. [The SPWVD was used to compute instantaneous components of HRV and systolic blood pressure (SBP) variability. It was performed with the cardiovascular toolbox developed in a scientific laboratory, SCILAB . The SPWVD provides a continuous evaluation of amplitude and frequency, giving a nearly “instantaneous” complex of the fast Fourier transform (FFT) spectrum for each beat, with a high resolution achieved by independent time and frequency smoothing. Then, according to the characteristics of measurement. , the ins. [. [The baroreflex sensitivity was assessed in LF and HF bands at rest. The spectral baroreflex sensitivity reflects the linear relation between the input (BP) and output (RR) of the model. The degree of linearity between the two signals was estimated using the value of the coherence function. Ranging from 0 to 1, the RR and SBP spectra were shown to have a reliable linear relationship when the coherence index was higher than 0.5. , 37. The. [. , 38, 39.All data sets were initially tested for normality using a Kolmogorov-Smirnov test.In order to determine the effect of treatment (SMT vs. Sham) and time conditions (D1 vs. D7) on cardiovascular variables and NPS score, a two-way analysis of variance (ANOVA) was performed. The mean of difference scores of cardiovascular variables between POST and PRE treatment was used to determine the effect of treatment (SMT vs. Sham).p < 0.05. All data are reported as means and SEM. Whenever the difference was significant, the effect size was computed with the Cohen’s d. It can be calculated as the difference between the means divided by the pooled SD. [All analyses were performed with Sigma Stat software . The threshold for statistical significance was set to oled SD. . Effect SMT intervention, .SHAM intervention, .Five patients (3 SMT and 2 Sham) were excluded from the study because they did not participate in the second session. There was no obvious difference between the SMT and Sham groups with regard to age, height and weight .p > 0.15), as shown in Table fHF) remained constant with an instantaneous fHF very close to 0.25 Hz during all the measures.Pretreatment physiologic baseline D1PRE) heart rate variability, systolic blood pressure variability and baroreflex sensitivity components were not significantly different between each baseline period  differed in the two groups, with a higher gain in the SMT than in the Sham group  and the second session (D7) of treatment for the two groups Tables , 3. With. [The main objective of this study was to quantify the SMT effectiveness in patients with acute low back pain from the analysis of cardiovascular variability. The main results of this study were that the components of cardiovascular variability linked to the vagal modulation of heart rate  were significantly higher with SMT than Sham intervention Fig. . Indeed,. , 42. Thu. [. [These findings were consistent with those reported by Giles. , who not. [. –45, the Although there was no difference between groups of the treatment on NPS, the NPS decreased with both SMT and Sham treatment. The score decreased over time during the first session of treatment and also during the second treatment session, indicating that this was due to the placebo effect. The decrease in NPS during the experiment can be explained by both the experimental period and the treatment. However, the increase of the vagal components of cardiovascular variability with SMT treatment can only partly be explained by the decrease in NPS during treatment sessions.. [Although the clinical use of the NPS score has been validated. , 46, it .  and SMT In our study, we used both manipulation and mobilization in the SMT group and the subjects received the same treatment. We were confident in using both these types of manual therapy, as studies , 48 haveThe main results of this study were that the vagal modulation of heart rate  was significantly higher after SMT than after the Sham intervention Fig. . It is iThe NPS score decreased over time during the first and the second session of treatment. However, we did not find a significant difference between the two sessions of treatment (D1 vs. D7). Perhaps this can be explained by the fact that two sessions of treatment are insufficient to have a significant improvement in the physiological components.Moreover, other factors such as the psychological stress or age difference might influence the results of this study.Furthermore, there is no significant effect between SMT and Sham for most of the variables of HRV, SBP and pain. These results may be due to the small sample size. Therefore, it would be important to consider the number of study subjects included in studies of this type. Although, our results are interesting, they should be considered with caution and whether these results are generalizable to other types of back pain populations, or indeed to people in general, is not known.. [This study has been conducted with patients suffering from acute back pain. It has already been shown that the presence of chronic pain significantly alters the nature of the interactions between blood pressure, baroreflex sensitivity and the perceived level of pain. . Thus, i. [Our results show that SMT shifted the sympathovagal balance towards an increase in the parasympathetic cardiovascular autonomic control in patients suffering from acute back pain. This effect is known to be beneficial to health. . Whereas


Pain control during surgery in order to cause analgesia and reduce the somatic and autonomic response may decrease the morbidity. Intrapleural catheter embedding during surgery under direct vision of surgeon is safe and easy and without potential risk of thoracic epidural block. The aim of this study was to investigate the effect of bilateral intrapleural infusion of lidocaine with fentanyl versus only lidocaine in relieving pain after coronary artery bypass surgery.In this prospective randomized double blind clinical trial,130 adult patients undergoing elective CABG with age range of 20 to 60 years were divided into two groups receiving either lidocaine and fentanyl (group A) or lidocaine (group B). The analgesia was evaluated every two hours in all intubated and non-intubated patients using Visual analog scale (VAS) and data were analyzed using SPSS software package.Of all patients, 67 (51.5%) were males and 63 (48.5%) were females. The average age of subjects was 53.49 ± 5.099 years. Mean pain score six hours after the surgery was statistically different between the groups at all times.The pain in patients receiving combination of lidocaine and fentanyl is less than patients receiving only lidocaine. Pain causes severe autonomic and physiological responses which can be very dangerous in patients with ischemic heart disease.7Local anesthesia through intrapleural catheter is another way to control pain. Intrapleural anesthesia was first described by Reiestad.9The intrapleural block in the supine position leads to lower thoracic ganglion block but cervical ganglion and lumbar network are not blocked thus hemodynamics during painful stimuli like thoracotomy remains relatively stable.10Bupivacaine is studied for its effect on the relief of pain after thoracic surgery. There are few reports of side effects associated with its use.12Due to different techniques of coronary artery bypass graft surgery (CABG) which differ the location and severity of pain in this group and as to the best of our knowledge, there is no study about pain control levels using intrapleural block after CABG, we decided to conduct a study to compare the effect of intrapleural lidocaine and fentanyl with only lidocaine in reducing pain after CABG.This prospective randomized double blind clinical trial study was conducted in Tabriz Shahid Madani Hospital, after obtaining approval of the university ethics committee and written consent from patients. This study was registered in IRCT with the registration number of: IRCT2015112714728N2. One hundred thirty adult patients between the age of 20 to 60 years and undergoing elective CABG having 3 to 6 hours operation time were divided into two groups.Inclusion criteria were EF≥30%, Cr ≤ 1.8, elective CABG surgery, age of 20 to 60 years. Exclusion criteria were previous pleural disease, COPD, Diabetic neuropathy, seizures, allergy to local anesthesia, drug addiction, drug habits to analgesics, calcium channel blockers, alpha2-agonists, history of previous heart surgery and surgery complications such as Aortic dissection, redo operation due to postoperative bleeding, high drainage after surgery (more than 1000 ml/24h).All patients received oral lorazepam (1mg) the night before surgery, and morphine (0.1mg/kg IM) and promethazine (0.5mg/kg IM) half an hour before going to the operating room. Induction of anesthesia was done using intravenous midazolam (0.1mg/kg), fentanyl (5μg/kg), atracurium (0.15mg/kg), lidocaine (1mg/kg) and maintenance of anesthesia by using TIVA method  with a combination of midazolam, fentanyl and atracurium. All patients were monitored under standard technique during surgery. In the later stage of operation sterile white suction catheter was bilaterally inserted to intrapleural space from the embedded chest tube site. To avoid interference of injection and discharging possible bleeding of the patient, and in order to prevent disrupting injection process when removing the Chest tube medication was not injected through Chest tube. After injection of intraplural drugs, Chest tube was clamped temporarily for 10 minutes to prevent the medication discharge. Long time clamping was avoided in order to prevent possible disorders in the process of unloading mediastinal bleeding in patients.Patients were divided into two groups receiving either lidocaine and fentanyl (group A) (65 patients) or lidocaine (group B) (65 people). At the end of the surgery and in the ICU, 20 ml of lidocaine 0.75% + fentanyl 2mcg/kg for group A and 20 ml of lidocaine 0.75% in Group B were injected by an anesthesiologist through the intraplural catheter every 6 hours . The analgesia was evaluated in all intubated and non-intubated patients using Visual analog scale (VAS) every two hours after the patient awaking and data were analyzed using SPSS software. If the VAS was 5 or more, intravenous morphine was injected at dose of 0.5mg/kg/IV. The VAS and the type and total amount of used analgesics were recorded.t-tests to compare parametric quantitative variables between two groups. Differences in variables during the study were assessed with a repeated measures analysis of variance. P<0.05 was considered as significant for all statistical tests.The data were analyzed using the statistical software program Statistical Package for the Social Sciences Version 16.0, SPSS. Kolmogorov–Smirnov test was used to assess the normality of the variables distribution. The data were analyzed using Chi-square test to compare parametric qualitative variables and Independent There was no significant difference in terms of demographic characteristics including age, sex and BMI between the two groups. 2 and PCO2 . There was not a significant difference in mean SpO2 average before anesthesia and at 2, 6, 12, 18 hours after surgery but SpO2 24 hours after surgery was statistically different between two groups. , HR , PH, PaO groups. Average pain score of patients in two-hour intervals after surgery is listed in The average dose of analgesic medication in subjects was 6.771±3.305. This amount in group A and B was 3.91±1.147 and 8.61±2.907 respectively. Average dose of oral analgesic in the subjects was 1240.25±595.319. This amount in group A and B were 764.189±497.721 and 1519/841±455.392, respectively. There was no side effect in any patient.Post thoracotomy pain is one of the most severe pains that a patient experiences in perioperative period, which can continue for months and even years. Inadequate control of pain impairs breathing and effective coughing, which leads to atelectasis and pulmonary complications, including infection,Ramajoli et al. observed that in patients suffering from pleuritic chest pain caused by benign or malignant disease, intrapleural block relatively stables the blood hemodynamic status within a painful stimulus during thoracotomy.10Karakaya et al in their study found that intrapleural bupivacaine and fentanyl combined with epinephrine have more analgesic effect compared to only bupivacaine.In the study of Pennefather et al of 68 patients undergoing thoracotomy, 39 patients were randomly assigned to two groups receiving either bupivacaine 0.25% (40 mg) intrapleural with epinephrine 1: 200,000 or saline. There was no statistical difference in VAS score between the two groups. They concluded that intrapleural bupivacaine does not produce adequate analgesia for shoulder pain control after unilateral thoracotomyIn the study of Raffin et al, 14 patients were under analgesics treatment with intrapleural lidocaine 2% and 16 patients were in the control group. They concluded that intra-pleural analgesia with lidocaine after thoracotomy has poor results. The mean VAS score in the group that received lidocaine after receiving bolus was 6.6.18Kambam et al. demonstrated that intrapleural anesthesia improves pain control in patients undergoing thoracotomy with posterior and lateral incision.21D’Andrilli et al examined pain relief after intrapleural-intercostal block after surgery in patients who were under mini-thoracotomy for pulmonary resection and concluded that in the group receiving bupivacaine pain, mortality, morbidity and duration of hospitalization is significantly less than the control group.Mashaqi et al. examined 40 patients who underwent CABG with sternotomy in two groups either intrapleural injection of 2% lidocaine or placebo and found that intrapleural lidocaine is a safe method to reduce chest tube related pain and improving lung function after CABG.It is the lack of data in use of LIMA  for CABG between the two groups. Given that harvesting LIMA from inside the chest wall may be more intense pain than no harvest after operation.Intrapleural lidocaine with fentanyl can more effectively suppresses pain compared to lidocaine alone in patients ndergoing elective CABG surgery. We recommend conducting further studies with more sample size, examining pain in the long term in two groups.


Fatigue is a prevalent symptom and major burden in neuroimmunological diseases. In neuromyelitis optica spectrum disorder (NMOSD), a severe autoimmune central nervous system (CNS) inflammatory disease with autoantibodies reactive to aquaporin-4, there are few reports about fatigue and quality of life (QOL). We aimed to evaluate the severity of fatigue and its relationship with QOL in patients with NMOSD. We prospectively studied patients with NMOSD who were in remission and seropositive for anti-aquaporin-4 antibody, and they were divided into 2 groups based on the presence of fatigue assessed using the Functional Assessment of Chronic Illness Therapy-fatigue score. Sleep quality, depression, pain, and QOL were also evaluated. A total of 35 patients were enrolled , and the median Expanded Disability Status Scale (EDSS) score was 2.0 . The patients with fatigue  had poorer sleep quality and more severe depression than those without fatigue (p = 0.009 and p = 0.001). Both the physical and mental QOL scores were lower in patients with fatigue than in those without fatigue (p = 0.033 and p = 0.004). Multiple linear regression analyses showed that the degree of fatigue with EDSS score and pain were independent predictors of physical aspects of QOL , whereas depression was the only predictor of the mental components of QOL . Fatigue is a common symptom and an important predictor of QOL in patients with NMOSD. Neuromyelitis optica (NMO) is an autoimmune relapsing inflammatory disorder of the central nervous system (CNS) characterized by optic neuritis, myelitis, and distinctive brain lesions. An antibWe prospectively studied consecutive NMO or NMOSD patients who were registered in the CNS Inflammatory Disease Registry at the Samsung Medical Center from June 2014 to May 2015. Patients were enrolled if they met the revised criteria for NMO or the suggestion of NMOSD with positive anti-AQP4, which isThe severity of fatigue was assessed with a Korean version of the Functional Assessment of Chronic Illness Therapy-fatigue scale (FACIT-fatigue), which is a 13-item questionnaire that assesses self-reported fatigue and difficulty of daily activities due to fatigue; its final scores range from 0 to 52, and higher scores indicate less fatigue., 15 ConsThe median score of FACIT-fatigue from a general population study in the United States with 1075 subjects was 43. The patiDepression was evaluated by the Beck Depression Inventory score-II (BDI), which is composed of 21 items, and ranges from 0 to 63; higher scores indicate more severe depression. The Brief Pain Inventory (BPI), used for the assessment of pain has questions regarding 2 categories: pain severity and pain-related interference in daily life (each category ranges from 0 to 10); pain severity index score was evaluated by the average score of pain severity questions. The Pittsburgh Sleep Quality Index score (PSQI), which is composed of 7 items, and ranges from 0 to 21, was used for measuring the sleep quality. Higher scores of PSQI indicate poor sleep quality, and a poor sleeper was defined as a patient with PSQI score above 5. QOL was assessed via the Short Form 36 Health Survey (SF-36) with scores from 0 to 100, where higher scores indicate better QOL. Two summary scores of SF-36 were used for analysis: Physical component summary (PCS) and Mental component summary (MCS).p < 0.05. All statistical analyses were performed using commercially available software .Appropriate summary statistics were used to describe categorical and continuous variables; continuous data are shown as mean with standard deviation (SD) or median with inter-quartile range (IQR); categorical variables are presented with absolute and relative frequencies. We analyzed the differences between the groups (without fatigue versus with fatigue) using the Chi-square test or Fisher’s exact test for categorical variables; Student t-test or Mann-Whitney U test for cotinuous variables. Correlations between scores of the questionnaires were assessed using Spearman’s rho, and multiple linear regression analysis was performed to evaluate the independent contribution of factors that influenced the QOL; age, disease duration, EDSS, FACIT-fatigue, BDI, PSQI score, and pain severity index were included as possible independent variables for each model. Regression coefficients with 95% confidence intervals and their significance from multiple linear regression analysis were given. The multicollinearity was not observed among variables. Differences were considered significant at a value of P = 0.771). The median disease duration was 3.0 years , median EDSS score was 2.0 , and the mean annualized relapse rate (ARR) was 1.6 ± 1.6. The most common clinical manifestation during the disease course was myelitis , followed by optic neuritis , brainstem or cerebellar syndrome , and cerebral or diencephalic syndrome . Demographic and clinical features such as age, sex ratio, disease duration, ARR, EDSS score, lesions of involvement, and preventive treatment including prednisolone and immunosuppressants were not different between patients with NMSOD with and without fatigue . Thee coexistence of other autoimmune diseases was observed in 7 patients (20.0%) .A total of 35 patients who were seropositive for anti-AQP4  were finally enrolled . 5 patiep = 0.009); moreover, poor sleepers (PSQI>5) were more common in patients with fatigue than those without fatigue . The mean BDI score in patients with NMSOD and fatigue was 17.9 ± 8.5, which was higher compared to that in patients without fatigue , and 8 patients with fatigue (22.9%) showed BDI score ≥ 20, suggesting moderate or severe depression. Pain severity index was higher in patients with fatigue but not significant . Physical and Mental component scores of SF-36 for QOL were lower in patients with NMSOD and fatigue (p = 0.033 and p = 0.004) (Results of self-administered questionnaires are summarized in = 0.004) .p = 0.021; r = –0.335, p = 0.049; and r = –0.788, p < 0.001), whereas the degree of fatigue was not correlated with EDSS score or disease duration  . Moreover, multiple stepwise linear regression analysis showed that EDSS score , FACIT-fatigue , and Pain severity index  were independent predictors of the physical aspects of QOL (R2 = 0.651), whereas BDI score was the only predictor of the mental components of QOL   . In addi= 0.365) .This study showed that fatigue was common and an important predictor of QOL in patients with NMOSD. In addition, higher fatigue severity was associated with severe depression, poor sleep quality, and severe pain intensity.Fatigue is a widespread symptom in various neuroimmunological diseases such as MS, myasthenia gravis, Behcet disease, neurosarcoidosis, and immune vasculitis. Recentlyp = 0.034). And the patients with ‘myelitis only’ showed more fatigue (lower FACIT-fatigue score) than those with ‘optic neuritis only’, but which was not significant . Recently, Magnetic Resonance Imaging (MRI) studies in patients with MS showed that grey matter pathology or occult white matter damage was associated with the pathogenesis of fatigue.[Generally, 2 types of fatigue exist in patients with neurological disorders. Central fatigue is considered as a characteristic of hypothalamic-pituitary-diencephalic syndrome; metabolic and structural lesions that disrupt the pathways interconnecting the basal ganglia, thalamus, limbic system, and higher cortical centers are implicated in the pathogenesis of fatigue. Previous fatigue.–26 Since fatigue.–29 furthFatigue in NMOSD also could be secondary to sleep disorders, mood disorders or medications. In this study, we found that patients with fatigue had poorer sleep quality and more severe depression than patients without fatigue, and that fatigue score was correlated with sleep quality and depression scores and pain severity index. A previous study showed that patients with fatigue had higher PSQI and BDI scores with more daytime sleepiness and lower blood oxygen level in polysomnography than observed in patients without fatigue. But consRegarding depression, it was reported that patients with depression showed a significantly higher cortisol awakening response, indicative of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity than healthy subjects. The relaMore importantly, we found that fatigue score was correlated with both the physical and mental scores of SF-36, and that fatigue, pain, and EDSS scores were independent predictors of the physical aspects of QOL, whereas depression was an independent predictor of the mental aspects of QOL. Previously, it was reported that very strong correlation was observed among global fatigue, global depression, and decrease in HRQOL scores in patients with NMO, and receThis study has several limitations. First, we included a single ethnic population at a single hospital, which can result in unintentional bias. In addition, only patients who were seropositive were enrolled because we did not perform the test of myelin oligodendrocyte glycoprotein (MOG) autoimmunity, a distinct spectrum differentiated from seronegative NMOSD, which can limit the generalization of our data to seronegative NMOSD., 42 FinaIn conclusion, fatigue is a common symptom and an important predictor of QOL in patients with NMOSD. The positive correlation of fatigue with depression, sleep disturbance, or pain may suggest that the mechanisms of these factors are interactively associated in NMOSD. The management of fatigue with the efforts to treat depression, poor sleep quality, and pain could help to improve QOL in patients with NMSOD.S1 Table(DOCX)Click here for additional data file.S1 FigThe degree of fatigue was not correlated with disease disability or disease duration. The dotted line represents the FACIT-fatigue score of 43. EDSS, Expanded Disability Status Scale; FACIT-fatigue, Functional Assessment of Chronic Illness Therapy-fatigue.(TIF)Click here for additional data file.


The underlying etiology of recurrent aphthous stomatitis (RAS) is unclear and treatment aims to provide symptomatic and faster relief. This study compared the efficacy of diode laser, a herbal combination of Acacia nilotica and Licorice (A and L) and Amlexanox in the management of RAS.Sixty patients with minor aphthae were selected and randomly divided into four groups of 15 each. Group I and II received adhesive preparations of a herbal mixture of A and L and a 2 mg Amlexanox paste respectively, group III received diode laser and the fourth group (control) used a placebo. Ulcer size, pain score were recorded on days 1, 2 and 5.Laser group showed the statistically highest mean percentage (%) of reduction in pain scores and ulcer size than the other groups. The mean % of reduction in pain scores was 43.3+20.0 at day 2 and 67.8+21.5 % at day 5 in the laser group while Amlexanox group demonstrated a 29.8 +11.3 and 61.9+24.5 mean % of reduction in pain scores at day 2 and 5 respectively. A and L group showed a lower mean % of reduction in pain scores than laser and Amlexanox groups with a 22.2+10.5 and 43.4+15.8 mean % reduction in pain scores at day 2 and day 5 respectively. Similarly the highest mean % of reduction in ulcer size was seen in the laser group being 52.7+19.8 at day 2 and 85.1+22.0 at day 5, while it was 48.1+16.5 at day 2 and 77.8+28.7 at day 5 in the Amlexanox group and 42.0+11.5 at day 2 and 63.0+20.5 at day 5 in the A and L group.All treatment modalities reduced pain and ulcer size than placebo group. Laser therapy demonstrated the highest percentage of reduction of pain score and ulcer size. Key words:Aphthous stomatitis, laser, herbal plants, Acacia nilotica, Licorice. Recurrent aphthous stomatitis (RAS) is the most common ulcerative disease of the oral mucosa affecting as high as 15-25 % of the general population worldwide . In seveAmlexanox 5%, a topical anti-inflammatory and anti-allergic drug was found to play a significant role in the management of minor aphthous ulcers. Amlexanox potentially inhibits the formation and release of histamine and leukotrienes from mast cells, neutrophils, and mononuclear cells. It has been shown to accelerate healing of aphthae and decrease pain, erythema and size of the lesion ,8. AmlexOn the other hand laser therapy constitutes an alternative therapy to oral diseases that present with pain and inflammatory reactions and that require tissue regeneration, since a laser provides better anti-inflammatory responses with edema reduction, pain reduction and cellular bio-stimulation . Apart fThe use of natural products, including medicinal plant preparations for pain reduction and shortening of healing time of oral aphthous ulcers are gaining more attention due to their decreased side effects and drug resistance .S. mutans (Acacia nilotica (A), commonly known as Indian gum Arabic tree is rich in flavonoids, simple phenolics, saponins, quinines, tannins, coumarins and polysaccharides  and is u. mutans . A was f. mutans .Licorice (L), the name given to the roots and stolons of Glycyrrhiza species, has been used since ancient times as a traditional herbal remedy . L contaMedicinal plants have a great capability for displaying a synergistic action owing to their multi-component nature . Hence cThe aim of this study was therefore to compare the efficacy of three different treatment modalities: diode laser, a herbal combination of A and L and Amlexanox in the management of RAS.-Plant materialGlycyrrhiza glabra L., Family Leguminosae and pods of Acacia nilotica LwilldFamily Leguminosae were purchased from a local market in Cairo, Egypt and authenticated by Dr. Abdel Haleem AbdelMotagaly, Dept. of Flora, the Agricultural Museum, Dokki, Giza, Egypt. The plants were crushed and grinded into suitable size for phytochemical study.Dried roots and rhizomes of -Preparation of biologically active fractions and identifications of compoundsA. nilotica and Glycyrrhiza glabra were extracted separately using solvents of increasing polarity in the following order: petroleumether, ether, chloroform, methanol, and water. These extracts were evaporated to dryness under vacuum at 40°C, lyophilized, and saved for pharmaceutical preparation. The collected polar extracts were subjected to phytochemical investigation using different chromatographic and spectral procedures as; PC, CC, TLC, Preparative HPLC, LC/MS, High field NMR, 1H-NMR, 13C-NMR,HMBC, HMQC, H1H1-COSY, and ESI-MS.Extraction, isolation and identification of the natural compounds from the two plants were carried out separately -Preparation of Herbal Adhesive PasteThe adhesive paste was dispensed containing both A and L dry extracts, each at 1% composition forming a total of 2% of the herbal paste. Gelatin, Polyethylene glycol 20000, glycerine, Polyethylene glycol 400, herbal extracts. Tween 20 and distilled water were mixed after weighing appropriate amounts and heated at 70°C till complete dissolution of the components. Similarly, sodium carboxy methyl cellulose and pectin were dispersed in liquid paraffin, mixed well and heated at 70°C. The oily portion was then poured on the aqueous portion with continuous stirring at 70°C till complete homogeneous blending. The formulation was removed from the hot plate and left to cool to room temperature before application by patients for treatment of dental lesions.-Patients and Methods:A total of 60 patients, females (62%) and males (38%) with mean age 28.5 years (19-40 years) and a current history of RAS were recruited from the outpatient clinic of Oral Medicine and Periodontology, Oral Diagnosis and Radiology department, Faculty of Dentistry, Ain Shams University. The study has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. Before entering the study, eligible subjects were informed regarding the purpose of this study and provided a signed consent to participate in this study. The protocol was approved by Ein Shams University’s Ethical Committee. Inclusion criteria included subjects with a history of at least two confirmed episodes of RAS during a 3-6 months untreated baseline period. Exclusion criteria included pregnant females, smokers or those suffering from psychological disturbances, inflammatory and allergic conditions, or those with special syndrome where RAS is one of its symptoms (e.g. Behcet’s syndrome); those with aphthous lesions older than 4 days, and patients that have received any other treatment for the last 4 weeks.-Study designSubjects satisfying the inclusion criteria were assigned randomly to one of the four-treatment groups: group I received adhesive pastes of A and L, group II received adhesive oral tablets of 2mg Amlexanox *, group III received diode laser irradiation and group IV assigned as the control group received a placebo adhesive tablet. Patients of group I, II and IV were instructed to apply the medication on the lesion q.i.d. after drying it with a small sterile cotton pad and refrain from eating at least for 30 min after the drug application. Treatment continued till for 5 days. A 970 nm diode lasers was used for the treatment of RAS in a non-contact mode. A 320 micron fiber optic tip diameter was used to deliver the laser beam; the initiation was done on an articulating paper. Then diode Siro laser ** was started at a defocused mode from the lesion (5-8 mm) and advanced slowly towards the area ending up 2-3mm away and continuously moving from the periphery of the lesion to the center “painting “ the entire area and moving away from the lesion if the patient feels warmth. The setting was put at 0.8w for 30-45 seconds with a refractory period of 15-20 seconds between laser “passes” to allow for tissue relaxation. The area was rubbed gently with a wet gloved finger to determine if a decrease in pain was felt by the patient. A 2nd or a 3rd laser pass was occasionally needed to decrease the pain with a maximum time of three minutes total irradiation time. The laser treatment consisted of one sitting which started at day 0. Each sitting consisted of a maximum of four sessions of applications.*Aphthatab, EVA pharma,. Cairo, Egypt. **970nm SIRO Laser Advance class IIIb, SIRONA The Dental company, Germany.After each pass, the area was checked with palpation. The patients were asked to refrain from using any medications over the next 5 days. The pain scores and sizes of the ulcers were evaluated on treatment days 0, 2 and 5. Pain was recorded using the visual analog scale (VAS), from 1-10 with 10 being most severe, and subjects were instructed to mark the number representing their level of perceived pain. The size of the ulcer was measured by a single oral specialist who was blinded to the subject’s status using a William’s graduated periodontal probe.-Statistical analysisP ≤ 0.05. Statistical analysis was performed with IBM® SPSS® Statistics Version 20 for Windows.Numerical data were explored for normality by checking the distribution of data, calculating the mean and median values as well as using tests of normality (Kolmogorov-Smirnov and Shapiro-Wilk tests). All data showed non-parametric distribution. Data were presented as mean and standard deviation (SD) values. Kruskal-Wallis test was used to compare between the four groups. Mann-Whitney U test was used to for pair-wise comparisons when Kruskal-Wallis test is significant. Bonferroni’s correction was applied for the pair-wise comparisons.The significance level was set at -Pain scorep=0.010), where mean pain scores were 7.7+1.1, 5.9+1.1, and 5.1+1.2 for A and L, Amlexanox and Laser groups respectively. At day 5 both Amlexanox and Laser groups demonstrated statistically significantly lower mean pain scores than A and L group (p < 0.001), where the mean pain score results for the Amlexanox group was 3.2+1.6 and for the laser group 2.9 +1.1 while that of A and L group was 5.6+1.3  at day 2 and 9.1+0.7 at day 5. No statistically significant difference was observed between the three treatment groups at day 2. , while Amlexanox and Laser groups; both showed the lowest mean ulcer sizes with no statistically significant difference between them. The mean ulcer size was 3.0+0.7, 1.8+0.6 and 1.1+0.3 for A and L, Amlexanox and Laser groups respectively  of reduction in pain scores and ulcer size than the other groups. The mean % of reduction in pain scores was 43.3+20.0 (at day 2) and 67.8+21.5 % (at day 5) in the laser group in comparison to Amlexanox group which demonstrated a 29.8+11.3 and 61.9+24.5 mean % of reduction in pain scores at day 2 and 5 respectively. A and L group showed a lower mean % of reduction in pain scores than laser and Amlexanox groups with a 22.2+10.5 and 43.4+15.8 mean % reduction in pain scores at day 2 and day 5 respectively. Similarly the highest mean % of reduction in ulcer size was seen in the laser group being 52.7+19.8 at day 2 and 85.1+22.0 at day 5, while it was 48.1+16.5 at day 2 and 77.8+28.7 at day 5 in the Amlexanox group and 42.0+11.5 at day 2 and 63.0+20.5 at day 5 in the A and L group. The control group showed the statistically significantly lowest mean % reduction in pain and ulcer size scores  group at all periods. The control group also demonstrated reduction in pain and ulcer size throughout the different study periods. This could be explained by the patients’ feeling of being treated giving them a sense of relief, or the placebo forming a film covering the ulcer thus providing a protective mechanical effect of the placebo possibly forming a film covering the ulcer and providing some soothing effect. It could be also due to the nature of the ulcer itself, being self-limiting .Laser group demonstrated the lowest mean percentage of reduction in both pain scores and ulcer size at day 2 and 5, with a statistically significant difference between laser group and both A and L and control group. The effect of Amlexanox on pain and ulcer size reduction was close to that of laser with no statistical significant difference observed between both groups except at day 2 where laser demonstrated a statistically significant lower percentage of pain reduction denoting the faster effect of laser in alleviating pain in RAS patients.et al. (It was proposed that LLLT accelerates wound healing and reduces pain by stimulating collagen production, altering DNA synthesis and improving the function of neurological tissue. In two case reports LLLT provided instant pain relief and rapid decrease in ulcer size which is in accordance with the results of the present study . De Souzet al.  revealedMany studies demonstrated improvement in healing with reduction of pain, size, duration and recurrence of RAS when Amlexanox paste was applied. Authors attributed this effect to Amlexanox causing inhibition of release of histamines and leukotrienes from mast cells and neutrophils and the release of inflammatory cytokine IL-1 beta, thus increasing the vascular permeability and aiding in the healing of the ulcer ,24. SincIn the present study, the group using A and L demonstrated better results than the placebo group, however the percentage of reduction in both pain scores and ulcer size in the A and L group was less than that of the laser and Amlexanox groups. The use of herbal extracts either individually or in a combination of more than one extract has shown to be effective in treating many diseases including oral ulcers , which iIt can therefore be concluded that all three treatment modalities reduced pain and ulcer size in comparison with placebo group, however RAS treatment using diode laser demonstrated the highest percentage of reduction in pain scores and ulcer size. Thus it is safe to assume that the choice of treatment modality might depend on the case itself. Since aphthous ulcers are recurrent, studies on a larger no of subjects and for a longer term may be needed for more beneficial results.


Sir,—Subacromial pain is a very common cause of visits to an orthopedic clinic. We have read with interest the paper “Specific exercises for subacromial pain” by Björnsson-Hallgren et al. The question whether an exercise program specifically developed to treat subacromial pain is superior to a regular training regime is important. Recognizing the strengths of the study, we would like to discuss some issues concerning the approach used by the authors when reporting the results. The main results were reported as absolute numbers of exposed and unexposed patients in each group along with p-values. The exposure was a decision to agree to a surgical procedure at the end of follow-up. Such an approach may create a problem: absolute estimates describe a particular single sample but say nothing about the entire population of interest. Based on the reported results, we discover that 14 of 47 patients in the intervention group and 28 of 44 controls ended in a decision to undergo surgery. Additionally, we find out that the difference between these two particular groups was statically significant as shown by the p-value <0.05.How substantial was the difference between groups—how much higher risk did controls have regarding the surgery decision?How wide could the possible boundaries of observed difference be if different random samples containing different individuals were drawn from the population of patients with subacromial pain?How many patients have to be treated by a specific training program in order to avoid at least one surgery decision?While such statistics are adequate to inform readers about certain differences between groups, several important questions remain unanswered:The first question can be answered by calculating, e.g., a relative risk ratio (RR), the second by drawing a confidence interval (95% CI), and the third question can be answered by estimating a number needed to treat (NNT). These statistics can be calculated in Excel, or by the majority of statistical packages available on the market, or even by hand.RR =0.47 ;p-value of RR =0.0025 ;95% CI for RR =0.27–0.77 (the risk ratio may vary within these limits if different patients are drawn from the population);NNT =3.0 (at least 3 patients need to be included in a specific exercise group in order to avoid 1 decision for surgery);95% CI for NNT is 1.9–6.9 .Thus, the following statistics may be added to the report:In this way, the report may come to be more robust and precise, emphasizing substantially the conclusion made by the authors. We encourage researchers to report statistics that describe a population  whenever possible.1 and Petri Virolainen 2Mikhail Saltychev 1 Physical and Rehabilitation Medicine and 2 Orthopedics, Turku University Hospital and University of Turku, Turku, FinlandDepartments of mikhail.saltychev@gmail.comEmail: Sir,—We thank M Saltychev and P Virolainen for their interest in our work. We appreciate their approach to the research question, which may provide an additional viewpoint and further demonstrates the differences between the study groups. We have controlled our data according to number needed to treat (NNT) and relative risk (RR) and confirmed that their calculations are accurate. These statistical results allow for a slightly different perspective on our results, which may be even clearer in presenting our results for the majority of readers treating subacromial pain patients. They further emphasize the importance of a specific exercise program and may very well be added to our results. We found their comments very helpful and valuable for our future research.Hanna Björnsson Hallgren, corresponding authorhanna.bjornsson.hallgren@regionostergotland.seEmail: Björnsson Hallgren H C, Adolfsson L E, Johansson K, Öberg B, Peterson A, Holmgren T M. Specific exercises for subacromial pain: Good results maintained for 5 years. Acta Orthop 2017; 88 (6): 600-605.


Despite persistent clinical pain in patients with painful diabetic neuropathy, longer pain duration was associated with more efficient CPM. Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN).To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients.In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain.P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group (P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics.Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = −0.417; Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to “normalize” with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN. Similar to other pain states, patients with painful diabetic neuropathy (PDN) demonstrate enhanced activity of facilitatory pain pathways40 Studies on surgical and medication treatments for pain have shown that the pain alleviation is accompanied by improvement of pro-nociceptivity, with transition from less efficient to efficient conditioned pain modulation (CPM).49 However, it is unknown whether the spontaneous alleviation of neuropathic pain along with PDN duration is similarly associated with reversal of pro-nociceptivity.An interesting feature of the neuropathic pain of diabetic origin relates to the reports of spontaneous pain improvement or resolution with disease progression.The aim of this study was to evaluate pain modulation in PDN of different pain duration and its association with pain levels. We hypothesized that longer neuropathic pain duration would be associated with lower clinical pain levels and reversal of the pro-nociceptive characteristics of pain modulatory system.49). Patients met the following inclusion criteria: (1) lower limb distal neuropathic pain for more than 3 months and (2) mean pain severity during the last month of ≥40 on a 0  to 100 (“most painful imaginable sensation”) numerical pain scale (NPS). The exclusion criteria were as follows: (1) intake of a monoamine oxidase inhibitor (MAO-I) within the last 14 days, (2) narrow-angle glaucoma, (3) inability to undergo psychophysical testing, (4) pain complaints at the upper limbs, and (5) chemotherapy for cancer and known vitamin B12 deficiency. Patients who were on regular use of serotonin–noradrenaline reuptake inhibitors (SNRIs) were tested after 1 month drug washout.Thirty-five patients with PDN participated in this study. The diagnosis of PDN was confirmed by a qualified neurologist or endocrinologist with special training in diabetes care. This article reports the results of baseline (pretreatment) assessment of the patients cohort who then underwent treatment with duloxetine  collected under same psychophysical protocol as for patients with PDN served as the control group. The inclusion criteria for the control group were as follows: (1) absence of chronic pain history; (2) no use of analgesic or psychiatric medication on a regular basis; (3) age between 40 and 80. All participants were able to communicate and understand the instructions of the study and were asked to refrain from any pain relief medications 24 hours before the experimental trial. The study was approved by the local ethics committee, and informed consent was obtained from all participants.All experiments were conducted in the same setting by the same experimenter (H.N.-A.) at the Laboratory of Clinical Neurophysiology in Rambam Health Care Campus, Haifa, Israel. Subjects sat comfortably in a quiet room with an ambient room temperature of 22°C to 23°C.Patients were asked to report duration of (1) diabetes, (2) sensory neuropathic symptoms such as, (3) mean and maximal neuropathic pain intensity during the last week, and pain duration. In addition, the information regarding current or past pain-relieving drugs consumption was collected.2 contact thermode according to the method of limits.45 The 32°C baseline temperature decreased or increased at a rate of 1.0°C/s and was stopped by pressing the response button at the moment that warm or cold sensation was perceived. Warm detection threshold and CDT were calculated as the mean values of the 3 measurements. The mechanical detection thresholds (MDT) were measured using von Frey filaments . The weight was increased using consecutive filaments until the patient reported that sensation was perceived. Each filament was applied 3 times until the filament pressure was detected in at least 2 of the 3 trials. The first filament to be detected at ≥2/3 times was determined as the MDT.As part of a clinical examination, sensory detection thresholds were measured at the dorsum of the foot to assess neuropathy severity. Warm detection thresholds (WDT) and cold detection thresholds (CDT) were measured 3 times each using the thermal sensory analyzer (TSA-II)  with a Peltier 30 × 30 mmAll participants, the patients with PDN and the control subjects, underwent CPM and temporal summation (TS) assessments to assess pain modulation. All tests were delivered to the volar aspect of the forearm. This site is less commonly affected by the neuropathy, allowing normal or near-normal peripheral sensory function. This is because genuine assessment of the central effect depends on intactness of the peripheral conduction of neural signals.Mechanical temporal summation of pain (TS)—the stimuli were delivered with an 180gr (# 6.45) von Frey filament applied to the volar forearm. Subjects were exposed to a series of 10 stimuli with an interstimulus interval of 1 sec, applied within an area of 1 cm in diameter. Subjects were asked to rate the level of pinprick pain intensity using verbal NPS for the first and the tenth stimuli. The difference between the tenth and the first pain scores served as a score of the TS.10 The baseline temperature was 32°C, which increased at a rate of 2°C/s to the destination temperature, which was held for 30 seconds, and decreased back to baseline at the same rate. Subjects were asked to rate the intensity of the test stimulus along the stimulus at the 10th, 20th, and 30th second. The mean pain score served as the pain level of “test stimulus.” After a 15-minute break, subjects were exposed to the conditioning stimulus by immersion of the nondominant hand into a hot water bath at 46.5°C  up to the wrist for 1 minute. Water-induced pain was rated every 10 seconds during the first 30 seconds of immersion; the mean score of the 3 ratings of the immersed hand served as the pain level of the “conditioning stimulus.” During the last 30 seconds of the conditioning stimulation, an identical test stimulus was repeated, and pain of the test stimulus was rated again every 10 seconds. The CPM effect was calculated as the difference between 2 test-stimuli applications: the conditioned test stimulus minus the stand-alone test stimulus, for each single individual pair of stimuli, obtained at 10, 20, and 30 seconds of test stimuli , and as CPMmean for averaged 3 CPM values. More negative values indicated more efficient CPM. This paradigm of conditioned pain stimulation is routinely used in our laboratory.43Conditioned pain modulation was assessed using the parallel paradigm in which 2 identical test stimuli were given; once before and then simultaneously with a noxious conditioning stimulus. The test stimulus was a tonic noxious contact heat stimulus applied to the volar aspect of the dominant forearm using TSA. The intensity of the test stimulus was predetermined individually based on the psychophysical parameter of Pain60 temperature. This method was based on delivery of several triplets of 7-sec long stimuli of various intensities; the closest temperature that induced pain at a level of 60 on a 0-100 NPS was considered as the Pain60 temperature.35 and anxiety levels .34 The patients with PDN also reported their self-perceived health by filling out a Hebrew version of the short-form 36 (SF-36) Health Survey.20 SF-36 contains the following subscales: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, and social role functioning. Higher scores on each summary scale agree with better general health.At the beginning of the experimental session, all participants completed several pain-related psychometric questionnaires for the assessment of pain catastrophizing P < 0.05. The data are presented as mean (SE) if not indicated otherwise. Statistical analyses were performed using Microsoft Excel  and JMP .The primary interest of this study is to characterize the relationship between pain duration and pain psychophysics. Preliminary examination of data indicated that skewed pain duration data distributions, with some extreme values, would result in problematic Pearson correlations, with extreme points having unacceptably high leverage. Therefore, nonparametric Spearman (rank-order) correlations were performed to test overall monotonicity of relationships between neuropathic pain level and duration and psychophysical measures. To further examine the effect of pain duration on pain modulation profile (PMP) characteristics, additional analyses were conducted by dividing the patients into 2 groups based on the median score of pain duration. The results of 2 subgroups of patients were compared with the control subjects with the addition of age as a covariate, in a regression model. The post hoc analysis was performed to confirm the group differences. The level of significance was set at P = 0.004); therefore, subjects' age was added as a covariate into the regression models.Two patients did not provide full information about their neuropathic pain duration, so the final sample of patients with PDN consisted of N = 33 . Demographic and clinical parameters as well as the values of PCS and STAI of the patients with PDN as well as the results of sensory quantitative sensory assessment are presented in Table P < 0.001); (2) higher severity of the neuropathy as measured by higher CDT  and warm detection threshold , all tested on feet. Because no consistent responses were obtained to the assessment of mechanical detection threshold, these data are not reported. It is important that the pain duration did not correlate with neuropathic pain intensity  or age .Patients with longer pain duration had (1) higher duration of neuropathy  or its temporal segments; CPM10 , and CPM20  or CPM30 . In line, no correlation was found between pain intensity and TS . However, looking at the relationships between pain duration and pain modulation capabilities, we found that patients with longer pain duration had (1) increased efficiency of CPMmean  and CPM20  but not for CPM30 , (2) a trend toward lower TS magnitude .No significant correlations were found between the neuropathic pain intensity and CPMmean  and 20 seconds (CPM20) of the CPM assessment, as compared with short-pain duration patients, and were not different of those from the healthy controls.Patients were divided into 2 groups based on the median split of the pain duration. Patients with pain duration of 2 years or less  were considered as short-pain duration group, whereas patients with pain duration longer than 2 years  were considered as long-pain duration group. The results of 3 group comparisons for psychophysical variables are presented in Table r = 0.055; P = 0.784), anxiety state , or PCS . Comparing the long- and short-pain duration PDN patients with the healthy subjects, no significant group differences were observed for the scores for anxiety state or trait; the PCS scores were significantly higher in the patients with PDN, with no differences between the 2 patient groups , or for the neuropathy severity in terms of foot warm  or cold sensation threshold  . In addition, the short- and long-pain duration patients were not different for any component of the SF-36 Health Survey . In addition, the number of used drug families was similar between short- and long-pain duration patients with PDN .Among the 33 patients, 17 (52%) were currently using pain medications . The proportion of patients on pain medications was not different between the short (10 patients with and 10 patients without medications) and long  pain duration groups , confirming a methodological advantage of shorter CPM assessment.11 Second, less-efficient CPM at early stages of painful neuropathy may suggest higher efficacy of mechanism-based analgesic choice (such as serotonin-norepinephrine reuptake inhibitors) during the first years of the neuropathic pain, whereas other treatment choices may be preferable for the long-time pain sufferers. This approach, however, should be confirmed from a study on a large group of patients with PDN.Our results shed light on 2 additional aspects of potential clinical implication of PMP; first, the significant relationship between pain duration and CPM was restricted to first 20 seconds of dual stimulation (CPM14 However, this issue is far from being conclusive because of contrary findings.38 The other limitation is that this is a cross-sectional study; the ideal design for a study that relates to durations is a longitudinal study. Because no prospective follow-up was designed, we rely on patients' memory as far the durations of both neuropathy and pain, rather than on documented data.Our main study limitation is the quite small sample, which is a general problem in clinical research. In addition, the middle-aged control subjects were significantly younger than the patients with PDN. Although age was included as a covariate in all group comparisons, the younger age of control subjects can be a potential bias for the results on CPM because of several reports on more-efficient CPM at younger ages.To conclude, this is a first report on the association between duration of neuropathic pain and pain modulation. Pain modulation seems to return to normal for longer duration of pain, whereas clinical pain levels seem to persist for a long time, at least in our cohort of patients with PDN. Our findings on the difference of antinociceptive PMP in PDN patients with longer pain duration highlight the significant role of the “time window” in which the assessment of PMP has clinical meaning and should be considered as a factor in treatment choice and evaluation of treatment efficacy.The authors have no conflicts of interest to declare.This study was sponsored by an IIT grant from Eli Lilly Inc.Y. Granovsky contributed to logistics of this study, data analysis, and the manuscript preparation. H. Nahman-Averbuch contributed to data collection. M. Khamaisi contributed to the patients recruitment and consenting. M. Granot contributed to data analysis and the manuscript preparation. All the authors approved the final draft of the manuscript.


To compare the effectiveness of pain relief of Sucralfate and lidocain antacid 50:50 solution in post esophageal variceal band ligation pain.All patients who had under gone Esophageal Variceal Band Ligation (EVBL) were included in the study. Patients un-willing to be included in the study or those who didn’t have post EVBL pain were excluded. Patients with post EVBL pains were divided into two groups: one group was given sucralfate and other was given lidocaine: antacid 50:50 solution. Both were inquired about the duration of the pain relief after the medication. The results were analyzed on SPSS 23. Independent samples T-test was performed to find out whether the difference in duration of pain relief was significantly different in the two groupsOut of 110 patients who have EVBL, 66(60.00%) had pain and 44(40.00%) were pain free. In the pain group 46 (69.7%) were given sucralfate and 20 (30.3%) were given lidocain: antacid 50:50 solution. Mean duration of pain relief in two groups was 2.78 (SD ± 2.096) and 2.5 days (SD ±. 0.76) respectively. Independent samples T-test results revealed that there was no statistically significant difference in the duration of pain relief between these two groups with p value 0.426.Both Sucralfate and Lidocain: antacid 50:50 solutions are effective in relieving the post EVBL pain. However, no statistically significant difference in duration of pain relief was detected in separate groups of patients treated with either treatment. Upper Gastrointestinal bleed secondary to esophageal varices is a life threatening situation in Decompensated Chronic Liver Disease (DCLD). With single bleed mortality increased to 20%, rebleed in 40% in six weeks’ time and 75% at one year.5Post Esophageal Variceal band ligation pain is a common complication, mostly it is mild to moderate in intensity but may be severe in few cases. Usually it settles itself but may require some intervention to relieve it. Esophageal pain is due to stimulation by chemoreceptors due to acid or hyperosmolar substances, mechano-receptors by distension or thermos-receptors by hot and cold food.This study was carried out in combined Military Hospital Kharian that is a tertiary care hospital. Study was carried out from Dec 2014 to September 2015. It was prospective therapeutical trial . Study was approved by ethical committee of the Hospital. Non-probability, purposeful, criterion sampling was done. After the informed consent, procedure of upper G I endoscopy and EVBL was explained. Throat spray with lignocaine 4% solution and conscious sedation with injection midazolam was done. Dose of Midazolam was adjusted keeping underlying disease and age of the patient in mind. Upper GI endoscopy with high definition video endoscope system was performed. Multi-band ligators manufactured by the Wilson-Cook Medical GI endoscopy company were used.All patients who had undergone esophageal variceal band ligation and had post EVBL pain were included and those unwilling to be included or didn’t have pain were excluded. Patients were inquired about the pain as per numeric pain rating scale (N-11).Out of 110 patients with EVBL, 66(60%) experienced post EVBL pain and were selected for the study. Out of the selected 66 patients, 45 (68.2%) were males and 21 (31.8%) females. Minimum age was 12 and maximum 82 years with mean of 53 and SD ± 13.41. Male to female ratio was 2.3:1. Frequencies of Child classes A, B & C of the patients were 35%, 60% and 15% respectively. Out of 66 patients with post-EVBL pain 15 (22.7%) had mild, 43 (65.2%) moderate and 8 (12.1%) severe pain after esophageal variceal band ligation. Main reason for endoscopy in these cases was upper G I bleed followed by screening for esophageal varices and surveillance of EVBL.In the initial 110 patients before case selection total of 255 banding sessions were done, minimum one and maximum of 10 with SD ± 1.31. Mode calculated for the number of sessions was two. 660 bands were applied with average of 6 per session. The selected 66 patients which were randomly divided into two groups, first group 46 (69.7%) were given sucralfate; their response in number of days is shown in Their response distribution in number of days is presented in SPSS version 23 was used for statistical analysis. Independent samples T test was applied at 95% significance level. Keeping “number of days for pain relief response” as independent variable, “type of treatment administered” was selected as the grouping variable. Results were interpreted as follows. T-test for differences in mean between two groups was not significant with p value 0.426. Therefore, no statistically significant difference in duration of pain relief was observed between the two groups.Pharmacological and EVBL is recommended mode of treatment for the control of esophageal variceal bleed.16nd day of post EVBL pain and 41(89.13%) by 4th day. In the 2nd group 13 (65.00%) patients were asymptomatic on 2nd and 100% on 4th day. It points to a quicker and sustained relief in second group on 2nd day and 4th day. 2(5%) patients had response on 10th day in first group and no patient was symptomatic beyond 4th day in the second group that again points more effectivity in lidocain: antacid group. Confounding factor being that the second group was smaller than the 1st one. Ulcers form once the band slough off at post esophageal variceal band ligation site leads to stricture formation and obliterates varices. Ulcers are superficial, resolve faster as compared to sclerotherapy induced ulcers i.e., 14 versus 21 days.In the first group 32 (69.56%) patients were pain free in on 2In the current study, the number of enrolled patients was good enough and study continued for ten months, still there were certain limitations. It was a single center based study and secondly GI cocktail was not easily available and had to be prepared in the hospital Pharmacy. Keeping effectivity of this medicine in post EVBL pain in mind its availability can be stressed upon.Both Sucralfate and lidocain: antacid solutions are effective in post EVBL pain relief. There was no statistical difference in mean pain relief duration between these two groups. However second group has slight edge in early and sustained response. More studies are required to strengthen the findings.


The study aims to validate a previously developed and published combined success criterion for patients after multimodal pain therapy . The criterion classifies treated patients as successful in the long term on the basis of pain severity, disability through pain, depressiveness, and health-related quality of life.Routine longitudinal data of 135 pain patients treated with multimodal pain therapy in 2014–2015 at the Interdisciplinary Pain Center of the University Clinic Erlangen were available at baseline, therapy start, therapy end, and 12 months after treatment. Patients were, on average, 51.0 (SD 11.1) years old and to 63.7% female, two thirds were employed (66.7%). We conducted an analysis of concurrent validity , criterion validity , convergent validity , and discriminant validity , objectivity, and reliability. Statistically, descriptive and inference statistics, graphical methods and MANOVAs were used.p < .001), significantly fewer Disability days (M = 15.31 (SD = 23.15) vs. M = 26.75 (SD = 29.15)); t (133) = 2.308; p = .024, less Anxiety  = 2.972, p = .034), less Stress  = 9.907, p < .001), and better Well-being  = 9.594, p < .001) 12 months after treatment than patients classified as not successful. The Spearman correlation between success classification and Chronicity stage was .094 (p = .280).Patients classified as successful had significantly better values on the 5 variables demonstrating concurrent validity  contains supplementary material, which is available to authorized users. Multimodal pain therapy can be counted as an effective interdisciplinary complex intervention. However, the comparability of results of such therapies has been impaired by a widely heterogenic use of outcome instruments . In factIn the meantime, we used the existing and, to date, consented “German Pain Questionnaire”  to definHowever, the tool for operationalizing success has yet to be validated with long-term data, a shortcoming that has been discussed. Thus, the present study is aimed at validating the previous pilot version of the combined success criterion with long-term (12-month follow-up) data. Furthermore, this validation study also presents additional analyses regarding convergent, discriminant, concurrent, and criterion validity as well as reliability and objectivity. The pilot version published in 2015 reported data on predictive validity and convergent validity with other constructs  .The aim of the study was to validate the core patient-reported-outcome measurement set  for classifying pain patients who received multimodal pain therapy with respect to their long-term success. For validation purposes concurrent validity, criterion validity, convergent and discriminant validity was assessed with objectivity and reliability also being evaluated.The data for the study are routine, longitudinal data from patients at the interdisciplinary pain center of the University Clinic in Erlangen. The patients participated in a semi-inpatient five-week multimodal pain therapy and were assessed by trained pain therapists and with self-report questionnaires at four time points: before the patients began therapy (= at screening), at the start and end of treatment, and 12 months later (= 12-month follow-up). The average time passed between screening and start of therapy was 3 months. To analyze the validity of the combined success criterion, we used the 12-month follow-up data.The data analyzed here were collected within the time frame of January 1, 2014 to June 30, 2015. The term routine data indicates that no extra data were collected for the study. Patients were asked to fill out a paper-pencil questionnaire which took approximately 60 min to complete. At the time points before the therapy and at follow-up, the collection took place at home, while at beginning and end of therapy patients assessments took place during the consultations. Routine data were used in the initial development and publishing of the success criterion [N = 135 was available for analysis. Data from patients with a chronic pain condition followed-up 12 months after enrollment in the 5-week multimodal pain therapy were used to validate the combined success criterion, which was based on patient-reported outcomes. The sample consisted of 63.7% women; the mean age was 51.0 (SD 11.1) years. 85.9% of the patients were German, 5% had a migration background, 62.2% were married, and 80.0% of the whole sample did not live alone. The majority (40.0%) had a general secondary school certificate (9 years) = “Hauptschulabschluss,” and one seventh of the patients had a University diploma (14.1%). The largest part of the sample had completed an apprenticeship (88.3%), and two thirds of the sample were employed (66.7%). However, 36.7% were on sick leave when the data were collected, and more than one fourth of the whole sample was permanently classified as sick and thus not working. A total of 15.6% of the sample received retirement payments. Almost half of the sample was officially recognized as disabled (42.7%), and 10.1% had filed a claim to receive a confirmation for a higher grade of disability. The majority of the patients reported suffering from pain for more than 5 years (39.3%), and an additional one fourth of the sample reported that they had been in pain for 2 to 5 years (24.4%). The mean number of pain days in the 3 months before treatment was 81.9 (SD 21.9), the mean number of physician assessments because of pain was 2.7 (SD 4.0), and the mean number of physiotherapist assessments because of pain was 3.0 (SD 6.0) in the 3 months before multimodal pain therapy. In Additional file A sample of All instruments used in this study were part of the German Pain Questionnaire, a validated collection of scales and items that is used in all pain therapy centers in Germany as part of the core data set assessed for internal and external quality assurance. The instruments we included were negotiated by the “Deutsche Schmerzgesellschaft” section of the “International Association for the Study of Pain” and have been examined in validation studies  was taken and multiplied by 10, yielding a value between 0 and 100 , which is reported to have satisfactory internal consistency values and also an acceptable retest reliability .We assessed depressiveness with a self-report scale that is part of the DASS  conWe assessed anxiety with a self-report scale that is also part of the DASS , 13 consWe used the third subscale of the DASS , 13 to aWe assessed the subjective habitual well-being of the pain patients with the FW-7  , 15, a sWe assessed patients’ physical- and mental-health-related quality of life with a short form of the SF-36 called the SF-12 . The SF-We assessed self-rated therapy success at follow-up with a single item: “If you look at it altogether, how do you judge the success of your treatment with us up to now?” The patient chooses one out of five Likert-scaled answer categories.We summed the number of co-morbidities that were diagnosed by trained pain therapists  and coded as ICD-10 diagnoses. Only psychic co-morbidities were included. The main diagnosis (not co-morbid) was always the predominant chronic pain condition.We assessed chronicity of pain with the Mainz Pain Staging Scale (MPSS) from Gerbershagen , 22. ThiN = 22 patients using the EM-algorithm [The analysis computed for the validation was based on a data set of 135 cases analyzed with SPSS 21. We imputed individual missing data values for lgorithm –26. ThosIn order to classify the sample according to the dichotomous success criterion (responder/non-responder after 12 months), we computed change values (mean and SD) between the 12-month follow-up and the start of therapy. Each individual was assessed for whether he or she improved by ½ SD or more for each of the five single criteria that were incorporated into the combined success criterion . After that, for each individual, we computed the number of single criteria for which the improvement was clinically relevant (at least ½ SD). All patients who showed improvement on four or all five of the single criteria that were used to create the combined success criterion were counted as “responders” or as “successful” and were coded as 1 on the final success criterion variable. All others were classified as “non-responders”/“not successful” and coded as 0 . The reaTable The previously published combined success criterion incorporating the five domains of pain severity, pain disability, depressiveness, and health-related quality of life  defines success if at least 4 out of the 5 single criteria have improved at least ½ standard deviation . Here, tThe mean changes (therapy start to follow-up) for all 135 patients were − 9.4 (SD 18.49) for pain severity, − 1.04 (SD 1.98) for disability through pain, − 2.10 (SD 5.07) for depressiveness, + 5.40 (SD 8.18) for physical-health-related quality of life, and + 2.71 (SD 10.34) for mental-health-related quality of life from the start of therapy to the 12-month follow-up. The success rate 12 months after therapy using the criterion was 24.5%. The two most successful single criteria were change in pain severity and increase in physical-health-related quality of life – about half of the treated patients showed a clinically relevant improvement on these two variables 12 months after they completed multimodal pain therapy  were compared with patients who were not classified as showing long-term success. Conceptually, the successful patients should have better values on each of the five single domains of Pain severity, Pain disability, Depressiveness, and Health-related quality of life  at the 12-month follow-up. This comparison is shown in Table p < .001). The mean change in Pain disability was −.32 (SD 1.53) for non-responders and − 3.28 (SD 1.44) for responders (t (133) = 9.786; p < .001). The mean change in Depressiveness was −.70 (SD 4.51) for non-responders and − 6.44 (SD 4.22) for responders (t (133) = 6.462; p < .001). The mean change in Physical-health-related quality of life was + 3.39 (SD 7.32) for non-responders and + 11.61 (SD 7.62) for responders (t (133) = − 5.546; p < .001); for Mental-health-related quality of life, it was −.12 (SD 8.92) for non-responders and + 11.47 (SD 9.60) for responders (t (133) = − 6.368; p < .001).The mean change (therapy start to follow-up) in Pain severity was − 4.31 (SD 16.21) for non-responders and − 24.95 (SD 16.44) for responders (t (133) = 6.334; p < .001). Thus, each of the five single criteria alone was sensitive enough to reflect the differences between patients who were classified as successful versus not successful in the long term.In conclusion, 12 months after therapy, patients classified as successful showed significantly lower values on Pain severity, were significantly less disabled through their chronic pain condition, were significantly less depressive, and had significantly higher Mental- and Physical-health-related quality of life .For one measure of criterion validity, we conducted a comparison of responders/non-responders concerning the item “If you look at it altogether, how do you judge the success of your treatment with us up to now?” The self-rated success should show a clear association with the classification of being a responder or not via the combined success criterion. This was the case as Fig. We also used a second measure of criterion validity: Disability days at the 12-month follow-up. To reflect validity, the patients classified as successful would have significantly fewer Disability days (in the last 3 months) than patients classified as non-responders.p = .024) 1 year after therapy.The t-test showed that the mean number of Disability days  in the group of responders was significantly lower than the mean number of Disability days in the group of non-responders ; (t (133) = 2.308; We examined convergent validity with the help of three constructs: Stress, Anxiety, and Well-being. These constructs are not inherently the same as Pain variables, Depressiveness, or Quality of life  but are related to the single criteria that make up the combined success criterion  and a significant interaction between Responder and Stress level over Time  = 9.907, p < .001). A main effect of the variable Responder could not be shown  = 2.004, p = .159) because, conceptually, a significant main effect diminishes or is not interpretable when a significant interaction effect exists. These results indicate that the stress level decreased in both groups during the time they were in therapy, but in the group of patients classified as not successful, the stress level increased again after the therapy ended. The main and interaction effects are depicted graphically in Fig. A MANOVA with the target variable Stress, the within-subject factor “Time” , and the between-subject variable “Responder” (yes/no) showed a significant effect of Time  = 29.625, , 131 = 2p = .001) and a significant interaction between Responder and Anxiety level over Time  = 2.972, p = .034). As expected from this interaction effect, the main effect of the Responder variable was not significant  = .506, p = .478). While the anxiety level of the responders decreased on a clinically relevant level during therapy and continued to fall slightly in the 12 months after therapy, the anxiety level of the patients classified as not successful showed a rather different trajectory , and the between-subject variable “Responder” (yes/no) also showed a significant effect of the inner subject factor Time  = 5.825, p < .001) and a significant interaction between Responder and the Well-being level over Time  = 9.594, p < .001). Again, due to the detection of an interaction effect, the main effect of the Responder variable was not interpretable or was nonsignificant  = 1.830, p = .178). In the 12 months until the follow-up assessment, the level of well-being was stable for the patients classified as successful, whereas the other group showed a loss in well-being between the end of therapy and the 12-month follow-up  = 97.626, Thus, for the variables Stress, Anxiety and Well-being we were able to demonstrate convergent validity of the combined patient-reported-outcome criterion.The combined success criterion for multimodal pain therapy based on patient-reported outcomes should conceptually not be related to the Chronicity stage of pain that characterizes patient collectives  and shoup = .280) and non-significant. Alternatively, the contingency coefficient was .114 (p = .618), which is also non-significant. The Gerbershagen Chronicity sum score, a second measure of chronicity, was also very weakly correlated with the combined success criterion (Eta = .110).The Spearman correlation coefficient between the Chronicity stage according to Gerbershagen and the responder variable (0/1) was .094 (p = .913). Alternatively, the Eta coefficient was .017. This is also a very weak/zero correlation.The Spearman correlation coefficient between the number of psychic comorbidities and the responder variable was .009  was in the lower range, whereas the inferential statistics showed a very clear difference between the patients classified as successful and those classified as not. This could be due to the large variance in the sample depicted in the standard deviations. On the other hand, correlation values between disability constructs and pain outcome measures close to .2 have also been reported in the literature: Wong and colleagues  validateThe success criterion was comprised of five single criteria , each of which was assessed with a widely used and validated scale. For each scale, the procedures guaranteed the objective assessment of the construct.Each of the five scales operationalizing the five single criteria has standardized instructions concerning the handling of the single items and the generation of sum scores/standardized values.The published algorithm  that conThe combined success criterion for multimodal pain therapy fulfilled the measures of objectivity for a) Implementation -, b) Evaluation - and c) Interpretation objectivity:The measurement of constructs such as pain severity as implemented in the German Pain Questionnaire has weaknesses as shown by a study that was conducted from the patient perspective . This deThe analysis of validity and the outcome measurement itself were based on routine data as implemented in the routine care of multimodal pain therapy patients at the treatment center of the University Clinic Erlangen. On the one hand, this was an advantage because data were available on all treated patients, but this was also a disadvantage due to the inflexibility of the variable set. The variables available for analysis were strictly bound to the implemented German Pain Questionnaire, and other potentially interesting constructs for testing validity were not available for analysis. For example, it would have been interesting to evaluate the success classification against a clinical rating of a patient’s success made by a treatment expert.Data of the validation study are based on one center. Thus the population of the pain treatment center in Erlangen cannot be seen as representative for all pain patients in Germany, especially since the treatment structure varies between in-patient and semi-in-patient multi-modal pain therapy within the therapy offers of the German Pain Centers.Only patients’ self-ratings were available to operationalize long-term success. For a closer look at the health-economic perspective, it would be desirable to validate the criterion against objective data such as sick days. The question that could be asked would be whether patients classified as successful have significantly fewer sick days as a facet of criterion validity. In Germany, such data are administered and protected by health insurance companies. Thus, it was not possible to include such data in the routine data assessment 1 year after treatment. Of course, self-administered questionnaires and thus ratings of patients’ health status underlie multiple influences  and have the potential to be affected by judgment biases.This study was not an efficacy or effectiveness study of multimodal pain therapy. Without a controlled design, it would not be appropriate to discuss the positive effects of multimodal pain therapy. The manuscript has to be understood as focusing on the validation of a classification measure based on a core outcome set used in multimodal pain therapy - even though there are hints about which constructs might be affected by multimodal pain therapy. The results concerning the associations of success with certain constructs were completely in line with the efficacy/effectiveness literature, and this is thus a sign that the multimodal pain therapy itself works as expected.Even though this study is not about efficacy, it is among the few studies that have even reported a precise number of patients who can be seen as showing successful treatment in the long run. By defining a classification measure that groups treated patients into responders and non-responders a definite number of how many patients are classified as clinically relevantly improved results. Because multimodal therapies are important and are accepted, it is just and equitable to name and discuss the frequency of success. The rate of one fourth of the treated patients showing a clinically relevant improvement for at least 1 year after a semi-inpatient treatment is comparable to rates that have been achieved in other in-patient rehabilitation treatments with chronic patients, for example, in addiction treatment where the long-term success rate is about 32% .The strength of the study is that it delivered one measurement that included five different outcome domains for pain patients a) that allowed us to classify patients into those who were successfully treated or not and b) were based on the most frequently used outcome domains in multimodal pain therapy thus far as identified by a systematic review . The meaThe algorithm is easy to use, considers clinically relevant changes, is based on a widely used, methodological agreed-upon amount of change, has demonstrated its predictive value before , and nowBy being able to classify patients as successful in the long term, an analysis of predictors of long-term success is possible. It generates new knowledge that is still incomplete for multimodal pain therapy about who profits and what factors are protective/resources for long-term success.As a result of this analysis, one could adapt the allocation of treatment processes especially in the light of undersupply. As Ruan et al.  reportedA closer analysis of the three quarters of the patients classified as less successful or not successful is possible and should be undertaken. The goal would be to identify factors that hinder long-term success and consequently provide information about how to appropriately adapt therapy routines and manuals. Kopf and Gjoni  emphasizThe use of the algorithm can be seen in the foreground in the following three fields of action:The study aimed to validate a core outcome measure set that is based on patient-reported-outcome measures (PROMs) for use in multimodal pain therapy. The results of the validation analysis allow judging this success criterion as valid in operationalizing clinically relevant improvements. Thus, it can be seen as a step in answering questions of assessment of efficacy and effectiveness of multi-modal pain therapy depicted in the widely heterogenic use of outcome instruments. Furthermore, future research can build on this research to develop a set of predictors of success in multi-modal pain therapy.Additional file 1:N = 133. (DOCX 14 kb)Baseline characteristics of the sample – group-specific analysis for patients classified long-term successful and not sucessful. Description of data: table showing group-specific sample description (descriptive statistics) for