Background. Obstetrics and gynecological conditions (OB-GYNc) are difficult to be differentiated from appendicitis in young adult females presenting with acute lower abdominal pain. Timely and correct diagnosis is clinically challenging. Method. A retrospective data analysis was performed on 542 female patients who were admitted to a tertiary care hospital with a chief complaint of acute lower abdominal pain. Diagnostic indicators of appendicitis and OB-GYNc were identified by stepwise multivariable polytomous logistic regression. Diagnostic performances of the scores were tested. Result. The developed clinical score is comprised of (1) guarding or rebound tenderness, (2) pregnancy, (3) sites of abdominal tenderness, (4) leukocytosis, (5) peripheral neutrophils ≥75%, and (6) presence of diarrhea. For diagnosis of appendicitis, the area under the ROC curve was 0.8696, and the sensitivity and specificity were 89.25% and 70.00%. For OB-GYNc, the corresponding values were 0.8450, 66.67%, and 94.85%, respectively. Conclusion. The clinical scoring system can differentiate the diagnosis of acute lower abdominal pain in young adult females. Time spent for diagnosis at the emergency room may be shortened, and the patients would be admitted to the appropriate departments in less time. Diagnosis of acute lower abdominal pain in young adult female is a clinical challenge. Appendicitis and obstetrics and gynecological conditions (OB-GYNc), such as ectopic pregnancy, pelvic inflammatory diseases, and complicated ovarian cyst, are common causes of acute lower abdominal pain in females during reproductive age . AccuratEmergency physicians play an important role in early diagnosis and prompt management of the conditions. Experienced emergency physicians can detect important clinical findings and give a provisional diagnosis to a patient before transferring her to general surgery or obstetrics and gynecology departments according to their judgment. Previous studies showed that some clinical indicators were helpful to distinguish appendicitis and common obstetrics and gynecological conditions (OB-GYNc) from nonspecific abdominal pain (NSAP) .To resolve the difficulty in diagnosis of acute lower abdominal pain in female patients, whose appendicitis is confounded by OB-GYNc, imaging studies had been done. Imaging investigations such as ultrasonography, computerized tomography (CT), and magnetic resonance imaging (MRI) have high accuracies in diagnosis of acute lower abdominal pain , 5. HoweClinical diagnostic scoring, on the other hand, may be more appropriate for early diagnosis in an emergency department setting. Clinical scoring for diagnosis of appendicitis was studied for its application as a guideline used for admission and investigations , 8. HoweThe objective of the present study was to develop a clinical scoring for diagnosis of acute lower abdominal pain in females of reproductive age that could either have appendicitis, OB-GYNc, or NSAP.We studied medical records of women aging between 15 and 50 years who were admitted to a surgical or obstetrics and gynecology department of a university affiliated tertiary care hospital, with a chief complaint of acute lower abdominal pain within 14 days during January–December 2008. Patients were categorized into 3 groups by their final diagnoses upon discharge. The first group was appendicitis (ICD-10 code K-35), the second group was obstetrics and gynecological conditions (OB-GYNc), such as ectopic pregnancy (ICD-10 code O-00), pelvic inflammatory disease (ICD-10 code N70), and complicated ovarian cyst (ICD-10 code N83). The third group was nonappendicitis and non-OB-GYNc  which was classified as nonspecific abdominal pain (NSAP). The diagnostic criteria for appendicitis were the presentation of any gross inflammation of appendix in operative records or successful conservative treatment with antibiotics in appendiceal abscesses. All medical records were reviewed for operative records, pathological reports, imaging studies, and follow-up records to ascertain their final diagnoses.Patients' characteristic , characteristics of pain and associated symptoms , and the presence of pregnancy and abnormal vaginal bleeding were reviewed. Body temperature, systolic blood pressure, location of abdominal tenderness, and presence of guarding or rebound tenderness on the first admission day were recorded. Initial laboratory results of complete blood count  and urine pregnancy test were noted. All these clinical indicators were studied for their predictive potential of the final diagnoses.We had an assumption that the pattern of missing data was missing at random (MAR). Therefore, the multiple imputation method was used in data analysis. We imputed missing data 20 times using the multivariate normal regression method. The imputation model variables included all nonmissing variables and outcome variables .P values less than 0.05 in one or both diagnoses. Item scores for appendicitis and OB-GYNc were derived from polytomous logistic coefficients of the corresponding diagnosis. We compared the sum of item scores for each diagnosis as the representative of diagnostic possibilities and designed an algorithm for prediction of diagnosis by the scoring system.The predictive model for prediction of final diagnosis of appendicitis or OB-GYNc was derived from manual backward stepwise polytomous logistic regression with multiple imputation estimation method, by using NSAP as the base outcome. Nonsignificant clinical diagnostic indicators were manually removed from the model until the remaining coefficients were significant at Performance of the scoring system was tested with the complete data set. Areas under the receiver operating characteristic (ROC) curves were calculated from disease-specific logistic models to determine discrimination abilities of the score. Accuracy of the scoring system was tested by comparing diagnosis suggested (predicted) from the scoring system with the final (true) diagnosis of patients, and diagnostic indices were calculated.This study was approved from the Ethical Committee of the Faculty of Medicine of Chiang Mai University and the Ethical Committee of Nakornping Hospital.n = 31), enteritis/gastroenteritis (n = 21), diverticulitis (n = 5), urinary tract infection (n = 2), radiation enteritis (n = 2), ileitis (n = 1), and twisted omentum (n = 1). There were 453 patients who underwent surgery, 362 of appendicitis, 69 of OB-GYNc, and 22 of NSAP. Twenty of appendiceal abscesses were treated with antibiotics without surgery. Clinical diagnostic indicators with missing data were: pulse rate (1.6%), systolic blood pressure (1.8%), hematocrit (12.9%), white blood cell count (23.2%), and percentage of neutrophil (26.0%). Significant differences between diagnosis groups were seen in diagnostic indicators of shifting of pain, anorexia, nausea and vomiting, diarrhea, abnormal vaginal bleeding, body temperature, pulse rate, systolic blood pressure, site of abdominal tenderness, guarding or rebound tenderness, hematocrit, white blood cell count, percentage of neutrophil, and pregnancy . The item score of each clinical indicator for diagnosis of appendicitis or OB-GYNc derived from polytomous logistic coefficients  tenderness, pregnancy, left lower quadrant (LLQ) tenderness, presence of diarrhea, and leukocytosis  of appendicitis score for diagnosis of NSAP was 0  for diagnosis of appendicitis was 3.3 , and for diagnosis of  OB-GYNc was 1.3. The median (p25 and p75) of OB-GYNc score for NSAP was 0 , 1.6  for appendicitis, and 2.4  for the diagnosis of OB-GYNc . Areas uBy the concept of relative probabilities, an algorithm for diagnosis from the scoring system was created . When usThe scoring system had a sensitivity of 89.25%, a specificity of 70.00%, and a likelihood ratio of positive test of 2.97 in diagnosis of appendicitis. For diagnosis of OB-GYNc, the scoring system had a sensitivity of 66.67%, a specificity of 94.85%, and a likelihood ratio of positive test of 12.94 .P-value of 0.270  of Alvarado's score were 6.19 ± 1.77 for appendicitis, 3.94 ± 2.06 for OB-GYNc, and 3.78 ± 1.63 for NSAP, respectively. At the “cut-off” point at 7, Alvarado's score yielded a sensitivity of 49.8%, a specificity of 90.7%, and a likelihood ratio of positive test of 5.34 for diagnosis of appendicitis. When comparing our appendicitis score and Alvarado's score in their abilities to discriminate appendicitis and “nonappendicitis,” the area under ROC of our appendicitis score was 0.8257  and the area under ROC of Alvarado's score was 0.8095 . The two areas under ROC were not significantly different at a of 0.270 .Acute lower abdominal pain in young adult females is a diagnostic challenge for general surgeons, gynecologists, and emergency physicians. Although ultrasonography and CT scan can increase diagnostic accuracy , 9, 10, The combination of clinical features and laboratory tests or clinical indicators is useful for the diagnosis of patients' conditions. Mathematically, these clinical indicators can be assigned as scores for diagnosis of difficult conditions. Alvarado's score, for example, was studied for the diagnosis of appendicitis in patients with abdominal pain with good results –17. HowePolytomous logistic regression had been studied for the diagnosis of conditions that can have more than two possibilities , 19. It If we use the present scoring system for diagnosis of acute lower abdominal pain in women of reproductive age, there would be “overdiagnosis” of appendicitis in 36 of 285 patients  while “underdiagnosis” of appendicitis would be observed in 30 of 279 patients. However, a caution should be made to be aware of the scoring system diagnosis of NSAP because of the high risk for appendicitis and OB-GYNc. These patients should be subjected to close observation or further investigations.Ultrasonography was also performed in uncertain cases in our institute. The results of ultrasonography were helpful in some cases, especially for diagnoses of OB-GYNc. There were 139 patients who underwent ultrasound in this study. Final diagnoses of OB-GYNc correlated well with ultrasound results . However, only 28 of 48 appendicitis patients were correctly diagnosed by ultrasound.The problem of appendicitis in pregnancy was one caution in using the present scoring system. Of the 37 pregnant women with acute lower abdominal pain in the complete data set, all were categorized into OB-GYNc, which would be correct in 30 of them. However, 4 of them were appendicitis and 3 were NSAP. Therefore, investigation such as ultrasound might be of value for pregnant women with acute lower abdominal pain. Appendicitis should be suspected in pregnant women with right iliac fossa pain unless other causes of pain are evident.The present scoring system has an advantage of high specificity and high negative predictive value in the diagnosis of OB-GYNc. This could help for ruling out OB-GYNc without further consultation with gynecologists, which may save some extra time in the emergency department. One disadvantage of the scoring system is the need to doubly compute both appendicitis score and OB-GYN score for comparison. However, an electronic calculator can be designed for such purpose.Some limitations in this study should be taken into consideration. The incompleteness of lower abdominal pain patients was likely, because patients from the internal medicine department were not included. As our routine practice, the emergency department staff would transfer a young adult female with acute lower abdominal pain to either surgical department or obstetrics and gynecology department rather than to the department of internal medicine or other departments. This preselection may limit the present results to be generalized to other emergency departments. In normal practice, it would be difficult to preselect some patients with overlapping symptoms of abdominal pain. This might possibly explain the low number of patients with diverticulitis or other nonsurgical conditions in our study.It may also be difficult to generalize the present scoring system to other settings, as it was derived from a tertiary care hospital. The clinical signs and symptoms of early presenting cases at primary settings may be quite different. The retrospective nature of the study may also limit its generalization. A prospective evaluation of the score in different settings should be conducted before it is used in routine clinical practice.The present clinical scoring system can help clinicians distinguish appendicitis and OB-GYNc from NSAP in child-bearing age women with acute lower abdominal pain. It may be used as a guideline for admitting patients to the general surgery or the obstetrics and gynecology wards or requesting further investigations. However, validation of the scoring system is needed before being used in clinical practice.


Study subjects were followed through 6 months posttreatment. Zurich Claudication Questionnaire (ZCQ) symptom severity scores improved 30% with Superion and 25% with X-STOP (both P < 0.001). Similar changes were noted in ZCQ physical function with improvements of 32% with Superion and 27% with X-STOP (both P < 0.001). Mean ZCQ patient satisfaction score ranged from 1.7 to 2.0 in both groups at all follow-up visits. The proportion of subjects that achieved at least two of three ZCQ clinical success criteria at 6 months was 75% with Superion and 67% with X-STOP. Axial pain decreased from 55 ± 27 mm at pretreatment to 22 ± 26 mm at 6 months in the Superion group (P < 0.001) and from 54 ± 29 mm to 32 ± 31 mm with X-STOP (P < 0.001). Extremity pain decreased from 61 ± 26 mm at pretreatment to 18 ± 27 mm at 6 months in the Superion group (P < 0.001) and from 64 ± 26 mm to 22 ± 30 mm with X-STOP (P < 0.001). Back function improved from 38 ± 13% to 21 ± 19% with Superion (P < 0.001) and from 40 ± 13% to 25 ± 16% with X-STOP (P < 0.001). Preliminary results suggest that the Superion interspinous spacer and the X-STOP each effectively alleviate pain and improve back function in patients with moderate LSS who are unresponsive to conservative care.A prospective, randomized, controlled trial was conducted to compare clinical outcomes in patients treated with an investigational interspinous spacer (Superion) versus those treated with an FDA-approved spacer (X-STOP). One hundred sixty-six patients with moderate lumbar spinal stenosis (LSS) unresponsive to conservative care were treated randomly with the Superion ( Lumbar spinal stenosis (LSS) is defined as a narrowing of the lumbar spinal canal and/or the intervertebral foramina due to disc degeneration, bulging of the annulus, facet joint hypertrophy, and/or thickening of the ligamentum flavum –3. This Nonsurgical management options such as activity modification, physical therapy, anti-inflammatory drugs, and epidural steroid injections represent the standard of care for initial treatment of mild claudication symptoms. The long-term effectiveness of these nonsurgical treatments is limited, however, since none hinders the progression of the disease –9. This Decompression surgery is often recommended to patients with severe claudication symptoms who fail conservative care. In fact, surgery is performed on 21% of patients within 3 years of an LSS diagnosis . HoweverImplantation with a minimally invasive interspinous spacer is an alternative treatment option for patients with mild to moderate neurogenic intermittent claudication secondary to LSS. An interspinous spacer is implanted between contiguous spinous processes and acts to limit back extension at the symptomatic level. The rationale for the utility of these devices is that low back pain secondary to LSS is often alleviated when patients flex their lumbar spine and is exacerbated with spinal extension . AlthougThis prospective, multicenter, randomized, controlled, FDA-IDE trial enrolled 166 patients  from 22 sites in the United States from September 2008 to December 2010. All research procedures performed in this trial were in strict accordance with a predefined protocol that was approved by all researchers and the institutional review board at each respective site. The procedures used in this clinical trial were in accordance with the recommendations of the Helsinki Declaration, and each patient gave written, informed consent before surgery. This trial is registered under ClinicalTrials.gov number NCT00692276.Inclusion criteria for this trial included (a) age ≥45 years, (b) persistent leg, buttock, or groin pain, with or without back pain, which was relieved by lumbar flexion, (c) symptomatic and undergoing unsuccessful conservative treatment for at least 6 months, (d) diagnosis of moderate LSS, defined as 25% to 50% reduction in lateral/central foramen diameter compared to adjacent levels, and radiographic evidence of thecal sac and/or cauda equine compression, nerve root impingement by either osseous or nonosseous elements, and/or hypertrophic facets with canal encroachment, (e) Zurich Claudication Questionnaire Physical Function score ≥2.0, (f) able to sit for 50 minutes without pain and to walk ≥50 feet, and (g) able to provide voluntary informed consent and to comply with the study procedures.2, (i) previous lumbar spine surgery, (j) pregnant or lactating female, and (k) any disease or condition that, in the investigator's opinion, may affect subject safety or confound trial outcomes.Exclusion criteria included (a) LSS at three or more levels, (b) concomitant surgical procedure required, (c) grade II to V spondylolisthesis, (d) unremitting back pain in any spinal position, (e) significant lumbar instability, defined by ≥3 mm translation or ≥5° angulation, (f) active systemic disease that may affect the welfare of the patient, (g) vertebral osteoporosis or history of vertebral fracture, (h) body mass index ≥40 kg/mSubjects were treated randomly with the superion interspinous spacer system  or the X-STOP Interspinous Process Decompression System . The Superion device Figures  is an inThe X-STOP device was approved for use in the United States by the FDA in November 2005 and served as the control device in this trial. The X-STOP device has been described in detail elsewhere .Baseline assessments included a complete physical examination, medical history, and study eligibility based on the inclusion/exclusion criteria. Preprocedural radiographic assessments included X-rays  and magnetic resonance imaging or computed tomography of the lumbar spine. The Zurich Claudication Questionnaire (ZCQ) was utilized to assess patient-reported measures of symptom severity, physical function, and patient satisfaction . ExtremiP < 0.001). The supraspinous ligament was longitudinally dissected at the symptomatic level and then dilated to ensure adequate room to maneuver within the interspinous space. A cannula was inserted over the dilator and proper alignment and depth were ensured before dilator removal. Next, an interspinous gauge was inserted through the cannula to determine proper implant size selection, and final midline positioning was confirmed under fluoroscopy. The appropriately sized spacer was delivered through the cannula using a device inserter that loaded, inserted into the interspinous space via the cannula, and deployed the implant. Proper device placement was confirmed with fluoroscopy. Finally, the inserter and cannula were removed, and the incision was sutured in a standard fashion. Proper postoperative placement of the Superion device is illustrated radiographically in Figures Despite minor differences in the surgical technique for insertion of these devices, the procedures are quite similar and are collectively described hereafter. Subjects were laid prone on a radiolucent table with the lumbar spine in a neutral or slightly flexed position. Under fluoroscopic guidance or direct visualization, the surgical level was identified and a midline incision was made  X-rays. The ZCQ, extremity and axial pain severity, and back-specific functional disability were assessed at 6 weeks, 3 months, and 6 months. The FDA-mandated primary endpoint of this IDE clinical trial is 2 years, with postmarket surveillance scheduled for 10 years.The sample size for this noninferiority trial was estimated by assuming a 2-year overall success rate of 62.5% with the Superion device, a 60% success rate with the X-STOP device, 90% statistical power, and a noninferiority margin of 10%. Based on these assumptions, 300 to 600 total subjects (depending on enrollment time) were required using a Bayesian adaptive approach. This paper describes the preliminary outcomes of the first 166 subjects enrolled in this clinical trial.Randomization was achieved by using a computer-generated master randomization list of treatment assignments using a 1 : 1 allocation. Sites utilized a web-based system to obtain randomization assignment before each subject was enrolled. Treatments were not concealed to investigators, outcome assessors, or trial participants.Data were analyzed using Predictive Analytics Software . Continuous data were reported as mean ± SD and categorical data were reported as frequencies and percentages. Longitudinal changes in clinical outcomes were assessed with two-way (time-by-treatment) repeated measures analysis of variance. Area under the curve (AUC) was calculated for pain severity and back function scores according to the methodology of Matthews et al. . Brieflyn = 12), declining to participate (n = 5), or other reasons (n = 2). Ultimately, 80 subjects were treated with the Superion device and 86 were treated with X-STOP. At the time of this analysis, 66 subjects  had passed the 6-month followup visit window.A total of 185 subjects were randomized in this clinical trial—90 to Superion and 95 to X-STOP . ApproxiBaseline subject characteristics , device P < 0.001) (P < 0.001) (ZCQ symptom severity scores improved 30% with Superion and 25% with X-STOP through 6 months (both < 0.001) . Similar< 0.001) . The mea< 0.001) . The pro< 0.001) .P < 0.001). Subjects treated with the X-STOP device realized axial pain median improvements of 64% (P < 0.001), from 54 ± 29 mm at pretreatment to 32 ± 31 mm at 6 months  reductions in extremity pain severity through 6 months posttreatment. Superion subjects improved from a score of 61 ± 26 mm at pretreatment to 18 ± 27 mm at 6 months, a 93% median decrease. Subjects treated with the X-STOP device improved from 64 ± 26 mm at pretreatment to 22 ± 30 mm at 6 months, an 81% median decrease  through 6 months posttreatment with the Superion device (38 ± 13% to 21 ± 19%) while improvements were 38% (40 ± 13% to 25 ± 16%) with X-STOP (P < 0.001) (Back function improved a median of 48% (< 0.001) . The bac< 0.001) . No rela< 0.001) .in situ. Spinal process fracture was noted in one subject.Device-related complications were note in 7 patients per treatment group through 6 months followup. In patients treated with the Superion device, 4 explants were performed between 1 and 4 months posttreatment due to persistent pain. Two revisions were performed—a foraminotomy at 4 months and a left-side decompression at 5 months with the Superion device left In patients treated with the X-STOP, two explants were performed following device dislodgement at 1 month and evidence of lumbosacral disc herniation at 4 months, respectively. Spinal process fracture was noted in three subjects, wound infection requiring readmission in one subject, and a nerve root block for persistent pain at 4 months.Short-term clinical outcomes following implantation with the Superion interspinous spacer system demonstrate amelioration of low back and leg pain and improvements in back function in patients with LSS who are unresponsive to conservative treatments. The Superion device is a promising therapeutic option in patients with moderate LSS with 6-month clinical outcomes similar to those achieved with the FDA-approved X-STOP device.P < 0.001). Extremity pain severity similarly decreased from 6.6 ± 1.4 at pretreatment to 2.8 ± 1.5 at 1 year, reflecting a 53% overall improvement (P < 0.001). Back function improved from 60 ± 8% at pretreatment to 21 ± 14% at 1 year, representing a 64% (P < 0.001) improvement. For comparison, median percent improvements 6 months following implantation with the Superion device in the current trial were 70%, 93%, and 48% for axial pain, extremity pain, and back function, respectively.The clinical outcomes with the Superion device in this clinical trial are comparable to those reported in the study of Bini and colleagues who reported 1-year outcomes of 52 patients treated with the Superion device for moderate LSS . In thatDespite significant pain relief following implantation with the Superion device, the mode of action with interspinous spacers remains controversial. Potential mechanisms include widening of the lumbar spinal canal and increases in disc heights via indirect decompression and reductions in intervertebral mobility although these have not been reliably demonstrated. A cadaver study demonstrated that implantation of the Superion device prevents supraphysiological motion at the symptomatic level and has no adverse impact on the local anatomy . HoweverA limitation of this clinical trial was the relatively short-term followup period. Subjects in this trial will, however, continue to be followed through 10 years posttreatment. In addition, these preliminary results should be interpreted with caution since total enrollment is anticipated to exceed 300 subjects. Blinding was not utilized in this trial and, therefore, the potential for ascertainment bias should be considered. Importantly, interspinous spacers are appropriate only for patients that meet strict clinical and radiographic criteria. Finally, we report no radiographic range of motion data and, therefore, cannot comment on the mechanism of improvement observed in these patients.In conclusion, the Superion and X-STOP interspinous spacers effectively ameliorate pain and improve back function through 6 months in carefully selected patients with moderate LSS who are unresponsive to conservative care.


A fundamental characteristic of neural circuits is the capacity for plasticity in response to experience. Neural plasticity is associated with the development of chronic pain disorders. In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP patients experienced high intensity LBP as compared with the low intensity condition. In addition, we also found increased cortical thickness in the bilateral S1 somatotopically associated with the lower back in cLBP patients as compared to healthy controls. Our results provide evidence of structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP patients. Chronic low back pain (cLBP) is one of the most common reasons for all physician visits in the USA and is a leading cause of disability ,2. The eRecent neuroimaging studies -11 have In addition to changes in brain function, multiple morphometric imaging studies report structural changes in the brains of patients with cLBP -21. For Few studies have been performed to simultaneously investigate the functional and structural changes in a single study. In one of the few such studies, Seminowicz and colleagues  found thIn this study, we investigated 1) brain resting state FC differences between cLBP patients and matched HC; 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain (before and after exercise maneuvers), and 3) morphometric differences between cLBP patients and matched HC. There are multiple methods to perform FC; here, we applied a whole-brain voxel-by-voxel hub FC method described in previous studies ,26. The We believe that a combined investigation of both structure and FC changes between cLBP patients and HCs, as well as the dynamic change of FC when cLBP patients were experiencing different endogenous low back pain intensities, will shed new light on our understanding of pathophysiological mechanism, adaptation and reorganization of brain structure and function in chronic pain conditions.18 cLBP patients  and 18 healthy controls, matched for age and gender, completed the study. The Institutional Review Board at Massachusetts General Hospital approved the study and all subjects gave written informed consent.All patients were clinically diagnosed with nonspecific cLBP with a duration of at least six months by a clinical evaluation, including the use of X-ray/MRI reports, when available. Only those patients meeting Quebec Low Back Pain Task Force classification criteria for Classes I or II were enrolled . For insMedication use per self-report was limited to non-steroidal anti-inflammatory drugs  and acetaminophen . Additional non-pharmacological methods of self-reported pain management included chiropractic massages, physical therapy, exercises, and acupuncture.All MRI data were acquired with a 3T Siemens whole-body scanner with echo-planar imaging capability using a 32-channel radio-frequency head coil at the Martinos Center for Biomedical Imaging. During the resting state fMRI scan, subjects were asked to keep their eyes open and look at a darkened screen for 6 minutes. The BOLD fMRI scan acquisition included 47 slices with slice thickness of 3 mm, TR 3000 ms, TE 30 ms, and a 3×3 mm in-plane spatial resolution. T1-weighted MPRAGE type structural images were acquired using the following parameters: voxel size 1.2×1.2×1.2 mm, TR, 2.2 s, TE, 1.54 ms, flip angle: 7 degrees, slices: 144; field of view: 230. Before and immediately after each 6 minute scan, subjects were asked to rate the intensity of their LBP using the 0–10 pain scale.After the first resting state scan, cLBP patients were taken out of the scanner to perform exercises for a period lasting up to 10 minutes to exacerbate their endogenous lower back pain. These exercises were tailored to each patient based on their report of which movements exacerbated their pain. They included lumbar flexion and extension exercises, sit-ups, or lumbar rotation exercises, where the subject rotated his or her body from side to side at a self-selected speed. The patients were required to perform their exercise(s) slowly, and at maximum flexion/extension, such that they might feel the exercise trigger low back pain. During the screening, all subjects were asked to confirm that they could perform these exercises. If at the end of the first resting state scan the patient’s cLBP pain rating was too strong  and the patient was reluctant to perform exercises to enhance their pain experience, they were asked to wait for 10 minutes in a comfortable position that they chose before starting the second half of the scanning session.During the exercises, cLBP patients were asked intermittently to report their level of pain using the 0–10 pain scale; the exercises were repeated until subjects reported an increase in pain of approximately 3 points on the pain scale. Once this level of pain was achieved, subjects were placed back in the scanner to repeat the same MRI scans that were acquired before the exercise maneuvers. For healthy controls, structural and resting state scans were only collected once.To summarize the procedures, data pre-processing included deleting the first four volumes to remove non steady-state images, slice-timing correction, motion correction, and co-registration to the standard brain atlas (MNI152). In addition, the images were corrected for linear trends over each run, low-pass filtered at 0.08 Hz and spatially smoothed with a 4 mm FWHM Gaussian kernel. Nine nuisance parameters  were also extracted. Finally, the data were down-sampled into 4 mm isotropic resolution to reduce the computational burden.Pearson correlation coefficients were calculated between time series data of each voxel and every other voxel of the whole brain. Cross-correlation measures were weighted by the number of strongly correlated links  across the entire brain to every given voxel to determine the degree of connectivity, and a z-transformation was applied to prepare for group comparison . The z-tPaired and unpaired two-sample t-tests were then used for group analysis to compare FC changes within patients with different endogenous LBP intensities, and between HCs and cLBP patients respectively using FSL. The results were cluster corrected for multiple comparisons and a threshold was set at Z > 2.3 and p < 0.05 with 10 contiguous voxels and spatially smoothed with 1mm spherical kernel for display. Mean Z values over the S1 region (Z > 2.3) were also extracted from individual subjects and plotted for different groups.To identify networks related to the change in endogenous pain intensity, the difference in subjective pain ratings before and after the maneuver (high pain – low pain) was used as a covariate of interest for regression analysis (Z > 2.3 and p < 0.05 with 10 contiguous voxels) across the whole brain.http://surfer.nmr.mgh.harvard.edu) using previously described methods [Automated cortical surface reconstruction was performed on the T1 MPRAGE scans in Free Surfer version 5.1 ( methods -33. Any a priori regions of interest (ROIs), including the lateral prefrontal cortex (LPFC), primary somatosensory cortex (S1), and insula, and restricted our analysis to a mask of these ROIs. The mask was created by merging the FreeSurfer parcellation labels for the rostral and caudal middle frontal areas, insula and the top portion of the postcentral gyrus. Based on the somatosensory homunculus as defined by Penfield [a priori ROIs, a vertex wise threshold was set at p < 0.05 corrected for multiple comparisons in FreeSurfer using Monte Carlo permutations with 5000 iterations within the mask.Group analyses were performed by resampling each subject’s data to the FreeSurfer average atlas, distributed as a part of FreeSurfer. Cortical thickness maps were smoothed using a Gaussian kernel with a FWHM of 10 mm. Vertex wise analyses of cortical thickness were performed using FreeSurfer. For both cLBP patients and HCs, a linear model of the cortical thickness was calculated at each vertex on the surface. Two-sample t-tests were used to compare the cortical thickness between cLBP patients and HCs. Based on previous structural studies ,18,22,23Penfield  we incluIn addition, we also conducted a whole brain cortical thickness comparison between cLBP patients and HCs using a vertex wise threshold (p < 0.05) corrected for multiple comparisons in FreeSurfer using Monte Carlo permutations with 5000 iterations. To further explore the relationship between brain cortical thickness changes and duration of cLBP, we also applied a regression analysis to investigate the relationship between cortical thickness and the duration of LBP within cLBP patients.The automated segmentation procedure for labeling different brain structures and extracting their volumetric measures is described in detail by Fischl et al. . This prt-test was then applied to compare the volume differences between the patients and controls in the bilateral top third of S1. As an exploratory control, we also applied the same analysis on the total S1 volume, as well as bilateral middle and bottom thirds of S1 separately.Using the automatic labeling of brain structures described previously, we obtained volumetric measures of the entire S1 cortical region as well as specific portions of S1, divided perpendicular to its long axis. For the present analysis, we divided S1 into 3 sections as determined by the length of the long axis. A two sample A total of 18 cLBP patients, and age- and gender-matched HCs, completed the study.Please see Table In this study, the LBP intensity was recorded before and after each resting state fMRI scan. We used the average of pre- and post-scan ratings to represent the LBP intensity level for the particular resting scan. All patients, except one who did not perform the exercises, reported an increase in low back pain intensity from pre- to post-maneuver. In our data analysis, we define the scanning period during which patients’ low back pain ratings are lower as the low pain (LP) condition, and the other as the high pain (HP) condition. The average LBP intensity was 3.8 ± 2.5 for LP condition, and 6.7 ± 2.0 for HP condition. No back pain was reported for healthy controls.t-test. Results showed that HCs had significantly greater FC in the right primary somatosensory and motor areas (S1 and M1) located in the upper portion of the pre- and postcentral gyrus compared with patients with cLBP LP condition  and the corresponding low back pain rating differences. The results showed significant positive correlations between FC and LBP rating changes at the left insula, precuneus, amygdala and fusiform Table .Volumetric analysis showed that there were no significant differences between cLBP patients and controls with regard to total gray volume (p = .78), subcortical gray volume (p = 0.52) and intracranial volume (p =0.87).Direct comparison between cLBP patients and the control group showed that the cortical thickness measure of the bilateral postcentral gyri was significantly greater in cLBP patients. No other brain regions showed significant differences between the two groups Table .3) and matched HCs (4781 ± 783 mm3) (LBP patients > HC) bilaterally in the top third of the postcentral gyrus (p = 0.033). When age and gender were included in the model as covariates, the p value remained significant (p = 0.17).To further explore the relationship between S1 morphometric changes and cLBP, we compared the volume of the top third of the postcentral gyrus bilaterally. The results showed a significant difference in volume between the cLBP patients , middle third  and bottom third of S1 , which highlights the specificity of the changes in the top third of S1 to cLBP patients.In a further test of volumetric differences, we compared the whole volume, middle and bottom third of the postcentral gyrus bilaterally. The results showed there were no significant differences between the cLBP patients and controls in total volume , but also that FC varies with endogenous low back pain intensity (high intensity pain condition showed stronger FC). In addition, we also found differences in brain structure  between the cLBP patients and HCs at S1. The combined neuroanatomical and functional changes of S1 imply that this brain region in particular may play an important role in the pathophysiology of cLBP.Recently, the spontaneous brain activity fluctuations observed in resting state fMRI, have drawn the attention of brain imaging investigators -43. It iThe involvement of S1 in pain processing has been known for a long time. Brain imaging studies -39,45-47In addition to FC changes, we also found increased cortical thickness in the superior section of S1 in the cLBP patients. A further analysis of brain volume in the top one third of the postcentral gyrus (S1), but not the whole S1 volume, also demonstrated that S1 was significantly larger in cLBP patients compared to HCs. This result is consistent with a recent study  in whichThese results are also consistent with previous animal studies that suggest S1 is highly plastic during both development and in adulthood . This plIn a recent study of chronic pain (migraine) patients , investiGray matter differences could result from changes in cell volume, synaptic densities, blood flow, or interstitial fluid ,56. In aAlthough consistent with a recent study with large cohort of patients , our finIn other studies, a discogenic back pain subgroup may have injured the nerve surrounding the affected region and prevented the function/movement of the related regions, which caused the gray matter decrease in the corresponding somatosensory region . In nonsAnother potential reason that we see conflicting observations  between studies is the age of study population. In a previous study , SchweinIn our study, the average age of cLBP patients was 36; the average ages in the previous studies were 50 in the Schmidt-Wilcke et al. study , 46 in tIn this study, we also found significant positive correlations between FC changes and LBP rating changes at the left insula and amygdala. The insula is one of the key regions in pain processing ,39,66,67There are some potential limitations in this study. We did not include medication in the model, and although it is unlikely for medication to affect our results, we cannot completely rule out the effect of medication. It is important to note, however, that we excluded all patients using opioids from this study, as a previous study  found thAnother potential limitation is the order effects between the high endogenous LBP and low endogenous LBP conditions. One challenge of cLBP studies is that once LBP is provoked, it is hard to control without any pharmacological intervention. In this study, we used exercise to provoke the patients’ LBP; thus, the high pain condition tended to follow the low pain condition. However, previous studies have suggested high test-retest reliability across different sessions ,71, indiFinally, we did not collect second scan data for healthy controls. However, previous studies have suggested that resting state FC measurements have moderate to high reliability ,73. In aIn summary, our study showed that compared with healthy controls, cLBP patients have increased cortical thickness and increased volume in the top one third of S1, and decreased FC during low intensity LBP conditions at S1. Interestingly, we also found that the FC at S1 increases when patients experience more endogenous back pain. We believe our results provide the evidence of structural plasticity co-localized with areas exhibiting dynamic FC characteristics in S1 in cLBP patients.There is no conflict of interest to claim for all authors.JK: experiment design, data collection, data analysis, manuscript preparation. RS: data collection, data analysis, manuscript preparation. HYW: data analysis, manuscript preparation. AC: data collection, data analysis, manuscript preparation. AC: data analysis, manuscript preparation. KJ: manuscript preparation. YT: data analysis. HSL: data analysis. DHW: data analysis. ML: manuscript preparation. VN: experiment design. JS: experiment design, manuscript preparation. AW: experiment design, manuscript preparation. RG: experiment design, manuscript preparation. All authors read and approved the final manuscript.


It is an established fact that patients in the Intensive Care Unit (ICU) experience a plethora of events such as lack of sleep, anxiety, fear, disturbances caused by the continuous and menacing noises of the ventilators, machines, trolleys and above all, pain caused by innumerable reasons such as the underlying disease, suctioning of the endotracheal tube or invasive procedures including arterial punctures for blood gas analyses, cannulation of the central veins for fluid therapy, tracheostomies and insertion of chest tubes etcetra etcetra. of over whelming concern is pain which seems to be rather neglected despite numerous protocols and strategies apparently aimed at providing pain relief and anxiolysis to facilitate mechainical ventilation and therapeutic and diagnostic interventions. Pain management likely has attracted less attention in the critically ill patients in the ICUs owing to the fear of the cumulative effect and subsequent delayed recovery from the traditionally employed opioids and sedatives in this particular setting. The fear prevailing among the care givers seems to be justified on the grounds that critically ill patients have organ impairment of some degree thus delaying metabolism and excretion of drugs. This scenario ushers in problems of weaning from mechanical ventilation and extubation. There is a general consensus that effective analgesia and sedation is of paramount importance for patients in ICU in controlling pain, relieving anxiety and aiding compliance with mechanical ventilation thus providing patient comfort and patient satisfaction. In the past, besides analgesics and sedatives, neuromuscular blocking drugs (NMBD) were part and parcel of the armamentarum utilized in ICUs. Vecoronium was considered to be the choice as it lacked cardiovascular effects but its active metabolite- 3 desacetylvecoronium- could still accumulate in patients with renal impairment. Today the use of NMBD has been waning and presently their use is limited to some special situations such as intractable raised intracranial pressure, status epilepticus and some other conditions. Among the long acting opioids, recommended by the consensus conference, morphine is the most widely used analgesic agent in the ICUs worldwide . Despite


Premature discontinuation of aromatase inhibitors (AIs) in breast cancer survivors compromises treatment outcomes. We aimed to evaluate whether patient-reported joint pain predicts premature discontinuation of AIs.We conducted a retrospective cohort study of postmenopausal women with breast cancer on AIs who had completed a survey about their symptom experience on AIs with specific measurements of joint pain. The primary outcome was premature discontinuation of AIs, defined as stopping the medication prior to the end of prescribed therapy. Multivariate Cox regression modeling was used to identify predictors of premature discontinuation.P = 0.016) and prior use of tamoxifen  were significant predictors of premature discontinuation of AIs. The most common reason for premature discontinuation was joint pain (57%) followed by other therapy-related side effects (30%). While providers documented joint pain in charts for 82% of patients with clinically important pain, no quantitative pain assessments were noted, and only 43% provided any plan for pain evaluation or management.Among 437 patients who met eligibility criteria, 47 (11%) prematurely discontinued AIs an average of 29 months after initiation of therapy. In multivariate analyses, patient-reported worst joint pain score of 4 or greater on the Brief Pain Inventory (BPI) (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.14-3.80, Worst joint pain of 4 or greater on the BPI predicts premature discontinuation of AI therapy. Clinicians should monitor pain severity with quantitative assessments and provide timely management to promote optimal adherence to AIs. Third-generation aromatase inhibitors (AIs) are commonly prescribed as standard adjuvant therapy for postmenopausal breast cancer survivors with hormone-receptor positive disease and are associated with improved disease-free survival compared with the previous standard of tamoxifen therapy-4. The rDespite the survival benefits of AIs, many women demonstrate some degree of non-adherence with their use. Non-adherence, a term which comprises both non-compliance with dosing, timing, and instruction of medication and non-persistence, or early discontinuation of medication, represents an emergent area to intervene for treatment benefit. Indeed, non-adherence of adjuvant endocrine therapy has been associated with increased mortality in breast cancer patients. In the Despite the prevalence of early medication discontinuation and its deleterious effects, little is understood about risk factors for premature discontinuation of AI therapy. The available adherence research largely consists of medical claims-based epidemiological studies in which younger age, increased cormorbidities, and higher medication co-payments have been noted as risk factors for nonadherence to adjuvant therapy-12. WhilParticipants were identified from the Wellness after Breast Cancer (WABC) study, an ongoing cohort study of breast cancer patients who completed a survey at the time of recruitment between March 2008 and July 2009 at the University of Pennsylvania . The incPremature discontinuation of AIs, defined as stopping medication prior to the end of prescribed therapy, was determined by chart review of outpatient electronic medical records (EMR). Medication events were evaluated from the survey date to December 2011 (follow-up period of 29–45 months). Each oncology visit progress note was reviewed for information concerning the prescribed AI and planned duration of therapy at the time of prescription. Patients varied in their duration of therapy depending on whether an AI was incorporated as primary, sequential, or extended adjuvant endocrine therapy and we deferred to the provider-determined end date for all patients as documented in the EMR[et al.[N=5), death (N=8), or loss to follow up from the outpatient clinic (N=20).We regarded premature discontinuation as an intentional action of the patient in line with the definition of non-persistence presented by Guth et al.. Disconta priori dichotomized patients into two groups: those reporting joint pain severity from 0–3 and those reporting joint pain from 4–10, a level at which pain becomes clinically important and interferes with daily functioning[Patient-reported pain outcomes were obtained from the one time baseline survey that established the cohort. To evaluate clinically important joint pain, we used the worst pain measure from the Brief Pain Inventory (BPI) with slight modifications. Particictioning. To evalctioning.Self-reported demographic variables included age, race/ethnicity, education level, date of last menstrual period (LMP), and reasons for menopause . Comorbidities were assessed using a standard checklist and categorized into 0, 1, or 2, or more conditions. Clinical variables such as tumor type, stage, treatment regimen, and treatment status were collected via medical chart abstraction.Provider encounter notes in the EMR on the date each subject completed the initial WABC survey were reviewed to compare provider and patient reports of joint pain. We analyzed the visit note for documentation of joint pain and, if present, indications of the level of joint pain using quantitative pain ratings and whether a plan to address joint pain was provided.P <0.10) and premature AI discontinuation. All statistics were two-sided with P <0.05 indicating significance.Data analysis was conducted using STATA 12 for Windows . Survival analyses were performed using the Kaplan-Meier method to examine individual predictors of premature discontinuation from the time of initial survey. Multivariate Cox proportional hazards regression models were used to estimate the association between predictive variables  were taking an AI at survey date. Twenty-four subjects (4.8%) were excluded after chart review revealed metastatic disease at the time of enrollment, leaving a total of 437 eligible patients  had completed their course of AI therapy for the full duration prescribed, while 193 (44%) continued to take an AI. Forty-seven women (11%) prematurely discontinued their course of AI therapy after an average of 29.4 ± 18.2 months . Higher education level (P = 0.071) and prior use of tamoxifen (P = 0.088) were also associated with early discontinuation but did not reach statistical significance (Table P = 0.016) .In univariate analyses, patient-reported joint pain severity ≥4 (measured at cohort entry) was significantly associated with premature discontinuation of AI therapy . Provider  documentation of joint pain was noted in 124 visits (82%), however, no quantitative assessments of pain were observed. Providers documented a plan for joint pain  in 43% of visits.We restricted our analysis of provider behavior to include only individuals reporting clinically important pain (worst joint pain rating 4–10) on the initial survey (In this retrospective analysis we evaluated whether patient-reported joint pain severity is predictive of premature discontinuation of AIs. After controlling for demographic and clinical characteristics, patients who reported worst joint pain severity of 4 or greater on the BPI were significantly more likely to prematurely discontinue AI therapy. However, patient-reported AIAA did not predict premature discontinuation. Although clinicians often documented the presence of joint pain in the EMR of patients with clinically important pain, no quantitative assessment was used, and only half offered a plan to further evaluate or treat pain. These findings warrant future clinical improvements in both pain diagnosis and management for breast cancer survivors receiving AI therapy.Premature discontinuation specific to AI therapy has been reported to range from 13-35% in the emerging literature-9. Theseet al. demonstrated an absolute increase in mortality of more than 7% in women who prematurely discontinued hormonal therapy with either an AI or tamoxifen compared to those who continued therapy over a 4.5 year period. Even with adjustment for relevant clinical and demographic variables, early discontinuation was associated with a relative 26% increase in all-cause mortality[Premature discontinuation, as one aspect of non-adherence, has substantial negative effects by the very meaning of its definition – the complete cessation of therapy. Hershman We found patient-reported worst joint pain severity of 4 or greater to be predictive of premature AI discontinuation. Interestingly, patient-reported AI-associated arthralgia was not a significant predictor, suggesting that it is the severity of joint pain, rather than its assumed origins, that may lead women to stop therapy. The finding of joint pain severity as a predictor of premature discontinuation is consistent with a recently published study in a clinical trial setting in which higher baseline pain is a positive predictor of early discontinuation of AI therapy. These fIn contrast to research suggesting physicians' failure to routinely assess patient pain, it is eIn multivariate modeling, we found that controlling for joint pain severity strengthened the association between prior tamoxifen use and premature discontinuation of AIs. This suggests that for patients who experience the same level of pain severity, they are more likely to discontinue AIs if they had prior use of tamoxifen. Based on clinical experience, it is possible that prior tamoxifen users who perceived that they had adequate hormonal therapy were therefore less tolerant of side effects of AIs. Another possible explanation is that prior tamoxifen users have gotten used to the side effects of tamoxifen over time and when they experience new side effects related to AIs, they prefer to switch back to tamoxifen rather than staying on AIs.Our study has several potential limitations. First, in our retrospective cohort study design, we assessed joint pain one time to predict premature discontinuation of AIs. As pain may change over time, our data does not provide an absolute cut-off pain level necessary to discontinue AIs and requires validation in independent datasets. Additionally, our retrospective design did not include patients who prematurely discontinued AIs prior to enrollment which may bias our results towards null. Thus, the strength of association between joint pain severity and premature discontinuation may in fact be even stronger. Third, our outcome focused on premature discontinuation based on chart-abstraction. Theoretically, patients may discontinue therapy without informing their providers; however, if that is the case, it should bias our results towards null. Lastly, our research was conducted in a large academic medical center which may limit the ability to generalize findings to community hospital settings.Despite these limitations, our study had a number of strengths including a large clinical population, incorporation of patient-reported outcome, and examination of provider pain diagnosis and management behaviors. We found that patient-reported joint pain severity of 4 or greater was significantly associated with early discontinuation of therapy. These results highlight the importance of medical providers performing quantitative assessments of pain and inquiring about other medication adverse effects in order to appropriately identify patients who may be at risk for stopping therapy. Targeting interventions for these patients will ultimately optimize adherence to AIs and improve both quality of life and survival outcomes for women with breast cancer.Written informed consent was obtained from each participant.RG has served on a Pfizer Data and Safety Monitoring Board for a drug unrelated to the treatment of breast cancer. JTF has consulted with Pfizer and AstraZeneca on design of clinical trials of pain therapeutics that are unrelated to aromatase inhibitors. AD has consulted and received research grants from Pfizer in the area of breast cancer. JM has consulted with Pfizer on pain medication unrelated to aromatase inhibitors or breast cancer.KC designed the study, collected data come and drafted the manuscript. SX designed and performed statistical analyses. QSL performed statistical analyses and drafted the manuscript. CS, RG, JF, and AD participated in study design, assisted in data interpretation, and helped to draft the manuscript. JJM designed the study, drafted the manuscript, and obtained funding. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/401/prepub


Deqi sensation is believed to be important in clinical efficacy according to TCM theory. The measuring method of Deqi sensation has significant implications for the result of research trials. This study makes an investigation on acupuncture-experienced patients and expert acupuncturists in China and aims to find out the patient's needling sensations and acupuncturist's sensations which can be acceptable as descriptors of Deqi sensation, so as to provide foundation for more systematic and sensitive quantitative evaluation method of Deqi sensation. Results of this survey indicated that the Deqi sensation noted by both patient and acupuncturist is equally important to the treatment efficacy. It is found that there are some differences between the patients' real-life experience and the acupuncturists' expectations on patients' Deqi sensation. The “dull pain,” “aching,” “sore,” “numb,” “distended,” “heavy,” “electric,” “throbbing,” “warmness,” “coolness,” “spreading,” and “radiating” can be considered as the main manifestations of Deqi sensations. The acupuncturists believed that Deqi sensations were mainly “pulling,” “tight,” and “throbbing.” We suggest developing a questionnaire measuring the Deqi sensations which includes both the sensations of the patient and acupuncturist, and this would be very important and necessary for a better understanding of the relationship between Deqi sensation and acupuncture effects in future studies. Deqi, which first appeared in the “Huang Di Nei Jing,” refers to the reaction of movement of qi  of the human body when acupuncture needles are inserted into acupoints. It is believed that Deqi was closely related to the treatment efficacy. In clinic, Deqi is mainly testified by needle sensation, which includes the patients' sensations and the acupuncturists' sensations. The patient's needle sensations mainly include sour, numb, swelling, heavy, pain, hot, cold, and the complex feeling and spreading based on these feelings; when the patients have those needling sensations, the acupuncturist can also feel heavy, tense, or needle stuck, or needle tremor [Deqi has been partly explored in some studies [Deqi may be an important factor of acupuncture analgesia [Deqi sensation by using the international scale was originated from the end of the 1980s [Deqi, quantitative measurement of Deqi attracts increasing attention. The representative scales include the MASS scale compiled by Kong et al.  [Deqi” is still lacking.e tremor –3. The c studies –9, but inalgesia –12. Meashe 1980s . In recen Scale)  and the n Scale) . In addin Scale) . Yu et an Scale) . HoweverDeqi. However, modern evaluation tools for Deqi and its related studies all ignore the acupuncturists' sensations. By taking a systematic investigation of the ancient and modern literature, we found that the current evaluation tools can be further improved based on well understanding of Deqi's connotation. In order to develop a validated method to measure the Deqi, we performed a descriptive survey with the following three specific aims: (1) understanding Chinese patients' and acupuncturists' attitudes and beliefs on acupuncture sensations and Deqi, (2) exploring the influence factors of Deqi and the effect of Deqi on acupuncture treatment efficacy, (3) summarizing the patients' Deqi sensations reported by patients and senior acupuncturists, and (4) investigating the acupuncturist's perceptions on Deqi.In traditional acupuncture, the acupuncturists must pay attention to eliciting and controlling of Deqi sensations in an acupuncture treatment session are widely accepted by the majority of Chinese patients. Some patients even require obtaining the needling sensations or some other special acupuncture feelings on their own initiative [Deqi sensation was significant different between Chinese patients and those from the US [In China, the health care system includes both modern medicine and TCM. As acupuncture is very popular in China, itiative . The patm the US . So in tDeqi were collected. The Chinese literature includes the ancient books, modern acupuncture text books, and the published articles related to Deqi. The English literature includes the questionnaires of Deqi, or needle sensation, and scales used for measuring Deqi [Zhang” (fullness/distention) in Chinese, and then we used the item “distention” in English in this paper.Prior to the formal investigation, a structured interview was setup through a literature review involving both ancient and modern, Chinese and English, and then the terms frequently used for describing the patients' and acupuncturists' perception on ing Deqi , 20, 21 ing Deqi , 22, 23.Deqi sensations of the patients?” some additional interpretations have been added for the terms that may be puzzled to common patients. For example, “dull pain” is interpreted as “mild, moderate or minor pain without a strong inimical feeling,” “sharp pain” is interpreted as “a severe pain with a sense of injury,” “twinge” as “an unbearable pain with the highest intensity,” “pain” as “a pain unable to clarify its nature.” In the questionnaire for the acupuncturists, the questions of “spreading distance” and “the direction of spreading” of needling sensation were added.The draft questionnaires were developed based on the interview with four doctoral candidates and four experts with senior professional titles from the School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine. These experts and doctoral candidates have rich experience in administrating acupuncture and being treated with acupuncture. Then, two expert acupuncturists and five patients completed the draft questionnaires. We also interviewed them regarding their opinions on using the questionnaires and modified the draft according to their comments. The major modifications for patient's questionnaire include making a detailed and more clear explanation to distinguish the similar items such as “pulling” and “tight,” “spreading” and “radiating.” In the options of the question “which terms can describe the Finally, the second presurvey was conducted through the interview on another six acupuncture-experienced undergraduates who were not majored in medicine. No modification was made in the first interview. After one week, we altered the order of the questions and conducted the interview for the same subjects again. The results were consistent with those obtained in the first interview.There are two types of questionnaires, one is for the patients and the other is for the expert acupuncturists, which are completed by the patients and the experts, respectively.Deqi. Part 2 includes questions about the patient's sensations experienced during acupuncture administration. There are two phases in part 2. Phase 1 involves questions mainly asking about the patients' needling sensations. Twenty-six terms are separated into four categories: pain, temperature, sensation spreading, and others. One supplementary blank was at the end for subjects to describe sensations in their own words. Phase 2 includes three questions asking about the patients' emotions during acupuncture. An open-ended question is added at the end, “What is your impression on Deqi?” The patient's questionnaire contained two parts and one open-ended question. Part 1 includes four single choice questions on the patients' perception of Deqi sensation of patients based on their clinical experience. Part 1 includes five multiple choice questions and three single choice questions regarding the understanding of Deqi by the experts. The questions in part 2 aimed to inquire expert's perceptions on needling sensations of the patient (the same questions in patient's questionnaire) and sensations felt by expert's needling hand. An open-ended question is added at the end, “What are your opinions on this questionnaire of Deqi?”There are also two parts and one open-ended question in the questionnaire for the experts. It includes some questions in the questionnaire for the patients in order to get experts' perceptions on Deqi occurrence rate in Chinese clinical trials is 100% [Deqi sensation only deriving from manual acupuncture with filiform needles . The investigators tried to not disturb the subjects during completing the questionnaires and answered any questions of the subjects in a unified way. Only when the investigators found some missed questions or apparently contradictory options, they would take some necessary reminding. As the  is 100% , it is hThe questionnaire data was independently collected by two persons. We made a statistics after verification and amending. Descriptive statistics were performed by using the computer and presented by percent (%). When inputting the data, we combined some terms which describe similar sensations, such as “warm” and “burnt,” considered to be a different degree of “warm,” are merged into “warm,” “cool” and “cold” are merged in to “cool.”P < 0.05 was determined to be of statistical significance, and all analyses were two-sided. Statistical analysis was performed using SPSS Statistics 17.0.Types of patients' needling sensations perceived by patients and understood by acupuncturists were compared using chi-square analysis. Chi-square analysis and Fisher's exact test (when appropriate) were then performed to explore the effect of expressing by patients and acupuncturists on types of patients' acupuncture sensations. A level of A total of 40 patients participated in this survey; 70% of them were men, with an average age of 60.2 years old. Each of them had prior acupuncture experience, and 83% of the respondents had more than 10 times acupuncture treatment experiences. When needles are insert, 58% of the patients stated that they achieved needle sensations in each treatment, while the others always (22%) or occasionally (20%) have such feelings, and nobody stated that they had never had such feeling. Forty acupuncturists participated in this survey; 65% were women, with the average age of 48.5 and working time of 20.7 years. Deqi.” Among the patients who know about Deqi, four thought that Deqi is a sensation during acupuncture, one thought that Deqi meant the channels were unblocked, and three of them cannot explain the specific meaning. 85% of the patients expected to have the needle sensations upon the treatment, and only one did not expect to have needling sensation. About 90% of the patients thought needling sensation is closely related to the treatment efficacy, and others did not know their relationship. About 58% of the respondents said that the acupuncturist will ask them about their needle sensations during every acupuncture treatment session. Nearly 40% of the patients said that they were always asked by their acupuncturists. The patients in this study all have been asked about their needling sensation by their acupuncturists during the treatment, as shown in In this study, nearly 70% of the patients never heard of “Deqi” should be elicited in the treatment, while others thought the treatment without needling sensation can also achieve the efficacy. Some experts said that needling sensation could not be elicited in every point due to limitation of treatment time. They said that the patients expected to get a stronger needling sensation, which is inconsistent with the results concluded from the questionnaires for the patients.In this study, 95% of the acupuncturists in China thought that “Deqi. Compared to the acupuncturists, the patients are more easily to get needling sensation. In this study, all of the acupuncturists believed that the sensations of the acupuncturists can be a sign of Deqi.Most acupuncturists (90%) held that acupuncturists sensations felt by their needling hand and the needling sensations of the patients are the typical characteristics of Deqi sensation is related to the treatment efficacy, but only 38% of them thought that the symptoms can be relieved immediately. Most acupuncturists believed that the patients' sense of Deqi and the acupuncturists sensations are equally important to the treatment efficacy, as shown in About 73% of acupuncturists thought that  Deqi sensation and treatment efficacy, most acupuncturists thought that the efficacy is closely related to the existence of Deqi sensation (87%), the realization of qi spreading to the affected parts (47%), and the intensity of Deqi sensation (37%). In addition, one-third of the acupuncturists thought that the time for inducing Deqi sensation and the direction of sensation spreading may affect the efficacy. Only a few patients thought that the lasting time of Deqi sensation (11%) and what kind of sensation (8%) may affect the efficacy.Regarding the relationship betweenIn addition, the acupuncturists held that the acupoint location (87.5%), point selection (82.5%), and the acupuncture manipulation (90%) are the three key elements in acupuncture. The physiques of the patients (80%), acupuncturist's needling skill (67.5%), needle depth (60%), the thickness of needle (57.5%), the type of disease (45%), the patient's emotional and psychological states (40%), acupoints selection (35%), needle inserting site (35%), needle retention time (22.5%), season while needling (25%), and time of acupuncture administration (15%) may all affect the efficacy.The most common acupuncture sensations reported as experienced by patients were “distended” (72.5%), “aching” (65%), “sore” (60%), those “spreading” (60%), and, reported as considered by acupuncturists were “warmness” (92.5%), “sore” (87.5%), “aching” (85%), “distended” (85%), and “spreading” (82.5%), as shown in Deqi sensation is not harmful in the treatment. However, nearly half of the patients considered that Deqi sensation is tolerable; none of them felt Deqi cannot be tolerated. Half of the respondents stated that Deqi sensation is comfortable. Some patients indicated that Deqi is just a series of sensations; they do not care whether it is comfortable or not, as shown in In this survey, 82.5% of the patients believed that P > 0.05). However, there are some differences between the patients' real-life experience and the acupuncturists' expectations among the others, as shown in In this study, we not only asked patients to select the terms on behalf of the needle sensation, but also invited some expert acupuncturists to filter them. It showed that there are no statistical differences among the 14 descriptors of the all 26 descriptors (P > 0.05), which indicated that the majority of patients and acupuncturists believed that Deqi sensation is associated with pain.As long as the patients or acupuncturists select one option among the feelings in the same category, it will be considered to select this kind of feeling in statistics. After comparison, it is found that there is no significant difference between the patients and acupuncturists in selecting the pain related feeling (P = 0.000), which suggested that patients actually feel the temperature changes and needling sensation spreading occurred less than the acupuncturists' expectation.There are significant differences between patients and acupuncturists in selecting the temperature feel and feeling spreading (P > 0.05). All of these sensations are selected by more than half of the patients and acupuncturists, indicating that the feelings are thought to present signs of Deqi sensations.There are no differences between the “dull pain,” “distended,” “electric,” and “throbbing” between two groups of subjects (P > 0.05). Moreover, all are below 20%, indicating that these feelings mentioned above are not the typical Deqi sensations. One-third of the patients selected “pricking” significantly higher than the selection rate of acupuncturists (P = 0.005). Referring to the terms “sharp pain,” “twinge,” “throbbing pain,” “burning,” “penetrating,” “formicating,” their supporting rate has no statistical difference between the two groups (The most common sensations reported by acupuncturists were “pulling” (95%), which was described as “as a fish biting the hook” in ancient books, and “tight” (70%) as shown in Deqi sensation and the acupuncturists' sensations, so as to develop proper clinical evaluation questionnaires on Deqi. So it is expected to select acupuncture-experienced subjects, especially those patients who already recognized the Deqi sensation. This study is different from some previous studies which selected naive volunteers without any acupuncture experience as their subjects [One purpose of this survey is to filter the descriptors of the patients' subjects , 14, 22.subjects , 26, butsubjects , 28; thesubjects , 30.Deqi sensation and could rule out the needle sensations by accident. Compared with the respondents in experimental models, a survey based on these respondents may reflect the real phenomena of Deqi sensation in the real world clinical setting.The long treatment course and large amount of stimulation in this treatment are particularly in consistent with the requirements of this survey. So in this study, we selected the patients from three outpatient acupuncture clinics of Beijing TCM hospitals for the survey. 70% of the respondents suffered from apoplexy and the others from facial paralysis, trauma, headache, low back pain, and gastrohelcoma. More than 80% of these patients have received more than 10 sessions of acupuncture treatment. They had more experiences in perceiving Deqi is comfortable. Although some patients may have felt uncomfortable sometimes, they also thought it is not harmful. Our result is consistent with Mao's et al. result [Deqi sensations indicated that the acupuncturist had good needling skills. The majority of the patients thought that needling sensations are related to the treatment efficacy and excepted to experience these sensations in the treatment. Nearly half of the patients thought . result . RegardiDeqi sensation is closely related to the treatment efficacy. Although 25% of the acupuncturists were not sure about the relationship between Deqi sensation and treatment efficacy, they still excepted to elicit the Deqi sensation in clinical. It may be influenced by the acupuncture education and the demands of the patients. Only one acupuncturist thought Deqi sensation is not related to treatment efficacy. So it is obviously shown that the acupuncturists and patients, especially the patients who suffered more severe diseases, are eager to achieve Deqi sensation and highly expected its influence on efficacy.In this survey, three quarters of the 40 experts thought Deqi sensations based on their memories. 92.5% of patients reported at least one pain related term. There are three terms used to describe the intensity of pain, “dull pain,” “sharp pain,” and “twinge.” Half of the patients chose dull pain, four of them chose sharp pain and dull pain, and one patient chose dull pain and twinge at the same time as the twinge occasionally occurred and it is difficult to distinguish them. Although most patients cannot distinguish pain and Deqi sensation, “dull pain” is widely accepted to be one of the Deqi sensations. In two terms of “deep pain” and “skin pain” associated with location of pain, more patients chose skin pain, indicating that the patients may have an incorrect understanding of Deqi sensation. Deqi sensation is the needle sensation when the needle was inserted into the acupoints with a certain depth, which pointed out that the pain caused by skin penetrating during needle inserting should be distinguished so as to avoid confusion of the skin pain and Deqi sensation. Among the twenty-six terms for needle sensations in this questionnaire, “fullness” was the most common sensation (72.5%), followed by the “aching” (65%) and “sore” (60%); approximately half of the patients selected “dull pain,” “numb,” “spreading,” which can be considered as the characteristics of Deqi sensations. This survey was a retrospective study, which filtered the terms to describe patient's Deqi sensation terms, the investigated objects include both patients and acupuncturists [Deqi sensations by the patients and expert acupuncturists in the same hospital at the same time. After comparing, it is found that there exist some differences between the real-life experiences of patients and acupuncturists' expectation. In previous studies of filtering cturists , 22, 23.P > 0.05), suggesting that both of them believe that Deqi sensation is associated with pain. There are experimental studies that confirmed that the basic material for generating acupuncture needles sensation is mainly the pain receptors located in the acupoints with a depth [Deqi and pain cannot be completely separated in physiology.It was found that there are no significant differences between the patients (92.5%) and acupuncturists (97.5%) in selecting the pain related terms . It suggests that patients actually rarely feel the temperature changes during acupuncture than the acupuncturist expected. A lot of heat- or cold-inducing needling manipulations recorded in acupuncture classics may be the reason that most acupuncturists tend to choose the warm feeling as the sign of Deqi (92.5%). Although the sense of cool is usually mentioned in the literature, but only 47.5% acupuncturists had successfully elicited a sense of cool and achieved a better efficacy at the same time.  As there is only 1 patient who had experienced such feeling, significant differences existed between the two groups (P = 0.000). However, we believed that the difference was just due to the small sample in this survey.There are much more acupuncturists (92.5%) selecting the temperature related sensation than the patients (25%) (P = 0.000) between the patients (72.5%) and acupuncturists (100%) in selecting the sensation spreading (P = 0.000), the choosing rates of the two groups of people are relatively high, which means that propagated sensation along channel is also one of the typical manifestations of Deqi sensations.Although it has a significant statistical difference . The terms “pricking” and “stinging” occurring rate is above 60% among the young females, which is nearly one time higher than the 32.5% in this study [Deqi sensations, but most acupuncturists thought that pricking is only a feeling during needle inserting and does not belong to Deqi sensation [Deqi sensation, so the acupuncturists should avoid pricking pain to the patients.About 1/3 of the patients chose the “sting” significantly higher than the choice rate of the acupuncturists .In recent nsations –16. HoweSome acupuncture sensations had to be translated from English into Chinese, and we have to add certain additional interpretations for better understanding by Chinese patients. Then, all the terms had to be retranslated to English again, whereby the delicate meaning of some of the items may not have been fully conveyed in its Chinese equivalent. The sample size of this study was not big enough, and the scope of this survey is narrow. Deqi sensations among the Chinese patients and acupuncturists. In the future, we would make an investigation with a larger sample and analyze the relation of the frequency of occurrence of different Deqi sensation with curative effect.All of the objects in this study were acupuncture-experienced patients, and more are men. However, this investigation can still reflect the general recognitions of Deqi sensations and highly expected to get better efficacy due to stronger Deqi sensation. Results of this survey indicated that acupuncturists and patients, especially the patients in serious condition, are eager to get Deqi sensations by the patients and experts in the same hospital at the same time. After comparing, it is found that there exist some differences between the real-life experiences of patients and acupuncturists' expectation. It is found that pain related feeling and sensation spreading feeling are the major manifestations of Deqi sensations. However, the patients actually feel the temperature changes, and acupuncture conduction occurred less than the acupuncturists' expectation.Different from previous studies, this survey filtered the terms of Deqi sensations, while “sharp pain,” “twinge,” “pricking,” “throbbing pain,” “burning,” “penetrating,” “pinch,” and “formicating” may not be the typical signs of Deqi sensations. The acupuncturists' Deqi sensations are mainly described as “pulling,” “tight,” and “throbbing”.The “dull pain,” “sore,” “aching,” “numb,” “distended,” “electric,” “throbbing,” “warmness,” “spreading,” “coolness,” “heavy,” and “radiating” can be considered as the main manifestations of


Pain in ICU patients should be managed effectively and safely. Fentanyl and Paracetamol are used frequently in ICU. However experience using IV Paracetamol in the setting of critically ill patients is limited. We evaluated the analgesic effect and adverse reactions of intravenous Paracetamol compared to Fentanyl in ICU patients with mild to moderate pain. Forty patients in a general ICU were randomized into two groups of IV Paracetamol and IV Fentanyl in a single blinded fashion. Pain was assessed by Visual Analogue Scale (VAS) before drug administration and six hourly for 48 h of 1 g IV Paracetamol every 6 h for 48 h in the first group and 25 μg Fentanyl intravenously every three hours for 48 h in the second group. Patients were monitored for significant adverse reactions particularly of CNS and hepatic nature. Results showed the age, sex and pain score before analgesia was matched in both groups. Pain scores were similar in both groups at 24 h 2.60 (± 1.2) and 2.40 (± 1.5) and at 48 h 2.25 (± 0.96) and 2.05 (± 1.1) in Paracetamol and Fentanyl groups respectively. Clinical and laboratory adverse reactions were also similar in both groups. The analgesic properties of Paracetamol and Fentanyl were similar in this study. We did not observe any significant adverse effects in the two groups. Clinical and laboratory findings including liver functions remained without any statistically significant difference in two groups. This study demonstrates intravenous Paracetamol may be as safe and effective as Fentanyl in ICU patients with mild to moderate pain.  Pain is one of the commonest symptoms of patients admitted to ICU. This should be managed safely and effectively not only from humane and patient comfort perspective but also for better overall care and healing of critically ill patients. There is heightened attention to pain management particularly after surgical interventions and procedures in recent times as we have better understanding of acute pain physiology, its complications and management modalities . Paracetamol is an effective and safe drug for managing mild to moderate pains . The oraNSAIDs are generally added to decrease the total doses of narcotics required for effective pain management. This is not without its harmfuleffects including GI bleeding as an added risk to ICU patients who are already prone to stress related gastric ulcer bleeding. Aghamir and coworkers compared IV Paracetamol with IV tramadol and demonstrated that Paracetamol is an effective and safe analgesic for acute postoperative pain management .et al demonstrated that IV Paracetamol utilization can decrease the doses of narcotic analgesics in postoperative period of CABG patients  and behavioral response in this group of patients. This study indicated that IV Propacetamol could reduce doses of morphine amongst children during their postoperative period  given in 15 min every 6 h and IV Fentanyl (Hameln Company Germany) 25 μg every three h, both for 48 h. Patients who had breakthrough pain or any need for supplemental analgesics were excluded from the study.Patients had to have adequate mental status to be evaluated for severity of pain with mild to moderate pain based on a Visual Analogue Scale (VAS 2-5) (Diagram 1). Midazolam was the sedative agent which was used with equal doses as needed, for both groups. The exclusion criteria were history of allergy to Paracetamol or Fentanyl, contraindications to Paracetamol or opioids use, severe pain (VAS ≥ 5), GCS ≤13, renal disease (Serume Creatinine> 1.5 mg/dL), liver disease , chronic lung disease, hemorrhagic conditions, coagulation abnormalities, alcoholic patients, history of addiction to opioids, pregnancy and lactation. i.e. before the analgesic administration and following study drugs administration every 6 h for 48 h. Other neurologic signs such as restlessness, hallucination, insomnia were recorded on hourly basis.The analgesic effects of the drugs were measured on the basis of VAS and physiologic factors like PR (Pulse rate), RR (Respiratory rate), BP (Blood pressure) and perspiration assessed by clinical examination. Pain was assessed by ICU medical staff under supervision of ICU fellows and using VAS at the time zero Blood pressure was measured and recorded 5 min before drug injections using non-invasive blood pressure monitors at 15, 30, 45, 60,120, 180 and 240 min after the injections then q4h for 48 h. Other Signs such as heart rate, respiratory rate, oxygen saturation and tympanic temperature were measured and absence or presence of perspiration was recorded.rd and 6th day following drug administrations. All patients had to have normal liver, renal and coagulation profiles before entering the study. The laboratory investigations including CBC, BUN, Creatinine, Na, K, PT, PTT,ESR, INR, ALT, AST, FBS, BS, Bilirubin  and Albumin were performed before and thereafter on 3Statistical analysis of the collected data was performed on SPSS (version 15) with the T-test method. Fisher exact test was used for comparative testing. The statistical significance with a p < 0.05 was considered valuable and all the results were recorded on the basis of percentage of the patient numbers or mean and standard deviation. A total of 40 patients were studied with 11 males and 9 females in Paracetamol group and 12 males and 8 females in IV Fentanyl group (p = 0.74). The age of patients were 42.4(± 16.2) and 41.7(± 15.4) in IV Paracetamol and IV Fentanyl respectively (p = 0.89).The pain score based on VAS prior to the administration of analgesics (day 0) were 4.40 (± 0.8) and 4.35 (± 0.8) in Paracetamol and Fentanyl group respectively with a p-value of 0.84. 24 h after administration of study drugs the pain scores were 2.60 (± 1.2) and 2.40 (±.1.5) in Paracetamol and Fentanyl groups respectively (p = 0.64). At 48 h the pain scores were 2.25 (± 0.96) and 2.05 (± 1.1) in Paracetamol and Fentanyl groups respectively (p = 0.54). Improvement in the pain scores in each drug category at 48 h reached statistical significance with a p-value of < 0.0001 (VAS at 48 h in Paracetamol group was 3 in 7 (35%) patients, 2 in 8 (40%) patients and 5 (25%) patients were pain free. Whereas in Fentanyl group VAS was 4 in 3 (15%) patients, 3 in 3 (15%) patients and 8 (40%) patients were free .The measured vital signs did not indicate any significant variations in heart rate, blood pressure, temperature or oxygenation, between the two groups during the course of study.We did not notice any significant differences in the laboratory values between the two groups during the study period .Adverse drug reactions such as fever, hypotension, gastrointestinal bleeding, headaches, agitation, hallucinations, skin reactions, liver and renal complications were monitored closely. One patient in Paracetamol group developed transient skin rash which resolved without treatment. We did not observe any significant neurological adverse reaction in either group. Paracetamol is a safe and effective analgesic agent for mild to moderate pain. The oral and rectal forms of this drug are commonly used for pain management. The intravenous form of this agent passes easily through the blood brain barrier and shows its central analgesic effects within 15-20 min which starts to decline after 4 h of administration.Although this agent represents a relatively good safety profile, there is scarcity of studie sregarding its IV use in critically ill patients of ICUs.We undertook this prospective randomized study to examine the efficacy and side effect profile of IV Paracetamol compared to IV Fentanyl in postoperative patients with mild to moderate pain in ICU.Our study did not indicate any statistically significant difference between the IV Paracetamol and IV Fentanyl groups in pain scores at 24 or 48 h. Neither did we note any significant difference in physiological parameters nor side effect profiles both clinical and laboratory, between the two groups.Of note there was no neurological or liver function abnormalities of any significance in the Paracetamol group with doses used in our study.In a study comparing one g IV Paracetamol and 2 g IV Propacetamol which showed comparable efficacy, less pain and discomfort was observed over the injection site with Paracetamol . We alsoIn another study, it was demonstrated that administration of 1 g Paracetamol intravenously before hysterectomy resulted in better postoperative pain control and lead to decreased use of morphine .A study in patients undergoing lower segment cesarean section, in which IV Paracetamolwas compared with oral Ibuprofen, as the analgesic supplementation agent to morphine, indicated that patients in IV Paracetamol had better pain control compared to Ibuprofen group .et al. on 40 patients in a randomized double blind clinical trial, studying post lumbar laminectomypain management, in addition to morphine administration, one group received one g IV Paracetamol every six hours and the other group received IV placebo. The amount of IV morphine used did not show any significant difference in the two groups. Vomiting was observed less frequently in the placebo group. The Paracetamol group had better pain management profiles than the placebo group  in Fentanyl group which did not reach statistical significance. We did not observe any adverse effects such as vomiting in our studied patients. Limitations of our study such as small sample size, lack of case diversity, lack of placebo arm, single blinded nature, short follow up duration and absence of baseline analgesic agent to compare IV Fentanyl and IV Paracetamol over its use, were reasons we could not draw further conclusions as to the other characteristics Paracetamol use in ICU. However this small study indicates similar pain management properties of IV Paracetamol and IV Fentanyl in mild to moderate pain management in ICU.Intravenous Paracetamol appeared as effective and safe as Fentanyl in the management of mild to moderate pain in ICU patients. In doses used in our study, we did not observe any significant intolerance or hepatic dysfunction in the Paracetamol group.IV Paracetamol could be considered another analgesic agent in ICU pain management armamentarium.Financial disclosureParacetamol injections (APOTEL)® were provided by the manufacturer Uni-Pharma pharmaceutical company, Greece. This research has been supported by Behavior Sciences Research Center of Shahid Beheshti Medical University, Tehran/Iran.


To test whether DoloTest , a new iDoloTest is a validated pain and quality of life assessment tool that has been applied to patients in different pain clinics, but newer tested in a headache clinic. It measures 8 different domains: Pain, problems with light physical activities, problems with more strenuous physical activities, problems doing your job, reduced energy and strength, low spirit, reduced social life and sleeping problems. The patient is asked to score an average of the past week on a VAS-scale for each domain. The maximum value of each domain score is 100 and 800 for the total score. The DoloTest provides a graphic picture of a patient’s pain, as well as a numeric score. Headache patients from the Danish Headache Center were referred to weekly psychoeducational group sessions within a cognitive framework including intensive relaxation training over a 9-weeks period, with 8 patients per group. Psychological treatment was given in addition to other multidisciplinary interventions. DoloTest was applied before, under and after the psychological treatment.Baseline data for 110 patients, 22 males and 88 females, with an average age of 36.1 years (range 18 – 69) are collected. Most of the patients suffer from more than one type of headache: primarily migraine with or without aura n=66, frequent or chronic episodic tension-type headache n=70, others n=45. At baseline the average frequency of headache is 24 days/month, and the average total DoloTest score was 358 (range 32 – 675).The DoloTest may be at valuable tool to measure the effect of psychological treatment, and further evaluation is ongoing.


To investigate pain perception before and during detoxification in patients with medication overuse headache (MOH).Previously, central sensitization has been found in chronic, primary headaches but pain perception in MOH patients has only scarcely been studied and never in long-tem follow-up studies.35 patients with MOH following structured detoxification programmes were tested before and 2, 6 and 12 months after withdrawal and 40 age and sex matched, healthy volunteers were tested for comparison. We measured cephalic and extra cephalic pressure pain thresholds (PPT) and supra-threshold pressure pain (STPP) as well as extra cephalic pain thresholds, supra-threshold pain and wind-up for electrical stimulation.At baseline, cephalic and extra cephalic PPTs were significantly lower in patients with MOH compared with healthy volunteers. Cephalic STPP was significantly higher in MOH patients compared with healthy volunteers but decreased significantly from baseline to the 6-month and 12-month follow-up. Supra-threshold pain for a single electrical stimulus was significantly higher in MOH patients compared with healthy volunteers. In contrast to healthy volunteers, patients with MOH did not exhibit wind-up before withdrawal. After 2 months, MOH patients had regained ability to wind-up and this persisted at 6-month and 12-month follow-up.Patients with MOH have altered pain sensation and exhibit both allodynia and hyperalgesia indicating central sensitization. Withdrawal from medication overuse causes significant decrease in central sensitization. The ability to wind-up is altered in MOH patients, probably as a consequence of medication overuse, but it can be regained after withdrawal. These findings emphasize the need for detoxification in MOH.