DETECT). Objectives were (1) to estimate whether neuropathic pain contributes to axial low back pain and if so to what extent. (2) To detect subgroups of patients with typical sensory symptom profiles and to analyse their demographic data and co-morbidities. (3) To compare patients with and without prior intervertebral disc surgery (IVD). Neuropathic pain components could be detected in 12% of the entire cohort. Cluster analyses of these patients revealed five distinct subgroups of patients showing a characteristic sensory profile, i.e. a typical constellation and combination of symptoms. All subgroups occurred in relevant numbers and some showed distinct neuropathic characteristics while others showed nociceptive features. Post-IVD-surgery patients showed a tendency to score more “neuropathic” than patients without surgery . Axial low back pain has a high prevalence of co-morbidities with implication on therapeutic aspects. From these data it can be concluded that sensory profiles based on descriptor severity may serve as a better predictor for therapy assessment than pain intensity or sole diagnosis alone. Standardized phenotyping of pain symptoms with easy tools may help to develop an individualized therapy leading to a higher success rate in pharmacotherapy of axial low back pain.Axial low back pain can be considered as a syndrome with both nociceptive and neuropathic pain components (mixed-pain). Especially neuropathic pain comprises a therapeutic challenge in practical experience and may explain why pharmacotherapy in back pain is often disappointing for both the patient and the therapist. This survey uses epidemiological and clinical data on the symptomatology of 1083 patients with axial low back pain from a cross sectional survey (pain Chronic axial low back pain has a high socioeconomic impact. With a lifetime prevalence of 30–50% for moderate and severe chronic back pain in an ageing society it depicts a large clinical and economic burden axial back pain. This entity has long been considered as purely nociceptive but clinical and diagnostic findings suggest a neuropathic influence Back pain is caused by complex interactions of biological, psychological and social factors. Suffering is often complicated by significantly associated co-morbidities like depression and anxiety. Thus, patient’s quality of life is seriously impaired leading to a complex and demanding therapeutic challenge DETECT questionnaire (PD-Q) was designed to screen for neuropathic pain on such considerations. It allows discrimination between neuropathic and nociceptive pain components in chronic pain syndromes through a score system based on 9 questions (7 pain descriptor questions and two concerning radiation and pain course). A validation study was performed in back pain patients DETECT data revealed a higher prevalence of depression, panic and anxiety disorders and sleep disorders When back pain patients describe their discomfort they frequently use different descriptors for pain qualities and sensory symptoms in various combinations. For nociceptive pain these descriptors include constant aching pain which is located deeply in the back, shooting pain attacks which are often elicited by slight movements or pain which is induced by a slight pressure stimulus at the back. Neuropathic pain components are often associated with burning and tingling sensations DETECT) performed in collaboration with the German Research Network on Neuropathic Pain (DFNS). The following hypotheses were tested:We analysed epidemiological and clinical data of 1083 patients with axial low back pain from a cross sectional cohort survey in Germany  from January 2006 to December 2010. Patients with lumbar axial back pain, at least 18 years old who had previously given written consent, used a hand-held computer  to complete electronic questionnaires for the epidemiological and clinical survey The patient selection was done based on pain drawings performed by the patients in the palm top device. This device is equipped with a body drawing with 34 predefined body areas. The patients were asked to mark their body areas with the most prominent pain. Only back pain patients in whom the lumbar axial back was the predominant complaint were included in the study. Patients with pain radiating into the leg or any other body site were excluded to ensure a homogenous group.DETECT questionnaire (PD-Q) was used. The questionnaire was originally developed to identify neuropathic pain components and was validated in a cohort of patients that included lumbar back pain To assess the somatosensory symptoms within the painful lumbar area the painPain intensity was acquired on a visual analogue scale (VAS) for worst and average pain in the past four weeks as well as current pain.Standard demographic questions and the following questionnaires were used to assess co-morbidities: for sleep disturbances the Medical Outcomes Study Sleep Scale (MOS-SS) and for depressive, panic and anxiety disorders the German-language Patient Health Questionnaire  Descriptive statistical analyses were performed with the SAS package, version 9.2. Relations between two dichotomous variables were assessed by 2×2 contingency tables, relations between categorical data in general using k×m contingency tables. Continuous variables were presented within tables by mean plus/minus standard deviation. Categorical data were tabulated using frequencies and percentages.In order to identify relevant subgroups of patients who are characterized by a typical constellation of 7 sensory symptoms cluster analyses were performed (PROC FASTCLUS) as described before Two calculations were performed: (1) The absolute values for each symptom intensity score were assessed. (2) To eliminate inter-individual differences of the general perception of sensory stimuli  the intensity scores of the questions were re-calculated. In detail, the given 0–5 score of each question was subtracted by the mean of all values marked in the 7 questions. In this individual score values above 0 indicate a sensation which is more intensive than the individual mean pain perception, values below 0 indicate a sensation which is less intensive than the individual mean pain perception.We identified a 5-cluster solution to be the optimal compromise between group size and stability of the clusters. The clusters are represented by the patterns of questionnaire scores, thus showing the typical pathological structure of the respective group. As this is a heuristic approach no statistical analysis was performed.Co-morbidities were analysed with Tukey’s studentized range HSD test.1083 patients  fulfilled the selection criteria as described above. The demographic profiles of the patients are shown in Of all patients 12.1% scored positive on the PD-Q , while 69.3% scored negative  and 18.7% unclear (n = 202)  “total”.A cluster analysis was performed to identify relevant subgroups which present with a characteristic constellation of sensory symptoms. Cluster 1  and cluster 2  demonstrate only one dominating symptom, i.e. painful attacks or pressure induced pain, respectively. In cluster 4  pressure-induced pain and burning sensations were prominent whereas nearly all other symptoms were moderately expressed. Cluster 3  is characterized by relevant prickling and burning sensations. The profile of cluster 5  is mainly concentrated around the zero-line for all parameters. This indicates that the patients tend to mark a similar score for all questions. Although the average pain intensity was VAS 4.9 in this group all sensory symptoms were only rated in the range of “never” to “hardly noticed” . An analysis of the different clusters was not performed because of low patient numbers within the corresponding subgroups.Of the patients with axial low back pain without IVD-surgery 70.3% scored negative in the PD-Q (n = 650), while 11.6% scored positive (n = 107). Post-IVD-surgery patients were negative in 63.3% (n = 100) and positive in 15.2% n = 24, . The freThe study revealed three main findings:Neuropathic pain components are prevalent in axial low back pain patients in more than 10% and co-morbidities occur to a large extent.Patients with chronic axial low back pain can be subdivided into subgroups with distinct patterns of perceived sensory abnormalities (sensory profiles).IVD-surgery influences the pain experience towards a more neuropathic perception.In this study 12.1% of axial low back pain patients scored positive on the PD-Q, i.e. suffered from sensory symptoms which are indicative of neuropathic pain components Our study revealed that patients with axial lumbar back pain are characterized by a variety of different pain types and sensory symptoms that are mechanistically distinct. We performed a cluster analysis to identify relevant subgroups of patients who demonstrate characteristic sensory profiles . In ordeDETECT positive: 4.8%).Nociceptive back pain is evoked by noxious stimulation of deep somatic structures in the lumbar spine, often induced by ingrowth of small nociceptive nerve-fibers into degenerated intervertebral discs. It is characterized by a dull and aching quality localized in the back DETECT positive: 3.38%). They express that even the slightest movement of the affected lumbar spine is capable of inducing a very severe, short lasting pain in the back that ceases immediately after seconds. However, in contrast to radicular pain, it is located in the lumbar region. Physiologically, it can be assumed that these attacks are evoked by ectopic discharges emanating from sensitized nerves e.g. innervating facet joints and outer layers of intervertebral discs Patients who fall into subgroup 1 (22%) predominantly suffer from “pain attacks” (painDETECT positive: 25% (cluster 3) and 17.2% (cluster 4)). These symptoms are characteristic for neuropathic pain syndromes Subgroups 3 and 4 (together 31% of the entire cohort) are characterized by burning and prickling sensations  to surrounding tissues including nerve fibers could explain this observation. High-risk surgical techniques giving rise to chronic postoperative pain have been identified In this cross-sectional survey patients filled out several self-assessed questionnaires . These tools are limited by the comprehension of the questions (e.g. does the patient understand what is intended by the question “does your skin feel numb?”). However, the large cohort of 1083 selected patients from 450 centers is expected to rule out inaccuracies. Also, sensory symptoms and co-morbidities are not the only variables which determine the response to analgesic treatments. The pharmacological response is also influenced by genetic susceptibility and psychological factors such as catastrophizing and expectation which were not assessed in the present investigations.Another methodological consideration may limit the results of our study and questionnaire-based studies in general: Despite good sensitivity and specificity of the PD-Q Our data suggest that sensory profiles based on descriptor severity may be a better predictor for therapy assessment than pain intensity alone especially considering the various underlying mechanisms operating in concert. Phenotypic differences in sensory profiles and co-morbidities as shown in this study as well as in others might explain some of the variance in treatment response and help to tailor an individualized therapy for patients in the future. To achieve this ultimate goal a phenotype-pathophysiology-dependent adaption of the therapeutic regimen for individual patients is required for a more satisfying rate of therapy responders.


Several methods for assessment of severity of pain have been proposed but all of them are subjective.This study evaluated the association concerning changes in electrical resistance (ER) between two acupuncture points and severity of postoperative pain in order to define an objective measurement of pain.In a cross-sectional study, 50 patients undergoing lower extremity orthopedic surgery with postoperative moderate to severe pain  were consecutively enrolled. In the recovery room, the patients' pain scores were assessed and in patients with VAS > 4, the electrical resistance between Li4 and Li11 acupuncture points as well as pain scores was measured prior and following analgesic administration.Following meperidine use, the mean VAS significantly decreased and the ER between the two acupoints was significantly increased. However, Pearson correlation analysis did not reveal any association between the trends of pain intensity and ER (P > 0.05). The ER change in patients operated under epidural anesthesia was significantly less than those who experienced general or spinal anesthesia.There is a coincidence of pain relief and change in the ER of acupuncture meridians without significant association. The diagnostic value of ER for pain, stress response or any other physiologic outcome needs to be investigated in clinical trials with a well-defined control group, with more accurate instruments and probably in different acupuncture meridians. Pain is a subjective sense expressed by the patients and cannot be effortlessly measured by the clinicians . AvailabThis study was conducted to evaluate the association between changes in the ER between Li4 and Li11 acupuncture points and severity of postoperative pain in order to define an objective measure of pain.In a cross-sectional study, a total of 50 American Society of Anesthesiologists (ASA) physical status I-III patients, aged 16–75 years, undergoing lower extremity orthopedic surgery with postoperative moderate to severe pain (VAS > 4) were consecutively enrolled. Patients with severe sweating, addiction to opioids, simultaneous injury, pain or surgery in upper extremities or major complications in the recovery room such as significant bleeding or hypotension were excluded. The study was approved by the regional ethics committee, and written informed consent was obtained from all patients.The surgeries were performed under general anesthesia or neuraxial block based on the decision of attending anesthetist. The general anesthesia was induced with fentanyl, thiopental sodium and atracurium and maintained with propofol and atracurium. The epidural and spinal anesthesia were performed with lidocaine and bupivacaine, respectively. In the recovery room, the patients' pain scores were assessed and in patients with VAS > 4, the ER between Li4 and Li11 acupuncture points were measured prior and following analgesic administration. The analgesic used was meperidine 0.3mg.kg-1. If the pain intensity was not reduced to VAS < 4, the meperidine dose was repeated. Following 20 minutes of the initial dose of analgesic, the ER of the acupoints as well as pain intensity was measured once more. Demographic variables, administered dose of meperidine and complications of treatment were recorded for all patients. Pain intensity was measured with a VAS, a 100-mm horizontal line with anchors of no pain and worst possible pain. Sedation score of the patients were assessed with a 5-point liker scale from 0 = agitate to 4 = unresponsive to verbal stimuli.To determine the location of Li4 acupuncture point the patients were asked to oppose their right thumb against their pointing finger. The prominence in the muscle near to the crease between first and second fingers was considered as Li4 acupoint . To locaData are presented as mean (standard deviation) and frequency (percentage). Electrical resistance prior and following analgesic administration was compared with a paired t-test. The association between changes in ER and pain intensity was evaluated with the Pearson correlation coefficient. The change in ER was compared among different anesthesia methods with One-way ANOVA. All the comparisons were two tailed. P values < 0.05 were considered statistically significant. Statistical analysis was performed with SPSS version 11.5 .Of 50 enrolled patients, 35 were men and 15 were women. Using sedation scale, only 10% of subjects were agitated following arriving at the recovery room was recovered in the following assessment. None of the patients were unresponsive to verbal stimuli. The mean administered meperidine dose was 22.2 ± 4.8 mg. Nausea was recorded in five patients and pruritis in one subject. Following meperidine use, the mean VAS significantly decreased and the ER between the two acupoints was significantly increased . In all Electrophysiologic studies of acupuncture points have been conducted from 1950s in the west with conflicting results up to the present time. Controversial findings may be due to the use of different acupoints, unlike instruments and the variable medical conditions of subjects. Several instruments have been suggested for measuring electrical skin resistance in acupuncture points. For instance in 2006 a new device including a field of 64 electrodes on a surface was presented for standardized measuring of electrical skin resistance. The authors claim that this device would eliminate the impact of various confounders such as pressure, angle of measurement, humidity of the skin and temperature in the measuring room . Another


Intra-articular analgesia is a pain reliever that is frequently administered following arthroscopic knee surgery.The purpose of this study was to compare the efficacy of intra-articular application of morphine and tramadol on postoperative pain after arthroscopic knee surgery.For this randomized double blinded clinical trial, 132 patients undergoing minor arthroscopic knee surgery were randomly assigned to receive either; 5 mg morphine or 50 mg tramadol intra-articularly. Pain was evaluated by means of the verbal pain rating score (VRS) preoperatively (at rest and on movement of the knee joint) and postoperatively at 0, 1, 2, 3, 4, 6, 12 and 24 hours. Meanwhile, the time of the first analgesic request and need for supplemental analgesic were also recorded.P < 0.007). Post-operative VRS scores at 6, 12, and 24 hours were significantly decreased when compared with previous scores in both morphine and tramadol prescribed subjects (P < 0.001), hence, both local analgesics can significantly reduce pain after minor knee surgery.There was no statistically significant difference in VRS scoring between the two groups during the preoperative period either at rest or on knee movement. Meanwhile, VRS scores did not differ significantly between the morphine and tramadol treated groups postoperatively, except for in the one-hour post-operative scores in which the tramadol-treated group experienced less pain (We have found a postoperative analgesic effect of intra-articularly administered morphine and tramadol following minor arthroscopic knee surgeries with a maximum effect 6 hours post injection. Arthroscopic surgery of the knee is frequently undertaken as either a diagnostic or therapeutic approach for knee problems. Postoperatively, different techniques have been applied for pain relief such as non-steroidal anti-inflammatory drugs, intra-muscular and intravenous opioids, intrathecal and epidural narcotics, and patient-controlled analgesia, most of which are associated with side effects , 2. IntrThe present study aimed to evaluate the efficacy of intra-articular application of morphine and tramadol on postoperative pain after arthroscopic knee surgery.For this randomized double blinded clinical trial, 132 patients undergoing minor arthroscopic knee surgery under general anesthesia were enrolled. We included patients who had undergone; partial meniscectomy, chondroplasty, removal of loose bodies and diagnostic arthroscopy. Patients were randomly assigned to receive 5 mg morphine or 50 mg tramadol intra-articularly. All solutions were injected at the end of the operation and before tourniquet release, with the tourniquet being released 10 minutes after the injection was administrated. Preoperatively, patients were instructed to report their pain with a verbal pain rating score (VRS) at rest and on movement of the knee joint. Postoperative pain was also assessed by VRS at 0, 1, 2, 3, 4, 6, 12 and 24 hours. VRS is a 10-point scale tool for evaluation of pain intensity; “0” represents “no pain,” while “10” is the “worst imaginable pain”. Furthermore, the patients were monitored post-operatively for a period of 24 hours for the following parameters; pulse rate, blood pressure, respiratory rate, level of analgesia, time of first analgesic request  and need for supplemental analgesic. Supplemental analgesia was provided with diclofenac sodium oral tablets and total consumption was recorded over 24 hours. Meanwhile, the following exclusion criteria were applied at baseline; evidence of any major systemic illness, major knee surgery, history of allergy to any of the drugs in the study, morphine addiction, regional anesthesia or history of convulsive disorders.P < 0.05. All statistical analyses were achieved using SPSS software .The study protocol was approved by the Ethics Committee of university and all patients were requested to give their informed consent. Results are expressed as mean ± standard deviation (SD) for continuous variables, unless otherwise stated. VRS results were analyzed by a Mann-Whitney U test, however, other data were assessed using a Student t-test and chi-square test, when appropriate. For all tests, significance was defined as The study population included; 53 males and 22 females in the morphine and 39 males and 18 females in the tramadol group with a mean age of 41.0 ± 11.6 and 40.5 ± 10.9 years, respectively. In total, 80% of the morphine vs. 84.2% of the tramadol-treated subjects received midazolam plus fentanyl for general anesthesia, however, the difference did not reach a statistically significant level. Knee arthroscopy is a common day-surgery procedure for which effective pain relief is of the utmost importance, not only for same day discharge, but also to improve comfort and mobility at home , 7. In tOur study had some limitations. Lack of a control group receiving a placebo is the major drawback. Like other studies of the same protocol, VRS is an insensitive scoring system. In conclusion, based on the data presented in this study, we have found a postoperative analgesic effect of intra-articularly administered local anesthesia following minor arthroscopic knee surgery with a maximum effect 6 hours post injection.


Background. The purpose of this study is to investigate the conditions of the temporomandibular joint relative to the effectiveness of an arthrocentesis-like enforced manipulation technique followed by irrigation under high pressure in patients with closed lock. Methods. We performed arthroscopic examination and manipulation followed by irrigation as the initial treatment in 50 joints with closed lock. Relationship between the effectiveness of the procedure and conditions of the temporomandibular joint was statistically analyzed using multiple regression analysis. Results. Significant inverse correlations were found between the extent of improvement in maximum mouth opening after treatment and the initial maximum opening before treatment. There were no significant correlations between improvement of joint pain at mouth opening and in biting and conditions of the temporomandibular joint. Conclusions. Pathologic conditions of the temporomandibular joint did not have an influence on the efficacy of the technique. This result suggests that this procedure has wider application than conventional arthrocentesis. Arthrocentesis is an easy, minimally invasive, and highly efficient procedure to decrease joint pain and increase the range of mouth opening in patients with closed lock of the temporomandibular joint (TMJ). This can be performed under local anesthesia in the outpatient clinic. The effectiveness of conventional arthrocentesis, irrigation under low-pressure with an elevated infusion bag or syringe, has been reported. In those studies –3, low p Previously, we reported the efficacy of a modified procedure with an arthrocentesis-like enforced manipulation technique followed by irrigation under high pressure 40 KPa). In that study 0 KPa. In, no signFifty patients (50 joints) with chronic closed lock of the TMJ who underwent arthroscopic examination and arthrocentesis under sufficient pressure at Tonami General Hospital, Tonami, Japan, from 2004 to 2008, were included in this study. The patients were 5 males and 45 females, ranging in age from 12 to 71 years, with a median age of 44 years. Duration of symptoms of the patients ranged from 3 to 48 months, with a median of 4 months. All of the patients were found to have anterior disc displacement without reduction, evident by magnetic resonance imaging.Magnetic resonance imaging was performed using a 1.5-T imager  with a dual 3-inch surface coil. T1-weighted and fat-saturated T2-weighted images were obtained in both the sagittal and coronal planes. The transaction plane was scanned to find the long axis of the condyle; the sagittal plane was considered to be perpendicular to this long axis with 3-mm section thickness and the coronal plane was considered to be parallel to the long axis with 3-mm section thickness. The degrees of disc shape and bone change were examined with these sequences.Arthroscopic examination and arthrocentesis were performed by the same specialist within 2 weeks after the magnetic resonance imaging, according to the technique of Yura et al. , 5. A 1.A schematic image of arthroscopic examination and arthrocentesis is shown in The patients were examined before arthrocentesis and every 2 weeks after arthrocentesis for 8 weeks. Their maximum mouth opening (MMO), joint pain at mouth opening, and joint pain in biting, measured on a visual analog scale (0 to 100), were evaluated. The effectiveness of the arthrocentesis was evaluated from any range of increase in MMO (in mm) and improvement rate of joint pain (percentage) after the procedure. With respect to conditions of the patients before arthrocentesis, we examined sex, age, duration of symptoms, MMO, joint pain, and degrees of disc deformity, bone change, synovitis, cartilage change, adhesion, and disc perforation.U test and Spearman's rank correlation coefficient were used for analysis of the correlation between the effectiveness of the procedure 1 month after surgery and conditions of the patients. Furthermore, these factors were statistically analyzed by multiple regression analysis .The Mann-Whitney's Eight weeks after arthrocentesis, the MMO of the patients improved a median of 13 mm  , the joiP value) between the effectiveness of arthrocentesis 1 month after surgery and conditions of the patients are shown in R2 = .450 was analyzed by multiple regression analysis. There were no significant correlations between improvement of joint pain at mouth opening and in biting and conditions of the TMJ .The correlations (In previous reports –3, the eA significant inverse correlation was found between the increase in the posttreatment MMO measurement and the initial pretreatment MMO measurement. In this study, the correlation supported the effectiveness of the procedure, which was evaluated by the increase in MMO. Adhesions did not have an influence on the efficacy of arthrocentesis under sufficient pressure, because the technique could remove adhesions and widen the joint space . On the R2 = .450 was analyzed by multiple regression analysis. The result indicated that the correlation could be somewhat explained. Alternatively, with respect to the factors related to improvement of joint pain, R2 < .20 was analyzed. The result indicated that the presence of other factors strongly related to the effectiveness of the procedure.In the correlation between the improvement of MMO and conditions of the patients, We studied the effectiveness of arthrocentesis under sufficient pressure and statistically analyzed the correlation between the effectiveness of the procedure. Pathologic conditions of the TMJ did not influence the improvement in MMO, joint pain at mouth opening and joint pain in biting. This procedure can be performed under local anesthesia in the outpatient clinic. This is an easy, minimally invasive, and highly efficient one in patients with persistent closed lock. The application of this procedure is wider than that of arthrocentesis under low pressure, and the technique should be introduced widely.


Adequate pain control is an important consideration in the post-surgical management of patients. Local nerve blockade added to general anesthesia can provide excellent pain control during and after most nasal surgical procedures. The aim of this study was to determine the combined effect of local anesthetic drugs with corticosteroids in nasal surgery.In this double-blind clinical study, 60 patients who underwent different nasal surgical procedures were matched and divided into two equal groups. Bilateral local nerve blockade was used in both groups. Bupivacaine or bupivacaine plus dexamethasone was administered by injection . Postoperative visual analog scale (VAS) pain values and the need for oral/intramuscular analgesic treatment in the first 24 h were recorded in all patients. Thirty-eight male (63.3%) and 22 female (36.7%) patients were included in this study, with a mean age of 28.3 ± 8.2 years. At 1, 2, 4, 6, and 12 h post surgery, VAS pain values were significantly lower in the B+D group than in the B group. The analgesic requirement was significantly lower in the B+D group compared with the B group. No relevant complications were seen during surgery or postoperative hospitalization. This study demonstrates the positive effect of a combination of a dexamethasone with a bupivacaine in reducing pain and the need for analgesic drugs after different nasal surgeries. No acute or short-term post-surgical complications were observed in this study.Appropriate pain control is an important consideration in the post-surgical management of patients. Physicians should ensure that therapeutic procedures are not the cause of extra and unnecessary pain to patients. Pain is particularly common after nasal surgery, especially when bone manipulation and periosteal irritation are involved. Substantial research and clinical observations suggest that pain reduction can be achieved in nasal surgery through use of local anesthesia.The use Lidocaine and bupivacaine are commonly used for local injection or nerve blockade in nasal surgeries . Numerous studies performed in Iran and other countries have demonstrated an advantage of topical administration, local injection, and nerve blockade with bupivacaine or lidocaine versus saline. Other studies have shown an advantage of bupivacaine over lidocaine with regard to pain control and duration of pain control.In this paper, we investigate the combined effect of dexamethasone with bupivacaine as local anesthesia after nasal surgery, in order to determine the optimal procedure for pain control and reduction of analgesic use post surgery. This double-blind clinical study was carried out in the otorhinolaryngology ward of Imam-Khomeini Hospital, Ahwaz. A total of 60 patients who underwent different nasal surgical procedures ) under general anesthesia were matched according to demographic factors such as age, sex, BMI, type of surgery,…and divided into two groups of 30. Bilateral local nerve blockade of the infraorbital nerve, supratrochlear nerve, and terminal branches of the nasopalatine nerve was used in both groups immediately after general anesthesia.®; 0.5%, 5–20 cm3, with a mean dose of 1–1.5 mg/kg and a maximum dose of 100 mg) and bupivacaine plus dexamethasone  was administered by injection to the B and B+D groups, respectively. Bupivacaine  pain scores (0–100) were recorded 1, 2, 4, 6, 12, and 24 h postoperatively in all patients. A 325mg Acetaminophen (Paracetamol) tablet was available upon patient request postoperatively, with intramuscular Pethidine (Ampul 20mg) as ‘‘rescue’’ analgesia. The need for analgesic agents, including oral treatment or intramuscular (IM) injection in the first 24 h after the operation was recorded in a double-blinded manner. Post surgical pain and need to analgesics in the first 24 hours was Calculated and compared in any type of nasal surgery separately,and then final results were gathered together and Analysised Generally.th Edition).T-tests and chi-square tests were used for comparison of quantitative and qualitative variables. Final data were analyzed with descriptive statistics using with SPSS software  and 22 female (36.7%) patients were included in this study, with a mean age of 28.3 ± 8.2 years. Patients underwent closed nasal bone reduction, septoplasty, FESS, and/or rhinoplasty . There wAt 1, 2, 4, 6, and 12 h post surgery, VAS pain scores were significantly lower in the B+D group than in the B group but there was no statistically significant difference between the groups in VAS at 24 h after surgery P=0.221 .The analgesic requirement was significantly lower in the B+D group compared with the B group (P=0.038), with 12 and 18 patients requiring post-surgical oral/intra muscular analgesics, respectively . No releLocal anesthetic injection and nerve blockade have been used for many years, but the techniques are now more popular than ever. The major advantages of these techniques, whether used alone or adjacent to general anesthesia are their inherent simplicity and safety. Recently, studies have shown that local injection with bupivacaine ≤0.25% density) causes in local anesthesia and vasoconstriction (% densityThe effect of different local anesthetic agents in comparison with normal saline and each other was reviewed in various studies. One study done by Edward and Colleagues in university of California demonstrated beneficial effect of bupivacaine versus normal saline in pain control after nasal surgery . This adAdvantage of local injection with bupivacaine 0.25% in comparison with lidocaine 2%+ Epinephrine 1/100,000 in pain control and reduction need for post-surgical analgesics was shown In another study done by Yavuz and Colleagues in 2008 .In this investigation, no study was seen relative to combination corticosteroids with local anesthetic agents in Otorhin- olaryngologic fields but using this technics in other body areas was reported, as in study done by Kopacz and Colleagues in university of Seattle adding dexamethasone to bupivacaine for intercostal nerve blockade reduced time for local anesthetic's onset and prolonged painless and senseless duration significantly . In anotThe results from the present study demonstrate a positive benefit for the combination of dexamethasone with bupivacaine in the reduction of pain and requirement for analgesic drugs after different nasal surgical procedures. No acute or short-term post-surgical complications were observed in our study. Further larger studies seems to be inevitable in order to fully investigate these positive benefits.


The upper cervical nerve roots (C1-3) are increasingly viewed as an important target for therapeutic intervention in headache, but their specific roles in the pathophysiology of head pain remain uncertain. An increased understanding of the role of C1-3 in primary and secondary headache disorders is important for progress with diagnostic and therapeutic interventions involving these structures.The Objectives of this study are to characterize the distribution of pain provoked by stimulation at the C1-3 levels, and to investigate the potential efficacy of a novel, brief low temperature radiofrequency rhizolysis (BLT-RF) as a therapy for patients with occipital neuralgia.This study is a retrospective review of data from 9 patients with occipital neuralgia  who underwent fluoroscopically guided multi-modal provocation at the C1, C2, and C3 levels followed by nerve root block with anesthetic and steroid. 7 patients underwent subsequent BLT-RF of the C1 spinal nerve and C2 and C3 dorsal root ganglia.Patients with migraine all reported retro-orbital or periorbital pain with C1 stimulation. By contrast, patients without migraine reported occipital or cervical pain with stimulation at the C1 level. C2 and C3 stimulation evoked pain in occipital and cervical distributions similar to those previously reported. BLT-RF produced sustained pain relief in patients who had only transient relief with nerve block.The orbital/peri-orbital pain evoked by stimulation at the C1 level indicates that the C1 nerve root may play an important role in conditions in which pain occurs in this distribution, including migraine and cluster headache. The C1 nerve root may therefore be an important target for therapy for these conditions. The BLT-RF technique appears to be a safe and effective therapeutic approach to occipital neuralgia, with a longer duration of action than nerve blockade with anesthetics and steroids.


Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for postoperative pain in patients undergoing hernia surgery. Methodology. Total 202 patients received single intramuscular injection of dexketoprofen 50 mg or diclofenac 50 mg postoperatively. The pain intensity (PI) was self-evaluated by patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were number of responders, difference in PI (PID) at 8 hours, sum of analogue of pain intensity differences (SAPID), and onset and duration of analgesia. Tolerability assessment was done by global evaluation and adverse events in each group. Results. Dexketoprofen showed superior efficacy in terms of number of responders (P = .007), PID at 8 hours (P = .02), and SAPID0–8 hours (P < .0001). It also showed faster onset of action (42 minutes) and longer duration of action (6.5 hours). The adverse events were comparable in both groups. Conclusion. Single dose of dexketoprofen trometamol 50 mg given intramuscularly provided faster, better, and longer duration of analgesia in postoperative patients of hernia repair surgery than diclofenac 50 mg, with comparable safety. Pain is a common surgery-related reason for unexpected hospital admissions. Inadequate pain control can result not only into harmful physiological consequences like nausea, vomiting, increased rate of venous thromboembolism, and delayed wound healing, but also psychological ill-effects like anxiety, anger, depression, and reduced patient satisfaction . Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are considered effective analgesics for postoperative pain control . NSAIDs Dexketoprofen or (S)-(+)-ketoprofen is several times more potent than its racemate, ketoprofen. The levorotatory isomer is 100 times less potent as a cyclooxygenase-2 inhibitor than dexketoprofen, however, may contribute to the ulcerogenic effect of the drug . Dexketoprofen has been shown to possess comparable efficacy and better tolerability over ketoprofen in several clinical studies . Earlierhttp://www.ctri.in/). Written and informed consents were obtained from all patients before their enrollment.Prior approval was obtained from Drug Controller General of India (DCGI) and appropriate ethics committees. The study was conducted in accordance with Good Clinical Practice guidelines  and according to the Declaration of Helsinki. The trial was registered at the Clinical Trials Registry—India . The major exclusion criteria were: known hypersensitivity to the study medications, complication during or after surgical procedure, active or suspected gastrointestinal ulcer or chronic dyspepsia or gastrointestinal bleeding, inflammatory bowel disease, history of bronchial asthma; major organ dysfunction, hemorrhagic diathesis, and other coagulation disorders. General contraindications to the use of NSAIDs as well as concomitant treatment with any anti-inflammatory or other therapy known to affect the study outcome were also considered criteria for exclusion.http://www.randomization.com/ in the blocks of ten. This was multicentric, open-label, randomized, comparative clinical trial conducted over 11 centers across India. The randomization was carried out online at Eligible patients were randomly assigned to receive either single intramuscular dose of dexketoprofen trometamol 50 mg  or diclofenac sodium 50 mg  postoperatively, when patient first complained of pain. The drugs were administered slow intramuscularly after a washout period of at least 45 minutes of intravenous and 4 hours of intramuscular analgesic, if given intraoperatively. Any medication which was considered necessary for the patient was given at the discretion of investigator provided it did not interfere with the study drug evaluation.The pain intensity (PI) was self-evaluated by the patients on visual analogue scale (VAS)  at intervals of 1, 2, 4, 6, and 8 hours after the injection. Patient showing at least 50% improvement was termed as a responder. Proportion of responders in each group (responder rate) at the end of 8 hours was taken as primary efficacy variable. The secondary efficacy variables included time of onset of significant decrease in VAS score, pain intensity difference (PID) at the end of 8 hours, and sum analogue of pain intensity difference (SAPID) over 8 hours. 0–8 hours was calculated as the weighted sum of the PIDs obtained from t = +1 hour (hr) to t = 8 hours (hr) on VAS using the following equation [PID was calculated for each observation by subtracting the present PI from the baseline value. SAPIDLaboratory investigations were done at baseline as well as at discharge or on 3rd postoperative day whichever was earlier. Tolerability was assessed by recording patient's global assessment about the tolerability of the drug and percent of the patients experiencing any drug-related adverse events.t test. The within-group comparison of VAS scores was done using paired t test. Tolerability was assessed by evaluating the percentage of patients reporting side effect. Analysis of adverse events and global assessment of safety and efficacy was done using Fisher's exact test. For all statistical tests, a “P” value of less than  .05 was considered significant.The sample size was calculated by using GraphPad StatMate version 2.00 for Windows, GraphPad Software. A sample size of 90 in each group had 80% power to detect an increase of 20% responder rate with a significance level  of 0.05 (two tailed). Fischer's exact test was applied to observe, if there are significant differences between the responder rates. The decrease in PI (VAS score), PID, SAPID, onset of analgesia, and duration of analgesia were calculated (Mean ± SD) for each group and compared between the groups by using unpaired Total 204 patients were screened and enrolled in the study. Two patients did not continue with the study as they did not report for the surgery. So, total 202 patients received the medications and completed the study; of whom 99 received dexketoprofen and 103 received diclofenac. Demographic parameters and baseline pain scores between the two groups are shown in P = .007). As shown in P < .0001) indicating the efficacy of each medication. The dexketoprofen group showed significantly greater reduction in mean VAS score compared to diclofenac group (P = .003). The responder rate in the dexketoprofen group (55.56%) was statistically superior to that in diclofenac group (35.92%) .As shown in P < .0001). The duration of analgesia for dexketoprofen was also significantly greater than diclofenac with the mean difference of about 50 minutes (P = .003). The onset of analgesia for dexketoprofen was significantly faster than diclofenac by a mean of approximately 18 minutes (P = .41). In addition to this, mild itching was observed in one patient receiving dexketoprofen.The incidence of adverse events in dexketoprofen group (26.26%) was comparable to that in diclofenac group (20.38%). Pain at the injection site was the most common adverse reaction with the incidence being 25.25% and 20.38% in dexketoprofen and diclofenac groups, respectively, (As shown in The goal of postoperative pain management is to relieve pain while keeping side effects to minimum. NSAIDs are effective analgesics without undesirable side effects of opioids like sedation, respiratory depression, nausea and vomiting, and so forth. They inhibit the synthesis of prostaglandins which are responsible for pain, fever, and vasodilatation in response to trauma. These drugs are particularly useful in managing the pain associated with minimally invasive surgery like hernia repair . As compared to several other NSAIDs, ketoprofen has relatively higher analgesic than anti-inflammatory activity favoring its use in acute pain conditions . DexketoIn the present study, single dose of dexketoprofen 50 mg given intramuscularly could provide adequate pain relief in postoperative pain which was significantly better than the comparator, diclofenac 50 mg, as reflected from increased number of responders. The higher values of PID and SAPID at the end of 8 hours indicates longer duration of action of dexketoprofen trometamol. The onset of action of dexketoprofen was also found to be faster than diclofenac which confirms the results of earlier studies. The overall adverse effect profile of dexketoprofen appeared to be no different from diclofenac with similar incidence of adverse events. However, the subjective assessment of tolerability and efficacy by patients and physicians distinctly reflected the superiority of dexketoprofen over diclofenac.The present study confirms the findings of earlier clinical studies on oral as well as parenteral dexketoprofen that have demonstrated faster onset of action and good safety and efficacy of dexketoprofen trometamol. The present study has a limitation that it was an open-label study. The dose of diclofenac was kept as 50 mg in order to compare equivalent milligram for milligram efficacy of dexketoprofen versus diclofenac. The 50 mg dose diclofenac has also been used in earlier studies with dexketoprofen .Single dose of dexketoprofen trometamol 50 mg given intramuscularly provided faster, better, and longer duration of analgesia in postoperative patients of hernia repair surgery than diclofenac 50 mg, with comparable safety.


Patient reported outcomes (PROs) are important measures in rheumatoid arthritis (RA). A register of patients with RA from all rheumatology care providers in Malmö, Sweden, was established in 1997 and has been continually updated. This register includes virtually all the RA patients in the area. The aim of this study was to analyse PROs in surveys of this population conducted between 1997 and 2009, and to assess differences in treatment and outcome in male and female patients.In 1997, 2002, 2005 and 2009, questionnaires were sent to the RA patients in the register . Response rates varied between 62 % and 74 %, and 72-74 % was women. Questionnaire data included medication and measures of disability and health related quality of life. Data on rheumatoid factor (RF) tests were retrieved from the databases of the two clinical immunology laboratories in the area. In order to limit the impact of changes in the case mix over time, the study was restricted to RF positive patients. The analyses were stratified by sex.Patients reported less severe outcomes for all measures in the later surveys compared to 1997, and patients’ global disease activity assessment and self-reported pain were further improved in 2009 compared to 2005. Treatment with biologics increased over time from 1997 (none) to 2009 (29%), with no difference between men and women. Visual analogue scales (0-100) for patients’ global assessment of disease activity [mean 45 (95 % CI (45-47) vs. 38 (35-40)] and pain [mean 46 (44-49) vs. 38 (36-40)] decreased from 1997 to 2009, with numerically greater improvement in male patients. The mean SF-36 physical component scores also improved, and were higher in men than in women in all surveys.Pharmacologic treatment of RA became more extensive over time, and there was improvement in all PROs. Despite similar treatment, male patients reported better outcomes, in particular for pain and physical function, compared to female patients. We suggest that patient reported outcomes should be reported separately in male and female patients with RA. Rheumatoid arthritis (RA) is a chronic, inflammatory disorder, which is characterized by progressive joint damage and has a major impact on physical function and health related quality of life (HRQoL). There is evidence indicating that the disease has become less severe during the last decades, possibly due to better management with more extensive treatment, or secular changes in other factors influencing disease severity. For example, a lower disease activity and disability in 1995 compared to 1978 has been demonstrated in Swedish patients with RA. FurtherA patient-reported outcome (PRO) is a questionnaire used in a clinical trial or a clinical setting, where the responses are collected directly from the patient. A number of PROs are validated measures that are considered relevant outcomes in quantitative research and feasOur aim was to investigate changes over time in PROs such as visual analogue scales (VAS) for patients’ global assessment of disease activity and pain, disability and HRQoL, as well as treatment in male and female patients in a population-based sample of patients with RA.In 1997, a register of all known patients with RA in the city of Malmö, Sweden, was established. Inclusion was based on a clinical diagnosis of RA by a rheumatologist and fulfilment of the 1987 American College of Rheumatology (ACR) criteria for RA[The corresponding background population of Malmö was 251,000 in 1997. Patients were recruited from the rheumatology outpatient clinic of Malmö University Hospital , which is the only hospital serving the city, and from the four rheumatologists in private practice in Malmö,2.The prevalence of RA in the area (approximately 0.5 % among those aged 20 years and above) and the sex and age distributions in the Malmö RA register were found to be comparable to the RA prevalence in a study from a population-based RA register in Oslo, Norway. SubsequIn 1997, 2002, 2005 and 2009, self-administered questionnaires were sent to the patients in the Malmö RA register. Demographics, working status, medication with disease modifying anti-rheumatic drugs (DMARDs), visual analogue scales (VAS) for general health and pain, use of healthcare, the Swedish version of the health assessment questionnaire (HAQ), and HRQSF-36 is a generic measure of eight health dimensions  with scale from 0 to 100 . A reminder was sent to patients who did not answer the questionnaire the first time.The study was approved by the regional research ethics committee in Lund, Sweden. Data on rheumatoid factor (RF) tests were retrieved from the databases of the two clinical immunology laboratories in the area. In order to limit the impact of changes in the case mix, in particular regarding mild, RF negative cases, over time, in the present comparison, only patients with at least one positive RF test were included. The analyses were stratified by sex.Data were analyzed with version 18.0 of the Statistical Package for the Social Sciences . As the questionnaire data in 1997, 2002, 2005 and 2009 included partly overlapping patient populations, no formal statistical comparisons were made between these patient cohorts. Too few had responded to repeated surveys to allow meaningful longitudinal data analyses. Variables with a normal distribution are presented as means with 95% confidence intervals (95% CI) whereas those with a non-normal distribution are presented as medians with interquartile ranges (IQR). As a conservative estimate we assumed that a significant change had occurred if the 95% CIs of a measure in 1997 and at subsequent years of examination did not overlap. The SF-36 scores were compared to the expected derived from normative values from the Swedish population for eachIn 1997, 2002, 2005 and 2008, questionnaires were sent to the RA patients in the register . Overall response rates were 74 %, 66 %, 64 % and 62 %, respectively. The demographics of responders with at least one positive test for RF are shown in Table More patients were treated with methotrexate in 2005 and 2009 compared to 1997 (Figure As expected, treatment with TNF inhibitors and other biologics was only reported in 2002 and later. Reported current treatment with biologics increased gradually over time from 2002 to 2009, without major differences between male and female patients Figure . In 2009Patients’ global assessment of disease activity and pain both decreased substantially from 1997 to 2009 Table . DespiteThere was no major difference in age between male and female responders in either of the surveys Table . Male paIn this study, we found that treatment with biologics and corticosteroids increased over time, and there was improvement in all patient reported outcomes. Despite similar treatment, male patients reported better outcomes and more improvement, in particular for the impact of pain, compared to female patients.Several previous studies have reported improved outcomes over time in comparisons of samples of patients with RA evaluated at different time points. Such improvements were observed in patients’ clinical status according to disease activity,17, funcTriple therapy with methotrexate, sulphasalazine and antimalarials was rarely used in this cohort. The low use of triple therapy in 2009 was similar to that observed in 2010 in a cross sectional study from Kristiansand, Norway, but lowImprovement of PROs in patients with RA is of major clinical relevance. Not only are reduced disability and improved HRQoL important treatment goals in themselves, but such measures also predict long term outcomes. For example, disability, measured using HAQ, has been shown to predict mortality in several studies,27,28.In the survey performed in 2009, patients with RA had significantly lower scores for physical as well as mental components of HRQoL compared to the expected based on normative data. This suggests that although patients with RA surveyed in 2009 were significantly improved compared to previous investigations in 1997, 2002 and 2005, there is still a major difference in HRQoL compared to the general population. Evidently, there is still need for further improvements in the management of RA.Influence of gender on various aspects of disease severity has been described in several studies. One retrospective review of a community based sample revealed a higher proportion with erosive disease in male patients, but a greater number of orthopaedic procedures in women. In studOne possible explanation for such differences could be lower muscle mass in women. However, in our study, there were major differences in SF-36 scores compared to the general population for both sexes, with greater numerical differences for women.The results of the present study are compatible with the concept that a higher pain perception in women is part of the explanation for these findings. This may reflect patterns that are not specific for RA, since chronic widespread pain is twice as frequent in women as in men in the general population, and femThe major strengths of this study include the use of a community-based register of patients with RA diagnosis from a well-defined area, with structured assessment using repeated questionnaires during a period of 11 years.Limitations include the sample size, which affects the precision of some of the outcome estimates, the lack of longitudinal data for analysis of individual cases, and the lack of available objective measures of disease activity due to the study design.In a well-defined population of patients with RA that received more aggressive treatment over time, we have demonstrated improvement in patient reported outcomes.Despite similar treatment, male patients reported better outcomes and greater improvements over time, especially for pain and physical function. We suggest that patient reported outcomes should be reported separately in male and female patients with RA.The authors have no potential conflicts of interest regarding this paper.KH performed the medical record review, participated in the design of the study and the statistical analysis, and drafted the manuscript. LJ and YL participated in the design of the study, developed the questionnaires and participated in the analysis and interpretation of data. JÅN participated in the design of the study and the statistical analysis. CT participated in the design of the study, assisted in the medical record review, participated in the statistical analysis and helped draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/15/44/prepub


Chest pain is a common diagnostic challenge in primary care and diagnostic measures are often aimed at confirming or ruling out acute ischaemic heart disease. The aim of this study was to investigate management of patients with chest pain out-of-hours, including the use of ECG and laboratory tests, assessment of severity of illness, and the physicians’ decisions on treatment and admittance to hospital.Data were registered prospectively from four Norwegian casualty clinics. Data from structured telephone interviews with 100 physicians shortly after a consultation with a patient presenting at the casualty clinic with “chest pain” were analysed.A total of 832 patients with chest pain were registered. The first 100 patients (corresponding doctor-patient pairs) were included in the study according to the predefined inclusion criteria. Median age of included patients was 46 years, men constituted 58%. An ECG was taken in 92 of the patients. Of the 24 patients categorised to acute level of response, 15 had a NACA-score indicating a potentially or definitely life-threatening medical situation. 50 of the patients were admitted to a hospital for further management, of which 43 were thought to have ischaemic heart disease. Musculoskeletal pain was the second most common cause of pain (n = 22). Otherwise the patients were thought to have a variety of conditions, most of them managed at a primary care level.over- and under-triage probably occur in out-of-hours primary care.Patients with chest pain presenting at out-of-hours services in Norway are investigated for acute heart disease, but less than half are admitted to hospital for probable acute coronary syndrome, and only a minority is given emergency treatment for acute coronary syndrome. A wide variety of other diagnoses are suggested by the doctors for patients presenting with chest pain. Deciding the appropriate level of response for such patients is a difficult task, and both  Chest pain is a common diagnostic challenge in primary care for both general practitioners (GPs) during day time surgery hours and in casualty clinics out-of-hours -4. DiagnIn Norway, patients with chest pain in need of acute medical assistance are encouraged to call the national three digits emergency telephone number ″113″. Still, many patients with chest pain choose to contact their GP directly, or the local casualty clinic out-of-hours. A recent study from Norway showed that patients with chest pain constituted 21% of all medical emergencies outside hospitals. The study also revealed that most of the patients were not as ill as initially assessed at the emergency medical communication centres, pointing to the challenges in deciding the appropriate level of response in patients with chest pain outside hospitals [Diagnosing chest pain in primary care is a complex task. Previous studies have confirmed the importance of a thorough patient history on sensation of pain  and concomitant symptoms when diagnosing acute IHD ,9. StillIn a hospital setting, patients with chest pain of suspected cardiac origin are often diagnosed and treated according to specific guidelines and to some extent clinical decision rules. The pre-test probability of IHD is greater  than in primary care  and diagnostic tools are readily available to make more definitive diagnoses. Previous studies have shown that Norwegian out-of-hours services generally are well-equipped with laboratory and diagnostic tools, but the selection of tests are mainly adapted to a primary care setting ,13. One Little is still known about the management of chest pain in Norwegian out-of-hours primary care. No research exists on the use of diagnostic tools; how patients with chest pain are treated; or how many patients that end up being admitted to a hospital.The aim of this study was to investigate the use of diagnostic tools and treatment of choice in patients with acute chest pain out-of-hours in Norwegian primary care. We registered the use of ECG and other laboratory tests, assessed the severity of illness, and also the physicians’ decisions on treatment and admittance strategies.Four Norwegian casualty clinics, located at Sotra, Haugesund, Drammen and Kristiansand, were involved in the study. The casualty clinics were chosen according to strategic sampling to cover both rural, suburban and urban districts, and to include both larger and smaller casualty clinics. Data were collected prospectively from February to July 2012.Data in the analyses come from structured telephone interviews with 100 physicians shortly after a consultation with a patient presenting at the casualty clinic with “chest pain” as his or her main symptom. Each physician could only be interviewed once, and the casualty clinics continued registration of patients until the predefined number of 100 unique physicians with 100 corresponding patients had been included. The number of included physicians and patients were chosen to ensure the possibility of interviewing all physicians shortly after the consultation, and to ensure a large enough sample to perform sub group analyses. The patients were registered prospectively by the nurses at the cooperating casualty clinics. All patients with “chest pain” or equivalent symptoms, independent of the probable cause of complaint, were registered with a unique identification number in a patient log. The variables recorded were consultation date and time, name, birth date, sex, age of the patient, response level and name and telephone number of the physician who treated the patient. Equivalent symptoms to chest pain included “tightness in chest”, “retrosternal pain” and “chest discomfort”. Patients with symptoms suggestive of mastitis were excluded. One of the authors (RAB) had daily contact with the four casualty clinics, gathering all registered patients and variables, excluding patient name and date of birth to achieve anonymous data collection. Before patient inclusion started, all nurses and physicians at the cooperating casualty clinics were informed of the study through information meetings and distribution of the inclusion criteria and the study protocol. Oral consent was obtained from the physicians at the beginning of the interview. To ensure anonymous data collection, the physicians were explicitly asked to not disclose the patient’s name and/or date of birth. If a physician could not be reached by telephone, and interviewed, within 2 days after the consultation, he or she was excluded from participation, to reduce recall bias. The variable “level of response” was set by the nurses at the casualty clinic using the Norwegian Index of Medical Emergencies . The IndThe questionnaire used in the telephone interview had two parts, where the first part consisted of questions related to the patient they just had treated, including diagnostic measures  and choice of treatment. Severity of illness was set by the physicians using The National Committee on Aeronautics (NACA) Score System . In the IBM Statistical Package for the Social Sciences (IBM SPSS version 20) was used for statistical analyses. Standard univariate statistics were used to describe the material, including mean and median. Student’s t-test was used to compare mean age between all registered patients and the included study patients. For other comparisons the Pearson Chi-Square test was used. A p-value of < 0.05 was considered statistically significant.The study was given approval by the Regional Committee for Medical and Health Research Ethics (REC West) before inclusion started (Reference number 2010/1499-10).A total of 832 patients with chest pain were registered at the four participating casualty clinics, of which 100 patients with corresponding structured telephone interviews with the physician on-call, were included in the study  and acetylsalicylic acid (ASA) , were most often the treatments of choice. Nine patients were given morphine, two patients received antacida and one patient was given a benzodiazepine.Table We included 100 individual patients after interviews with 100 unique physicians, from a sample of 832 patients with chest pain. Median age of the included patients was 46 years, men constituted 58%. An ECG was taken in 92 of the patients, other laboratory tests in a majority. Of the 24 patients categorised to an acute level of response, two thirds had a NACA-score indicating a potentially or definitely life-threatening medical situation. Half of the patients had suspected ischaemic heart disease; the rest had a variety of conditions. Half of the patients were admitted to a hospital for further care, of which a large majority were thought to have heart disease.A main strength of the study is the prospective registration of all patients with chest pain at the collaborating casualty clinics. To avoid dependency and an unbalanced weighting of the data; each patient and physician could only be included once. Answering of the questionnaire through telephone interviews enabled the interviewer to give precise instructions. We aimed to reduce recall bias by reaching the physicians shortly after the consultation, but some recall bias will be expected when interviewing a physician about a specific patient one or two days after an out-of-hour shift. The NACA-score has been widely used in studies concerning pre-hospital emergency medicine, and all included physicians were thoroughly explained how to use the scoring system. However, most of the interviewed physicians did not know the scoring system before the interview, and this might limit the reliability of its use. The data does not include the place of consultation , and the study design did not allow physician appraisal on how they decided the level of care for treatment. Due to resources available for interviews, the study was limited to 100 patients and doctors, a number that may limit the inclusion of more seldom diagnoses.A recent study from Belgium  examinedPatients with chest pain account for approximately 1-2%  of all cOur study confirms that acute chest pain is a common diagnostic challenge in a primary care setting ,2,5,6, aThe introduction of high-sensitivity (hs) troponin-tests, also in primary care, might change how GPs diagnose patients with acute chest pain in the near future. But it is important to bear in mind that an increased level of hs-troponin concentration alone does not give the diagnosis of acute myocardial infarction, according to recent guidelines . Diagnosover-triage”, well known to be resource demanding. On the other hand, 11 of the 76 patients (14%) given a yellow or green response level were also in need of rapid diagnostics and/or treatment (NACA ≥ 4), indicating possible “under-triage” and a potentially harmful underestimation of the patients’ severity of illness.Deciding the appropriate level of response can also be a difficult task, especially in patients with chest pain . Our stuhow physicians’ diagnose patients with chest pain in out-of-hours primary care and their reasons for deciding if the patient should be admitted to the hospital or not. More research is needed to elucidate this important part of GPs out-of-hours work.Half of the 100 patients in the study were admitted to hospital, and as many as 86% of the patients with an initial diagnosis of heart disease were admitted urgently. A recent study from the UK  showed tover- and under-triage probably occur in out-of-hours primary care.Patients with chest pain presenting at out-of-hours services in Norway are investigated for acute heart disease, but less than half are admitted to hospital for probable acute coronary syndrome, and only a minority is given emergency treatment for acute coronary syndrome. A wide variety of other diagnoses are suggested by the doctors for patients presenting with chest pain. Deciding the appropriate level of response for such patients is a difficult task, and both The authors declare that they have no competing interests.RAB, EZ and SH planned and established the project, including the procedures for data collection, and designed the paper. RAB performed the analyses and drafted the first manuscript. All authors took part in rewriting and approved the final manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/15/51/prepub


We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism.Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis .sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA.These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA. Pain is the most prominent and disabling symptom of knee osteoarthritis (OA) and is an increasingly important public health problem -4. Pain The gold standard for assessing joint damage is still the plain radiograph. However, this method only provides a historical view of the skeletal damage that has already occurred. Radiography is relatively insensitive, and does not allow for the early detection of pathological changes in joint tissues and early joint damage. In addition, often weak associations have been reported between pain and radiographic change .There is an urgent need for an improved understanding of the origins of joint pain and tests that allow for the evaluation of treatment responses designed to arrest joint destruction and control pain . In joinThis study of early knee OA and joint pain was designed to test the hypothesis that there exist interrelationships between the onset of early stage radiographically defined knee OA, the presence and absence of knee pain and changes in skeletal and synovitis biomarkers of tissue turnover and joint inflammation, respectively, that can be measured in body fluids. Based on earlier work with tissue specific biomarkers we believe that their use may aid in the understanding of the source(s) of knee pain.Prior studies of OA knee pain involving biomarkers are limited but results have been encouraging. Briefly, elevations of serum cartilage oligomeric matrix protein (COMP) have shown an association with knee pain but not for the cartilage collagen biomarker CTX-II , the latSince it is known that structural changes in OA joints involving articular cartilage, as revealed by Kellgren and Lawrence grading  and MRI Five commercial biomarker assays were used in these analyses: serum cartilage type II collagen cleavage by collagenase (sC2C) ,15; urinThe study protocol was approved by the institutional review board of Juntendo University. We received a written consent from each of the patients enrolled in this study.A total of 46 patients with a Kellgren-Lawrence (K/L) grade of 1 or 2 were enrolled in this study among the patients who visited the hospitals from September 2007 to March 2008. Patients with knee pain had complained of pain in the medial femorotibial compartment of the studied knee on most days of the month prior to examination and removal of body fluids. Patients had not experienced any traumatic episodes during this period. Knee pain was assessed using a visual analogue scale . The subjects were defined as those without pain if they indicated a VAS score of zero for this same period. Conversely, subjects were defined as having pain if they indicated a score of more than zero, and they fulfilled the criteria of knee OA of the medial femorotibial joint as defined by the American College of Rheumatology (ACR) criteria . StandinBoth serum and urine samples were obtained from all patients on the day that pain and function were assessed, and radiographs taken. The non-fasted second void urine samples and non-fasted morning blood samples were collected for serum analyses. The urine and serum samples were stored at -80°C until analysed.The biomarkers used were sC2C, sCPII, sHA, uCTX-II, and uNTx. uCTX-II and uNTx values were corrected for urine creatinine concentration.All assays, including measurement of urine creatinine levels, involved an ELISA format and were supplied with the following specifiations: uCTX-II ; uNTx ; sCPII and sC2C ; sHA . The measurement of urinary creatinine concentration was performed by a peroxidase-coupled kinetic enzymatic procedure  .P-value of less than or equal to 0.05 was considered to be statistically significant.The statistical analyses were conducted using the SPSS version 17.0 for Windows software program . As the distribution of these biomarkers was found to be positively skewed, a logarithmic transformation ) was therefore applied to these biomarkers to obtain an approximately normal distribution. This was evaluated by the Kolmogorov-Smirnoc test before performing the statistical analyses. The serum and urinary levels of these biomarkers were adjusted for age, gender and body mass index (BMI) for comparison using parametric comparisons analysis of variance (ANOVA). The Bonferroni correction for multiple comparisons was applied. Significant differences were evaluated if ANOVA was significant. A Of the 46 patients, 30 had a K/L grade of 1  and 16  had a K/L grade of 2 (Tables The patients were divided into two groups according to the presence (K/L grade 2) or absence (K/L grade 1) of radiographic OA, and the characteristics of these two groups were examined by biomarker analyses. There were no significant differences for the cartilage collagen degradation markers sC2C and uCTX-II between K/L grade 1 and grade 2. sCPII, a cartilage collagen synthesis marker, was significantly reduced in K/L grade 2 compared to grade 1. No significant differences in uNTx, the bone resorption biomarker, were observed between K/L grade 1 and grade 2. But sHA was significantly increased in K/L grade 2 compared to grade 1. As ratios combining type II collagen degradation markers with type II collagen synthesis markers have previously also provided important insights into the balance between type II collagen degradation and synthesis, which is changed in OA ,36, thesP = 0.05) significant difference for the bone biomarker uNTx in patients with or without knee pain irrespective of grade. The presence of pain did not influence the ratio of sC2C/sCPII nor that of uCTX-II/sCPII.Patients were divided into two groups according to the presence or absence of knee pain, and these two groups were evaluated by biomarker analyses. The levels of cartilage biomarkers sC2C, uCTX-II, sCPII and the synovitis biomarker sHA were all significantly increased in patients with knee pain compared to those without knee pain irrespective of K/L grade. In contrast, there was only a marginally (The participants were further divided into four groups according to the presence (K/L 2) or absence (K/L 1) of both radiographic knee OA and knee pain. sC2C in K/L grade 1 patients with knee pain was significantly increased in comparison to the same grade group without knee pain. No such differences were seen in K/L grade 2 patients. sCPII in K/L grade 1 patients with knee pain was significantly increased in comparison to those with no pain in this grade. Again such differences were not seen in K/L grade 2. In contrast, uCTX-II in K/L grade 2 patients with knee pain was significantly increased in comparison to those in K/L grade 2 without knee pain. Such pain-related differences were not seen in K/L grade 1 patients. No significant differences in sC2C/sCPII were observed between sub-groups with and without pain for either grade. uCTX-II/CPII in K/L 2 patients with knee pain was significantly increased in comparison to those in K/L grade 2 without knee pain. No such pain-related differences were seen for uCTX-II/CPII in grade 1 patients. In contrast to the cartilage biomarkers, there were no significant differences in uNTx or sHA between sub-groups with and without pain for either grade.We set out to determine with skeletal biomarkers and a synovitis biomarker whether we could identify early systemic differences in cartilage, bone and synovial metabolism that may be associated with joint pain in K/L grade 1  patients and in early (K/L grade 2) knee OA. Previously reported changes in a reduction of sCPII  and an iAs cartilage is aneural, it is not a tissue that can directly generate pain . But chaP = 0.06) in grade 1, probably due to the smaller study population.Subchondral bone, periostium, synovium, ligaments, and joint capsule are all richly innervated and contain nerve endings that may be the source of pain in OA patients ,4,5. TheSubchondral bone has been proposed as a source of joint pain in knee OA ,4,5. We The interface between subchondral bone and articular cartilage is a site of potential remodeling in OA, as elsewhere intraarticularly, although it has attracted limited attention. The recent discovery that the biomarker CTX-II originates primarily from calcified cartilage at this site  is of spIt has been generally accepted that a K/L grade of 2 is the cut-off for defining radiographic knee OA features. It has also been suggested that since no clear consensus exists as to whether K/L grade 1 subjects also represent early OA, they should be treated as patients of separate grades . In addiThe current study had some limitations. The interpretation of the results was limited by the small number of patients. However, the results usually showed convincing statistical significance. This investigation was a single-arm study and not a randomized trial. Therefore, the design may have introduced certain bias into the results. The serum and urine sample collections were not timed or fasted. Diurnal and activity related variation of some biomarkers have been reported ,42. But In spite of these reservations, our results reveal that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain in both health and disease. The results also suggest that synovitis and bone remodeling may contribute to joint pain. The observation that K/L grade 1 patients with knee pain exhibit biomarker features of early knee OA is of special interest regarding the radiographic identification of early OA. This and previous but limited biomarker studies together suggest that biomarkers have value in helping identify the source of knee pain in patients with early OA and in the early detection of knee OA.ACR: American College of Rheumatology; ANOVA: analysis of variance; C2C: cartilage type II collagen cleavage by collagenase; CI: confidence interval; COMP: cartilage oligomeric matrix protein; CP II: cartilage type II procollagen carboxy propeptide; CTX-II: cartilage type II collagen C-telopeptide; DMORDs: disease-modifying drugs; HA: hyaluronic acid; ICC: Interclass correlation coefficient; K/L grading: Kellgren-Lawrence grading; Ln: natural log; MRI: magnetic resonance imaging; NTx: N-terminal crosslinking telopeptide of type I collagen; OA: osteoarthritis; VAS: visual analogue scale.RP is a consultant to IBEX. The other authors declare that they have no competing interests.MI, KYI, TY, IN and HK conceived and designed the study. MI, TW, KN, HK, IF and AT undertook measurement of knee structures. MI, HK, IN, KK and RP had the major role in analysis and interpretation of the data, and contributed to drafting the report. HY supervised the statistical analysis. All authors have read and approved the final manuscript.


Acutepostoperative pain is among the worst experience that patient scan undergo, and many analgesics have been used to suppress it; especially in chronic opium abusers. Ketamine is an N-methyl-D-aspartate antagonist analgesic, having both anesthetic and analgesic properties, which are not affected to the same extent in chronic opium abusers.In this study, we assessed the analgesic effects of ketamine added to morphine as a patient-controlled analgesia method for acute pain management, compared with a placebo, inchronic maleopium abusers.After institutional review board approval for ethical considerations, a randomized double-blinded placebo controlled clinical trial was conducted. A total of 140 male patients aged 18-65 years, undergoing orthopedic surgery, were entered into the study after matching inclusion and exclusion criteria. All patients received the same anesthesia method; while the first group received ketamine (1mg/mL) and morphine (0.5 mg/mL) as a patient-controlled analgesia (70 patients), the second group received morphine (0.5 mg/mL) plus normal saline (70 patients). P value less than 0.05 was considered statistically significant.The ketamine and morphine group of patients experienced less postoperative pain and required less postoperative rescue analgesia. However, the unwanted postoperative side effects were nearly the same; although increased levels of postoperative nausea and vomiting were observed in the ketamine and morphine groupThis study demonstrated improved analgesic effects after using intravenous patient controlled analgesia with ketamine on postoperative pain in opium abusers. Acute postoperative pain is one of the most difficult experiences that patients must tolerate. Many different analgesics have been used; each having their own special drawbacks . Among pKetamine is an N-methyl-D-aspartate antagonist -10, and In this study, we assessed the analgesic effects of ketamine when added to a morphine sulfate solution as a PCA method for acute pain management, compared with a placebo in male patients with a history of chronic opium abuse.This was a randomized double-blinded placebo controlled clinical trial. The proposal of the study was approved for ethical considerations by the institutional review board of Shahid Beheshti University of Medical Sciences, Tehran, Iran. Furthermore, the manuscript was approved by the Ethics Committee, Research Deputy, Shahid Beheshti University of Medical Sciences and the following comments were followed throughout all stages of the study:1) The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki.2) Informed written consent was taken from each patient separately, before entering the studyAll male patients, aged 18-65 years undergoing orthopedic surgery in a university hospital, were considered as the target population. After considering the inclusion and exclusion criteria and calculating the sample size, the patients entering the study were selected. The inclusion criteria consisted of; male gender, elective orthopedic surgery of the lower limb, history of opium abuse , application of general anesthesia, no contraindication for general anesthesia, and having no significant co-morbid disease  class I or II patients). The exclusion criteria included; female gender, other anesthetic methods , ASA class more than III, duration of anesthesia less than one hour, other routes of drug abuse , and patient's refusal to continue the study after primary approval for study entry. The patients were then randomly assigned to one of the two study groups based on a computer table of random numbers:1) The first group consisted of 70 patients who received ketamine plus morphine (KM group) as a PCA method. In this group, a combined solution of 1 mg/mL ketamine and 0.5 mg/mL morphine was prepared as the PCA analgesia protocol. This was started immediately in the postoperative period, at 10 minutes intervals, and each bolus contained 2 mL of the solution (i.e. 2 mg ketamine plus 1 mg morphine).2) The second group also consisted of 70 patients, and they received a combination of morphine (0.5 mg/mL) plus normal saline solution (M group). Again, PCA analgesia was started immediately in the postoperative period at 10 minutes intervals, using 2 mL of the solution in each PCA bolus (i.e. 1 mg morphine in each bolus). A brief presentation of these stages is demonstrated in Sample size determination was done after a power analysis  using sample size software . The observed frequency for acute postoperative pain in similar patients requesting analgesics was also considered as the clinical criterion for determination of the sample size, and based on the following data and sample size equation -27:Where:Considering a possible 10% dropout, 70 patients were considered as the sample size for each study arm, and consequently total number of 140 patients were selected and entered the study after matching the inclusion and exclusion criteria as follows.All patients were visited the night before surgery and the study protocol was described to them. This visit was the task of the authors ‘colleague. He explained the process of the study and took informed written consents for entering the study during this visit. He also explained that entering the study was a completely voluntary issue and any patient entering the study could exit the research process at any time during the study period. In addition, acceptance or refusal to enter the study, or refusal to continue, had no effect on the treatment process (including the treatment of acute pain).2, and noninvasive blood pressure. For each patient, two intravenous lines were inserted for the administration of fluids, blood and drugs, all according to the study's protocol and the patient's needs. Anesthesia was induced using 0.2 mg/Kg IV midazolam, 200 μg fentanyl, 5 mg/Kg sodium thiopental, and 5 mg/Kg atracurium. Before anesthesia induction, 10 ml/Kg of Ringer's solution was administered freely to compensate for NPO time deficit. For maintenance of the anesthesia, 0.6-1% isoflurane was used to keep the anesthesia depth between 40-60, using Bispectral Index (BIS) monitoring. During final skin suturing, isoflurane was discontinued, and the patients were reversed pharmacologically, using 0.05 mg/kg neostigmine plus 0.02 mg/Kg atropine. After full muscle force recovery and an appropriate level of consciousness, the patients were extubated. Ketamine was not used for anesthesia induction or maintenance at any time during the study. The patients were transferred to the postanaesthetic care unit (PACU) for hemodynamic control, and regaining a full level of consciousness before starting acute pain control remedies.The patients underwent general anesthesia for elective lower limb orthopedic surgery. After entering the operating theatre their vital signs were monitored using; electrocardiogram, pulse oximeter, end tidal CO2) below 92%. However, postoperative pain scores greater than 3 out of 10, mandated postoperative pain control using analgesics through the following protocol:During the postoperative period, the patients' postoperative pain scores were controlled using a visual analog scale (VAS), and their respiratory status; using pulse oximetry and respiratory rates, were measured. Postoperative pain was documented and registered at 1, 6 and 24 hours after the operation. In addition the patients received supplementary nasal oxygen, if they had any decline of oxygen saturation (SpO Starting PCA as defined in the patient groupings (KM group vs. M group). Respiratory monitoring including pulse oximetry.2 was less than 92%. Adding supplementary nasal oxygen if SpO Administration of supplementary intravenous morphine to each of the patients having a VAS score more than 3 out of 10 in the postoperative period, regardless of their study group. Calculating the extra morphine doses in each patient during the first 24 hour period after the operation. Assessment of postoperative nausea and vomiting frequencies in each patient in the first 24 hour period after the operation.Data were collected and analyzed using SPSS software, (version 16). A Student's t-test was used for data analysis. P value less than 0.05 were considered statistically significant.The two study groups had no significant difference regarding baseline demographic data . While tThe results of this study demonstrated improved analgesic effects of intravenous patient controlled analgesia with ketamine on postoperative pain in opium abusers. The effects of chronic opium abuse in altering the threshold of pain tolerance have previously been studied in a number of studies since the issue became a high priority in acute pain research , 28-32. There is no doubt that acute pain treatment in such patients is a real challenge , 34 and During recent years, there have been a number of studies stating their concerns regarding the possible unwanted effects of ketamine -46. ThesThere are a number of limitations in our study; first of all, our patients did not include females and some unwanted effects of ketamine are more commonly seen in women (including the emergence reaction). In addition, our patients were only in the orthopedic ward, while other types of procedures that produce postoperative pain  were not involved, and therefore the side effects of ketamine could be more severe in such cases. Overall, our study demonstrated the effectiveness of ketamine's analgesic effects when used as an adjuvant analgesic accompanied with morphine, and as a PCA analgesia in opium abuser patients undergoing orthopedic surgery.


Chronic pain is one of the main conditions for which patients seek integrative medicine care. Many integrative medicine centers rank chronic pain as the complaint that they treat most effectively. We evaluated the impact of an individualized integrative intervention for chronic pain.Patients seeking their initial treatment for chronic pain at one of the nine centers in an integrative medicine practice-based research network were eligible. Enrolled patients received a personalized integrative medicine intervention over the 24-week study period. In addition to the Brief Pain Inventory (BPI), participants also completed the SF-12, PSS-4, CES-D 20 and various numerical rating scales. Repeated measures analyses were used to assess data from baseline, week 6, week 12 and week 24 visits.252 participants completed the 24-week study. Participants were predominantly female (74%) with an average age of 49.8 years and 8.6 years of chronic pain. Pain was mainly in the axial skeleton, shoulders, knees and hips. The integrative intervention included combinations of acupuncture, massage, chiropractic manipulation, yoga, supplements  and others. At baseline, median BPI Severity and Interference scores were both 5 . By 24 weeks, BPI Severity decreased 20% to 4 (p=0.0006) and Interference decreased 40% to 3 (p<0.0001). Where 52% had symptoms suggestive of depression at baseline, only 35% did at week 24 (p<0.0001). Both the mental and physical components of the SF-12 improved significantly (p<0.0001) as did perceived stress (p<0.0001), sleep (p<0.006), fatigue (p<0.0001) and sense of control (p<0.0001).An individualized integrative medicine intervention successfully decreased chronic pain in participants with long-standing symptoms. Consistent with the suggestion that integrative interventions frequently impact on more than one endpoint, significant and consistent improvement was also documented in symptoms of depression, stress, and fatigue with positive effects on quality of life and sense of control.