The Short Form McGill Pain Questionnaire (SF-MPQ) is one of the most widely used instruments to assess pain. The aim of this study was to translate and culturally adapt the questionnaire for Farsi  speakers in order to test its reliability and sensitivity.We followed Guillemin's guidelines for cross-cultural adaption of health-related measures, which include forward-backward translations, expert committee meetings, and face validity testing in a pilot group. Subsequently, the questionnaire was administered to a sample of 100 diverse chronic pain patients attending a tertiary pain and rehabilitation clinic. In order to evaluate test-retest reliability, patients completed the questionnaire in the morning and early evening of their first visit. Finally, patients were asked to complete the questionnaire for the third time after completing a standardized treatment protocol three weeks later. Intraclass correlation coefficient (ICC) was used to evaluate reliability. We used principle component analysis to assess construct validity.2 = 0.202 to r2 = 0.739. Sensitivity or responsiveness was evaluated by pair t-test, which exhibited a significant difference between pre- and post-treatment scores (p < 0.001).Ninety-two subjects completed the questionnaire both in the morning and in the evening of the first visit (test-retest reliability), and after three weeks (sensitivity to change). Eight patients who did not finish treatment protocol were excluded from the study. Internal consistency was found by Cronbach's alpha to be 0.951, 0.832 and 0.840 for sensory, affective and total scores respectively. ICC resulted in 0.906 for sensory, 0.712 for affective and 0.912 for total pain score. Item to subscale score correlations supported the convergent validity of each item to its hypothesized subscale. Correlations were observed to range from rThe results of this study indicate that the Iranian version of the SF-MPQ is a reliable questionnaire and responsive to changes in the subscale and total pain scores in Persian chronic pain patients over time. Pain is the most common reason for patients seeking medical attention; but due to the inherent nature of pain, being a subjective personal experience spanning both physical and emotional consequences, assessment and treatment of pain disorders is challenging. Although scales like numerical rating, verbal rating and visual analogue scale (VAS) have been frequently and successfully used in pain sensation intensity recording, they lack the ability to assess the qualitative aspects of this personal experience -3. MelzaTaking these aspects into consideration, Melzack developed the short form of the MPQ (SF-MPQ) in 1987. The SF-MPQ was developed to collect data from patients in a short time, when more information rather than intensity measures such as VAS and Present Pain Intensity scale were needed. It has similar MPQ properties but takes less time , so it clingua franca of most of these groups [Farsi is the official language spoken in Iran, Afghanistan and Tajikistan, and is widely used in Uzbekistan. Moreover, it is spoken to some extent in Iraq, Bahrain, Oman and Kazakhstan as well as large communities in the US (413845) and Canada (121510), according to the US and Canada Census of 2006. As a result of new waves of immigrations to the US and Canada since then, it may be reasonable to assume that these numbers have increased. Finally, in diverse ethnic groups in different parts of Iran whose native languages include Turkish, Kurdish, Baluchi and Arabic, Farsi is the e groups -30.The aim of this study was to translate and culturally adapt the short form of the McGill Pain Questionnaire into Farsi, the official language of Iran, in order to make an easily understood, faithful, reliable, valid and sensitive translation of SF-MPQ to be used as a tool to assess pain in the Iranian population. The new measure, the Iranian Short-Form McGill Pain Questionnaire (I-SF-MPQ), was tested for its reliability and responsiveness in chronic pain patients.Guillemin's guidelines for cross-cultural adaptation of health related questionnaires was used ,32. Two The SF-MPQ consists of three parts. The main component consists of 15 descriptive adjectives, 11 sensory and four affective, which are rated by the patients according to their severity on a four point scale , yielding three scores. The sensory and affective scores are calculated by adding sensory and affective item values separately, and the total score is the sum of the two above-mentioned scores.The second part is the VAS, which is a 10-centimeter horizontal line with clearly defined boundaries with descriptive anchors ranging from "no pain" to the "worst possible pain". The intensity of pain was calculated from point zero to the point where the patient had marked in centimeters, and represented the intensity of pain at the time of completing the questionnaire.The third part of the SF-MPQ is present pain intensity (PPI), which is a six-point verbal rating scale. In this scale, patients were asked to choose between six words, from none (0) to the worst excruciating (5); choosing the word that best describes the overall intensity of their pain at the time of completing the questionnaire Figure .We used a convenience sampling method for case selection from a diverse group of chronic pain patients who were referred to our tertiary pain and rehabilitation clinic over three months. The inclusion criteria were: having chronic pain (more than three months), age over 18, ability to speak and understand Farsi, and a willingness to sign the consent form and participate in the study. The exclusion criteria were: intellectual disability, psychosis, and dementia.Among the patients referred to our Pain Clinic supported by the department of Physical Medicine and Rehabilitation, the first 100 patients who fulfilled above criteria were asked to complete the questionnaire three times; the first time (T1) was on the morning of their first visit (between 11 am & 1 pm); the second (T2) was on the evening of the same day (between 5:00 and & 7:00 pm); the third time (T3) was three weeks later. The subjects did not receive any treatment or intervention between T1 and T2. Eight patients who had not completed the questionnaire all three times were excluded. All subjects underwent a three-week supervised multidisciplinary rehabilitation program which included a combination of education, relative rest, relaxation, stretching, exercise, case specific physical modalities and pain medications based on their problem. The questionnaire was delivered to the patients all three times by the same assessor. An assistant read the questionnaire for three illiterate patients to fill out the items. An informed consent was obtained from all patients.All statistical analysis was completed using the SPSS 17 . The demographic data of the patients were described by the use of mean and standard deviations. Alpha was set at 0.05 to indicate a statistical significance. Cronbach's alpha was used to assess internal consistency of the I-SF-MPQ. Test-retest reliability was assessed by means of the ICC. The principle component analysis (PCA) was done to assess construct validity. Sensitivity or responsiveness to change was assessed by pair t-test analysis.From 100 patients, 92 of the patients finished the standardized treatment protocol, and completed the questionnaire after three weeks. Patients were 66 (71.7%) women and 26 (28.2%) men, with a mean age of 45.2 ± 15.6 years. 4.3% had elementary (6 years) education, 44.5% completed high school and 47.8% had a university degree. Housewives constituted 34.8% of the participants. The patients comprised a diverse group of musculoskeletal pain  carpal tunnel syndrome and other types of radiculopathic pain. The demographic data are shown in Table The following are some words that proved difficult during translation:1. "Throbbing": on translation of this word, we were in doubt to choose between "pulsating" [3. "Stabbing": In the Farsi language, there are two synonyms for this word: "got hit by a knife" or "got hit by a dagger"; both experts committee and patients preferred one of these meanings: "got hit by a dagger" [4. "Sharp": all agreed on the word [6. "Gnawing": was the most controversial word of all. The back translation of synonyms would be: "continuous pressure", "chewing", "erosive", and "pressing". The meaning, "continuous pressure", [8. "Aching": the back translation synonym means a "continuous dull pain", [10. "Tender": in order to differentiate it from Allodynia, we decided to add a short expression in parenthesis, "sensitive (painful by pressure)" [13. "Sickening": the back translation synonym means, "pain that causes nausea", [The internal consistency of the test using Cronbach's alpha was found to be 0.951 for sensory, 0.832 for affective, and 0.840 for total scores. For test-retest reliability, the ICCs were found to be 0.906 for sensory, 0.712 for affective, and 0.912 for total scores  was 0.951, 0.832 and 0.840 for sensory, affective and total scores respectively, demonstrating higher than -26. The To evaluate the construct validity of the questionnaire, we used the PCA Table . Each seInaccurate translation of items may change the factorial structure of a questionnaire, but this factorial difference has been reported as a result of cultural differences. Zinke and colleagues examined the cross-cultural validity of the English version of the SF-MPQ . They foDifference in the pre and post-treatment mean total score in our patients was clinically non-significant, but the decrease was statistically significant in all items. This sensitivity indicates that an instrument can be used to evaluate small improvements in chronic pain diseases, such as osteoarthritis, in which usually pain changes are incremental. The ability to discriminate improved and non-improved patients with musculoskeletal pain in the Norwegian version  was alsoOne of our limitations is the lack of a parallel scale as a gold standard to validate treatment results with the I-SF-MPQ scores. Validated quality of life questionnaires or objective activity measurement scales are suitable for this purpose. The second limitation was the selection of chronic pain patients. The response to treatment is usually gradual in these patients; therefore, they are suitable for a test-retest evaluation instead of an evaluation of responsiveness to change. We should have planned at least a two-month treatment regimen to be able to use the SF-36 as a quality-of-life questionnaire.Our study revealed a high test-retest reliability and construct validity. Most of the previous studies have used a restricted group of patients, such as osteoarthritis patients , lower bFurther assessment of the I-SF-MPQ reliability, validity and sensitivity should be done in patients with acute pain. The discriminative capability of the I-SF-MPQ should be examined in different pain conditions.In conclusion this study supports the use of the Iranian version of the SF-MPQ as a reliable, valid and sensitive multidimensional measure to assess musculoskeletal pain in Farsi speaking patients. It can be used by Iranian clinicians and researchers working in the field of pain to communicate internationally.The authors declare that they have no competing interests.FA was the main investigator and analyzed the data, wrote the first draft, and revised the final manuscript. AA and HR contributed to the study design and the analysis. SMK contributed to the acquisition of data. GR helped as a consultant in all parts of the study, especially proposal writing, data analysis, and revising manuscript. All authors read and approved the final manuscript.


Dear Editor, Acute pain has emerged as a leading stressor for ICU (Intensive Care Unit) patients, moderate to severe pain intensity which has been observed in nearly 50% of ICU patients. While pain is widely recognized as the so-called fifth vital sign and we believed pain relief is an essential human right , 2. ReseIn traumatic and surgically critical ill patients, the pain associated with ventilatory function impairment and increases pulmonary morbidity such as nosocomial pneumonia, atelectasis and etc.  and in sRegional analgesia could provide single shout techniques for painful procedures in critically ill patients and also continuous techniques for prolonged analgesia. Richman demonstrated in a meta-analysis report that continuous peripheral nerve blocks provided superior postoperative pain relief and reduced opioid side effects . Single-Immediate extubation after vast majority of patients, especially cardiac surgery and two-stage oesophagectomy in patients with thoracic epidural analgesia is safe and associated with low morbidity and mortality. This has cost-saving and logistical implications , 12. IndOdoom and Sih used continuous epidural analgesia (EA) without problem in 1000 vascular operations for patients receiving oral anticoagulants preoperatively . DespiteEpidural analgesia should be delayed for at least 10 to 12 hours after the last dose of LMWH, post procedure treatment with LMWH should be delayed at least 12 hours, and removal of the epidural catheters should take place 10 to 12 hours after the last dose, with subsequent dosing delayed for at least two hours . EpiduraDexmedetomidine is a class of alpha-2 agonist and It acts on both pre and post synaptic sympathetic nerve terminal and central nervous system, which has numerous beneficial effects including decreasing the sympathetic outflow and nor-epinephrine release causing sedative, anti-anxiety, analgesic, sympatholytic and hemodynamic effects , 17. DexBy avoiding high systemic doses of opioids, several complications like withdrawal syndrome, delirium, mental status changes, and gastrointestinal dysfunction can be reduced or minimized. Because of limited patient cooperation during placement and monitoring of continuous regional analgesia, indications for their use must be carefully chosen based on anatomy, clinical features of pain, coagulation status, and logistic circumstances. High-quality nursing care and well-trained physicians are essential prerequisites to use these techniques safely in the critical care environment .


This study was designed to evaluate the utility of transdermal fentanyl  for the treatment of pain due to osteoarthritis  of the knee and hip, which was not adequately controlled by nonopioid analgesics or weak opioids. WOMAC is a reliable, valid, and responsive multidimensional, self-administrated outcome measure designed specifically to evaluate patients with OA of the knee or hip. TDF significantly increased pain control and improved functioning and quality of life. Metoclopramide appeared to be of limited value in preventing nausea and vomiting. Osteoarthritis (OA) is a slowly progressing disease, characterized mainly by degeneration of articular cartilage which is manifested clinically by gradual increase of pain, stiffness, and reduction of mobility. OA affects also articular capsule being the main reason of musculofascial pain and limitation of everyday activities. About 40–60% of patients with radiologically confirmed lesions suffer from pain, stiffness, and reduction of mobility in the affected joint, and about 55% of patients say that pain is the worst aspect of the disease . OA is iDiagnosis of osteoarthritis is based, most of all, upon clinical evaluation and a radiological picture. Radiological lesions occur most often in the sites of the highest load. In the advanced osteoarthritis, deformity of articular ends of bones occurs. They have forms of fungus-like deformities, oblateness of epiphyses. There is abnormal, varus, or valgus position of epiphyses, subluxation, or dislocation of the joint , 3. The Before occurrence of radiological lesions, the diagnosis of osteoarthritis is difficult. Therefore the American College of Rheumatology  proposedIn OA treatment, the stopping of deterioration of disease is of prime importance, facilitation of patient's gait and articular mobility by a decrease of pain, what influences quality of life. In the individual treatment plan, pharmacological and nonpharmacologic treatment are taken into consideration, for example, physiotherapy, mechanical aids, and surgical treatment. In current recommendations of American College of Rheumatology –7 concerPurpose of the Study. Clinical question is, what is efficacy of transdermal fentanyl in pain relief and clinical symptoms relief in patients with osteoarthritis, most of whom used paracetamol/NSAIDs before?Patient Selection. The following persons were included in the study:ambulatory treated persons aged ≥55 years with osteoarthritis of the knee or hip in 2° and 3° of radiological lesions according to Altman,pain intensity during walking expressed by WOMAC index ≥80 mm ,lack of satisfactory pain control after inclusion of tramadol within 1 week,deterioration of disease symptoms in the opinion of the physician by ≥1 point in 5-point Likert scale,persons qualified for surgery.patients after arthroscopic procedures within last 3 months,patients receiving intra-articular steroids within last 3 months,diseases increasing the risk of complications related to administration of opioids,opioid drugs intolerance.Exclusion criteria arePatients with the liver, kidney, cardiac, and endocrine glands diseases, haematologic diseases, asthma, and/or chronic obstructive bronchial disease were excluded from the study. During the study, administration of antirheumatic drugs and analgesics was prohibited as well as muscle relaxant drugs excluding paracetamol used as needed.Comparison of demographic data and data obtained from history taking at the beginning of treatment was shown in Figures Description of the Intervention. After inclusion into the study, the patients in the first week of treatment received paracetamol + tramadol in generally recommended doses. Insufficient pain and clinical symptoms control qualified for stopping current treatment and inclusion of transdermal fentanyl in the following week with a release of 25 mcg/hr of the active substance. The patches were replaced every 72 hours. Participants were encouraged to take metoclopramide (supplied as 10 mg tablets) immediately if they experienced any nausea or vomiting. They were also encouraged to take a laxative if they had constipation.Evaluated Parameters. Principal, pain, stiffness, and activity of the affected joint are expressed by WOMAC index (Western Ontario and McMaster Universities Osteoarthritis Index—WOMAC index) [C index) . This inAdditionally, treatment efficacy was evaluated by a treating person on 5-point Likert scale .All the above mentioned parameters were evaluated in the beginning , in one week after treatment start, four weeks after treatment start, and after the end of treatment . This observation period, as observations show, is sufficient for proper evaluation of treatment efficacy.In the beginning of observation and during pharmacotherapy, the physician evaluated the degree of reduction of joint function based on main disease symptoms , noted down the first improvement of joint function, and evaluated treatment result after its end . The end of treatment was a procedure of plastic surgery with endoprosthesis of the damaged joint in every patient. bioethics commission approved the study.During 10-week treatment, a significant decrease in value of global WOMAC index was observed as well as sub scale values, that is, group of questions about pain and stiffness in relation to starting values.Functional index WOMAC, which describes physical function of the impaired joint based on 17 details with consideration of difficulties in everyday life of the patient, had similar values in both groups in the beginning of treatment.Exactly, these situations in which patient's ailments were especially severe may be considered the leading symptoms. Thus, the highest initial pain scores  were found in categories of such activities as “descending/climbing the stairs”, “bending down to the floor”, and “tiring home works”. At the same time, exactly in these categories, the improvement of indexes was the highest (between 20 and 27 mm) .Other limitations of function were reported by the patients regarding situation in which locomotor efficiency and stable balance are required, as for example, with “getting on/getting off the car”, “getting into and getting off the bathtub”, or “getting off the bed or chair”. In general, it should be indicated that in all 17 categories, after 10 weeks of treatment, a significant improvement of function of impaired joint occurred, while after 6 weeks, the obtained effects in both groups were similar. The confirmation of the improvement of impaired joint mobility and a decrease of pain upon movement were shown also in a study with the use of the Likert scale (improvement in the range of 1.6 and 2.0 points) .Now, it should be concluded that similar improvement was observed by the team carrying out rehabilitation activities (not included in the study).The observed adverse events of fentanyl use were shown in Nausea and somnolence were of prime importance among adverse events. Metoclopramide was effective for nausea or vomiting. It was included on the first day of treatment, predicting occurrence of these symptoms, at a dose of 20–30 mg/daily p.o. Excessive somnolence did not requir treatment and subsided spontaneously in 7–10 days after treatment started. Each patient was carefully examined before inclusion into the study and informed in details about possible adverse events resulting from use of transdermal fentanyl.P < 0.05.The statistical analysis of the obtained results was carried out with the use of Statistica 5.0 PL software. A nonparametric test for dependent variables was used, the Wilcoxon test of matched pairs. The selection of the test resulted from the character of analyzed variables. The differences were accepted as statistically significant at the level of significance of In both examined groups of patients, significant differences were determined at the level of WOMAC index regarding pain after 7 days, after 30, and after 60 days compared to the initial level, regarding stiffness, after 7 days, after 30, and after 60 days compared to initial level, regarding function, after 30 and after 60 days compared to baseline and regarding global index, after 7 days, after 30 days, and after 60 days compared to baseline. Statistically significant differences regarding the level of WOMAC index between observations were not determined.In the analysis of a degree of subsiding of main osteoarthritis symptoms determined in 5-point Likert scale, statistically significant differences were determined in both groups compared to initial observations, regarding pain intensity in the beginning of movement in examination after 7, after 30, and after 60 days, regarding pain intensity at movement/load in the examination after 7, after 30, and after 60 days, regarding pain intensity with fatigue after 30 and after 60 days, and regarding the level of tension/stiffness in the examination after 7, after 30, and after 60 days. Only in pain intensity in the beginning of movement, in a group of patients with osteoarthritis of the knee, onset of statistically significant decrease compared to the level of this parameter in study after 7 and 60 days was determined.Due to lack of causal treatment of osteoarthritis of the knee or hip, pharmacologic treatment is, on one hand, directed to pain relief, on the other hand—due to treatment of inflammation—to the inhibition of progression of impairment. The used pharmacotherapy includes analgesics and anti-inflammatory drugs, NSAIDs. Clinical trials carried out in order to show the efficacy of any method of therapy use usually evaluation criteria of ailments experienced by examined patients. Often, in OA treatment, NSAIDs are used, included by many centres in the standard procedure. Regarding the fact that the purpose of use of these drugs is a decrease of pain and maintenance of locomotor ability and minimization of functional reduction, at the same time, these drugs may cause adverse events  which may also lead to a decrease of quality of life; the individual, subjective evaluation of patient well-being plays a significant role , 12–16. WOMAC questionnaire is an evaluation instrument specific for osteoarthritis . It is cStart of treatment with potent opioids requires the detailed information for the patient about possible and expected drug adverse events from treating person. Patients receiving strong opioids might require rapid dosage escalation to achieve satisfactory pain relief. Dosage escalations might reduce the benefit/risk ratio of opioid treatment and the potential for improvements in functional capacity and quality of life that opioid treatment can provide. The transdermal opioid formulations have been developed to guarantee long-term pain relief and avoid excessively high serum opioid concentrations. It clearly decreases patient anxiety and increases safety of the therapy .The above report should be considered as initial. It regards a small group of patients treated in a limited period of time (ultimately—treatment end—arthroplasty of the damaged joint). Randomized multicentre study should be designed in order to prove efficacy and safety of the proposed treatment.Treatment of pain in advanced stages of osteoarthritis with the use of transdermal fentanyl leads to clear improvement of mobility of increasing of efficiency of joint function, which is related to improvement of quality of life of the patient.The observed adverse events occur mainly in the first week of treatment. Nausea, vomiting decreases with simultaneous use of metoclopramide, and the other—somnolence, dizziness, and so on subsided gradually upon treatment.


Aim. Regional analgesia has been introduced as better analgesic technique compared to using systemic analgesic agents, and it may decrease the adverse effects of them and increase the degree of satisfaction. Several additives have been suggested to enhance analgesic effect of local anesthetic agents such as opioids and steroids. We designed this randomized double-blind controlled study to compare the analgesic efficacy of the dexamethasone and fentanyl added to lidocaine using axillary block in patients undergoing operation of forearm fracture. Materials and Methods. Seventy-eight patients 20–60 years old were recruited in a prospective, double-blinded, randomized way. Axillary block was performed in the three groups by using 40 mL lidocaine and 2 mL distilled water (L group), 40 mL lidocaine and 2 mL dexamethasone (LD group), and 40 mL lidocaine and 2 mL fentanyl (LF group). The onset time of sensory and motor block, duration of sensory and motor block, the total analgesic dose administered during 6 hours after the surgery, and hemodynamic variables were recorded. Results. The duration of sensory and motor block was significantly longer in LD group compared to other groups (P < 0.001). Similarly, the total analgesic consumption in LD group was smaller compared to other groups (P < 0.001). Comparison of hemodynamic consequences of axillary block and surgery failed to reveal any statistically significant differences between all groups. Conclusion. Addition of dexamethasone to lidocaine significantly prolonged the duration of analgesia compared with fentanyl/lidocaine mixture or lidocaine alone using axillary block in patients undergoing forearm fracture surgery. This trial is registered with IRCT2012120711687N1. Postoperative pain is associated with neuroendocrine responses, catecholamine release, and increased morbidity and the central sensitization is believed to be among the mechanisms implicated in the persistence of postoperative pain .Regional techniques have been suggested to produce superior analgesia, compared to systemic opioids, and they may even improve the final outcomes and also decrease the adverse effects of narcotics and increase the degree of satisfaction .There are many additives to be used to enhance analgesic effect of regional block such as clonidine, magnesium, opioids, vasoconstrictor agents, and steroids , 4.Opioids are considered as cornerstone for treatment of pain following surgery. Furthermore, it is reported that opioid antinociception can be initiated by activation of peripheral opioid receptors . The preThe addition of opioids to local anesthetics injected into brachial plexus network was shown to increase the success rate and postoperation analgesia by some authors –13, wherNevertheless, it is reported that a single administration of an opioid may also induce a long-lasting increase of threshold pain sensitivity, leading to delayed hyperalgesia .On the contrary, it is reported that dexamethasone increases the regional block-associated analgesia due to either inhibitory activity of potassium channels on pain-sensitive sensory neurons or production of some extent of vasoconstriction . The useWe hypothesized that dexamethasone may provide a better pain relief after orthopedic surgery under axillary block compared to fentanyl. In addition, unlike opioids, dexamethasone does not produce pruritus, respiratory depression, or hyperalgesia. To test our hypothesis, we designed this randomized double-blind, placebo-controlled study to compare the postoperative analgesic effect and the success rate of axillary block while dexamethasone or fentanyl was added to lidocaine in patients undergoing forearm surgery.μg (2 mL). The 3 study groups were further marked as 6 blocks  based on A, B, and C alphabets and numbers from 1 to 6. In the final stage, based on the random number table, blocks were arranged next to each other. The ward secretary, anesthetist, surgeon, and statistician were all unaware of blocks arrangement while the A, B, and C alphabets were placed in envelops and opened in the operation room before the performance of axillary block. There were 26 patients in each group.Following the approval by the Ethics Committee of Medical School, Qazvin University of Medical Sciences, and obtaining informed patient consent, seventy-eight patients 20–60 years old, with American Society of Anesthesiologists (ASA) physical status I or II, scheduled elective open reduction forearm fracture surgery under axillary block, were recruited in a prospective, double-blinded, randomized way. The Consolidated Standards of Reporting Trials (CONSORT) recommendations for reporting the randomized, controlled clinical trials  were folAfter administration of 1 mg midazolam as premedication, axillary block was performed by transarterial technique. During the operative period, other sedative or analgesic agents were not administered. The intensity of pain was measured according to the visual analogue scales (VAS), graded from no pain (zero) on the left and the worst imaginable degree of pain (10) on the right. The injection time, blood pressure, and pulse rate were recorded. Following injection, the blood pressure and heart rate (HR) were measured every 5 min for a total of 20 min. The onset of sensory and motor block was evaluated by the pin-prick and the gripping force, respectively, at 30-seconds intervals. After the surgery, the return of sensory block was evaluated by pinprick technique and that of the motor block by the gripping force. The pain intensity with VAS, for a total duration of 6 hrs and at 2 hrs interval was evaluated. After the surgery, patients were requested to choose a point on the scale depending on the intensity of pain and in case of an intensity higher than 4 (based on VAS), routine analgesic (pethidine 25 mg) was administered. Eventually, the time for the commencement of pain, the quantity of VAS at the beginning of pain, and the total analgesic dose administered during 6 hrs after the surgery were recorded. The time of onset of sensory block was defined as the interval between the time of end of injection and loss of pain in pinprick test at around the injury site of forearm. The duration of sensory and motor block, respectively, was taken as the time interval between the time of loss of pain sensation at forearm and reappearance of paresthesia or complete recovery of motor function. The duration of analgesia was defined as the period from drug injection to the first occasion when the patient complained of pain. The duration of analgesia was the primary outcome variable on which sample size estimation was based. To calculate the sample size, data from previous similar studies were taken into consideration –15. SampAmong 78 patients initially enrolled in this study, 15 patients had to be excluded because of logistical reasons or violations of the study protocol. Sixty-three patients were included and randomly assigned to the treatment groups. A total of 58 patients, allocated to 3 groups marked as L (19), LD (21), and LF (18), received intervention and the data were further analyzed by descriptive and analytical statistics.P = 0.73).As shown in P < 0.001) and L (P < 0.001). Also, P < 0.001) and L (P < 0.001). Patients who were given combined lidocaine-dexamethasone demonstrated a significantly prolonged duration of analgesia compared with the lidocaine alone (P < 0.001) and fentanyl-lidocaine mixture groups (P < 0.022). As shown in P = 0.68) between three groups was insignificant. As demonstrated in As shown in The results found in the present study showed that addition of dexamethasone to lidocaine provided longer duration of analgesia compared to fentanyl/lidocaine mixture or lidocaine alone using axillary block in patients with forearm fracture surgery. Furthermore, patients experienced pain at lower intensity following the operation compared to the other two groups. Moreover, the analgesic dose administered for the group that received dexamethasone after the surgery was significantly lower than that used in the other two groups.More recent publications since the aforementioned review indicate that 8 mg dexamethasone added to perineural local anesthetic injections augments the duration of peripheral nerve block analgesia –22. On tShrestha and coworkers reported that addition of dexamethasone for brachial plexus block significantly prolongs the duration of analgesia without any unwanted effects .In a study by Vieira et al., it was also shown that the addition of dexamethasone to bupivacaine increases the duration of analgesia, but no further evaluation on the intensity of pain and analgesic dose after the surgery was made . In a paThere are several theories to explain this effect of dexamethasone; among those is the one representing on degree of vasoconstriction produced by steroids and this in turn decreases the absorption of local anesthetics , 17. SecIn the present study, we showed that the addition of fentanyl to lidocaine significantly increased the duration of analgesia and motor block compared to the group given lidocaine alone; however, this drug combination failed to decrease the intensity of pain and analgesic dose, after operation. Furthermore, the time course for the onset of sensory and motor blocks remained unchanged and the hemodynamic changes were found to be similar to those observed for the lidocaine group. In a study by Nishikawa et al., it was also observed that the addition of fentanyl to lidocaine, similar to our study, increased the duration of analgesia and improved the success rate of sensory blockade . Similarμ-opioid receptor activation leads to a sustained increase in glutamate synaptic effectiveness at the NMDA receptor level and is associated with central hypersensitivity to pain [However these apparently controversial results may be due to either the difference in methodology or population variation. Although it is reported that opioid antinociception can be initiated by activation of peripheral opioid receptors , 25, it  to pain .Based on the data found in our study, it could be concluded that addition of dexamethasone to lidocaine significantly prolonged the duration of analgesia compared with fentanyl/lidocaine mixture or lidocaine alone using axillary block in patients undergoing forearm fracture surgery. Furthermore, patients experienced pain at lower intensity following the operation compared to the other two groups. Moreover, the analgesic dose administered for the group that received dexamethasone after the surgery was significantly lower than that used in the other two groups. Considering the significant effect produced by the addition of dexamethasone to lidocaine, it is recommended that the combination of dexamethasone/lidocaine be used in axillary block. It is also suggested that similar comparisons by adding other agents such as ketamine, ephedrine, and clonidine to lidocaine be made in future studies while using both children and adult age groups, separately.


Osteoarthritis (OA) knee pain is common in older patients and contributes to decreased quality of life. Older patients are generally at higher risk of adverse drug reactions due to age-related changes in physiology that affect drug disposition, metabolism, and response. These analyses examined efficacy and safety outcomes of older (≥65 years) versus younger patients from clinical trials of duloxetine in the management of OA knee pain.This is a post hoc analysis of two 13-week studies, in which patients were randomized to duloxetine 60 mg/day or placebo. Both studies allowed potential dose changes after 7 weeks of dosing, with Study I re-randomizing duloxetine treated patients to either stay on 60 mg/day or increase to 120 mg/day; while Study II more closely mimicked clinical practice by escalating only non-responding patients to 120 mg/day. For all analyses patients were subgrouped by age: older (≥65 years) and younger (40–64 years). Overall efficacy and safety age-group comparisons of duloxetine versus placebo were performed using pooled data from both studies with all duloxetine dose levels combined. Safety analyses included discontinuation rates, treatment-emergent adverse events, and serious adverse events. To evaluate the effects of increasing the dose in non-responding patients, only Study II data were evaluated. Treatment arms were defined post hoc as placebo, duloxetine 60 mg/day, and duloxetine 60/120 mg/day.At study end, patients in each age group who were treated with duloxetine versus placebo had significantly greater improvement in pain , and there was no significant effect of age on treatment (p=.72). Increasing the dose to 120 mg in non-responding patients was not found to have a significant advantage. Among treatment-emergent adverse events with duloxetine treatment, only dizziness had a significantly differential treatment effect (p=.02) with greater incidence over placebo in younger patients , but not in older patients .Duloxetine was efficacious and generally well tolerated for management of symptomatic knee OA in both older and younger patients, but increasing the dose to 120 mg in non-responding patients did not provide additional benefit. Osteoarthritis (OA) of the knee is the most common form of arthritis in older individuals and a leading cause of pain and disability , which cPrescription pain management options for OA knee pain include topical or oral non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular injections of corticosteroids and hyaluronates, and opioids . NSAIDs Current evidence-based literature addressing the pharmacological management of chronic pain in older persons is sparse . As a reIn clinical studies, duloxetine  has demonstrated efficacy in four distinct chronic pain conditions: diabetic peripheral neuropathic pain ,10, fibrData were from two published 13-week, randomized, placebo-controlled studies in male and female outpatients who were at least 40 years of age, and met American College of Rheumatology clinical and radiographic criteria for the diagnosis of OA of the knee ,16. In b2; a diagnosis of inflammatory arthritis or an autoimmune disorder; having received invasive therapies within the prior 3 months, or joint replacement to the knee; being non-ambulatory or needing assistance walking with crutches or walker; any serious medical condition or psychiatric disorder, including major depressive disorder, as identified by the Mini International Neuropsychiatric Interview [For both studies, patients were required to have pain for ≥14 days of each month for 3 months prior to study entry, with a mean pain severity ≥4 on daily pain diary ratings during the screening and baseline periods. In addition, patients had to agree to maintain their usual activity level throughout the course of the study. Key exclusion criteria for both studies included having a body mass index >40 kg/mnterview  that couPatients were randomly assigned 1:1 in double-blind fashion to treatment with duloxetine 60 mg/day or placebo as determined by a computer-generated random sequence using an Interactive Voice Response System (IVRS). All patients randomized to duloxetine were started on 30 mg/day for one week then escalated to 60 mg/day. After 7 weeks, the duloxetine dosing regimen could change. In Study I , patientFor this post hoc analysis, two patient groups were defined by their age at study entry: older patients were at least 65 years of age, and younger patients were less than 65. For the efficacy and safety analyses comparing duloxetine with placebo within age groups, studies were pooled and doses were pooled. In addition, a subgroup analysis was conducted to determine the efficacy of duloxetine in the “oldest of the old” (>75 years) as compared with the “younger of the old” (65 to <75 years) patients. For comparing the effect of increasing duloxetine to 120 mg in non-responding patients, only data from Study II were evaluated as it most closely reflected clinical practice; whereas re-randomization to a higher dose does not. Treatment arms were defined post hoc as placebo, duloxetine 60 mg/day (patients who remained on 60 mg for the entire study), and duloxetine 60/120 mg/day . Safety assessments included spontaneously reported treatment-emergent adverse events (TEAEs), discontinuation rates due to TEAEs, serious adverse events (SAEs), and treatment-emergent abnormal vital signs.Categorical baseline characteristics were compared between age groups using a logistic regression model with terms for study, treatment, age group and the treatment-by-age group interaction. Quantitative baseline characteristics were compared using an analysis of variance model with similar explanatory terms. Weekly means of change from baseline in the average pain severity ratings from patient diaries were analyzed using a likelihood-based, mixed-effects model repeated measures (MMRM) approach that used all available observations. The model included the fixed categorical effects of site, treatment, week, age group, treatment-by-week interaction, age group-by-week interaction, treatment-by-age group interaction, treatment-by-age-group-by-week interaction, as well as the continuous fixed covariates of baseline score and baseline-by-week interaction.The analysis of completion rates, discontinuation rates due to adverse events (AEs), and incidence of spontaneously reported TEAEs and SAEs were compared using a logistic regression model with terms for study, treatment, age category, and the treatment-by-age interaction. For comparison among treatment groups and age groups, test results were considered statistically significant if p≤.05; for tests of interaction, results were considered statistically significant if p≤.1. Statistical analyses were performed using SAS, version 9.1 .Demographic characteristics and baseline pain severity of patients stratified according to age group and treatment arms are summarized in Table Over the course of 13-weeks of treatment, both older and younger patients experienced significantly greater pain reduction each week with duloxetine treatment versus placebo Figure .Study completion rates did not differ between age groups (p=.69), but significantly more patients treated with placebo versus duloxetine completed the study . There was no significant treatment-by-age group interaction in rates of discontinuation due to adverse events (p=.74), but the rate was significantly greater in patients treated with duloxetine versus placebo , and was significantly greater in older versus younger patients (p=.05). AEs that were reasons for discontinuation in the older group treated with duloxetine included: arthralgia (n=2), asthenia (n=3), nausea (n=4), and one incident for each of these: abnormal dreams, anxiety, bronchitis, diarrhea, drug intolerance, ejaculation disorder, erectile dysfunction, flatulence, headache, hypercreatinemia, insomnia, migraine, rash, and supraventricular tachycardia. In the younger group, patients treated with duloxetine discontinued due to nausea (n=3), and n=1 for each of the following: anxiety, condition aggravated, constipation, dizziness, dyspepsia, fatigue, hemorrhoids, hot flush, insomnia, memory impairment, palpitations, sleep disorder, and somnolence.TEAEs that occurred with a frequency of ≥5% are summarized in Table The frequency of SAEs did not differ significantly between age or treatment groups and there was no significant treatment-by-age interaction Table . SAEs reTreatment-emergent vital sign abnormalities are summarized in Table This post hoc analysis did not find a differential effect of age on duloxetine treatment in non-depressed patients with OA knee pain. This is an important finding as it suggests that duloxetine is efficacious in the treatment of OA knee pain regardless of age. The lack of an age effect on pain reduction in this patient population is supported by similar findings in a post hoc age-stratified subgroup analysis of duloxetine in the treatment of diabetic peripheral neuropathic pain .In both older and younger patients, treatment with duloxetine 60 mg/day was associated with significantly greater pain reduction as compared to placebo. However, increasing the dose of duloxetine in older and younger patients, who were not experiencing adequate pain reduction, was not found to provide additional benefit. These findings may be particularly relevant to the treatment of older patients to avoid unnecessary dose escalation.Overall, duloxetine was generally well tolerated by patients in each age group, considering that rates of completion and discontinuation due to adverse events did not differ significantly or show a tendency toward more drop outs in the older population, and were similar to findings in other studies across indications. Further, adverse events with duloxetine generally did not differ between age groups except that dizziness was associated with greater risk among younger patients relative to older ones. While orthostatic hypotension was the most common treatment-emergent vital sign abnormality reported in each age and treatment group, there was no significant treatment-by-age group interaction.The interpretation of this post hoc analysis has limitations to be considered. First, neither study was specifically designed to assess safety or efficacy in exclusively older patients. Furthermore, the results of subgroup analyses should generally be interpreted with caution due to concerns about multiple testing and increased likelihood of finding potentially spurious and un-reproducible results .Duloxetine 60 mg was efficacious for managing OA knee pain in both age groups, but increasing the dose to 120 mg in non-responding patients did not provide additional benefit. There was no consistent signal indicating that the safety of duloxetine might differ significantly between older and younger patients.This work was supported by Lilly USA, LLC, Indianapolis, IN, USA.JLM is on the speaker's bureau and advisory board for Eli Lilly and Company. DR, JA, and MMW are employees and stockholders of Eli Lilly and Company.JLM contributed to interpretation of the data and critical review of the manuscript. DR contributed to study design, interpretation of the data, and critical review of the manuscript. JA prepared the manuscript and contributed to interpretation of the data. MMW contributed to study design, interpretation of the data, and critical review of 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/1471-2474/14/137/prepub


The effectiveness of multidisciplinary treatment in chronic widespread pain (CWP) is limited. The considerable heterogeneity among patients is a likely explanation. Knowledge on predictors of the outcome of multidisciplinary treatment can help to optimize treatment effectiveness. The purpose of this study was to identify predictors of multidisciplinary treatment outcome in patients with CWP.Data were used from baseline and 6 months follow-up measurements of a prospective cohort study of 120 CWP. Regression models were used to assess whether baseline variables predicted treatment outcome. Outcome domains included: pain, pain interference, depression, and global perceived effect (GPE). Potential predictors included: psychological distress, illness and self-efficacy beliefs, fear-avoidance beliefs and behaviour, symptoms, disability, and socio-demographic factors.Greater improvement in pain was predicted by more pain at baseline and male gender. Greater improvement in interference of pain in daily life was predicted by more interference of pain in daily life at baseline, lower levels of anxiety, a stronger belief in personal control, less belief in consequences, male gender, and a higher level of education. Greater improvement in depression was predicted by higher baseline values of depression, stronger beliefs in personal control, and a higher level of education. Better outcome on GPE was predicted by less pain, less fatigue, and a higher level of education.Less anxiety, stronger beliefs in personal control, less belief in consequences, less pain, less fatigue, higher level of education, and male gender are predictors of better outcome of multidisciplinary treatment in CWP. Tailoring treatment to these specific patient characteristics or selecting eligible patients for multidisciplinary treatment may further improve treatment outcome. Chronic widespread pain (CWP) is a syndrome of unknown aetiology which is characterized by widespread musculoskeletal pain, fatigue and poor sleep ,2. A subMultidisciplinary treatment programs are recommended in patients with FM and CWP and the associated problems ,6. The munselected sample of patients and with treatment not targeting factor A, factor A is expected to predict a poor treatment outcome. Conversely, in an unselected sample and with treatment targeting factor A, factor A is not expected to predict treatment outcome: because factor A is targeted during treatment, it is expected to loose its predictive value. The same reasoning applies to a sample selected for factor A. Finally, in a selected sample, with patients with factor A excluded from treatment, factor A will not predict treatment outcome: if factor A is not present, it cannot predict treatment outcome.Symptoms and patient characteristics may predict treatment outcome, depending on the selection of patients and the nature of treatment, as is illustrated in Figure . Let us Psychological distress (depression and anxiety) is commonly found in CWP patients ,13 and iA wide variety of cognitive concepts  have been shown to play an important role in chronic widespread pain (CWP). In our previous work we found overlap between these cognitive concepts . BecauseIllness and self-efficacy beliefs play an important role in the adaptation of the patient to symptoms of the illness and its associated problems -19. IllnFear-avoidance beliefs and behaviour  are assumed to lead to persistence of pain and disability ,24. As mHigher levels of pain and disability are known to predict persistence of pain and disability -27. BothFinally, socio-demographic factors may predict the outcome of multidisciplinary treatment. Few studies  have focIn summary, depression, anxiety, illness beliefs, self-efficacy beliefs, the extent of symptoms, and socio-demographic factors are expected to predict the outcome of multidisciplinary treatment; whereas factors related to fear avoidance and disability are not. This study aims to evaluate these hypotheses on predictors of the outcome of multidisciplinary treatment in patients with CWP.The data of the present study were obtained in a longitudinal observational study. The baseline measurements (predictors and outcome measures) took place before start of treatment (T0). The second assessment (outcome measures) was performed 6 months after baseline [T1]. The ethical review board of Reade in Amsterdam approved this study. Written informed consent was obtained from each subject.Patients with CWP were referred by rheumatologists and general practitioners to the pain management team of our centre. Inclusion criteria for the study were: (i) a diagnosis of CWP according to the American College of Rheumatology criteria (ACR) ; (ii) elA consecutive series of patients was included in the study. Recruitment took 14 months. The baseline measurements were integrated in the existing intake for the multidisciplinary treatment in our centre. For the follow-up measurements participants were phoned and letters were send to encourage them to return questionnaires.The main goal of the intervention was to teach patients to cope with pain and to reduce the interference of pain in daily living. The treatment included cognitive behavioural therapy (CBT), the acquisition of pain management skills , physical training (e.g. exercise), relaxation training, education about neuro-physiology and medication management, and assertiveness training. The components of the multidisciplinary treatment were in line with the core elements of multidisciplinary treatment in CWP ,8. In thFour outcome domains were defined in accordance with the recommendations of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), i.e. pain, physical functioning, emotional functioning, and global perceived effect .Pain was assessed with the Numerical Rating Scale Pain (NRS) (range 0–10). The endpoints of the scale are no pain and worst possible pain. Adequate psychometric properties have been documented [cumented .Physical functioning was assessed with the Multidimensional Pain Inventory (MPI), subscale interference. The MPI consists of 13 empirically derived scales that measure different pain-related aspects. The subscale interference assesses patients perceptions about how pain interferes with their daily lives. A higher score of interference (range 0 to 54) means more interference of pain in daily life. The MPI has been widely used with diverse chronic pain samples and has good psychometric properties [operties .Emotional functioning was assessed with the Beck Depression Inventory II (BDI-II). The BDI-II is a self-reported measure that assesses the cognitive, affective, and somatic symptoms of depression [pression ,33. The pression .Global perceived effect (GPE) due to treatment was assessed with a 7-point Likert scale ranging from the complaints in global health ‘have disappeared’ to ‘very much deteriorated’. The scale was dichotomized in 0 = no change/worse and 1 = improved.Depression was assessed with the BDI-II. The BDI-II has been described previously.Psychological functioning was assessed with the Dutch version of the Symptom CheckList (SCL90). The SCL 90 is a self reported questionnaire and measures psychological and physical distress. The items are rated on a 5 point scale: 1  to 5 (very much). The total score of the SCL 90 (range 90 to 450) reflects psychoneurotism, where a higher score means a higher degree of psychoneuroticism. The Dutch version of the SCL-90 has been shown to have adequate psychometric properties [operties .Anxiety was assessed with the Hospital Anxiety Depression Scale (HADS), subscale anxiety. The scale measures anxiety based on 7 items. A higher score (range 0 to 21) means a higher level of anxiety. The HADS is widely used and have adequate psychometric properties [operties .Illness beliefs were assessed with the Revised Illness Perceptions Questionnaire (IPQ-R). Seven subscales of the Revised Illness Perceptions Questionnaire (IPQ-R) were used to measure beliefs about 1)‘consequences’- expected effects and outcome of the illness; 2)‘coherence’- patient’s logical and complete understanding of the illness; 3)‘emotional representations’- negative emotional reactions like anger and fear related to the illness; 4) ‘timeline’- chronic timeline expectancies of the illness; 5) ’timeline cyclical’- expectancies on the variability of the illness; 6)‘personal control’- extent to which patients believe they can control the illness; and 7) ‘treatment control’- belief in treatment and recommended advice. Items in these scales are rated on a 5-point Likert scale ranging from ’strongly disagree’ to ‘strongly agree’. Higher scores on personal control (range 6 to 30), treatment control (range 5 to 25) and low scores on illness coherence (range 5 to 25) demonstrate positive beliefs about the controllability of the illness and a personal understanding of the illness, respectively. High scores on timeline (range 6 to 30), timeline cyclical (range 4 to 20), consequences (range 6 to 30) and emotional representation (range 6 to 30) demonstrate strongly held beliefs about the chronicity of the illness, the cyclical nature of the illness, negative consequences of the illness, and more emotional representations, respectively [ectively ,38. The ectively .Self-efficacy beliefs were measured with the Dutch General Self-efficacy Scale (DGSS). General self-efficacy is defined as a broad and stable sense of personal competence to deal effectively with a variety of stressful situations [tuations . The DGStuations ,42.Fear-avoidance was measured with the Tampa Scale of Kinesiophobia (TSK). The TSK measures self-reported fear of movement and (re) injury. The scale consists of 17 items and the items are evaluated on a 4-point Likert scale, ranging from ‘strongly disagree’ to ‘strongly agree’. A higher score (range 17 to 68) indicates a higher degree of fear-avoidance [voidance .Avoidance behaviour was measured with the Pain Coping Inventory (PCI), subscale resting. The PCI subscale resting assesses the level to which patients avoid physical activity. The scale consists of five items, and is rated on a 4-point Likert scale ranging from ‘rarely or never, to very frequently’. A higher score (range 5 to 20) on the PCI means more avoidance. Adequate psychometric properties have been documented [cumented .Catastrophizing was measured with the Dutch adaptation of the Coping Strategy Questionnaire (CSQ), subscale catastrophizing. The subject indicated to what extent this particular coping strategy was utilized, based on 6 items. A higher score indicated (range 0 to 60) that the subject made more use of this coping style. The validity and reliability of the CSQ have been documented [cumented .Pain was assessed with the NRS. The NRS has been described previously (see above).Impact of FM was assessed with the Fibromyalgia Impact Scale (FIQ). The scale evaluates physical functioning, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well-being. A higher score (range 0 to 80) indicate a higher impact of FM. The FIQ has been widely used with diverse chronic pain samples, and has good psychometric properties [operties .Fatigue was measured with the subscale fatigue of the FIQ. A higher score indicate a higher level of fatigue.Physical functioning was assessed with the MPI -subscale interference. The MPI has been described previously (see above).General activity was measured with the MPI -subscale general activity. The subscale general activity (range 0 to 18) assesses the frequency of activity of household chores, outdoor work, activities away from home, and social activities.Socio-demographic variables were recorded of each patient: age was rated in years and gender, partnership, ethnicity and level of education were coded as dummy variables.U test. Differences between T0 and T1 scores on the outcome measures BDI-II, MPI- subscale interference and NRS pain were analyzed using two tailed paired t–tests (with a significance level of P < 0.05). Univariate and multiple regression analyses were performed to evaluate the predictors of treatment outcome. The change in the outcome variables and GPE were entered as the dependent variable. The potential predictors were entered as independent variables. First an explorative univariate regression analysis was performed with each potential predictor of the outcome of multidisciplinary treatment. Variables that reached a statistical significance below 0.20 were selected as potential predictors for the multivariate analyses. The bivariate correlation coefficients were computed to establish the relationships between the selected predictors of the outcome variables that reached a statistical significance at P < 0.20. When correlations coefficients of r > 0.70 were found, one of the variables was excluded from the model, to avoid multicolinearity. Multiple linear regression analyses (backward selection) were performed to identify predictors of change in outcome on NRS pain, MPI- subscale interference and BDI-II. A multiple logistic regression analysis (backward selection) was performed to identify predictors of GPE. A significance level of P < 0.05 was used to include a predictor in the final model. In secondary analyses, the variable ‘treatment frequency’ was forced into the final model of the multiple regression analysis to determine whether treatment frequency was a potential confounder of the found relationships.Descriptive statistics for baseline patient characteristics were tabulated as means (SD) or medians (IQR) if data was not normally distributed. Patient characteristics  of participants with complete datasets (N=120) and drop-outs (N=13) were compared and analyzed with a Mann–Whitney drop-out = 26.23, SD = 7.36; Mparticipants = 20.78, SD = 8.85; P = 0.02). Baseline characteristics of the participants are shown in Table Of the 361 patients referred to and evaluated by the pain management team, 165 patients fulfilled the inclusion criteria for this study. Of these patients, 138 consented to participate in the study. Reasons for not participating were: dyslexia, not interested in completing the necessary paperwork, too busy or no specific reason. Of these 138 participants, 133 participants provided data at T0. Reasons for missing cases at this stage were: withdrawal from treatment (n=3) and no specific reason (n=2). One hundred twenty participants provided data at T1. Reasons for missing cases at this stage were: no further consent for participation in the study (n=3) or no specific reason (n=10). Participants who dropped-out of the study at T1 did not differ significantly from participants who completed the measurements at T1, except for depression (MP= 0.02) and depression (BDI-II) (P< 0.001). Forty-eight percent of the patients improved on GPE.Table P < 0.20 were used for multiple regression analyses. The correlation coefficients between the potential predictors of the outcome measure pain ranged from .27 (i.e. pain (NRS) and depression (BDI)) to .52 (i.e. pain (NRS) and the impact of fibromyalgia (FIQ)). The relationships between the potential predictors of the outcome measure interference of pain ranged from .18 (self-efficacy (DGSS) and beliefs in consequences (IPQ)) to .67  and anxiety (HADS)). In addition, the relationships between the potential predictors of the outcome measure depression ranged from .21 (i.e. beliefs in timeline (IPQ) and resting (PCI)) to -.31  and resting (PCI)). Finally, relationships between the potential predictors of the outcome measure global perceived effect ranged from -.20 (i.e. timeline beliefs (IPQ) and treatment control (IPQ)) to .62 (i.e. fatigue (FIQ) and impact of fibromyalgia (FIQ)). Only variables that showed a statistically significant association (at P < 0.05) with change scores in the outcome measures were included in the final model. The results of the multiple linear regression analyses are shown in Table Greater improvement in pain (NRS) was associated with more pain (NRS) at baseline (P < 0.001) and male gender (P = 0.02). Greater improvement in interference of pain in daily life (MPI) was associated with more interference of pain (MPI) at baseline (P < 0.001), less anxiety (HADS) (P = 0.03), stronger beliefs in personal control (IPQ) (P < 0.004), less beliefs in consequences (IPQ) (P < 0.001), male gender (P = 0.02), and a higher level of education . Greater improvement in depression (BDI-II) was associated with more depressive symptoms at baseline (P < 0.001), stronger beliefs in personal control (P < 0.001), and a higher level of education . Better global perceived effect was associated with less pain (NRS) (P = 0.01), less fatigue (FIQ) (P = 0.03), and a higher level of education (P = 0.03). The explained variance (R2) for the final models ranged from 25.7% to 38.1%. In summary, five of our eight hypotheses were confirmed while one hypothesis was partly confirmed  , fatigue and education were no longer factors in the final model.The present results show that psychological distress (i.e. anxiety), illness beliefs , symptoms of pain and fatigue, and socio-demographic factors (i.e. gender and level of education) are associated with the success of multidisciplinary treatment in patients with CWP. In addition, for all outcome measures, higher baseline values  were associated with greater improvement in outcome.In line with one of our hypotheses, we found that higher levels of anxiety at baseline were associated with less improvement in interference of pain with daily life after multidisciplinary treatment. To our knowledge, this is the first study that has focused on anxiety as a potential predictor of multidisciplinary treatment outcome in patients with CWP. These results indicate that higher levels of anxiety are a barrier to effective multidisciplinary treatment. Contrary to our hypothesis derived from the literature  that depAs expected, stronger beliefs in personal control were associated with greater improvement of depression and interference of pain with daily life after multidisciplinary treatment. In addition, less belief in the negative consequences of the illness appeared to be associated with a greater improvement in interference of pain with daily life. These results are congruent with those of Glattacker et al. , who demFear-avoidance beliefs and behaviour did not predict the outcome of multidisciplinary treatment. We expected that fear-avoidance beliefs and behaviour would not predict treatment outcome because they are often targeted during multidisciplinary treatment to increase daily activity and therefore lose their predictive value.As expected, patients with lower levels of pre-treatment pain and fatigue reported a better global treatment effect. This suggests that patients with pronounced symptoms benefit less from standard multidisciplinary treatment including CBT. Thieme et al.  also fouFinally, the results indicate that socio-demographic factors predict the outcome of multidisciplinary treatment. Male gender predicts a greater improvement in interference of pain with daily life and post treatment pain. Since our study population only included 5 men, this finding requires further investigation. In addition, a higher level of education predicts a greater improvement in depression, interference of pain with daily life and a better global perceived effect. These results are in line with the findings of other studies in FM patients ,51. Our Another finding was that higher baseline values of outcome measurements  were associated with greater effects of multidisciplinary treatment. This can be explained by a methodological effect (i.e. regression to the mean) : patientThere are several limitations in our study that warrant discussion. We chose our predictors based on theory and previous research instead of an explorative approach. However, this still led to a relatively large number of predictors which we reduced using statistical pre-selection. This procedure may have caused some instability in our results . FurtherAlthough the improvements in outcome were small on a group level, individual differences in patients characteristics were related to the differences in the effect of treatment outcome. For multidisciplinary treatment this suggests that it is important to find out which clinical characteristics are present in each patient with CWP. Tailoring treatment or strategies to specific patient characteristics may further improve multidisciplinary treatment outcome.The present results may have implications for treatment planning. Patients with pronounced psychological distress (i.e. anxiety), or negative illness beliefs might benefit from treatment components which specifically focus on the treatment of psychological distress or maladaptive thoughts about their illness, respectively. For these patients it might be worthwhile to add these specific components to multidisciplinary treatment. In addition, as pronounced symptoms predicted poorer treatment outcome, an approach based on operant behaviour therapy may be more effective than an approach based on cognitive behaviour therapy . With reIn conclusion, less anxiety, stronger beliefs in personal control, lower beliefs in consequences, less pain, less fatigue and a higher level of education are predictors of greater improvement in the outcome of multidisciplinary treatment. Tailoring treatment to specific patient characteristics or selecting eligible patients for multidisciplinary treatment may further improve treatment outcome.The authors declare that they have no competing interests.JD, MS and AR designed the study. AR coordinated the data collection, performed the statistical analysis. AR, JD and MvdL wrote the manuscript. MS helped to draft the manuscript. LR participated in the design of the study and helped to 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/1471-2474/14/133/prepub


Background: Intravenous Valproate (IVVP) has been used in the treatment of migraine in some studies; however, it is far better known in the management of status epilepticus. Methods: Consecutive patients with migraine in our Headache Clinic were enrolled in this prospective, randomized clinical trial in 2011. The patients were randomized into two therapeutic groups, one receiving 900 mg IVVP (Orifil) and the other 16 mg IV Dexamethasone (IVDEX) diluted in 150 CC normal saline and infused for 10 minutes. Worst severity of pain before treatment and least severity at 3 hours after the infusion using a 0-10 point numeric rating scale were recorded. An interview with the patient was performed 72 hours after treatment to detect a possible relapse of headache.Results: Thirty-one migraine status patients, comprising 28 women and 3 men at a mean±SD age of 33.355±12.373 SD, were investigated. Differences in the therapeutic effects of IVVP (Orifil) and IVDEX on pain score were not significant between the two groups . Relapse of headache occurred in 68.42% of the IVVP (Orifil) group and 66.67% of the IVDEX group. Distribution of relapse was not significantly different between the two therapeutic groups of patients (P=0.870).Conclusion: IVVP (Orifil) was similar in efficacy to IVDEX as abortive therapy in patients with migraine status. IVVP (Orifil) appears to offer a safe and well-tolerated abortive treatment. Trial Registration Number: IRCT13891146234N2 Meanwhile, the treatment of migraine status remains a therapeutic challenge in some cases. There is an ongoing search for new treatment approaches for patients suffering from migraine and other headaches that are refractory to the usual abortive therapies.5New Triptan drugs such as Almotriptan,1,2 Intravenous Valproate (IVVP) as abortive therapy has been administered in different doses for the management of migraine status in some studies.6,7 Many patients suffer prolonged, moderate, or severe migraines, and IVVP offers another weapon against these prolonged migraines. IVVP (Orifil) was studied for the treatment of migraine attacks in Israel,8 where the loading dose of IVVP (Orifil) was 900-1200 mg and the average time to best response for headache severity was 50 minutes. In addition, there was a significant reduction in pain severity (P<0.0001), and there were no serious adverse events. Oral Valproate is utilized widely as a preventive drug for migraine and for chronic daily headaches of migraine.9 To review the literature regarding the use of intravenous valproic acid in aborting an acute migraine attack, a Medline (1967-June 2007) and bibliographic search of the English language literature was conducted using the search terms “valproic acid” and “migraine disorders”.10 All articles identified through the search were included.10 The use of intravenous valproic acid has been studied as a possible treatment for acute migraine.10 Available studies are small, mostly open-label and non-placebo-controlled, and used variable doses.10 Valproic acid has not been shown to be superior to comparator drugs.10 A few non-randomised and open lable studies were found, and intravenous valproate has shown better rsults in abortion of migraine attacks than placebo or comparating drugs.10 Future trials should be larger and placebo-controlled, and they should use a standardized dose and outcome measures. The present study is the first pilot study to compare the therapeutic effects between IVVP (Orifil) and IV Dexamethasone (IVDEX) in patients with migraine status.The ease of IVVP administration and absence of side effects are also important considerations; be that as it may, future double-blind studies will help clarify the situation.11 whereby migraine status was defined as a debilitating severe migraine attack lasting for more than 72 hours, and a present attack was that not attributable to another disorder. Interruption of headache during sleep and short lasting relief due to medication is disregarded disorder.11This prospective, controlled clinical trial recruited patients from our Emergency Division and Headache Clinic during 2011. Randomization was performed by a computerized software package. Neurologist and patient were blind to the selected therapeutic approach for each patient. Blinding was done by a research fellow. Diagnosis of migraine status was made by a neurologist according to the second edition of the International Headache Society (IHS) criteria,12 Patients with dementia, aphasia, and psychiatric disorders were also excluded. The severity of pain was classified based on the Pain Intensity Instrument, using a 0-to-10 point numeric rating scale.13 The patient was asked about what number on the 0-to-10 scale he/she would give for pain before treatment.12,13 Patients with migraine status were randomized into two therapeutic groups. An IV line was then established. In the first group, 16 mg IVDEX was diluted in 150 cc normal saline and infused for 10 minutes. (Patients at a minimum weight of 90 kg received 20 mg IVDEX.) The second group received 900 mg IVVP (Orifil) diluted in 150 cc normal saline and infused for 10 minutes. (Patients at a minimum weight of 90 kg received 1200 mg IVVP.) The patients were thereafter asked to rate the severity of their headache when it had the highest relief over a 3-hour period following the infusion.12 IVDEX has been the routine management of migraine status in our hospital in the recent decade. This standard of care in our hospital was fully explained to the patients; and if they agreed to receive IVVP, they were recruited in the case group. The worst severity of pain before treatment and the least severity over a 3-hour period after the infusion were recorded. The time to maximum relief and the time to onset of relief were recorded as well.12 Additionally, mean age, mean history of migraine, mean number of attacks per month, presence of aura, full recovery of headache post treatment, and recovery from nausea and photophobia post treatment were recorded in the questionnaire. Full recovery from headache post treatment was defined as pain-free response. The therapeutic effects of the drugs on the pain score, pre- and post-treatment periods, were defined as pain relief. An interview with the patient took place 72 hours after treatment to detect a possible relapse phenomenon.13 The relapse was categorized as mild and severe. Mild relapse was defined as recurrent headache requiring self-medication or no medication but not limiting activity, and severe relapse was defined as recurrent migraine attacks provoking another physician visit or interfering with daily activity.14Patients aged less than 18 years, pregnant women, and patients with liver failure were excluded.The research was approved by the local Ethics Committee , and an informed consent was obtained from all the patients. The patients’ CONSORT 2010 Flow Diagram is depicted in Thirty-one migraine status patients, consisting of 28 women and 3 men with a mean age of 33.355, SD±12.373, were investigated. Nineteen cases  received IVVP and 12 patients  received IVDEX. All the patients had been taking preventive agents and abortive treatments. 14,15 In one study, 85 patients with refractory migraine not responding to usual abortive treatments, including Triptans, Dihydroergotamine, and opioids, were treated with IVVP and the results demonstrated an 88% decrease in headache severity. In the study in question, the average dose of IVVP was 720 mg and the average time to best response was 50 minutes.16 In Czech Republic, 36 patients were prospectively treated in a non-randomized, open-label study to investigate the effectiveness of 500 mg IVVP in managing moderate to severe migraine headache. A meaningful reduction in headache within 2 hours was achieved in 20 out of 24 patients who had not been on oral Valproate prophylaxis and in all 12 patients in the subgroup with oral Valproate prophylaxis.17 In a US study, patients with severe migraine received a stat bolus of IVVP, immediately followed by an IV infusion of Methylprednisolone (500 mg) over a one-hour period, which was repeated every 3 weeks for one year. Among the 13 treated patients, 10 patients showed more than a 50% decline in the severity and frequency of pain.15 IVVP was also effective in the management of severe pediatric migraine in the US and 40% of those children experienced pain reduction.18 A clinical study in the US compared the therapeutic effects of Rizatriptan, Dexamethasone, and both in the acute treatment of menstrual migraine: in the assessment of 24-hour sustained pain relief and 24-hour sustained pain-free response, Rizatriptan was significantly superior to Dexamethasone and their combination was also superior to Rizatriptan and Dexamethasone separately.19 A Portuguese clinical study compared IVDEX (4 mg) and IV Haloperidol (5 mg) in the treatment of acute migraine: both drugs were equally efficient in pain relief after two hours.20 Another assessment of the effects of 300 mg IVVP in 61 Canadian patients with acute migraine revealed that 73% had significant pain relief in 30 minutes.21 However, in a placebo-controlled study of 126 patients with acute migraine headache, IVDEX (18 mg) failed to reduce headache relapses.22 A single 8 mg oral Dexamethasone following intravenous Phenothiazine treatment for migraine attack did not reduce the rate of recurrent headache in an Australian study.23 A placebo-controlled study was conducted by Fiesseler et al.24 on 173 patients with migraine. The authors did not find a statistically significant therapeutic effect of 10 mg IVDEX in patients with acute migraine headache.The differences in terms of the pain relief effects of IVVP (Orifil) and IVDEX did not constitute statistical significance in our patients (P=0.358), denoting similarity in the therapeutic effects of IVVP and IVDEX in the treatment of migraine disorders. Other case series and open-label investigations, however, have documented clinically significant improvement of acute migraine headaches in patients treated with IVVP, particularly in a headache clinic setting.25 Friedman et al.26 determined the efficacy of 10 mg IVDEX in a placebo-controlled study in 205 migrainous patients. Their study confirmed that a moderate dose of IVDEX should not be administered routinely in acute migraine, although it might be useful for patients with migraine status. Adding 3.5 mg of Prochlorperazine to 20 mg of IVDEX significantly shortened the response time for the abortive therapy of migraine status in one study.27 Elsewhere, the administration of IVDEX decreased the incidence of severe recurrent headache following the treatment of migraine attack,14 whereas it had no preventive effect on the recurrence of migraine in another study.28The distribution of the relapse patterns was not significantly different between the two therapeutic groups in the present study (P=0.870). A pooled analysis of seven trials, involving 742 patients, suggested a modest but significant benefit in preventing headache recurrence when IVDEX was added to standard antimigraine therapy.=0.704). A meta-analysis of the effects of single-dose IVDEX, by comparison with a placebo, showed that IVDEX and placebo provided similar acute pain reduction; nevertheless, IVDEX was significantly more effective than the placebo in reducing headache recurrence within 72 hours.29 Another US study included 40 participants with prolonged severe migraine, who alternatively received either 500 mg IVVP or 10 mg Metoclopramide intramuscularly, followed by one mg Dihydroergotamine. The study reported that IVVP was similar in effectiveness to Metoclopramide/Dihydroergotamine as abortive therapy for prolonged severe migraine.30 It is deserving of note that although textbooks on headache have mentioned the usefulness of IVVP in the treatment of severe acute migraine,31 further research is required to shed sufficient light on this issue.The distribution of pain-free response was not significantly different between the IVVP and IVDEX groups of our patients  in patients with migraine status. In our study, IVVP (Orifil) was similar to IVDEX as abortive therapy and IVVP (Orifil) appears to offer a safe and well-tolerated abortive treatment.


Background. Postconcussion symptoms (PCSs)—such as fatigue, headache, irritability, dizziness, and impaired memory—are commonly reported in patients who have mild traumatic brain injuries (MTBIs). Evaluation of PCS after MTBI is proposed to have a diagnostic value although it is unclear whether PCS are specific to MTBI. After whiplash injuries, patients most often complain of headaches and neck pain; the other PCS are not as closely evaluated. In patients with chronic pain because of other injuries, the presence of PCS is unclear. This study aimed to describe the frequency of PCS in patients with injury-related pain and to examine the relationships between PCS, pain, and psychological factors. Methods. This study collected data using questionnaires addressing PCS , pain intensity , depression, anxiety , and posttraumatic stress . Results. Fatigue (90.7%), sleep disturbance (84.9%), headache (73.5%), poor concentration (88.2%), and poor memory (67.1%) were some of the most commonly reported PCS. Significant relationships were found between PCS and posttraumatic stress, depression, and anxiety. Conclusion. To optimize treatment, it is important to assess each patient's PCS, the mechanism of injury, and factors such as posttraumatic stress and depression.  The great majority 80–90%) of traumatic brain injuries is classified as mild traumatic brain injury (MTBI)/concussion , 2. Thes0–90% of Whether PCS are specific to MTBI is unclear since symptoms commonly reported after MTBI have been reported in the general population and by patients with chronic pain. Some of the factors that have been found to contribute to the persistence of symptoms are depression and posttraumatic stress , 10.Chronic pain is an acute and/or intermittent pain that persists more than three months , and theAlthough most studies suggest that female gender is a potential prognostic factor related to poor recovery both after MTBI  and whipThe aims of the present study were (i) to describe the frequency of postconcussion symptoms in patients with injury-related chronic pain, (ii) to study the relationships between postconcussion symptoms and pain intensity, posttraumatic stress, and depression, (iii) and to examine gender differences regarding these variables.A cross-sectional study design was used to study patients with chronic pain caused by an injury and referred by regional general practitioners to the Pain Rehabilitation Clinic at the Umeå University Hospital . The study included 86 patients—59 women and 27 men (aged 41.1 ± 10.3 years). The participants suffered from pain caused by falls (14.0%), whiplash injuries (44.4%), other nonwhiplash traffic injuries sustained as the result of bicycle and motorcycle accidents (8.1%), horseback riding (8.1%), sports (1.2%), assaults (5.8%), and other injuries such as work-related injuries (18.4%). For all patients, the time between injury and assessment was more than one year.During assessment in the clinic, the patients answered a set of questionnaires. Information about each participant's trauma history was collected from hospital records. Symptoms (pain intensity and whiplash-related symptoms) were assessed using the Visual Analogue Scale , the RivPain intensity was rated using the Visual Analogue Scale (VAS) . The scaThe Rivermead Postconcussion Symptoms Questionnaire (RPQ)  is a valThe Impact of Event Scale (IES) is a widely used self-report scale . It is aTo measure anxiety and depression, the Hospital Anxiety and Depression Scale (HAD) was developed and validated on nonpsychiatric medical patients . The que+ standard deviations unless indicated otherwise. Comparisons of populations were made using the Mann-Whitney U test. Pearson's correlation coefficient was calculated for the analysis of bivariate correlations. Statistical significant level was set at 0.05.All statistical analyses were performed with SPSS for Windows (version 19.0). Data are reported as means The study was approved by the ethics committee of Umeå University.For all patients, the pain intensity on the VAS was 65.8 ± 20.2 mm. No statistically significant difference was found between women (65.5 ± 21.1 mm) and men (66.8 ± 18.2 mm).The most common PCSs reported were fatigue, sleep disturbance, and poor concentration . The mosThe total score of the IES for all patients was 19.3 ± 15.0, and the scores for the subscales were avoidance 9.8 ± 9.1, and intrusion 9.5 ± 7.3. Mild level of posttraumatic stress was reported by 37.2%, moderate stress by 22.1%, and severe stress by 8.1%. No statistically significant differences between men and women were found with respect to total IES , avoidance , and intrusion .P = 0.038).Depression scores on the HAD for all patients were 6.9 ± 4.4 mm . A significantly higher proportion of women (47.5%) reported possible-probable depression (HAD score ≥ 8) compared to men (22.2%) , HAD anxiety , and HAD depression . No significant correlation was found between RPQ and VAS .Total score of RPQ was significantly correlated to posttraumatic stress (The present study shows that patients with injury-related pain often reported postconcussion symptoms several years after injury. Although more women than men participated in the study, few differences between genders were found. A significant relationship was found between postconcussion symptoms and posttraumatic stress and between postconcussion symptoms and depression and anxiety.As whiplash is reported as the most common traffic injury, it was not surprising that most patients related their chronic pain condition to a previous whiplash trauma. Previous studies have used several different constructions of questionnaires to ask about postconcussion-like symptoms after whiplash , 15. NecThe frequencies of symptoms were high and clearly higher than that for MTBI patients who reported on the RPQ from our hospital one year after the trauma . The mosSome limitations of this study should be noted. General practitioners referred patients to a pain rehabilitation clinic because they reported injury-related chronic pain due to an injury sustained more than twelve months since the referral. Thus the results represent a selected group of patients with chronic pain and with severe consequences after the injury. Although patients reported high frequencies of symptoms, these are seldom assessed in patients with chronic injury-related pain. The results in the present study agree with Smith-Seemiller et al.; they demonstrated that post-concussion symptoms were common in patients with chronic pain . Since s


To assess the impact of new therapeutic strategies on outcome and cost of hospitalization among patients with myasthenia gravis (MG) who are mechanically ventilated in United States.Using a retrospective analysis of cross sectional survey, we determined the rates of occurrence, in-hospital outcomes, and mean hospital charges for patients hospitalized with MG requiring mechanical ventilation in 1991–1992 using the Nationwide Inpatient Survey (NIS) and compared these outcomes with homologous data from 2001–2002. NIS is the largest all-payer inpatient care database in the United States.p=0.0002). The length of hospitalization (in days ± standard deviation) was not different (22 ± 19 vs. 21 ± 16). Discharge to home occurred less frequently  and in hospital mortality minimally lower (13% vs. 15%). There was a significant increase in mean hospital charges . In hospital mortality was higher among urban teaching hospitals compared with urban non teaching hospitals in 2001–2002.When comparing data from 2001–2002 with data from 1991–1992, we found a higher number of admissions for MG that required mechanical ventilation (994 vs. 652). The proportion of women was similar (53% vs. 60%). The average age (in years ± standard deviation) was significantly higher (65 ± 17 vs. 58 ± 18, Despite improvement in therapeutic strategies from 1991 to 2002, there was only a modest reduction in mortality and no substantial reduction of length of hospitalization for patients with MG requiring mechanical ventilation. Myasthenia gravis (MG) is an acquired, immune mediated disease that affects the neuromuscular junction at the postsynaptic level , 2. Myashttp://www.hcup-us.ahrq.gov. We identified adult (age >20 years) patients using the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) code for primary diagnosis of MG (358.0) and either primary or secondary procedure codes for continuous mechanical ventilation .We used the data from the Nationwide Inpatient Survey (NIS) sponsored by the Agency for Healthcare Research and Quality (AHRQ) –21. The http://www.bls.gov/cpi/). We also evaluated the association between various patient outcomes and the hospitals in which they were treated . The definitions are as follows: urban hospital-located in a metropolitan statistical area; and teaching hospital with American Medical Association approved residency program and either membership in the Council of Teaching Hospitals or a ratio of full-time equivalent interns and residents to beds of 0.25 or higher.During the first period, we looked at 1991–1992, when none of the new treatment modalities for MG exacerbations were available, whereas by 2001–2002 several strategies were widely available including specialized neuro-intensive care units and effective immunotherapies. We determined the rates, hospital outcomes, and charges incurred among patients hospitalized with MG requiring mechanical ventilation in 1991–1992 and compared these variables among those hospitalized in 2001–2002. The variables analyzed were: age, sex, race/ethnicity, length of stay, discharge status , and total hospitalization charges. We used the SUDAAN  softwarep=0.0002).The demographic and clinical characteristics of mechanically ventilated MG patients are shown in Table The length of hospitalization (days ± standard deviation) in both time periods was similar: 22 ± 19 in 2001–2002 and 21 ± 16 in 1991–1992. In hospital mortality was 13% in 2001–2002 and 15% in 1991–1992. Discharge to home was lower (29%) in 2001–2002, compared with 1991–1992 (60%), however, transfer to skilled nursing and an intermediate facility was increased (37% vs. 9%).p=0.0001). The average daily hospitalization charges per patient (inflation-adjusted) were $5500 and $3932, respectively.The mean charges for hospitalization of each patient, after adjustment for inflation, increased by 51% in 2001–2002 compared with 1991–1992 . In patients aged >50 years, 20% were discharged home in 2001–2002 vs. 54% in 1991–1992. Their average length of stay was 22 days ± 19 in 2001–2002 vs. 22 ± 15 in 1991–1992 (p=0.7855). In neither age group was there a significant decrease in the rate of in hospital mortality in 2001–2002 compared to 1991–1992.We compared the demographic and outcome characteristics of mechanically ventilated MG patients under the age of 50 years with those 50 and older Table . There wp=0.0001). However, this trend was not seen in urban nonteaching hospitals . In both time periods, the urban teaching hospitals had a longer average length of stay, and higher mortality  of patients admitted in 2001–2002 compared with those admitted in 1991–1992 , the following trends were revealed:et al. (With improved treatment strategies, the mortality rate had dramatically reduced in the past 40 years. It fell from 43% in mid 1950s to 4.5% in 1979 –25. In aet al.  examinedet al. . The morIn our subgroup of patients below 50 years age, the death rate was lower than in the Johns Hopkins and Columbia Presbyterian studies , 17. OveThe average length of hospitalization in our study was 21 days in 1991–1992 and 22 days in 2001–2002. The average hospitalization was 35 days in the Columbia Presbyterian study . In the Initially considered as a disease of young adults , MG was Late onset myasthenia, defined by onset after the age of 50 years, has specific epidemiological, immunological and clinical characteristics , 35. It It is well known that in less than 5% of MG patients, no progress in their treatment have been achieved since the introduction of immunosuppressive medication with frequent MG crisis and increased morbidity and mortality , 41. WitIn summary, a modest improvement in mortality and no substantial change in length of stay have been observed among MG patients requiring mechanical ventilation in 2001–2002 compared with 1991–1992 despite a dramatic increase in hospitalization charges. This may be explained by higher proportion of older patients with MG admitted in recent years. The increase in prevalence of late onset MG and the aging of early onset MG patients has also increase the prevalence of MG patients less responsive to standard treatments. We believe that better understanding of national trends will allow for appropriate resource allocation among patients with MG.