Psychological flexibility has been suggested as a fundamental process in health. The Psychological Inflexibility in Pain Scale (PIPS) is one of the scales employed for assessing psychological inflexibility in pain patients. The aim of this study was to validate the Spanish version of the PIPS and secondly, to compare it to two other psychological constructs, the acceptance of pain and mindfulness scales.The PIPS was translated into Spanish by two bilingual linguistic experts, and then, back-translated into English to assess for equivalence. The final Spanish version was administered along with the Pain Visual Analogue Scale, Fibromyalgia Impact Questionnaire, Hospital Anxiety Depression Scale, Pain Catastrophizing Scale, Chronic Pain Acceptance Questionnaire and the Mindful Attention Awareness Scale, to 250 Spanish patients with fibromyalgia. Face validity, construct validity, reliability  and convergent validity were tested. Also a multiple regression analysis was carried out.The usual guidelines have been followed for cross-cultural adaptations.r = 0.55), anxiety (r = 0.54), depression (r = 0.66), pain catastrophizing (r = 0.62), pain acceptance (r = −0.72) and mindfulness (r = −0.47), as well as correlating modestly with pain intensity (r = 0.12). The multiple regression analyses showed that psychological inflexibility, acceptance and mindfulness are not overlapped.Data were very similar to the ones obtained in the original PIPS version. The construct validity confirmed the original two-components solution which explained 61.6% of the variance. The Spanish PIPS had good test-retest reliability (intraclass correlation coefficient 0.97) and internal consistency reliability . The Spanish PIPS’ score correlated significantly with worse global functioning (The Spanish PIPS scale appears to be a valid and reliable instrument for the evaluation of psychological inflexibility among a sample of fibromyalgia patients. These results ensure the use of this scale in research as well as in clinical practice. Psychological inflexibility measures processes different from other related components such as acceptance and mindfulness. Over the last few decades, Cognitive Behavioral Therapy (CBT) has become the most commonly standard psychological treatment for chronic pain patients who have to deal with psychological distress and disabilities. AlthougPsychological inflexibility appears when these two processes dominate an individual’s experience.In recent years, there has been growing interest in Contextual Therapies, and specifically in the field of chronic pain, interest has grown in the Acceptance and Commitment Therapy (ACT). In thisThe expressed goal of ACT is to improve functioning by increasing psychological flexibility, defined as the ability to act effectively in accordance with personal values in the presence of negative private experiences such as pain or distress. PsycholPsychological flexibility is the psychological construct that captures the overarching ACT model in its most current form,14. AccoAlthough the results generally show that Psychological Flexibility is associated with reports of less pain intensity and interference, less anxiety and depression and better physical and mental functioning,17, the These results implied the potential of improved outcomes of focusing on psychological inflexibility for chronic pain management. The aim of this paper is to validate the Spanish version of the PIPS in patients suffering from fibromyalgia. For this purpose, face validity, construct validity, reliability  and convergent validity were tested. This validation will enable us to research the construct in Spanish populations as well as expand our limited knowledge concerning psychological inflexibility.We recruited patients from primary care settings, who were assessed at the Somatoform Disorders Fibromyalgia Unit at Miguel Servet University Hospital, Zaragoza, Spain, during 2011. The inclusion criteria were as follows: Patient ages ranged from 18 to 65 years and patients agreed to participate and fulfill the American College of Rheumatology criteria for primary fibromyalgia, accordiAfter consenting to the study, the recruited patients were administered a battery of questionnaires, including a pain form for demographic and pain-related variables, including the translated Spanish version of the PIPS to be validated, a Pain Visual Analogue Scale (PVAS) for pain intensity, the validated Spanish versions of the Fibromyalgia Impact Questionnaire (FIQ), the Hospital Anxiety and Depression Scale (HADS), the Pain Catastrophizing Scale (PCS), the Chronic Pain Acceptance Questionnaire (CPAQ), and the Mindful Attention Awareness Scale (MAAS).Background information from participants included age, gender, level of education , and duration of pain.The PIPS is a 12-item scale designed to measure psychological inflexibility in pain patients. Two studies have supported a 2-factor solution (avoidance and cognitive fusion related to pain) with satisfactory statistical properties,17. The The FIQ is a 10-item self-report questionnaire that measures the health status and global functioning in patients with fibromyalgia. The firThe HADS is a selThe PVAS was designed to allow for a subjective assessment of pain. It consists of a 10 cm long straight line whose extremities represent the limits of pain intensity (“no pain” to “maximum pain ever experienced”). The patients estimated the pain intensity experienced on the same day between 0 and 100. Previous studies have demonstrated PVAS to have adequate psychometric properties.The PCS is a 13-item self-report questionnaire that comprises three dimensions: (a) rumination, (b) magnification and (c) helplessness. Each item is scored from 0  to 4 , and scores range from 0 to 52. Its validity and reliability have been previously reported. The SpaThe MAAS is a 15-The CPAQ is a 20-Permission to translate and validate the PIPS was obtained from the original authors. AlthougAssessments took place at two different points over a 1–2 week interval. There is no evidence available to aid in the selection of the time interval between questionnaire administrations for a study of test-retest reliability for health status instruments. This tir correlation coefficient. The internal consistency of the questionnaire was determined using Cronbach’s alpha. Item-total correlations were also inspected to determine the item internal consistency. Test-retest reliability, evaluated with the intraclass correlation coefficient, was assessed for the 1- to 2-week follow-up interval, during which time the patients did not change their baseline treatment.To determine the suitability of the data for principal components analysis, the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO) and Bartp < .05 to enter, p > .10 to remove). Secondly, pain intensity was entered to control its contribution to the prediction of each criterion variable (except in the case where pain was the criterion variable). Thirdly, the three process scores for the acceptance of pain, mindfulness and psychological inflexibility were entered together in a single block to examine their contribution. Finally, the relative role of the three separate processes was gleaned from standardized regression coefficients and from the squared semi-partial correlation coefficients. Lastly, we also attempt to address one of the hypotheses raised by Wicksell regarding the identification of discrete subgroups using the two PIPS subscales[k-means cluster analyses were conducted. A number of cluster solutions were considered, ranging from two to four subgroups. Firstly, demographic differences among the groups were tested via chi-square or Analyses of Variance (ANOVA’s). In order to explore the potential clinical utility of the clusters, a second series of one-way ANOVA’s was conducted using cluster membership as the independent variable and the scores on the seven measures of functioning as the dependent measures. These comparisons used a Bonferroni-corrected alpha . All statistical analyses were performed with SPSS software, Release 15 .To confirm that psychological inflexibility, acceptance and mindfulness are different constructs, and to provide data regarding their relative contributions to functioning and health variables, a multiple regression analysis was performed. Hence five regression equations were calculated. In each of these equations, the potential predictors were tested hierarchically. Firstly, patient age, sex, education, and duration of pain were tested and retained in the equations when significant  declined to participate. None of the participants were ruled out because of the exclusion criteria. The final study sample consisted of 250 patients, 240 (95.6%) women and 10 (4.0%) men, aged 31–70 , all self-described as White European. The ratio of women/men is higher in the sample reflecting a similar ratio in the prevalence of fibromyalgia in either gender. Most of the patients were married . Regarding education, nearly half of the sample had attended primary school education . On average, the patients who participated in the study had suffered from fibromyalgia for 18.3 years . A significant proportion of the subjects were retired, not working, or working part-time due to their pain .The mean PIPS total score was 57.1 . This amounted to a mean item rating of 4.7, which corresponds with a medium-high range of the 1–7 scale and the rating category between “Sometimes true” and “Often true” for the average psychological inflexibility item. There was not a significant association between the PIPS’ total score and most demographic characteristics including gender, age, marital status, duration of pain, education level or work status.For assessing face validity, a sample of patients (N = 150) randomly recruited from the Spanish Association of Fibromyalgia was asked whether they thought that the test could adequately measure their psychological inflexibility. A total of 94% (141 out of 150) of them agreed.2 = 1594, p < 0.001), supporting the suitability of the data for a principal components analysis. A principal components analysis (PCA) with varimax rotation yielded a two-component solution with eigenvalues greater than 1. The first component, labeled avoidance, accounted for 50.5% of the total variance. The second component, labeled cognitive fusion, accounted for 11.1% of the total variance. The loadings of the pattern matrix are presented in Table The KMO was found to be 0.91, which exceeds the recommended minimum value of 0.60. Bartlett’s Test of Sphericity was highly significant , indicating a high degree of internal consistency. Cronbach’s α for Factor 1 and Factor 2 were 0.92 and 0.61 respectively. All corrected item-total correlations were above 0.30 , which is the cut-off criterion established by De Vellis.The response to the PIPS-Spanish provided by a random subsample of 141 patients with fibromyalgia  showed a satisfactory temporal stability of the scale over a 1–2 week interval, during which the patients did not change their baseline treatment. The test-retest correlation assessed with the intraclass correlation coefficient was 0.97 (Factor 1 = 0.96 and Factor 2 = 0.95).r = 0.12, p = 0.043), whereas the subscale for cognitive fusion was non-correlative.The Pearson correlation was used to assess the relationship between the PIPS-Spanish and other psychometric instruments, and the results are summarized in Table r = −0.72, p < 0.01) and with mindfulness  were particularly high, as one could expect since they are psychological constructs derived from acceptance-based interventions. This raised concerns that psychological inflexibility might be largely redundant with these two constructs. The regression results are shown in Table The correlations of the total PIPS with acceptance (n = 81) had scores that were discordant in that they demonstrated a tendency that was slightly lower on the Avoidance subscale and high on the Cognitive Fusion subscale. The PIPS scores for each cluster differed significantly from one another . The third  in patients with fibromyalgia and, in addition, to examine the impact of the PIPS in fibromyalgia compared with other psychological constructs, and to identify potential subgroups using the PIPS.The results mainly suggest that the PIPS might provide an additional useful tool to assess psychological risk for problematic outcomes in fibromyalgia. The PIPS-Spanish showed high internal consistency and high test-retest reliability, as well as significant correlations with associated constructs such us pain severity, global functioning, anxiety, depression, catastrophizing, acceptance and mindfulness. Furthermore, the Scree plot indicated a two-factor construct of the translated questionnaire similar to its original English version. Both factors had eigenvalues greater than one. Principal components with varimax rotation revealed a satisfactory percentage of Total Variance explained (61.6%) by the two factors. Looking at the component matrix of the two-factor construct, individual items could be allocated to the same subscales as they were in the English version. Therefore, construct validity of the translated PIPS can be supported.Results showed that patients with lower psychological inflexibility were associated with better global functioning and well-being. Interestingly, the correlation between the PIPS and its subscales in terms of pain intensity was modest or non-existent. This might be due to the fact that ACT scales are mainly designed to measure functioning and wellbeing. The current results are consistent with previous studies from other contextual constructs such as acceptance or mindfulness and their relatively low correlations with pain intensity-42. In oThe correlations among these three ACT constructs were strong and the results from multiple regression analyses illustrate their relevant, combined contribution to explained variance in global functioning and well-being. More importantly, the findings also confirmed that there was no overlap among these processes. Indeed, each one of them made significant contributions to the outcomes. This study was not designed to identify which is the most important construct, but in comparison with the other two processes, acceptance of pain seems to achieve slightly higher correlations with the measures of functioning and health.Specifically it is somewhat surprising that CPAQ and PIPS are not overlapped. The reason seems to be that although items in CPAQ are clearly related to avoidance and cognitive fusion, PIPS constitutes an attempt to refine the assessment of these specific subcomponents of psychological inflexibility and to produce a measure with clearly discernible factors of avoidance and cognitive fusion. Indeed, data from the present study support the fact that PIPS provides a measure of processes previously not quantified in pain patients.Cluster analyses rendered additional support for the two-factor model and indicated three discrete patient groupings. The first two were as expected and contained individuals who were either high or low on both subscales. In subsequent comparisons, these two groups differed statistically in six out of the seven measures of functioning and well-being. In four out of six measures, with the exception of fibromyalgia impact and mindfulness, the high PIPS group reported difficulties with emotional disturbances or functioning that were approximately twice those reported by the low group. These results highlight the need for adequate treatments for those with fibromyalgia who are particularly unable to be active for reasons of pain and struggle unsuccessfully for control over pain.Based on our clinical experience, the presence of the third cluster was somewhat expected. This cluster demonstrates that individuals who do not present for treatment report an exaggerated avoiding pattern, but at the same time they identify a strong need for pain control. In fact, these individuals may report that they were functioning well to a degree; however, in the present data they also report significant disturbances in wellbeing and functioning. It is possible that this particular group would benefit from treatment to enhance techniques that allow the individuals to disentangle from thoughts. Perhaps these same individuals would also benefit from treatment that paid somewhat less attention to methods for increasing physical activity specifically, although future investigation will be necessary to explore the accuracy of this hypothesis.Notably, high scores on the avoidance subscale did not co-occur with low scores on the Cognitive Fusion subscale. This is coherent with what ACT proposes that the individual is trapped by self-barriers limiting their lives. People who experience cognitive fusion tend to misinterpret “thoughts” as facts, therefore serving as excuses for their behaviors. Patterns of discordance between the two PIPS subscale scores deserve further study. Previous studies have shown the relevance of targeting “Cognitive Fusion”-44. The The current study has a number of limitations that call for a cautious interpretation of some of the results. Firstly, our correlation methods cannot unambiguously determine whether psychological inflexibility leads to decreased levels of functioning and wellbeing or vice versa. Secondly, the main target of this study was to validate the scale so it might be that the total sample for the cluster was limited. Lastly, the processes examined are technically complex to measure and, in many ways, the instruments being used are relatively recent developments.Indeed, currently, there is some ongoing critical discussion within the ACT research field in regards to the processes underlying psychological flexibility. For instance, the PIPS as well as another questionnaire, the Brief Pain Coping Inventory,46, consThe Spanish version of the PIPS scale has been shown to be a valid and reliable instrument for measuring psychological inflexibility in patients with fibromyalgia. Although psychological inflexibility is considered to be one of the key treatment processes influencing change in primary outcome variables e.g. pain disability, there have been hardly any studies to enhance our knowledge of this concept. This study will make it easier to assess psychological inflexibility in Spanish populations. Secondly, psychological inflexibility measures different processes than other ACT components such as acceptance or mindfulness. Finally, the PIPS might be used to identify different clusters of fibromyalgia patients that may benefit from individually tailored interventions with different areas of emphasis.The authors declare that they have no competing interests.JGC, BR, JPP and MJRCR are the principal researchers and developed the original idea for the study. ASB, BC and MCPY participated in the design and planning of the intervention that is evaluated here. JVL developed the statistical methods. All authors have read and corrected draft versions, and approved the final version.


Pain is one of the major concerns of patients underwent Total Knee Arthroplasty (TKA); appropriate pain management is a key factor in patient's early physical fitness to move, physiotherapy, and most importantly, patient satisfaction.In this study the analgesic effect of single injection femoral nerve block (SFNB) was compared with local infiltration analgesia (LIA).Forty patients who underwent TKA under spinal anesthesia were randomized to receive single femoral nerve block (group F) or intra-periarticular infiltration (group I). Group F received single injection 20cc ropivacaine (10mg/cc) and in group I, a combination of 300mg ropivacaine, 30mg ketorolac and 0.5mg epinephrine diluted to a volume of 150cc and locally injected in and around the knee joint in 3 stages. Postoperative pain intensity measured by Visual Analog Scale (VAS). Morphine consumption, mobilization time and patients’ satisfaction evaluated as well.Group I had significantly lower morphine consumption in the first postoperative day . Within 6 hours postoperatively, VAS score was statistically lower in group I compared to group F . However, within 12 hours it was statistically higher in group I than group F . Other parameters were not statistically different in two groups.Both methods LIA and SFNB provided excellent pain relief and lower morphine consumption following TKA. LIA is a surgeon-controlled analgesic technique, which can be used to enhance patients’ satisfaction and reduce the pain in the very early postoperative period by surgeon independently. As life expectancy increases, the number of total knee arthroplasty (TKA) has also increased in order to improve life quality and mobility . The numVarious methods have been examined and used to control TKA postoperative pain; simple methods like oral NSAIDs and intravenous opioid administration, newer techniques like epidural block and femoral nerve block in two forms ,single injection and continuous infusion (24 - 72 hours) of anesthetic with catheter or the most recent analgesia methods such as local infiltration analgesia (LIA) -3, 5, 6;Taking opioids leads to notable side-effects such as nausea, vomiting, pruritus, drowsiness and urinary retention . These mIn the previous studies contradictory results regarding the comparison of LIA and femoral nerve block have been reported. Although some studies reported femoral nerve block as more efficient in range of motion (ROM) and pain control postoperatively , many otMost of studies carried out so far have used catheter to infuse the anesthetic (24 to 48 hours) and the comparisons have been made on this basis. Using catheter is more expensive, requires follow-up and has probable side effects and infections.This prospective, double- blind, randomized, : clinical trial designed to compare the quality of analgesia offered by single injection femoral nerve block (SFNB) and LIA and their effects on morphine consumption, patients' satisfaction, pain control and physical rehabilitation postoperatively.The present study is a randomized, double- blind clinical trial according to the ethical principles of Helsinki Declaration and approved by the Ethical Committee of Iran University of Medical Sciences (Project number: 92/130/96). All the patients signed the written, informed consent of the study procedure. During January to June 2013, the study included 40 inpatients from orthopedic ward in Rasoul Akram Hospital, Tehran, Iran.Forty patients with osteoarthritis scheduled for TKA were screened for eligibility. The inclusion criteria were: age 20 to 85 years old, American Society of Anesthesiologists (ASA) physical status classification between (I-III), and normal preoperative mobility. Exclusion criteria were patients with neuropathic pain or sensory disorders of the leg being operated, failed spinal anesthesia, therefore conversed to general anesthesia, a medical history showing previous operations on the suffering knee, allergy to the medicine used in the study, BMI > 40, diseases of kidney, heart or liver, joint inflammatory disease, chronic pain and disorders resulting in bleeding, such as GI bleeding. According to 40% difference in morphine consumption during the first 48 hours after surgery (regarding previous studies), 80% strPatients, researchers, physiotherapists and all nursing staffs were blinded to the grouping. Only the surgeon was not blind to both groups and he had no role in later care of the patients.Premedication of 0.01 - 0.02 mg/kg midazolam was administered. Patients were placed in a lateral position. The drugs were injected by a 25-gauge Crawford needle in midline of L3 - L4 or L4 - L5 level by an anesthesiologist. For inducing spinal anesthesia, 15 mg of isobar intrathecal Marcaine® 0.5%  was administered without any additives. Then the patients were changed their position into supine and intranasal 100% oxygen was administered. Blood pressure less than 100 mmHg of 30% from the baseline was corrected by 5 mg ephedrine and crystalloids and all the pulse rate drops (less than 60/min) was treated with 0.5 mg intravenous atropine. Midazolam, ephedrine and atropine were provided from a regional pharmaceutical company .All TKAs were carried out by medial parapatellar approach, A tourniquet was used for all patients and drain was removed on the day after surgery. Adhesive bandages were used in compressive form in a way that blocked venous and lymphatic channels.In group I the injected substances included 300 mg ropivacaine 1% , 30 mg ketorolac  and 0.5 mg 1:100,000 epinephrine ; of which 150 cc was prepared in 3 syringes (50 cc each).When the bone surface was prepared for the prosthesis to be placed, the first injection (50 cc of the mentioned solution) was done to the knee surrounding soft tissuefrom anterior to the posterior part and with 3 mm depth in the surrounding tissue . The second injection was made after placing the tibial and femoral components and again 50 cc was injected around the medial and lateral collateral ligament. The third injection (25 to 50 cc) was made before wound closure in the edges of the incision but deeper than subcutaneous tissue so that it prevents necrosis caused by epinephrine  and 3.In group F a nerve stimulator was inserted1-1.5 cm lateral and inferior to the femoral artery, when the sensory level reached L1in the recovery room setting until the quadriceps twitch at 0.5 mA could be seen. At this time 20 cc of ropivacaine 10 mg/cc was injected. In order to control pain in the first 48 hours, Acetaminophen 1 gr /BID orally, Ibuprofen 400 mg/ TDS orally and Ranitidine 50 mg/ BID (IV) were administered. The patients were instructed that no pain and worst possible pain equal to 0 and 10, respectively, on the visual analog scale (VAS). When patients’ VAS pain scores reach 4, morphine (5 mg) can be administered intravenously by nursing staff on the patients’ request . Higher doses should be prescribed by physician order. Pain was controlled after 48 hours only with acetaminophen and oral tramadol.In the present study, primary outcomes were morphine consumption 24 to 48 hours postoperatively, the VAS pain score, the patients’ satisfaction about the pain control in 48 hours postoperatively , mobilization time which was the period between the operation and first walking experience (for 3 meters).Secondary outcomes included side effects , clinical outcome (compared with the measurement of knee flexion/extension at the time of patients’’ discharge and 3 months afterwards) and the number of hospitalization days  after surgery. Data were recorded in a questionnaire designed for the present study and Statistical Package for the Social Sciences (SPSS) software version 20  was used to analyze the findings. Analysis of variables using Kolmogorov–Smirnov test showed that except ROM variable other variables did not follow normal distribution that is why Mann-Whitney U test was used instead of T-test to calculate P-values. Student’s T-test was used for the variables with normal distribution and Mann-Whitney U test was used for other parameters not normally distributed. Dichotomous data were analised using chi-square test or Fisher’s exact test. P < 0.05 was considered statistically significant.The flow diagram of patients through the study is shown in All the patients in both groups used morphine or oral tramadol to control pain within 48 hours postoperatively. After changing tramadol to its morphine equivalent  it turned out that its consumption (10 mg) in group I in the first 24 hours after the surgery was significantly less than group F (12.5 mg) ; however, there was no difference between the two groups within 48 hours after the surgery.Patients in group I suffered less pain (pain score 3) in the first 6 hours after the surgery compared with the patients in group F (pain score 4) but within 12 hours after the operation, group F reported less pain, and eventually 24 hours after the surgery the pain scores of the two groups did not demonstrate a significant difference . Mobilization time is the time it takes for the patient to be able to walk at least 3 meters (with or without the help of physiotherapist) after the operation. No significant difference was observed between the two groups and a median of almost 12 hours was reached by each patient to first walk . Group F reported side effects such as dizziness , nausea Comparison of the number of hospitalization days (after surgery until showing appropriate conditions for discharge) in the two groups revealed no significant differences. Group F patients were hospitalized for 5.3 days and group I, 5.8 days on average . The satisfaction of the patients with the measures taken to control pain, did not reveal a significant difference between the two groups at the end of 48th hour after the surgery  and the patients had described the result as “satisfactory”.In group I the results were as follows; “good” , “satisfMean range of motion at the time of discharge was 66.9° in group F and 69.5° in group I. 3 months after the surgery, Mean range of motion was 112.2° in group F and 114.4° in group I. The results were not statistically significant . In the present study F and I methods were selected to be compared because previous studies had well indicated the effectiveness of these two methods in relieving pain after knee replacement surgery , 8, 18. To our knowledge, there are few studies comparing single injection femoral nerve block with peri- and intra-articular methods. Ropivacaine dosage (300 mg) was derived from Ker and Kohan’s study  who pionLimitations of this study included converting palliative opioid amounts to their morphine equivalent which does not necessarily have to be the calculated doses, also utilizing a patient-controlled analgesia (PCA) set was not possible in this study and considering that a nurse was responsible to administer the opioid so another human factor affects the study. Double-blinding was strictly observed as far as possible, but paralyzed quadriceps muscle and numbness of the anterior thigh and medial side of the calf can distinguish group F from group I and have roles in administering more palliatives by the nurse. Considering the uprising of opioid receptors in the incision area due to inflammation and tissues trauma , 25, theIn the study at hand, morphine consumption in the first 24 hours after surgery in group I (10 mg) was less compared to group F (12.5 mg) which accords with the results of a study carried out by Karen Toftdah et al.. Also inMorphine consumption doses during the first 48 hours were not significantly different between the two groups which can be suggestive of the disappearance or decrease in the effectiveness of these two methods after 24 hours . The VAS scores of the first 6 hours were lower in group I compared to group F; however, 12 hours after the surgery the patients in group F reported lower VAS scores  that may stem from the hemobag drain (that was on for 10 minutes every 2 hours) and thus wash-out effect generated in method I. In this clinical trial walking time, side effects, patients’ satisfaction with pain control and the number of hospitalization days were not significantly different between the two groups .Also the clinical outcome (measured by ROM) did not show a significant difference between the two groups at the time of discharge and 3 months after the operation. These results accord with the findings of Won Sik Choy et al. (22)and Francis V. Salinas (19). This result does not seem unlikely considering the new rehabilitation protocols emphasizing ROM restoration in outclinic form (outpatients and patients outside the clinic) which bases the discharge criteria on the physical ability not pain control. According to Francis V. Salinas’s study mean hospitalization period is 4 days, the present study comes close to that figure with almost 5 days and reduce the role of pain control protocols in reducing length of stay.The time it takes for both groups to walk for the first time after the surgery was almost 12 hours which shows no statistically significant difference .Local infiltration analgesia (I) and femoral nerve block (F) methods are two appropriate methods to control TKA postoperative pain satisfactorily. Compared to femoral nerve block, local infiltration analgesia resulted in lower VAS scores in the first 6 hours and less morphine consumption in the first 24 hours after the surgery. It is also a surgeon-controlled analgesic technique; taking into account the fact that during the 24 to 48 hours of post-surgery all parameters showed not much difference and lack of statistically significant difference in the clinical outcome, hospitalization length and patients’ satisfaction level, with slight preference of local infiltration analgesia technique both methods can be used interchangeably depending on facilities and resources. It seems that pain control does not have a large effect on the improvement of final clinical outcome and length of stay. New physical therapy protocols (mostly outclinic) have diminished the role of pain control in achieving this goal. Fear of post-surgical pain is one of the most important concerns for the patients but by using (I) and (F) pain-relieving methods the fear can be dealt with and consequently patients’ satisfaction level can be improved to a great extent. We also recommend well-structured clinical trials to determine the dosage and kinds of other analgesic drugs with such protocols.


Objective. To investigate the question of whether duration of pain before surgery ultimately affects sperm parameters after varicocelectomy. Methods. Fifty patients with painful grade-3 varicocele were investigated prospectively. The patients were divided into two groups according to their symptom period. The patients having had grade-3 varicocele for less than 1 year were included in Group-1 . Twenty-five patients who had painful grade-3 varicocele for more than 1 year  were classified in Group-2. Semen analysis was performed after 3 days of sexual abstinence twice a month. Total sperm concentration (TSC), rapidly progressive motility (SPa), and slow or sluggish motility (SPb) rates were noted. Pain was evaluated by using 10 cm visual analogue scale (VAS). Results. Postoperative TSC and %SPb were significantly higher in both groups (P = 0.01). There was no difference between two groups for preoperative and postoperative TSC, %SPa, % and SPb values. VAS significantly declined in both groups (P = 0.005). This postoperative decline was not significant for intergroup comparison. Conclusions. Our results show that increase in semen quality and decrease in the pain after microsurgery varicocelectomy do not depend on the duration of the preoperative pain. Varicocele is the dilatation and tortuosity of plexus pampiniformis leading to a retrograde reflux. It is estimated in 15–22% of adult male population and 30–40% of men presenting with infertility to the urology clinics [Varicose veins may cause pain. The etiology of varicocele is similar to peripheral varicose veins. It is not enlightened yet whether varicocele may cause pain because of testicular damage. Our hypothesis is that if the pain was due to testicular damage, the longer duration of pain before surgery would negatively influence varicocelectomy outcomes.n = 25) whereas Group-2  included the patients who had grade-3 painful varicocele for more than one year. In the first visit, duration of the symptoms, type of the pain, other scrotal pathology or scrotal surgeries, duration of the pain, sexual partner, and number of children were inquired. The patients who have undergone varicocelectomy previously were excluded to avoid bias. The degree of varicocele was evaluated by physical examination and graded as described in urological literature. Color Doppler testicular ultrasound (CDT USG) was performed to every patient to reveal other scrotal pathology and testis atrophy. Semen analysis was performed after three days of sexual abstinences twice a month. Total sperm concentration (TSC), rapidly progressive motility (SPa), and slow or sluggish motility (SPb) rates were noted. TSC was reported as million/mL. The rates for SPa and SPb were calculated as percents. Pain was evaluated by 10 cm visual analogue scale (VAS). Total testosterone values were only checked in patients who had a TSC of 5 million/mL. The cases had a TSC of 10 million/mL and/or %Spa + SPb < 50%, or severe scrotal pain persistent to conservative methods was encouraged for the surgery. All of the patients were informed about the surgery and informed consent was obtained. Microscopic subinguinal varicocelectomy  was performed by the same surgery team. All visible dilated spermatic veins and collaterals were dissected and ligated. Postoperative TSC, SPa, SPb, and VAS were investigated 3 months after the surgery and checked every month in the following visits for four years. The data were taken as the mean and standard error of mean (SEM). Statistical analysis was made by paired samples two test and P < 0.05 was accepted as statistically significant.After being approved by the Ankara Mevki Military Hospital Local Ethical Committee (2008), 50 patients with painful grade-3 varicocele were investigated between 2008 and 2012, prospectively. The patients were divided into two groups according to their pain duration. Before randomising patients, one year was accepted as a cut-off value for preoperative pain duration. The patients who had grade-3 painful varicocele for less than one year were included in Group-1  months in Ge and 21 (±4.27 SD) months in Gs. All of the cases had left varicocele in Ge. Eight patients had bilateral varicocele in Gs. Two patients in Ge and 1 patient in Gs represented with infertility. None of the patients had atrophic testes. Preoperative and postoperative TSC, SPa, SPb, and VAS values are emphasized in Tables P = 0.01). However, when two groups were compared, TSC value did not show difference after surgery. For each group, there was no difference between preoperative and postoperative SPa rates. Increment in SPb after varicocelectomy was statistically different either in Ge or in Gs (P < 0.05). On the other hand, it was not different when two groups were compared. VAS declined in two groups after surgery (P = 0.005). This decline showed no difference in intergroup assessment.For intragroup comparisons, TSC was significantly higher after varicocelectomy .Varicocele may be accompanied with chronic scrotal pain in 2–14% of the patients . Also 2–The major indication for varicocelectomy is infertility. Scrotal discomfort or pain in patients with varicocele is estimated as 2–10% . The paiThe results of varicocelectomy recommended in scrotal discomfort or pain are controversial, in the literature. Chen, investigated 76 men with painful varicocele and normal sperm quality . He concThe patients who have palpable varicoceles and abnormal sperm parameters may be encouraged for varicocele repairment. The success rates for painful varicocele were reported as 86–88% for pain resolution; however, the surgical technique is still a dilemma , 15. ArmAltunoluk et al. suggested that subinguinal microscopic varicocelectomy was an effective treatment for painful varicocele. Also, they concluded that the duration of pain preoperatively might predict outcomes .As Armagan et al. conclude, we believe that microsurgical varicocelectomy is a useful method for pain improvement and RECOVERS sperm parameters in patients with varicocele-related pain . HoweverFew authors have investigated the duration of scrotal pain in varicocele as a predictive factor , 19. In Microscopic varicocelectomy is useful in patients with scrotal pain, scrotal discomfort, or bad semen quality. Since varicocele is a progressive disease, varicocelectomy may be recommended in cases that have abnormal semen parameters.We conclude that increase in semen quality and quantity and decrease in the pain after microsurgery do not seem to be related with preoperative duration of pain.


Ambroxol has a local anaesthetic action and is marketed for pain relief for sore throat. The objective is to examine the efficacy and safety of ambroxol for the relief of pain associated with acute uncomplicated sore throat.A systematic review of the literature and meta-analysis. Selection criteria consisted of randomized controlled trials which compared ambroxol to placebo or any other treatment for sore throat. Two reviewers independently assessed for relevance, inclusion, and risk of bias. Weighted mean differences (WMDs) were calculated and are reported with corresponding 95% confidence intervals (CIs).From 14 potentially relevant citations, five trials reported in three publications met the inclusion criteria, three of them were published twice. Ambroxol lozenges were compared in different dosages (5–30 mg) with mint flavoured lozenges and once with benzocaine. Main outcome was a ratio of pain reduction measured repeatedly over 3 h compared to baseline on 6-item verbal rating scale. A total of 1.772 adult patients participated in the trials. Pain intensity decreased in both study arms. A meta-analysis of the 5 controlled trials resulted in a difference in pain reduction compared to placebo of -0.11  favouring ambroxol 20 mg. Quality of reporting of the studies was low. Ambroxol is slightly more effective in relieving pain in acute sore throat than mint flavoured lozenges over a period of 3 h. However, the additional benefits of ambroxol beyond three hours, remain unclear given that more than 50% of patients using mint flavoured lozenges for pain relief reported good or very good efficacy after 1 day compared to 69% with ambroxol. Ambroxol is a safe option for individual patients with mainly local symptoms asking for treatment. Pharyngitis or sore throat is a highly prevalent mostly self-limiting condition for which most people do not seek medical attention . Viral oGargling, drinking warm liquids and oral antipyretic or analgesic drugs are common supportive treatments . AmbroxoWe performed a systematic review and meta-analysis of the effects of ambroxol to relief pain of sore throat compared to placebo in outpatients and discuss the implications for practice.This is a meta-analysis conducted according to the guidance of the PRISMA statement .We searched in the three following electronic bibliographic databases: MEDLINE, EMBASE and Central of Cochrane Data Base of systematic reviews. We included studies published between 1966 and May 31, 2011. The search algorithm contained the following keywords and MeSH-terms: [Ambroxol AND (pharyngitis OR tonsillitis OR rhinopharyngitis OR tonsillopharyngitis OR pharyngotonsillitis OR sore throat OR pharynx* OR tonsil*)]. Additionally, we searched manually through the reference list of the identified articles. We also contacted the manufacturer of Ambroxol and searched ClinicalTrials.gov  for regiEligibility criteria: Our search included published randomized controlled trials (RCTs) that compared ambroxol as treatment for sore throat with a placebo. We did not place restrictions on eligibility according to drug dosing, duration of application or publication language and did not exclude specific populations or age groups.Screening process: Two independent reviewers  screened the citation titles and abstracts using a predesigned orm. We excluded titles and abstracts that clearly did not meet the inclusion criteria. For those titles fulfilling inclusion criteria full-text articles were obtained. The two reviewers resolved disagreements by consensus.We extracted information from the original reports onto standardized forms. All data was entered into Review Manager (RevMan) . The pri2 measure and a formal hypothesis test. Forest plots showing the effect estimates of the individual studies and the combined effect allow visual assessments of the heterogeneity and provide an overview of the results. Subgroup analyses were carried out for different doses of ambroxol. We tested for subgroup differences and report the p-values.We used the Cochrane Collaboration tool for assessment of the risk of bias . The assOverall 14 potentially relevant publications were initially identified. We extracted five relevant RCTs reported in three publications . Three RThe characteristics of the included five trials are given in Table Inclusion criteria were sore throat not lasting longer than three days before inclusion in the study. Patients with suspected bacterial infection were excluded on the basis of clinical findings absence of seropurulent or fibrinous exudates. There are inconsistencies in the reporting participants’ age as inclusion criterion. Throat swabs were not taken. Although it is specified that all patient were outpatients it remains unclear if patients were recruited in ambulatory care, emergency departments or especially set up clinics.Risk of bias is presented in Table Reported pain reduction from baseline over a period 180 minutes ranged from:• 37 to 42% from ambroxol 20 mg• 40 to 49% from ambroxol 30 mg• 27 to 35% from mint flavoured placebo lozenges.95 ) for 20 mg and -0.17  for 30 mg of ambroxol. Although it seems that Ambroxol 30 mg is more effective than 20 mg the difference is statistically not significant (p=0.15). The standardized mean differences are -0.34  and -0.43  for 20 mg and 30 mg of ambroxol, respectively. These translate into probabilities of 59% and 62% that the pain reduction is greater or faster with ambroxol compared to placebo. The two unpublished trials also reported statistically significant differences in pain relief favouring ambroxol 20 mg, but did not provide enough data to be included in this meta-analysis.The Forest plots show the difference of pain reduction of ambroxol 20 mg and 30 mg over 3 h compared to placebo  after 1 day. The observed adverse effects although more frequent in the treatment arms were usually mild or could be attributed to the medical condition. All patients were selected based on clinical presentation to minimize the presence of streptococcal throat infection and did not receive concomitant antibiotics. This is in line with recommendations from most European guidelines ,19.Sucking candy is a popular home remedy and it is likely that sucking lozenges is not just a placebo but decreasing pain e.g. by increasing saliva flow and reducing dryness of the oral mucosa. Additionally menthol is a pharmacologically effective ingredient known to affect sensation of the oral mucosa .95 ) for 20 mg ambroxol suggesting roughly 10% more pain reduction compared to placebo after 3 hours seems small. Ambroxol is available as 20 mg preparation.The primary outcome as defined in the studies cannot be interpreted easily in clinical terms. Therefore, it is unclear what should be considered a minimal important difference (MID) on that scale for sore throat. The summarized observed pain reduction of -0.11  declare that they have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in this paper. Jean-Francois Chenot hat acted in 2009 and 2010 as consultant for Böhringer Ingelheim the manufacturer of ambroxol lozenges.The literature search and data extraction was done by JF and PW. Statistical analysis was done by JFC and TF. All authors drafted and reviewed the manuscript. JFC is a General Practitioner and health scientist, PW is a resident in Internal Medicine and TF is a biostatistician. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/15/45/prepub


In chest pain, physicians are confronted with numerous interrelationships between symptoms and with evidence for or against classifying a patient into different diagnostic categories. The aim of our study was to find natural groups of patients on the basis of risk factors, history and clinical examination data which should then be validated with patients' final diagnoses.We conducted a cross-sectional diagnostic study in 74 primary care practices to establish the validity of symptoms and findings for the diagnosis of coronary heart disease. A total of 1199 patients above age 35 presenting with chest pain were included in the study. General practitioners took a standardized history and performed a physical examination. They also recorded their preliminary diagnoses, investigations and management related to the patient's chest pain. We used multiple correspondence analysis (MCA) to examine associations on variable level, and multidimensional scaling (MDS), k-means and fuzzy cluster analyses to search for subgroups on patient level. We further used heatmaps to graphically illustrate the results.A multiple correspondence analysis supported our data collection strategy on variable level. Six factors emerged from this analysis: „chest wall syndrome“, „vital threat“, „stomach and bowel pain“, „angina pectoris“, „chest infection syndrome“, and „ self-limiting chest pain“. MDS, k-means and fuzzy cluster analysis on patient level were not able to find distinct groups. The resulting cluster solutions were not interpretable and had insufficient statistical quality criteria.Chest pain is a heterogeneous clinical category with no coherent associations between signs and symptoms on patient level. People rarely experience one symptom in isolation. Physicians are confronted with numerous interrelationships between symptoms and with evidence for or against classifying a patient into a diagnostic category. They categorize patients with regard to diagnosis, prognosis, and/or further management. Therefore, finding groups in patient data is important in several respects. One might identify subgroups of patients who can benefit from different interventions. Certain symptom configurations might be a cue for further investigations . DiagnosCoronary heart disease (CHD) is one of the main underlying aetiologies for chest pain in primary care . PrimaryStatistical measures for grouping variables or patients have rarely been applied to chest pain data, mostly in connection with finding subgroups in acute coronary heart disease. We only found one study in chest pain which performed a k-means cluster analysis on variable level to determine whether there are characteristic patterns in chest pain locations described by patients . The groWe intended to use statistical methods to identify natural groups of patients with chest pain on the basis of a larger, comprehensive data set with information on history, risk factors, and physical examination ,11. ThesPatients were enrolled consecutively in a primary care setting so that patient recruitment was not distorted by referral patterns. This could have been the case if we had included specialized physicians (e.g. cardiologists) who get a selection of patients referred to them by primary care doctors.We conducted a cross-sectional diagnostic study in a primary care setting  with theWe approached 209 general practitioners (GPs) in the Land of Hesse of whom 74 (35.4%) agreed to participate in the study. Participating practices had to recruit consecutively every attending patient who had chest pain. The recruitment period lasted 12 weeks for each practice.Every patient above 35 years with chest pain was to be included. Patients were eligible irrespective of the acute or chronic nature of their complaint, or of previously known conditions including CHD or risk factors. Patients whose chest pain had subsided for more than one month, whose chest pain had been investigated already and/or who came for follow-up for chest pain were excluded. This resulted in a total of 1199 patients.The data collection strategy was based on the current literature on chest pain and on feedback by GPs . The GPsRandom audits were performed searching routine documentation of participating practices to identify cases of chest pain not included in the study.After 6 months a reference panel consisting of one cardiologist, one GP and one research staff of the department of General Practice/Family Medicine decided about the presumed diagnosis at the time of patient recruitment on the basis of the GP's documentation and follow up data.http://www.almo-statistik.de).For statistical grouping techniques like cluster analysis it is important that the underlying constructs are reliably measured and relevant variables are included in the analyses . Consequstats (http://www.R-project.org).Based on the results of MCA, we applied two visualization techniques in order to get a first idea of any specific structure in the data, notably in terms of a natural clustering into subgroups. We used multidimensional scaling (MDS) and hierarchical clustering combined with a so-called heat map representation. Both techniques are implemented in the R package The first method, MDS, seeks to embed the original observations as vectors in a low-dimensional space, typically the two-dimensional Euclidean space, so as to preserve the pairwise distances between these observations as far as possible . Thus, MDS only requires dissimilarities between observations as input. If data are given as multidimensional vectors, the dissimilarities can be computed as Euclidean distances between these vectors. If natural clusters exist within the data, these clusters should also become visible in the low-dimensional representation of the data .A heat map represents the pairwise distance (similarity) matrix in terms of an image, with distance (similarity) degrees indicated by colours : The darker the colour, the more similar the observations are. Prior to printing the image, the sequence of observations is reordered in such a way that similar observations tend to be neighboured. More specifically, this reordering is determined by means of a hierarchical clustering of the data, and the corresponding dendrogram is added to the left and to the top side of the image. Since the similarity matrix is symmetric, both dendrograms are the same, and the image itself is symmetric, too. Clusters within the data become visible as "warm-shaded squares" along the diagonal of the heat map.2 for each cluster solution is calculated that indicate the contribution of the classification variables to the separation of the clusters. One may then choose the solution with the highest F value and largest explained variance (eta2). If this solution is not reasonably interpretable with regards to content, then it is admissible to choose another solution [In a next step, we performed k-means cluster analyses on patient level, generalized to all scales of measurement with weighted squared euclidean distances ,20. The solution .http://www.ncss.com) [To account for a possible fuzziness in our data, we additionally undertook fuzzy cluster analyses with the programme NCSS2007 (css.com) . In commcss.com) ,23. Anot2 value is explained by the six factors. In our case, the GFIR shows that 57.5% of the total χ2 value is explained by the six factors. This is a satisfactory result.At first, by applying multiple correspondence analysis (MCA), we explored if the variables on our case report form capture relevant aspects of chest pain. We used the oblique quartimin rotation to enhance interpretability of the results. Six factors emerged from the analysis. The highest correlation between these factors is -.36 so that these factors can be regarded as being orthogonal. The eigenvalues of the six factors range from 2.08 to 3.72. The total explained variance is 24.8%. The explained variance gives a too pessimistic picture about model fit. Consequently, the fit index GFIR is recommended  which inTable Factor 1 can be interpreted as „chest wall syndrome“, as it contains characteristic pain related items for this entity. Factor 2 can be named „vital threat“. It contains items typical for a life-threatening symptomatology. Factor 3 can be characterized as „stomach and bowel pain“. It consists of male patients with vomiting, radiation of pain into the upper abdomen, and with no risk factors. Factor 4 can be labelled „angina pectoris“ because of the characteristic symptoms having highest loadings on this factor. Factor 5 is interpreted as „chest infection syndrome“ and Factor 6 as „self-limiting chest pain“.Figure We also present heat maps based on the pairwise similarities between data points, using 6 and 20 factors from MCA Figures  and 5. L2 of .073. This solution was not interpretable and had only 7.3% explained variance. Other cluster solutions were also not interpretable because of worse quality criteria.A k-means cluster analysis on patient level with all variables of our case report form resulted in a three cluster solution with a small F value of 46.8 and an eta2 smaller .10 as a contribution of a single variable to cluster formation [2 of .135. This solution was not interpretable and had only 13.5% explained variance. Again, other cluster solutions were also not interpretable because of worse quality criteria. The k-means approach was therefore not able to form meaningful patient groups in our data.Cluster analysis is an iterative process ,21. Therormation . Even afThe best interpretable solution in fuzzy cluster analysis after excluding variables with no meaningful theoretical and numerical contribution consisted of four clusters. Cluster 1 (n = 221) can be characterized as "acute and/or threatening chest pain", Cluster 2 (n = 402) as "subacute chest pain", in Cluster 3 (n = 288), there are mainly women ≧ 65 years of age with no acute chest pain, and in Cluster 4 (n = 288), there are mainly men ≧ 55 years of age with no acute chest pain. The average silhouette of this solution was 0.54 which hardly denotes a reasonable structure in the data. The Fc(U) with .49 was low and the Dc(U) with .42 was relatively high and both indicated a high fuzziness in our data. We concluded that fuzzy clustering also was not able to partition patients into meaningful entities that have a statistical or clinical relevance.2 of .326. This solution, although statistically acceptable, was clinically not interpretable. For example, patients with vital threat and chest infection syndrome were grouped into the same cluster. Other cluster solutions with lower F values and higher number of clusters were also not clinically interpretable. The best statistical solution in fuzzy cluster analysis consisted of two clusters. The average silhouette of this solution was 0.25 which means that there was no substantial structure in the data. The Fc(U) with .50 was low and the Dc(U) with also .50 was relatively high and both again indicated a high fuzziness in our data. In this second order analysis, fuzzy clustering was not able to form patient groups that are interpretable on a statistical or clinical level.We further cluster analyzed the factor scores on each of the six factors that resulted from our MCA. Each patient had a certain score on these six factors so that we ran a second order analysis with six variables. A k-means cluster analysis resulted in a two cluster solution with a F value of 578.2 and an etaIn our study, clinical data of patients with chest pain had an underlying structure on variable level but not on individual patient level. As a result, patients could not be grouped into clinically meaningful clusters by multivariate analyses and therefore no validation against patients' final diagnoses was possible.A multiple correspondence analysis (MCA) supported our data collection strategy on variable level. It showed that relevant aspects were captured by the case report form. Six factors emerged from this analysis: „chest wall syndrome“, „vital threat“, „stomach and bowel pain“, „angina pectoris“, „chest infection syndrome“, and „self-limiting chest pain“. Therefore, the clinical category chest pain had a meaningful underlying structure. MCA supported our measurement strategy.However, k-means and fuzzy cluster analysis on patient level were not able to find distinct groups. The resulting cluster solutions were not interpretable and had insufficient statistical quality criteria. The absence of any pronounced cluster structure was also confirmed by multidimensional scaling (MDS) and heat map representations of the data.Strengths of this study are the prospective design, a large and representative consecutive sample in a primary care setting not distorted by referral patterns, and small drop out rates. Study procedures, including random audits, reduced the possibility of selection bias, and an interdisciplinary team provided a precise diagnosis as reference standard.Individual configurations of patients on our variables were widespread with no typical groupings. This conclusion is supported by Eslick  who perfOther studies using multivariate techniques were done with patients already given a cardiac diagnosis. Crichton and Hinde used multiple correspondence analysis to classify patients with chest pain into those with high cardiac risk and those with low cardiac risk . CorrectTo our knowledge, ours is the first study to apply MCA and MDS to chest pain data and to use cluster analysis in such detail to search for patient groups in this area. We found an underlying structure of the construct chest pain on variable level but no structure on individual level. Perhaps we have not measured all relevant aspects but we consider this to be unlikely on the basis of previous studies. We even recorded subjective impressions of physicians and patients in addition to objective medical data.Chest pain seems to be a heterogeneous and multi-faceted clinical category that has no prototypical manifestations on patient level. This might be a disillusioning result because the physician is expected to construct a diagnosis on an individual level and to categorize whether the patient has a serious condition and needs special care or not. Nevertheless, it has to be emphasized that classification of patients into a diagnostic category is possible without finding natural groups in data . This waThe authors declare that they have no competing interests.OH developed the concept for data analysis, performed the statistical analyses, and drafted the manuscript. SB participated in the concept for data analyses, participated in performing the statistical analyses, and helped to draft the manuscript. EH developed the concept for data analysis, performed the statistical analyses, and helped to draft the manuscript. RS developed the concept for data analysis, performed the statistical analyses, and helped to draft the manuscript. KD developed the concept for data analysis, performed the statistical analyses, and helped to draft the manuscript. NDB participated in the study design and coordination, the rationale for the data analyses, 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/1471-2288/11/155/prepub


Falanga torture (beatings on the foot soles) produces local chronic pain and severe walking difficulties. We have previously reported signs of neuropathic pain in the feet of falanga victims. The objective here was to clarify underlying pain mechanisms by quantifying sensory impairments in the feet of torture victims who had experienced both generalized torture and those who had been exposed to falanga in addition. An ethnically matched control group was available.We employed quantitative sensory testing (QST) by investigators blinded to whether the patients, 32 male torture victims from the Middle East, had (n=15), or had not (n=17) been exposed to falanga. Pain intensity, area and stimulus dependence were used to characterize the pain as were interview data on sensory symptoms. QST included thresholds for touch, cold, warmth, cold-pain, heat-pain, deep pressure pain and wind-up to cutaneous noxious stimuli in the foot soles. Clinical data on anxiety and depression were retrieved.Almost all falanga victims had moderate or strong pain in their feet and in twice as large an area of their foot soles as other torture victims. One-third of the latter had no pain in their feet and many reported slight pain; in spite of this, there were no differences in foot sole QST data between the tortured groups. A comparison with normal data indicated that both tortured groups had hypoesthesia for all cutaneous sensory fibre groups except those transmitting cold and heat pain, in addition to deep mechano-nociceptive hyperalgesia.A comparison of the QST data between victims having been exposed to generalized torture and victims who in addition had been exposed to falanga, showed no differences on the group level. The sensory disturbances in relation to our control group are compatible with central sensitization and de-sensitization, pointing to a core role of central mechanisms. A further analysis to create individual sensory profiles from our measurements is in progress. The use of falanga (beatings on the soles of the feet) is a torture method which deliberately aims at inflicting intense pain in the feet and lower legs ,2. The mThe pathophysiological mechanisms of the chronic pain after falanga have puzzled clinicians and researchers. Some have hypothesized that a plantar closed compartment syndrome was the cause of pain and resulted in being unable to walk more than short distances ,9,10. OtChronic pain is common among torture victims. Olsen at al.  found thIt is well known that nerve lesions may cause chronic neuropathic pain . ThomsenIn a group of persons exposed to falanga torture, we found  sensory Extending the observations that neuropathic conditions occur in the feet after falanga torture, the primary objective of this study was to help clarify the underlying pain mechanisms ,20 by quThe patients recruited were torture victims who had been granted asylum in Denmark. They were all referred to our centre from their general practitioner, because of their long-term sequelae from various types of torture that they had been subjected to several years earlier in their homeland. The patients were screened by an assessment team , with reference to the centre’s admission criteria: 1) torture victim with asylum in Denmark; 2) physical, psychological and social needs; 3) no overt psychosis; 4) no drug or alcohol abuse; and 5) available treatment capacity.Following the main study, by snowball sampling, we managed to recruit 14 ethnically and age matched healthy men from the Middle East community in Copenhagen to form a control group, going through exactly the same QST methods as the patients. They had lived in Denmark for an average of 15.8 years (range 7–26), all spoke Danish and they were integrated and active in the Danish society. Their mean age was 37 years (range 21–55).The inclusion criteria for this study were tortured male patients originating from the Middle East speaking their native language, which was Arabic or Farsi . Seventy-nine consecutively referred patients were identified via the electronic patient records  informed them about the purpose and methods used in the study. If the patient agreed to participate an informed consent form was signed and dates for the assessments arranged. Seventeen turned down the offer, and three started but dropped out during the test sessions. Thus 32 patients participated in all three sessions. All participants were offered compensation for travel expenses. Arabic or Farsi interpreters assisted at all sessions. The project had been carefully introduced to the three interpreters involved, all of whom had long experience in interpreting for torture victims. Well informed about the procedures, they even volunteered for being tested with the techniques.The examiner (KP) and a research assistant were blinded with regard to patient history, diagnosis and whether falanga torture had occurred or not. Breaking of the blinding took place only after the completion of all examinations and data analyses of the individual patients.All examinations were scheduled to 3x2 hour sessions within a two week period and took place in a quiet room (stable temperature of 22–24°C) in the research department at our centre. For training the various QST methods were first practiced on healthy Danish volunteers.st session included an interview about pain and other sensory experiences, location and size of painful area [nd session tactile and thermal thresholds were examined [rd session pressure pain thresholds  and wins , in theAt all foot examinations the participants lay on a couch with a special soft mattress. Individual needs were met to avoid painful body positions and make the patient as comfortable and relaxed as possible. Applications of the test stimuli were not visible to the patient at any time. All assessments and tests were performed by KP. A research assistant and an interpreter were also present.To our knowledge only few studies have examined the arch of the foot sole with respect to normal QST values, and those existing are mostly recorded from the dorsum of the foot ,31,32.th metarso-phalangeal joint. However, when the patients were asked which was the most painful area of their foot soles, they usually answered ‘under the arch’. Therefore, we chose the arch of the foot sole bilaterally for all remaining QST sensory tests. This site has been reported to be the most sensitive in the foot sole, both by our patients and in the literature [Five sites were identified by palpation for examining mechanical detection thresholds  and PPTterature ,27.This All participants were asked about pain in the foot soles at rest and when walking and the findings were registered on a 3-point Likert scale  to deteTwo pain drawings were used to assess pain locations . The exaSelf-reported current pain intensity was assessed on a visual analogue scale , with rWe tested sensory modalities related to all major types of sensory nerve fibres using QST within the time constraints available for these vulnerable patients in both feet.Tactile sensitivity under the foot soles was assessed bilaterally by measuring the mechanical detection threshold (MDT) to light touch using Semmes-Weinstein monofilaments . We used 17 out of the 20 available monofilaments, from size 2.83 (target force 0.07 g) through to size 6.65 (target force 300 g). The detection threshold was defined as the least force that elicited a sensation of touch. The monofilament was applied at a 90° angle against the skin until it bowed during 1.5 s, held for 1.5 s and slowly released during 1.5 s . The exatm– Brush-05; Somedic, Hörby, Sweden). Three consecutive strokes were applied with the brush to the skin in the arch of both foot soles over a 60 mm long distance [Dynamic mechanical allodynia is a painful or unpleasant sensation evoked by a cutaneous mechanical stimulus which does not normally evoke pain. To examine this phenomenon we used a qualitative test with light strokes with a soft brush  were measured to assess deep mechanical nociception  by applyst and 4th stimulus. A 5-minute pause followed. Thereafter, to produce a more intense stimulation, 10 consecutive stimuli were applied at the rate of 1.0 Hz. The patients rated their pain after the 1st and 10th stimulus. If the VAS difference between the 1st and last stimulus was positive, a temporal summation (wind-up) had occurred.Wind-up pain -44 referWe chose to analyse the data from the right and left feet separately, since they may share common analysis mechanisms in the central nervous system, even if separate. The mean, SD, 95% CI, median, and range were calculated for all ten variables, as were the correlations between both feet. Students t-test or Fisher’s exact test was used to test for differences between sides.post hoc Tukey analysis was performed to indicate the differences between data in the respective groups. Acceptable p-values were set to ≤0.05.To detect differences between the torture groups and the controls, identified after breaking the blinding as victims not exposed to falanga (NF) and victims exposed to falanga (F), we used univariate ANOVA’s test. A The data were analysed using the Statistical Package for Social Sciences (SPSS) version 18, Software for Windows .Each participant was informed verbally about the study and was also given an information kit containing a comprehensive written description translated into their respective languages. They also received translated guidelines concerning participation in medical research issued by the Danish Ethical Committee. The assessments comply with the Helsinki II Declaration  and the Figure The mean age did not differ between the two groups: NF = 44.5 years (range 34–63) and F = 46.3 years (range 38–55). The NF victims had been tortured for the first time during the years 1979–2000 and had spent a median of 180 days (range 1–2372) in prison, whereas the F victims had been tortured for the first time during the years 1989–1996 and had spent a median of 365 days (range 15–1700) in prison.All 32 patients reported pain in many parts of the body, located in at least 3 out of 4 quadrants. When asked about their one most painful region, neck, shoulder and low-back pain were the most common complaints, and only two patients in the F group reported their foot pain as being the most severe. The mean body pain area size in the NF patients was 13.8% of the total body area  whereas for the F patients it was 21.0% . The mean current body pain intensity (VAS) in the NF patients was 48 mm  whereas for the F patients it was 60 mm . Neither of these differences was significant (Student’s t-test).Since we could collect data from 64 feet but the central pain processing occurred in 32 persons, we examined whether QST data from the two sides of a single individual corresponded. It turned out that the Pearson correlation coefficient from the right versus left data of the torture victims was generally high Table  and the It was possible to retrieve data on anxiety and depression in 26 out of our 32 patients  from HADS forms. The median anxiety score in NF victims was 19.5 points (11 out of 12 patients had ≥ 15 points) and in F victims was 19.0 points (13 out of 14 patients had ≥ 15 points) demonstrating severe anxiety in both groups. The median depression score in NF victims was 16.5 points (8 out of 12 patients had ≥ 15 points) ) and in F victims was 17 points (10 out of 14 patients had ≥ 15 points), likewise pointing to severe depression.The 32 patients were categorized according to their reported activity related foot pain when walking. Seven feet (NF/F: 4/3) exhibited stimulus-independent foot pain, whereas stimulus-evoked pain was perceived in 45 feet (NF/F: 20/25). No pain was reported in 12 feet (NF/F: 10/2). Thus only 2/30 F feet were pain free whereas 10/34 NF feet were so . A corresponding comparison between pain free feet and those with stimulus-evoked pain (NF/F: 10/2 vs. 20/25) was barely significant .Current foot pain intensity at rest was ≤ 30 mm  in 20/3From the interviews regarding the 64 feet (relation NF/F 34/30 feet), numbness was experienced in 21/14 feet; cold sensation in17/12 feet; burning sensation in 20/22 feet and a pricking sensation in 17/20 feet, respectively.The brush test (NF/F) demonstrated dysesthesia in 15/14 feet, and dynamic mechanical allodynia in 4/2 feet. Thus, there were no obvious differences between those exposed to falanga or not regarding irritative phenomena.As can be seen in Tables Immediately before thermal testing the plantar skin temperature was measured and the mean was found to be 30.8°C (NF) and 30.4°C (F), similar to values found in the literature . During The mean pre/post difference in pain intensity for the F group after repeated cutaneous mechanical stimulation at 0.3 Hz (cf. ) was 16 Using correlation analysis we also explored other variables to explain our findings and found a clear correlation between the severity of HADS anxiety score and foot pain intensity . Regarding body pain intensity, only a tendency to correlation was seen . The same was found for body pain area size . There were no correlations between body pain intensity/body pain area size and the HADS depression scores. Regarding the QST variables, there were no significant correlations to HADS scores at all.We compared the sensory findings from victims exposed to generalized torture to victims who had additionally been exposed to falanga, as an extension to earlier studies from our centre ,6,19. InIn spite of the expected clinical differences in foot pain symptoms between the two tortured groups, our main observation was that there were no significant differences between them regarding the QST findings. However, in comparison to our control data, the picture is instead dominated by a generalized hyposensitivity to non-noxious cutaneous stimuli in the foot soles in combination with deep mechanical hyperalgesia. A possible interpretation of these unexpected findings could be that the impact of generalized torture is so heavy on the central nervous system that the situation of the individual is dominated by a global change in central function. This would consist of a blend of sensory sensitization , de-senThe elevated MDTs indicate that both groups had reduced protective sensation. According to Bell-Krotoski  the 2.83HPTs and CPTs were within normal range in both groups of torture victims. Regarding PPTs, we found hyperalgesia to deep mechanical stimuli in both groups, probably due to a central sensitization, or possibly due to peripheral sensitization of C-fibre nociceptors .In a sense, our QST findings comply well with the results of researchers studying other neuropathic pain conditions. Their study results have been found to comprise a complex web of different pain and sensory characteristics ,53-57 raThe only previous study of chronic pain in patients suffering from PTSD was conducted by Defrin et al. . They foThe patients were refugees with residence permit in Denmark and referred by their general practitioner to our specialized clinic, making our sample highly selected and therefore probably not representative of all torture victims.With our traumatized patients, it was not possible to collect exact information on the extent of falanga torture, that is, how often and how severely the victims had been beaten. Attempts to retrieve such information may produce intense anxiety and flash backs. Moreover, all patients had been subjected to various forms of torture, usually during extended periods of detention, increasing the risk of brain injuries , which mSince many of these patients have been imprisoned for long time periods, it is important to distinguish the present findings from those elicited by peripheral neuropathy, whether from toxic, nutritional or infectious causes. However, the victims were carefully examined for such comorbidities during the medical assessment (see Methods) and secondly, motor deficits, typical for severe polyneuropathies, were never found among the included patients. Furthermore, the combination seen in our patients, cutaneous hypoesthesia, normal nociceptive transmission and deep mechanical hyperalgesia, is not typical for peripheral neuropathies but has been reported in, for example, chronic regional pain syndrome (Appendix A in ). NevertRecently there has been a debate on whether QST is of value in assessing sensory disturbances in single patients ,64. The In conclusion, a comparison of the QST data between victims having been exposed to generalized torture and victims who in addition had been exposed to falanga, unexpectedly showed no differences at the group level. This was so even though almost all the falanga victims had moderate to strong pain in their feet and in twice as large an area of their foot soles as the torture victims not exposed to falanga. One-third of the latter did not report pain in their feet at all and many reported only slight pain. On the other hand, the comparison to our normal data indicated that there was hyperalgesia to deep mechano-nociceptive stimuli, irrespective of exposure to falanga or to other forms of torture. In addition, the cutaneous sensory fibre groups, except those transmitting cold and heat pain, were less sensitive to external stimuli. The findings are compatible with central sensitization and de-sensitization, pointing to a core role of central mechanisms. One way to strengthen the analysis is to create sensory profiles from our data on the individual level, which has been done in the subsequent paper .The authors declare that they have no competing interests.KP has been active in all aspects of the study: conception, design, acquisition of data (main responsibility), analysis and interpretation of data, writing of the manuscript and final approval. ALP contributed to the conception, design, analysis, and interpretation of data (main responsibility), writing of manuscript and final approval. BHS had main responsibility for the conception and design of the study, contributed to the interpretation of data and participated in writing of manuscript and final approval. All authors read and approved the final manuscript.KP, PT, MSc, has long experience of treating victims of torture since more than twenty years at our centre. This research is intended to become part of her PhD - thesis. ALP, PT, PhD, is a Senior Researcher in pain and rehabilitation research at our centre and has extensive experience of multidisciplinary pain rehabilitation. BHS, MD, DMSc, Professor of Rehabilitation at the University of Southern Denmark, is a pain management physician and was till recently Director General of our centre.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-698X/12/39/prepub


Fibromyalgia (FM) is characterized by chronic, widespread pain, fatigue, and other symptoms; yet few studies have comprehensively assessed its humanistic burden. This observational study evaluates the impact of FM severity on patients' symptoms, health-related quality of life (HRQoL), and productivity in the United States.203 FM subjects were recruited from 20 physician offices. Subjects completed a questionnaire including the EuroQol 5D (EQ-5D), Fibromyalgia Impact Questionnaire (FIQ), Multidimensional Assessment of Fatigue (MAF), Medical Outcomes Study Sleep Scale (MOS-SS), and Hospital Anxiety and Depression Scale (HADS) and questions about demographics, pain and other symptoms, HRQoL and productivity. FIQ total scores were used to define FM severity, with 0- < 39, 39- < 59, and 59-100, representing mild, moderate, and severe FM, respectively. Sites recorded subjects' clinical characteristics and FM treatment on case report forms using medical records. Summary statistics were calculated for continuous variables and frequency distributions for categorical variables. Differences across FM severity groups were evaluated using the Kruskal-Wallis or Chi-square tests. Statistical significance was evaluated at the 0.05 level.Mean (SD) age was 47.9 (10.9); 95% were female. Most (92%) were prescribed medication for FM; 24% and 66% reported moderate and severe FM, respectively. Mean (SD) scores were: 6.3 (2.1) for pain intensity; 0.35 (0.35) for EQ-5D; 30.7 (14.2) for MAF; 57.5 (18.4) for MOS-SS Sleep Problems Index; 10.2 (4.8) for HADS anxiety and 9.4 (4.4) for HADS depression. Subjects with worse FM severity reported significantly increased pain severity, HRQoL, fatigue, sleep disturbance, anxiety and depression (p < 0.001). Overall, 50% of subjects reported some disruption in their employment due to FM; this differed across severity levels (p < 0.001). Employed subjects missed a mean (SD) of 1.8 (3.9) workdays during the past 4 weeks; this also differed across severity levels (p = 0.03).FM imposes a substantial humanistic burden on patients in the United States, and leads to substantial productivity loss, despite treatment. This burden is higher among subjects with worse FM severity. Fibromyalgia (FM) is characterized by chronic, widespread, musculoskeletal pain and is estimated to affect 2 to 6 percent of the general population in the United States (US), primarily women ,2. FM paThe Outcome Measures in Rheumatology Clinical Trials (OMERACT) workgroup on FM has identified domains that should be captured in clinical trials for FM therapies and aspects of domains and outcome measures that should be part of a concerted research agenda for FM researchers . The ideRecent studies in Europe have explored the impact of FM on HRQoL and other OMERACT domains more comprehensively;  however,The objective of this study was to better understand FM patients in the US by conducting a comprehensive evaluation of their clinical and comorbid profile, and the impact of FM severity on HRQoL, symptom domains , and productivity loss for patients and caregivers.This cross-sectional, observational study included 203 FM subjects recruited from 20 community-based physician offices  in the US. Subjects were required to have the following: a prior FM diagnosis by a rheumatologist or pain specialist, experienced widespread pain (above and below the waist and on both sides of the body) for 3 months or more, experienced pain in the past 24 hours, and been in treatment at the enrolling physician's practice for at least 3 months. Additionally, all subjects had to be between 18 and 65 years of age and were excluded if they had participated in an investigational drug study within 30 days prior to the survey or had a concomitant illness unrelated to FM that was likely to confound the assessment of FM, such as osteoarthritis, lupus, or rheumatoid arthritis.The protocol was approved by a central institutional review board and all subjects provided written informed consent. No medical interventions were required by the study protocol. Site study staff identified potential subjects during routine visits. Once consent was obtained, subjects were asked to complete a questionnaire that assessed FM's impact on the core OMERACT domains, as well as productivity (subject questionnaire). Site staff completed a case report form (CRF) based on review of the subject's medical records and assessed FM using the Manual Tender Point Survey (MTPS) exam . Data caThe subject questionnaire included 5 validated HRQoL questionnaires: the EuroQol (EQ-5D) , the FibThe EQ-5D describes HRQoL across 5 dimensions: mobility, self-care, performance of usual activities, pain or discomfort, and anxiety or depression . SubjectThe FIQ measures FM subject's status, progress, and outcomes in 10 areas: physical impairment, feeling good, work missed, doing work, pain, fatigue/tired, rested, stiffness, anxiety, and depression . The impThe MAF measures 4 dimensions of fatigue: severity, distress, timing, and degree of interference in ADLs . The scoThe MOS-SS includes the 9-item Sleep Problems Index score and 6 subscales: sleep disturbances, snoring, awakening short of breath or with a headache, sleep adequacy, somnolence, and sleep quantity . With thThe HADS is designed to detect the presence and severity of mood disorders and has been used extensively in a variety of populations . The HADTo assess pain intensity, subjects were asked to rate their average pain due to FM over the past 24 hours with an 11-point numeric rating scale ranging from 0 (indicating no pain) to 10 (indicating pain as bad as you can imagine). Higher scores indicate greater pain severity. Based on previous analyses, scores of 0 to 3 are considered mild, 4 to 6 are considered moderate, and 7 to 10 are considered severe [Study-specific questions also were developed to assess the following: average pain over the past 24 hours, impact of FM on daily life, overall health status, cognitive function, and subject and caregiver productivity over the past four weeks .Means, standard deviations (SD), medians, and ranges were calculated for continuous variables and frequency counts and percentages were calculated for categorical variables. To evaluate the impact of FM severity, outcomes reported on the subject questionnaires and CRFs were compared across 3 FM severity level classifications  using the Kruskal-Wallis test. Categorical outcomes were compared across FM severity level using a Chi-square test. FM severity level was defined based on the subject's FIQ total score where 0 to < 39 was classified as mild, 39 to < 59 was classified as moderate, and 59 to 100 was classified as severe . StatistThe study enrolled 203 subjects. Subject demographics are summarized in Table On average, subjects reported having FM symptoms for longer (mean of 10.7 years) than having an FM diagnosis (mean of 6.9 years) or than having received prescription medications for FM (mean of 6.3 years) Table .Severe FM subjects, on average, had more positive MTPS points with mean of 15.2 compared to mild subjects with a mean of 13.7 and moderate subjects with a mean of 13.8 (p = 0.036). Additionally, over half (54%) of the subjects reported severe average pain intensity with a higher proportion of severe FM subjects (66%) reporting severe average pain intensity compared to mild (14%) and moderate (37%) FM subjects (p < 0.001) (Table Subjects were actively seeking care at the time of the study. Most 92%) were taking 1 or more prescription medications for FM and approximately half (47%) were taking 3 or more. In addition, subjects reported a mean of 16.9 physician visits over the past year , there was a trend toward an increasing number of comorbid conditions as FM severity worsened from 2.9 for mild FM subjects to 4.4 for severe FM subjects Table . DepressWhen asked to rank areas of daily life affected by FM, most subjects reported pain (91%) and lack of energy/fatigue (87%). Over half reported that FM impacted their sleep 54%) and caused them difficulty walking, moving, or exercising (51%)  with mean scores of 3.4 for mild, 5.6 for moderate, and 7.0 for severe , on average, if they had complete relief of FM-related pain. The current Overall Health Score decreased as FM severity worsened (p < 0.001) as did subjects' estimates of their pain-free overall health (p < 0.001)  of the subjects reported some disruption in their work status due to FM, including reduced work schedule (10%), disabled (21%), unemployed or retired early (19%) Figure . AdditioEmployed subjects reported missing a mean of 1.8 days of work due to FM over the last 4 weeks Table . ExtrapoThe mean number of days missed from work during the past 4 weeks also increased with FM severity with mild subjects reporting missing 0.4 days, moderate reporting 1.0 day, and severe reporting 3.0 days (p = 0.030); corresponding to an annual average of 5, 13, and 39 days of worked missed per year for mild, moderate, and severe FM subjects, respectively Table . AdditioFM caregivers provided mild, moderate, and severe FM subjects unpaid help for ADLs a mean of 3.6, 22.8, and 35.4 hours over the past 4 weeks, respectively (p = 0.003). This corresponds to an average of 47, 296, and 460 hours a year of unpaid caregiver help for ADLs for mild, moderate, and severe FM subjects, respectively.This is one of the few studies in the US to comprehensively assess the core FM symptom dimensions identified by OMERACT and to explore the disease burden of FM by disease severity levels. Although the majority of patients in this study were receiving prescription medications to treat FM, they reported high levels of pain, anxiety, depression, sleep disturbance, cognitive dysfunction, and functional limitations. These findings were consistent with some previous study results:• Pain, anxiety, and depression - Over half of all patients reported being in severe pain due to FM, and a majority reported some level of anxiety (70%) or depression (65%), which is consistent with other research [research ,7,8.• Sleep, shortness of breath and headache - Overall, patients experienced substantially more sleep problems than the general US population, as indicated by a higher MOS-SS Problem Index score of 57.5, versus the US norm of 25.8  than age-matched controls and that patients' performance on these measures were similar or worse than adults 20 years older [rs older .• Functional limitations - Our findings also are consistent with published studies showing FM patients report much higher functional limitations compared to the general population. In our study, the mean FIQ score was 63.2. A Canadian study that compared FM patients with general population controls found a mean FIQ score of 61.2 among FM patients versus 21.9 among the controls [controls . A natioPatients also demonstrated diminished global health and HRQoL. Mean EQ-5D scores for subjects in our study, overall (0.35) and at all FM severity levels , were substantially lower than the mean EQ-5D score for the US population age 45 to 54 (0.87) . These rPerhaps due to the large pain burden and detrimental impact on various domains of health, the overall HRQoL found in FM patients, especially in those with severe form of disease, was not only worse than that of the general population but also in comparison with many other chronic conditions reported in the utility and generic HRQoL literature . This fiOur study showed that FM has a substantial negative impact on productivity, with the overall sample reporting an average of more than 23 days missed from work per year. A meta-analysis of FM burden reviewed studies that reported that FM patients missed between 11 and 31 days of work per year . Of thosThis is the first US study to explore the impact of FM on caregiver productivity. The study found that, on average, caregivers spent the equivalent of almost 10 work weeks (378 hours) providing unpaid help to patients with FM per year. This finding highlights the importance of incorporating caregivers' time when assessing the full economic impact of FM on society.This study is also the first in the US to comprehensively report the burden of FM by disease severity levels. FM severity was negatively and significantly associated with most patient-reported outcomes, such as pain intensity, anxiety and depression, sleep problems, cognitive dysfunction, as well as overall HRQoL and utility scores. Severe FM also was more likely to be accompanied by comorbid depression, anxiety, or chronic fatigue syndrome than mild or moderate FM.This new understanding of FM by severity level is very important for the evaluation of FM treatments and priority setting in health care, for example by providing input data for the evaluation of medical resource utilization, costs and quality of life adjustments in the health economic evaluation of alternative FM treatments.Although this study was comprehensive, it had some possible limitations. Only practices that volunteered to participate were included in the study. Although there is no specific reason to assume that these sites may differ from other practices that treat FM, there may be unknown underlying variations. Additionally, data were collected from patients who were actively seeking care; we do not have similar objective data for patients who did not enroll. Therefore, our results may not be generalizable to the overall FM population. Our study's inclusion criteria required that patients have experienced pain in the past 24 hours; perhaps biasing our overall sample towards more severe FM. Therefore, results for the overall FM population should be taken with some caution, and where appropriate, results reported by severity groups should be used as comparative or input data in future research. Finally, this study was cross-sectional, and therefore we cannot establish causality, only the association between FM and outcomes.This study represents one of the first attempts to characterize the full patient experience of FM patients' disease, function, HRQoL, and productivity losses in the US. Although the majority of patients were receiving medical attention and prescription medications for FM, they reported high levels of pain, anxiety, depression, sleep disturbance, cognitive dysfunction, and diminished HRQoL, as well as substantial losses in productivity for them and their caregivers. Patients' health status and other key symptom domains worsened as FM severity increased. These results highlight the disease burden and limitations of treatment options currently available in the US.ADLs: Activities of Daily Living; CRF: Case Report Form; EQ-5D: EuroQol 5 Dimensions; FIQ: Fibromyalgia Impact Questionnaire; FM: Fibromyalgia; GFI: Global Fatigue Index; HADS: Hospital Anxiety and Depression Scale; HRQoL: Health Related Quality of Life; MAF: Multidimensional Assessment of Fatigue; MOS-SS: Medical Outcomes Study - Sleep Scale; MTPS: Manual Tender Point Survey; OMERACT: Outcome Measures in Rheumatology Clinical Trials; SD: Standard Deviation; US: United States.This study was funded by Pfizer, Inc. Arthi Chandran and Gergana Zlateva are employees of Pfizer Inc. Caroline Schaefer, Meghan Hufstader, and Rebecca Baik are employees of Covance Market Access Services Inc, and served as paid consultants to Pfizer during the conduct of this study and the development of this manuscript.CS, MH, RB, AC and GZ were integral to this study and to the development of this manuscript MM, DG, and RG served as clinical reviewers and contributors to the analysis and discussion sections. All authors have read and approved the final manuscript.