Statistical calculations were performed by Statistica software. In regards to RODI, RMQ, QDS, NDI and CNFDS , statistically significant differences (p <0.001) between both samples were found, indicating higher levels of pain and neck and lower back pain-related disability among persons with scoliosis. Associations exist between RODI and RMQ (rS = 0.76) QDS (rS = 0.70), NDI (rS = 0.69) and CNFDS (rS = 0.60). RMQ was associated with QDS (rS = 0.71) and NDI (rS = 0.69), whereas QDS correlated with NDI (rS = 0.80) and CNFDS (rS = 0.60). NDI was also associated with CNFDS (rS = 0.81). Persons with scoliosis treated in adolescence with a Milwaukee brace display significant restrictions in everyday activities, due to lower back pain (LBP) and neck-related disabilities, compared to healthy controls. In addition, back pain is associated with curve progression in long-term follow-up after conservative treatment. Moreover, LBP-related disability coexists with restrictions experienced due to neck pain.We aimed to explore the long-term outcomes of back and neck pain and functionality in adult females with adolescent idiopathic scoliosis (AIS), who had been treated with a Milwaukee brace, in a follow-up study a minimum of 23 years after the completion of the treatment, using radiological, clinical and socio-demographical data. Thirty AIS patients (scoliosis group–SG), were included in the study based on an extensive search of Pediatric Orthopedics and Traumatology Clinic charts. All treatments were successfully completed between 1974 and 1990. In all cases, scoliosis had not been detected before the age of 10 and was not combined with any major spinal deformities at the time when the brace treatment was implemented. In those patients, the Risser sign 4 and minimum two years post-menarche was defined as a maturity, after that time the brace treatment was completed. Patients were excluded from the study if they, at the time of the follow-up examinations, suffered from any other disease leading to trunk deformity. Forty patients met the criteria for inclusion, but due to change some personal details, not all of them were contacted. Finally, 30 women returned for a follow-up evaluation. Patients’ follow-up period was mean 27.77 yrs. ± SD 3.30 (range 23–35). Curvature change from the end of the treatment until the present day was mean 9.1 degrees ± SD 7.64 (range 0–27). A control group of 42 healthy females  matching the age profile of the patient group was randomly selected for comparative purposes.Both SG and HG completed the Polish versions of the Revised Oswestry Lower Back Pain Disability Index (RODI), the Rolland-Morris Questionnaire (RMQ), the Quebec Back Pain Disability Scale (QDS), the Neck Disability Index (NDI) and the Copenhagen Neck Functional Disability Scale (CNFDS). Descriptive statistics were calculated for demographics and baseline questionnaire scores. To determine if the investigated sample sizes are equivalent, the chi-square test was used. The chi-square test was used to compare qualitative features between persons with scoliosis and healthy controls. In addition, a Mann-Whitney test was utilized to compare differences between both groups in regard to quantitative characteristics. To establish relations between quantitative data such as e.g. age, duration of brace application, apical translation, Cobb angle, and questionnaire results, we used Spearman's rank correlation (marked as rS). To determine dependency between quantitative and qualitative characteristics, e.g. between questionnaire numerical data and marital status, place of residence or curve type, ANOVA Kruskal-Wallis test was used. A  Many researchers' results indicate that patients with adolescent idiopathic scoliosis, (AIS) suffer from back pain more frequently than healthy populations . It was It was revealed that the stabilization of scoliosis with a brace may decrease the likelihood of back pain induced by the altered scoliotic spinal mechanics, and presumably a failure to stabilize the spine (curve progression) may increase the incidence of spinal pain . AdditioConsidering the incidence of spinal pain in the long-term follow-up to treatment for AIS, most results refer to patients treated surgically –8. For iAt the same time, very little has been written about problems in the cervical spine and neck pain-related difficulties in performing everyday activities in AIS patients, especially in a long-term follow-up after the completion of brace treatment. The first signs of a problem were described by Moskowitz et al. , who revTherefore, taking into account some inconsistencies between study results relating to back and neck pain in AIS patients after completing Milwaukee brace treatment and, in particular, the lack of comprehensive long-term assessments of cervical pain in adult persons with scoliosis, special emphasis should be placed on the following research questions: do adult persons with scoliosis treated with a Milwaukee brace during adolescence have more lower back pain (LBP) and neck pain compared with non-scoliotic subjects? How does spinal pain affect the daily life and the activities of these patients? Is there any correlation between the intensity of the pain, radiographic data and brace treatment-related variables? Thus, we aimed to provide a complex assessment of adult females with scoliosis treated with a Milwaukee brace, in a minimum 23-yrs follow-up. To sum up, the purpose of this report is to explore the long-term outcomes in terms of back and neck pain and functionality, in relation to radiological, clinical, pulmonary function and socio-demographic data.Our hypothesis is that no difference is expected between study and control groups in terms of socio-demographic characteristics, pain level and neck- or low back pain-disability. In addition, we assumed that there will be a significant relationship between pain intensity, patients’ everyday activities and radiographic, clinical, pulmonary and brace treatment-related variables. All study aims have been achieved.Results concerning back- and neck pain and function in consecutively selected adult AIS females (scoliosis group-SG) treated with a Milwaukee brace were evaluated. Based on an extensive search of Pediatric Orthopedics and Traumatology Clinic charts, we retrospectively reviewed the clinical records and radiographs of all female patients who had successfully completed a course of treatment with the Milwaukee orthosis between 1974 and 1990. In those patients, the Risser sign 4 and minimum two years post-menarche was defined as a maturity, after that time the brace treatment was completed. Forty patients met the criteria for inclusion, but due to change some personal details (such as address or family name after getting married), not all of them were contacted. Finally, 30 women returned for a follow-up evaluation. To make the obtained data more reliable, an age- and sex-matched control group of 42 healthy individuals  was selected and asked to complete the same questionnaires as the patient group.Study participants from both groups were examined using the same protocol, except for the radiological evaluation. The contents of interview in both study groups included age, work, marital status, number of children, incidence of caesarian sections and complications during delivery, educational level, place of residence and the pursuit of active hobbies. In addition, to evaluate the implications of the brace for back and neck pain and functionality, all study participants were asked to fill in the same series of questionnaires.rd study author, and the radiographic measurements were conducted by JG and MG, the 2nd and the 5th study authors, respectively.Clinical and radiological examinations were performed three times, before and after completing the treatment and then in the follow-up, and were taken in an upright position with the iliac ala exposed in an anterior-posterior projection. Data concerning former treatment regimens and radiological findings were gathered from reviews of charts and radiographs. The physical examinations were performed by AO, the 3th study author.The success rate at maturity was calculated according to Nachemson and Peterson, who defined a successful treatment as an increase in the curve of less than 6° from the start of bracing . The chaThe exclusion criteria for the control group were as follows: previous back surgery or significant scoliosis, which was ruled out by clinical examination, including using Perdriolli’s scoliometer. None of the controls had a trunk rotation of more than 5°, according to Danielsson et al. .Thirty AIS patients, with a minimum of 23-yrs of follow-up after completing Milwaukee brace treatment, were included in the study. All treatments were completed before the patient reached 19 yrs of age. In all cases, scoliosis had not been detected before the age of 10 and was not combined with any major spinal deformities at the time when the brace treatment was implemented. In addition, patients were excluded from the study if they, at the time of the follow-up examinations, suffered from any other disease leading to trunk deformity. The investigated sample sizes are equivalent (p = 0.157).During the whole treatment non-compliance monitoring such as temperature probe was not used. The average values were based on interviews with patients during the clinical examination. In addition, to make the obtained data more credible, daily duration of brace wearing was confirmed during the separate interviews carried out with parents.All study participants were informed in detail about the objective of the study. They understood that they would be anonymous and that their personal information would not be disclosed. All participants signed written informed consent forms in order to participate in the study. The study was approved by the Bioethics Commission of Poznan University of Medical Sciencesand was carried out following universal ethical principles.Polish versions of Revised Oswestry Low Back Pain Disability Index (RODI), Rolland-Morris Questionnaire (RMQ), Quebec Back Pain Disability Scale (QDS), Neck Disability Index (NDI) and Copenhagen Neck Functional Disability Scale (CNFDS) enabled us to assess the intensity of cervical and lumbar pain and the ability to perform everyday activities among both study samples –19.The RODI is a revised version of the original Oswestry Disability Index [= 0.83 to 0.99 and vary according to the time interval between measurements [ty Index  and focuty Index ,21. A rety Index ,21. The ty Index –26. The ty Index ,25. Testurements –25. The urements . Responsurements ,24.The RMQ is widely used to evaluate the degree of disability due to lumbosacral back pain [ack pain . It compack pain . Test-reack pain , and Croack pain . Consideack pain .The QDS is comprised of 20 questions and 6 domains, reflecting everyday activities such as sleep/rest; sitting/rising; walking; moving; bending/squatting; lifting heavy objects. The responses are marked on a scale of 0–5, where 0 corresponds to no limitations, whereas 5 signifies maximum restrictions to everyday functional status. The overall result varies from 0 (no worsening of spine function) to 100  [ status) , 30. TesThe NDI questionnaire assesses pain intensity and related limitations to cervical spine function during everyday activities [tivities . The NDItivities . Each ittivities . Test-retivities .The CNFDS consists of 15 items that evaluate the impact of neck pain. Three items evaluate pain severity directly, including the patient’s perception of the future impact of neck pain, eight items evaluate disability during everyday activities and four items focus on social interaction and recreation [creation . There acreation .The Cronbach's alpha coefficient of the CNFDS for internal consistency was 0.9 for the entire scale, and the coefficients for individual items were all greater than 0.88. Disability scale scores correlated strongly to pain scores as well as to doctor and patient global assessments, indicating good construct validity . Relativp<0.05 indicates statistical significance. Statistical calculations were performed by Statistica software. See the supplementary material file containing clinical, radiological, socio-demographic and questionnaire data.For statistical quantitative  features, e.g. age, apical translation, Cobb angle, number of children or questionnaire results, we calculated the mean, a 95% confidence interval, the range and standard deviation (SD). With respect to qualitative features (information that has aspects that are impossible to be measured), e.g. curve type, educational level, marital status or place of residence, we gave the number of units that belong to the described categories of a given feature and respective percentages. To determine if the investigated sample sizes are equivalent, the chi-square test was used. The chi-square test was used to compare qualitative features between persons with scoliosis and healthy controls. In addition, a Mann-Whitney test was utilized to compare differences between both groups in regard to quantitative characteristics. To establish relations between quantitative data such as e.g. age, duration of brace application, apical translation, Cobb angle, and questionnaire results, we used Spearman's rank correlation (marked as rS). To determine dependency between quantitative and qualitative characteristics, e.g. between questionnaire numerical data and marital status, place of residence or curve type, ANOVA Kruskal-Wallis test was used. A Patients’ follow-up period was mean 27.77 yrs ± SD 3.30 (range 23–35). The Milwaukee brace was worn for a mean of 22.9 hrs daily ± SD 0.31 (range 22–23). The duration of treatment was mean 45.47 months ± SD 20.00 (range 24–104).3 ± SD 561.98 in the pretreatment evaluation, 2983.33 cm3 ± SD 617.05 after treatment and 2569.64 cm3 ± SD 591.41 in the final evaluation. For additional clinical and radiological characteristics of the patient sample, see Following the criteria of the Scoliosis Research Society regarding the location of the apex , thoraciThe age of the patients during the follow-up was mean 41.13 yrs ± SD 3.87 (range 35–55), whereas age of the controls was mean 42.05 yrs ± SD 7.41 (range 22–61). Twenty-eight females with AIS (93.4%) and 29 healthy controls (69%) were married. Of 30 female patients, 29 (96.67%) had children, and the number of children was mean 2.0 ± SD 0.83 (range 0–4), whereas in HC group 33 females (78.57%) had children, and the number of children in this subgroup was mean 1.48 ± SD 0.99 (range 0–3). The rate of cesarean section was 30% (9 patients) in SG and 27.3% (9 controls) in HG. Ten patients (34.48%) and 8 controls (23.53%) had experienced problems during delivery  showed minimal disability, 16 subjects (53.33%) reported moderate disability and severe disability was indicated in 6 patients (20%), whereas 37 healthy controls (88.10%) reported minimal disability, and 4 and 1 participants, that is, 9.52% and 2.38% respectively, suffered moderate and severe restrictions in everyday activities.The value of the RMQ was mean 5.60 ± SD 4.68 in the SG, indicating a low degree of disability, and mean 1.79 ± SD 2.35 in HG, meaning no disability. In SG 12 patients (40%) reported no disability, 13 subjects (43.34%) reported low degree of disability, moderate disability was indicated in 4 patients (13.33%), and severe disability was identified in 1 patient (3.33%). 26 healthy controls (85.72%) reported no disability, and 5 and 1 participants, or 11.90% and 2.38% respectively, revealed low and moderate levels of restriction. The mean QDS-PL scores were 23.28 Mean ± SD 14.53 in SG and 8.23 Mean ± SD 7.79 in HG. Considering the results for particular criteria, the highest scores, relating to the most severe limitations, are related to moving and leaning/squatting in both study samples .The value of the NDI general result equaled mean 11.66 ± SD 7.43 in SG and mean 4.38 ± SD 4.02 in HG. Considering results expressed as percentage values, SG scored 23.32%, whereas HG scored 8.76%, which is interpreted as mild and no disability respectively.In SG 5 patients (16.67%) reported no disability, 15 subjects (50%) reported mild disability, moderate disability was indicated in 8 patients (26.67%) and 2 patients (6.67%) demonstrated severe restrictions to their everyday activities, whereas 27 healthy controls (64.29%) reported no disability, and 14 and 1 participants, or 33.33% and 2.38% respectively, revealed mild and moderate levels of disability.Concerning the CNPDS total score, patients scored mean 12.63 ± SD 3.48, whereas the value in the healthy control sample was mean 2.14 ± SD 3.48. The highest values among both SG and HG concern the disability subscale (mean 8.17 ± SD 4.2.57 and mean 1.24 ± SD 1.75 respectively).Among a variety of socio-demographic variables which might be affected by an individual’s spinal function, significant differences could be found between the groups such as marital status , educational level , place of residence , working time per week , no. of children  and time spent on active hobbies per week . For details, see It was also revealed, regarding RODI, RMQ, QDS, NDI and CNFDS , statistically significant differences (p <0.001), between both samples, have been confirmed, indicating higher levels of pain, and neck and lower back pain-related disability among persons with scoliosis. For details see In particular, regarding RODI, significant differences concerning personal care, lifting, walking, sitting, rising/standing, social life, traveling and changes in pain intensity (p < 0.001), except for sleeping (p = 0.099) were confirmed. For details see Considering lower back pain-related physical impairment, we identified significant associations between RMQ and BMI before treatment (rS = -0.44) and Cobb angle after completing the treatment (rS = 0.36). We also identified significant associations between particular subscales of QDS (moving and BMI before treatment (rS = -0.42)), VC before treatment (rS = -0.39), between lifting and Cobb angle during follow-up examinations (rS = 0.38) and between total score and apical translation after completing the treatment (rS = 0.38) and thoracic kyphosis during the follow-up (rS = 0.39) see .Considering neck pain, a significant correlation was discovered between the level of education and CNPDS total score . Moreover, the level of education was found to be associated with pain severity, social interaction and disability . For details see As seen in The aim of this report was to elucidate the long-term outcomes of back and neck pain and functionality in a group of patients treated with a Milwaukee brace. The Milwaukee brace has been a standard of nonsurgical treatment for scoliosis since 1954. The Milwaukee brace, which should be worn for 23 hours every day, is most effective for the treatment of adolescent idiopathic scoliosis. Spinal deformity is corrected with the Milwaukee brace, in theory, by both passive and active forces. Passive correction is achieved by direct pressure from the pads or by traction from the brace design. Active correction is believed to occur through active movement of the body away from pressure points, as the patient’s muscles acted to pull the trunk away from contact with the lateral pads or chin support ,36.The Milwaukee brace remains the orthosis with the longest clinical history and the highest reported success rate in halting the progression of AIS, with the caveat that, because of the prior lack of standardization in bracing studies, direct comparison with studies of alternative brace designs is problematic ,38. CurrSeveral authors have claimed that idiopathic scoliosis is not associated with a higher incidence of back pain . For exaLange et al.  evaluateHaefeli et al.  in a retConsidering the associations between LBP-related disability and clinical and radiological factors, Danielsson and Nachemson indicated that pain and reduced back function was not related to a variety of curve-related factors, including degenerative lumbar disc changes. This lack of correlation between curve and functional outcome scores have been previously reported . RamirezAs previously stated, very little has been said on neck pain and cervical pain-related restrictions in performing everyday activities, such as social interaction and recreational activities, especially in long-term follow-up after the completion of brace treatment. As previously stated, Moskowitz et al.  revealedFurthermore, some interesting associations discovered between the level of education and CNPDS must be discussed. It was revealed that patients with university education declared higher levels of neck pain-related disability than patients with lower levels of education. Those results are in accordance with several cross-sectional studies which also have found a positive association between the duration of occupational sitting and occurrence of pain in the neck–shoulder region –51, whilIn addition, concerning associations between all study questionnaires, we identified intercorrelations between neck and lower back pain-related disability. Bearing in mind the advantages and disadvantages of the correlational study design, we cannot provide a conclusive reason as to why this relationship exists, but at the same time we are able to make some predictions e.g. about the incidence of neck pain, based on the LBP already reported by AIS patients.Some limitations of the current study must be pointed out. Firstly, a long-term assessment of conservative treatment of AIS is necessarily retrospective, since the tools specific to LBP- and neck pain-related disability assessment, such as RODI or NDI, were not available at the time when the conservative treatment was implemented. Secondly, the response rate (n = 30) was relatively low. Thirdly, the current study specifically investigated female patients only, which may have had an impact on the distribution of scores and limit the scope of the findings. Fourthly, brace compliance monitoring was a speculation and lastly, as indicated above, a correlational study cannot be used to draw conclusions about the causal relationships between selected variables. To sum up, we cannot determine which is the cause and which is the effect in the relationships between e.g. neck- and LBP-related disability, which are significantly intercorrelated.Despite the aforementioned limitations, we can provide clinicians with reliable data concerning the incidence of lumbar and cervical pain and disability in the long-term follow-up after completing a Milwaukee brace treatment. In addition, we believe long-term follow-up studies can provide reliable information to patients who will undergo conservative treatment for AIS. Further investigations, with a longer follow-up and in a group of patients treated surgically for comparative purposes, are needed to improve upon the results of our research.This retrospective examination of the function of the lumbar and cervical spine, in a highly specific subset of patients, revealed that persons with scoliosis treated in adolescence with a Milwaukee brace display significant limitations in everyday activities, due to LBP- and neck-related impairment. In addition, back pain is associated with curve progression in a long follow-up after conservative treatment. Moreover, LBP-related disability coexists with restrictions experienced due to neck pain.S1 File(XLS)Click here for additional data file.


In high income countries, cancer is one of the leading causes of death, with co-morbid depression contributing to the risk of increased mortality. However, both cancer and depression are neglected conditions in low income countries. The current study assessed the magnitude of depression and the association of pain complaints with depression among patients with cancer in a low income country.In this cross-sectional study participants were 390 patients with established diagnosis of cancer, who were recruited consecutively when visiting a tertiary treatment centre in Addis Ababa, Ethiopia. The occurrence of depression was determined using the nine items Patient Health Questionnaire (PHQ-9). Major depressive disorder was confirmed: (1) when five or more of the PHQ-9 symptoms were endorsed as occurring for at least ‘more than seven days’, with the exception of suicidal ideation item which counted as a positive rating if it had occurred even once in the previous fifteen days. (2) one of the symptoms has to be either depressed mood or loss of interest. Pain complaint was measured by Numeral Rating Scale (NRS) and severity of pain was assessed using Verbal Rating Scale (VRS).The prevalence of major depressive disorder was 16.4% , and subthreshold depression was 17.4% . Pain complaints occurred in 69.0%  of the participants. The odds of having a major depressive symptom was over four times higher among participants who had pain.The study was cross sectional and liable to recall bias. Recruitment was carried out in a tertiary referral hospital, which might lead to the selection of more economically well-off and educated participants limiting generalizability of the study. Moreover, we did not control for cancer types, which may be related to pain and the experience of depression. Some of the somatic symptoms in PHQ9 may also be related to the cancer itself.This study highlights the clinical significance of both depression and pain complaints in patients with cancer in a low income country. Exploration of the impact of depressive disorders on quality of life and outcome of cancer is an important area for further research in low income countries. One in six deaths worldwide are due to cancer, establishing it as the second leading cause of death globally . ApproxiAmong other causes, one of the factors that seem to increase death related to cancer is depression , 14, oneDepression is a common and most burdensome neuropsychiatric condition, with the Disability adjusted life years projected to rank second by 2020. From African regions, north Africa has the highest depression rates . The latDepression commonly co-exists with pain. Pain is the most important symptom affecting quality of life of patients. Pain is also a common problem in patients with cancer with reported prevalence of 44% to 87% , 25.Pain and depression together can worsen the clinical condition of a patient than either condition alone; and there is strong association between the two . Pain isThis cross-sectional study was conducted in a public tertiary treatment centre in Addis Ababa. In addition to inpatient services, the centre provides radiotherapy and chemotherapy services. The Radiotherapy unit accepts referrals from all over the country and offers care for an average of 118 patients per week. Women make up 70% of the patients using this service.Study was conducted in January 2012. Patients, 18 years of age and above, with established diagnosis of cancer for a minimum of one month were eligible for the study. Patients who were unable to communicate either because of illness or inability to speak the language of interview (Amharic) were not included. Inpatients were approached in the wards while outpatients were approached while waiting for their follow up or therapy. Interviews were carried out in a private room near the waiting area. Consenting consecutive patients were recruited until the required sample size (shown below) was obtained. The interview was conducted in Amharic and took an average of 20 minutes.Sample size was calculated assuming that the prevalence of depression and pain among patients with cancer to be 37% and 73% respectively  with an th revision (DSM-IV) through patients’ self-report  and moderate pain [Adjusted OR (95%CI) = 4.71] were significantly associated with increased likelihood of having major depression. Similarly, odds of having a major depression was more than four times higher among those with pain score of more than three in the NRS.This study finds a high prevalence of uncontrolled pain, which was also associated with symptoms of major depression. Almost 70% of those with depression had pain complaints.The prevalence of depression in patients with cancer in this tertiary center is higher when compared to the prevalence of the general population in Ethiopia. The limited studies available from Ethiopia are population (community) based and report a prevalence ranging from 1.2% to 12% , 39–43. Studies from Asia and Africa are few in number; however, they have reported higher prevalence. Thus studies from Pakistan and Nigeria reported a prevalence of 61.6%  and 37.2Unmanaged pain was high in our study population but these values fall within the reported prevalence of pain among patients taking anticancer therapy worldwide. A systematic review, mostly based on studies from high income countries, found a prevalence of 59% ; similarConsistent with previous literature, this study shows the strong association between depression and cancer pain where the odds of having a major depression is more than four times higher in those with pain complaints. In using a VRS the odds of having a major depression shows an increasing trend towards severity of pain. Different studies in different setups have shown association between depression and pain, prevalence of pain was observed to be much higher together with a depressive symptom than one condition alone, 52–54. There are several limitations that should be considered. The study is cross-sectional and direction of association between pain and cancer could not be established. The study was conducted in the capital city in a tertiary hospital. Although this is the only hospital that provides radiotherapy and comprehensive cancer care, the participants are more likely to have more severe illness and also to have more favorable socio-economic status. Therefore, the findings may not be generalizable to the broader population of patients with cancer. Some of the somatic symptoms, which are part of the PHQ9 symptom list, may have been due to the cancer itself or its treatment rather than due to depression. The impact of treatment and pain relief was not assessed in this study. We have also used a criterion based diagnosis for clinical utility reasons than the typical score based diagnosis of depression employed in many studies. The sensitivity analysis confirmed our assumption that the criterion based diagnosis may be a more conservative estimate of the prevalence of MDD and that both categories may be qualitatively similar. This is the first study of its kind in Ethiopia and one of the very few in Africa. Therefore, the study is an important contribution to our knowledge regarding the potential role of depression and pain in the management of cancer in these settings.This study reveals that a substantial number of adult cancer patients were depressed and have a suicidal ideation, causing a significant functional impairment. This study clearly demonstrated a significant association between pain complaint and depression among adult cancer patients. Therefore psychological and physical pain assessment should be incorporated as part of standard cancer care.S1 Table(DOCX)Click here for additional data file.


Numbers of knee replacement surgeries have been rising over the past years. After having ameliorated operation techniques and material, pain management and anesthetic methods have come into focus. All 15326 patients included had undergone primary knee arthroplasty within this multicenter cohort-study, conducted in 46 orthopedic departments. Parameters were evaluated on first postoperative day. Primary outcome values were pain levels . Pain medication necessity was analyzed. Parameters were compared between the types of anesthesia used: general, regional and combination anesthesia. Pain scores and pain management satisfaction were significantly better in the groups of either spinal or peripheral anesthesia combined with general anesthesia . Patients who received the combination of general and spinal anesthesia were associated with the lowest need for opioids (p < 0.001). The use of a combined general and spinal anesthesia as well as using a combination of general and peripheral anesthesia in knee arthroplasty was associated with a highly significant advantage to other anesthetic techniques regarding perioperative pain management in daily clinical practice, but maybe below clinical relevance. Furthermore they were associated with positive tendency considering side effects and subjective well-being parameters. Although perioperative pain might lead to delayed mobilization and thereby impair the overall outcome after knee arthroplasty, postoperative pain management is still controversially discussed. In the past, a couple of trials favored peripheral or epidural anesthesia3.Numbers of knee replacement surgeries have been rising over the past years, especially due to demographic changes4 and high postoperative pain levels seem to raise the risk of chronic pain6. In addition, patients’ recovery and mobilization ability might be improved, which could potentially shorten length of hospital stay and reduce postoperative complications. This, after all, might also reduce costs on the medical system.Usually, pain medication used in the postoperative course comprises non-opioid drugs and opioids, both potentially causing side effects. Thus, the choice of anesthetic methods and its influence on the need of postoperative pain medication as well as its effect on patient-reported outcome parameters is of high interest. The risk of chronic pain after total knee replacement surgery has been reported to occur in up to 1/3 of the casesBeneath other factors, type of anesthesia might influence postoperative pain.3, reduce mortality7, have less blood loss as well as a lower transfusion rates8, show smaller amounts of site infections9 and shorter duration of operation10. In conclusion, these factors allow faster rehabilitation and shorten the duration of inpatient treatment7 thus resulting in economization of the health care system12.Most commonly used anesthesia methods throughout the operation for knee replacement surgery are general and spinal anesthesia as well as peripheral nerve blocks or the combination of the mentioned methods. In the past years, many studies have favored regional anesthesia over general anesthesia for various reasons. Regional anesthesia was found to cause less cardiovascular and pulmonary complications13.Peripheral nerve blocks (PNBs) are another regional anesthetic method used to control intraoperative pain, possibly combined with both general or spinal anesthesia. Peripheral nerve blocks have been shown to be able to reduce opioid consumption and lower cardiac, pulmonary and thromboembolic risk14. Both hematoma and infection may also occur after neural blocks. However, perineural hematoma seems to occur more likely after epidural anesthesia17. Neural infections may occur, but it still should be considered that the risk of infection is rather low compared to the risk of neural deficits caused by the surgery itself18.Adverse effects of regional anesthesia such as urinary retention and lack of bladder control, perineural hematoma or neural infection seem to account for patients’ fear of regional anesthesia3 because of lack of expertise by anesthesiologists and shortage of time14. The utilization rate of peripheral nerve blocks seems to be comparably low19. Thus, it can be stated that general anesthesia is still widely performed. The combination of general anesthesia and regional anesthesia has been investigated in the past and shown a decrease of blood loss compared to general anesthesia only20.In many hospitals, general anesthesia is still preferred to regional anesthesia22. To improve postoperative pain management and knowing the side effects of pain medication, finding the anesthetic method leading to least amounts of postoperative pain medication is essential. Optimal pain treatment demands sufficient staff education as well as multidisciplinary cooperation, which is often lacking23.In the postoperative course the conventional treatment consists of non-opioid drugs plus, if necessary, opioids. The combination of Non-steroidal anti-inflammatory drugs (NSAID) and regional anesthesia has shown to be able to decrease postoperative pain scoresInsufficient pain management can be detected by continuous quality improvement (CQI) strategies. By using this knowledge, the “Quality Improvement in Postoperative Pain Management” (QUIPS) project is an outstanding tool to assess and compare pain management.This large-scale multicenter study evaluates different types of anesthesia in knee replacement surgery in daily routine, in order to compare general, spinal and combined general and regional anesthesia regarding need for pain medication, subjective functional scores as well as pain scores and patient’s satisfaction in the postoperative course. We hypothesized that regional anesthesia and combined regional and general anesthesia is superior to general anesthesia in terms of postoperative pain values and pain medication use.In the present cohort study 15326 patients were evaluated between 2009 and 2015 after primary knee arthroplasty, conducted nationwide in 46 orthopedic departments at the time of data evaluation. All knee replacement surgeries meeting the inclusion/exclusion criteria were evaluated. Inclusion criteria were: (1) patients older than 18 years of age (2) able to communicate adequately (3) after primary knee arthroplasty. Written and oral information was supplied to all potential patients. Participation was voluntarily. A written informed consent to participate was received by every subject. Exclusion criteria were: (1) patients who refused to participate and (2) patients who were asleep or sedated at the time of data collection and interview on first postoperative day, respectively.st postoperative day. The QUIPS-project is endorsed by the German Society of Surgeons and the German Society of Anesthesiologists25.Within the scope of the “Quality Improvement in Postoperative Pain Management” (QUIPS) project, an initiative to compare outcome parameters in participating hospitals, parameters were analyzed on 126. The medication was registered as “received” or “not received”, and percentages of patients who received this type of pain medication were calculated. The use of patient-controlled analgesia was recorded as well. The use of PCA was registered as “received” or “not received” as mentioned above.Using the standardized QUIPS questionnaire form, minimum, maximum and activity pain as well as pain management satisfaction was rated using the numerous rating scale . Furthermore, side effects were evaluated with the two possible answers “Yes” or “No”, and percentages of patients answering “Yes” was calculated: “Pain affecting the ability to sleep”, “Pain affecting the ability to move the operated leg”, “Vomiting since surgery”, “Pain affecting the ability to cough or to take a deep breath”, “Tired since surgery”, “Felt vertiginous since surgery”, “Pain affecting the mood” and “Felt nauseous since surgery”. Postoperative pain medication was obtained from patients’ records. Type of postoperative pain medication was classified according to the WHO pain ladder: non-opioids (WHO ladder step 1) and opioids (summarization of WHO ladder step 2 and step 3)To avoid selection bias and patient-interviewer interaction bias, all patients were randomly visited and informed by the staff member that their work is independent from the healthcare team. The interviewers were blinded to the anesthetic technique used. Data was anonymized after collection.Standardized data assessment in each site to collect clinical data and obtain the questionnaire parameters was guaranteed due to data collection by specially educated staff using a standardized protocol. A multidisciplinary team of anesthesiologists, orthopedic surgeons and nurses regularly analyses data for internal benchmarking and comparison to other departments.Patients were divided into five groups: (1) general, (2) spinal, and the combination of (3) spinal and peripheral, (4) general and spinal and (5) general and peripheral anesthesia. The groups were defined as following: all general narcotic techniques were summarized in group 1, all neuroaxial blocks in group 2, all peripheral nerve blocks (PNB) in combination with neuroaxial blocks in group 3, all sedation techniques in combination with neuroaxial blocks in group 4 and all sedation techniques in combination with PNBs in group 5.Continuous variables are presented as mean (standard deviation) or as median (interquartile range) depending on the underlying distribution. Categorical data are presented as absolute numbers and/or relative frequencies. To compare the need for pain medication, side effects and functional parameters between the study groups, a Pearson’s chi-squared test was used for each pairwise comparison. Differences in NRS values between the study groups were analyzed using an analysis of variance (ANOVA) with Bonferroni pairwise post-hoc tests. A p-value < 0.05 was considered statistically significant. No imputation methods were performed. All analyses were performed using SPSS 22.0 .The study was approved by the Ethics Committee as well as the Data Security Board of the Jena University Hospital, Jena, Germany, as well as by the Ethics Committee of the University of Regensburg. Furthermore, the project was registered in the German Register of Clinical Studies (DRKS) with the approval number DRKS00006153 (WHO register). The study was applied in accordance with the ethical standards of the Declaration of Helsinki 1975.15326 patients were enrolled and evaluated after receiving knee arthroplasty between 2009 and 2015 in the present study , 61.6% of all patients were female, the median American Society of Anesthesiologists (ASA) score was 2 (IQR 2–3). Mean duration of surgery was 89 minutes (±32) regarding all groups. Pain levels before surgery showed a median of 7 (IQR 2–8).The groups in question, demographic and general data were homogenous Table .Table 1DMean activity pain was 4.6 ±2.3) in the general anesthesia group, 4.3 (±2.7) in the spinal anesthesia group, 4.4 (±2.3) in the combination of spinal and peripheral anesthesia group, 4.0 (±2.2) in the combination of general and spinal anesthesia group and 3.9 (±2.5) in the combination of general and peripheral anesthesia group.  in the general anesthesia group, 5.3 (±2.9) in the spinal anesthesia group, 5.8 (±2.6) in the combination of spinal and peripheral anesthesia group, 5.1 (±2.5) in the combination of general and spinal anesthesia group and 4.9 (±2.7) in the combination of general and peripheral anesthesia group.  in the general anesthesia group, 1.8 (±1.9) in the spinal anesthesia group, 2.0 (±1.8) in the combination of spinal and peripheral anesthesia group, 1.7 (±1.6) in the combination of general and spinal anesthesia group and 1.6 (±1.7) in the combination of general and peripheral anesthesia group.  in the general anesthesia group, 8.0 (±1.9) in the spinal anesthesia group, 8.0 ±2.0) in the combination of spinal and peripheral anesthesia group, 8.1 (±1.8) in the combination of general and spinal anesthesia group and 8.4 (±1.8) in the combination of general and peripheral anesthesia group. Fig. . Signifi.0 in theThe postoperative need for opioid pain medication and their significance levels are shown in Table Side effects “Pain affecting the ability to sleep”, “Pain affecting the ability to move”, “Vomiting since surgery”, “Pain affecting the ability to cough or to take a deep breath”, “Tired since surgery”, “Felt vertiginous since surgery”, “Pain affecting the mood” and “Felt nauseous since surgery”, depending on the anesthetic technique used intraoperatively are shown in Table The aim of our study was to compare general, spinal and combined general and regional anesthesia regarding need for pain medication, patient-reported functional parameters as well as pain scores and patient’s satisfaction in primary knee arthroplasty.3, site infections9 and mortality7 after both general and regional anesthesia. Furthermore, the postoperative pain management has been put into focus in a large number of studies without taking into account which anesthetic method had been used. To date, not many large-scale studies have compared anesthetic methods with regard to patient’s satisfaction and pain medication needed postoperatively.In the past years, many studies have investigated end-points such as cardiovascular and pulmonary complications, length of stayst postoperative day.In the present study, the use of combined spinal and general, as well as general and peripheral anesthesia was associated with less minimum, maximum and activity pain and improved patients’ postoperative pain management satisfaction on 1et al. who compared 443 patients that underwent knee replacement surgery under different types of anesthesia 27. In this study, postoperative pain at 24 h  as well as postoperative opioid consumption was documented. In contrast to our NRS results, VAS-scores didn’t differ significantly between the different groups of anesthesiologic technique. Patient satisfaction has not been investigated.This differs from the findings of Pope et al. compared spinal anesthesia and psoas compartment with sciatic block (PCS) in 60 patients undergoing total knee arthroplasty28. VAS-scores were measured in the postoperative course until 24 h postoperative on a scale from 0–100. In this study no significant difference has been found between the two techniques at 24 h . Again, direct comparison to our study is not possible as this study investigates two very well-defined techniques and PCS has not been pointed out as an independent category in our study. However, the results are consistent with our findings showing no significant difference in postoperative pain scores between spinal and peripheral anesthesia.Canakci et al. published a consecutive and randomized study of 120 patients undergoing total knee arthroplasty under general or spinal anesthesia6. Besides, all patients received local infiltration in the perisurgical area towards the end of operation. In this study, postoperative pain was measured taking VAS-scores 0–100 at 0, 2, 4, 6, 10 h postoperatively as well as at 8 a.m. and 2 p.m. both at first and second day after operation at rest, knee flexion, straight knee and walking. As 2 p.m. on first day postop is most likely to be equivalent to our setup of pain evaluation 24 h postop, these are the results we took a closer look at. In all four groups (different movements and rest), the group of general anesthesia had significantly lower pain levels than spinal anesthesia. The results of this study differ strongly from the findings not only of our study but also of many studies of the past years. Nonetheless, because of the randomized setup the results are of high interest. Concerning patient satisfaction, which was also investigated in the study conducted by Harsten et al., anesthesia groups did not differ in satisfaction score. Still, many patients receiving spinal anesthesia would have wanted to change anesthesia method if operated again.In 2013, Harsten et al.29 conducted a randomized, double-blinded study investigating 60 patients undergoing total knee replacement under spinal anesthesia receiving either obturator, femoral nerve block or a placebo. The obturator block group didn’t show any difference to spinal-placebo group whereas femoral nerve block reduced pain at rest (p = 0.02) and at movement  significantly. However, these findings weren’t persistent exceeding 24 hours postop. This may be comparable to our findings because addition of peripheral nerve block to spinal anesthesia only reduced maximum pain levels but didn’t reduce minimum pain levels. In a metaanalysis by Macfarlane et al.30 regional anesthesia resulted in lower postoperative pain levels.Kardash Although our results are statistically highly significant favoring the combination of general and regional anesthesia with highest NRS differences of 0.9 points for pain, relevance in clinical practice remains unclear. Still, in a large-scale study like the present, the realistic difference of pain on NRS is small.et al. reports chronic pain to occur in 10–34% after total knee replacement and 7–23% after total hip replacement4. As the risk of chronic pain seems to be related to high postoperative pain levels6, improvement of pain management might help to reduce development of chronic pain resulting in faster recovery and mobilization.In knee replacement surgery, the risk of development of chronic pain is reported to be even higher than in e.g. hip replacement surgery. Beswick 31. Likewise, our evaluated differences in side effects and subjective well-being were relatively small. This being said, as illustrated by the above mentioned studies, so far no consensus has been found concerning the question which anesthesia technique leads to least postoperative pain.The minimally clinically significant NRS difference is a difference of 2, some pain researchers state, although this was only stated for chronic painFurthermore, using combined general and spinal as well as general and peripheral anesthesia was associated with a reduced need for opioid pain medication.et al.32 in the group of peripheral nerve block in comparison to general anesthesia. This trend persisted after 72 hours. These findings are consistent with Memtsoudis et al.13 who describes patients receiving a peripheral nerve block (PNB) in total knee arthroplasty requesting significantly less opioids than the ones without : 310; (no PNB): 321; p < 0.001). In contrast, Harsten et al.6 states a significantly lower median morphine consumption 24 hours after surgery in the general anesthesia group  19 mg, spinal anesthesia (median) 54 mg; p < 0,001). An opioid sparing effect is also described by Szczukowski et al.33 comparing 40 patients receiving general anesthesia with or without femoral nerve block in a randomized study . In our findings, both combination of general and spinal as well as general and peripheral anesthesia was associated with less opioid consumption than anesthesia techniques effecting only central or peripheral nervous system. Still, low rates of oral morphine consumption can often be explained by higher rates of PCA usage.Morphine administration was significantly lower 24 hours postop in the study conducted by Liu Overall, most studies favor peripheral nerve blocks in combination with either spinal or general anesthesia, which is consistent with our findings. Consequentially, least consumption of opioids is due to least amounts of postoperative pain.Furthermore, combinations of anesthetic techniques  were associated with a positive influence on some of patients’ subjective parameters such as the ability to move, cough, take a deep breath, tiredness, nausea and impact on mood. Though the magnitude of differences was small, these findings are of high interest because patient’s quality of life after surgery might be ameliorated by functional improvements.34.In the past, it was demonstrated that regular benchmarking of pain management programs using the QUIPS questionnaire is able to improve postoperative subjective resultsLimitations to be mentioned include first of all the lack of randomization to anesthetic technique groups. All patients have been treated according to both anesthesiologist’s and surgical experience and possible comorbidities. Thus, the study represents clinical routine and selection bias cannot be excluded even though big data studies reduce this possible bias.Furthermore, the detailed techniques of the anesthetic type used may differ within the participating departments, which may cause bias; describing these techniques was not the aim of this study.Because of organizational reasons postoperative pain and pain management have only been recorded on first postoperative day and doses of medication applied could not be homogenized throughout the participating departments. Thus, differences in the further postoperative period could not be pointed out and the intensity of pain medication usage could not be compared regarding e.g. opioid-equivalent doses. Then, groups have been divided to the above-mentioned anesthetic methods, but peripheral anesthesia could not be differentiated into different methods ; which might be a missing but potentially interesting detail. The use of local infiltration anesthesia (LIA), intensively discussed recently, had not been investigated in this survey. This both might influence NRS value outcome, the latter as groups contain a summarization of patients with and without LIA.Preoperative use of opioids has not been recorded in this study, another possible limitation. Opioid dependence might influence postoperative pain levels. As the patient quantity is huge in this study, this possible bias is reduced to a minimum as patients with opioid consumption preoperatively occur in all study groups.Restriction in explanatory power of big data studies is caused by the fact that even small value differences result in significant differences in the final results due to huge data quantity. However, their great importance in evaluation of effectiveness regarding medical interventions in everyday clinical routine remains undeniable.Summarizing, the combination of general and spinal as well as general and peripheral anesthesia during primary knee replacement surgery was superior regarding postoperative need for pain medication, side effects, pain scores, patient satisfaction, and subjective well-being parameters in a large number of patients in daily clinical routine. Still, as already mentioned, value differences might be below clinical relevance. Thus, further investigation in terms of large-scale, randomized studies is needed to further analyze the effect of intraoperatively used anesthetic techniques on patient satisfaction and pain scores perioperatively.


Despite the wide use of the neck disability index (NDI) for assessing disability in patients with neck pain, the NDI has not yet been translated and validated in Urdu. The first purpose of the present study was to translate and cross-culturally adapt the NDI into the Urdu language (NDI-U). The second purpose was to investigate the reliability, validity and responsiveness of the NDI-U in Urdu-speaking patients experiencing chronic mechanical neck pain (CMNP).pain) and disability (VASdisability) were administered to all the participants at baseline and to the patients 3 weeks after receiving physiotherapy intervention. The global rating of change scale (GROC) was also administered at this time. Test-retest reliability and internal consistency were carried out on forty-six randomly selected patients two days after they completed the NDI-U. The NDI-U was evaluated for factor analysis, content validity, construct validity  and responsiveness.Translation and cross-cultural adaptation of the original version of the NDI were carried out using previously described procedures. Seventy-six patients with CMNP and thirty healthy participants were recruited for the study. NDI-U and visual analogue scales for pain intensity  revealed excellent test-retest reliability for all items  and total scores  of the NDI-U. The NDI-U was found internally consistent with a Cronbach’s alpha of 0.90 and a fair to good correlation between single items and the NDI-U total scores (r = 0.34 to 0.89). Factor analysis of the NDI-U produced two factors explaining 66.71% of the variance. Content validity was good, as no floor or ceiling effects were detected for the NDI-U total score. To determine discriminative validity, an independent t-test revealed a significant difference in the NDI-U total scores between the patients and healthy controls (P < 0.001). For convergent validity, Pearson’s correlation coefficient showed a strong correlation between NDI-U and VASdisability  and a moderate correlation between NDI-U and VASpain . To measure responsiveness, an independent t-test showed a significant difference in the NDI-U change scores between the stable and the improved groups (P < 0.001). Furthermore, moderate correlations were found between the NDI-U change scores and the GROC , VASdisability change scores  and VASpain change scores .An intra-class correlation coefficient  contains supplementary material, which is available to authorized users. Neck pain is a major health problem with an annual prevalence ranging from 4.8 to 79.5% in the general population , 2. In 5Self-reported generic and region-specific questionnaires are frequently used to measure disability in patients with neck pain , 7. The Many studies adapt previously recognized and frequently used assessment tools instead of developing a new questionnaire , 31. TheThe translation and cultural adaptation processes were started after obtaining approval from the developer of the original NDI. These processes were performed according to the guidelines previously described  and to tTwo native Urdu-speaking translators who were also fluent in English independently translated the NDI from English into Urdu. One of the translators was an English linguistic teacher, and the second was a physiotherapist. Both translators were instructed to aim for conceptual rather than literal translation. They both provided written reports.The original translators and one of the authors produced a consensus version by synthesizing the results of both translated versions and discussing disagreements.The agreed upon Urdu version was translated back into English by two professional translators who were blinded to the original version. Both translators were not aware of the questionnaire concept.An expert committee including translators, researchers, a healthcare professional and a methodologist developed a pre-final version by reviewing all the translations, the consensus version, and the original questionnaire. The entire procedure was recorded.The pre-final version of the NDI-U was tested on 30 patients with neck pain to test for face validity. The patients were requested to complete the questionnaire. Afterwards, all the items of the questionnaire were discussed with the patients one by one. We asked patients to describe what they understand about each question and to provide their impressions of the relevance of the items to their situation and their ability to complete the questionnaire on their own. Patients were also encouraged to note any problems with the wording, instructions or layout of the questionnaire. All findings from this phase of the adaptation process were evaluated by the expert committee, and the final NDI-U was then developed following consensus ” and “worst possible restriction (100)” at the line’s ends. Patients were asked to quantify how much their neck pain restricts their daily activities by drawing a vertical mark on the area of the horizontal line that best represented their degree of restriction. The VASdisability has been shown to have good reliability in patients with chronic musculoskeletal pain [The VAStal pain .The GROC is a 15 point scale that is used to assess a patient’s self-perception of pain deterioration or improvement over time . PatientPsychometric testing of the NDI-U was performed according to COSMIN guidelines .Patients with CMNP were recruited from two hospitals located in Rawalpindi and Islamabad, Pakistan, over a period of 12 months. Neck pain was defined as chronic if the duration of the symptoms was more than three months . Both maThe study was approved by the Institutional Review Board of the University of Lahore, Lahore, Pakistan. All the participants provided informed written consent. The screening of the participants was carried out by physiotherapists with more than ten years of clinical experience.pain and VASdisability were completed by the healthy participants and patients with neck pain. Weight, height and other demographic details were also recorded. After 48 h, 46 randomly selected patients completed the NDI-U again. These patients received 9 sessions (3/week) of physiotherapy treatment with each session lasting for 30 min. These were provided by physiotherapists with clinical experience of more than twelve years. After 3 weeks of physiotherapy, patients again completed the NDI-U, VASpain and VASdisability. Additionally, patients also filled out the GROC scale at this time.During the first visit, self-report measures for the NDI-U, VASOne fundamental problem with the NDI is that a few items  are frequently omitted by some patients . DiffereSimilar to previous studies, all patients were asked to explain why a question was not answered in a space provided at the end of the NDI-U , 21. FurAll analyses were carried out using IBM SPSS 21  statistical software. The significance level was set at 0.05. Participants’ characteristics were compared using descriptive statistics.Reliability is defined as “the extent to which the measurement of a variable is free from measurement error” . In the 2,1) and 95% confidence intervals (CIs) [Test-retest reliability was determined using an intra-class correlation coefficient (ICCls (CIs) , 15, 32.ls (CIs) , 50. Crols (CIs) . Alpha vls (CIs) . The strls (CIs) . Measurels (CIs) . The SDCls (CIs) , 53.Factor analysis is frequently used to determine if items of an instrument form one or more than one dimension , 55. FacContent validity is the degree to which the content of an instrument has an adequate reflection of the construct being measured . Contentt-test. We predicted that there would be a significant difference in total scores between these two groups [disability and VASpain  using Pearson’s correlation coefficients [disability [pain [Construct validity was assessed by determining the differences in the NDI-U total scores between patients and healthy controls  with an independent o groups . Construficients . A modersability , 46, 47 ty [pain , 46, 47 ty [pain .t-test [pain and VASdisability [disability and VASpain change scores.Responsiveness is defined as “the ability of an instrument to detect change over time in the construct to be measured” . After tt-test , 60. We t-test , 60. We t-test , 29 and sability . Pearsonr < 0.25 indicates no or little correlation, 0.25 ≤ r < 0.50 indicates fair correlation, 0.50 ≤ r < 0.75 indicates moderate correlation, and 0.75 ≤ r ≤ 1 indicates good correlation.Portney and Watkins  criteriaThere were 13 patients who did not know how to drive a car, so they did not respond to item 8, which was related to driving. One patient did not answer item 4 related to reading, stating that he did not want to give an answer based on an assumption, as the item was not related to his life. It was decided not to change these sections since these problems could be overcome by any type of modification.After thoroughly discussing replacing the word “pain” with “neck pain” for the items related to lifting, personal care and pain intensity and adding the option “never done” for the item related to driving, modifications performed in other translations , 29, 46,pain, VASdisability and GROC scale upon the completion of treatment. The data of these patients were not included in the follow-up analysis. The healthy participants were sex-matched to the patients. The demographic and clinical characteristics of the participants are shown in Table Ninety-two patients with chronic neck pain were assessed for eligibility. Twelve patients did not meet the inclusion criteria and were excluded from the study Fig. . Four pa2,1 = 0.86–0.98) and total scores  of the NDI-U. An excellent internal consistency was demonstrated with Cronbach’s alpha of 0.90. A fair to good correlation was found between single items and total scores of the NDI-U with Spearman’s correlation coefficients of 0.34 to 0.89, confirming that the NDI-U is internally consistent. The SEM and SDC for NDI-U total scores were 0.84 and 2.33, respectively.The mean and standard deviation for scores of all the items, the total scores, and the reliability results of the NDI-U are shown in Table P < 0.001). Based on eigenvalues > 1, a two-factor structure was demonstrated. The eigenvalue of the first factor was 5.59, which explained 36.16% of the variance. The second factor had an eigenvalue of 1.08, which explained an additional 30.55% of the variance. The total variance explained by the two factors was 66.71%. A Scree Plot  and that the Bartlett’s test was significant . Subgroup analyses between patients (n = 23) and healthy controls (n = 30) of similar age groups also showed significant differences in the total scores (P < 0.001). A good correlation was found between NDI-U and VASdisability , and a moderate correlation was observed between NDI-U and VASpain . The results are shown in Table Results showed a significant difference in the NDI-U total scores between patients and healthy controls . A moderate correlation was found between the NDI-U change scores and GROC values . A moderate correlation was also found between NDI-U and VASdisability change scores  and between NDI-U and VASpain change scores .An independent As far as we know, this is the first study that translated and cross culturally adapted the NDI into Urdu and tested the reliability, validity and responsiveness of the NDI-U. The psychometric properties of the NDI-U were tested using pre-defined hypotheses. The results indicated that NDI-U has good reliability, validity and responsiveness.Studying the adaptation process showed that the NDI-U was successfully developed according to established guidelines. The difficulties encountered during the adaptation process were handled by consensus decisions and the use of careful wording. The NDI-U was found to be simple and easy to use in clinical settings.In the present study, there were more females (60.5%) than males (39.5%). This is comparable to earlier studies that have also recruited more females (52–78%) , 62–65 bAn excellent internal consistency was demonstrated by a Cronbach’s alpha value of 0.90, which is well in the range of the findings of earlier studies (0.74–0.96) , 60, 64.Based on the results of the current study, a change of at least 3 points on the NDI-U  is required to label the change as a “real change”. This result is well within the range of findings observed in other studies  , 27, 65.Many studies have analysed the factor analysis of the NDI and other translations. Some studies found a one-factor structure , 64, 72,The present study had 32 patients (42.10%) who did not complete item 8 (driving). These results are comparable with the Japanese and Greek versions where 38.2% and 44.6% of the patients, respectively, did not answer this item , 60. In There were also 5 patients (6.58%) who did not complete item 4 (reading). This result was slightly lower than that reported by Trouli et al. (9.2%) . The patThe present study did not find any floor or ceiling effects for the NDI-U total scores. However, floor effects were observed for individual items . These results were comparable to those of the Finish (2 items) , Korean pain or VASdisability, consistent with previous studies [disability was good (r = 0.83) in the present study but only moderate (r = 0.52) in the Dutch version of the NDI [pain (r = 0.58) was similar to the findings of the Iranian, Spanish, Turkish and German versions (r = 0.51–0.71) [r = 0.22–0.43) [Criterion validity of the NDI-U was not analysed due to the unavailability of a gold standard for health-related questionnaires . The NDI studies , 25, 64.51–0.71) , 19, 22 pain and VASdisability change scores.Regarding responsiveness, the NDI is considered to be a suitable test to detect changes over time. The NDI is frequently used in patients with neck pain to evaluate the effectiveness of treatment strategies . The preFirst, a short interval was used to ensure patient conditions remained as stable as possible to determine test-retest reliability. Therefore, memory effects on our results cannot be completely ruled out. Second, our sample mainly included patients with mild to moderate disability from CMNP. Therefore, it may not be appropriate to extrapolate our results to patients with severe or (sub)acute disability or to patients having neck pain secondary to non-mechanical causes. Third, data were mainly collected from patients attending outpatient physiotherapy clinics. Therefore, the sample may not be a true representation of the general population experiencing neck pain. Consequently, the results cannot be generalized to inpatients. Finally, healthy controls were not age-matched to the patients. The authors believe that the generalizability of the results to the general population should not be affected, as the subgroup analysis between patients and healthy controls of a similar age group also found a significant difference in total scores between the two groups.disability.The strength of this study is that the psychometric properties of the NDI-U were tested using pre-defined hypotheses. Another strength of the study is that, to the best of the authors’ knowledge, it was the first study to measure the responsiveness on the index by determining the correlation of change scores between the NDI-U and the VASThe NDI-U is a reliable, valid and responsive questionnaire that has a 2-factor structure. It consists of simple words that can be easily understood by the patients. Therefore, the NDI-U can be used to evaluate neck disability in Urdu-speaking patients with CMNP in clinical and research settings.


IntroductionThe use of intrathecal morphine has the potential to help alleviate the pain that patients experience undergoing spinal surgeries. Complications can cause immobilization, which can lead to vascular thrombosis and ileus. Studies have shown epidural analgesia significantly lowered postoperative pain scores in scoliosis surgeries. Intrathecal anesthesia has been shown to have good pain control over the initial 24-hour postoperative period.PurposeDetermine if intrathecal morphine would reduce postoperative pain with minimal side effects.MethodsThe surgical case logs from three spinal deformity surgeons from a single academic medical center were reviewed retrospectively. This included cases where more than five levels of fusion occurred and surgery involved an osteotomy. The records of 17 patients were queried, and patient and surgical data were collected. The patients were divided into two groups: eight patients were administered intrathecal morphine and nine patients received no morphine. Postoperative pain scores were obtained hourly over the initial 24 hours postoperatively by nurses trained to obtain pain scores from the Numeric Pain Rating Scale. In addition, the rates of any noted side effects were recorded. Analysis of variance (ANOVA) and Fisher’s exact tests were used to calculate any statistical significance with p < 0.05 considered to be significant.ResultsThe maximum and total 24-hour postoperative pain scores had a mean of 5.6  and 69.3 , respectively, for patients administered intrathecal morphine. The patients who did not receive intrathecal morphine had total pain scores of 3.9 (standard deviation = 4.5) and 65.7 (standard deviation = 79.7), respectively. Though the results were not statistically significant, there was a potential trend toward decreased in pain mean scores in the first 10 hours for the intrathecal morphine group. There was no statistical difference in the rate of side effects between patients.ConclusionsThe use of intrathecal morphine did not significantly appear to reduce postoperative pain in patients when compared to intravenous or oral narcotics. There was a potential trend in a reduction in postoperative pain during the first 10 hours postoperatively, but this did not reach a statistically significant value and did not hold up after the first 10 hours postoperatively. However, it was noted that intrathecal morphine was safe to use in postoperative spinal deformity surgery as no statistical significance in side effects was noted. Patients who undergo spinal deformity surgery often have great difficulty in recovery in part due to the high intensity of pain reported over the course of their recovery. This pain often results in difficulty in mobilization for the patient who then is put at higher risk for developing serious complications, such as venous thrombosis and ileus, and thus, also delaying rehabilitation. Methods that would reduce the pain reported by patients who have undergone spinal deformity surgery would, therefore, increase the quality of their postoperative care and potentially aid in progressing their rehabilitation and recovery. Previous studies have reported the use of epidural analgesia significantly lowered the reported pain scores of patients who underwent surgeries to correct diagnosed scoliosis . FurtherWith Institutional Review Board approval from our institution, the medical records of 17 consecutive adult patients who received spinal instrumentation involving more than five levels with osteotomy were reviewed. These patients were under the care of three fellowship-trained spinal deformity surgeons from a single academic medical center from October 2008 to October 2012. The data that was reviewed and collected included patient demographic data, gender, age at the time of surgery, and surgical data. The surgical data collected included the number of levels of fusion, the postoperative pain scores, and the rates of any noted side effects, including pruritus, nausea, nausea medication use, vomiting, ileus, constipation, urinary retention, change in the neurologic examination, and rates of infection. The postoperative pain scores were obtained hourly, recorded, and measured by nurses trained in obtaining pain scores. The Numeric Pain Rating Scale (0-10) was used to calculate the pain scores: 0 = no pain, 1-3 = mild, 4-6 = moderate, and 7-10 = severe .Patients were categorized based on intrathecal morphine (IM) use. A single dose of morphine (0.6 mg) was administered using an intrathecal catheter, which was placed during surgery in the lumbar region to control postoperative pain in the intrathecal morphine group. The protocol for the management of postoperative pain in patients with and without IM group was same, i.e, continuous intravenous patient-controlled anesthesia (IV PCA); fentanyl was used in IV PCA. From the recorded 24-hour pain scores, we calculated postoperative Day 1 total pain scores by adding all pain scores for those who received intrathecal morphine and those who did not receive intrathecal morphine separately.We compared the postoperative Day 1 total pain scores between patients (with and without morphine) using analysis of variance (ANOVA) to see whether there was any difference in those pain scores. Summary statistics and ANOVA were performed with standard statistical testing, depending on data type and distribution. Fisher’s exact test was used to compare categorical data, whereas ANOVA tests were used to make comparisons on the basis of means. SAS  9.4  was used to perform the statistical analysis and Microsoft Excel®  was used to plot the graph. Statistical significance was defined by a probability value of < 0.05.Of the 17 total patients included in this study, eight patients who had spinal deformity surgery with more than five levels of fusion with instrumentation and involving an osteotomy received standard intrathecal morphine (IM) dosage, while the remaining nine patients did not receive intrathecal morphine (NIM). Patient demographics are summarized in Table The maximum and total 24-hour postoperative pain scores had a mean of 5.6 (standard deviation = 4.2) and 69.3 (standard deviation = 57.8), respectively, for patients administered intrathecal morphine. This is in comparison to a 24-hour postoperative pain score maximum and total pain score of 3.9 (standard deviation = 4.5) and 65.7 (standard deviation = 79.7), respectively, for patients who did not receive intrathecal morphine. The resulting p-values for each category of data were 0.4266 and 0.9189, respectively (Table While these results were not statistically significant, there was a potential trend toward decreased mean pain scores in the first 10 hours postoperatively for the intrathecal morphine group Figure . RespiraOverall, this pilot study showed that patients treated with intrathecal morphine did not have a statistically significant reduction in postoperative pain when compared to patients who were not treated with intrathecal morphine. However, there was a potential trend where the patients that received intrathecal morphine showed a reduction in postoperative pain reported in the first 10 hours after surgery. In addition, another trend observed was that patients not receiving intrathecal morphine showed a reduction in reported pain from 13 to 24 hours postoperatively. However, it should be noted that neither of these observed trends achieved statistical significance.        These observed results stand in contrast to studies in the published literature where intrathecal administration of medications have been able to relieve the pain associated with cancer treatments along with acute and chronic pain management. Deer and Chapple, et al. reported data from the National Outcomes Registry for Lower Back Pain on patients with chronic lower back and leg pain that received intrathecal drug delivery . This daThis method of pain management has also shown potential to reduce pain following spinal surgeries. Demircan comments on a study by Ross, et al., where a prospective, double-blind, placebo-controlled study of the use of intrathecal morphine after lumbar spinal surgery, showing that patients receiving intrathecal morphine saw a reduction in parenteral narcotics over the course of their hospitalization as well as a reduction in the mean length of hospitalization when compared to patients who had systemic narcotic administration , 14. AnoOur study also showed that there were no statistically significant observations of noted side effects associated with intrathecal morphine administration. Rathmell, et al. detailed the use of intrathecal drugs in the treatment of acute pain, as well as noting common side effects seen in intrathecal opioid administration, such as pruritus, urinary retention, and nausea and vomiting, along with the most feared side effect of respiratory depression seen in patients receiving large doses of opioids . GehlingLimitations of our study include the small sample size, which could reduce the power of the study enough to not be able to detect a statistically significant difference in postoperative complication rates or change in postoperative pain scores. This study should be repeated to include a larger sample size in order to increase the power of the study and allow for statistically significant differences to be detected in the primary and secondary outcomes. Another potential variable that could be investigated in a follow-up study would be the introduction of other local anesthetics in combination with opioids intrathecally for management of pain after spinal deformity surgery. Deer and Caraway, et al. published a study comparing the effects of a combination of bupivacaine and opioids intrathecally with opioids alone for the treatment of pain of spinal origin . Their sIn conclusion, the use of intrathecal morphine did not significantly appear to reduce postoperative pain in patients when compared to intravenous or oral narcotics. There did appear to be a potential trend in a reduction in postoperative pain during the first 10 hours postoperatively, but this did not reach a statistically significant value. However, it was noted that intrathecal morphine was safe to use in postoperative spinal deformity surgery as no statistical significance in side effects was noted.


The aim of this prospective, randomized, double-blind study was to investigate the effect of articaine combined with ketamine on the success rate of inferior alveolar nerve block (IANB) in posterior mandible teeth with symptomatic irreversible pulpitis. t, Mann-Whitney and Chi-square tests. Forty two adult patients with diagnosis of symptomatic irreversible pulpitis of a mandibular posterior tooth were selected. The patients received two cartridges of either containing 3.2 mL 4% articaine with epinephrine 1:200000 and 0.4 mL 50 mg/mL ketamine hydrochloride (A-ketamine group) or 3.2 mL 4% articaine with epinephrine 1:200000 and 0.4 mL normal saline  using conventional IANB injections. Access cavity preparation started 15 min after injection. Lip numbness was required for all the patients. Success was considered as no or mild pain on the basis of Heft-Parker visual analog scale recordings upon access cavity preparation or initial instrumentation. Data were analyzed by independent student P=0.437).The success rates were 55% and 42.9% for A-ketamine and A-saline group, respectively, with no significant differences between the two groups (Adding 0.4 mL 50 mg/mL ketamine hydrochloride to the articaine local anesthetic did not increase the efficacy of IANB for posterior mandibular teeth with symptomatic irreversible pulpitis. Inferior alveolar nerve block (IANB) is currently considered the most frequent local anesthesia technique for endodontic treatment of mandibular teeth , 2. ClinKetamine hydrochloride is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors which has analgesic effects in sub-anesthetic doses. The analgesic effect of ketamine is strong through both the central and peripheral nervous system paths . It has et al. [It should be noted that providing an effective, safe and painless anesthesia in teeth with symptomatic irreversible pulpitis is critical , 12. Kavet al. , showed Forty two adult patients participated in this prospective, randomized, double-blind study. They were referred to an approved dental clinic of Isfahan University of Medical Sciences for endodontic treatment. The Regional Ethics Committee affiliated to Isfahan University of Medical Sciences approved the study protocol (Grant No.: 388485). Also this study has been registered in the Iranian Registry of Clinical Trial (IRCT138905024440N1). A full description of the study was given to the patients with irreversible pulpitis, and an informed consent was obtained from each of the patients.The participants of this study included the healthy (ASA I or ASA II) patients, aging between 18 to 50 years, who had a vital posterior mandibular tooth (premolar or molar) with pain and a prolonged response (in comparison with control group) to cold testing with Endo-Frost cold spray  and diagnosed with irreversible pulpitis, had no severe periodontal disease, or any periapical pathological defect seen in the dental radiographs and no contraindications for the drugs and substances used in the study. The exclusion criteria were set in patients showing signs of pulp necrosis upon access cavity opening, patients showing any signs or symptoms of allergy to anesthetic solution, pregnancy and breast-feeding, patients with pain in more than one mandibular tooth, and those who refused to continue at any stage point. Therefore, each patient had a vital mandibular molar tooth with a clinical diagnosis of symptomatic irreversible pulpitis.The patients marked their initial pain on a Heft-Parker Visual Analogue Scale (HP-VAS) . The scaArticaine plus ketamine (A-ketamine) local anesthetic solution was prepared as follows: Under sterile conditions, 0.2 mL from a 1.8-mL cartridge of 4% articaine with 1:200000 epinephrine  was drawn and replaced with 0.2 mL ketamine  using a glass micro liter syringe . For articaine plus normal saline  local anesthetic solution, 0.2 mL from a 1.8 mL cartridge of 4% articaine with 1:200000 epinephrine was drawn and replaced with 0.2 mL of normal saline. A trained dental assistant prepared the two local anesthetic formulations and coded them in a random manner. Patients were assigned equally into two groups of A-ketamine or A-saline. One operator administered two cartridges of either A-ketamine or A-saline local anesthetic solution using IANB technique for each patient in a double-blind trial. Therefore, none of the participants and operators was aware of the group assignment. All the injections were performed using a 27-gauge, 1.5-inch needle  attached to a standard aspirating dental injection syringe. Lip numbness was set as a criterion to IANB achievement. If lip numbness was not profound 15 min after the injection, the patient was excluded from the study. In the present study, no participant was excluded from the study as a result of a lack of lip numbness. Then, the teeth were isolated with a rubber dam, and access cavities were prepared.The patients were asked to rate the pain during the preparation of access cavity or initial file placement. If the patient felt pain, the treatment was stopped, and the patient marked their pain by using HP-VAS. The IANB injection was considered successful if patient felt no pain or mild pain (HP-VAS score≤54).Chi square test; age was analyzed by independent t-test and initial pain was analyzed using the Mann-Whitney test. The comparison was considered significant at P<0.05.Data were statistically analyzed using SPSS software  software. Comparisons between A-ketamine and A-saline groups for the success of the IANB, gender, and tooth type differences were analyzed by P>0.05). Distribution of teeth for A-ketamine and A-saline groups is presented in P=0.68). The success rate of IANB was 55.0% for A-ketamine and 42.9% for A-saline group. There was no statistically significant difference in success rates between the two groups (P=0.437).Out of 42 adult patients, 18 were women and 24 were men. The age range was 19-56 years, with mean±SD of 30±9.2 and 33±9.4 years in the A-ketamine and A-saline groups, respectively. The age, gender, and initial pain ratings for the A-ketamine and A-saline groups are presented in This study was carried out to investigate the effect of articaine plus ketamine on the success rate of IANB in posterior mandible teeth with symptomatic irreversible pulpitis. The results showed that the success rate of IANB in A-ketamine group was a little more than A-saline group. However, the difference was not statistically significant.The participants’ age, sex, tooth types and initial pain records were not different between the two experimental groups; therefore, any possible effect from these factors was minimized. Lip numbness indicates successful IANB but does not guarantee pulpal analgesia or anesthesia in all patients -18. Moree.g. thermal stimulus, electrical stimulus, or clinical treatment), and population differences [The success rates of anesthesia in the case of pulpitis have been reported to be as low as 20% , 21 to aferences .Combining anesthetic solution with some medications has been evaluated to overcome the local anesthetic failure of mandibular molars with irreversible pulpitis . EvidencKetamine interferes with sodium ion channels as a local anesthetic and shares with a binding site of commonly used local anesthetics, increasing their anesthetic effect .et al. [via a peripheral mechanism and increases the anesthetic and analgesic actions of local anesthetics completely [Tverskoy et al.  showed tmpletely . In addimpletely . AccordiThe insignificant effect of adding ketamine to articaine might be partly because of their different onset of action. The effects of ketamine following an intramuscular injection starts in approximately 30 min and lasts for about 15-30 min . Intravenous injection of ketamine may results in the complete emergence of its systemic side effects such as fidgetiness, dizziness, and pulmonary distress . HoweverUnder the limited conditions of this study, adding 0.4 mL 50 mg/mL ketamine hydrochloride to the articaine local anesthetic did not improve the success of the IANB for posterior mandibular teeth in patients with symptomatic irreversible pulpitis.


Objective: Chronic pain is a well-known morbidity associated with neurofibromatosis (NF) for which better therapies are needed. Surgery, radiation, and pain medications have been utilized, but often fail to relieve debilitating pain. One patient at our institution was noted to have near complete resolution of pain after treatment with bevacizumab for progressive neurologic deficit associated with NF2, suggesting its potential as an effective pain control method. We aim to better characterize the use of bevacizumab for pain control in this subset of patients. Patients and Methods: We retrospectively reviewed 38 NF patients treated at our institution.  Results: Of the 38 total NF patients, we found that 63% reported chronic pain, with 18% reporting chronic opiate usage. Nine patients with chronic pain were considered for bevacizumab treatment and five went on to receive infusions. Of these patients, four out of five had previous surgical debulking and two out of five had previous radiation for attempted pain control. One patient had a lesion not amenable to surgery or radiation. Patients received a median of 13 cycles of bevacizumab, and four out of five patients reported a decrease in subjective pain. All patients that had pain relief had a relapse of pain symptoms when the dose was reduced or infusions were paused. Seventy-five percent were able to decrease opiate use. No major complications were noted. All five patients have elected to continue infusions for pain control. Conclusion: Bevacizumab was, in general, well tolerated and should be considered as a treatment option in NF patients with chronic pain refractory or not amenable to surgical decompression and debulking, radiation, and pain medication.   Neurofibromatoses (NF) represent a family of neurocutaneous disorders characterized by the development of multiple neuronal tumors, including schwannomas and neurofibromas. Neurofibromas in these patients can be numerous and plexiform, involving multiple nerve roots at a time. In addition to neuropathy, these tumors can cause a significant pain burden for patients and represent a serious source of overall morbidity. All NF patients report more impairment from body pain compared to age-matched controls without NF -2. In stThe traditional method of pain control in the NF patient is to identify the most symptomatic lesion and attempt surgical resection and decompression of that specific lesion. However, surgical resection remains fraught with difficulties as lesions are often vascular and can cause significant intraoperative blood loss. Furthermore, invasion into the nerve by tumor leads to either incomplete resection or new postoperative neurologic deficits. Even with complete resection, 20% of lesions will recur at the same location. Furthermore, there are some locations, such as plexiform neurofibromas of the face, that are essentially unresectable -6. RadiaOther methods of pain control have been reported, primarily as case reports. Individual patients have benefited, for example, from ketamine, occipital nerve stimulator, physical therapy, pirfenidone, and thalidomide , 10-12. A 34-year-old woman first presented in 2005 with a diagnosis of NF2. She underwent resection of a Grade 2 cervical ependymoma two years prior with subsequent fractionated radiotherapy. Her primary complaint was pain in the neck and bilateral shoulders. At the time she was taking ibuprofen, carisoprodol, and occasional hydrocodone/ acetaminophen. She previously tried fentanyl patches, amitryptiline, baclofen, and gabapentin. The following year her MRI remained stable, but she increased her hydrocodone/acetaminophen usage and developed new right-hand numbness. She was referred for acupuncture and cyclobenzaprine, which she self-discontinued later due to sleepiness. She subsequently tried desipramine and duloxetine, which produced mood alterations and were also stopped. Her hydrocodone/ acetaminophen usage increased over time from one tab a day to multiple tabs a day. She was hospitalized in 2008 briefly following a fall with a worsening of bilateral upper extremity numbness and pain. She was given a dexamethasone taper at that time with some improvement in pain. She continued to have lower extremity discoordination off steroids and developed a right upper extremity claw hand. Given her instability, she was fitted for a walker and a wheelchair. She also developed a left thigh neurofibroma that was painful to the touch and was referred back to Neurosurgery for evaluation. Surgery was deferred for concern that it may further worsen the neurologic deficit in her leg. In November 2009, the patient was wheelchair-bound from debilitating pain and frequent falls. She increased her opiate from occasional hydrocodone/ acetaminophen, soma, and ibuprofen in 2005 to oxycodone/ acetaminophen every four to six hours with supplemental oxycodone for breakthrough pain. The pain was not controlled with carisoprodol, fentanyl patch, amitryptiline, baclofen, gabapentin, cyclobenzaprine, duloxetine, and desipramine. On November 24, 2009, the patient began bevacizumab, 7.5 mg/kg every two weeks for three cycles, for tumor growth and pain control. In her first follow-up in January, she reported a subjective decrease in pain and improvement in clinical status, such that the patient was beginning to drive again. By June 2010, the patient reported significant improvement in pain and had begun walking again without the wheelchair. In September 2010, she reported walking daily. Her bevacizumab infusions were spaced to every four weeks. She reported using hydrocodone/acetaminophen, 0-3 times a day, and was no longer using oxycodone for breakthrough pain.Under the Stanford University Hospital and Clinics IRB protocol 32041, we retrospectively identified 38 patients diagnosed with NF evaluated in the Stanford Neuro-Oncology clinic. Patient demographics, including age, gender, NF type, the presence of chronic pain at the time of first evaluation, and previous treatments for pain, were recorded. For those treated with bevacizumab, pain medications, start and stop dates for bevacizumab, a number of cycles, the presence of subjective pain reduction, time to pain reduction, and the clinical course after infusions were stopped were also recorded.  Patient demographics for all patients with NF are summarized in Table Ten NF patients received bevacizumab infusions. Bevacizumab was administered for all patients every two to four weeks at a dose of 7.5 mg/kg. For each infusion, a complete blood count, chemistry panel, and urinalysis were obtained and vital signs taken for blood pressure. For five patients, the primary reason for treatment was a concern for tumor progression; for five patients, treatment was administered for tumor-related pain. In the five patients receiving bevacizumab for non-pain indications, two patients did have pain complaints prior to starting infusion, with one of these patients able to stop anti-inflammatories for burning leg pain four weeks after starting the infusions. The other patient did not have improved pain with the infusions.  Characteristics of the five patients receiving bevacizumab for pain control are outlined in Table Neurofibromatosis is a common neurocutaneous disorder associated with both central and peripheral tumors. Pain can frequently become the primary disease-related morbidity requiring multiple surgical interventions, radiation treatments, and pain medications. In our study, we found that 63% of patients complained of chronic pain and over half were taking pain medications. Many had already received prior surgery and radiation to attempt to alleviate pain. These results correlate well with previous studies showing that pain is reported by a majority of NF patients -4.While surgery and radiation can both offer local control if one responsible lesion can be determined, the frequent presence of multiple or plexiform lesions often creates major difficulties in pinpointing just which one is the etiology. Even if a particular cause of pain is identified, surgery carries a significant risk of nerve damage and heavy blood loss -6. Our iFor the NF pain patient, therefore, a systemic treatment that could address complex or multifocal sources of pain with a low side effect profile would be of great benefit. Bevacizumab is an anti-VEGF-A agent that has been frequently used in other settings for tumors and radiation necrosis to reduce permeability and edema, often with an alleviation of associated pain -14. BevaVEGF has been shown to be upregulated in neurofibromas and schwannomas -19. TherExperimental evidence exists as well supporting the contention that that VEGF also plays a direct role in pain sensation. In murine models, VEGF is upregulated in mechanically injured nerves . In suchChronic pain is prevalent in the NF population and is a source of significant morbidity. While previously reported in the context of controlling acoustic neuroma growth, we report a series of NF patients with refractory pain that was successfully treated with bevacizumab. Bevacizumab was overall well tolerated and all patients have elected to pursue continued therapy for pain control. We believe that bevacizumab should be considered for as an option for NF patients with refractory pain.