Chronic post-surgical pain (CPSP) remains a major clinical problem which may be associated with impaired activities of daily life and decreased health-related quality of life. Although cesarean section is one of the most commonly performed operations, chronic pain after cesarean delivery has not been well-studied. The purpose of this prospective study was to assess the incidence and risk factors of chronic pain at 3, 6 and 12 months after cesarean delivery.We prospectively investigated preoperative demographic and psychological factors, intraoperative clinical factors, and acute postoperative pain in a cohort of 527 women undergoing cesarean section. The women were interviewed and completed pain questionnaires after 3, 6 and 12 months. Questions were about pain intensity, frequency, and location, as well as medical treatment and impact on daily living.The incidence of CPSP at 3, 6 and 12 months after cesarean section was 18.3 %, 11.3 % and 6.8 %, respectively. Most of the women with CPSP experienced mild pain at rest. The incidence of moderate and severe pain on movement was high at 3 month, and then has a significant decrease at 6 and 12 months. CPSP had a negative influence on the activities of daily living. Independent predictors of CPSP at 3 months included higher average pain intensity on movement within 24 h postoperatively, preoperative depression, and longer duration of surgery. At 6 months, more severe pain during movement within 24 h of surgery and preoperative depression were predictive of pain persistence. And 12 months after surgery, only higher average pain score on movement within 24 h following cesarean section was found to be significant associated with CPSP. The three models all showed moderate discrimination and good calibration for the prediction of CPSP at 3, 6 and 12 months postoperatively.CPSP was not rare in women undergoing cesarean section. Patients with more intense of acute postoperative pain on movement, preoperative depression, and longer surgical time had greater risk for CPSP following surgery.The online version of this article (doi:10.1186/s12871-016-0270-6) contains supplementary material, which is available to authorized users. Chronic post-surgical pain (CPSP) has been defined by the International Association for the Study of Pain (IASP) as persistent continuously or intermittently for more than 3 months after surgery . CPSP reThe cesarean section rate continues to increase in many parts of the world for both medical indications and maternal choice –9. In maAlthough cesarean section is one of the most commonly performed operations, chronic pain after cesarean section has not been well-studied. For example, the prevalence of chronic pain after cesarean section is usually observed in retrospective studies, and varies considerably from one study to another. Moreover, the number of studies that have examined the risk factors of CPSP after cesarean section is limited. Some possible risk factors that have been identified for CPSP after cesarean delivery include severe acute postoperative pain, previous pain, non-private insurance status and general anesthesia –18. PsycTherefore, further research is needed to provide a more comprehensive assessment of CPSP after cesarean section. In addition, factors that might predispose to this type of problem need to be evaluated more closely. The purpose of this prospective study was to assess chronic pain 3, 6 and 12 months after cesarean delivery in a cohort of women in China. We also aim to elucidate the relative contribution of clinical and psychological risk factors for the development of CPSP following cesarean section.This prospective observational cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University - a teaching hospital in China. Women hospitalized for cesarean section from July 2014 to December 2014 were recruited on the hospital ward one day before or on the day of surgery, except during weekends and holidays when research interviewers were unavailable. Patients who agreed to participate were interviewed in person preoperatively and 24 h postoperatively by a trained investigator. Telephone follow-up interviews were conducted 3, 6 and 12 months following surgery. Intraoperative information was collected from the patient record by a research assistant. Additional file Study-specific questionnaires concerning demographic and medical variables were given to the patients for self-administration after being admitted to the obstetric ward. Questions about age, gestational age, previous vaginal delivery, cesarean delivery, and pelvic surgery, history of diabetes mellitus and hypertension, and preoperative pain  were included.Body mass index (BMI) was calculated from height and weight measured on admission for surgery.In addition, standardized instruments were used to measure psychological well-being. The validated Chinese version of the Edinburgh Postnatal Depression Scale (EPDS) was used to capture depressed mood, with higher scores indicating poorer mental health . AlthougThe State Trait Anxiety Inventory (STAI) measures state and trait anxiety. The STAI scale consisted of 40 statements describing various emotional states, which have been translated into Chinese, and its reliability and validity were acceptable . Twenty Surgery was performed by one of six experienced obstetricians in a standardized protocol. In cesarean section, the incision was performed via a Pfannenstiel incision except in women with a previous vertical skin incision and a transverse lower uterine segment incision. Intraoperative variables obtained from the operating room record surgical approach , operation time and the volume of blood loss.All patients followed the anesthesia protocol routinely used in our department. For elective cesarean section, an epidural technique is the most common form of anesthesia. With the patient in the lateral position, the epidural block was performed in the midline at the L1-2 or L2-3 interspace using a loss of resistance technique.General anesthesia was used in patients with failure of epidural block or with contraindications to epidural anesthesia. Propofol with succinylcholine was given for induction of general anesthesia, with maintenance by sevoflurane or infusion of propofol combined with remifentanil. Rocuronium or vecuronium was given if additional muscle relaxation is needed.After surgery, postoperative pain relief was provided by intravenous tramadol patient-controlled analgesia via a Rythmic Pump  . The subjects were monitored every 6 h for 24 h for pain control, tramadol consumption, and relevant side effects.Patients were visited within 24 h after surgery. Pain intensity was assessed as average pain at rest and on movement during the past 24 h using a numerical rating scale (NRS), with 0 indicating “no pain” and 10 indicating “worst pain imaginable”.The presence of chronic pain at 3, 6 and 12 months was defined as pain persisting beyond the normal healing time of 3 months, with an NRS value of above 0 at rest and/or with movement. The point prevalence was determined by the proportion of patients reporting chronic pain at the time of the survey.Patients were contacted by telephone by one of the authors at 3, 6, and 12 months following surgery. This telephone interview usually takes no longer than 15 min. CPSP was measured using the short form Brief Pain Inventory (BPI) . The shoDescriptive analyses were conducted to assess the demographic, clinical, and psychological characteristics of the sample. The results are expressed as means ± standard deviation (SD) for continuous variables or as number and percentages for categorical variables.t test or Mann–Whitney U test was used, depending on whether data were normally distributed. For categorical variables, comparison of groups was performed with the χ2 test.The initial analyses were conducted to compare women with and without chronic pain at 3, 6 and at 12 months postoperatively to identify risk factors associated with chronic pain after cesarean delivery. For continuous variables, the independent samples P-values less than 0.25 in the univariate analysis were entered in the multivariate model. In multiple regression, covariates were selected by stepwise backwards likelihood ratio variable selection with P to enter 0.05 and P to remove 0.10. The discriminatory power of the multivariate model was evaluated by using the area under the receiver operating characteristic curve (ROC AUC) and its 95 % confidence interval (CI). An AUC of 0.5 indicates that the model has a predictive discrimination no better than chance, whereas an AUC of 1.0 indicates a perfectly discriminating model. Generally, an AUC of 0.5–0.7 is interpreted as a model with low discriminatory power, 0.7–0.9 moderate and > 0.9 as a model with a high discriminatory power. The calibration of the multivariate model was evaluated using the Hosmer-Lemeshow goodness-of-fit statistic, where a high P-value indicates good calibration.Univariate logistic regression analysis was performed to test the influence of possible risk factors on chronic pain at 3, 6 or 12 months after surgery, and candidate covariates were chosen based on statistical significance or possible clinical importance. Only covariates with P-values of 0.05 were considered statistically significant.Statistical calculations were performed using SPSS for Windows version 17.0. Two-sided n = 24), inability to complete the questionnaire because of postoperative complications or intensive care unit admission (n = 2), and refusal of the whole inhospital interview (n = 12). Hence, 527 patients (94.6 %) who completed the first postoperative questionnaire at 24 h after surgery were included in the analysis. Patient baseline characteristics together with data about surgery and anesthesia are summarized in Table From July 2014 to December 2014, 597 patients were invited to participate in the study and 32 were declined. Of the 565 patients who were included, 38 were excluded for the following reasons: operation cancelled , 487 (92.4 %), and 472 (89.6 %), respectively. Using the primary study definition, 92 of 502 patients (18.3 %) reported characteristic of CPSP 3 months after surgery. Rates are based on any symptom of pain, ache, or discomfort in the operated area that was experienced in the previous week of the survey. By 6 months postoperatively, the observed rate of pain fell to 55 of 487 (11.3 %). At 12-month follow-up only 32 of 472 patients (6.8 %) still complained of persisting postoperative pain. Of the subjects with persistent pain, the timing and severity are shown in Table Most women with chronic pain reported mild pain at rest during the first year after giving birth. The incidence of moderate to severe chronic pain at rest was 25 % (23 of 92), 5.5 % (3 of 55) and 0 among mothers reporting chronic pain at 3, 9 and 12 months, respectively. At 3, 6 and 12 months postoperatively, approximately 80 %, 35 % and 3 % of those with persistent pain reported moderate to severe pain on movement. Among the patients with CPSP at 3 month after surgery, only a small proportion of them reported having taken analgesics (27.2 %). And 6 months and 12 months after surgery, 18.2 % and 21.9 % of the patients with CPSP reported having used analgesic medication during the week preceding the survey, respectively.At 3 months, pain was present daily or several times per week in majority of the patients with CPSP. At 6 months, pain was present several times per week or once a week in about half of the patients with CPSP, and by 12 months postoperatively pain occurred once a week or less than once a week in nearly two thirds patients who reported CPSP. The two most common sites of CPSP were the area of incision and the pelvis. Further locations affected were low back, buttocks and legs  of individuals with pain reporting that this aspect of their life was affected (Table Table P < 0.25 for the comparisons between patients who did and did not develop chronic pain. As Table P < 0.001), higher average pain intensity on movement within 24 h postoperatively , and longer duration of surgery . At 6 months postoperatively, preoperative depression and more severe pain during movement within 24 h of surgery were found to independently associate with occurrence of CPSP. At 12 months, only average pain score on movement within 24 h following cesarean section remained significantly associated with CPSP in the multivariate analysis .As Table χ2 = 9.542, P = 0.299 (3 months), χ2 = 5.395, P = 0.715 (6 months) and χ2 = 5.862, P = 0.663 (12 months), respectively. This indicates that the models had moderate discriminatory power and good calibration.The predictive models for CPSP at 3, 6 and 12 months yielded ROC AUC of 0.708 (95 % CI 0.641 - 0.755), 0.726 (95 % CI 0.646 - 0.805) and 0.744 (95 % CI 0.648- 0.840), respectively. And the three models showed good calibration by Hosmer-Lemeshow goodness-of-fit statistic with In our prospective cohort study of 527 women who underwent cesarean delivery, the incidence of CPSP was 18.3 % at 3 months after surgery. And we found 11.3 % of patients still had pain 6 months following surgery, and the incidence of CPSP subsequently reduced to 6.8 % at 12 months. In 2004 Nikolajsen et al. . Liu et As indicated, the prevalence of CPSP is highly dependent on its definition. We defined CPSP as pain that persists beyond 3 months with an NRS value of above 0 after surgery using the IASP’s recommendations . A speciWe found most of the women with CPSP experienced mild pain at rest, few women experienced severe or unbearable rest pain. Moderate and severe pain on movement was frequent 3 month following cesarean section, whereas the incidence of moderate to severe pain on movement significantly decreased at 6 and 12 months. The severity of the pain reported by patients in the present study with chronic pain was comparable to most other studies , 15, 18.The present study found that CPSP had a negative influence on the activities of daily living of patients undergoing cesarean section. Physical and social consequences of chronic pain were predominated in general activity, mood and enjoyment of life. This exemplifies the impact of chronic pain on the mental health of this relatively young population. Moreover, there seems to be a psychic component that explains some repercussions of chronic pain.One of our objectives was to identify demographic, clinical, and psychological risk factors for chronic pain after cesarean section. The results of our multivariate analyses indicate that patients with higher average pain intensity on movement within 24 h postoperatively have a greater risk of chronic pain at 3, 6 and 12 months after cesarean section. Therefore, our results indicate that attempts to better manage postoperative pain are needed in CPSP prevention.Substantial evidence has been generated over the last decade suggesting that severe acute pain after delivery and specifically after cesarean delivery may progress to chronic pain , 15, 16.It has been shown that depression during pregnancy is associated with increased maternal mortality . The preIn this study, the duration of the surgery is found to be associated with CPSP at 3 months following cesarean section. Previous studies have not evaluated this variable as a risk factor for CPSP following cesarean section. As operations with longer duration may be associated with more extensive tissue injury during surgery, there is a higher risk of damaging nerves in the area that may increase the risk of subsequent chronic pain , 42.Unlike Nikolajsen et al. , we did Previous surgery has been recognized as a risk factor for chronic pain in general after surgery . In the Our study has limitations and strengths. The present study relied on the patients’ selfreport, and physical examinations, quantitative sensory testing, or both, were not undertaken. This may be seen as a limitation of our study. Another limitation of this study was that we did not have the ability to examine the effect of nonresponse because we did not have permission to access information on prospective subjects who declined to participate. However, characteristics of our sample are similar to other reports in the literature. Age, BMI, and previous pelvic surgery status were similar between our sample and the literature. A final limitation of the current study was that our sample was drawn from a single teaching hospital, and all the women in our study were Asian, that is, we do not know if the figures can be generalised to other settings. Therefore, it would be important to evaluate the generalizability of our findings to more heterogeneous samples of patients.Despite these limitations, methodologic features of our study and its results contribute to knowledge of chronic pain following cesarean section. The strengths of the study are the prospective design, the consecutive inclusion of patients and the use of validated tools for symptom measurements. Unlike retrospective studies relying on patient recall of events occurring months or even one year previously, patients in our study were asked to report pain at the time of their interview, rather than recalling previous pain experiences. The study included 90 % of all patients operated on during the study period and had high response rates at follow-up. The inclusion of patients was restricted to 6 months; consequently, the surgical procedures and post-operative pain management were similar for all patients.In summary, we found that the incidence of CPSP in patients undergoing cesarean section was 18.3 % at 3 months, and subsequently reduced to 6.8 % at 12 months. Pain intensity was mild to moderate in most of women with CPSP. Predictors for CPSP included higher average intensity score of acute postoperative pain on movement, preoperative depression and longer surgical duration. Preventive strategies should target these risk factors to reduce adverse sequelae of procedure, supplemented with broader efforts to support the longer-term recovery in parturient.


To describe the epidemiology of joint pains and document analgesics usage in an African context.Patients suffering from joint pain were recruited from nine sites located in Antananarivo, Madagascar, including 6 hospital services and 3 clinics. Doctors collected information on the etiology and characteristics of the patients’ pain. Analgesics prescribed by these doctors were also documented.In total, 400 patients were enrolled in the study . Pain of mechanical type was found in 260 participants, 65%; 95% CI [60.1% to 69.6%] and inflammatory type pains in 128 cases 32%; 95% CI [27.5% to 36.9%]. Mixed pains were found in 12 patients (3%). The median duration of pain prior to the consultation was 6.5 days. The average pain intensity was 57.9 ± 19.9 mm of a total of 100 mm maximum on a visual analogue scale, VAS. The etiologies of mechanical type pains were dominated by fracture, common low back pain and tendonitis. Arthrosis was the dominant cause of inflammatory type pain, followed by rheumatoid arthritis and gout. NSAIDs (74.5%) were the most frequently prescribed analgesics followed by paracetamol (49.5%), weak opioids (23%) and corticosteroids (12.25%). Two-thirds of medical prescriptions (65.3%) were of combined analgesics.These findings demonstrated that mechanical type pains were the main reason for consultations for joint pain in these situations in Antananarivo, Madagascar. The most frequently prescribed pain-relieving medications were NSAIDs, paracetamol, weak opioids and corticosteroids. This descriptive study may be a useful starting point for further epidemiological studies of pain in the African context. Pain and its management remain a serious public health problem worldwide. Pain represents the main reason for consultation . The costs of its management vary from one country to another. In the United Kingdom, back pain management costs to society were found to be £6.600 million to £12.300 million [In the African world, research on the use of analgesic on joint pain is almost non-existent. Indeed, there are very few publications that deal with this subject. With the keyword « joint pain, analgesic, Africa », only 17 publications were found from the PubMed database in August 2015 of which two directly related to the assessment of the effects of analgesic in arthritis , 5 and and 2013 to July 2nd 2013 from nine different sites . Outpatients coming to a private clinic or to an emergency service or any recent inpatients coming to hospital for joint nociceptive pain regardless of duration with either acute or chronic pain were included. Patients with bone or joint pain following surgery, or due to cancer, and those with neuropathic pain or other types of pain were excluded.The study was a multicenter descriptive, cross sectional, observational and quantitative study conducted during routine medical consultations in Antananarivo, capital of Madagascar. Four hundred patients were recruited in 3 months from April 2Nine doctors on the nine recruitment sites led the study. On each site, two or three other physicians were assigned the inclusion of patients with joint pain. Variables entered onto the proforma used in this study included personal information, clinical parameters such as characteristics of pain, diagnoses and the analgesics prescribed by physicians. For each patient, information was recorded on survey sheets after obtaining their informed signed consent.Data were entered and analyzed using Epi-info software 3.5.3. The Site-Patient codes were the unique ID for each patient. Each file had an individual assigned code. After entering the 400 cases, missing data on mandatory fields and some outliers was controlled and verified on each sheet. Related corrections was done first on Epi Info and then on Excel 2007. Quality control of data entry was undertaken by random sampling and checking 10% of the data entered. The texts, graphics, and tables were produced using Excel 2007 and Word 1999-2003 and Word 2007 software. Qualitative variables were expressed as proportions presented as percentages and graphically; quantitative variables were expressed as arithmetic means. A 95% confidence interval was given for many results these being given as means + standard deviation with medians being given with minimum and maximum values.For comparisons, the selected significance threshold chosen corresponded to p < 0.05. Statistical analysis was made in univariate. For comparisons of percentages Chi-square was used with corrections using the Fischer test or the test of Yates for low numbers. To give acceptable statistical power, for a total population of 22,000,000 in Madagascar, a representative sample of 385 patients was sufficient. Calculation of the sample size was made in a rational way as the ability of the center to recruit new patients.Clinical data confidentiality and the anonymity of the patients have been followed throughout the process of inclusion and analysis.Recruitment objectives were achieved at 100% (R/0=100%) with the recruitment of 400 patients during the study period. One hundred and ninety patients were been enrolled in 4 emergency units, 150 were recruited in a Rheumatology service, 45 in three different private clinics and 15 in a trauma surgery service.One hundred and ninety men and 210 women were recruited with a sex ratio of 0.9. Their mean age was 42.34 ± 17.7 years. This distribution was symmetrical with a median at 42 years, a minimum of 4 years and a maximum of 86 years. Full-time workers represented 40.3% of the sample and the unemployed represented one fifth (19.3%).Physicians stratified the patients on presentation by diagnosis using a pre-established list of diseases; secondary classification was done at the data analysis step. The complaints of the patients were classified in terms of the type of pain with of mechanical pain occurring in 260 cases  and inflammatory type of pain presenting in 128 cases . Twelve patients had joint pain combining features of both types of pain.Diseases causing joint pain were divided in two groups, those where there is a mechanical type pain and those which have an inflammatory type pain. Twenty four patients had two diagnoses which caused joint pains. Thirty-six rare diseases have been identified including joint sickle cell crisis, chondropathy, hallux valgus, scoliosis and articular manifestations of psoriasis as seen in Frequencies of pain types depending on patient ages were shown in Osteoarthritis (40.9%) was the most frequent disease causing inflammatory pain type, followed by rheumatoid arthritis (20%), gout (14.5%), undetermined arthritis (12.7%), connective diseases (5.5%) and other rare diagnoses. Osteoarthritis was here classified in inflammatory diseases because flares-up had caused inflammatory type pain at the time of consultation even though there was a mechanical basis of the chronic pain. A positive correlation was found between body mass index and pain of inflammatory type as shown in Where mechanical type pain was found, the three most common diagnoses were articular fractures (24.5%), nonspecific knee pain (17.4%) and common low back pain (15.8 %) followed by tendonitis (14.7%), sprain (11.5%), dislocation (9%), common back pain (4.3%) and common neck pain (2.9%).Mean pain magnitude assessed with Visual Analogue Scale (0-100) was 57.9 ± 19.9 mm with a median of 60 the range being from 10 to 100. Moderate pain (30 to 60 mm) was found in three quarters of patients painful events (75.5%). Mild pain was present in 4.8% and severe pain in 19.8%. Mean pain duration was 265.30 ± 797.94 days, with a median of 6.5 days, ranging from 1 day to 5475 days or 15 years. Acute pain of less than 3 weeks was present in almost two thirds of patients (61.5%). Patients who had subacute pain constituted 16% of the whole and chronic pain with duration more than three months represented 22.5%.Considering on the various categories of analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) were the most prescribed (74.5%), followed by analgesics level 1 (49.5%), analgesic level 2 (23%) and corticosteroids (12.25%) as listed in Two-thirds of prescriptions (65.3%) were of tablets in which two analgesics were combined. The analgesics prescribed, with their dosage forms have been listed in order of frequency. The most prescribed was paracetamol in tablet form (38.25%) followed by ketoprofen gel and the combined paracetamol + codein tablet as listed in Tablets were prescribed in almost all patients, followed by topical gels and suppositories as shown in Analgesics are widely used in the management of joint pains. In our study fracture was found to be the main cause of mechanical pain type and degenerative joint disease was main cause of inflammatory pain type entailing analgesics prescription. The most prescribed analgesic drug for these diseases, namely the paracetamol, was used alone or in combination with an NSAID.Our study population study was relatively young, with an average age of 42.34 years. There was a clear division between mechanical type pains that predominated in young people and inflammatory type pains which predominated in the elderly. Here there was a high incidence of osteoarthritis in those over 45 years, and who were frequently seen during an inflammatory exacerbation of their disease. This finding in our study is corroborated by other studies confirming that the coxarthrosis, gonarthrosis and low back pain are the main reasons for consultations for osteoarticular diseases , 7. In aIn our study, the major diseases causing inflammatory type pain were osteoarthritis, rheumatoid arthritis and gout. Although osteoarthritis is a degenerative condition usually manifested by mechanical type pain, patients in our series only seemed to consult when there was an inflammatory flare up. It is known that the delay to diagnosis is long in Madagascar and Africa perhaps because of the cost of treatment which is mostly supported by the patients . In rheuThe intensity of pain in this study averaged 57.9 ± 19.9 mm for an average duration of 265.30 days. This intensity is high compared with other studies but may be associated with the predominance of traumatic pain in our study where the pain is acute. The average was lower in chronic pain, being 44 + 23 mm for an average duration of 7.4 years . In a deAs pain was only moderate in many patients in our study, the prescription of weak opioids is less than might be expected because of the effectiveness of NSAIDs. This choice of the NSAID is commonly seen in young populations especially in the pediatric world where their effectiveness and safety are widely appreciated . NSAIDs Muscle relaxants were rarely prescribed in our study. According to a published review, in patients with rheumatoid arthritis, they bring no demonstrated benefit after one week. Adverse effects such as drowsiness and dizziness are significantly elevated even with short duration administration .Injection of corticosteroids provides a short term relief (four to eight weeks) of the flare-ups of osteoarthritis of the knee while visco-supplements by hyaluronic acid can maintain the improvement of symptoms for longer period . The lowOne limitation of our study is that recruitment came from limited sources predominantly hospital consultations, hospital emergencies departments and recent inpatients in rheumatology service. Thus there is a strong bias to the hospital. It would be useful to replicate the study in remote health centers and private clinics in towns to determine the characteristics and causes of such pain of the majority of the population. First contacts of patients with the Malagasy health system are made in these centers. Consultations at general practitioners may give similar findings.Mechanical type pains were the main reasons for consultations for joint pain in Antananarivo. The etiologies of these pains were dominated by fracture, common low back pain and tendonitis. The main causes of inflammatory pain were flare-ups of osteoarthritis, rheumatoid arthritis and gout. A positive correlation was demonstrated between advanced/advancing age and pain of inflammatory type and in the young mechanical type pain predominated. Two-thirds of patients consulted for acute pain. The average pain intensity was moderate. The most frequently prescribed analgesic were NSAIDs, paracetamol, weak opioids and corticosteroids. It may be useful to do similar studies of joint pains in different situations in Africa to determine their causes and the frequency of various methods of pain management.Joint pain type in developed country;Analgesics use in developed country.Types of joint pain in a developing country (Madagascar);Joint pain characteristics;Main analgesics used to treat join pain in a developing country (Madagascar).


FM) is a chronic pain disorder characterized by widespread pain, sleep disturbance, fatigue and cognitive/affective symptoms. Functional imaging studies have revealed that FM and other chronic pain syndromes can affect resting brain activity. This study utilized electroencephalographic (EEG) recordings to investigate the relative power of ongoing oscillatory activity in the resting brain.Fibromyalgia syndrome  examination was performed to quantify tonic pain and tenderness on the day of testing along with measures of mood, arousal and fatigue. Oscillations in delta, theta, alpha, beta and gamma frequency bands were analysed using Standardised Low‐Resolution Brain Electromagnetic Tomography to evaluate sources of spectral activity throughout the whole brain.A 64‐channel FM patients exhibited greater pain, tiredness and tension on the day of testing relative to healthy control participants and augmented theta activity in prefrontal and anterior cingulate cortices. No significant differences were seen in other frequency bands. Augmented frontal theta activity in FM patients significantly correlated with measures of tenderness and mean tiredness scores.FM, and manifest in brain regions relevant for cognitive‐attentional aspects of pain processing and endogenous pain inhibition. Enhanced low‐frequency oscillations were previously seen in FM and other chronic pain syndromes, and may relate to pathophysiological mechanisms for ongoing pain such as thalamocortical dysrhythmia.The findings indicate that alterations to resting‐state oscillatory activity may relate to ongoing tonic pain and fatigue in EEG could benefit our understanding of fibromyalgia pathophysiology.Increased prefrontal theta activity may contribute to persistent pain in fibromyalgia or represent the outcome of prolonged symptoms. The findings point to the potential for therapeutic interventions aimed at normalizing neural oscillations, while further research utilizing quantitative analysis of resting  Stern and colleagues  bands , a resonant interaction between thalamus and cortex activity elicited by low‐threshold calcium spike bursts in the thalamus  diagnosed with FM took part in the study. Patients were recruited from outpatient fibromyalgia clinics at two regional National Health Service Foundation Trust hospitals; the Walton Centre, Liverpool, United Kingdom, and Wirral University Teaching Hospital, Wirral, United Kingdom. All patients fulfilled American College of Rheumatology criteria for diagnosis with fibromyalgia  at 60 dB sound pressure level using LabTec Spin‐50 stereophonic speakers  placed 0.8 m from the subject. Participants were given standardized instructions in line with methodological recommendations for resting EEG . Bootstrapping method (1000 samples) was utilized for t‐tests and a 95% confidence interval was employed throughout.The Activation‐Deactivation Adjective Check list (AD‐ACL) questionnaire Thayer,  was admi2.3EEG data was recorded using a 64 channel Biosemi Ag‐ACl active‐two electrode system . Electrode positions were allocated according to the extended 10–20 system with respect to anatomical landmarks; pre‐auricular points and the nasion. Two bipolar, flat Ag‐ACl external reference electrodes were attached to the mastoid processes. The recording bandpass filter was 0.16–100 Hz, and the sampling rate was 512 Hz.2.4t‐test indicates that there was no difference in the mean duration of data retained for spectral analyses in FM and healthy groups (t(35) = −0.58, p = 0.56).EEG data was first exported to Matlab v.8.10  for pre‐processing utilizing EEGLAB toolbox  covering the mantle of the brain. A 95% confidence level was employed throughout, and permutation analysis with 5000 randomizations was utilized to correct for the performance of multiple tests across all voxels. Mean spectral power from clusters of voxels demonstrating significant differences between the FM patient and control groups were exported for each subject and frequency band. Spearman's correlation analysis was conducted to evaluate the relationship between clinical symptoms and spectral power in FM patient and control groups using SPSS .Standardized low‐resolution brain electromagnetic tomography  = 8.95, p = 0.005) and tense (F(35) = 6.84, p = 0.013) than healthy participants, but no differences were found between for pre‐post testing changes in energy, tiredness, tension or calmness, nor was there any interaction between FM status and pre‐post changes on any scale (p > 0.05).Table t(35) = 3.58, p = 0.002) in prefrontal cortex. The peak difference was located in medial prefrontal cortex , but the bulk of the region demonstrating augmented theta oscillations covered voxels in the vicinity of the anterior cingulate cortex . The cluster also extended laterally to infringe on the dorsolateral prefrontal cortex . Anatomical locations are according to the digitized probability atlas provided by the Brain Imaging Center, Montreal Neurological Institute  = 0.65, p = 0.002), and also with mean (average of pre and post recording) tiredness scores measured using the tiredness scale of the AD‐ACL questionnaire (r(17) = 0.51, p = 0.024). Furthermore, mean tiredness and MTPS scores were also found to be correlated in patients (r(17) = 0.59, p = 0.008). Neither correlation was significant in healthy participants (p > 0.05). Fig. Spearman's correlation analysis indicated that frontal theta activity in FM patients correlated with measures of pain and tenderness on the day of testing indexed by MTPS scores (4Our findings indicate that FM patients exhibit increases in frontal theta power during resting EEG. Augmented low‐frequency oscillations were localized to anterior cingulate, medial prefrontal and dorsolateral prefrontal cortices. Furthermore, subjective power of low‐frequency oscillatory activity was associated with increased tenderness and tiredness scores in patients, which points to potential relevance for resting‐state electrophysiology in the manifestation of clinical symptoms of FM.The present findings correspond with a recent MEG study of resting oscillatory activity which also demonstrated enhanced frontal theta oscillations in FM patients (Lim et al., Enhanced theta oscillations seen in FM patients in this study were localized to frontal regions including mPFC, DLPFC and ACC, and also evident in fronto‐central regions of scalp electrodes. These loci are consistent with the aforementioned MEG research (Lim et al., Increases in low‐frequency resting EEG power were previously proposed to relate to TCD which may represent a pathophysiological model for chronic pain across multiple disorders including FM (Llinas et al., Further research is needed to evaluate whether TCD represents a valid potential pathophysiological mechanism for FM, and whether the differences seen reflect a predisposition for chronic pain or a maladaptive change associated with years of ongoing symptoms. However, if TCD can be shown to play an active role in the experience of FM and other syndromes, then this could have important clinical implications. For example, frontal theta power in neuropathic pain patients was shown to normalize, aligned with improvement in pain symptoms, following therapeutic lesions of the thalamus (Sarnthein et al., In addition to FM, it is also worth highlighting that similar patterns of enhanced frontal theta activity were previously reported in neuropathic pain (Sarnthein et al., This study has some obvious limitations. As mentioned, the cross‐sectional design means that it is impossible to infer whether the changes seen represent a predisposing pathophysiological cause of FM symptoms, or a consequence of years of chronic pain and other symptoms such as fatigue. This is further complicated by the existence of a clear relationship between these symptoms in patients, and the role of sleep deprivation in maintaining pain symptoms is a focus of discussion for FM Choy, . SecondlMeasures were taken to ensure participants remained awake and alert throughout recordings, and stringent levels of control were applied during recruitment. However, it is still possible that low‐level medications permitted in the study, or other confounding factors such as drowsiness, could unduly influence findings. Alternatively, the methodology employed to restrict drowsiness could have some influence on EEG signals, and the auditory task could unduly affect patients who may exhibit hypervigilance to their surroundings. However, EEG studies using spectral analysis have shown a high degree of similarity between resting and ‘task waiting’ data (Fingelkurts et al., To conclude, FM patients exhibited enhanced theta oscillatory activity in brain regions which is important for endogenous pain inhibition and attentional‐cognitive aspects of pain processing. The alterations show a relationship with ongoing symptoms including pain and tiredness indicating that increased prefrontal theta activity may contribute to persistent perception of pain in FM or represent the outcome of years of pain and fatigue. The findings suggest that therapeutic interventions aimed at normalizing neural oscillations may lead to some relief of ongoing symptoms for patients, or reveal more about FM pathophysiology. However, further research is needed to clarify the precise nature and time course of oscillatory changes in FM.NF takes responsibility for the integrity and accuracy of the data. AS and TN conceived and designed the study. NF collected the data, and NF and AS performed the data analyses. NF drafted the manuscript. All authors discussed the results and commented on the manuscript and approved the final version.


Shoulder pain is a major musculoskeletal problem. We aimed to identify which baseline patient and clinical characteristics are associated with a better outcome, 6 weeks and 6 months after starting a course of physiotherapy for shoulder pain.1030 patients aged ≥18 years referred to physiotherapy for the management of musculoskeletal shoulder pain were recruited and provided baseline data. 840 (82%) provided outcome data at 6 weeks and 811 (79%) at 6 months. 71 putative prognostic factors were collected at baseline. Outcomes were the Shoulder Pain and Disability Index (SPADI) and Quick Disability of the Arm, Shoulder and Hand Questionnaire. Multivariable linear regression was used to analyse prognostic factors associated with outcome.Parameter estimates (β) are presented for the untransformed SPADI at 6 months, a negative value indicating less pain and disability. 4 factors were associated with better outcomes for both measures and time points: lower baseline disability , patient expectation of ‘complete recovery’ compared to ‘slight improvement’ as ‘a result of physiotherapy’ , higher pain self-efficacy  and lower pain severity at rest .Psychological factors were consistently associated with patient-rated outcome, whereas clinical examination findings associated with a specific structural diagnosis were not. When assessing people with musculoskeletal shoulder pain and considering referral to physiotherapy services, psychosocial and medical information should be considered.http://www.biomedcentral.com/1471-2474/14/192.Protocol published at  First episode of shoulder pain accounts for nearly 1.5% of visits to the general practitioner (GP) annually within the UK.Prognostic factors associated with the outcome of physiotherapy for shoulder pain are unclear, and currently cannot support clinical decision-making.The objective of this multicentre longitudinal cohort study was to identity which patient and clinical characteristics, commonly assessed at the first physiotherapy appointment, were associated with patient-rated shoulder pain and function, at 6 weeks and 6 months.The study protocol for this multicentre longitudinal cohort study has been published in detail elsewhere,A postal invitation was sent to the patients whose referral to physiotherapy indicated that they may be eligible for the study. Patients were eligible if they were aged 18 years or older and described shoulder or arm pain aggravated by shoulder movements. Patients with significant reproduction of shoulder pain on spinal movement, or greater reproduction on spinal movement compared to shoulder movement, were excluded from the study. Patients with the following aetiology for shoulder pain were excluded: radiculopathy, postsurgery, postfracture, posttraumatic dislocation or systemic source. Participants provided written informed consent at their first physiotherapy appointment. Patients who decided not to participate in the study, or did not respond to later follow-ups, were not required to provide a reason.Data for 71 putative prognostic factors, determined and defined a priori, were collected from each participant and their physiotherapist. Summary baseline characteristics are presented in 10.1136/bjsports-2016-096084.supp1Supplementary file10.1136/bjsports-2016-096084.supp2Supplementary file10.1136/bjsports-2016-096084.supp3Supplementary filePrior to the first physiotherapy appointment, participants completed a bespoke questionnaire. At the first appointment, using standardised clinical data forms, physiotherapists recorded the history of the participant's shoulder problem and clinical examination findings. At discharge, physiotherapists recorded details of treatment and attendance on a standardised clinical data form. The delivery and content of treatment were unaffected by participation in the study.Participants were sent a postal follow-up questionnaire, 6 weeks and 6 months after starting their course of physiotherapy. This included two validated patient-reported outcome measures also collected at baseline: the Shoulder Pain and Disability Index (SPADI)2) with the outcome of up to 0.5. Therefore, 1000 participants were allowed for up to 22% loss to follow-up and this was the target sample size. All the participants providing outcome data at 6 weeks and/or 6 months were included in the analysis for that time point, whether or not they had completed their course of physiotherapy. Missing data at one time point were not imputed from other time points. All statistical analyses were carried out in STATA V.12.Using the approach suggested by Lipsitz and Parzen,For each outcome (the SPADI and QuickDASH) and time point (6 weeks and 6 months), general linear models were constructed. These were constructed with and without the inclusion of baseline SPADI and QuickDASH values. Also, as the residuals were not normally distributed, a logit transformation was applied to the outcomes and the transformed data were also modelled. For ease of clinical interpretation, the parameter estimates presented here are for the untransformed models.Initially, all putative prognostic variables were singularly entered into simple linear regression models. Those with a statistically significant relationship with the outcome, at the 10% level, were entered into a multivariable linear regression model. A stepwise selection process, based on change in scaled deviance, was then applied. The explanatory variable with the least significant p Value was removed. This process was continued until all the remaining variables had regression coefficients significant at the 5% level . Each variable removed on backward elimination was then individually re-entered and remained in the model if it attained a statistical significance of 5%.2), a proportional measure indicating the amount of variation in outcome explained by the models, is presented.This process was carried out for each of the nine subgroups of variables indicated in online Logistic regression was used to compare consenters with non-consenters, and the characteristics of participants who provided and did not provide outcome data. Adjusted odds ratio (OR) with 95% CIs are presented for statistically significant differences at p≤0.05.One thousand and fifty-five participants were recruited and consented to be in the study, 1030 of whom were eligible, provided adequate baseline data and were included in the study. Details of patient characteristics and baseline measures investigated as potential prognostic factors are presented under their respective subgroup headings in There was no significant difference in mean age or sex between consenters  and non-consenters . Having provided baseline data, 17 participants withdrew from the study, 1 died and 151 did not return their questionnaire or respond to reminders at either follow-up point. Participants who provided outcome data at 6 weeks and 6 months differed at baseline from those who did not . They weAfter multivariable linear regression, each model contained between 7 and 12 prognostic factors explaining between 0.34 and 0.48 of the variance at 6 weeks and between 0.30 and 0.43 of the variance at 6 months. Parameter estimates for the non-transformed SPADI at 6 months are presented in The factors relating to outcome for either the SPADI or QuickDASH at 6 weeks and 6 months are summarised in At 6 weeks only, a better outcome for both measures was associated with the absence, compared to the presence, of pain in the opposite upper quadrant  and no previous, compared to a previous, major operation (shoulder surgery excluded) .At 6 months only, a better outcome for both measures was associated with a shorter duration of symptoms, no additional health problems compared to one and in particular two or more and a reduction in pain or increase in the range of shoulder elevation with manual facilitation of the scapula during elevation of the arm .2425A number of clinical examination findings, commonly associated with specific shoulder disorders, were not associated with outcome. For example, (1) restricted passive external rotation, due to pain or stiffness, indicative of a frozen shoulder,Ten prognostic factors were consistently associated with the SPADI and QuickDASH at one or both time point(s). This is the first known study to investigate the association of five of these factors with the outcome of physiotherapy management for shoulder pain. These five factors that were associated with a better outcome include: (1) patient expectation of ‘complete recovery’ compared to a ‘slight improvement’ as ‘a result of physiotherapy treatment’, (2) lower pain severity specifically at rest, (3) the absence of a previous major operation (shoulder surgery excluded), (4) the absence of pain in the opposite upper quadrant and (5) change in pain or range of shoulder elevation with manual facilitation of the scapula during elevation of the arm.For the physiotherapy management of shoulder pain, this multicentre prospective study of over 1000 participants is the first to include a range of biopsychosocial factors with a validated psychological measure and clinical examination findings with predefined standard operating procedures. It is the first study of this magnitude to include patients who start but do not complete their course of physiotherapy. The results are generalisable to the wide range of patients and presentations of shoulder pain commonly seen within physiotherapy practices within primary and secondary care.As part of their treatment, 99% of participants were required to carry out a home exercise programme prescribed by their physiotherapist. Prognostic factors associated with outcome for this active intervention on behalf of the patient may differ from those identified for more passive management options such as surgery or other conservative options.The limitations associated with this study must be acknowledged when interpreting the results. Only prognostic factors significant in three of four models for each outcome and time point were presented. Factors remaining in the models for the transformed and non-transformed outcome data were generally the same with no discrepancies in the direction of association; we presented parameter estimates for non-transformed outcome data to facilitate clinical interpretation.There was a differential non-response at follow-up. There was a greater likelihood of missing outcome data for younger participants and those not partaking in leisure time physical activity. This may have decreased the power of the study to detect a more consistent association of these factors with outcome and represent a potential source of bias. Similarly, low numbers of patients with extreme anxiety and depression participated in the study, which decreased the power of the study to detect an association between anxiety and depression and outcome.Baseline disability and pain self-efficacy have been investigated in previous studies: in our study, higher disability at baseline was associated with higher disability at follow-up, which is consistent with three previous studies.Not being in employment due to redundancy, unemployment or disability was significantly associated with poorer outcomes for the QuickDASH at 6 weeks and for both measures at 6 months. Heterogeneity on a number of levels, in particular differences in the case definition of comparator groups, inhibits direct comparison with the two additional studies for which this has been investigated,Symptom duration and comorbidities have been investigated in previous studies. Of five studies investigating an association between symptom duration and end point scores, two demonstrated that a longer symptom duration was associated with a poorer outcome,The most consistent factor associated with outcome in our study, patient expectation of recovery, is recognised as a prognostic factor for a wide range of other health problems.Shoulder pain severity at rest was another consistent factor associated with outcome. Shoulder pain severity has been investigated as a prognostic factor in four previous studies,This is the first study to investigate the prognostic value of symptom modification with scapular facilitation techniques.This study provides evidence to support the NICEPhysiotherapists stated their expectation of change using a similar seven-point Likert scale to that completed by their patient. However, physiotherapists completed the scale following rather than prior to the assessment. The physiotherapists' expectation of change was not associated with outcome. Nor was it associated with the patient's expectation of recovery. This suggests that physiotherapists' predictions of how well a patient will respond to treatment cannot be relied on. A more formalised approach is required.We suggest that baseline psychological factors such as pain self-efficacy and patient expectation should be formally assessed using standardised measures. These psychological factors have a prognostic value, not just at extreme values, but also throughout a range of possible values and responses. For example, there was a statistically significant difference in outcome at 6 months between patients rating expectation of recovery on adjacent points of the seven-point Likert scale: patients who expected a ‘complete recovery’ had better outcomes compared to those who expected to ‘much improve’.We did not investigate the effect of different treatment approaches. However, poorer outcomes in individuals with certain factors might suggest that addressing these factors could result in better outcomes. We, therefore, encourage doctors and physiotherapists to consider integrating psychological interventions within their everyday practice to manage all patients with shoulder pain. For example, motivational interventions used by physiotherapists can improve self-efficacy for a range of musculoskeletal and medical problems,A multidisciplinary team may enhance outcomes for some patients. For patients with lower self-efficacy or only a slight expectation of recovery, who have not responded to psychological interventions within the GP or physiotherapist's practice, we suggest early involvement of psychological experts. For patients complaining of resting shoulder pain or pain associated with other comorbidities, particularly previous major surgery, we suggest treatments aimed at pain relief. Given the magnitude of association between unemployment and a poorer outcome from physiotherapy, we also encourage physicians to consider referral to employment support services for patients unable to work due to their shoulder pain. We also suggest that patients not engaging in leisure time physical activity are encouraged to do so and those taking part are encouraged to remain doing so, in some capacity.Higher patient expectation of recovery as a result of physiotherapy, higher pain self-efficacy, lower pain severity at rest, and for patients not retired, being in employment or education were associated with a better outcome.Clinical examination findings suggestive of a structural diagnosis were inconsistently associated with outcome.Physiotherapists’ predictions of how well a patient will respond to treatment cannot be relied on. A more formalised approach is required.Psychosocial in addition to biomedical information should be formally assessed and feed into decision-making about management options.Physicians referring patients to physiotherapy should reinforce a positive expectation of recovery as a result of physiotherapy treatment.Psychological factors, such as patient expectation and pain self-efficacy should be formally assessed using standardised measures.Patients with resting pain and/or pain arising from other comorbidities may be provided and guided on appropriate pain medication or other pain-relieving treatments prior to or at the same time as referral to physiotherapy.A multidisciplinary approach should be considered for patients with more extreme psychological responses associated with a poorer outcome, resting shoulder pain not responding to medication provided by their physician, and patients not currently employed or in education but of working age.Future research is needed to externally validate a clinical prediction model based on the prognostic factors identified in this study including the question of which prognostic factors can be successfully modified with treatment delivered by physiotherapists and if this improves outcome. Future research should identify which factors predict how subgroups of patients are likely to benefit from individual treatments offered by physiotherapists. This would form the basis of personalised or stratified healthcare for the treatment of shoulder pain.


Currently many TKA protocols rely on multimodal analgesic protocols with patient-controlled analgesia systems that administer opioids through a patient controlled IV infusion pump, in addition to concomitant peripheral nerve blocks and local anesthetics. Although effective, PCA IV opioids do not provide optimal results with fast track rehabilitation protocols.The present is a retrospective study comparing the novel sublingual sufentanil PCA system (SSTS) to our standard of care foreseeing continuous femoral nerve block (cFNB) within a multimodal analgesic in a TKA fast-track protocol. The study evaluated 95 patients on SSTS (SSTS group) and 87 on cFNB (cFNB/control group) and collected data on numeric rating scores for pain from day 1–3 after surgery , both at rest (NRS) and during movement (mNRS), patient’s ability to walk, need for supplementary analgesia (rescue dose), occurrence of adverse effects, length of hospital stay, and usability rating for SSTS by both patients and hospital staff.p <  0.001). Rescue doses were needed by 5% of SSTS patients vs 60% of cFNB. The fewer adverse events and lower pain scores for the SSTS group were associated to a notably better ability to ambulate, with all patients (100%) of the SSTS group being able to stand and walk for 10 m from T1 on; patients in the cFNB group showed a slower recovery with only 40% being able to stand and walk on T1, 70% on T2 and 85% on T3. All patients of the SSTS group had a length of stay of 4 days (day of surgery plus 3 after) as foreseen by the fast track protocol, in comparison only 36% of cFNB. Lastly, patient and nursing staff judged SSTS easy to use.NRS at rest was lower in the cFNB than in the SSTS group for all 3 days after surgery, whereas mNRS scores were lower in the SSTS group at all time points measured. Adverse effects were significantly fewer among patients of the SSTS group (6% patients) than those of the cFNB (74% patients) (Our experience suggests that SSTS is a valuable strategy for routine postoperative analgesia following TKA in the context of a multimodal analgesic approach within the fast-track setting. In recent years, a number of surgical procedures, including total knee arthroplasty (TKA), have turned to the fast track approach , which has been acknowledged as the most effective in TKA , which are extensively used concomitantly with peripheral nerve blocks and local anesthetics, are also less suitable in the setting of fast track recovery. Furthermore, in the case of local infiltration anaesthesia (LIA) –despite it being effective in controlling pain on the day of surgery– it is not effective in management of movement-evoked pain in the days following surgery.Hence, driven by the need to overcome the limits to early rehabilitation posed by LIA and abductor canal block in the fast track protocol, our department decided to implement a relatively new patient-controlled analgesia system Zalviso® , approved for marketing in Europe in 2015. Zalviso is a novel drug/device delivery system for in-hospital management of moderate-to-severe post surgical pain. It provides patients with single-dose 15 μg sufentanil nanotablets with a 20-min lockout period. Upon need, the patient can access a sublingual nanotablet by pressing the handheld ZALVISO® dispenser, which is pre-programmed by the manufacturer and thus cannot be altered by users , and which does not require the patient being connected to any IV infusion pumps   to the new SSTS Zalviso®.This was a retrospective observational study on a representative group of typical TKA hospital patients undergoing unilateral total knee replacement under perioperative multimodal analgesia, including data from patients consecutively admitted to the Hip and Prosthetic Orthopaedics Department, Humanitas Research Hospital in Rozzano  between July 2016 and May 2017. Specifically, the study compared a group of TKA patients receiving the new SSTS postoperative analgesia (SSTS group) versus a group of patients with matching characteristics who were treated according to our standard pain-management protocol by multimodal analgesia, i.e. cFNB, plus administration of oxycodone/naloxone, and ketoprofene (cFNB group/control).Inclusion criteria were limited to age > 18 years, suitability for a fast track approach, and the patient’s ability to describe and report pain; whereas exclusion criteria were the administration of general anaesthesia during surgery, admission to the intensive care unit, history of chronic pain other than preoperative knee pain, alcohol or drug addiction, and cognitive or psychiatric disorders. All data used within the study were obtained through the patients’ hospital records and included patient demographic data, all data regarding intraoperative management and postoperative analgesia, and pain scores.In accordance with our hospital protocol, general anaesthesia was not foreseen for this procedure. Both groups received sub-aracnoid anesthesia with bupivacaine 12/15 mg prior to surgery and LIA with ropivacaine 400 mg around the surgical wound immediately after surgery. In addition to these, the routine surgical protocol also included administration of ondansetron 4 mg, metoclopramide 10 mg, tranexamic acid 1000 mg in 200 ml saline , methylprednisolone 125 mg, and ranitinidine 50 mg.After surgery, patients in the SSTS group received sublingual sufentanil SSTS (15 μg upon need) plus etoricoxib 120 mg (1 capsule/24 h) or –in the case of intolerance to FANS– paracetamol 1 g three times a day. Conversely, patients treated according to our standard protocol (cFNB group/control) underwent continuous femoral nerve block (cFNB) at the inguinal canal with continuous infusion of local anaesthetic (ropivacaine 0.125% 5 ml\h) and oxycodone/nalaxone10 mg/5 mg tablets twice daily plus ketoprofene 100 mg 2 capsule/24 h or, in the case of intolerance to FANS, paracetamol 1 g three times a day,In the event pain was not properly controlled (NRS ≥4) by prescribed analgesic therapy, patients of both groups received a “rescue dose” of oral morphine 10 mg, upon need.The primary objectives were to (i) assess the efficacy of SSTS in fast track recovery , and (ii) safety in comparison to cFNB. Secondary objectives of the study were to gather feedback on the ease of use of the Zalviso® drug delivery device system by healthcare staff and patients.Endpoints measured were pain intensity at rest and upon movement, ability to stand and walk, number of discontinued treatment, number of side effects/adverse events, number of rescue doses length of hospital stay and usability scores. Specifically, pain was measured using the NRS numeric rating scale . Movement-evoked NRS (mNRS) was also recorded in response to passive motion and in active transition to sitting and standing positions, and in motion. Pain scores available in patient records for both groups were the mean scores for T1 throughout T3 (T1 to T3 are the 3 days post surgery). For the SSTS group, further evaluations were recorded for the day prior to surgery (T-1), the day of surgery at delivery of the SSTS device to the patient (T0), the first administration of sufentanil sublingual nanotablets, and after 2, 4, 8 and 16 h from the first nanotablet.The assessment on usability of the drug delivery device by staff and by patient was assessed through semi-quantitative data including time for preparation, number of doses administered and subjective evaluation scales  measuring the nurse’s ease of use of the device, as well as the patients’ ability to understand the functioning of device and of putting instructions into practice.In accordance with our hospital regulation, the study was submitted to and evaluated by the internal Ethics Committee (Comitato Etico Indipendente – IRCCS Istituto Clinico Humanitas). As to informed consent, all patients being referred to our Institution signed a written informed consent for data analysis and result reporting upon admission.All data are reported as descriptive variables, normal distributed data should be displayed as means ± standard deviations (SD) and non-parametric data as median . Accordingly, to compare distributions between groups, we used T-test, non-parametric Kruskal-Wallis test or chi-square test. Pairwise post-hoc comparisons were performed with unpaired-samples t-test, Mann-Whitney test or chi-square test, as appropriate; in all cases we used a Sidak correction. Chi-square test was computed with Yates’ continuity correction for 2 × 2 contingency tables.Pain intensity was evaluated through analysis of variance (ANOVA) for repeated measures with multiple comparisons versus the baseline. The baseline value is the average between the value at initial dose and any following (maximum 4) provided during the first 24 h and, for each visit , the average pain intensity between the four . Pain intensity between the groups was also evaluated using the Kruskal-Wallis test comparing the baseline observation with the most recent available data.p <  0.05 (5%). Data were analysed using SAS 9.4 SAS Institute Inc. 100 SAS Campus Drive Cary, NC 27513–2414, USA.Statistical significance was set as The study evaluated a total of 95 patients using the SSTS drug/device Zalvisio® (SSTS group) and compared it to a control group of 87 patients on continuous femoral nerve block (cFNB group) which was representative of the typical TKA hospital population, presenting similar characteristics as to age, comorbidities, type of operation with the SSTS group, differing limitedly to the analgesic technique received Table . There wOverall, patients from the SSTS group had significantly fewer adverse effects , a slightly better pain control upon movement, and lesser need for supplemental rescue dose (5% vs 60%) compared to the cFNB group, which altogether allowed patients in the SSTS group to ambulate earlier after surgery and achieve the goals set by the fast track protocol. Moreover, patients from the SSTS group were all dismissed from the hospital within the three days from the intervention (LOS = 4 days) in keeping with the fast track protocol, compared to only 36% of the cFNB patients with the remaining having a median LOS  of 5(2).p < 0.05) throughout T1- T3 compared to SSTS  (Table P < 0.01) as evidenced by the paired t-test.With specific reference to pain perception during the postoperative period T1 to T3, the cFNB group (control) had lower NRS at rest  was slightly less than 48 h, with no patients using SSTS for more than 72 h. On T0, the mean time from receiving the device and self-administration between tablets was 1.5 h to the first tablet, 5 h between the first and the second tablet, 3.5 h between the second and third tablet, and 2.5 for the fourth tablet. The mean consumption of tablets was 9 tablets during T0 (the day of surgery), 6 during T1, and 3 during T2, with all patients (97%), using less than (or at most) one cartridge (40 sufentanil nanotablets) throughout the entire postoperative period. While most patients were able to discontinue treatment early (before 72 h) given the absence of moderate-severe pain, 2 patients (2.1%) discontinued SSTS due to ineffective pain relief, and 2 (2.1%) due to the malfunctioning of the device.Rescue doses were required less often in the SSTS group (5% of SSTS patients) than the cFNB control .p < 0.001) in the SSTS group, with 7 events (7.4% of patients) in the SSTS group, compared to 132 events (73.6%) in the cFNB group  as shown Table Among the adverse effects reported were post-operative nausea and vomiting (PONV), erythema, numbness, and dizziness. The number of AEs was significantly lower p < 0.00 in the SThe SSTS drug/delivery system in our population was typically prepared by a nurse, with a mean set up time 2.7 min (±1.8) Table . Most ofThe present study evaluated the efficacy and safety of Zalviso® sublingual sufentanil tablet system (SSTS) in comparison to our standard of care for postoperative pain management, a multimodal analgesic approach with cFNB, in a population of TKA patients managed according to fast track rehabilitation principles. Results from the study confirmed the efficacy and safety of the SSTS in TKA –in agreement with previous studies in literature– providing herein new evidence specifically in the fast track setting , compared to the cFNB group (7 events in the SSTS vs 132 in the cFNB) and the satisfactory control of pain which determined the patients’ (i) ability to comply with the fast track rehabilitation program and (ii) their fitness for dismissal on T3, the third day after surgery.Overall, the adverse effects were significantly fewer in the SSTS group compared to the cFNB group. The larger number of AEs experienced by patients in the cFNB group appeared most likely to be due to the higher rate of adjunctive analgesic “rescue doses”  needed to compensate for the scarce management of pain, and thus to the higher exposure to opioids. Certainly, this was to some extent linked to analgesic gaps and adjustments to the analgesic protocol ensuing from catheter dislodgement.Another key factor in the better outcome for patients receiving SSTS was also the good control over pain. Patients using Zalviso® (SSTS group) reported lower pain upon movement than cFNB patients (control group) at all times measured, and pain was properly managed also when LIA had worn off. Despite the difference in pain scores between the two groups was minimal in terms of absolute values, these were, however, clinically relevant as well as meaningful to the patient in terms of ambulation and function. As suggested by several authors, evaluations derived from patient reported outcomes on pain should be considered within a broader concept of “minimally important differences” and of “thresholds of improvement” and should be considered when evaluating success of interventions . In fact, rescue dose was needed for 60% of patients on cFNB compared to only 5% of those using SSTS.1/2Ke0 of 6 min compared to 168 min with morphine), and its sublingual administration provides rapid onset of analgesic activity with a constant median plasma half-time following repeated administration   and its functioning easy to explain to patients. While these aspects may appear trivial, from an operational point of view they translate in saving of time, easier streamlining of procedures, and better prevention of human error   the effectiveness in managing movement-evoked pain which allowed the patient to ambulate right from T0 (i.e. same day of surgery) and the days after surgery, (ii) the reduction of negative stimuli  that could interfere with the fast track rehabilitation, (iii) the high patient compliance to analgesic treatment, (iv) the simplicity of use for both health professionals and patients.With no doubt, these results must be considered as evidence of real-life clinical practice, and cannot have the strength of a randomized controlled trial. Future targeted randomized studies could further evaluate SSTS by addressing parameters such as “minimally important difference” and “threshold of improvement”, as suggested recently by several working groups on patient reported outcomes on pain. Nonetheless we believe this study provides useful information on pain management in the fast track approach of TKA setting.In conclusion, results from this pilot study proved Zalviso® SSTS to be particularly suitable in the multimodal analgesic approach in a fast track protocol. The fewer adverse events and lower pain scores for the SSTS group were associated to a better ability to ambulate early after surgery compared to cFNB, which allowed patients to go through the fast track management and be dismissed on the third day after surgery.From the point of view of principles of pain physiology, the high levels of efficacy for the management of dynamic pain represents somewhat an interesting outcome –particularly when compared to the other standards of pain management, such as regional continuous techniques.


We studied 8 patients with spinal cord stimulation (SCS) devices which had been previously implanted to treat neuropathic chronic pain secondary to Failed Back Surgery Syndrome. The aim of our study was to investigate the effects of SCS on posture and gait by means of clinical scales  and instrumented evaluation with 3D Gait Analysis using a stereophotogrammetric system. The latter was performed with the SCS device turned both OFF and ON. We recorded gait and posture using the Davis protocol and also trunk movement during flexion-extension on the sagittal plane, lateral bending on the frontal plane, and rotation on the transversal plane. During and 30 minutes after the stimulation, not only the clinical scales but also spatial-temporal gait parameters and trunk movements improved significantly. Improvement was not shown under stimulation-OFF conditions. Our preliminary data suggest that SCS has the potential to improve posture and gait and to provide a window of pain-free opportunity to optimize rehabilitation interventions. Chronic pain of moderate to severe intensity occurs in 19% of adult Europeans, seriously affecting the quality of their social and working lives . The preBeneficial effects of SCS on balance and risk of fall have been reported in a study on 11 subjects . A case A biomechanical study in 2005  addresseThe aim of our study was therefore to verify by means of 3D Gait Analysis whether SCS is able to improve posture and gait in FBSS patients.We studied 8 patients with SCS devices which had been implanted to treat neuropathic chronic pain secondary to FBSS. The patients were 4 males and 4 females, mean age 65.3 ± SD years. They had been previously referred for continued pain after spinal surgery to the Pain and Palliative Care Clinic of the Santa Corona Hospital in Pietra Ligure, Italy, for SCS implant. At the time of the implant, patients had been complaining of recurring or persistent leg pain, greater than back pain, despite one or more anatomically successful back surgeries for the same original pain.The year of implant of the SCS device ranged from 2010 to 2014. Four different models of SCS device had been implanted in our 8 experimental patients. The patients' characteristics, the SCS devices and their year of implant, and the scores of the clinical scales used in the study are described in We studied those patients in the Movement Analysis Research Laboratory of the same hospital. The study has been performed in accordance with the Declaration of Helsinki. All subjects provided informed consent to the study approved by the Ethics Committee of the Santa Corona Hospital.Subjects were evaluated with both clinical scales and an instrumented-quantitative evaluation in order to evaluate the effects of SCS in terms of perceived physical functioning, pain, health status, and movement.Before (T0) and after (T1) the stimulation, all of the subjects were asked to fill the Short Form Health Survey-36 (SF-36) , rate tThe SF-36 is a 36-item, patient-reported survey of patient's health. SF-36 includes one multi-item scale measuring each of 8 health concepts: (1) physical functioning; (2) role limitations because of physical health problems; (3) bodily pain; (4) social functioning; (5) general mental health ; (6) role limitations because of emotional problems; (7) vitality (energy/fatigue); and (8) general health perceptions. The 8 scaled scores are the weighted sums of the questions in their section. Each scale is directly transformed into a 0–100 scale on the assumption that each question carries equal weight. Lower scores evidence more disability.The Visual Analogue Scale (VAS) consists of a 10 cm straight line with the endpoints defining extreme limits such as “no pain at all” and “pain as bad as it could be.” The patient is asked to mark his pain level on the line between the two endpoints. The distance between “no pain at all” and the mark then defines the subject's pain.The HAM-D is a multi-item questionnaire used to provide an indication of depression and as a guide to evaluate recovery. The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. Each item on the questionnaire is scored on a 3- or 5-point scale, depending on the item. A score of 0–7 is considered to be normal; scores of 8–17 indicate a mild depression, scores of 18–24 a moderate depression, and scores > 25 a severe depression.Instrumented evaluation was performed in a morning section under two different conditions: with the SCS device turned off (OFF) and on (ON).All subjects were asked to switch off the device 12 hours before the evaluation. In the morning, they were first evaluated with the SCS device turned off (OFF). Then, the device was switched on (ON) and, after 30 minutes of SCS, they were evaluated again. This lapse of time was chosen for the patients to fully perceive the effects of the stimulation (paresthesia).Instrumented movement analysis was performed with a stereophotogrammetric system . The system is composed of eight infrared cameras  and four force platforms .We recorded the position of 22 reflective markers positioned on the patient body according to the Davis protocol  for 3D gAfter measuring anthropometric parameters  subjects were first asked to stand still on a force platform for 5 seconds; then, they were asked to walk, at their preferred speed on a 9-meter walkway at least five times to obtain a minimum of three trials complete of kinematic and kinetic data.Trunk kinematics were assessed under three different movement conditions: flexion-extension on the sagittal plane, lateral bending on the frontal plane, and rotation on the transversal plane.In the flexion-extension task, subjects were asked to bend forward as much as possible from an upright position with the arms loose towards the floor and the knee extended and then to lean backwards to the maximal extension.In the lateral bending task, subjects were asked to bend the trunk sideways in the frontal plane with the arms adducted and knee extended.In the third task, rotation in the transversal plane to the maximal excursion was required.Each trial consisted of three complete movements . Subjects performed this evaluation test with their feet placed on a force platform in order to register Center of Pressure (CoP) data during movement. We record also the position of nine markers placed on the spinal processes  and bilaterally on the acromion and the superior iliac posterior spine .Gait and kinematics data were analyzed by SMART Tracker and SMART Analyzer  and MATLAB .t-test was performed for the comparison between stimulation OFF and ON. Data were considered significant with p < .05.Student's Comparison at T0 and T1 of all self-reported scales of health status showed an improvement in performance and a reduction of negative symptoms in all subjects (p = 0.0032), evident in both legs and in both stance and swing phases. As for cadence, a general improvement was shown in all of the subjects, except for 2 (subjects 1 and 4), where statistically significant reduction of the cadence was recorded. A small but significant increase in step length was evident in all of the subjects during ON. Also, improvement in stride length was demonstrated. Finally, a significant improvement of the left-right symmetry of the gait cycle, due to an increase of the stance phase duration on left side during ON, was evident in all subjects. Those improvements produced an overall reduction of the stance phase and an increase of the swing phase of the gait cycle, more evident on the unaffected side , we considered both the vertical and anterior-posterior components.We considered the maximum peak of the GRF vertical component. Comparison between OFF and ON showed inconsistent increases in vertical force peaks; therefore no statistical significance was evident. Different strategies were observed: in 3 subjects  the pattern was normal during OFF and did not change during ON; in 1 subject (number 2), both limbs showed an increase of both first and second peaks during ON; in 2 subjects (numbers 5 and 7) an improvement on the affected side was present during ON. During ON, no differences on the affected side were observed in 1 subject (number 1), and in another subject (number 8), only a small increase in the vertical force peak was evident.p = 0.0517) for the right limb and +0.78 ± 0.25 SE (p = 0.01) for the left , an increased ROM in the coronal plane corresponded to an increase in the vertical axis but also to a higher forward shift of the trunk. In 2 subjects (numbers 5 and 7), an increased ROM in both vertical and coronal components and a reduction of the forward bending were evident. One subject (number 3) showed an increased ROM only in the coronal plane and in another subject (number 1), no difference in ROM was evident between OFF and ON.Three subjects  had the same pattern as in the contralateral bending. In three subjects , an increase in the vertical and lateral ROM and a decrease in forward bending were evident. One subject (number 3) showed an increase in lateral and forward bending components but a decrease in the vertical one. One subject (number 6) showed a reduction in the vertical one.Other indexes, such as path length, duration, distance, smoothness index jerk (not shown in the paper), and speed, were also analyzed. However, speed was the best index to demonstrate the improvement of performance during the ON phase .In our study, patients were evaluated in the morning under two different conditions: (1) stimulation OFF for the previous 12 hours, (2) 30 minutes after the stimulator had been ON. The latter condition served to investigate not only the effects on pain relief, but also the direct impact on gait and posture.Our preliminary data indicate that stimulation positively affects patient's walking and reduces compensatory patterns, as shown by kinematic parameters. This provides some initial evidence that SCS may be useful in providing a window of pain-free opportunity to intensify rehabilitation interventions and to maximize function. This could widen the range of effective interventions of rehabilitation professionals and boost further research in the rehabilitation of complex chronic pain patients.Data from the trunk during ON showed an increase in range of motion and smoothness of the trunk motion during the tasks. A reduced compensatory strategy of the trunk was also evident. Our results provide quantification of the compensations occurring in posture and gait in patients with chronic pain and a deeper insight into the components of gait or trunk control that improve after implant of an SCS device. A better understanding of these mechanisms can help generate tailored and more effective rehabilitation programs. For instance, reduction of ground reaction forces on the unaffected lower limb improves the symmetry of loading, thus alleviating joint overload. From the 3D analysis of the trunk motion, a smoother movement was evident. Meanwhile, the compensation strategies partially persisted, meaning that pain could not entirely account for the modifications observed in movement patterns. These observations have to be taken into account for ad hoc rehabilitation programs.Our preliminary study yields some evident limitations: firstly, the study is performed in 8 patients only, 4 of whom complained of hypoaesthesia and 4 of disaesthesia; secondly, there is a lack of appropriate sham or concealed observation; thirdly, our results refer exclusively to the immediate effects of neuromodulation; and also, different models of SCS device had been previously implanted in our 8 subjects at different times, from 2010 to 2014, which, together with different positioning of the electrodes, depending on the type of pain, may have influenced results. However, modalities of neuromodulation delivery were consistent across the types of devices used and, technically, the devices differed only in recharging capacity and compatibility with MRI investigations. Therefore, any generalization about the clinical utility of SCS in FBBS from our data is premature and needs support from larger and also long-term studies.A multilevel kinetic and cinematic 3D analysis in a small sample of patients with failed back syndrome with SCS implant has provided additional quantitative information regarding posture and gait modifications secondary to spinal cord stimulation.


The probability that a patient will need an MRI scan at least once in a lifetime is high. However, MRI scanning in cochlear implantees is associated with side effects. Moreover, MRI scan-related artifacts, dislodging magnets, and pain are often the most frequent complications. The aim of this study was to evaluate the occurrence of pain in patients with cochlear implant systems using 1.5T MRI scans.In a prospective case study of 10 implantees, an MRI scan was performed and the degree of pain was evaluated by a visual analog scale. Scans were performed firstly with and depending on the degree of discomfort/pain, without a headband. Four of the cochlear implants contained a screw fixation. Six cochlear implants contained an internal diametrically bipolar magnet. MRI observations were performed with a 1.5 T scanner.MRI scans were performed on all patients without causing any degree of pain, even without the use of a headband.Patients undergoing 1.5 T MRIs with devices including a diametrically bipolar magnet or a rigid implant screw fixation, experienced no pain, even without headbands. Cochlear implantation is the treatment of choice for patients with severe hearing loss, and those who have profound hearing loss (deafness affecting one or both ears). So far, about 400,000 patients have been provided with a cochlear implant.MRI observations in cochlear implantees are a longterm problem. Because the fixation of the implant audio processor is magnet–based, MRI scans need special modifications to circumvent possible inaccuracy. On the other hand, previous trials with magnet-free implant systems did not lead to significant acceptance .The internal cochlear implant magnet leads to a number of testing difficulties. The magnet generates significant artifacts, leading to the inability to assess specific ipsilateral structures . Magnet Concerning how specific devices measure rates of pain, Grupe et al.  describeKim observed pain/discomfort in 7 out of 19 cases without performed general anesthesia  describeTherefore, the use of an MRI in a cochlear implantee warrants special consideration. Because all of these side effects are well-known, manufacturers  recommend head bandages for safety reasons for 1.5T , or magnet removal at 3T  or headbands for 3T (Medel Synchro-ny). Generally different from other systems are two MRI-relevant device specifications. One option is to use screws to anchor the implant , and the other is to incorporate a diametrically bipolar magnet  to decrease the force on the implant and therefore prevent magnet dislocations, demagnetization and pain.The aim of this study was to evaluate the occurrence of pain in patients with cochlear implant systems using 1.5T MRI scans.The study was approved by the institutional review board of the Unfallkrankenhaus Berlin, Germany (IRB-ukb-HNO-2016/01). Patients gave their written informed consent for the use of their clinical records in this prospective study.In this prospective case study, from 2014 through 2016, 10 patients under-went a 1.5T MRI observation provided in a tertial referral center with varying cochlear implant types. Six patients were implanted with a Medel Synchrony implant  and a bipolar magnet. The implant was intraoperatively anchored with a absorbable suture. An implant bed was drilled for these cases. Four patients were implanted with an Oticon Neuro ZTI implant . The implant was only fixed with two selftaping screws. An implant bed was not drilled.All examinations were performed in a 1.5 Tesla MR imaging unit  using an 8-channel array head coil. All patients underwent two MRI scans. First the patient was introduced into the MRI scanner with a headband. The headband consists of a tight self-taping wrap with a hard plain piece to prevent dislodging of the magnet. After the evaluation of pain and inspection of the implant area, the patient was introduced into the scanner without a headband a second time.The evaluation of pain was performed with a visual analog scale (VAS) scoring from 0 to 10. Zero indicated the non-occurrence of pain and discomfort. Ten indicated a pain-related interruption during the scan. The questionnaire was used directly after the first and directly after the second scan. Magnet strength was subjectively evaluated by the attraction force of the antenna coil. Magnet displacement was evaluated by the digital control of the implant magnet area.Scanning parameters:TSE T2 2 D: TR: 3300 ms, TE 120 ms, slice thickness 1.5 mm, reconstruction resolution of 0.55 × 0.55 × 1.5 mm, F0 V 120  ×  120. 12 slices.TSE T1 2 D: TR: 550 ms, TE 20 ms, slice thickness 3 mm, reconstruction resolution of 0.23 × 0.23 × 3 mm, F0 V 120  ×  120. 20 slices, matrix size: 400  ×  318.In all patients, two MRI scans at 1.5T were performed without complications, in terms of magnet dislocation and pain. One scan with the headband and one scan without the headband were performed. In all cases, a headband was not necessary to prevent pain or magnet dislocation. The mean VAS with and without head-band, in terms of pain, was 0. The evaluation was performed directly after the scan. Individual data are given  or non-head-related reasons. The probability for an MRI once in a lifetime has been described to be 50–75% . 1.5T MRWhile manufacturers recommend a headband during the MRI scan to prevent pain and magnet dislocation, it has been shown to be ineffective  in many It can be assumed that the mechanism of pain occurrence is related to the magnet movement inside the MRI magnet field which results in a hard-to-contact signal between magnet,periostium and inner skin layer.Clinically the effectiveness of a diametrically bipolar magnet and screwing fixed implant modification to prevent this complication is unknown and therefore the first description of this topic.Medel Synchrony implant includes a diametrically bipolar magnet, which directs itself in the magnetic field of an MRI scanner. This direction was assumed to prevent demagnetization at 3T. The effect on pain prevention is so far unclear. We were able to show that the implant magnet configuration even prevents the occurrence of pain. A magnet dislocation was not observed.The second implant (Oticon Neuro ZTI) includes a rigid implant corpus with a magnet to screw in and out of the corpus. The implant itself is fixed with screws on the skull. This anchor seems to prevent a torsion of implant and magnet to press on the periost and skin. Magnet dislocation could not be observed.The prevention of pain and magnet dislocation is of high importance because these two factors are the most frequent and relevant in the clinical routine.The ability to perform an MRI scan without pain or the risk of magnet dislocation offers the clinician and the radiologist the field to perform 1,5T MRI scans routinely with only some limitations .Patients undergoing 1.5 T MRIs with devices including a diametrically bipolar magnet or a rigid implant screw fixation have no pain, even without headbands.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.