Neuropathic pain (NP) can occur as a chronic complication of leprosy neuropathy. NP epidemiology and its impact on patients have not been well documented. This study investigates NP prevalence and impact in the years after patients are declared “released from treatment” (RFT) following multidrug therapy (MDT) completion.In this cross-sectional study, 85 RFT patients were recruited within leprosy referral services in Nepal. The Douleur Neuropathique 4 Questionnaire (DN4) was used to screen for NP. Pain severity, impacts on patients’ daily activities and mental health were measured by using the Brief Pain Inventory (BPI), Screening of Activity Limitation and Safety Awareness (SALSA), and General Health Questionnaire-12 (GHQ-12) respectively.p = 0.023) and current reactions (p = 0.018) were significant risk factors for NP. Patients with NP suffered significantly higher intensity pain (p = 0.023) and daily life interference (p = 0.003) and were more likely to have moderate to extreme daily activity limitations (p = 0.005). 13 (43%) exhibited psychological distress, and medications only reduced moderate degree (50–60%) of pain.96% surveyed had been treated for multibacillary leprosy. 44 (52%) complained of pain of which 30 (68%) were diagnosed with NP. NP was not associated with age, gender, or presence of skin lesions or nerve symptoms at leprosy diagnosis. 70% of patients with NP had either history of or ongoing reactions and 47% had grade 2 disability. Nerve tenderness (In our study, 35% of RFT patients had ongoing NP. Risk factors include nerve tenderness and reaction. They suffer from more daily life interference and psychological distress. Leprosy patient care should include recognition and management of NP. Leprosy could present with chronic neuropathic pain, which might severely disturb daily life and mental health of leprosy-infected patients. This complication could also occur even years after antibiotics therapy completion, and we noticed that it is associated with recent leprosy reactions and nerve tenderness on physical examination. This is the first study that describes the epidemiology of neuropathic pain in leprosy patients in Nepal. More than one-third of leprosy patients who had completed multidrug therapy, are still suffering from neuropathic pain, and this study demonstrated that it has caused a great impact to their daily activities and psychological status. Therefore, prompt recognition and management of neuropathic pain are mandatory while taking care of the patients with leprosy. Mycobacterium leprae (M. leprae). It is characterized by the inflammation of skin and nerve, which could lead to disabling peripheral neuropathy. Since the introduction of multidrug therapy (MDT), leprosy became a treatable disease; and its prevalence decreased globally over the past two decades. However, it continues to persist as an important public health issue in endemic areas [Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by ic areas . As one ic areas .M. leprae which can leave persistent antigen capable of stimulating inflammatory episodes years after cure. Inflammatory or immune complication episodes are called leprosy reactions and are classified into three types: neuritis (nerve involvement only), Type 1 reactions  and Erythema Nodosum Leprosum . Leprosy reactions can affect up to 30–50% of leprosy patients and can, therefore, initiate or progress leprosy neuropathy at any time before diagnosis, during treatment, and even years after MDT [Nerve involvement in leprosy, or leprosy neuropathy, is primarily caused by the infection of Schwann cells by fter MDT .M. leprae burden [Clinically, leprosy neuropathy can present with nerve thickening, sensory, autonomic or motor impairment and pain. The most frequently affected peripheral nerve is the ulnar nerve, and multiple nerve involvement is common especially in patients with high e burden . Neuropae burden .As a non-visible and possibly late complication, NP can be difficult to diagnose; and its mechanisms are different from nociceptive pain. Continuous intraneural inflammation is believed to be the cause of small-fiber nerve damage, which could result in central and peripheral sensitization leading to chronic pain , 8. MeanStudies in Brazil have demonstrated a prevalence of about 56% to 64% for NP in all leprosy patients, clinically defined as characteristic pain with associated symptoms along a leprosy-affected nerve distribution –14. Howep < 0.001) and psychological health (p = 0.04) domains compared to patients with nociceptive pain [The presence of NP can severely affect a patient’s quality of life and generate psychological distress , 18. Appive pain .p < 0.05) [In terms of activity limitation, Arco et al. found about 90% of leprosy patients with NP had Grade 1 or 2 disability, and there is an association between NP and degree of disability ( < 0.05) . Althoug < 0.05) , only on < 0.05) . The stuThus, NP is an important complication of leprosy which is usually associated with negative impact on patients’ daily life, physical and psychological well-being. The prevalence of NP in people affected with leprosy has not been studied in many endemic countries, including Nepal. We hypothesized that NP remains a severe problem in Nepalese RFT patients. In order to evaluate this population, RFT patients associated with a referral hospital were interviewed and screened for NP using the DN4 then evaluated with the short form of Brief Pain Inventory (BPI-short) for pain severity; Eye, Hand and Foot (EHF) assessment and WHO grading for disability severity; SALSA for impact on activities; the General Health Questionnaire-12 (GHQ-12) for psychiatric morbidity alongside collection of leprosy demographics obtained from medical chart review.This cross-sectional observational study was conducted using screening tools and questionnaires to obtain quantitative data from RFT patients who had completed MDT at Anandaban Hospital in Kathmandu, Nepal. The hospital is the central referral hospital for leprosy complications management in Nepal with a patient base reporting from across the nation. Purposive sampling of RFT patients was performed in one month period (August of 2016) based on medical records from the inpatient ward, outpatient clinic and, the monthly satellite leprosy clinics in the southern flatlands (Terai) region.The following criteria were employed for the recruitment: leprosy patients 18 years old or above, who completed MDT (RFT) and agreed to sign voluntary informed consent to participate in the study. This study had been approved by the Ethics Committee of the London School of Hygiene and Tropical Medicine  and the Nepal Health Research Council .All patients were interviewed in Nepali or Hindi language according to patient preference. Demographic data and a detailed history of leprosy were collected from the medical chart and interview. Comprehensive leprosy diagnosis according to WHO definitions had been based upon clinical exam with lesion count, physiotherapist exam for neuropathy, slit skin smear reports for bacterial index and skin biopsy histopathology. Leprosy is diagnosed clinically in patients with one or more of the following signs: anaesthetic skin lesions, thickened peripheral nerves, or acid-fast positive in skin smear or biopsy.  The WHO All patients were asked about a history of leprosy-related pain. However, only the patients who reported current pain were assessed by the DN4 questionnaire for NP and required to complete BPI-short for the evaluation of pain severity and inventory of medications taken for pain control. BPI-short includes a body chart for the localization of the area with pain, four severity items with numerical pain rating scale, a measure of response to medications and an evaluation of pain interference with seven items. Regarding the DN4 criteria, light finger touch and Semmes-Weinstein monofilaments were applied to the area of pain to determine touch hypoesthesia and pinprick hypoesthesia respectively . Cotton All patients, with or without current pain, were asked to complete the SALSA and the GHQ-12 questionnaires for the assessment of daily activity limitation and psychiatric morbidity, respectively. Both questionnaires had Nepalese versions available that had previously been used in leprosy investigations –29. The In accordance with DN4, NP was defined as pain with a score of 4 or more based on the DN4 criteria (DN4 ≥ 4) . There ap-value < 0.05 was considered as significant evidence. Variables with a p-value less than 0.05 were chosen for multivariate logistic regression, using the stepwise forward method.Statistical analyses were performed by using commercial statistical software STATA version 12.1 . Comparisons between NP and patients without NP or non-NP group were analyzed using the Chi-square test or Fisher’s exact test for categorical variables, and t-test or Mann-Whitney test for continuous variables. A 99 RFT patients were initially screened from hospital wards or various clinics within Nepalese leprosy referral services in August of 2016. Six patients under 18 years old were excluded as were 6 patients with severe hearing impairment due to aging and 1 patient who understood neither Nepali nor Hindi. Only 1 eligible patient refused to participate.Following informed consent, 85 RFT patients were examined and questioned. The mean age was 43 ± 14 years and 64% (54/85) were male. Most RFT patients  had MB; and Ridley-Jopling classifications were primarily 44% (37/85) borderline tuberculoid (BT), 21% (18/85) borderline lepromatous (BL) and 25% (21/85) lepromatous (LL). Most  were within five years of MDT completion. Just over half  had a history of reactions, and one-third  were in reaction at the time of interview: 17 with ENL, 3 with T1R, and 9 with neuritis. 66 (78%) had NFI and 47 (55%) had grade 2 disability (G2D).65 (76%) of RFT patients had experienced leprosy-related pain in the past. During the interview, 44 (52%) complained of current pain and 30 (35%) had NP according to DN4 criteria . 14 of tIn RFT patients with NP, 21 (70%) had nerve thickening and 12 (40%) had nerve tenderness on physical examination. The ulnar nerve was the most predominantly affected nerve in our study population . The preOf the symptoms tested by the DN4 questionnaire, the most common was tingling , followed by burning  and numbness  . On physp = 0.003). More than half had a moderate to severe degree of interference in general activity, mood, walking ability, normal work, sleep and enjoyment of life  suffered from moderate pain and 37% (11/30) with severe pain. The mean worst pain score was higher in NP compared to non-NP RFT patients (6.5 ± 2.8 vs. 4.4 ± 3.1). Concerning pain interference, those with NP had a moderate degree of daily life disturbance with a mean interference score of 5.2 ± 2.7, comparing to that of non-NP group . The most common problem in RFT patients with NP was walking barefoot, as 80% found it difficult or they just physically could not do it (p = 0.013). However, the mean EHF score and G2D rates were similar in both groups. This result highlights that even with similar degree of disabilities, those with NP experienced more activity restriction.In RFT patients with NP, 83% (25/30) had some level of activity restriction in their daily life and nearly half  had moderate to extreme limitation . In compot do it . SALSA sp = 0.252).With the GHQ-12, the mean score for all RFT patients was 10.2 ± 7.7 when using the Likert-type scale. A cut-off point of 11 was used to identify patients with psychological distress. 30 (35%) RFT patients were found to have some degree of psychological distress, of which 13  also had NP. Only 20% (6/30) of them had current reaction, but 73% (22/30) had G2D and 50% (15/30) had moderate to extreme activity limitation. 43% (13/30) of RFT patients with NP demonstrated GHQ-12 scores that indicated psychological distress compared to 31% (17/55) of RFT cases without NP; however, this difference was not significant  and current reactions .Within this cohort, NP was not associated with any presentation variables taken at leprosy diagnosis, including: gender, age, classification, presence of skin lesions or nerve involvement . At the Although leprosy is known for neuropathy leading to sensory loss, pain is a common complaint in patients with leprosy and often clinically ignored in standardized assessments . Within Differentiation between nociceptive pain and NP is important as therapeutic options may vary. However, a patient and field-friendly standardized screening tool could be helpful for leprosy clinicians. By using the DN4 questionnaire, we found that tingling  was the most common term used by RFT patients (90%) to describe NP, followed closely by burning (80%) and numbness (80%). However, this result could perhaps vary depending on cultural and language inferences across different endemic populations. In addition, the DN4 has been shown to sometimes underestimate NP prevalence with a predictive value of 86% or even lower in some settings , 15. ThePain measurement is crucial to understanding the severity and effects of NP. Within our RFT patient group, the BPI-short did provide a quantitative method of pain measurement, including response to medications. Our study demonstrated that NP severity and related interference in daily life is much more severe than with other types of pain reported. Moreover, our RFT patients reported only moderate response to tricyclic antidepressants and anticonvulsants, which are regarded as the first-line treatments for NP. A recent study by Raicher et al showed that the pain characteristics of NP due to leprosy are similar to NP cause by other etiologies, and their management should not be different . HoweverIn our study, we used SALSA scores to measure the degree of activity limitation for correlation with NP. Compared to previous studies, a lower proportion of RFT patients with NP had moderate to extreme limitation in our study (46.7% vs. 66.7%) . RegardlPsychological morbidity is known to be associated with both leprosy and NP , 32, 33.M. leprae and its antigenic residues to persist along peripheral nerve pathways creates neuropathic vulnerability for all patients, although risk for occurrence would be anticipated to be similar to reaction development risks  [The ability to predict which leprosy patients may suffer NP after RFT may be limited, as none of the other variables from initial leprosy diagnosis demonstrated association. Mechanisms of NP involve a complicated neural pathway from peripheral afferent nerves to the central nervous system. The potential for e loads) . TherefoFinally, our analysis revealed that nerve tenderness and ongoing reactions are significant risk factors for the development of NP. The study by Lasry-Levy et al. in India also demonstrated that nerve tenderness is a risk factor for NP . ConsideThere were limitations within this study. First of all, this was an opportunistic cross-sectional study of RFT patients attending leprosy referral services for ongoing issues; therefore, it likely does not represent NP incidence for all RFT patients. People without any complication after RFT would not attend to the hospital and thus, our study population represents leprosy-affected people that developed more clinical issues. However, it is important to emphasize the importance of NP while taking care of the patients who completed MDT in those settings. Prospective studies with larger sample sizes could improve statistical accuracy for broader estimations.On the other hand, there was risk for some bias within the study. First to mention is the possible underestimation of NP prevalence. Although DN4 has a relatively good predictive accuracy for NP, it might fail to detect NP in 10–20% of patients compared to clinical diagnosis according to the IASP guideline . HoweverNevertheless, our results clearly emphasize the importance of pain and NP in regard to leprosy clinical care. Foremost, a significant proportion of RFT patients suffer from NP years after technical cure; therefore, NP should be more often considered during formal assessment. Appropriate patient counseling to set realistic expectations prior to RFT could also better prepare patients in advance to report NP and reaction issues early for management, thereby potentially lowering risk for disability development.Our findings demonstrate that even years after RFT, 76% of patients reported history of pain and 52% report ongoing pain, of which roughly two-thirds were found to have NP. Patients with NP suffer from more severe pain and more physical restrictions in their daily life. The response to medical therapy is only moderate. There is also a significant proportion of NP sufferers exhibiting psychological distress, which may require interventions other than pain control.In conclusion, there is currently no method to predict or prevent NP in leprosy patients; and mechanisms of NP development are poorly understood. There is a dearth of evidence for how to effectively treat NP. Randomized controlled trials are needed to provide reliable evidence for NP treatment in leprosy patients and for relevant impact on activity limitations and psychological well-being. To provide comprehensive care, leprosy clinicians need to have contextually appropriate and reliable screening tools for detecting NP and measuring its impact. The DN4 is currently the best single tool for diagnosis of NP, but the tool has limitations and risks of underestimation. Pain measurement indicators such as BPI-short are mandatory to determine pain severity in reference for therapeutic decisions and response management. NP significantly impacts activity limitation and psychological morbidity, for which SALSA and GHQ-12 scores could be used.S1 Checklist(DOC)Click here for additional data file.


BackgroundThe rate of the caesarean section has been on a progressive rise ever since its association with improved fetal prognosis was established. This study was conducted to assess the effect of local wound infiltration with ropivacaine on the postoperative analgesia requirement and pain scores in caesarean section patients.MethodsThis was a prospective single-blinded randomized control trial conducted at the Department of Obstetrics and Gynecology, KRL Hospital, Islamabad, Pakistan over a duration of six months from January 2018 to June 2018. All the women aged 19 to 40 years, who underwent elective caesarean sections under spinal anesthesia, with American Society of Anesthesiologists (ASA) score II, were included in the study and randomized into two groups. The primary outcome studied was the efficacy of ropivacaine in controlling postoperative wound pain compared to no local analgesic. Pain severity was assessed using the visual analog scale (VAS) which was explained to the patient beforehand and which comprised a range of score from zero (no pain) to 10 (worst pain imaginable). Initially, paracetamol 1 g intravenous (IV) was given every six hours, over 24 hours. If pain did not settle on this, ketoprofen 3 mg/kg IV was given every eight hours, and in case of further analgesic demand by the patient, nalbuphine 10 mg was given IV, if necessary. The data was collected on a specific questionnaire and analyzed on the Statistical Package for Social Sciences  version 23.0. A p-value of less than 0.05 was considered significant.ResultsA total of 100 patients were randomized into two groups. Pain scores were significantly reduced in the ropivacaine group at four, six, and 12 hours after surgery. The percentage of patients who requested the multiple doses of IV paracetamol, ketoprofen, and nalbuphine, was significantly lowered in the ropivacaine group as compared to the placebo group (p<0.001).ConclusionsLocal infiltration with ropivacaine during caesarean section significantly reduces the postoperative analgesic requirement and visual analog scores, reducing the incidence of side effects. The rate of the caesarean section has been on a progressive rise ever since its association with improved fetal prognosis was established . WorldwiNowadays multimodal analgesia, which means the use of combination drugs for pain relief with decreased side effects, is in practice . OpioidsRecently preventive analgesia has been introduced, which means intraoperative or postoperative analgesic intervention, is capable of reducing the postoperative pain and further drug consumption . VariousThis study was a prospective single-blinded randomized controlled trial conducted in the Department of Obstetrics and Gynecology, KRL Hospital, Islamabad, Pakistan over a period of six months duration from January 2018 to June 2018. It was conducted after the approval of the hospital’s ethical committee and patients were prospectively enrolled in the study. This was all managed and followed by the same resident doctors in the operation theater and intensive care units for postoperative care. Prior to being enrolled, all patients were well-informed about the purpose and method of the study and only those patients were included who gave written informed consent. All the women aged 19 to 40 years, who underwent elective caesarean sections under spinal anesthesia, with American Society of Anesthesiologists (ASA) score II, were included in the study. Emergency caesarean sections, use of general or epidural anesthesia, contraindication to the use of non-steroidal anti-inflammatory drugs (NSAIDs), history of cardiopulmonary disorders, allergy to the study drugs, drug dependence or history of chronic and neuropathic pain syndrome led to exclusion of the patients from the study.Randomization was performed using random number allocation and patients were divided into two groups, group R (ropivacaine group) and group P (placebo group). All participants received spinal anesthesia under ASA grade II, were operated upon by the same surgical team under standard circumstances so that the bias could be alleviated, and received Pfannenstiel incision with a peritoneal opening. At the time of skin closure, ropivacaine 5 mg/ml (diluted to 20 ml) or 0.9% normal saline 20 ml was infiltrated in the subcutaneous tissue. Half of the volume (10 ml) was injected at the upper edge and remaining half at the lower edge of the incision. Patients were not aware of the group to which they belonged.The primary outcome studied was the efficacy of ropivacaine in controlling postoperative wound pain compared to the placebo group. Pain severity was assessed using the visual analog scale (VAS) which was explained to the patient beforehand and which comprised a range of score from zero (no pain) to 10 (worst pain imaginable). VAS scoring was done by a resident doctor at two, four, six, and 12 hours after caesarean section. Postoperative analgesics were administered either on the patient’s demand or if the VAS was greater than four. Initially, paracetamol 1 g intravenous (IV) was given every six hours, over 24 hours. If pain did not settle on this, ketoprofen 3 mg/kg IV was given every eight hours, and in case of further analgesic demand by the patient, Nalbuphine 10 mg was given IV if necessary.The secondary outcomes were the total amount of analgesic administered to the patient in the first 12 hours, any complications like respiratory depression, nausea, vomiting, paralytic ileus or pruritis, and time to bowel sounds. Patients were also followed for any drug-related complications.All the data was analyzed on the Statistical Package for Social Sciences  version 23.0. The qualitative variables were analyzed by using the chi-square test. Means for quantitative variables like age, weight, pain scores, duration of anesthesia, duration of surgery, and time to first analgesic demand were compared by independent samples t-test. A p-value below 0.05 was considered statistically significant.All the patients completed the study and successfully underwent a lower segment caesarean section including wound infiltration with a prearranged solution. Parturients in the two groups were comparable in terms of age, weight, duration of surgery, and duration of anesthesia as shown in Table Pain scores were significantly lower in the ropivacaine group at four, six, and 12 hours after surgery as shown in Table Our study showed that among the patients who requested for the postoperative analgesia, about 82% of patients in the placebo group required three doses of paracetamol as compared to 44% of patients in the ropivacaine group. Similarly, 14% of patients in the placebo group required three doses of nalbuphine as compared to 10% of patients in the ropivacaine group who required only two doses and none of them required three doses. The results are shown in Table In both groups, the patients were monitored for the presence of nausea and vomiting, paralytic ileus, and pruritis during the first 24 postoperative hours and the findings were recorded on a chart. No case of nausea, vomiting, pruritis or ileus was reported in the study. The urinary catheter was removed after 12 hours of surgery and normal bladder function resumed with no cases of urinary retention noted amongst the participants.Wound infiltration with local anesthetic is an addition to multimodal analgesia approach for postoperative pain relief in a number of surgeries including breast, hernia repair, and laparoscopic procedures . Mainly Nguyen et al. conducted a study determining the efficacy of Pfannenstiel incision infiltration with 7.5 mg/ml ropivacaine for a caesarean section in 2010 by dividing the patients into the ropivacaine group and control group. He concluded that this intervention led to a reduction of 30% in the overall consumption of analgesics, especially opioids in the first 24 hours following surgery. It also significantly increased the time until the first analgesic request by the patient by two hours and 26 minutes. There was no significant difference in the threshold of VAS in the two groups [Another study compared epidural morphine and continuous caesarean wound infusion with ropivacaine for 48 hours postoperatively for pain relief and side effects relief. A total of 58 women were randomly allocated to one of the two respective groups. The results were in favor of the ropivacaine group as better pain relief, lesser side effects, lesser nursing care, and shorter hospital stay was seen (p<0.001) . This waSeveral studies have been conducted comparing the local infiltration of bupivacaine with placebo or other drugs like tramadol for post-caesarean pain relief. One of the studies conducted in Iran by Sahmeddini et al. compared local infiltration of bupivacaine and tramadol. This study concluded no significant difference in pain relief until 16th postoperative hour but after that, the tramadol was statistically significant in reducing the pain after the 16th hour. No significant difference in side effects like postoperative nausea, vomiting, and respiratory depression was observed .In another study conducted in India, Sachidananda et al. compared bupivacaine with a mixture of bupivacaine and tramadol for post-caesarean pain relief. They showed that time for the first analgesic request was delayed in the mixture group compared to the bupivacaine group alone. Additionally, the total diclofenac consumption in the first 24 hours was also reduced in the mixture group and patient satisfaction was more in this group . A localAnother study conducted by Sarwar et al. in Pakistan compared mean narcotic analgesia requirement in patients undergoing caesarean section with and without bupivacaine infiltration. The results showed a significantly lowered mean pain score of 1.98 ± 0.91 in bupivacaine group whereas a mean pain score of 2.8 ± 1.23 in the non-bupivacaine group. While at the same time, mean postoperative narcotic analgesia requirement of 32 ± 51.27 mg in the bupivacaine and 82 ± 84.97 mg in the non-bupivacaine group, with a significant p-value of less than 0.001 was shown. Hence the study revealed that patients with bupivacaine infiltration required significantly lower doses of narcotic analgesia .The limitation of our study included decreased time duration and a small study population.This study concludes that the use of ropivacaine for local wound infiltration at the time of the caesarean section reduces the overall consumption of systemic analgesics in the postoperative period by reducing the pain scores. This also delays the patient’s on-demand analgesic by more than four hours and hence increases the pain-free interval following surgery.


Obesity and radiological severity have been identified to be independent predictors of a low rate of response to viscosupplementation (VS), in patients with knee osteoarthritis (OA). Is that enough to formally refute VS in such patients in whom surgery is sometimes contraindicated?To compare pain and function scores before and 6 months after knee VS, according to the weight status (obese versus non obese), the radiological severity (mild/moderate versus severe) and both combined.− 2), OARSI radiological grade (1–2 versus 3) and OMERACT-OARSI response criteria (Yes/No). WOMAC between-group comparisons  in all patients and in OMERACT-OARSI Responders, were achieved using Mannn-Whitney U test.Post-hoc analysis of a prospective, double blind, randomized, multicentre trial, comparing 2 viscosupplements, in patients with symptomatic knee OA. Patients were classified according to body mass index (BMI < or ≥ 30 kg.p > 0.05). Six months after VS, WOMAC pain decreased significantly in all patient sub-groups . At month 6, WOMAC pain sub-score was significantly lower in non-obese than in obese patients  and in patients OARSI 1–2 versus 3 . However, in responder patients there was no difference in pain score and pain decrease related to the weight status and the radiological score.One-hundred and sixty-six patients were analyzed: 28.3% were obese, 44% were OARSI grade 3, 42,2% were neither obese nor OARSI 3, whereas 14.5% were obese and OARSI 3. At baseline WOMAC pain score did not differ according to the patients sub-groups (These results do not confirm our previous conclusions that recommended not performing VS in obese patients with severe knee OA. Although the chances of being a responder were much reduced in these patients, the benefit of patients who respond to treatment was similar to that of subjects with normal weight and mild/moderate OA. Different pain phenotypes, more than overweight and advanced disease, might be the main reason for the success or failure of VS. Knee osteoarthritis (OA) is a major cause of pain and disability in subjects over 50 years with a significant impact on physical performance and quality of life. Standard conservative therapy for knee OA includes a combination of non-pharmacological and pharmacological approaches , 2. HoweThe aim of the present work was to answer this question by assessing the impact of obesity, radiographic severity and their combination, not in term of response rate but in term of pain improvement and clinical status 6 months after IA-HA injections.The present study was a post-hoc analysis of a prospective, double-blind, randomized, multicenter and parallel-group trial, registered under the name HAV-2012 trial (N° EudraCT 2012-A00570–43). The primary goal of the study was to compare the efficacy and safety of 3 weekly injections of HANOX-M  to BioHA , according to a non-inferiority trial design, in patients with symptomatic knee OA , 27. TheMales and females, aged 40–85, fulfilling the ACR criteria for knee OA , who faiPatients under 40 or older than 85, absence of tibio-femoral JSN on standard X-rays, KOFUS (Knee OA Flare-Ups Score) > 7 , tibial Paracetamol (up to 4 g/day), weak opioids, ibuprofen (up to 800 mg/day) and naproxen (up to 500 mg/day), topical NSAIDs, and symptomatic slow-acting drugs for OA if started at least 2 months before screening and not modified during the study duration. Discontinuation of analgesics was required 48 h before each evaluation visit.− 2), medical history , and concomitant therapies were recorded. Bilateral knee X-rays were performed including standing postero-anterior view, Lyon-schuss view . Between-group comparisons were achieved using Mann-Whitney U test.P values < 0.05 were considered statistically significant. XLSTAT© 2015 software  was used for the statistical analysis.The statistical analysis was performed from the intent-to-treat (ITT) population. − 2. Forty-seven patients were classified as obese (28.3%). Ninety-three patients (56.0%) had OARSI score 1–2 and 73 (44.0%) had OARSI score 3  women, mean age 65.2 [95% CI 63.7–66.8] years, average disease duration 48.7 [95% CI 38.4–59.0] months and mean BMI 27.7 [95% CI 26.9–28.5] kg.mp-values are given in Table At baseline, the average WOMAC pain 0–20) and function scores (0–68) were 9.8 [95% CI 9.3–10.3] and 27.5 [95% CI 25.7–29.4] respectively. At baseline there was no statistical difference in WOMAC pain score according to the weight status, the radiological grade and their combination. All data and 0 and funInversely, WOMAC function score was statistically higher in obese versus non-obese subjects and moreover in obese/OARSI 3 than in non-obese/OARSI 1–2 patients. All data and p-values are given in Table p = 0,006) and in patients with OARSI grade 1–2 versus 3 (p = 0.02). Similarly, the decrease of WOMAC pain over time was greater in patients with OARSI grade 1–2 than in those with grade 3 (p = 0.008). The decrease of WOMAC pain was also greater in non-obese than in obese patients (p = 0.049). Unsurprisingly WOMAC pain decrease was twice greater in non-obese patients with OARSI 1–2 than in obese patients with OARSI grade 3 (p = 0.007). At month 6, the WOMAC pain score, was 85,7% higher in obese/OARSI 3 patients than in non-obese/OARSI1–2 subjects (p = 0.0001).At month 6, 113 patients (68.1%) fulfilled the OMERACT-OARSI responder criteria. WOMAC pain and function scores at baseline and month 6 are given in Tables At month 6, as for pain, WOMAC function score was significantly higher in obese versus non-obese patients, in OARSI 3 versus OARSI 1–2 and, even more in obese/OARSI 3 than in non-obese/OARSI 1–2. A similar trend was found for WOMAC function variation (Table N = 113) there was no significant difference between subgroups  both for WOMAC pain score and WOMAC pain decrease . It is therefore possible to obtain a significant pain improvement in obese patients, even if the chances of achieving an excellent result are lower than in normal weight subjects.Our previous study also showed a strong relationship between obesity and risk of VS failure . SimilarWe previously showed a very low rate of response (about 40%) in patients who cumulated obesity and severe JSN. Interestingly similar trends have been reported after IA corticosteroid injection, in a cohort of 100 patients with knee OA .In our study the decrease of pain was two-fold greater in non-obese patients with mild to moderate JSN than in obese patients with OARSI grade 3 (− 58.2% versus − 28.6%).However, in the sub-group of obese patients with severe JSN who were classified as “responders” according to the OMERACT-OARSI criteria, the WOMAC pain score at month 6 and the decrease of pain over time (3.3 ± .9 and − 6.6 ± 3.4 respectively) did not differ from that of patients with no risk factor (3.2 ± 2.8 and − 6.7 ± 2.3 respectively). These results raise a crucial issue regarding the reasons for the efficacy or non-efficacy of HA injections in patients with severe OA and/or obesity. It is currently unknown whether patients with different pain phenotypes may respond differently to viscosupplementation. For example, in some patients synovitis may be the main cause of pain, while in others the bone origin may be predominant , 40. MorAnother interesting data to point out, is that WOMAC function was significantly higher in obese than in non-obese subjects, regardless of the level of pain or of the X ray grade. It is obvious that obese patients may give higher scores to questions regarding the difficulties to get in or out of the bathtub or the bed, and to put or remove socks or to do housework. This must be known and taken into account by physicians when assessing the functional status of patients with knee OA.Our study has limitations, especially because it is a post-hoc analysis of a trial, which has not been designed for this purpose. Thus, only 166 of the 205 patients from the intent-to-treat population had full data allowing to include them in the post-hoc analysis. Furthermore the sample of patients with both obesity and severe JSN was small, limiting the power of the analysis. To explain the lack of effectiveness of VS in obese patients, we cannot exclude a bias due to the increased risk of needle misplacement, leading to extra-articular HA injection related to larger subcutaneous adipose tissue, in obese subjects . This coOur results do not confirm our previous conclusions that recommended not performing viscosupplementation in obese patients with anatomically severe knee OA. Although the chances of being a responder are much reduced in these patients, the benefit of patients who respond to treatment is similar to that of subjects who do not have these two risk factors of treatment failure. This knowledge should avoid of not recommending a therapeutic option that benefit a substantial number of patients, in a chronic and debilitating pathology in which few effective and well-tolerated treatments are available.


Chronic low back pain is potentially disabling for older adults, and exercise is considered the best treatment. The Pilates method and aerobic exercises have been proven to be effective in pain and function improvement in patients with low back pain, but evidence in the treatment of older adults with low back pain is scarce. Therefore, the objective of this study is to investigate the effectiveness of the Pilates method compared to aerobic exercises in the treatment of older adults with chronic nonspecific low back pain.n = 37) with exercises based on the Pilates method and Aerobic Group (n = 37) with treadmill aerobic exercise. The primary outcomes will be pain intensity and general disability, assessed eight weeks after randomization. The secondary outcomes will be: pain intensity and general disability, assessed six months after randomization; and global perceived improvement, specific disability, dynamic balance, muscle strength , and pressure pain threshold, assessed eight weeks and six months after randomization. Therapists and patients will not be blinded.This is a randomized controlled trial with blinded assessor, to be held in a physical therapy clinic in Sao Paulo, Brazil. Seventy four patients aged 65 to 85 years with chronic nonspecific pain will be randomized into Pilates Group  contains supplementary material, which is available to authorized users. The aging process causes functional changes such as reduction in muscle mass and strength, increase in joint stiffness, and postural instability . When acCurrently, physical exercise is one of the best treatment options for patients with chronic low back pain , as it rThere is reliable evidence that aerobic exercises decrease pain and improve physical and psychological functioning in patients with chronic low back pain . HoweverThe Pilates method is based on six basic principles: power house, concentration, control, precision, flow of movement, and breathing , 13. PilExercise is indicated for chronic pain management in older adults, and studies show positive effects of aerobic exercise  and PilaThis will be an assessor-blinded, 2-arm, randomized controlled trial.The study will be conducted at a physical therapy outpatient clinic in Sao Paulo, SP, Brazil.Older adults aged 65 to 85 years, of both sexes, with chronic nonspecific low back pain and pain intensity equal to or greater than 3 points in the last seven days in the Pain Numerical Rating Scale  will be Before assessment, written consent will be obtained from the patients. A blinded assessor, who is a physical therapist with five years of clinical experience, will evaluate the eligible participants in person. The evaluation will consist of: personal data, clinical data, and evaluation of outcomes. The initial assessment will be conducted prior to the random distribution of the patients into the treatment groups, in a reserved place. The assessment of the outcomes will be repeated eight weeks and six months after randomization in the same place. To prevent loss of follow-up, patients will be asked to be available nearly the dates of follow-ups.The primary outcomes will be pain intensity and disability, assessed eight weeks after randomization. Secondary outcomes will be as follows: global perceived improvement, specific disability, dynamic balance, muscle strength , and pressure pain threshold, assessed eight weeks and six months after randomization. Pain intensity and disability assessed six months after randomization will be considered as secondary outcomes too. All the questionnaires/scales used in this study show adequate measurement properties , 26, 27.The pain intensity perceived by the patient in the last seven days will be evaluated by the 11-point Pain Numerical Rating Scale , with zeDisability associated with low back pain in the last 24 h will be assessed using the Roland Morris Disability Questionnaire , 26, 27,The global perceived improvement comparing the onset of symptoms to the last few days will be assessed using the Global Perceived Effect Scale . It is aSpecific disability will be assessed using the Patient-Specific Functional Scale , which eDynamic balance will be assessed by the Sit-to-Stand Test and the 10-Meter Walk Test. These tests show adequate reproducibility  and deteIsometric muscle strength will be assessed using a dynamometer . The gluteus medius, gluteus maximus, and lateral hip rotators will be assessed bilaterally, since these muscles are directly related to pelvic stabilization . The glu2 in area, will be positioned at a 90-degree angle on the skin and will be pressed with approximately 50 kPa/s of speed. The instruction given to the participants will be to push the button when the feeling of pressure or discomfort becomes painful. The measurements in kPa will be repeated three times at each point with a 30-s interval between measurements [Pressure pain threshold evaluates the lowest stimulus in which a patient perceives pain  and willurements . The aveRandomization will be performed by a researcher not involved in the recruitment, assessment, or treatment of the participants by means of a random numerical sequence generated by Microsoft Excel 2010, before the beginning of the study. Treatment allocation will be concealed through sealed, opaque envelopes sequentially numbered. After the baseline assessment, one of the therapists responsible for the intervention will open the sealed envelope to identify the group to which the participant was allocated (Pilates Group or Aerobic Group). This is a single-blind study because only the assessor will be blind to the allocation of the participants in the treatment groups. Due to the nature of the interventions, it will not be possible to blind participants and therapists. At the end of the study, the assessor will say to which group he believes the participants were allocated in order to test the blinding of the study.Both groups will receive 16 individual, twice-weekly exercise sessions lasting 60 min each over a period of 8 weeks. To improve adherence, participants will receive a calendar with the sessions date and the available days for missed sessions. This will ensure that the intervention period and the make-up sessions do not exceed 10 weeks, when the treatment will end, independently of the number of sessions achieved. Additionally, in São Paulo, older adults aged above 60 years do not pay for public transportation, which could ensure participants to come to the intervention site. Sessions will be supervised by two physical therapists. The Pilates Group will be supervised by a physical therapist certified in Pilates with four years of experience with the method, and the Aerobic Group will be supervised by a physical therapist specialized in Sports Physical Therapy with one year and six months of experience and specifically trained with the proposed exercises. Patient chart will be audited monthly for protocol deviations by an independent researcher. The treatments are described in Table The study was designed to detect a clinically significant 2-point difference in pain intensity assessed by the Pain Numerical Rating Scale (estimate for standard deviation = 2.5) and a 5-point difference in disability assessed by the Roland Morris Disability Questionnaire (estimate for standard deviation = 6.5) , 50 eighThe data collected will be stored in locked cabinets, and only the blinded assessor will have access to this information. Data will be saved in a computer spreadsheet with password protection to ensure confidentiality. To ensure no error, the spreadsheet will be monthly monitored and audited by a researcher who is blind to the participants’ group allocation and has no conflict of interest. The mean effects of the interventions and the differences between groups for all outcomes and their respective 95% confidence intervals will be calculated using linear mixed models, which will incorporate terms for the treatment groups, time , and interaction terms (treatment groups versus time). Treatment coefficients versus time interactions will be equivalent to the estimates of the differences between groups. The analyses will follow the principles of intention to treat and no interim analyses will be performed. No additional analysis will be performed. If a patient drops out of treatment, no additional outcome will be collected. The significance level will be set at 5%, and SPSS for Windows will be used for the statistical analysis.Pilates method and aerobic exercises have been shown to improve balance and reduce pain and disability in patients with chronic low back pain , 16, 19.Therefore, the results of the present study will contribute to more accurate estimates of the therapeutic effects of Pilates and aerobic exercises in older adults and will be the largest randomized controlled trial in this field. The present study will be conducted with low risk of bias to obtain an eight score on the PEDro scale. Therefore, a sample calculation has been performed to identify a significant clinical effect and a pragmatic study has been proposed, taking into account the individuality of each patient through an exercise protocol Additional file 2:Equipment-based exercises. The appendix 2 contains photos and description of Pilates exercises that could be performed on equipment. (PDF 2285 kb)


Due to conflicting evidence regarding first-line therapies for chronic post-surgical pain (CPSP), here we comparatively evaluated the efficacy and safety of first-line therapies for the prevention of CPSP.MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched for randomized, controlled trials (RCTs) of systemic drugs measuring pain three months or more post-surgery. Pairwise meta-analyses (a frequentist technique directly comparing each intervention against placebo) and network meta-analyses  compared the mean differences for primary efficacy , secondary efficacy (reduction in moderate or severe pain), and primary safety (drop-out rate from treatment-related adverse effects). Ranking probabilities from the network meta-analysis were transformed using surface under the cumulative ranking analysis (SUCRA). Sensitivity analyses evaluated the impact of age, gender, surgery type, and outlier studies.Twenty-four RCTs were included. Mexiletine and ketamine ranked highest in primary efficacy, while ketamine and nefopam ranked highest in secondary efficacy. Simultaneous SUCRA-based rankings of the interventions according to both efficacy and safety revealed that nefopam and mexiletine ranked highest in preventing CPSP. Through the sensitivity analyses, gabapentin and ketamine remained the most-highly-ranked in terms of efficacy, while nefopam and ketamine remained the most-highly-ranked in terms of safety.Nefopam and mexiletine may be considered as first-line therapies for the prevention of CPSP. On account of the paucity of evidence available on nefopam and mexiletine, gabapentin and ketamine may also be considered. Venlafaxine is not recommended for the prevention of CPSP. Chronic (or persistent) post-surgical pain (CPSP) is a pain syndrome characterized by pain at the surgical site that continues at least two months post-surgery after all other etiologies have been excluded  . The mosThus, there is conflicting evidence regarding the efficacy of gabapentinoids and ketamine for the prevention of CPSP. Moreover, although literature regarding serotonin-norepinephrine reuptake inhibitor (SNRI) use for the prevention of CPSP is limited, the SNRI venlafaxine has also shown promising results . To compThis study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions , 12. TheWe identified English studies relevant to our network meta-analysis by performing a comprehensive search of the MEDLINE, EMBASE, and Cochrane CENTRAL databases published up to April 2017. The following search strategy was applied:  AND (post-op* OR postop* OR post-surg* OR postsurg* OR “after op*” OR “follow* op*” OR “after surg*” OR “follow* surg*”) AND  AND (chronic* OR constant* OR continu* OR persist* OR long* OR phantom) AND . Additional reports were identified from the reference lists of retrieved studies and relevant reviews.Only (i) randomized, controlled trials (RCTs) of (ii) one or more drugs  administered systemically before, during or after surgery, or both, which (iii) measured pain  three months or more after surgery on (iv) adult participants of both genders (18 years of age and older) undergoing (v) planned surgical procedures involving tissue injury were included in the meta-analysis. The drugs could be systemically administered immediately before, during, or after the procedure by any dose, route, or frequency.We excluded (i) non-RCTs , (ii) studies administering drugs non-systemically , (iii) studies administering gabapentin enacarbil or (S)-ketamine, and (iv) studies in which the results of CPSP patients could not be segregated from patients with other types of pain.Two reviewers independently assessed studies for eligibility and extracted the data from each RCT using a standardized data extraction form. Disagreements were resolved through discussion with a third author. The following parameters were extracted from each RCT: first author, year of publication, country of study, study design, number of patients per treatment arm (n), patient age (mean/median ± standard deviation [SD]), patient sex , drug regimen , type of surgical procedure, number and proportion (%) of patients with follow-up at three months or more post-surgery, and number and proportion (%) of patients for three outcomes: (i) the primary efficacy outcome -- proportion of participants reporting any pain at the anatomical site of the procedure or pain referred to the surgical site, or both  three months or more after the procedure; (ii) the secondary efficacy outcome – proportion of participants reporting moderate or severe pain (at least 4/10) at the anatomical site of the procedure or pain referred to the surgical site, or both  three months or more after the procedure; and (iii) the primary safety outcome – proportion of participants dropping out of the study due to treatment-related adverse effects.All included RCTs were graded for risk of bias using the Cochrane Risk of Bias tool . The toojb represents the outcome for intervention b in study j, and δjbk represents the trial-specific differential effect of intervention k relative to intervention b that follows a normal distribution N as follows .–52.29–522 > 75%) for several pairwise comparisons in the primary and secondary efficacy analyses, including gabapentin vs. placebo, ketamine vs. placebo, pregabalin vs. placebo . Moreover, there was no evidence of significant inconsistency in the secondary efficacy analysis, as the median MD of 1.24 (95% CrI: 0.06–2.41) did not significantly differ from the median random-effects MD of 0.48 (95% CrI: 0.03–1.37) (p > 0.05). Finally, there was no evidence of significant inconsistency in the primary safety analysis (median MD of 0.54 (95% CrI: 0.03–1.05) vs. median random-effects MD of 0.54 (95% CrI: 0.03–1.04) (p > 0.05).There was no evidence of significant inconsistency in the primary efficacy analysis, as the median MD of 2.07 (95% CrI: 0.10–4.01) did not significantly differ from the median random-effects MD of 0.50 (95% CrI: 0.09–1.28)  were significantly superior to placebo in reducing pain  are the safest and most effective interventions for preventing pain in CPSP patients Figure . Additiop = 0.040 and p < 0.0001, respectively, p = 0.736, There was evidence of publication bias in the primary efficacy and secondary efficacy meta-analyses by Egger's testing  receptor-channel complex, thereby reducing calcium ion flux through the channel and consequently inhibiting neurotransmitter release . AlthougAs opposed to selective serotonin reuptake inhibitors (SSRIs) that selectively function on serotonergic receptors and fail to provide adequate analgesia, SNRIs like venlafaxine display other pharmacological actions that may contribute to their observed analgesic actions, including interference with the opioid system, interaction with NMDA receptors, and inhibition of ion channel activity . VenlafaThere are several limitations to this study. First, although nefopam and mexiletine display superiority to other interventions in terms of efficacy and safety, there was only one small RCT directly involving venlafaxine Amr 2010 ), only o , only oIn conclusion, based on a Bayesian network meta-analysis of 24 RCTs, nefopam and mexiletine displayed superiority to other first-line therapies in the prevention of all pain in CPSP patients in terms of efficacy and safety. Moreover, nefopam, mexiletine, and pregabalin displayed superiority to other first-line therapies in the prevention of moderate or severe pain in CPSP patients in terms of efficacy and safety. On account of the paucity of evidence available on nefopam and mexiletine, gabapentin and ketamine may also be considered due to their efficacy and safety. The use of venlafaxine is not recommended for the prevention of CPSP. Further trials comparing these agents in large, diverse populations of CPSP patients are needed to validate our findings.


Metal sensitivity as a cause for painful joint replacement has become increasingly prevalent; however, there is a lack of reported clinical outcome data from total knee arthroplasty patients with metal allergies. The purpose of this study was to determine whether patients presenting with a painful total knee arthroplasty with a positive metal sensitivity have improved outcomes following revision to a hypoallergenic implant.A retrospective review was conducted for patients that underwent a revision total knee arthroplasty after metal sensitivity testing over a 3-year period from January 1, 2015, to December 31, 2017. Based on the results of sensitivity testing, patients underwent revision total knee arthroplasty to a hypoallergenic component or a standard component. Following revision, patients returned to the clinic at an interval of 6 weeks, 5 months, and 12 months for functional, pain, and satisfaction assessment. Outcomes were compared within and between sensitivity groups.p < 0.001) Whereas, the non-reactive group only saw a moderate, non-significant improvement in pain reduction at 6 weeks post-revision . Frequency of pain experienced did not vary significantly between groups. Maximum metal lymphocyte transformation test (LTT) sensitivity score did not correlate with pain level at the time of revision  or percent improvement after revision . Overall, all patients reported being very satisfied after revision total knee arthroplasty; there was no difference between positive and negative sensitivity groups .Of the included patients, 78.3% (39/46) were positive for metal sensitivity. The most common metal sensitivity was to nickel . Both non-reactive and reactive patients significantly improved in range of motion after revision arthroplasty. The reactive group saw a 37.8% decrease in pain at 6 weeks post-revision  contains supplementary material, which is available to authorized users. Primary knee arthroplasty is one of the most common orthopedic procedures performed each year in the USA. Due to the aging population, the number of total knee arthroplasty (TKA) procedures, and subsequently revision TKA, continue to rise . DespiteThe most common causes leading to revision TKA reported in the literature include infection, instability, and malalignment . PatientRecently, the idea of metal sensitivity as a cause for painful joint replacement has become increasingly prevalent. In general, 10–15% of the population demonstrate metal cutaneous sensitivity with the most prominent being nickel followed by cobalt and chromium . The allMultiple studies have shown that metal allergy in TKA exists and can be associated with a painful joint replacement and/or aseptic loosening. According to Hallab et al., the prevalence of metal allergy in patients with a well-functioning TKA is 25% and can be as high as 60% in those with a poorly functioning implant . AdditioTraditionally, dermal patch testing has been the gold standard for detecting metal sensitivity reactions . This coThe LTT is an in vitro test that measures the proliferation of lymphocytes after exposure to tested antigens . When compared to dermal patch testing, LTT has been found to have a greater sensitivity but a lower specificity . In addiA retrospective chart review was conducted in compliance with the Health Insurance Portability and Accountability Act (HIPAA) and with institutional review board (IRB) oversight. The study was deemed to be exempt from full IRB review. Charts from a single center were identified for patients that underwent a revision TKA after metal LTT sensitivity testing over a 3-year period from January 1, 2015, to December 31, 2017. Patients were referred for metal LTT sensitivity testing after other causes of a painful knee arthroplasty had been excluded . Patients underwent revision TKA to a hypoallergenic component or a standard component, based on the results of sensitivity testing. Patients testing positive for metal LTT sensitivity were revised to a hypoallergenic component, while those testing negative were revised for arthrofibrosis. Following revision, patients returned to the clinic at an interval of 6 weeks, 5 months, and 12 months for clinical assessment. Patients were excluded if they had incomplete pre-revision data sets. Results from metal LTT sensitivity testing, functional outcomes, pain scores, and satisfaction were analyzed.Patients were referred for metal LTT sensitivity testing after all other causes of a painful knee arthroplasty had been excluded, including infection, malalignment, or instability via laboratory, radiographic, or mechanical testing, respectively. For sensitivity testing, venous blood was drawn in the out-patient clinic and sent to a third-party laboratory . Lymphocytes were isolated and incubated for 5 days with a panel of metal allergens  of the operative knee was measured in flexion, extension, and total ROM. Instability, measured by varus and valgus laxity, was also recorded. Repeat ROM measures were made at each post-operative visit. Patients were also provided a survey prior to revision and at each post-operative visit to assess their function. The primary outcome variable was walking distance, measured as unable to walk, indoors only, less than 5 blocks, 5–10 blocks, and unlimited. Walking distance categories were entered into the database as an ordinal variable.Patients were surveyed prior to their revision regarding multiple characteristics of their TKA pain. They were asked how long the pain has persisted, the intensity of pain 6 months ago on a pain intensity numerical rating scale (PI-NRS) , and current intensity of pain . Change in pain was reported by calculating the percent change in PI-NRS for each patient between time points . GraphicAt each post-operative visit, patients were asked if they were satisfied with the revision and if they would elect to have the surgery again. Satisfaction was measured as extremely satisfied, very satisfied, moderately satisfied, slightly satisfied, not at all satisfied, and it is too early to tell. Satisfaction was converted to a numeric scale of 1–5  and entered into the database as an ordinal variable. Patient’s willingness to have the surgery again was entered into the database as a binomial variable of yes = 1 or no = 0 .t tests for continuous dependent variables and Mann-Whitney U tests for ordinal dependent variables. One-way analysis of variance (ANOVA) was used to test for differences between metal LTT sensitivity levels and pain or ROM; Bonferroni post hoc test were used when appropriate. Pearson’s chi-squared test was used to compare the frequency of willingness to repeat the surgery between the non-reactive or reactive groups. Paired t tests were applied for within-group comparisons between pre-revision pain and ROM and post-revision follow-ups. Post-operative pain and ROM were normalized as percentages of baseline (pre-operative) measurements and compared between groups using unpaired two-tailed t tests. Correlations between metal LTT sensitivity and percent change in pain or pre-revision pain were tested using Pearson’s product-moment correlation  or Spearman’s rank correlation tests . Data was aggregated and analyzed using open-source R  or 6 weeks post-revision . However, walking distance ability before revision was significantly higher in the non-reactive group . On average, non-reactive patients could walk 5–10 blocks versus less than 5 blocks in the reactive patients. This significant difference in walking distance persisted at 6 weeks post-revision with the reactive patients maintaining their walking ability of less than 5 blocks, but the non-reactive patients improving to unlimited walking . While both groups average walking distance improved after revision, the increase was not significant (p > 0.05).Prior to and 6 weeks post-revision, there was no significant difference in knee flexion/extension ROM between the non-reactive and reactive groups Fig. . Howeverp = 0.21) or at 6 weeks post-revision (p = 0.97). However, when comparing metal LTT sensitivity within groups between time points, the reactive group saw a 37.8% decrease in pain at 6 weeks post-revision (p < 0.001)  and at 1-year post revision . The non-reactive group only saw a moderate, non-significant improvement in pain reduction at 6 weeks post-revision . Frequency of pain experienced did not vary significantly between groups at follow-up and did not change significantly between follow-up time points.Intensity of pain was measured at each follow-up visit and compared to the patient’s pre-operative pain level at the time of revision. When comparing metal LTT sensitivity between groups, there was no difference in pain experienced at the time of revision (01) Fig. . This reR2 = 0.02, p = 0.38) or percent improvement after revision   = 0.498, p = 0.61]. Post hoc comparisons indicate patients with medium LTT sensitivity had a significantly higher pain score than low LTT sensitivity patients (p = 0.046). No other comparisons were significant.Overall, combining patients from both groups, maximum metal LTT sensitivity score did not correlate with pain level at the time of revision (81) Fig. a, b. WitW = 62, p = 0.89).Only one patient in the cohort reported an unwillingness to undergo the revision arthroplasty again. Overall, all patients reported being very satisfied after revision TKA; there was no difference between positive and negative sensitivity groups Additional file 2:Figure S2. Sample metal-LTT sensitivity report. Provided by Orthopedic Analysis, Chicago, IL [cago, IL . (PDF 21


Somatoform pain disorders (SPD) are common, disabling and do not respond well to existing treatment modalities. We investigated the usefulness of 18 sessions of high frequency repetitive transcranial magnetic stimulation delivered at the left dorsolateral prefrontal cortex (DLPFC) in five right-handed patients with SPD. All patients reported significant improvement in pain relief and activities of daily living. High-frequency repetitive transcranial magnetic stimulation (rTMS) delivered at the left DLPFC may be useful in SPD. Somatoform disorders including somatoform pain disorders (SPD) are among the most common psychiatric disorders and are frequently comorbid with depressive disorders . They arThe study protocol was passed by the institute ethics committee and the study was carried out in the rTMS service of the department of psychiatry of a tertiary hospital in North India. A prospective, open-label design was adopted. Purposive sampling was used to recruit five patients of either gender and aged at least 18 years referred to the service with a diagnosis of persistent somatoform pain disorder (F45.4) as per the ICD-10. All the patients were referred for rTMS treatment because of inadequate response to conventional treatment . All patients provided written informed consent. History and clinical assessment was reviewed and diagnosis was confirmed. All patients were treated with rTMS as per a commonly used protocol . The F3 All patients were right-handed. None of the patients had any diagnosable physical illness. All patients were able to complete 18 sessions. No serious side-effects were noted or reported.Our results indicate that HF rTMS delivered over the left DLPFC was effective in our cohort with SPD. The improvement started by the second week (after six sessions) and continued over the rest of the duration of rTMS. Improvement was sustained at two weeks after last session of rTMS. All patients also reported subjective improvements in activities of daily living and that the pain was reduced and bothered them a lot less than before. All patients were satisfied with the treatment. These results are in keeping with other reports that have shown the effectiveness of rTMS in chronic pain . Our stuSPDs are generally poorly researched and have low quality evidence with regards to the effectiveness of treatment options . Both phOur study found that HF PFC rTMS was effective in alleviating pain in SPD. The speed of improvement was similar to that has been reported in other trials for chronic pain due to fibromyalgia . Thus siOur study indicates that rTMS needs to be investigated more thoroughly as a treatment option in SPD. This is important because existing treatment options in SPD are of limited utility.


Identify patient subgroups defined by trajectories of pain and disability following surgery for degenerative lumbar spinal stenosis, and investigate the construct validity of the subgroups by evaluating for meaningful differences in clinical outcomes.We recruited patients with degenerative lumbar spinal stenosis from 13 surgical spine centers who were deemed to be surgical candidates. Study outcomes  were measured before surgery, and after 3, 12, and 24 months. Group-based trajectory models were developed to identify trajectory subgroups for leg pain, back pain, and pain-related disability. We examined for differences in the proportion of patients achieving minimum clinically important change in pain and disability (30%) and clinical success (50% reduction in disability or Oswestry score ≤22) 12 months from surgery.p < .001).Data from 548 patients  were included. The models estimated 3 unique trajectories for leg pain , back pain , and disability . The construct validity of the trajectory subgroups was confirmed by between-trajectory group differences in the proportion of patients meeting thresholds for minimum clinically important change and clinical success after 12 postoperative months (Subgroups of patients with degenerative lumbar spinal stenosis can be identified by their trajectories of pain and disability following surgery. Although most patients experienced important reductions in pain and disability, 29% to 42% of patients were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. These findings may inform appropriate expectation setting for patients and clinicians and highlight the need for better methods of treatment selection for patients with degenerative lumbar spinal stenosis. Degenerative lumbar spinal stenosis (LSS) is a common musculoskeletal disorder, experienced by 1 in 5 adults 65 years or older . AlthougSurgery for LSS is the most frequent type of spinal surgery performed on older adults and will become increasingly common as the population ages . ConsistA recent systematic review and meta-regression of data from 39 (pain outcome) and 31 (disability outcome) primary studies identified the average postoperative outcome trajectories experienced by patients with LSS . The aveNo prior studies have attempted to identify outcome trajectory subgroups following surgery for LSS. This knowledge can further our understanding of the prognosis and outcomes experienced by these patients. The aims of this study were to 1) identify patient subgroups defined by trajectories of pain and disability following surgery for LSS, and 2) investigate the construct validity of the trajectory subgroups by evaluating for meaningful differences in clinical outcomes.This study was a retrospective analysis of prospectively collected data from patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN), a multicenter initiative of orthopaedic and neurological spine surgeons. The CSORN includes a surgical registry comprising preoperative baseline and postoperative follow-up data to document the clinical outcomes experienced by patients undergoing spine surgery. The accuracy and completeness of registry information is monitored and audited by a dedicated Data Quality Coordinator. Clinical outcome data were collected at the preoperative baseline and after 3, 12, and 24 months postoperatively.In the current study, we included data from all patients 50 years and older with a chief pathology of lumbar spinal stenosis, as identified by the consulting spine surgeon. All patients underwent surgery for decompression at one or more spinal levels with or without fusion. The CSORN project was originally approved by Research Ethics Boards local to each data collection site. Prior to study enrolment, all patients reviewed information about the study and provided written informed consent by signing forms approved by the relevant Research Ethics Board. The current study protocol was approved by Research Ethics Boards of the Horizon Health Network (2017–2568) and University of New Brunswick (2018–025).After obtaining consent, preoperative data collection included demographic  and clinical information . The attending spine surgeon and surgical staff recorded the surgical details including type of surgery, number of spinal levels and the use of minimally invasive techniques.Leg pain intensity and back pain intensity were measured separately with 11-point numeric pain rating scales , 13. TheThe modified Oswestry disability questionnaire was used to quantify disability related to leg and back pain . PatientAll analyses were conducted with Stata 15.1 software . Pain and disability outcomes at preoperative baseline and 3, 12, and 24 months after surgery were used to assign each patient to a trajectory group using group-based trajectory modeling. Compared to variable-centered analyses that seek to describe associations between variables , person-centered approaches such as group-based trajectory modeling identify groups of individuals who share particular attributes . This appSeparate group-based trajectory models were created to identify trajectory subgroups for each outcome variable  applying a censored normal distribution. We excluded patients with missing outcome scores at baseline and those with less than two follow-up outcome measures. Group-based trajectory models handle missing data with maximum likelihood estimation, resulting in asymptotically unbiased parameter estimates when data are missing at random .Some patients with degenerative lumbar stenosis have predominant leg pain, some have predominant back pain, and some have a surgical indication other than pain . Given the nature of the outcome measures, we excluded patients with minimal pain or disability at the preoperative baseline to help isolate clinically-relevant symptoms or impairments and permit judgements of clinically-important change. When modeling leg or back pain intensity, we excluded patients with baseline pain intensity scores less than 3 out of 10. When modeling disability, we excluded patients with baseline Oswestry scores ≤20 .Initially, single class quadratic models were constructed and the number of classes were increased until optimal models were identified. Judgments regarding optimal model specification cannot be reduced to a single metric . Our moda priori diagnostic criteria: 1) a minimum average posterior probability of individual group membership of 0.7 for each group; 2) obtaining close correspondence between the estimated probability of group membership and the proportion of participants assigned to each group based on the posterior probability; 3) reasonably tight confidence intervals around estimated group membership probabilities  and 4) minimum odds of correct classification >5 [The final models were subsequently evaluated with 4 ation >5 , 22. We To explore the construct validity of the leg pain, back pain, and disability trajectory groups, we generated descriptive statistics for each pain and disability outcome, stratified by trajectory class. Additionally, we calculated the proportion of patients within each trajectory who met 5 clinical benchmarks at the 12-month follow-up: minimum clinically important change (30%) in 1) leg pain, 2) back pain, and 3) disability, as well as 4) relative (50% improvement) and 5) absolute (≤ 22) estimates of successful disability outcome. Differences between trajectory groups in the proportion of patients meeting each clinical benchmark were examined with Fischer’s exact test. Alpha was .05 for all analyses.Data from 606 patients were assessed for eligibility. After applying our selection and analysis criteria, we excluded data from 58 participants . In total, data from 548 patients who underwent surgery performed by one of 34 surgeons from 13 sites were included in one or more analysis . Preoperp < .001) differences between trajectory groups in the proportion of patients who met each of the 5 clinical benchmarks were identified  were classified as members of a pain or disability trajectory group that experienced little or no benefit from surgery, underscoring the need for better methods of patient selection.The average pain and disability trajectories identified in our study were very similar to a recent systematic review and meta-analysis reporting the average pain and pain-related disability experienced by patients undergoing surgery for LSS . HoweverShared decision making is an essential component of patient-centered care that promotes interaction between informed, engaged patients and clinicians to make optimal healthcare decisions . High-quThere are strengths and limitations of this study. The primary study strengths include the large sample of patients from 13 spine centers and the long-term follow-up with patient-centered clinical outcomes of pain and disability. Additionally, we implemented a novel statistical technique to understand complex longitudinal data resulting in the identification of previously unknown pain and disability phenotypes. Although our study was conducted in Canadian spine centers, and the surgical outcomes experienced by patients in other countries may differ, the average back and leg pain outcomes experienced by patients in the current study were similar to those reported in a systematic review comprising outcome reports from 22 countries . This spThe use of trajectory modeling in spine surgery can advance our understanding of the outcomes experienced by patients, and help to identify clinically-relevant subgroups of patients who are more or less likely to respond to surgery. Significant clinical utility would be gained if the trajectory subgroups identified in this study could be accurately predicted prior to surgery, as this knowledge would enhance patient selection. It will also be important to determine whether membership in a particular trajectory group could be modifiable. For example, little is known about the effectiveness of postoperative care following spine surgery , 26 and In conclusion, the current study identified subgroups of patients with LSS who can be identified by their trajectories of pain and disability following surgery. The construct validity of these subgroups was confirmed, and they may represent useful patient phenotypes. Although most patients experienced important reductions in pain and disability, many patients (29% to 42% depending on outcome) were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. These findings highlight the need for better methods of treatment selection for patients with LSS.S1 Table2 Minimum acceptable size at least 5% 3 Bayesian information criterion  4 Bayesian information criterion .Bayesian information criterion value closest to zero indicates best model fit (DOCX)Click here for additional data file.S1 Figa1. sample 1 leg pain trajectories (N = 264), a2. sample 2 leg pain trajectories (N = 265); b1. sample 1 low back pain trajectories (N = 255), sample 2 low back pain trajectories (N = 255); c1. sample 1 disability trajectories (N = 259), c2. sample 2 disability trajectories (N = 260). Point estimates are average outcome scores . Dotted lines represent 95% confidence intervals.(DOCX)Click here for additional data file.


Hemodialysis patients suffer from long-term pain that drains their energy and contributes to behavioral interference and other negative effects on their daily lives that result in or exacerbate functional limitations. In addition, they deal with dietary restrictions, symptoms such as itching, lack of energy, and psychological stressors like the loss of self-concept and self-esteem. Self-regulation involves the capacity to notice, inform, and modulate responses and behavior, and research indicates that it promotes rehabilitation in chronic pain patients. Research on the aspects of self-regulation afforded by the Japanese psychotherapy Dohsa-hou correspond to psychological processes tied to the sense of self-control that clients realize over their body movements. This study pilot tested a hospital-integrated implementation of Dohsa-hou relaxation tasks as a chronic pain management behavioral intervention for five female hemodialysis patients between the ages of 59–62 years. We conducted an ABABABA single-case design to compare baseline A-phases  taken at recurring 1 week intervals  with an intervention of Dohsa-hou B-phases every 4 weeks  over the span of 4 months to compare effectiveness. Visual Analogue Scale (VAS) pain scores between phases were taken and self-regulatory progress was tracked and summarized from a series of semi-structured interviews. Visual analysis of scores for each participant as single cases indicated decreases for the Dohsa-hou phase compared to baseline treatment-as-usual. As a result, participants reported using Dohsa-hou to reduce pain and experienced improvements in quality of life associated with greater self-regulatory capacity to attend to personal care and domestic activities. These preliminary findings suggest that Dohsa-hou body movement relaxation tasks were feasible as a coping skill in a hospital-integrated setting and at home and show promise for promoting quality of life vis-a-vis the management of severe and chronic bodily pain associated with end-stage renal disease and its treatment, particularly by improving aspects of pain-mediated self-regulatory fatigue. Patients with chronic conditions are faced with the challenging prospect of comprehensively managing their disease and its symptoms. The discomfort of pain is a source of exacerbating demand under these circumstances. Pain becomes especially troublesome as patients are already making negotiations about the quality of their lives in the form of adjusting to the changes that are required to adhere to the treatment regimen of their disease. Psychologically, regaining control in the face of the adversity posed by the life event of chronic disease diagnosis, the onset of symptoms, and their treatment is a priority. While chronic conditions each have their own subset of challenges, the treatment of end-stage renal disease (ESRD) is characterized by not only the management of its symptoms, but also by the requisite difficulties imposed by its treatment, often in the form of chronic bodily pain. The primary aim of the current study was to develop a program to provide psychological support through relief from the bodily pain that patients experience under the duress of prolonged treatment for ESRD, and to pilot test and qualitatively evaluate its proof-of-concept for indications of changes in quality of life.ESRD patients are treated with various modalities such as hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation. In an overview of the status of treatment for ESRD globally, Grassmann et al.  reportedPsychosocial elements play a role in the adaptation to ESRD because undergoing dialysis treatment requires being physically connected to the HD machine three times a week over the course of a year, incurring a host of major stressors  gained from executing body movements with a sense of agency  , the clinical staff members at the hemodialysis unit of a regional hospital in southern Japan participated in a stress-management program using Dohsa-hou relaxation tasks given by a psychotherapist with a supervisory license from the Japanese Association of Rehabilitation Psychology. The clinical psychologist demonstrated Dohsa-hou techniques for 5–10 min during staff meetings twice a month. The chief of staff requested that the clinical psychologist teach the clinical staff how they could apply Dohsa-hou to hemodialysis patients with chronic pain. All the staff agreed with this procedure: 7–10 patients had severe chronic pain, and the staff members were encouraged to give the patients the best care they could. In Japan, a HD patient normally receives dialysis treatment three times a week, with each session lasting 4 h. The staff at HD units provided patients with assistance not only in health matters but also with regard to matters of their daily activities. This facilitated the establishment of a cooperative relationship. It was observed that when patients suffer severe pain during dialysis treatment, analgesics are unable to provide sufficient relief. Thus, as recognized by the staff, the need to provide full treatment by alleviating pain for such patients served as an impetus for this study.HD patients typically suffer severe chronic pain at the shoulder, and in the neck and blood vessels, especially on the punctured side. In Dohsa-hou, there are two general types of tasks: relaxation and motor-action tasks. We selected relaxation tasks to be used on the patients in this study because they function to release excess muscle tension. The following Dohsa relaxation tasks were carried out by the patients in the supine position on a bed: (1) opening and closing the hand to achieve flexibility; 2) bending and stretching the wrist in a smooth movement; and (3) moving the arms and shoulders to relax stiffness in the shoulder and neck. The Dohsa-tasks performed and their effectiveness determined by phase are shown in  bending The various steps in the Dohsa tasks were explained by means of diagrams for expanding participants' normal movement range. The Dohsa tasks were shown to be learned and replicable by the clinical staff . The staff was instructed to focus on the patient's body movement and the muscle tension they were undergoing; the staff members were also told to provide the patients with positive rather than negative feedback . Studies of Dohsa-hou in Japan have indicated that it is important to provide patients with positive feedback in regard to the awareness of their physical condition so as to improve their mental situation  (12 recordings) A-phases and all intervention measurements were B-phases lasting for 4 weeks (36 recordings). The Dohsa-hou intervention was applied three times a week during HD therapy. To evaluate the effect of Dohsa-hou, VAS was used to measure pain intensity before and after the Dohsa-hou intervention. Drawing from time-based pacing used in cognitive behavioral therapy, a relatively brief restful pause is known to indicate that the patient is recovering to a predetermined safe amount of activity  about their complaints of prolonged chronic pain. Nine patients  complained of chronic pain and seven patients  gave their informed consent to participate in the study. Two male patients (71 and 69 years old) who underwent HD for a shorter period (0.3 and 0.8 years) and expressed apparent anxiety about HD from evaluation of the study, were excluded to maintain a focus on the effects of the intervention for long-term patients of severe pain and pain-related life interference associated with long-term hemodialysis treatment. This resulted in five patients who suffered from chronic bodily pain, all of whom had been recipients of hemodialysis treatment for over 10 years.M age = 61 years old) who reported chronic pain that was particularly long-lasting and severe remained as the target participants for the present study. The patients underwent hemodialysis treatment over a long period . The patients were unable to do any work, having been inactive and housebound for approximately 5 years or more because of their condition. They complained of chronic pain (shoulder stiffness and pain in the vein that was punctured by the needle) during dialysis and often had to halt the treatment because of the severity (shoulder stiffness or vein pain), and this also caused difficulties in their daily lives. They took analgesics, but the effectiveness was variable . The VAS used response scales for a single item with a horizontal form: a 100 mm line anchored upward by “pain as bad as it could be” (10) and anchored downward by “no pain” (0); the patient was instructed to mark any point on the VAS continuum corresponding to their present pain intensity , including treatment for pain and other medical conditions, such as hypertension. The Dohsa-hou intervention was conducted on an individual basis and consisted of 36 sessions for each patient. The Dohsa-hou intervention schedule consisted of three terms. Complaints of pain from the five participants usually occurred around 2 h after starting HD. We conducted the Dohsa-hou tasks when participants complained of their pain. If participants did not complain of pain, we implemented Dohsa-hou at around the 2 h mark. Each intervention term lasted a total of 5 weeks, comprising 4 weeks of Dohsa-hou intervention and 1 week of TAU see .The VAS pain scores were averaged at 2, 3, and 4 h, and compared between intervention and TAU. The VAS pain scores were divided into two groups: one group consisted of pre-intervention values; the other consisted of post-intervention values. Participants received intervention at peak times of pain. Pre-intervention VAS pain scores were averaged from pre-dialysis treatment to before intervention. Post-intervention VAS pain scores were averaged from after intervention to 4 h after dialysis treatment. The VAS pain scores were analyzed for differences between pre-intervention and post-intervention. Visual analysis of the scores was adopted to clarify the effectiveness of the Dohsa-hou B-phases compared to the TAU baseline A-phases within the single-case design. Data plots for the series of sessions of each case are depicted in All participants were interviewed at the end of the first, second and third terms within the baseline TAU A-phases. The interview questions were structured to determine applied effectiveness of pain management  over a long period. The participants reported having experienced severe pain during dialysis and at home for the previous 1–3 years. All the participants complained of difficulty performing everyday activities  because of their pain. Previous studies found that HD patients with chronic pain held their role as a member of their family with meaningful contributions to domestic activities as an important aspect of their self-concept under the circumstances of dealing with their chronic condition and its treatment . In terms of sequences completed, all five participants were able to complete almost all of the sessions to undergo the Dohsa tasks except at four data collection points  Scale  patients reported chronic pain when we interviewed possible patients for recruitment to this study. This differs from Brkovic et al.  who repoIn addition, we cannot ignore the fact that positive outcomes could be explained by non-specific factors, such as the treatment expectancy effects of being in a clinical study and receiving extra attention from treatment staff. An especially notable limitation in our study is that our data cannot tease apart the effects of positive feedback itself. Improving communication skills (Ricka et al., As this was a chiefly idiographic assessment of single-case series with a simple phase design using participants as their own control, the RoBiNT Scale as a resource indicates a number of other possible risks of bias that will need to be carefully addressed in future studies (Tate et al., In sum, although limited, in light of the feasibility indicators of procedural fidelity and proof-of-concept in a cohort of a longitudinally applied clinical context for five participants of a known group, some degrees of effectiveness of the intervention for the clinical end points were observed to allow for the stratification of future patient groups (Lillie et al., The findings indicated areas of support in the domain of the promotion of self-regulation through Dohsa-hou as an adaptive pain coping skill. Specifically, this study suggested that applying body movement relaxation tasks shows promise as a psychotherapeutic approach for managing severe chronic pain, especially in a sample of individuals affected by renal disease. Dohsa-hou provided indicators of effectiveness by reducing pain during dialysis as well as improving quality of life through reports of recouped control over patient-driven desired commitments to personal care and domestic activities. Overall, this study suggested that hemodialysis patients are capable of learning to manage their chronic pain on their own through the deliberate practice of movement tasks aimed at changing feeling states and that a collaborative program to facilitate the care of chronic pain can be provided by clinical staff using Dohsa-hou. Although more research is needed, this study indicated that one way to facilitate quality of life change in low-functioning patients undergoing dialysis is to relieve the burden of chronic bodily pain by promoting self-management with body movement-based relaxation.This study was carried out in accordance with the recommendations of the Ethical Committee of the Graduate School of Education, Hiroshima University. The protocol was approved by the Ethical Committee of the Graduate School of Education, Hiroshima University. All subjects gave written informed consent in accordance with the Declaration of Helsinki.YH conducted the research, supervised the progress of the patients, and served as the primary author of the manuscript. RK provided manuscript preparation, analysis, revisions, summary, and literature review. KA provided ratings for the self-regulation categories, analytical insights, and revisions. TY contributed to confirmation of the research protocol, analysis, and manuscript preparation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.