Systemic Scleroderma Induced by Nivolumab in Malignant Melanoma.

BACKGROUND: Immunotherapy using immune checkpoint inhibitors is not devoid of immune-related adverse events (irAEs) including rheumatological conditions. CASE REPORT: We report a rare case of a 47-year-old woman with metastatic melanoma who developed systemic scleroderma after initiating nivolumab. The patient displayed inflammatory arthralgias, morning stiffness, and classical cutaneous manifestations of the disease. Clinical evaluations also revealed carpal tunnel syndrome, cardiac involvement, and dyspnea. RNA-Polymerase III antibodies were positive. Nivolumab, an anti-PD-1 antibody, was considered as a potential trigger for this condition. CONCLUSION: To our knowledge, this is the first case of nivolumab-induced systemic scleroderma in the context of melanoma described in the literature that fulfills the classification criteria of the disease. This case underscores the need for increased awareness of immune-related adverse events in patients receiving immune checkpoint inhibitors, emphasizing timely intervention and further research.

Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis.

OBJECTIVE: To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA). METHODS: In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)). CONCLUSION: The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.

[ACACIAS 3: Learning about announcement consultations in the second cycle of medical studies]. / ACACIAS 3 : Apprentissage des consultations d'annonce dans le deuxième cycle d'études médicales.

INTRODUCTION: The second cycle of medical studies is a key time for developing interpersonal skills and the doctor-patient relationship. High-fidelity simulation is an initial learning option that enables learners to confront situations involving empathy. METHODS: This is a feedback report from May 2023 on the implementation of simulation as a training tool for 2nd cycle medical students in the announcement consultation. The training consists of two parts: theoretical teaching via a digital platform with an assessment of theoretical knowledge and a practical part with a simulation session with an actress playing a standardized patient. The acquisition of skills and the reflexivity of learners are assessed by means of a pre- and post-test. RESULTS: Twenty-nine externs took part in this project. Student satisfaction was 96 %. The feedback was very positive, both in terms of the quality of the sessions and the briefings/debriefings. Almost all the students wanted to repeat the experience. The simulation exercise was beneficial for the students in terms of the development (before vs. after) of their skills (verbal, emotional and relational) (1.05±0.25 vs. 1.22±0.19, P=0.047) and appeared to be relevant to the development of reflexivity (3.29±0.72 vs. 3.48±0.9, P=0.134). CONCLUSION: This first published French study demonstrates the feasibility and value of training in announcing a diagnosis, combining teaching via a digital platform and high-fidelity simulation for second cycle medical students.

Diet and Disease Activity in Patients with Axial Spondyloarthritis: SpondyloArthritis and NUTrition Study (SANUT).

Axial Spondyloarthritis (axSpA) patients with inflamed intestines have higher SpA activity. Diets that modulate microbiota may influence inflammation and SpA activity. Today, data concerning the impact of diet on SpA activity are scarce. SANUT was a single-center, noninterventional, cohort study that assessed dietetic profiles associated with SpA activity in axSpA. Demographic, clinical, SpA-related, quality of life (QoL), fatigue, physical activity, and dietary data were collected. SpA activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) and by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). We assessed whether high SpA activity was associated with nutriment consumption. Between 12 February 2018 and 12 February 2020, 278 patients participated. High SpA activity, as measured by ASDAS and BASDAI, was significantly associated with higher body mass index and waist circumference, negative HLA-B27, lower QoL, higher fatigue, and higher digestive-symptom scores. Furthermore, high SpA activity, as measured by BASDAI, was associated with female sex, smoking status, patients who were not actively employed, reduced physical activity, and high intake of ultra-transformed foods, while high SpA activity, as measured by ASDAS, was associated with low intake of omega-3 PUFAs and fiber. Therefore, low intakes of omega-3 PUFAs and fiber, and high intake of ultra-transformed foods, are associated with high SpA activity.

Ruthenium-based assemblies incorporating tetrapyridylporphyrin panels: a photosensitizer delivery strategy for the treatment of rheumatoid arthritis by photodynamic therapy.

Ruthenium-based assemblies containing tetrapyridylporphyrins (TPyP) in their structure have been evaluated as photosensitizers (PS) to treat rheumatoid arthritis (RA) by photodynamic therapy (PDT). TPyP is useless by itself as a PS due to its low solubility in biological media, however, incorporated in metallacages it can be internalized in cells. The study shows a cellular antiproliferative activity in fibroblast-like synoviocyte (FLS) in the lower nanomolar range in the presence of light, and no dark toxicity at 1 µM concentration, thus having an excellent photoactivity index. The presence of diamagnetic (Zn2+) and paramagnetic (Co2+) metals in the center of TPyP impairs the effectiveness of PDT, showing no (Co) or reduced (Zn) photoactivity. A total of five metallacages with different structural characteristics have been evaluated, and our results suggest that the incorporation of PS in metalla-assemblies is not only an elegant method to increase solubility in biological media for TPyP but also appears to be an efficient hybrid system to treat RA by PDT.

eDOL mHealth App and Web Platform for Self-monitoring and Medical Follow-up of Patients With Chronic Pain: Observational Feasibility Study.

BACKGROUND: Chronic pain affects approximately 30% of the general population, severely degrades quality of life (especially in older adults) and professional life (inability or reduction in the ability to work and loss of employment), and leads to billions in additional health care costs. Moreover, available painkillers are old, with limited efficacy and can cause significant adverse effects. Thus, there is a need for innovation in the management of chronic pain. Better characterization of patients could help to identify the predictors of successful treatments, and thus, guide physicians in the initial choice of treatment and in the follow-up of their patients. Nevertheless, current assessments of patients with chronic pain provide only fragmentary data on painful daily experiences. Real-life monitoring of subjective and objective markers of chronic pain using mobile health (mHealth) programs can address this issue. OBJECTIVE: We hypothesized that regular patient self-monitoring using an mHealth app would lead physicians to obtain deeper understanding and new insight into patients with chronic pain and that, for patients, regular self-monitoring using an mHealth app would play a positive therapeutic role and improve adherence to treatment. We aimed to evaluate the feasibility and acceptability of a new mHealth app called eDOL. METHODS: We conducted an observational study to assess the feasibility and acceptability of the eDOL tool. Patients completed several questionnaires using the tool over a period of 2 weeks and repeated assessments weekly over a period of 3 months. Physicians saw their patients at a follow-up visit that took place at least 3 months after the inclusion visit. A composite criterion of the acceptability and feasibility of the eDOL tool was calculated after the completion of study using satisfaction surveys from both patients and physicians. RESULTS: Data from 105 patients (of 133 who were included) were analyzed. The rate of adherence was 61.9% (65/105) after 3 months. The median acceptability score was 7 (out of 10) for both patients and physicians. There was a high rate of completion of the baseline questionnaires and assessments (mean 89.3%), and a low rate of completion of the follow-up questionnaires and assessments (63.8% (67/105) and 61.9% (65/105) respectively). We were also able to characterize subgroups of patients and determine a profile of those who adhered to eDOL. We obtained 4 clusters that differ from each other in their biopsychosocial characteristics. Cluster 4 corresponds to patients with more disabling chronic pain (daily impact and comorbidities) and vice versa for cluster 1. CONCLUSIONS: This work demonstrates that eDOL is highly feasible and acceptable for both patients with chronic pain and their physicians. It also shows that such a tool can integrate many parameters to ensure the detailed characterization of patients for future research works and pain management. TRIAL REGISTRATION: ClinicalTrial.gov NCT03931694; http://clinicaltrials.gov/ct2/show/NCT03931694.

Effectiveness of Repetitive Transcranial Magnetic Stimulation on Fibromyalgia Patients Responding to a First Repetitive Transcranial Magnetic Stimulation Induction Course After Six Months of Maintenance Treatment: A Randomized Pilot-Controlled Study.

BACKGROUND: Fibromyalgia is a chronic painful condition without real, effective treatment. The administration of repetitive transcranial magnetic stimulation (rTMS) has been shown to have a therapeutic effect on pain, but there are still questions about the maintenance of its effect over time. Continuation of the treatment upon clinical response through maintenance sessions is promising and merits further exploration. MATERIALS AND METHODS: We conducted a randomized, parallel-group, controlled study involving 78 patients to evaluate the effect of rTMS vs sham stimulation after a three-week induction treatment and six months of maintenance treatment (three-week periodicity) on 22 patients who presented a clinical response to the induction treatment. The clinical response was defined as a ≥30% decrease of the baseline visual analog scale (VAS) for pain and a score for the Patient Global Impression of Change (PGIC) >5. The clinic global impression, fibromyalgia impact questionnaire, symptom severity score, and Beck's depression inventory were also studied. RESULTS: A significant clinical response to treatment with rTMS was observed after the induction phase and maintained over six months, particularly as measured by the PGIC parameter of pain, as well as of the intensity of fatigue and depression, with an absence of adverse effects induced by this method. CONCLUSION: A three-week rTMS treatment, characterized by a reduction in pain, as evaluated by VAS, should be continued with the administration of rTMS maintenance sessions for an additional six months to maintain the best possible long-term effects.

Ketamine in chronic pain: A Delphi survey.

BACKGROUND: There is no recommendation in Europe for the use of ketamine in patients with chronic pain. The heterogeneity of practice highlights the need to seek the advice of experts in order to establish a national consensus. This Delphi survey aimed to reach a national consensus on the use of ketamine in chronic pain in Pain clinics. METHODS: A collaborative four-round internet-based questionnaire was used. It was created after literature search on ketamine administration in chronic pain and included about 96 items. It discussed utility and advantages, adverse events and deleterious aspects, methods of administration, concomitant treatments and assessment of results. RESULTS: Twenty-eight experts completed all rounds of the survey with a total of 81.3% items reaching a consensual answer. Neuropathic pain represents the first indication to use ketamine, followed, with a good to moderate utility, by other situations (fibromyalgia, complex regional pain syndrome, central neuropathic pain, peripheral neuropathic pain, nociceptive pain, sensitization, opioid withdrawal, palliative care, depression). Experts agreed on the rare occurrence of adverse events. Concerning routes of administration, intravenous infusion with doses of 0.5-0.9 mg/kg/d for 4 days of treatment is preferred. Place of care is hospital, as in- or out-patient, with a quarterly administration of ketamine. Finally, ketamine effectiveness is assessed 1 month after infusion, and experts encourage combination with non-pharmacological treatment. CONCLUSIONS: This Delphi survey established a consensus of pain specialists on the use of ketamine in refractory chronic pain, thus providing a basis for future comparative trials. SIGNIFICANCE: This Delphi survey in chronic pain reached agreement on four main aspects: (1) Priority to treat neuropathic pain with evaluation of effectiveness at 1 month; (2) No deleterious effects in the majority of listed diseases/situations with the absence or <3% of suggested adverse events; (3) 0.5-0.9 mg/kg/d IV infusion; (4) Combination with non-pharmacological treatment.

Evaluation of Ruthenium-Based Assemblies as Carriers of Photosensitizers to Treat Rheumatoid Arthritis by Photodynamic Therapy.

For the first time, ruthenium-based assemblies have been used as carriers for photosensitizers in the treatment of rheumatoid arthritis by photodynamic therapy (PDT). These metallacages are totally soluble in physiological media and can transport photosensitizers (PS) in their cavity. After an incubation period, the PS is released in the cytoplasm and irradiation can take place. This strategy allows photosensitizers with low or null solubility in biological media to be evaluated as PDT agents in rheumatoid arthritis. The systems in which 21H,23H-porphine and 29H,31H-phthalocyanine are encapsulated show excellent photocytotoxicity and no toxicity in the dark. On the other hand, systems in which metalated derivatives such as Mg(II)-porphine and Zn(II)-phthalocyanine are used show good photocytotoxicity, but to a lesser extent than the previous two. Furthermore, the presence of Zn(II)-phthalocyanine significantly increases the toxicity of the system. Overall, fifteen different host-guest systems have been evaluated, and based on the results obtained, they show high potential for treating rheumatoid arthritis by PDT.

Chronic pain and neuroinflammation.

In rheumatology, chronic pain most often sets in after a musculoskeletal injury. Its persistence is not always due to the progression of the initial injury, but in some cases to the onset of central sensitization. Much scientific data suggests that this central sensitization is caused by multiple complex interactions between the nervous system and immune system. Afferent nerve fibers carrying pain information are responsible for peripheral sensitization partly linked to inflammation molecules. These afferent fibers release neurotransmitters in the dorsal root ganglion and dorsal horn of the spinal cord, capable of activating microglia, which are the local immune cells. The activated microglia will produce pro-inflammatory cytokines, chemokines and neuropeptides capable of interacting with the second-order neuron, but also segmental and descending inhibitory neurons. This is referred to as neuroinflammation, which will amplify the hypersensitivity of second-order neurons, otherwise called central sensitization. This neuroinflammation will be able to reach the higher brain structures, which are involved in pain modulation and the emotional and cognitive aspects of pain. The aim of this update is to describe the pathophysiology of chronic pain, incorporating the latest scientific data on neuroplasticity and neuroinflammation.

Use of eHealth by Patients With Rheumatoid Arthritis: Observational, Cross-sectional, Multicenter Study.

BACKGROUND: The use of eHealth tools (eg, the internet, mobile apps, and connected devices) in the management of chronic diseases and for rheumatoid arthritis is growing. eHealth may improve the overall quality of care provided to patients with chronic diseases. OBJECTIVE: The primary objective of this study was to describe eHealth use by patients with rheumatoid arthritis in France. The secondary objectives were to identify associations between patient demographics and disease characteristics and the use of eHealth tools, and assess their expectations of eHealth. METHODS: In this cross-sectional, multicenter study, patients with rheumatoid arthritis, according to the 2010 ACR/EULAR classification criteria, were recruited from 5 university hospitals (Bordeaux, Clermont-Ferrand, Limoges, Montpellier, and Toulouse). Patients completed an anonymous self-questionnaire, including demographic data, evaluating their eHealth use (ie, access, support, frequency of use, type of use, and reason for use). The rheumatologist in charge of each patient completed an independent medical questionnaire on disease characteristics, activity of rheumatoid arthritis, and treatments. Data were collected between December 2018 and July 2019. RESULTS: Questionnaires were completed by 575 participants, with a mean age of 62 (SD 13) years, 447 (77.7%) of whom were female. Overall, 82.2% (473/575) of the participants had access to eHealth through a computer (402/467, 86.1%), tablet (188/467, 40.2%), or smartphone (221/467, 47.3%). Of these, 36.4% (170/467) of the participants used the internet for health in general, and 28.7% (134/467) used it specifically for rheumatoid arthritis-related reasons. All these 134 patients used eHealth to learn about disease pathology, and 66.4% (89/134) of them used it as a tool to help monitor rheumatoid arthritis. Most patients (87/125, 69.6%) had a paper file, 19.2% (24/125) used a digital tool (spreadsheets, 10/125, 8%; mobile app, 9/125, 7.2%; or website, 5/125, 4%), and 24.8% (31/125) did not use any tools for monitoring. Few patients (16/125, 12.8%) used tools for treatment reminders. About 21.6% (27/125) of the patients using eHealth used a specific app for rheumatoid arthritis. Univariate analysis showed that age, education level, employment status, treatment, comorbidities, membership of a patient association, and patient education program were associated with eHealth use for rheumatoid arthritis. Multivariate analysis showed that membership of a patient association (odds ratio [OR] 5.8, 95% CI 3.0-11.2), use of biologic disease-modifying antirheumatic drugs (OR 0.6, 95% CI 0.4-1.0), and comorbidities (OR 0.7, 95% CI 0.6-0.8) remained associated with eHealth use for rheumatoid arthritis. Recommendation by a doctor (225/330, 68.2%), ease of use (105/330, 31.8%), and data security (69/330, 20.9%) were factors favoring the use of eHealth. CONCLUSIONS: To date, few patients have used eHealth for disease management. The use of a reliable and validated eHealth tool for rheumatoid arthritis could therefore be promoted by rheumatologists and could optimize therapeutic adherence.

Opioid epidemic: Does rheumatological practice favors risk for patients? National survey on rheumatologists' opioid prescriptions and compliance to guidelines for strong opioid prescription.

OBJECTIVES: Given the scope of rheumatology and its prevalence of pain, it seems needed that a study should focus on prescription habits, in the midst of the international opioid epidemic and given the moderate efficacy of strong opioids in chronic musculoskeletal conditions. We compared rheumatologists' opioid prescribing patterns in non-cancer pain with recommended practice. METHODS: We performed a cross-sectional study of the French health insurance database, including all patients aged 16 years or over reimbursed for at least one strong opioid prescription from a rheumatologist in 2015. A nationwide survey of all registered rheumatologists in France was performed with a 47-item questionnaire in June 2015. RESULTS: Only 2.4% of the patients receiving a strong opioid in 2015 (n=700,946) had at least one prescription from a rheumatologist. Rheumatologists prescribed mostly morphine, and significantly less oxycodone and fentanyl (P<0.00001) than other specialists. Rheumatologists prescribed a mean of 35.8mg morphine equivalent/day. A response rate of 33.7% was obtained to the questionnaire. Acute musculoskeletal pain was the principal condition for strong opioids prescription, with 94.5% re-evaluating opioid treatment within two weeks of initiation. For efficacy, 80% said that they stopped treatment if no benefit was observed after a test period (mean=1.2 months). Rheumatologists with pain management training were significantly more likely to evaluate pain before prescribing strong opioids (P=0.001), evaluate efficacy within three months (P=0.01) and screen for risk factors for misuse at initiation (P<0.0001). CONCLUSIONS: For non-cancer pain, rheumatologists generally prescribe opioids for short periods, at low doses, mostly according to national recommendations. Pain education strongly affected opioid prescription by rheumatologists.

The burden of pain in rheumatoid arthritis: Impact of disease activity and psychological factors.

BACKGROUND: Pain remains a prevalent symptom for rheumatoid arthritis (RA) patients despite a wide therapeutic choice. The objective of this study was to provide a multidimensional evaluation of pain. METHODS: A total of 295 RA patients from 7 French rheumatology centres were enrolled in a cross-sectional study. Patients completed a chronic pain assessment questionnaire approved by the French National Authority for Health, the health assessment questionnaire (HAQ) as well as depression and anxiety scales (HAD, Beck Depression Inventory, STAI). Disease activity (DAS28) and ESR were recorded. A multivariate descriptive analysis was undertaken using principal component analysis (PCA). RESULTS: 38.4% of patients had a pain score > 40 mm/100, although 83% were on biological treatment and 38.7% were in remission based on the RA activity score. The PCA analysis found four axes representing 70% of total variance. The axes, per cent of variance and variables represented were as follows: (a) axis 1, 41% variance, anxiety and depression scores, sensory and affective qualifier score, HAQ and pain impact on daily life; (b) axis 2, 13% variance, disease activity score (DAS28) and pain relief with current treatment; (c) axis 3, 9% of variance, RA duration and radiographic score and (d) axis 4, 6% of variance, DAS28 and ESR. Moderate to severe pain was significantly associated with axes 1 and 2. CONCLUSIONS: Despite a high proportion of patients on biological treatments, 38.4% of patients continue to experience moderate to severe pain. Pain is associated with the RA activity score, but also with the depression and anxiety scores. SIGNIFICANCE: Substantial proportion of rheumatoid arthritis (RA) patients still experiences relevant pain, although more than 80% on biological treatment. Pain is primarily associated with anxiety and depression scores and with disease activity score. These findings highlight the need to assess patients' mental well-being alongside. Clinical measures of disease activity to better manage pain and guide treatment decisions.

Factors influencing the choice of biologic therapy following Rituximab in patients with rheumatoid arthritis: A retrospective study using propensity score.

OBJECTIVES: To assess factors influencing the choice and effectiveness of biological disease-modifying antirheumatic drugs (DMARDs) following failure of rituximab (RTX) in rheumatoid arthritis (RA), taking patient profile into account. METHODS: In a retrospective, multicenter study, data about RA patients starting a new biologic during the year after RTX discontinuation were collected at baseline (when the biologic was introduced after RTX), and during follow-up (3, 6, and 12 months). Characteristics of patients receiving tocilizumab (TCZ), abatacept (ABA), or a TNFα inhibitor (TNFi), EULAR response, and retention rate were compared using multidimensional factorial analysis for patient profiles and multivariate analysis including propensity score built on the patient profile. RESULTS: Among 152 patients analyzed (37.5% TCZ, 31.6% ABA, 30.9% TNFi), sex, disease characteristics and activity, concomitant DMARDs or glucocorticoids, and previous use of RTX and TNFi were similar at baseline. Patients receiving ABA were slightly older. Multimorbidity index was higher but not significantly different. Multidimensional factorial analysis showed a distinct profile of patients receiving ABA, characterized by older age, more men, more smokers, more comorbidities, and higher anti-cyclic citrullinated peptide antibody. At 1 year, drug retention was higher for ABA than TNFi after adjustment for disease duration, concomitant DMARDs, glucocorticoids, and propensity score (P=0.04). Tolerance and serious infections were similar among groups. CONCLUSIONS: The profile of patients receiving ABA following failure of RTX differed from TNFi and TCZ using multidimensional factorial analysis. After adjustment for propensity score, drug retention rate remained higher with ABA than TNFi.

Management of neuropathic pain after knee surgery.

Chronic postsurgical pain (CPSP) affects 10 to 30% of surgical patients overall and 16 to 20% of patients after knee surgery. Patients report persistent pain in the absence of infection, mechanical disorders, or complex regional pain syndrome type I. In many cases, the mechanism is neuropathic pain related to an intraoperative nerve injury or impaired pain modulation with central sensitization. The clinical risk factors and pathophysiology of CPSP are being actively investigated. Risk factors include preoperative pain; diffuse pain; severe pain during the immediate postoperative period; anxiety, depression, or cognitive distortions such as catastrophizing; and comorbidities. The diagnosis rests on clinical grounds and should be established as early as possible to optimize the chances of improvement. The management of CPSP combines a number of perioperative prophylactic strategies and the treatment of chronic neuropathic pain. Local treatments consist of transcutaneous electrical nerve stimulation and lidocaine patches combined with tramadol. When this treatment is inadequately effective, an antidepressant or anticonvulsant can be added. A capsaicin patch is the third-line treatment, and step III opioids are the last option. Rehabilitation therapy and physical exercises are beneficial. Psychological counseling and/or cognitive behavioral therapy should be offered, if indicated, by the results of the evaluation.

[Use of strong opioids in chronic non-cancer pain in adults. Evidence-based recommendations from the French Society for the Study and Treatment of Pain]. / Utilisation des opioïdes forts dans la douleur chronique non cancéreuse chez l'adulte. Recommandations françaises de bonne pratique clinique par consensus formalisé (SFETD).

OBJECTIVES: An urgent need is to improve the efficacy and safety of use of strong opioids in chronic non-cancer pain (CNCP) through responsible prescription rules supported by scientific evidence. METHODS: Clinical questions addressing the indication, the benefice, the risk and the precautions were formulated. A task force composed of physicians from several medical specialties involved in managing CNCP was charged to elaborate evidence-based recommendations. A systematic literature search was performed using CENTRAL, MEDLINE and EMBASE databases. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. RESULTS: We selected 21 meta-analyses and 31 cohort studies for analysis. Fifteen recommendations are provided. Strong opioids are not recommended in fibromyalgia and primary headaches. Strong opioids have been shown to be moderately effective against CNCP due to osteoarthritis of the lower limbs, and for back pain and neuropathic pain. Their introduction is advised only after the failure of first-line treatments, combined with patient care, provided that the patient is made aware of the advantages and risks. It is not advisable to continue strong opioids treatment for longer than three months if no improvement in pain, function or quality of life is observed. It is also recommended not to prescribe doses exceeding 150mg/day morphine equivalent. Misuse risk factors should be investigated before prescription and misuse should be assessed at each renewal. Priority should be given to extended-release forms. It is recommended not to use transmucosal rapid-release forms of fentanyl for the management of CNCP. CONCLUSION: These recommendations are intended for all doctors needing to prescribe strong opioids in CNCP.

A randomised, double-blind, placebo-controlled trial of dolasetron, a 5-hydroxytryptamine 3 receptor antagonist, in patients with fibromyalgia.

OBJECTIVE: The purpose of the study was to evaluate the efficacy and safety of dolasetron for symptomatic relief of pain associated with fibromyalgia (FM). METHODS: This prospective, double-blind, placebo-controlled trial randomly assigned 60 patients with FM to receive placebo (n = 31) or dolasetron (n = 29) 12.5mg/d via the intravenous route on 4 days at baseline (M0), 1 month (M1), 2 months (M2) and 3 months (M3) with follow-up to month 12. The primary outcome variable was the reduction in pain intensity measured by visual analogue scale (VAS) between M0 and M3. The secondary outcome variables were patient global impression of change (PGIC), the FM impact questionnaire, assessment of quality of life (SF-36), the hospital anxiety and depression scale, the manual tender point count, and functional symptoms associated with FM. RESULTS: Reduction in pain intensity at M3 was significantly greater in dolasetron-treated patients (p = 0.04, -21.3 on a 0-100 scale) compared with placebo controls (-5.9). More patients in the dolasetron group had ≥ 30% and ≥ 50% improvement in pain (42.5% and 28% respectively in the dolasetron group versus 25% and 16% in the placebo group). The PGIC was significantly greater in the dolasetron group at M3 (p = 0.02). The other secondary outcomes failed to reach statistical significance. The most common adverse events were constipation, nausea, dizziness and headache, with no significant differences between the two groups. CONCLUSION: Intermittent IV dolasetron was safe and efficacious for the reduction of pain intensity associated with FM at 3 months.

Ultrasonography in chondrocalcinosis.

Ultrasonography can visualize calcific deposits within soft tissues. The appearance and location of the deposits distinguishes articular chondrocalcinosis from other crystal deposition diseases. The most common findings are hyperechoic dots or lines running parallel to the joint surface, hyperechoic images within fibrous cartilage (menisci and triangular fibrocartilage complex), and deposits within tendons (Achilles tendon). Studies found that ultrasonography was highly sensitive and specific for detecting calcifications, using calcium pyrophosphate dihydrate crystal detection in joint fluid as the reference standard. Good agreement has been demonstrated between radiographs and ultrasonography for the detection of calcifications. Thus, ultrasonography is valuable for diagnosing articular chondrocalcinosis via the detection of calcifications within the joint cartilage, fibrocartilage, and tendons. In addition, ultrasonography is a noninvasive, widely available, inexpensive investigation that requires no radiation exposure.