Musculoskeletal pain in female asylum seekers and hypovitaminosis D3

Résumé de l'article L'hypovitaminose D3 est bien connue et courante chez la population âgée en Occident. Toutefois, elle est probablement sous-diagnostiquée chez les jeunes femmes immigrantes, bien qu'elle soit bien documentée, principalement en Angleterre dans la population Indo-Pakistanaise. Lorsque ce déficit est diagnostiqué, le traitement substitutif est simple et bon marché. Nous avons suspecté une haute prévalence chez de jeunes femmes requérantes d'asile, surtout chez celles provenant de cultures différant quant à l'exposition solaire et la diète. Nous publions donc une série de 11 cas de patientes avec une hypovitaminose D symptomatique issues de la consultation générale de la Policlinique Médicale Universitaire. Toutes les patientes présentaient une anamnèse d'une faible exposition solaire et de douleurs osseuses diffuses, d'une fatigue, d'une faiblesse musculaire ou des modifications de la marche. Toutefois, les premiers diagnostics évoqués par les médecins étaient une possible somatisation (3 patientes), des douleurs dorso-lombaires chroniques (4 patientes) et des symptômes somatiques multiples et inexpliqués (3 patientes). Le diagnostic a été posé d'emblée chez une patiente seulement. La durée moyenne des plaintes avant la pose du diagnostic était de 38 mois et 5 jours. Avec le traitement de cholecalciférol et de calcium, les symptômes disparaissaient entre 1 et 3 mois, chez une patiente ils ont duré sept mois. Le taux moyen de 250H vitamine D3 était de 10.9 nmol/l (IR 21-131). Le taux moyen de calcium était de 2.19 mmol/l (2.15-2.55) et quatre patientes présentaient une hypocalcémie. Nous pensons donc que les femmes requérantes d'asile sont à risque d'une durée prolongée de symptômes, de part la possible haute prévalence de cette condition et la difficulté chez les médecins à la reconnaître. Le diagnostic d'hypovitaminose devrait être recherché chez les femmes requérantes d'asile souffrant de douleurs musculo-squelettiques de longue durée. Le premier diagnostic souvent évoqué, dans un contexte psychosocial souvent difficile, était de l'ordre d'un trouble somatoforme douloureux ou de somatisations. Toutefois, les douleurs liées à l'hypovitaminose D3 sont relativement bien définies ; elles sont symétriques, osseuses, débutent souvent dans la région lombaire pour ensuite s'étendre au bassin, aux membres inférieures proximalement et à la cage thoracique. Le traitement substitutif est simple, peu onéreux et il serait judicieux d'initier d'autres études pour évaluer le besoin d'une substitution de routine dans la population présentée. Abstract: Deficiency of vitamin D, which can lead to osteomalacia, is common in elderly patients in Western countries. However, it is still widely underdiagnosed in young immigrant women, even though the condition has been extensively reported in the immigrant Indo- Asian population in the United Kingdom since the 1960s. A recent study reports an average 59 months before diagnosis was established, and another study found a prevalence of 78% of hypovitaminosis D3 (compared with 58% in controls) in an Indo-Asian population attending a UK rheumatology clinic. When recognised, hypovitaminosis D3 is easily treatable. A study on osteomalacic myopathy in veiled Arabic women in Denmark found that muscle strength returned to normal (except in maximal voluntary con-traction) after six months' treatment. We expected to see this disease in female asylum seekers, especially in those from societies with different customs regarding exposure to sunlight and diet We report 11 cases of symptomatic hypovitaminosis D3 in female asylum seekers (table 1). We focus on the pathology encountered by the primary care doctors caring for these 11 patients, the length of time between the appearance of symptoms, and the establishment of the diagnosis of hypovitaminosis D3 as well as the women's response to treatment by the improvement of a wide range of clinical symptoms-bone pain, muscular weakness, and fatigue.

The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used.

BACKGROUND/OBJECTIVES: To assess the distribution of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) according to the different definitions of metabolically healthy obesity (MHO). SUBJECTS/METHODS: A total of 881 obese (body mass index (BMI) > or =30 kg/m2) subjects derived from the population-based CoLaus Study participated in this study. MHO was defined using six sets of criteria including different combinations of waist, blood pressure, total high-density lipoprotein cholesterol or low-density lipoprotein -cholesterol, triglycerides, fasting glucose, homeostasis model, high-sensitivity CRP, and personal history of cardiovascular, respiratory or metabolic diseases. IL-1β, IL-6 and TNF-α were assessed by multiplexed flow cytometric assay. CRP was assessed by immunoassay. RESULTS: On bivariate analysis some, but not all, definitions of MHO led to significantly lower levels of IL-6, TNF-α and CRP compared with non-MH obese subjects. Most of these differences became nonsignificant after multivariate analysis. An posteriori analysis showed a statistical power between 9 and 79%, depending on the inflammatory biomarker and MHO definition considered. Further increasing sample size to overweight+obese individuals (BMI > or =25 kg/m2, n=2917) showed metabolically healthy status to be significantly associated with lower levels of CRP, while no association was found for IL-1β. Significantly lower IL-6 and TNF-α levels were also found with some but not all MHO definitions, the differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity or percent body fat. CONCLUSIONS: MHO individuals present with decreased levels of CRP and, depending on MHO definition, also with decreased levels in IL-6 and TNF-α. Conversely, no association with IL-1β levels was found.

Nedd4-2 ubiquitin ligase: a contributor to experimental neuropathic pain?

Background: Neuropathic pain is associated with altered expression of voltage-gated sodium channels (VGSCs) leading to peripheral nerve hyperexcitability. Interestingly, in cell expression systems, the ubiquitin ligase Nedd4-2 regulates the cell membrane density of the most abundant peripheral and pain-related VGSC, namely Nav1.7, and decreases its sodium current. Yet nothing is known about the involvement of Nedd4-2 in nociception and chronic pain. Therefore, the goal of this study is (i) to characterize Nedd4-2 and Nav1.7 expression in an experimental model of neuropathic pain (ii) to design by viral vector-mediated gene therapy an approach to depict the implication of Nedd4-2 in chronic pain. Methods: Western Blot and immunohistochemistry experiments detecting Nav1.7 and Nedd4-2 were performed in rodent DRGs 7 days after spared nerve injury (SNI). For the viral vector-mediated gene therapy, a recombinant Adeno-Associated Virus (rAAV2/6) was generated expressing the Nedd4-2 gene. Intrathecal injection of rAAV2/6 was followed 2 weeks after by the SNI surgery. Data are expressed in mean ± SEM, n = 4 in each condition. Results: Immunofluorescence on DRGs neurons reveals a decreased number of positive Nedd4-2 cells in the SNI model (27.0 ± 1.2%) versus sham group (43.4 ± 3.5%; p <0.005), as well as an increase in positive Nav1.7 cells in SNI (50.1 ± 2.9%) versus Sham (41.6 ± 1.8%; p <0.05). The change of Nedd4-2 expression was confirmed by western-blot analysis. In addition, we show that Nedd4-2 and Nav1.7 are largely expressed in overlapping cell populations, chiefly colocalizing with markers of small nociceptive neurons. Furthermore, we report that intrathecal injection of rAAV is able to counteract the reduction of Nedd4-2 expression in SNI animals. Conclusion: Our results indicate that Nedd4-2 is mainly expressed in nociceptors and downregulated after nerve injury. Moreover, our data suggest that the reduction of Nedd4-2, after nerve injury, may modulate Nav1.7 activity and contribute to hyperexcitability in neuropathic pain. A normal level of Nedd4-2 can be restored using a viral vector and we will further assess its functional effect on pain sensitivity.

Regulation of inflammatory responses by the commensal microbiota.

It is well established that dysregulation of the interactions between the immune system and commensal bacteria is one factor that underpins the development and chronicity of a number of inflammatory diseases. Certain phyla of bacteria within the microbiota have been associated with 'health', but the mechanisms by which the presence of these bacteria supports a healthy environment are still being unravelled. Recent evidence indicates that one such mechanism involves the anti-inflammatory properties of fermentation products of fibre, short-chain fatty acids and their signalling through the G-protein coupled receptor GPR43. Recent findings also indicate that, even in health, bacterial communities harbour in the airways, indicating that direct exposure to bacterial products at this site may provide a further explanation for how commensal bacteria can regulate chronic airway inflammation.

The spared nerve injury model of neuropathic pain.

The spared nerve injury (SNI) model mimics human neuropathic pain related to peripheral nerve injury and is based upon an invasive but simple surgical procedure. Since its first description in 2000, it has displayed a remarkable development. It produces a robust, reliable and long-lasting neuropathic pain-like behaviour (allodynia and hyperalgesia) as well as the possibility of studying both injured and non-injured neuronal populations in the same spinal ganglion. Besides, variants of the SNI model have been developed in rats, mice and neonatal/young rodents, resulting in several possible angles of analysis. Therefore, the purpose of this chapter is to provide a detailed guidance regarding the SNI model and its variants, highlighting its surgical and behavioural testing specificities.

Douteur testiculaire, un défi diagnostique [Testicular pain, a diagnostic challenge?].

Scrotal pain is frequently encountered in practice, as it affects 4 men in 1000, with a peak of incidence between the ages of 45 and 50. After excluding an urological or gastrointestinal cause, referred pain of musculoskeletal origin should be considered, even in the absence of back pain. Described by Dr. Robert Maigne, this referred pain originates from a minor intervertebral dysfunction of the thoracolumbar junction. Imaging of the spine is not helpful. Rather, the diagnosis is made by seeking pain triggered by the mobilization of the lumbar vertebrae; the pinch and roll skin manoeuvre will highlight this referred pain. Treatment is symptomatic, though manual therapies by spine specialists are also recommended.

Pharmacological treatment of heterotopic ossification following hip and acetabular surgery.

Heterotopic ossification is a common complication following total hip arthroplasty and surgery following acetabular trauma. It is associated with pain and a decreased range of movement. Prophylaxis is achieved by either non-steroidal anti-inflammatory drug treatment or localised irradiation therapy. The objective of this study was to evaluate the evidence for pharmacological agents used for the prophylaxis of heterotopic ossification following hip and acetabular surgery. The study used a comprehensive literature search to identify all major clinical studies investigating the pharmacological agents used in the prophylaxis of heterotopic ossification following hip and acetabular surgery. It was concluded that indometacin remains the 'gold standard' for heterotopic ossification prophylaxis following total hip arthroplasty and is the only drug proven to be effective against heterotopic ossification following acetabular surgery. Following total hip arthroplasty, other non-steroidal anti-inflammatory drugs, including naproxen and diclofenac, are equally as effective as indometacin and can be considered as alternative first-line treatments. Celecoxib is also of equal efficacy to indometacin and is associated with significantly fewer gastrointestinal side effects. However, serious concerns were raised over the safety of selective cyclooxygenase-2 inhibitors for the cardiovascular system and these should be used cautiously.

Postoperative Cognitive Dysfunction (POCD) and Inflammatory Markers in Elderly Patients

Introduction: Particularly in elderly patients, the brain responds to a systemic inflammatory response with an increased production of inflammatory mediators. This has hypothetically been linked to the development of postoperative cognitive dysfunction (POCD). Methods: We investigated 31 patients aged >65 yrs undergoing elective major surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl, atracurium). Cognitive function was measured preoperatively and 7 days postoperatively using the extended version of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB, validated German version) for which we developed a diagnostic cut-off in healthy elderly volunteers. Systemic C-reactive protein (CRP) and interleukin 6 (IL-6) were measured preoperatively, 2 days postoperatively, and 7 days postoperatively. Values for CRP, IL-6, operative characteristics and hospital length of stay in patients with POCD and without POCD were compared using the Mann- Whitney U test and are shown as median [range]. Results: Fourteen patients (45%) developed POCD. Values for CRP were not statistically different in patients with POCD and without POCD but tended to be higher in patients with POCD 2 days postoperatively. Patients with POCD had significantly higher IL-6 values on postoperative days 2 and 7 (table 1). These patients also had a significantly longer duration of anaesthesia (305 [195-620] vs.190 [150-560] min, p = 0.034), larger intraoperative blood loss (425 [0-1600] vs. 100 [0-1500] ml, p = 0.018) and longer hospital stays (15 [8-45] vs. 8 [4-40] days, p = 0.008). Table 1 POCD (n = 14) No POCD (n = 17) p value CRP (mg/dl) preop. 4.0 [1.0-245] 4.2 [0.3-36.2] 0.6 2 days postop. 223 [20-318] 98 [4.5-384] 0.07 7 days postop. 58 [15-147] 44 [11-148] 0.2 IL-6 (U/ml) preop. 2[2-28.1] 2 [2-7.3] 0.8 2 days postop. 56 [17-315] 20 [2-123] 0.009 7 days postop. 9[2-77] 4 [2-16] 0.03 Interpretation: In this small group of patients, high IL-6 values postoperatively were associated with POCD supporting a role for systemic inflammation in the development of POCD. In patients with POCD, duration of anaesthesia was significantly longer, and intraoperative blood losses were larger. These risk factors will need to be confirmed in a larger group of patients. The difference in length of stay may be indicative of postoperative complications, which have been linked to POCD earlier.

Parents' willingness to pay for diminishing children's pain during blood sampling.

BACKGROUND: Blood sampling is a frequent medical procedure, very often considered as a stressful experience by children. Local anesthetics have been developed, but are expensive and not reimbursed by insurance companies in our country. We wanted to assess parents' willingness to pay (WTP) for this kind of drug. PATIENTS AND METHODS: Over 6 months, all parents of children presenting for general (GV) or specialized visit (SV) with blood sampling. WTP was assessed through three scenarios [avoiding blood sampling (ABS), using the drug on prescription (PD), or over the counter (OTC)], with a payment card system randomized to ascending or descending order of prices (AO or DO). RESULTS: Fifty-six responses were collected (34 GV, 22 SV, 27 AO and 29 DO), response rate 40%. Response distribution was wide, with median WTP of 40 for ABS, 25 for PD, 10 for OTC, which is close to the drug's real price. Responses were similar for GV and SV. Median WTP amounted to 0.71, 0.67, 0.20% of respondents' monthly income for the three scenarios, respectively, with a maximum at 10%. CONCLUSIONS: Assessing parents' WTP in an outpatient setting is difficult, with wide result distribution, but median WTP is close to the real drug price. This finding could be used to promote insurance coverage for this drug.

Revue de la littérature 2013--les neuropathies inflammatoires [2013: what's new in inflammatory neuropathies].

Several high-quality publications were published in 2013 and some major trials studies were started. In Guillain-Barré syndrome, events included the launch of IGOS and a better understanding of diagnostic limits, the effect of influenza vaccination, and better care, but uncertainty remains about analgesics. A new mouse model was also described. In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), diagnostic pitfalls can be recalled. Our knowledge of underlying pathophysiological processes has improved, and the value of monitoring with function and deficit scores has been demonstrated. IVIG can sometimes be effective longer than expected, but CIDP remains sensitive to corticosteroids, particularly with the long-term beneficial effects of megadose dexamethasone. The impact of fingolimod remains to be demonstrated in an ongoing trial. Advances concerning multifocal motor neuropathy, inflammatory plexopathy, and neuropathy with anti -MAG activity are discussed but treatments already recognized as effective should not be changed. Imaging of peripheral nerve progresses.

Pain and beliefs after musuloskeletal trauma: Complex relationships during the first year of rehabilitation

Introduction.- Pain and beliefs have an influence on the patient's course in rehabilitation and their relationships are complex. The aim of this study was to understand the relationships between pain at admission and the evolution of beliefs during rehabilitation as well as the relationships between pain and beliefs one year after rehabilitation.Patients and methods.- Six hundred and thirty-one consecutive patients admitted in rehabilitation after musculoskeletal trauma, were included and assessed at admission, at discharge and one year after discharge. Pain was measured by VAS (Visual Analogical Scale) and beliefs by judgement on Lickert scales. Four kinds of beliefs were evaluated: fear of a severe origin of pain, fear of movement, fear of pain and feeling of distress (loss of control). The association between pain and beliefs was assessed by logistic regressions, adjusted for gender, age, native language, education and bio-psycho-social complexity.Results.- At discharge, 44% of patients felt less distressed by pain, 34% are reinsured with regard to their fear of a severe origin of pain, 38% have less fear of pain and 33% have less fear of movement. The higher the pain at admission, the higher the probability that the distress diminished, this being true up to a threshold (70 mm/100) beyond which there was a plateau. At one year, the higher the pain, the more dysfunctional the fears.Discussion.- The relationships between pain and beliefs are complex and may change all along rehabilitation. During hospitalization, one could hope that the patient would be reinsured and would gain self-control again, if pain does not exceed a certain threshold. After one year, high pain increases the risk of dysfunctional beliefs. For clinical practice, these data suggest to think in terms of the more accessible "entrance door", act against pain and/or against beliefs, adpated to each patient.

Prevalence of Joint Hypermobility and Joint Hypermobility Syndrome in a Swiss population with Chronic Low Back Pain

Objective¦Joint hypermobility (JH) and Joint Hypermobility Syndrome (JHS) are often underdiagnosed¦and were never specifically assessed in a selected population of chronic low back pain¦(LBP). This study aimed to assess JH and JHS among a population with chronic LBP using the¦Beighton and the Brigthon criteria.¦Methods¦We conducted a retrospective cross-sectional study based on a prospective data base¦among 143 patients with non-specific chronic LBP. Patients were seen by the same rheumatologist,¦who looked for JH and JHS and took their medical history. Data were analysed using logistic¦regression.¦Results¦We found a JH prevalence of 33,3% (CI 95% 22.0-44.6) among women and 21,4% (11.7-¦31.2) among men, and for JHS, of 37,9% (26.0-49.8) among women and 30,9% (19.7-42.0) among¦men. JH was less frequent among people older than fifty (P < 0.02). JHS was more prevalent among¦Swiss individuals (P < 0.01) and among individuals having a non-manual job (P<0.03) compared to¦there opposites. Patients having an important limitation for daily living activities were four times¦more likely to have JHS. Degenerative spinal disorders were negatively associated with JH (OR¦0.31 (0.13-0.73) and JHS (OR 0.31 (0.14-0.68).¦Conclusion¦A high prevalence of joint hypermobility was found in our population. JHS should be¦part of differential diagnosis in individuals with chronic non-specific LBP.

Validation of a clinical prediction score for ruling out coronary heart disease in primary care patients with chest pain.

Background: A patient's chest pain raises concern for the possibility of coronary heart disease (CHD). An easy to use clinical prediction rule has been derived from the TOPIC study in Lausanne. Our objective is to validate this clinical score for ruling out CHD in primary care patients with chest pain. Methods: This secondary analysis used data collected from a oneyear follow-up cohort study attending 76 GPs in Germany. Patients attending their GP with chest pain were questioned on their age, gender, duration of chest pain (1-60 min), sternal pain location, pain increases with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the curve (ROC), sensitivity and specificity of the Lausanne CHD score were calculated for patients with full data. Results: 1190 patients were included. Full data was available for 509 patients (42.8%). Missing data was not related to having CHD (p = 0.397) or having a cardiovascular risk factor (p = 0.275). 76 (14.9%) were diagnosed with a CHD. Prevalence of CHD were respectively of 68/344 (19.8%), 2/62 (3.2%), 6/103 (5.8%) in the high, intermediate and low risk category. ROC was of 72.9 (CI95% 66.8; 78.9). Ruling out patients with low risk has a sensitivity of 92.1% (CI95% 83.0; 96.7) and a specificity of 22.4% (CI95% 18.6%; 26.7%). Conclusion: The Lausanne CHD score shows reasonably good sensitivity and can be used to rule out coronary events in patients with chest pain. Patients at risk of CHD for other rarer reasons should nevertheless also be investigated.