[Transition from pediatric to adult care: Recommendations of the French network for autoimmune and autoinflammatory diseases (FAI2R)]. / La transition de la pédiatrie à l'âge adulte : recommandations de prise en charge de la filière des maladies auto-immunes et auto-inflammatoires rares FAI2R.

Autoimmune and autoinflammatory diseases (AIDs) are a heterogeneous group of diseases. They can occur in childhood and account for significant morbidity and mortality. Transitioning from pediatric to adult healthcare can be difficult for patients and their families. It can interfere with patient follow-up and management, and eventually lead to complications. Although recommendations exist for the successful transition of patients with chronic diseases, few are specifically adapted to children and adults with AIDs (Suris et al., 2015-Solau-Gervais, 2012). The French working group on transition of the rare autoimmune and autoinflammatory diseases presents its reflections and recommendations for a successful transition. Preparation for transition should start early. Its goals are to empower adolescents by providing them with the knowledge to manage their own care, respond appropriately to changes in their condition, and evolve within the adult healthcare system. This requires the active participation of the patient, his or her family, as well as the pediatric and adult medical teams. The transition process involves multidisciplinary care and dedicated therapeutic education programs. Finally, the identification of medical specialists by region, trained in rare AIDs and accompanied by expert patients, may improve the management of patients with rare AIDs from adolescence to adulthood.

Patients' association programs for adolescents and young adults: The JAP study.

INTRODUCTION: A dozen innovative care clinics have recently opened in France to support the transition of adolescents with chronic conditions between pediatric and adult healthcare units through various interventions. Some patients' associations have set up specific programs for adolescents and young adults (AYAs) in order to facilitate the transition process, but they are not well-known among healthcare professionals. Our aim was to describe these programs and to evaluate the quality of their implementation and transferability into transition clinics. MATERIEL AND METHODS: We conducted semistructured interviews with representatives of associations that proposed interventions dedicated to AYAs with chronic conditions. We collected quantitative and qualitative data to describe these interventions. Descriptive statistics were run on quantitative data and a thematic analysis of the qualitative data was made. RESULTS: A questionnaire was sent to 55 associations, 19 (36%) of them had established programs and were contacted; interviews were conducted with 16 of them. Thirteen were national associations, 11 focused on a specific chronic disease, three supported multiple chronic conditions, and two were available to any AYA with chronic disease. Programs were mainly camps (n=5; from 2days to 3weeks) and workshops (n=5). Educational considerations and hobbies were more frequently discussed when peers were directly involved in the program. Stakeholders were mainly other patients and peers (9/16). Fourteen out of 16 were perceived as successful (perceived improvement in AYA quality of life and/or positive feedback). Twelve out of 16 associations thought that their program could be transferable to transition clinics and all were interested in collaboration. DISCUSSION: This work highlights five key points to be considered in the clinical care setting before building programs: unique tailoring and customization, complementarity with existing programs in patients' associations, viability based on peer involvement and evaluation, a common main goal, and using transition clinics' assets to direct AYAs towards the most suitable program.

Transition from paediatric to adult care: what makes it easier for parents?

OBJECTIVE: To assess differences between parents of adolescents with chronic illness (CI) going through a self-reported easy or difficult transfer. METHODS: Seventy-two parents of CI youths who had already transferred to adult care were divided according to whether they considered that the transfer had been easy (n = 45) or difficult (n = 27). We performed a bivariate analysis comparing both groups and variables with a significance level < .1 were included in a logistic regression. Results are presented as adjusted odds ratio (aOR). RESULTS: Over one third of parents (27/72) reported a difficult transfer. At the multivariate level, higher socioeconomic status (aOR: 7.74), parents feeling ready for transfer (aOR: 6.54) and a good coordination between teams (aOR: 7.66) were associated with an easy transfer. CONCLUSIONS: An easy transfer for parents is associated with feeling ready and considering that the coordination between teams is good. Health providers should consider these requisites for a successful transfer.

[Practice guidelines of the use of bisphosphonates in solid tumours with bone metastases and in multiple myeloma]. / Guide de recommandations d'utilisation des bisphosphonates dans les lésions osseuses malignes des tumeurs solides et du myélome multiple.

Bisphosphonates are indicated for the treatment of bone lesions in patients with solid tumours or multiple myeloma. Bisphosphonates have proven their effectiveness in reducing the number of bone complications (hypercalcemia, pain, disease-related fractures, spinal cord compression) and delaying their occurrence in patients with bone tumours; they have also been shown to reduce the need for bone surgery and palliative or pain-relieving radiotherapy in these patients. International recommendations for the treatment of bone lesions related to malignant solid tumours and multiple myeloma have been established. We have elaborated clinical practice guidelines on the use of bisphosphonates to assist treatment decision-making in bone oncology. The guide contains decision trees and tables with information to guide pre-treatment evaluation and patient follow-up, as well as indications and conditions of use of bisphosphonates. In 2007, the regional cancer network of Rhône-Alpes, ONCORA, formed a working group (GIP ONCORA) to elaborate the guideline. The final version was then discussed and adopted at a plenary session in July 2009, during a collaborative workshop on supportive care recommendations organized by ONCORA and the regional cancer network of Lorraine.

[Monoarthritis caused by Streptococcus pyogenes after nasal septoplasty: interest of the nasal decontamination in preoperative care]. / Monoarthrite àStreptococcus pyogenes dans les suites d'une septoplastie: intérêt de la décontamination nasale en préopératoire.

The nasal septoplasty is a very current intervention in otorhinolaryngology surgery. The infectious complications of this intervention are rare and mostly mild. We report here the case of a patient hospitalized in ambulatory surgery within a fracture of the nose with luxation of the septum in the nasal fossa. This patient was operated for a reduction of this fracture with septoplasty. Twelve hours after the intervention the patient presented septic arthritis due to Streptococcus pyogenes. The tracks of prevention are presented.

Management of haemophilic arthropathy.

Despite the tremendous benefit offered by primary prophylaxis, recurrent joint bleeding with progression to chronic synovitis and haemophilic arthropathy is still a daily concern for the multidisciplinary health care teams managing patients with severe haemophilia or haemophilia complicated by inhibitor development. Advanced stages of arthropathy could be prevented by regular assessment of musculoskeletal status and thus early detection of symptoms, daily rehabilitation exercises at home, and implementation of appropriate physiotherapy and medical training. Patient's education and psychological counselling are crucial. New tools such as magnetic resonance imaging are promising for the monitoring of these patients and might promote early detection of arthropathy and thus appropriate preventive measures to avoid further joint deterioration can be implemented. Medical synovectomy such as radionucleide synoviorthesis is a simple and non-invasive procedure that often delays the need for surgery which despite considerable improvement in techniques and postoperative rehabilitation remains a high-risk strategy in patients with severe haemophilia, especially those with inhibitors. In these high risk patients, availability of specific clotting factors such as activated prothrombin complex concentrate (FEIBA, Baxter, Vienna, Austria) and more recently, recombinant factor VIIa (rFVIIa, NovoSeven, Bagsvaerd, Denmark) has allowed to perform effective and safe orthopaedic procedures. The on-going EUREKA study will undoubtedly provide additional information about the optimal use of rFVIIa in this context.

The French version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

[Standardization and automation of HLA B27 typing by flow cytometry: validation and comparison with microlymphocytotoxicity]. / Standardisation et automatisation du typage HLA B27 par une technique cytofluorimétrique: validation par comparaison à la microlymphocytoxicité.

One of the strongest known association between human leukocyte antigen (HLA) phenotype and disease is that of ankylosing spondylitis and HLA-B27. Thus, the determination of HLA-B27 status is an useful tool in the diagnosis of ankylosing spondylitis. To date, the 2 reference methods for HLA typing (microlymphocytotoxicity and molecular biology techniques), are costly in terms of both technician time and materials, and require a great deal of experience. In total, these techniques are not well-suited for routine application in clinical immunology laboratories. Use of flow cytometry has recently been applied for HLA-B27 typing. Nevertheless, it requires an extensive validation protocol. We developed a flow cytometry technique as standardized as possible (whole blood, automated lysing system, automated photomultiplier voltage calibration, definition of thresholds stable with time) and validated our results by comparison with microlymphocytotoxicity. In total, 326 samples were analyzed. We found 99% of concordant results between the 2 techniques, and neither false positive results nor false negative results with flow cytometry could be observed. These results illustrate the reliability of the protocol. It should be remembered that reference technique remains necessary to confirm the few results (< 1%) found in "grey zone" by flow cytometry. Standardization of flow cytometry techniques, as described in this work for HLA B27, seems to be a reasonable goal for the next decade in clinical immunology laboratories.

Upper lumbar disk herniations.

Specific features of upper lumbar disk herniations are reviewed based on data from the literature and from a retrospective study of 24 cases treated surgically between 1982 and 1994 (seven at L1-L2 and 17 at L2-L3). Clinical manifestations are polymorphic, misleading (abdominogenital pain suggestive of a visceral or psychogenic condition, meralgia paresthetica, isolated sciatica; femoral neuralgia is uncommon) and sometimes severe (five cases of cauda equina syndrome in our study group). The diagnostic usefulness of imaging studies (radiography, myelography, computed tomography, magnetic resonance imaging) and results of surgery are discussed. The risk of misdiagnosis and the encouraging results of surgery are emphasized.

A randomized trial of testosterone therapy in males with rheumatoid arthritis.

Thirty-five male patients, aged 34-79 yr, with definite rheumatoid arthritis (RA) were recruited from out-patient clinics and randomized to receive monthly injections of testosterone enanthate 250 mg or placebo as an adjunct therapy for 9 months. Endpoints included disease activity parameters and bone mineral density (BMD). At baseline, there were negative correlations between the ESR and serum testosterone (r = -0.42, P < 0.01) and BMD (hip, r = -0.65, P < 0.01). A total of 29.6% of all patients had at least one vertebral fracture, most having multiple fractures. Back pain, however, was not more prevalent in fracture patients (55% vs 50%). Disease activity was significantly higher in the fracture group (joint score P < 0.05, rheumatoid factor P < 0.01). Thirty patients completed the trial, 15 receiving testosterone and 15 receiving placebo. There were significant rises in serum testosterone, dihydrotestosterone and oestradiol in the treatment group. There was no significant effect of treatment on disease activity overall, five patients receiving testosterone underwent a "flare'. Differences in mean BMD following testosterone or placebo were non-significant (spine: +1.2% vs -1.1%; femur: -0.3% vs +0.3%). There was no suggestion of a positive effect of testosterone on disease activity in men with RA.

Direct degradation of articular cartilage by rheumatoid synovial fluid: contribution of proteolytic enzymes.

OBJECTIVE: To test the effects of synovial fluids (SF) on human cartilage in an in vitro model. METHODS: Freshly collected SF were incubated with cryostat sections of articular cartilage, and glycosaminoglycan (GAG) loss determined by microdensitometry after alcian blue staining. RESULTS: Of 20 rheumatoid SF, 11 induced significant GAG loss compared with only 3 out of 15 osteoarthritic SF. The effect of rheumatoid fluids appeared to be related to disease activity. GAG loss was partially prevented by a broad spectrum serine protease inhibitor and a specific elastase inhibitor. Cartilage degrading activity was lost on storage which may explain why it has not been widely reported before. CONCLUSION: Rheumatoid SF can directly degrade cartilage through the action of proteases. There is an involvement of serine proteases, elastase in particular.

Cartilage contribution to gender differences in joint disease progression. A study with rat articular cartilage.

OBJECTIVE: Rheumatoid arthritis is associated with a worse prognosis in females and is influenced by sex hormone changes. Similar observations in osteoarthritis support the hypothesis that gender differences in cartilage make a hitherto unrecognized contribution to gender differences in arthritis. The aim of the present study was to investigate potential gender differences in articular cartilage biochemistry, metabolism and response to inflammatory mediators. METHODS: Femoral head cartilages from age-matched male and female Wistar rats were analysed for the water, glycosaminoglycan, hydroxyproline and collagen crosslink contents. Proteoglycan loss and synthesis were assessed in vitro, and in the presence and absence of serum and interleukin-1. An in vivo model of inflammation-induced cartilage degradation was employed to investigate gender differences in cartilage susceptibility to erosion caused by granulomatous tissue. RESULTS: Articular cartilage from male Wistar rats presented higher levels of both proteoglycan and collagen and showed a lower spontaneous glycosaminoglycan loss and higher proteoglycan synthesis in vitro than cartilage from females. Proteoglycan synthesis from female, but not male, cartilage was significantly stimulated by foetal calf serum. Female cartilage was more sensitive to IL-1 inhibition of proteoglycan synthesis while the opposite was observed in IL-1-induced proteoglycan loss. Female cartilage was more susceptible to granuloma-induced degradation than male when implanted into female mice, but no differences were observed between male and female cartilage implanted in male mice. CONCLUSION: These results demonstrate important gender differences in cartilage biochemistry, metabolism and susceptibility to inflammatory mediators which may have important consequences for the joint destruction in arthritis and support a role for hormone therapy.

Sex differences in inflammation induced cartilage damage in rodents. The influence of sex steroids.

OBJECTIVE: To investigate sex differences in granulomatous inflammation and its effects upon articular cartilage and to assess the potential role of sex steroids in the process. METHODS: The cotton-pellet cartilage implant model was used with male and female mice in the presence and absence of gonadectomy and hormone replacement. The effects of granulomatous tissue upon articular cartilage was assessed and tissue content of interleukin 1 (IL-1) was determined. The expression of sex hormone receptors in inflammatory tissue was investigated by immunocytochemistry. RESULTS: Female mice showed a higher ability than males to degrade cartilage irrespective of the sex of the cartilage implanted. Gonadectomy resulted in a significant acceleration of cartilage damage in both sexes, which was reverted by estrogen replacement in females and androgen replacement in males. Female granulomata had significantly higher IL-1 content than those from males. Gonadectomy was associated with an increased IL-1 content in males but not in females, the effects being abolished by androgen replacement in males. Estrogen and androgen receptors were identified in inflammatory cells from the granulomatous tissue. CONCLUSION: Our data demonstrate that sex hormones affect inflammation induced cartilage degradation in male and female mice probably through the modulation of cytokine production and release in the granulomatous tissue. Further investigation on the effects of sex steroids in inflammation induced cartilage degradation may help elucidate their pathogenic role and therapeutic potential in human disease.

Protective effect of androgens against inflammation induced cartilage degradation in male rodents.

OBJECTIVES: Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents. METHODS: An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals. RESULTS: Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage. CONCLUSIONS: Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability.

Arrhythmogenicity of antiarrhythmic drugs and intraventricular conduction disorders: possible aggravation by myocardial ischemia--study in the porcine in situ heart.

The effects of three antiarrhythmic drugs were investigated in anesthetized, open-chest pigs, in a left ventricular area, under pacing at a constant high rate (180 beats/min), in the absence and presence of ischemia. Ischemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin. In addition to the surface electrocardiogram, conduction time and monophasic action potential were recorded in the contractile fibers. In the absence of ischemia, intravenous flecainide and propafenone 2.5 mg/kg, and intravenous cibenzoline 2.0 mg/kg considerably lengthened conduction time (by 50-90%) but had no significant effect on the monophasic action potential duration. Consequently, the cited antiarrhythmic drugs enhance the prolongation of conduction time by 60% but do not limit the 30% shortening of the monophasic action potential caused by ischemia. Contrary to what was expected, they largely reduced the time to onset of the fibrillation due to ischemia from about 120 to 25 seconds. Thus, they manifested profibrillatory properties (more pronounced than those of other antiarrhythmic drugs of class I), which might be explained by their potent action on depolarization.

Cartilage degradation by polymorphonuclear leucocytes: in vitro assessment of the pathogenic mechanisms.

Polymorphonuclear leucocytes (PMNs), which predominate in inflammatory synovial fluid, can degrade cartilage. This was measured by a novel in vitro model; PMNs were incubated for up to one hour with 2 or 3 microns sections of cartilage and the glycosaminoglycan loss determined by microdensitometry after alcian blue staining. Glycosaminoglycan loss could be as a result of damage from reactive oxygen species, proteolytic enzymes, or a combination of the two. The relative contributions of these mechanisms were evaluated using selective inhibitors. The results show that activated PMNs will degrade cartilage and that this degradation is due to proteolytic enzymes and not reactive oxygen species. There is a specificity involving elastase but not other serine proteases. It is suggested that enzyme inhibition may play a part in reducing PMN mediated cartilage damage.

Calcium channel modulators and susceptibility to ischaemic ventricular fibrillation: modification of cellular calcium overload.

The effects of the calcium channel modulators, Bay k 8644, infused i.v. at a rate of 2.5 micrograms/kg/min, and diltiazem, injected i.v. in a dose of 0.5 mg/kg, on the susceptibility to fibrillation induced by ischaemia, were investigated in anaesthetized, open-chest pigs. Ischaemia was produced, under ventricular pacing at constant high rate (180 beats/min), by transient complete occlusion of the left anterior descending coronary artery, near its origin. It was maintained till the triggering of fibrillation. The propensity to fibrillation was judged from the time elapsing between the onset of occlusion and the onset of fibrillation (time to fibrillation). In addition to the surface electrocardiogram, conduction time and monophasic action potential were recorded in the ventricular contractile fibres, as were dP/dtmax in the left ventricle and blood pressure in the carotid artery. At the end of a 10 min infusion, Bay k 8644 lowered to a large extent (about 40%) the time to fibrillation, which returned to its control values within the following 20 min. Conversely, diltiazem increased the time to fibrillation by a factor 4 or 5 at 5 min after its administration. This time to fibrillation remained substantially increased 25 min later. These changes were not associated with alterations in conduction time or monophasic action potential duration in the absence of ischaemia, but with significant alterations in myocardial contractility and blood pressure: in the direction of an increase with Bay k 8644 and of a decrease with diltiazem. These results are in agreement with the enhancement by Bay k 8644 and the prevention by diltiazem of cell calcium overload which is at present recognized as being the essential determinant of the fibrillatory process.