Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study.

INTRODUCTION: We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis. METHODS: In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to--or had contraindications for--non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version). RESULTS: At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab 150 mg group approached those for the US general population by seven days post-dose and reached norm values by eight weeks post-dose. CONCLUSIONS: Canakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvements in HRQoL were seen in both treatment groups with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg. TRIAL REGISTRATION: clinicaltrials.gov: NCT00798369.

Epidemiologic study of low back pain in 1398 Swiss conscripts between 1985 and 1992.

The two objectives of this study, based on a sample of 1398 Swiss army conscripts born in 1966 who participated in a first study in 1985, were to measure the prevalence of low back pain (LBP) at age 26 years and its incidence between 19 and 26 years and to analyze the relationship between LBP and occupational, nonoccupational, or physical risk factors. The lifetime prevalence of LBP at age 26 was 69.1% and the incidence of LBP between 19 and 26, 44.7%. A history of LBP or a pathological physical examination result at age 19 did not predict the prevalence or the incidence at age 26. Standing, twisting, vibration, and heavy work were significantly associated with chronic LBP and/or the 1-year prevalence of LBP at age 26 (P<0.05). The evolution of sport and leisure-time activities from age 19 to 26 did not differ between people with or without LBP. The ergonomic organization of the workplace should represent a major element of future strategies to prevent LBP.

Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients.

Epstein-Barr virus (EBV) contributes to the pathogenesis of post-transplant lymphoproliferative disease (PTLD) in more than 70% of cases. EBV DNAemia surveillance has been reported to assist in the prevention and treatment of PTLD in hematopoietic stem-cell transplantation (HSCT) recipients. Derived from experience in HSCT and taking into account that PCR-based EBV monitoring techniques are currently available in most solid organ transplant (SOT) centres, there is a great interest in EBV surveillance and prevention of PTLD in SOT recipients. In the present document we have tried to address from a practical perspective different important topics regarding the prevention and management of EBV-related PTLD in SOT. To this end, available information on SOT was analysed and combined with potentially useful data from HSCT and expert observations. The document is therefore structured according to different specific questions, each of them culminating in a consensus opinion of the panel of European experts, grading the answers according to internationally recognized levels of evidence. The addressed issues were grouped under the following topics. (i) Timing and epidemiological data of PTLD. Prophylaxis guided by clinical risk factors of early and late PTLD in SOT. (ii) Relationship of EBV DNAemia load monitoring and the development of PTLD in solid organ transplant recipients. (iii) Monitoring of EBV DNAemia after SOT. Which population should be monitored? What is the optimal timing of the monitoring? (iv) Management of SOT recipients with persistent and/or increasing EBV DNAemia.

Approche multidisciptinaire des coûts humains des lombalgies [Human cost of low back pain: a multi-disciplinary approach]

The valuation of human costs is a necessity, but this task poses many problems of method. A team made of a philosopher, a psychologist and a physician has been working with economist researchers in order to look into the meaning that the preferences announced at the time of the inquiries on human costs by QALY methods could assume. These methods are often used to obtain a valuation of the impact of a health attack on people's quality of life. The methods--in the frame of the argument assumed by the economic theory on well-being--hypothesize that people's choices depend mainly on cognitive work. The qualitative interviews show that the psychological construction process for the announced preferences largely overlap this frame. In this paper the authors hastily tackle the factors which have an effect on the preferences. They conclude that the QALY methods don't seem to be able to assess the quality of life nori to valuate the damage that the quality of life could include.

A non-invasive assessment of hepatic glycogen kinetics and post-absorptive gluconeogenesis in man.

A novel approach to the study of hepatic glycogen kinetics and fractional gluconeogenesis in vivo is described. Ten healthy female subjects were fed an iso-caloric diet containing 55% carbohydrate energy with a 13C abundance of 1.083 atom percent for a 3-day baseline period; then, a diet of similar composition, but providing carbohydrate with a 13C abundance of 1.093 atom percent was started and continued for 5 days. Resting respiratory gas exchanges, urinary nitrogen excretion, breath 13CO2 and plasma 13C glucose were measured every morning in the fasting state. The enrichment in 13C of hepatic glycogen was calculated from these measured data. 13C glycogen enrichment increased after switching to a 13C enriched carbohydrate diet, and was identical to the 13C enrichment of dietary carbohydrates after 3 days. The time required to renew 50% of hepatic glycogen, as determined from the kinetics of 13C glycogen enrichment, was 18.9 +/- 3.6 h. Fractional gluconeogenesis, as determined from the difference between the enrichments of glucose oxidized originating from hepatic glycogen and plasma glucose 13C was 50.8 +/- 5.3%. This non-invasive method will allow the study of hepatic glycogen metabolism in insulin-resistant patients.

Prise en charge du syndrome post-thrombotique [Management of post-thrombotic syndrome].

Post-thrombotic syndrome (PTS) is the most frequent chronic complication of deep vein thrombosis with an estimated prevalence of 30-50%. PTS is a significant cause of disability, especially when complicated by venous ulcers. Therefore, it has important socio-economic consequences for both the patient and the health care system. Aim of this review is to resume state of the art literature on the management of PTS.

Sudden death: ethical and legal problems of post-mortem forensic genetic testing for hereditary cardiac diseases.

Hereditary non-structural diseases such as catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT, and the Brugada syndrome as well as structural disease such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) cause a significant percentage of sudden cardiac deaths in the young. In these cases, genetic testing can be useful and does not require proxy consent if it is carried out at the request of judicial authorities as part of a forensic death investigation. Mutations in several genes are implicated in arrhythmic syndromes, including SCN5A, KCNQ1, KCNH2, RyR2, and genes causing HCM. If the victim's test is positive, this information is important for relatives who might be themselves at risk of carrying the disease-causing mutation. There is no consensus about how professionals should proceed in this context. This article discusses the ethical and legal arguments in favour of and against three options: genetic testing of the deceased victim only; counselling of relatives before testing the victim; counselling restricted to relatives of victims who tested positive for mutations of serious and preventable diseases. Legal cases are mentioned that pertain to the duty of geneticists and other physicians to warn relatives. Although the claim for a legal duty is tenuous, recent publications and guidelines suggest that geneticists and others involved in the multidisciplinary approach of sudden death (SD) cases may, nevertheless, have an ethical duty to inform relatives of SD victims. Several practical problems remain pertaining to the costs of testing, the counselling and to the need to obtain permission of judicial authorities.

Glial cells and chronic pain.

Over the past few years, the control of pain exerted by glial cells has emerged as a promising target against pathological pain. Indeed, changes in glial phenotypes have been reported throughout the entire nociceptive pathway, from peripheral nerves to higher integrative brain regions, and pharmacological inhibition of such glial reactions reduces the manifestation of pain in animal models. This complex interplay between glia and neurons relies on various mechanisms depending both on glial cell types considered (astrocytes, microglia, satellite cells, or Schwann cells), the anatomical location of the regulatory process (peripheral nerve, spinal cord, or brain), and the nature of the chronic pain paradigm. Intracellularly, recent advances have pointed to the activation of specific cascades, such as mitogen-associated protein kinases (MAPKs) in the underlying processes behind glial activation. In addition, given the large number of functions accomplished by glial cells, various mechanisms might sensitize nociceptive neurons including a release of pronociceptive cytokines and neurotrophins or changes in neurotransmitter-scavenging capacity. The authors review the conceptual advances made in the recent years about the implication of central and peripheral glia in animal models of chronic pain and discuss the possibility to translate it into human therapies in the future.

La dysménorrhée: un problème pour le pédiatre [Dysmenorrhea: a problem for the pediatrician?].

Dysmenorrhea is common in adolescent years, especially after the onset of ovulatory cycles, usually 2 to 3 years after menarche. Pain and symptoms are responsible for school absenteeism and interruption of sports and social activities. OBJECTIVES: This study aims to measure the prevalence of severe dysmenorrhea and its consequences on adolescent girls in Switzerland. Treatment of dysmenorrhea is discussed and recommendations for clinical practice are given. STUDY DESIGN: Cross sectional survey (SMASH 02) on a nationally representative sample of adolescents (n=7548; 3340 females), aged 16 to 20 years who attended post-mandatory education. A self-administered questionnaire was used to assess the severity of dysmenorrhea and its consequences on daily life pursuit of medical help and medications used. RESULTS: Among 3340 girls, 86.6% suffered from dysmenorrhea-related symptoms: 12.4% described having severe dysmenorrhea and 74.2% moderate dysmenorrhea. Girls with severe dysmenorrhea described heavier consequences on daily activities compared with girls without dysmenorrhea: 47.8% of girls with severe dysmenorrhea reported staying at home and 66.5% declared reducing their sportive activities. Yet, fewer than half have consulted a physician for this complaint and even fewer were treated properly. RECOMMENDATION: The pediatrician has a pivotal role in screening young patients for dysmenorrhea, as well as, educating and effectively treating adolescent girls with menstruation-associated symptoms. Non-steroidal anti-inflammatory drugs are considered the first-line of treatment for dysmenorrhea, and adolescents with symptoms that do not respond to this treatment for 3 menstrual periods should be offered combined oestroprogestative contraception and must be followed up, as non-responders may have an underlying organic pathology. CONCLUSION: Dysmenorrhea is a frequent health problem in adolescent years and adolescent care providers should be able to care for these patients in an efficient way.