Disease status, costs and quality of life of patients with rheumatoid arthritis in France: the ECO-PR Study

ObjectiveTo investigate resource consumption and quality of life (utility) in a sample of patients covering the full spectrum of the disease, modalities of patient management and geographic areas.MethodsInformation on demographics, disease parameters, work capacity and resource consumption (in the past 1, 3 or 12 months depending on the resource) was collected in an anonymous mail survey from all members of a national patient association (ANDAR). Results are presented for the sample and by level of functional capacity, in €2005.Results1487 patients were included in the analysis (response rate 49%). Mean age was 62.7 years and 83.5% of respondents were female. Mean disease duration was 18 years; mean HAQ was 1.42; fatigue and pain ranked 5.6 and 4.8 on a scale between 0 and 10, respectively. Of patients below 60 years, 34% had taken early retirement due to RA, and only 15% of patients with a HAQ of 2 or higher were working. Productivity losses were estimated at €5076, of which indemnity payments covered €1944. Direct health care costs were €11,757 in the societal perspective and €9216 in the perspective of the national health insurance. Direct non-medical costs (including informal care) were €4857 and €136 respectively. Costs to society increased from €9400 in mild disease to €40,700 in severe disease, and to public payers from €6000 to €19,000. Utility decreased simultaneously from 0.80 to 0.06.ConclusionThe study confirms overall findings in other studies in other countries, and provides the first estimate of all costs by disease severity in France.     

No association of seropositivity for anti-Borrelia IgG antibody with mental and physical complaints

Undiagnosed chronic Lyme disease caused by Borrelia burgdorferi is considered a differential diagnoses in medically unexplained symptoms like arthralgias, distal paresthesias, depressive symptoms, lack of concentration and fatigue. The aims of the study were to assess the association of mental and physical complaints with seropositivity for anti-Borrelia IgG in a general population sample. Seropositivity indicated an infection with Borrelia in the past. The Study of Health in Pomerania was conducted in a community living in a region with endemic Lyme disease. Mental and physical complaints were assessed on 38 items with the von Zerssen's complaint scale. IgG antibodies to Borrelia were determined by ELISA in 4264 individuals. Seropositivity was analyzed applying two cut-off scores (>5 and >10 IU/ml). IgG antibodies to Borrelia were found positive in 388 subjects (9.1%) applying the >5 IU/ml cut-off and in 130 subjects (3.0%) applying the >10 IU/ml cut-off. In multivariate analyses (MANCOVA), both definitions of seropositivity were not associated with increased mental or physical complaints while adjusting for gender, age, employment status, rural residency, physical activity, diabetes mellitus and number of chronic diseases. In the general population, seropositivity for anti-Borrelia IgG antibodies was not associated with an increase of self-rated mental or physical complaints or impairments. Therefore, clinicians should not overvalue seropositivity for anti-Borrelia IgG as a medical cause for unexplained mental or physical complaints.     

Abnormal amygdala activation profile in pedophilia

Despite considerable public interest research in neurobiological correlates of pedophilia is scarce. Since amygdala activation is central for emotional valuation, arousal, and salience, we investigated the activation profile of this structure in 10 male subjects with pedophilia (exclusively attracted to boys), all convicted sex-offenders and sentenced to forensic psychiatric treatment along with ten male heterosexual matched controls. We used a sexually non-explicit functional Magnetic Resonance Imaging (fMRI) paradigm with images of men, women, boys or girls randomly embedded in neutral target/non-target geometrical symbols. We applied statistical parametric mapping (SPM2) and SPSS 14 for image processing and analysis. While controls activated significantly less to pictures of children compared to adults, the activation profile was reversed in subjects with pedophilia, who exhibited significantly more activation to children than adults. The highest activation was observed for boys in the patient group, and for women in control participants. Our data show enhanced activation to children's pictures even in an incidental context and suggest the provocative hypothesis that a normally present mechanism for reduced emotional arousal for children relative to adults is reversed in pedophilia, suggesting a neural substrate associated with deviant sexual preference in this condition. More extensive research in this field would be of benefit for both the victims and the offenders.     

Visual noise effects on emotion perception: brain potentials and stimulus identification

Event-related potential (ERP) studies revealed an early posterior negativity (EPN) for emotionally arousing pictures. Two studies explored how this effect relates to perceptual stimulus characteristics and stimulus identification. Adding various amounts of visual noise varied stimulus perceptibility of high and low arousing picture contents, which were presented as rapid and continuous stream. Measuring dense sensor event-related potentials, study I determined that noise level was linearly related to the P1 peak. Subsequently, enlarged EPNs to emotionally arousing contents were observed, however, only for pictures containing low amounts of noise, which also enabled stimulus identification as shown by study II. These data support the notion that the EPN may serve as a measure of affective stimulus evaluation at an early transitory processing period.     

Clinical, genetic, and cardiac magnetic resonance imaging findings in primary desminopathies

We report the clinical, genetic and cardiac magnetic resonance imaging (MRI) findings in 11 German patients with heterozygous E245D, D339Y, R350P and L377P desmin mutations and without cardiac symptoms. Clinical evaluation revealed a marked variability of skeletal muscle, respiratory and cardiac involvement even between patients with identical mutations, ranging from asymptomatic to severely affected. While echocardiography did not show any pathological findings in all 11 patients, cine MRI revealed focal left ventricular hypertrophy in 2 patients and MR delayed enhancement imaging displayed intramyocardial fibrosis in the left ventricle in 4 patients indicating early myocardial involvement. Our data argue against distinct genotype-phenotype correlations and suggest that comprehensive cardiac MRI is superior to conventional echocardiography for the detection of early and clinically asymptomatic stages of cardiomyopathy in desminopathy patients. Therefore, cardiac MRI may serve as a screening tool to identify patients at risk, which might benefit from early pharmacological and/or interventional (e.g. implantable cardioverter-defibrillator devices) therapy.     

Apparent relapse of imported Plasmodium ovale malaria in a pregnant woman

A 27 week pregnant woman who had lived in Bangkok, Thailand, for 18 months presented to her obstetrician with a 1-week history of intermittent fever and malaise. Medical history was significant for multiple episodes of malaria during her 10 years of employment in sub-Saharan Africa before her relocation to Thailand. The initial malaria smear was negative. She returned a week later with no resolution of her symptoms, at which time she was found to have Plasmodium ovale by microscopy and polymerase chain reaction. She had an excellent response to chloroquine, which she continued weekly until 36 weeks of gestation. She delivered a healthy term infant and received radical cure with primaquine after cessation of breastfeeding. This case shows challenging issues in detection and management of imported P. ovale malaria.     

Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Bangladesh

Bangladesh faces increasing levels of chloroquine resistance, and drug sensitivity to sulfadoxine-pyremethamine is already compromised. Therefore, the Ministry of Health recently changed the national treatment guidelines to artemisinin-based combination therapies. The purpose of this study was to determine the baseline therapeutic efficacy of artemether-lumefantrine used as a six-dose regimen for the treatment of uncomplicated Plasmodium falciparum malaria. Sixty-seven patients were enrolled in the study; the cure rate in a 42-day follow-up after an adjustment by polymerase chain reaction was 94.3%. The treatment led to rapid fever (mean +/- SD = 25.82 +/- 12.14 hours) and parasite (30.36 +/- 19.43 hours) clearance. These data suggest that artemether-lumefantrine is a highly efficacious and well-tolerated treatment for uncomplicated P. falciparum malaria in Bangladesh.     

TNF polymorphisms in psoriasis: association of psoriatic arthritis with the promoter polymorphism TNF*-857 independent of the PSORS1 risk allele

OBJECTIVE: Single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor gene TNF at positions -238 and -308 have been associated with psoriasis vulgaris and psoriatic arthritis (PsA). The strong linkage disequilibrium (LD) at chromosome region 6p21, a region known to harbor risk factors for psoriasis susceptibility (PSORS1) other than just SNPs of the TNF gene, renders the interpretation of these findings difficult. The aim of this study was to analyze several SNPs of the TNF gene and its neighboring LTA gene for independent and dependent carriage of the PSORS1 risk allele. METHODS: SNPs in the promoter of the TNF (-238G/A, -308G/A, -857C/T, and -1031T/C), LTA (+252A/G), TNLFRSF1A (+36A/G), and TNLFRSF1B (+676T/G) genes were genotyped in 375 psoriasis patients, 375 PsA patients, and 376 controls. The Trp- Trp-Cys-Cys haplotype of the CCHCR1 gene (CCHCR1*WWCC) was used as an estimate of the risk allele PSORS1. RESULTS: Whereas we were able to confirm the previously described strong association of allele TNF*-238A with psoriasis, our study revealed that this association was completely dependent on carriage of the PSORS1 risk allele. For PsA, but not psoriasis vulgaris without joint involvement, a strong association with the allele TNF*-857T (odds ratio 1.956 [95% confidence interval 1.334-2.881]; corrected P = 0.0025) was also detected in patients negative for the PSORS1 risk allele. CONCLUSION: Our results indicate that there are genetic differences between psoriasis vulgaris patients with and without joint manifestations. While the previously reported association between TNF*-238A and psoriasis seems to primarily reflect LD with PSORS1, TNF*-857T may represent a risk factor for PsA that is independent of the PSORS1 allele.     

The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo

In addition to the ARF/p53 pathway, the DNA damage response (DDR) has been recognized as another oncogene-provoked anticancer barrier in early human tumorigenesis leading to apoptosis or cellular senescence. DDR mutations may promote tumor formation, but their impact on treatment outcome remains unclear. In this study, we generated ataxia telangiectasia mutated (Atm)-proficient and -deficient B-cell lymphomas in Emu-myc transgenic mice to examine the role of DDR defects in lymphomagenesis and treatment sensitivity. Atm inactivation accelerated development of lymphomas, and their DNA damage checkpoint defects were virtually indistinguishable from those observed in Atm+/+-derived lymphomas that spontaneously inactivated the proapoptotic Atm/p53 cascade in response to Myc-evoked reactive oxygen species (ROS). Importantly, acquisition of DDR defects, but not selection against the ARF pathway, could be prevented by lifelong exposure to the ROS scavenger N-acetylcysteine (NAC) in vivo. Following anticancer therapy, DDR-compromised lymphomas displayed apoptotic but, surprisingly, no senescence defects and achieved a much poorer long-term outcome when compared with DDR-competent lymphomas treated in vivo. Hence, Atm eliminates preneoplastic lesions by converting oncogenic signaling into apoptosis, and selection against an Atm-dependent response promotes formation of lymphomas with predetermined treatment insensitivity.