Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort.

OBJECTIVE: To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assess anti-JCV serostatus in samples obtained before diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: This was a blinded, retrospective cross-sectional and longitudinal analysis for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples obtained from 2,253 patients nationwide for routine testing for anti-natalizumab antibodies during open-label treatment between 2007 and 2010. RESULTS: Of the natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV antibodies. The rate of seropositivity was higher in males and increased with age, with a plateau between age intervals 20-29 and 30-39 years. In longitudinal analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to seropositive status over 7.7 months; 4.7% reverted from antibody-positive to seronegative status over 7.9 months. Antibody levels, especially in the latter group, were low, indicating fluctuations around the lower cut point of the assay. Neither anti-JCV serostatus nor antibody levels were associated with immunosuppressive pretreatment, duration of natalizumab treatment, or anti-natalizumab antibodies. All samples obtained from 10 patients who developed PML were seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2 samples at diagnosis). Antibody levels in these samples were higher than those in samples from seropositive patients who did not develop PML. CONCLUSIONS: These data argue for the potential clinical utility of JCV serology for PML risk stratification. However, further investigations of fluctuations in serostatus and of antibody levels for a more precise understanding of the predictive value are warranted.

[Clinical trials with medical devices: lack of quality illustrated for faecal incontinence]. / Therapiestudien mit Medizinprodukten: Mangelnde Qualität illustriert anhand analer Inkontinenz.

BACKGROUND: Medical devices must be safe and functioning states the law. Treatments with medical devices need not be efficacious to be allowed. We investigated special requirements and problems arising from the law. METHODS: The market for medical devices is contrasted with that for drugs. The requirements of relevant laws are discussed. Finally, published clinical studies on anal incontinence are analysed with respect to their methodological quality. RESULTS: Clinical trials of medical devices for treat-ing anal incontinence are of poor methodological quality thus preventing evaluation of the devices' utility. CONCLUSION: Large, high quality clinical studies of the efficacy of medical devices for treating anal incontinence are urgently needed. Only such studies enable health technology assessment and comprehensible decisions on reimbursement by health insurance.

Glycaemic control is positively associated with prevalent fractures but not with bone mineral density in patients with Type 1 diabetes.

AIM: There are conflicting data regarding the risk of osteoporosis in patients with Type 1 diabetes. We investigated an association between diabetes, bone mineral density and prevalent fractures. METHODS: A single-centre, cross-sectional study of men and pre-menopausal women with Type 1 diabetes (n = 128) and a matched control group (n = 77) was conducted. The primary outcome measure was bone mineral density and secondary measures were markers of bone metabolism and prevalent fractures. RESULTS: Hip and total body bone mineral densities were significantly lower in women with diabetes compared with control subjects. In men, no difference in bone mineral density was found. A multivariate regression analysis in women with diabetes revealed higher BMI as the strongest predictor of higher total hip, femoral neck and total body bone mineral density, whereas previous fractures were inversely associated with total hip bone mineral density and C-terminal telopeptide of type I collagen with total body bone mineral density. Poor long-term glycaemic control was not associated with low bone mineral density. Fracture frequency was higher in patients with diabetes compared with control subjects (1.64 vs. 0.62 per 100 patient-years; P < 0.05). In a multivariable model, long-term HbA(1c) control was associated with increased clinical fracture prevalence (OR 1.92; 95% CI 1.09-2.75) in those with diabetes. CONCLUSIONS: Type 1 diabetes contributes to low bone mineral density in women. Previous fractures and low BMI were strong predictors of impaired bone mineral density and should therefore be considered in risk estimation. Fractures are more frequent in Type 1 diabetes. Long-term hyperglycaemia may account for impaired bone strength, independently from bone mineral density.

[Percentiles of body mass index of 18-80-year-old German adults based on data from the Second National Nutrition Survey]. / Perzentilen des Body-Mass-Index auch für 18- bis 80-Jährige? Daten der Nationalen Verzehrsstudie II.

BACKGROUND: Obesity is associated with an increasing risk of morbidity and mortality. The World Health Organization (WHO) defines obesity as a body mass index (BMI) > or = 30.0 kg/m2. In contrast, percentiles depending on age and sex are used in adolescence. DATA AND METHODS: Using the LMS method, age and gender specific BMI percentiles for adulthood are estimated. Data basis is the Second Germany National Nutrition Survey (NVS II) which was surveyed in 2005 and 2006. This study is representative for the German population, and it is based on more than 13,000 adults. RESULTS: Percentiles increase in both sexes with age. It can be observed in females in nearly all age groups. In males, percentiles are saturated around the sixth decade. Only 9 % of 20 to 29 years old adults are obese using WHO criteria, while there are 29 % of 60 to 69 years old adults having a BMI > or = 30.0 kg/m2. CONCLUSIONS: Percentiles reflect age and sex dependencies of the BMI. They show that there is a larger part of the population in higher BMI intervals with increasing age. Thus, the adequacy of the WHO definition should be questioned. Based on the NVS II, current and representative BMI percentiles for adulthood are now available for Germany. These can be used as base for age and sex dependent evaluation of the BMI.

[The influence of phenylephrine and tropicamide on higher order monochromatic aberrations]. / Einfluss von Phenylephrin und Tropicamid auf Aberrationen höherer Ordnung.

BACKGROUND: For wave-front guided corneal surgery, measuring higher order monochromatic aberrations in mydriasis is needed. However, a potential influence of mydriatic drugs on such aberrations could distort the ablation profile. METHOD: Wave-front analysis was carried out on 20 (tropicamide) and 19 (phenylephrine) eyes after dark adaptation, followed by measurement after the instillation of the mydriatics one after another. RESULTS: Phenylephrine had no significant influence on the wave-front; neither sphere nor RMS data differed from those taken after dark adaptation. After instilling tropicamide, significant changes in Z(2) (0) and, in parallel, also of the sphere were found. The RMS showed no significant difference, only the spherical aberration Z(4) (0) was reduced by an average of 0.035 microm. CONCLUSION: The wave-front changes individually through the mydriasis due to phenylephrine and tropicamide. In the case of tropicamide, the deviation is statistically significant. Therefore, abandonment of these mydriatics before refractive surgery can be recommended, as can the use physiological pupil dilatation. Because of its lower influence, phenylephrine should be the first choice if dimout effects no adequate mydriasis.