Search for the best indicators for the presence of a VPS13B gene mutation and confirmation of diagnostic criteria in a series of 34 patients genotyped for suspected Cohen syndrome

BACKGROUND: Cohen syndrome is a rare autosomal recessive inherited disorder that results from mutations of the VPS13B gene. Clinical features consist of a combination of mental retardation, facial dysmorphism, postnatal microcephaly, truncal obesity, slender extremities, joint hyperextensibility, myopia, progressive chorioretinal dystrophy, and intermittent neutropenia.PATIENTS AND METHODS: The aim of the study was to determine which of the above clinical features were the best indicators for the presence of VPS13B gene mutations in a series of 34 patients with suspected Cohen syndrome referred for molecular analysis of VPS13B. RESULTS: 14 VPS13B gene mutations were identified in 12 patients, and no mutation was found in 22 patients. The presence of chorioretinal dystrophy (92% vs 32%, p=0.0023), intermittent neutropenia (92% vs 5%, p<0.001), and postnatal microcephaly (100% vs 48%, p=0.0045) was significantly higher in the group of patients with a VPS13B gene mutation compared to the group of patients without a mutation. All patients with VPS13B mutations had chorioretinal dystrophy and/or intermittent neutropenia. The Kolehmainen diagnostic criteria provided 100% sensibility and 77% specificity when applied to this series. CONCLUSION: From this study and a review of more than 160 genotyped cases from the literature, it is concluded that, given the large size of the gene, VPS13B screening is not indicated in the absence of chorioretinal dystrophy or neutropenia in patients aged over 5 years. The follow-up of young patients could be a satisfactory alternative unless there are some reproductive issues

Cost-effectiveness model of using zoledronic acid once a year versus current treatment strategies in postmenopausal osteoporosis

OBJECTIVES: To compare effectiveness, associated cost of outcomes and cost-effectiveness of a single annual infusion of zoledronic acid versus current treatment strategies plans for postmenopausal osteoporosis in France. METHODS: Twelve simulation-based models were built to investigate three types of fractures: vertebral (VF), non-vertebral excluding hip (NVF) and hip (HF), comparing two groups: zoledronic acid and current postmenopausal antiosteoporotic treatment strategies. Two effectiveness comparability assumptions have been tested: specific agent efficacy values, and same standard efficacy values for all active agents. Direct medical costs included drug costs, medical visits, monitoring and fracture management. Adherence levels were integrated into the model under the assumption that non-adherent patients had treatment effects similar to the levels of placebo effectiveness. RESULTS: Using the most conservative assumption (same standard efficacy values for all active agents), zoledronic acid strategy results in less vertebral, non-vertebral and hip fractures than other current antiosteoporotic treatment options over 3 years: 12.04% vs. 14.18%, 10.61% vs. 11.28% and 2.82% vs. 4.64% respectively, (p<0.001). In addition, zoledronic acid is more cost-effective than the current treatment strategies in all types of fractures (p<0.001): 1497 euros vs. 1685 euros per VF avoided, 1337 euros vs. 1404 euros per NVF avoided and 1216 euros vs. 1323 euros per HF avoided. CONCLUSION: Zoledronic acid is a cost-effective treatment strategy regardless of fracture type or effectiveness comparability assumptions

Functional Biomedical Images of Alzheimer's Disease a Green's Function based Empirical Mode Decomposition Study

Positron emission tomography (PET) provides a functional imaging modality to detect signs of dementias in human brains. Two-dimensional empirical mode decomposition (2D-EMD) provides means to analyze such images. It decomposes the latter into characteristic modes which represent textures on different spatial scales. These textures provide informative features for subsequent classification purposes. The study proposes a new EMD variant which relies on a Green's function based estimation method including a tension parameter to fast and reliably estimate the envelope hypersurfaces interpolating extremal points of the two-dimensional intensity distrubution of the images. The new method represents a fast and stable bi-dimensional EMD which speeds up computations roughly 100-fold. In combination with proper classifiers these exploratory feature extraction techniques can form a computer aided diagnosis (CAD) system to assist clinicians in identifying various diseases from functional images alone. PET images of subjects suffering from Alzheimer's disease are taken to illustrate this ability