A national clinical decision support infrastructure to enable the widespread and consistent practice of genomic and personalized medicine

<p>Abstract</p> <p>Background</p> <p>In recent years, the completion of the Human Genome Project and other rapid advances in genomics have led to increasing anticipation of an era of genomic and personalized medicine, in which an individual's health is optimized through the use of all available patient data, including data on the individual's genome and its downstream products. Genomic and personalized medicine could transform healthcare systems and catalyze significant reductions in morbidity, mortality, and overall healthcare costs.</p> <p>Discussion</p> <p>Critical to the achievement of more efficient and effective healthcare enabled by genomics is the establishment of a robust, nationwide clinical decision support infrastructure that assists clinicians in their use of genomic assays to guide disease prevention, diagnosis, and therapy. Requisite components of this infrastructure include the standardized representation of genomic and non-genomic patient data across health information systems; centrally managed repositories of computer-processable medical knowledge; and standardized approaches for applying these knowledge resources against patient data to generate and deliver patient-specific care recommendations. Here, we provide recommendations for establishing a national decision support infrastructure for genomic and personalized medicine that fulfills these needs, leverages existing resources, and is aligned with the <it>Roadmap for National Action on Clinical Decision Support </it>commissioned by the U.S. Office of the National Coordinator for Health Information Technology. Critical to the establishment of this infrastructure will be strong leadership and substantial funding from the federal government.</p> <p>Summary</p> <p>A national clinical decision support infrastructure will be required for reaping the full benefits of genomic and personalized medicine. Essential components of this infrastructure include standards for data representation; centrally managed knowledge repositories; and standardized approaches for leveraging these knowledge repositories to generate patient-specific care recommendations at the point of care.</p

Vitamin D status is inversely associated with markers of risk for type 2 diabetes: A population based study in Victoria, Australia

A growing body of evidence suggests a protective role of Vitamin D on the risk of type 2 diabetes mellitus (T2DM). We investigated this relationship in a population sample from one Australian state. The data of 3,393 Australian adults aged 18±75 years who participated in the 2009±2010 Victorian Health Monitor survey was analyzed. Socio-demographic information, biomedical variables, and dietary intakes were collected and fasting blood samples were analyzed for 25, hydroxycholecalciferol (25OHD), HbA1c, fasting plasma glucose (FPG), and lipid profiles. Logistic regression analyses were used to evaluate the association between tertiles of serum 25OHD and categories of FPG (&lt;5.6 mmol/L vs. 5.6±6.9 mmol/L), and HbA1c (&lt;5.7% vs. 5.7±6.4%). After adjusting for social, dietary, biomedical and metabolic syndrome (MetS) components (waist circumference, HDL cholesterol, triglycerides, and blood pressure), every 10 nmol/L increment in serum 25OHD significantly reduced the adjusted odds ratio (AOR) of a higher FPG [AOR 0.91, (0.86, 0.97); p = 0.002] and a higher HbA1c [AOR 0.94, (0.90, 0.98); p = 0.009]. Analysis by tertiles of 25OHD indicated that after adjustment for socio-demographic and dietary variables, those with high 25OHD (65±204 nmol/L) had reduced odds of a higher FPG [AOR 0.60, (0.43, 0.83); p = 0.008] as well as higher HbA1c [AOR 0.67, (0.53, 0.85); p = 0.005] compared to the lowest 25OHD (10±44 nmol/L) tertile. On final adjustment for other components of MetS, those in the highest tertile of 25OHD had significantly reduced odds of higher FPG [AOR 0.61, (0.44, 0.84); p = 0.011] and of higher HbA1c [AOR 0.74, (0.58, 0.93); p = 0.041] vs. low 25OHD tertile. Overall, the data support a direct, protective effect of higher 25OHD on FPG and HbA1c; two criteria for assessment of risk of T2DM

Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders

Background: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown. Method/Principal Findings: 53 healthy individuals between 18–59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject’s sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 39 untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia. Conclusions: Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brai

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered

Brazilian Consensus on Photoprotection

Brazil is a country of continental dimensions with a large heterogeneity of climates and massive mixing of the population. Almost the entire national territory is located between the Equator and the Tropic of Capricorn, and the Earth axial tilt to the south certainly makes Brazil one of the countries of the world with greater extent of land in proximity to the sun. The Brazilian coastline, where most of its population lives, is more than 8,500 km long. Due to geographic characteristics and cultural trends, Brazilians are among the peoples with the highest annual exposure to the sun. Epidemiological data show a continuing increase in the incidence of nonmelanoma and melanoma skin cancers. Photoprotection can be understood as a set of measures aimed at reducing sun exposure and at preventing the development of acute and chronic actinic damage. Due to the peculiarities of Brazilian territory and culture, it would not be advisable to replicate the concepts of photoprotection from other developed countries, places with completely different climates and populations. Thus the Brazilian Society of Dermatology has developed the Brazilian Consensus on Photoprotection, the first official document on photoprotection developed in Brazil for Brazilians, with recommendations on matters involving photoprotection

Relation between calcium absorption and serum calcitriol in normal men: evidence for age-related intestinal resistance to calcitriol

Copyright © 2004 Nature Publishing GroupObjectiveTo obtain information on the causes of age-related bone loss in men and the concomitant decline in calcium absorption.DesignCross-sectional study.SettingAdelaide, South Australia, Australia.SubjectsA total of 95 healthy, Caucasian men (age range 27-87 y).ResultsCalcium absorption declined with age (r=-0.46, P-0.21, P0.41, PConclusionsIn healthy Caucasian males (i) calcium absorption falls, but serum calcitriol does not change with age, (ii) the relation between calcium absorption and serum calcitriol changes with age, indicative of an intestinal resistance to calcitriol and (iii) calcium absorption is a significant determinant of 24-h urinary calcium excretion.F Scopacasa, JM Wishart, M Horowitz, HA Morris and AG Nee

Suppression of parathyroid hormone and bone resorption by calcium carbonate and calcium citrate in postmenopausal women

The original publication can be found at www.springerlink.comThis study was conducted to compare the suppressive effects of calcium carbonate and calcium citrate on bone resorption in early postmenopause. Calcium citrate is thought to be better absorbed. We therefore tested the hypothesis that calcium as citrate is more effective than calcium as carbonate in suppressing parathyroid hormone (PTH) and C-terminal telopeptide. Twenty-five healthy postmenopausal women were recruited in this double blind crossover study. The subjects were randomly allocated to receive either 1,000 mg of elemental calcium as carbonate or 500 mg of calcium as citrate. They were given the alternate calcium dose 1 week later. Serum measurements of total and ionized calcium, phosphate, PTH, and CrossLaps were repeated 12 hours after each dose. Analysis of variance found no significant difference between measures for the two salts. Tests for equivalence indicated that 500 mg of calcium citrate may be superior to 1,000 mg of calcium carbonate in raising serum total and ionized calcium (P = 0.04 and 0.05, respectively). For all parameters measured, 500 mg of calcium citrate was at least as beneficial as 1,000 mg of calcium carbonate. Calcium citrate is at least as effective as calcium carbonate in suppressing PTH and C-terminal telopeptide cross-links, at half the dose. This may be because calcium as citrate is better absorbed than calcium as carbonate. If calcium citrate can be used in lower doses, it may be better tolerated than calcium carbonate.Sunethra D. C. Thomas, Allan G. Need, Graeme Tucker, Peter Slobodian, Peter D. O’Loughlin and B. E. Christopher Nordi

Vitamin D in health and disease: Current perspectives

Despite the numerous reports of the association of vitamin D with a spectrum of development, disease treatment and health maintenance, vitamin D deficiency is common. Originating in part from the diet but with a key source resulting from transformation by exposure to sunshine, a great deal of the population suffers from vitamin D deficiency especially during winter months. It is linked to the treatment and pathogenesis and/or progression of several disorders including cancer, hypertension, multiple sclerosis, rheumatoid arthritis, osteoporosis, muscle weakness and diabetes. This widespread deficiency of Vitamin D merits consideration of widespread policies including increasing awareness among the public and healthcare professionals