The Burden and Management of Dyslipidemia: Practical Issues

Abstract The objective of this study is to describe briefly the burden of dyslipidemia, and to discuss and present strategies for health professionals to improve dyslipidemia management, based on a review of selected literature focusing on interventions for dyslipidemia treatment adherence. Despite the availability of effective lifestyle and pharmaceutical therapies for dyslipidemias, they continue to present a significant economic burden in the United States. Adherence to evidence-based guidelines for the treatment of dyslipidemias is unsatisfactory. The reasons for medication nonadherence are complex and specific to each patient. The lack of progress in achieving optimal lipid targets is caused by many factors: patient (medication adherence, cost of medication, literacy), medication (adverse effects, complexity of regimen), provider (lack of adherence to evidence-based practice guidelines, poor communication), and the US healthcare system (being focused on acute care rather than prevention, lack of continuity of care, general lack of use of an electronic health record). Combined interventions that target each part of the system have been effective in improving treatment adherence and achieving lipid goals. Patients, providers, pharmacists, and employers all play a role in management of dyslipidemia. No single approach will solve the complex issue of improving dyslipidemia management. The required lifestyle changes are known and effective medications are available. The challenge is for all interested parties?including nurses, nurse practitioners, doctors, pharmacists, other health care professionals, employers, and health plans?to help patients achieve behavioral changes. (Population Health Management 2012;15:302?308)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98471/1/pop%2E2011%2E0081.pd

Analysis of the Association between Metabolic Syndrome and Disease in a Workplace Population over Time

Objectives:  While research has confirmed an association between metabolic syndrome (MetS) and diseases such as heart disease and diabetes, none of these studies have been conducted in a worksite population. Because corporations are often the primary payer of health-care costs in the United States, they have a vested interest in identifying the magnitude of MetS risk factors in employed populations, and also in knowing if those risk factors are associated with other health risks or medical conditions. Methods:  This study identified the prevalence of MetS risk factors and self-reported disease in employees (N = 3285) of a manufacturing corporation who participated in a health risk appraisal and biometric screening in both 2004 and 2006. Health-care costs, pharmacy costs, and short-term disability costs were compared for those with and without MetS and disease. Results:  The prevalence of MetS increased from 2004 to 2006 in this employed population. Those with MetS were significantly more likely to self-report arthritis, chronic pain, diabetes, heartburn, heart disease, and stroke. Employees with MetS in 2004 were also significantly more likely to report new cases of arthritis, chronic pain, diabetes, and heart disease in 2006. The costs of those with MetS and disease were 3.66 times greater than those without MetS and without disease. Conclusions:  MetS is associated with disease and increased costs in this working population. There is an opportunity for health promotion to prevent MetS risk factors from progressing to disease status which may improve vitality for employees, as well as limit the economic impact to the corporation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75375/1/j.1524-4733.2009.00651.x.pd

Contrasting Population Structures of the Genes Encoding Ten Leading Vaccine-Candidate Antigens of the Human Malaria Parasite, Plasmodium falciparum

The extensive diversity of Plasmodium falciparum antigens is a major obstacle to a broadly effective malaria vaccine but population genetics has rarely been used to guide vaccine design. We have completed a meta-population genetic analysis of the genes encoding ten leading P. falciparum vaccine antigens, including the pre-erythrocytic antigens csp, trap, lsa1 and glurp; the merozoite antigens eba175, ama1, msp's 1, 3 and 4, and the gametocyte antigen pfs48/45. A total of 4553 antigen sequences were assembled from published data and we estimated the range and distribution of diversity worldwide using traditional population genetics, Bayesian clustering and network analysis. Although a large number of distinct haplotypes were identified for each antigen, they were organized into a limited number of discrete subgroups. While the non-merozoite antigens showed geographically variable levels of diversity and geographic restriction of specific subgroups, the merozoite antigens had high levels of diversity globally, and a worldwide distribution of each subgroup. This shows that the diversity of the non-merozoite antigens is organized by physical or other location-specific barriers to gene flow and that of merozoite antigens by features intrinsic to all populations, one important possibility being the immune response of the human host. We also show that current malaria vaccine formulations are based upon low prevalence haplotypes from a single subgroup and thus may represent only a small proportion of the global parasite population. This study demonstrates significant contrasts in the population structure of P. falciparum vaccine candidates that are consistent with the merozoite antigens being under stronger balancing selection than non-merozoite antigens and suggesting that unique approaches to vaccine design will be required. The results of this study also provide a realistic framework for the diversity of these antigens to be incorporated into the design of next-generation malaria vaccines

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder