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

A Worksite Occupational Health Clinic-Based Diabetes Mellitus Management Program

This study is an analysis of a workplace diabetes management program offered to employees of a Fortune 100 financial services corporation located in the United States. The 12-month worksite-based educational program was for employees who were at risk for diabetes, had prediabetes, or were diagnosed with diabetes. This employed population, with health benefits, generally had acceptable control of their diabetes at the start of the program. They statistically improved most self-efficacy measures, but improvement in biometric tests at 6 and 12 months were not significantly different from baseline. Mean hemoglobin A1c at baseline, 6 months, and 12 months was 7.2%, 7.2%, and 7.3%, respectively. At 12 months, about 40% of preprogram survey participants completed all screenings and the post-program questionnaire. Disease management programs at the workplace can be an important component in helping employees enhance their knowledge of diabetes and maintain and improve their health. (Population Health Management 2015;18:429?436)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140190/1/pop.2014.0141.pd

Asthma Disease Management: A Worksite-Based Asthma Education Program

Asthma accounts for an estimated 3 million workdays lost each year in the United States in addition to reduced worker productivity. Although asthma disease management programs are relatively common in managed care organizations, they have generally not been offered at the workplace. Seventy-six employees participated in a five-session worksite-based asthma education program. A total of 47 of 76 (61.8%) employees completed baseline and 12-month follow-up Asthma Therapy Assessment Questionnaires (ATAQ). The ATAQ includes measurement of poor asthma control, behavior/attitude barriers, knowledge barriers, patient/provider communication barriers, and efficiency. Significant improvement was noted in measures of asthma control (p < 0.05), communication (p < 0.005), knowledge (p < 0.001), and the total ATAQ Index declined from 5.53 to 4.04 (p < 0.001). Employee satisfaction results for the program were exceptionally high. A worksite-based asthma education program should reduce medical care costs, worker absenteeism, and improve worker productivity. The worksite can be a very effective location for disease education programs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63128/1/109350701300038208.pd

Worker Productivity Loss Associated with Arthritis

This study at a major financial services corporation sought to investigate the association of arthritis with on-the-job productivity, also termed "presenteeism." Using a modified version of the Work Limitations Questionnaire (WLQ) incorporated into a Health Risk Appraisal (HRA), 17,685 employees responded to the survey in 2002. Of the 16,651 respondents meeting inclusion criteria, 2,469 (14.8%) reported having arthritis, and 986 (39.9% of those with arthritis) also reported that they were under medical care and/or taking medication for arthritis. Employees with arthritis were older, predominantly female, and reported a higher number of comorbidities. Although all four domains of the WLQ (physical, time, mental, and output) were impacted by arthritis, the greatest productivity effect, as expected, was on physical work tasks. Health risks also play a role in the relationship between arthritis and presenteeism, with high-risk individuals reporting 7%–10% additional loss of productivity compared to lowrisk individuals. In addition, those who reported receiving medication and/or treatment for arthritis had a 2.5% excess productivity loss independently attributed to their arthritis, which equals approximately $1,250 per employee per year, or$5.4 million to the corporation. This arthritis effect was discernible in those with low and moderate levels of health risk, but was not as evident in those with high health risks; in that group, health-associated decrements in productivity were much larger. Arthritis is associated with work productivity loss. Disease management programs should focus on pain management and arthritis-associated health risks and comorbidities in order to significantly decrease arthritis-related losses in on-the-job productivity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63221/1/dis.2006.9.131.pd

Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model.

Many risk genes for the development of Alzheimer's disease (AD) are exclusively or highly expressed in myeloid cells. Microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for their survival. We designed and synthesized a highly selective brain-penetrant CSF1R inhibitor (PLX5622) allowing for extended and specific microglial elimination, preceding and during pathology development. We find that in the 5xFAD mouse model of AD, plaques fail to form in the parenchymal space following microglial depletion, except in areas containing surviving microglia. Instead, Aβ deposits in cortical blood vessels reminiscent of cerebral amyloid angiopathy. Altered gene expression in the 5xFAD hippocampus is also reversed by the absence of microglia. Transcriptional analyses of the residual plaque-forming microglia show they exhibit a disease-associated microglia profile. Collectively, we describe the structure, formulation, and efficacy of PLX5622, which allows for sustained microglial depletion and identify roles of microglia in initiating plaque pathogenesis

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD

Broadly Neutralizing Human Anti-HIV Antibody 2G12 Is Effective in Protection against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers

Developing an immunogen that elicits broadly neutralizing antibodies (bNAbs) is an elusive but important goal of HIV vaccine research, especially after the recent failure of the leading T cell based HIV vaccine in human efficacy trials. Even if such an immunogen can be developed, most animal model studies indicate that high serum neutralizing concentrations of bNAbs are required to provide significant benefit in typical protection experiments. One possible exception is provided by the anti-glycan bNAb 2G12, which has been reported to protect macaques against CXCR4-using SHIV challenge at relatively low serum neutralizing titers. Here, we investigated the ability of 2G12 administered intravenously (i.v.) to protect against vaginal challenge of rhesus macaques with the CCR5-using SHIVSF162P3. The results show that, at 2G12 serum neutralizing titers of the order of 1∶1 (IC90), 3/5 antibody-treated animals were protected with sterilizing immunity, i.e. no detectable virus replication following challenge; one animal showed a delayed and lowered primary viremia and the other animal showed a course of infection similar to 4 control animals. This result contrasts strongly with the typically high titers observed for protection by other neutralizing antibodies, including the bNAb b12. We compared b12 and 2G12 for characteristics that might explain the differences in protective ability relative to neutralizing activity. We found no evidence to suggest that 2G12 transudation to the vaginal surface was significantly superior to b12. We also observed that the ability of 2G12 to inhibit virus replication in target cells through antibody-mediated effector cell activity in vitro was equivalent or inferior to b12. The results raise the possibility that some epitopes on HIV may be better vaccine targets than others and support targeting the glycan shield of the envelope