Antiparkinson Drug Adherence and Its Association with Health Care Utilization and Economic Outcomes in a Medicare Part D Population

AbstractObjectivesWe examine the associations of adherence to antiparkinson drugs (APDs) with health care utilization and economic outcomes among patients with Parkinson’s disease (PD).MethodsBy using 2006–2007 Medicare administrative data, we examined 7583 beneficiaries with PD who filled two or more APD prescriptions during 19 months (June 1, 2006, to December 31, 2007) in the Part D program. Two adherence measures— duration of therapy (DOT) and medication possession ratio (MPR)—were assessed. Negative binomial and gamma generalized linear models were used to estimate the rate ratios (RRs) of all-cause health care utilization and expenditures, respectively, conditional upon adherence, adjusting for survival risk, sample selection, and health-seeking behavior.ResultsApproximately one-fourth of patients with PD had low adherence (MPR < 0.80, 28.7%) or had a short DOT (≤400 days, 23.9%). Increasing adherence to APD therapy was associated with decreased health care utilization and expenditures. For example, compared with patients with low adherence, those with high adherence (MPR = 0.90–1.00) had significantly lower rates of hospitalization (RR = 0.86), emergency room visits (RR = 0.91), skilled nursing facility episodes (RR = 0.67), home health agency episodes (RR = 0.83), physician visits (RR = 0.93), as well as lower total health care expenditures (−$2242), measured over 19 months. Similarly, lower total expenditure (−$6308) was observed in patients with a long DOT versus those with a short DOT.ConclusionsIn this nationally representative sample, higher adherence to APDs and longer duration of use of APDs were associated with lower all-cause health care utilization and total health care expenditures. Our findings suggest the need for improving medication-taking behaviors among patients with PD to reduce the use of and expenditures for medical resources

Insulin Gene Expression Is Regulated by DNA Methylation

BACKGROUND:Insulin is a critical component of metabolic control, and as such, insulin gene expression has been the focus of extensive study. DNA sequences that regulate transcription of the insulin gene and the majority of regulatory factors have already been identified. However, only recently have other components of insulin gene expression been investigated, and in this study we examine the role of DNA methylation in the regulation of mouse and human insulin gene expression. METHODOLOGY/PRINCIPAL FINDINGS:Genomic DNA samples from several tissues were bisulfite-treated and sequenced which revealed that cytosine-guanosine dinucleotide (CpG) sites in both the mouse Ins2 and human INS promoters are uniquely demethylated in insulin-producing pancreatic beta cells. Methylation of these CpG sites suppressed insulin promoter-driven reporter gene activity by almost 90% and specific methylation of the CpG site in the cAMP responsive element (CRE) in the promoter alone suppressed insulin promoter activity by 50%. Methylation did not directly inhibit factor binding to the CRE in vitro, but inhibited ATF2 and CREB binding in vivo and conversely increased the binding of methyl CpG binding protein 2 (MeCP2). Examination of the Ins2 gene in mouse embryonic stem cell cultures revealed that it is fully methylated and becomes demethylated as the cells differentiate into insulin-expressing cells in vitro. CONCLUSIONS/SIGNIFICANCE:Our findings suggest that insulin promoter CpG demethylation may play a crucial role in beta cell maturation and tissue-specific insulin gene expression

Kupffer Cells Hasten Resolution of Liver Immunopathology in Mouse Models of Viral Hepatitis

Kupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV)-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1) protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

The Effect of Managed Care on Prescription Drug Costs and Benefits

This review discusses the approaches to prescription drug payment practices taken by managed care to influence drug use and costs, and presents the research evidence supporting these interventions. In the US, drugs were infrequently covered as an ambulatory benefit under fee-for-service indemnity insurance; however, health maintenance organisations almost always provide outpatient drugs and consequently have developed approaches to influence drug use and manage its costs. Managed care as a set of tools and as an organisational form is moving toward more restrictions on direct access to pharmaceuticals as a covered benefit. Options for influencing drug use and cost may address access, ingredient costs, dispensing fees and cost sharing. The formulary process is the foundation for a managed pharmacy benefit and integrates these options. The limited empirical evidence for an effect of managed care on drug costs and use is reviewed. A proposed research agenda includes evaluation of the effects of restrictive formularies, capitation, disease management and other programmes to influence the cost and use of pharmaceuticals.Reviews-on-treatment, Pharmacoeconomics, Managed-care, Prescribing, Reimbursement, Formularies, Cost-containment