Publications

BACKGROUND

There is a paucity of data on the adequacy of the resources and tools used by the Centers for Medicaid and Medicare Services (CMS) in making national coverage determinations about services for beneficiaries. The objective of this study was to determine the extent to which clinical trials relied on by the CMS are applicable to Medicare beneficiaries.

METHODS

We performed a meta-analysis of data on 40 009 individuals from all 141 trials included in the technology assessments for the 6 cardiovascular disease meetings of the CMS advisory panel and compared them with the demographics of the Medicare population.

RESULTS

Medicare beneficiaries differ significantly from the cardiovascular clinical trial participants used to inform Medicare coverage decisions. Clinical trial participants, compared with beneficiaries, are more likely to be younger (60.1 vs 74.7 years), male (75.4% vs 41.8%), and non-US residents (60% vs 0%). The clinical trials, moreover, rarely included outcome stratification by age, sex, and race.

CONCLUSIONS

Participants in cardiovascular studies relied on by the CMS for coverage determinations differ substantially from the Medicare population. Data frequently are not available on relevant subgroup populations. Suggestions are made that address the need for data more relevant to Medicare beneficiaries by increasing enrollment of, and reporting on, women and elderly individuals in clinical trials and use of relevant data for coverage decisions.

Azaspiracid-1 (AZA-1) is a marine biotoxin reported to accumulate in shellfish from several countries, including eastern Canada, Morocco, and much of western Europe, and is frequently associated with severe gastrointestinal human intoxication. As the mechanism of action of AZA-1 is currently unknown, human DNA microarrays and qPCR were used to profile gene expression patterns in human T lymphocyte cells following AZA-1 exposure. Some of the early (1 h) responding genes consisted of transcription factors, membrane proteins, receptors, and inflammatory genes. Four- and 24-h responding genes were dominated by genes involved in de novo lipid biosynthesis of which 17 of 18 involved in cholesterol biosynthesis were significantly up regulated. The up regulation of synthesis genes was likely in response to the ca. 50% reduction in cellular cholesterol, which correlated with up regulated protein expression levels of the low-density lipoprotein receptor. These data collectively detail the inhibition of de novo cholesterol synthesis, which is the likely cause of cytotoxicity and potentially a target pathway of the toxin.

Liver disease is a major health problem for individuals with a history of injection drug use. This is mainly from the hepatitis C virus (HCV), with or without co-infection with HIV. HCV-associated liver disease takes decades to develop into cirrhosis, from which it can adversely affect health. HIV coinfection is among the factors that are often associated with liver disease progression, and efforts to understand liver disease progression in HIV-HCV coinfected patients remain important. Maintaining high CD4 counts and avoiding alcohol intake are associated with slower liver disease progression. Pegylated interferon and ribavirin combination therapy has the potential to clear HCV, which provides the strongest health benefit to patients affected by the virus, although this can be difficult to accomplish for many reasons. Steatosis, fat within the liver, may also have important pathological implications for liver disease related to HCV. Limiting liver disease progression in IDUs with hepatitis C may well be best accomplished through promoting their full utilization of health care.