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Biomedical subjects

Mark McClellan

Publications and source records attributed to Mark McClellan.

15 recordsLinked to original sources
PubMed2005

Mortality after acute myocardial infarction in hospitals that disproportionately treat black patients.

BACKGROUND: African Americans are more likely to be seen by physicians with less clinical training or to be treated at hospitals with longer average times to acute reperfusion therapies. Less is known about differences in health outcomes. This report compares risk-adjusted mortality after acute myocardial infarction (AMI) between US hospitals with high and low fractions of elderly black AMI patients. METHODS AND RESULTS: A prospective cohort study was performed for fee-for-service Medicare patients hospitalized for AMI during 1997 to 2001 (n=1,136,736). Hospitals (n=4289) were classified into approximate deciles depending on the extent to which the hospital served the black population. Decile 1 (12.5% of AMI patients) included hospitals without any black AMI admissions during 1997 to 2001. Decile 10 (10% of AMI patients) included hospitals with the highest fraction of black AMI patients (33.6%). The main outcome measures were 90-day and 30-day mortality after AMI. Patients admitted to hospitals disproportionately serving blacks experienced no greater level of morbidities or severity of the infarction, yet hospitals in decile 10 experienced a risk-adjusted 90-day mortality rate of 23.7% (95% CI 23.2% to 24.2%) compared with 20.1% (95% CI 19.7% to 20.4%) in decile 1 hospitals. Differences in outcomes between hospitals were not explained by income, hospital ownership status, hospital volume, census region, urban status, or hospital surgical treatment intensity. CONCLUSIONS: Risk-adjusted mortality after AMI is significantly higher in US hospitals that disproportionately serve blacks. A reduction in overall mortality at these hospitals could dramatically reduce black-white disparities in healthcare outcomes.

Black People↗
PubMed2005

Rewiring of the yeast transcriptional network through the evolution of motif usage.

Recent experiments revealed large-scale differences in the transcription programs of related species, yet little is known about the genetic basis underlying the evolution of gene expression and its contribution to phenotypic diversity. Here we describe a large-scale modulation of the yeast transcription program that is connected to the emergence of the capacity for rapid anaerobic growth. Genes coding for mitochondrial and cytoplasmic ribosomal proteins display a strongly correlated expression pattern in Candida albicans, but this correlation is lost in the fermentative yeast Saccharomyces cerevisiae. We provide evidence that this change in gene expression is connected to the loss of a specific cis-regulatory element from dozens of genes following the apparent whole-genome duplication event. Our results shed new light on the genetic mechanisms underlying the large-scale evolution of transcriptional networks.

Aerobiosis↗
PubMed2005

Detecting Medicare abuse.

This paper identifies which types of patients and hospitals have abusive Medicare billings that are responsive to law enforcement. For a 20% random sample of elderly Medicare beneficiaries hospitalized from 1994 to 1998 with one or more of six illnesses that are prone to abuse, we obtain longitudinal claims data linked with social security death records, hospital characteristics, and state/year-level anti-fraud enforcement efforts. We show that increased enforcement leads certain types of types of patients and hospitals to have lower billings, without adverse consequences for patients' health outcomes.

Fraud↗
PubMed2004

Cassettes for the PCR-mediated construction of regulatable alleles in Candida albicans.

The recent availability of genome sequence information for the opportunistic pathogen Candida albicans has greatly facilitated the ability to perform genetic manipulations in this organism. Two important molecular tools for studying gene function are regulatable promoters for generating conditional mutants and fluorescent proteins for determining the subcellular localization of fusion gene products. We describe a set of plasmids containing promoter-GFP cassettes (P(MET3)-GFP, P(GAL1)-GFP, and P(PCK1)-GFP), linked to a selectable nutritional marker gene (URA3). PCR-mediated gene modification generates gene-specific promoter, or gene-specific promoter-GFP, fusions at the 5'-end of the gene of interest. One set of primers can be used to generate three strains expressing a native protein of interest, or an amino-terminal GFP-tagged version, from three different regulatable promoters. Thus, these promoter cassette plasmids facilitate construction of conditional mutant strains, overexpression alleles and/or inducible amino-terminal GFP fusion proteins.

Alleles↗
PubMed2004

The costs of decedents in the Medicare program: implications for payments to Medicare + Choice plans.

OBJECTIVE: To discuss and quantify the incentives that Medicare managed care plans have to avoid (through selective enrollment or disenrollment) people who are at risk for very high costs, focusing on Medicare beneficiaries in the last year of life-a group that accounts for more than one-quarter of Medicare's annual expenditures. DATA SOURCE: Medicare administrative claims for 1994 and 1995. STUDY DESIGN: We calculated the payment a plan would have received under three risk-adjustment systems for each beneficiary in our 1995 sample based on his or her age, gender, county of residence, original reason for Medicare entitlement, and principal inpatient diagnoses received during any hospital stays in 1994. We compared these amounts to the actual costs incurred by those beneficiaries. We then looked for clinical categories that were predictive of costs, including costs in a beneficiary's last year of life, not accounted for by the risk adjusters. DATA EXTRACTION METHODS: The analyses were conducted using claims for a 5 percent random sample of Medicare beneficiaries who died in 1995 and a matched group of survivors. PRINCIPAL FINDINGS: Medicare is currently implementing the Principal Inpatient Diagnostic Cost Groups (PIP-DCG) risk adjustment payment system to address the problem of risk selection in the Medicare+Choice program. We quantify the strong financial disincentives to enroll terminally ill beneficiaries that plans still have under this risk adjustment system. We also show that up to one-third of the selection observed between Medicare HMOs and the traditional fee-for-service system could be due to differential enrollment of decedents. A risk adjustment system that incorporated more of the available diagnostic information would attenuate this disincentive; however, plans could still use clinical information (not included in the risk adjustment scheme) to identify beneficiaries whose expected costs exceed expected payments. CONCLUSIONS: More disaggregated prospective risk adjustment methods and alternative payment systems that compensate plans for delivering care to certain classes of patients should be considered to ensure access to high-quality managed care for all beneficiaries.

Actuarial Analysis↗
PubMed2003

Cardiac procedure use and outcomes in elderly patients with acute myocardial infarction in the United States and Quebec, Canada, 1988 to 1994.

BACKGROUND: Studies from the early 1990s have documented greater intensity of treatment for patients with acute myocardial infarction (AMI) in the United States compared with Canada, with little difference in health outcomes. Little is known about whether treatments and outcomes are changing differently over time in the two countries, and whether the differences vary with patient age. METHODS: We conducted a retrospective cohort study of trends in cardiac procedure use, mortality, and recurrent AMI for patients 65 years or older hospitalized with AMI in the United States and Quebec. We examined Medicare claims and enrollment data from the United States (1.5 million) and provincial claims data from Quebec (35,000) between 1988 and 1994. RESULTS: Use of cardiac procedures grew more rapidly between 1988 and 1994 in the United States, particularly for patients 75 years or older; unlike in Quebec, these cardiac procedures were performed soon after AMI. Both countries experienced significant declines in 1-year mortality: the decline averaged 1.27% points per year in the United States and 1.05% points in Quebec (P = ns). For AMI patients 75 years or older, 30-day and 1-year mortality declined approximately twice as rapidly in the United States as in Quebec (P < 0.01). The decline in mortality in the United States relative to Canada was significantly greater among patients 75 years or older but not among those age 65 to 74 years. Readmission rates with recurrent AMI were almost unchanged. CONCLUSIONS: Over time, the use of cardiac procedures in elderly patients with AMI has risen more rapidly in the United States than in Quebec. These differences in procedure trends were associated with reductions in overall long-term AMI mortality in both countries.

Aged↗
PubMed2003

mRNAs encoding telomerase components and regulators are controlled by UPF genes in Saccharomyces cerevisiae.

Telomeres, the chromosome ends, are maintained by a balance of activities that erode and replace the terminal DNA sequences. Furthermore, telomere-proximal genes are often silenced in an epigenetic manner. In Saccharomyces cerevisiae, average telomere length and telomeric silencing are reduced by loss of function of UPF genes required in the nonsense-mediated mRNA decay (NMD) pathway. Because NMD controls the mRNA levels of several hundred wild-type genes, we tested the hypothesis that NMD affects the expression of genes important for telomere functions. In upf mutants, high-density oligonucleotide microarrays and Northern blots revealed that the levels of mRNAs were increased for genes encoding the telomerase catalytic subunit (Est2p), in vivo regulators of telomerase (Est1p, Est3p, Stn1p, and Ten1p), and proteins that affect telomeric chromatin structure (Sas2p and Orc5p). We investigated whether overexpressing these genes could mimic the telomere length and telomeric silencing phenotypes seen previously in upf mutant strains. Increased dosage of STN1, especially in combination with increased dosage of TEN1, resulted in reduced telomere length that was indistinguishable from that in upf mutants. Increased levels of STN1 together with EST2 resulted in reduced telomeric silencing like that of upf mutants. The half-life of STN1 mRNA was not altered in upf mutant strains, suggesting that an NMD-controlled transcription factor regulates the levels of STN1 mRNA. Together, these results suggest that NMD maintains the balance of gene products that control telomere length and telomeric silencing primarily by maintaining appropriate levels of STN1, TEN1, and EST2 mRNA.

Cell Cycle Proteins↗
PubMed2002

Low docosahexaenoic acid levels in rod outer segments of rats with P23H and S334ter rhodopsin mutations.

PURPOSE: Previous studies have shown that the level of docosahexaenoic acid (22:6n-3, DHA) is lower in the rod outer segment (ROS) membranes of dogs and mice with inherited retinal degeneration than in ROS from appropriate controls. In the present study, we analyzed the ROS fatty composition of several lines of transgenic rats with P23H and S334ter rhodopsin mutations. Lines were chosen that have different rates of retinal degeneration. METHODS: At 21-22 days of age, animals were perfused and eyes fixed and sectioned for morphologic examination. Others were killed and retinas isolated for preparation of ROS by sucrose step-gradient centrifugation. Fatty acid composition of ROS phospholipids was determined by gas-liquid chromatography. Membrane purity was assessed by polyacrylamide gel electrophoresis. RESULTS: Retinas of the slow degenerating lines were indistinguishable from controls, whereas there was a 15-20% and 50-60% loss of photoreceptor cell nuclei in intermediate and fast degenerating lines, respectively. Except for the slow P23H line, all mutant lines had lower levels of 22:6n-3 and total n-3 fatty acids in ROS phospholipids, compared to wild-type controls, and the level of 22:6n-3 was lowest in those lines with the fastest rate of degeneration. The relative levels of the other fatty acid families (saturated, monoenoic, and n-6) increased proportionately. The n-6/n-3 ratio increased in the more rapidly degenerating lines, but the phospholipid/protein ratios did not change. The low levels of 22:6n-3 in the ROS membranes were not compensated for by an increase in 22:5n-6, which always occurs in the retina of animals where 22:6n-3 levels are reduced by dietary manipulation. CONCLUSIONS: Rats that express mutant rhodopsins have lower levels of 22:6n-3 in their ROS phospholipids than wild-type animals. We propose that photoreceptor-specific mutations provoke a metabolic stress in rod photoreceptor cells that generates an oxidant stress in these cells. The retina responds to this stress by reducing the level of substrate for lipid peroxidation (22:6n-3).

Animals↗
PubMed2002

Racial and sex differences in refusal of coronary angiography.

PURPOSE: To determine the effect of patient refusal on racial and sex differences in the use of coronary angiography and in outcomes among elderly patients with acute myocardial infarction. SUBJECTS AND METHODS: We included Medicare beneficiary patients admitted to hospitals performing coronary angiography from February 1994 through July 1995. In-hospital use and refusal of coronary angiography were determined, and adjusted for patient, hospital, and physician characteristics. RESULTS: Of 124,691 patients, 53,671 (43%) underwent angiography during hospitalization and 2881 (2.3%) refused. Patients refusing angiography were more likely to be female (odds ratio [OR] = 1.37; 95% confidence interval [CI]: 1.23 to 1.53), black (OR = 1.26 vs. whites; 95% CI: 1.02 to 1.56), and older (OR = 2.25 per 10-year increase; 95% CI: 2.05 to 2.43) than patients who underwent angiography. Angiography use was lower in blacks (OR = 0.78; 95% CI: 0.72 to 0.83) than in whites, and lower in women (OR = 0.83; 95% CI: 0.80 to 0.86) than in men. Increased refusal explained 6% (95% CI: -3% to 15%) of the difference in angiography use between whites and blacks, and 16% (95% CI: 10% to 22%) of the difference between men and women. After adjustment for patient characteristics, refusal of angiography was not associated with worse survival at 1 year (OR = 0.99; 95% CI: 0.82 to 1.20). CONCLUSION: Among Medicare beneficiaries, elderly female and black patients are more likely to refuse angiography than are male and white patients. However, patient refusal is uncommon and accounts for only a small fraction of the racial and sex differences in use of angiography after myocardial infarction.

Black or African American↗
PubMed2002

The relation between managed care market share and the treatment of elderly fee-for-service patients with myocardial infarction.

PURPOSE: To determine if greater managed care market share is associated with greater use of recommended therapies for fee-for-service patients with acute myocardial infarction. SUBJECTS AND METHODS: We examined the care of 112,900 fee-for-service Medicare beneficiaries aged > or = 65 years who resided in one of 320 metropolitan statistical areas and who were admitted with an acute myocardial infarction between February 1994 through July 1995. Use of recommended medical treatments and 30-day survival were determined for areas with low (<10%), medium (10% to 30%), and high (>30%) managed care market share. RESULTS: After adjustment for severity of illness, teaching status of the admission hospital, and area characteristics, areas with high levels of managed care had greater use of beta-blockers (relative risk [RR] for greater use = 1.18; 95% confidence interval [CI]: 1.06 to 1.29) and aspirin at discharge (RR = 1.05; 95% CI: 1.02 to 1.07), but less appropriate coronary angiography (RR = 0.93; 95% CI: 0.86 to 1.01) and reperfusion (RR = 0.95; 95% CI: 0.85 to 1.03) when compared with areas with low levels of managed care. CONCLUSIONS: Medicare beneficiaries with fee-for-service insurance who resided in areas with high managed care activity were more likely to have received appropriate treatment with beta-blockers and aspirin, and less likely to have undergone coronary angiography following admission for myocardial infarction. Thus, the effects of managed care may not be limited to managed care enrollees.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Managed care, hospice use, site of death, and medical expenditures in the last year of life.

BACKGROUND: We examined deaths of Medicare beneficiaries in Massachusetts and California to evaluate the effect of managed care on the use of hospice and site of death and to determine how hospice affects the expenditures for the last year of life. METHODS: Medicare data for beneficiaries in Massachusetts (n = 37 933) and California (n = 27 685) who died in 1996 were merged with each state's death certificate files to determine site and cause of death. Expenditure data were Health Care Financing Administration payments and were divided into 30-day periods from the date of death back 12 months. RESULTS: In Massachusetts, only 7% of decedents were enrolled in managed care organizations (MCOs); in California, 28%. More than 60% of hospice users had cancer. Hospice use was much lower in Massachusetts than in California (12% vs 18%). In both states, decedents enrolled in MCOs used hospice care much more than those enrolled in fee-for-service plans (17% vs 11% in Massachusetts and 25% vs 15% in California). This pattern persisted for those with cancer and younger (aged 65-74 years) decedents. Decedents receiving hospice care were significantly (P<.001 for both) less likely to die in the hospital (11% vs 43% in Massachusetts and 5% vs 43% in California). Enrollment in MCOs did not affect the proportion of in-hospital deaths (those enrolled in fee-for-service plans vs MCOs: 40% vs 39% in Massachusetts; and 37% vs 34% in California). Expenditures in the last year of life were $28 588 in Massachusetts and $27 814 in California; about one third of the expenditures occurred in the last month before death. Hospital services accounted for more than 50% of all expenditures in both states, despite 77% of decedents being hospitalized in Massachusetts and just 55% being hospitalized in California. Among patients with cancer, expenditures were 13% to 20% lower for those in hospice. CONCLUSIONS: Medicare-insured decedents in California were more than 4 times more likely to be enrolled in MCOs, were 50% more likely to use a hospice, and had a 30% lower hospitalization rate than decedents in Massachusetts, yet there are few differences in out-of-hospital deaths or expenditures in the last year of life. However, patients with cancer using hospice did have significant savings.

Aged↗
PubMedDate not supplied

Think globally, protect locally: a conversation with Mark McClellan.

Departing Food and Drug Administration (FDA) Commissioner Mark McClellan outlines the major initiatives of his sixteen-month tenure at the agency, including an expanded role for economic analysis in FDA policy, steps to promote "e-prescribing" and other information technologies, broadened use of external advisory panels to reduce political conflict between the agency and its various stakeholders, and an uncompromising stance against allowing U.S. citizens to reimport drugs from foreign sources. McClellan's policy interests and positions at the FDA may offer some insight into his approach to future policy positions at the Centers for Medicare and Medicaid Services.

Administrative Personnel↗
PubMedDate not supplied

Reducing uninsurance through the nongroup market: health insurance credits and purchasing groups.

The president's proposal to introduce tax credits for the purchase of health insurance will enable millions of Americans to purchase private health insurance, improving the functioning of private markets, empowering patients to make informed decisions, and increasing the use of high-value health care. Evidence points to the availability of comprehensive individual insurance for the young and the old, the sick and the healthy. There are a number of policies that would increase access to the nongroup market, none of which would adversely affect group markets. These policies together will ensure that all Americans have good, affordable health insurance choices available to them.

Insurance, Health↗