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This article addresses the content of the workshop, including a panel discussion relevant to delineation of a path forward in relation to risk assessment of essential metals. The state of the art of risk assessment and associated issues for essential metals are outlined initially, followed by brief illustration by the case studies considered at the workshop (i.e., copper, zinc, and manganese). Approaches for the future testing strategies of essential metals are discussed in terms of options to increase efficiency and accuracy of assessments. Subsequently, recommendations for pragmatic next steps to advance progress and facilitate uptake by the regulatory risk assessment community are presented.

BACKGROUND: Several studies have shown that use of medications to treat chronic conditions is highly sensitive to out-of-pocket price and influenced by changes in insurance coverage. Because antibiotics target infections and are used for a short period, one may expect antibiotic use to be less responsive to price. However, no studies have evaluated how antibiotic use changes with drug coverage. We evaluate changes in ambulatory oral antibiotic use after implementation of the Medicare drug benefit (Part D).

METHODS: We conducted a comparison group analysis 2 years before and after implementation of Part D using insurance claims data from a large Medicare Advantage plan (January 1, 2004, through December 31, 2007). Outcomes included the likelihood of using any oral antibiotics and major antibiotic subclasses among 35 102 older adults and rates of antibiotic use among those with pneumonia and other acute respiratory tract infections.

RESULTS: Overall antibiotic use increased most among those who did not previously have drug coverage (relative odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36-1.85). Use of the broad spectrum antibiotic subclasses of quinolones (OR, 1.70; 95% CI, 1.35-2.15) and macrolides (1.59; 1.26-2.01) increased more than the use of other subclasses, especially for those with prior drug coverage. Rates of ambulatory antibiotic use associated with pneumonia increased (OR, 3.60; 95% CI, 2.35-5.53) more than those associated with other acute respiratory tract infections (2.29; 1.85-2.83).

CONCLUSIONS: Antibiotic use increased among older adults whose drug coverage improved after Part D implementation, with the largest increases for broad spectrum, newer, and more expensive antibiotics. Our study suggests reimbursement may play a role in addressing inappropriate antibiotic use.

BACKGROUND: Adherence to pharmacotherapy for heart failure is poor among older adults in part because of high prescription drug costs. We examined the impact of improvements in drug coverage under Medicare Part D on utilization of, and adherence to, medications for heart failure in older adults.

METHODS: We used a quasi-experimental approach to analyze pharmacy claims for 6,950 individuals aged >or=65 years with heart failure enrolled in a Medicare managed care organization 2 years before and after Part D's implementation. We compared prescription fill patterns among individuals who moved from limited (quarterly benefits caps of USD 150 or USD 350) or no drug coverage to Part D in 2006 with those who had generous employer-sponsored coverage throughout the study period.

RESULTS: Individuals who previously lacked drug coverage filled approximately 6 more heart failure prescriptions annually after Part D (adjusted ratio of prescription counts = 1.36, 95% CI 1.29-1.44, P < .0001 relative to the comparison group). Those previously lacking drug coverage were more likely to fill prescriptions for an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker plus a beta-blocker after Part D (adjusted ratio of odds ratios = 1.73, 95% CI 1.42-2.10, P < .0001) and more likely to be adherent to such pharmacotherapy (adjusted ratio of odds ratios = 2.95, 95% CI 1.85-4.69, P < .0001) relative to the comparison group.

CONCLUSIONS: Medicare Part D was associated with improved access to medications and adherence to pharmacotherapy in older adults with heart failure.

BACKGROUND: Little is known about how Medicare Part D affects the medication refill adherence for cardiovascular and diabetes medications, particularly among beneficiaries without prior drug coverage.

OBJECTIVES: To evaluate Medicare Part D's effect on medication adherence among beneficiaries with hyperlipidemia, hypertension, and/or diabetes enrolled in Medicare Advantage products.

RESEARCH DESIGN: We used a quasi-experimental pre-post design, with 3 treatment groups and a comparison group, to assess the effect of Part D on several measures of adherence to prescription medications.

SUBJECTS: Adults aged 65 or older with hyperlipidemia, hypertension, and/or diabetes in 2003 continuously enrolled between 2004 and 2007 in a large Pennsylvania insurer's Medicare Advantage products.

MEASURES: Medication possession ratios (MPR), good adherence with MPR >0.8, and intensity of treatment measured by average daily counts of pills per day of treatment.

RESULTS: Part D improved MPRs in the group without prior drug coverage by 13.4 percentage points (95% CI, 10.1-16.8), 17.9 (95% CI, 13.7-22.1), and 13.5 (95% CI, 11.5-15.5) for those with hyperlipidemia, diabetes, and hypertension, respectively. Adherence improved less in the other 2 groups with limited prior drug benefits. Although the proportion of beneficiaries in the intervention groups who attained good adherence levels increased after Part D, less than 50%, 68%, and 78% of beneficiaries with hyperlipidemia, diabetes, and hypertension, respectively, attained good adherence.

CONCLUSION: Part D increased adherence to medications that reduce the risk of cardiovascular events for patients with hypertension, diabetes, and hyperlipidemia. This should improve the health of the elderly people in the long run.

The Patient Protection and Affordable Care Act will expand insurance coverage to millions of Americans with mental disorders. One particularly important implementation issue is the scope of mental health and substance abuse services under expanded health insurance coverage. This article examines current public and commercial insurance coverage of the range of services used by individuals with mental illnesses and substance use disorders and assesses the implications of newly mandated standards for benefit packages offered by public and private plans. The authors note that many services needed by individuals with mental or substance use disorders fall outside the scope of benefits currently covered by a typical private insurance plan. Compared with other insurers, Medicaid currently covers a broader range of behavioral health services; however, individuals moving into Medicaid under new eligibility pathways will receive "benchmark" or "benchmark-equivalent" coverage rather than full Medicaid benefits. If behavioral health benefits are set at those currently available in typical private plans or in benchmark coverage, some newly insured individuals with mental illnesses or substance use disorders who are covered by private plans or Medicaid expansions are still likely to face gaps in covered services. Policy makers have several options for addressing these likely gaps in coverage, including requiring states to maintain coverage of some support services, including certain behavioral health services in the "essential benefits package," and expanding eligibility for full Medicaid benefits.

The core histone proteins H2A, H2B, H3 (histone H3) and H4 are known to form nucleosomes with nuclear DNA, but are historically considered to be absent from mitochondria. We suggest that H3 is a dual-targeted protein, found in mitochondria as well as N (nuclei). WoLF PSORT and MitoProt analyses of H3 sequences revealed mitochondrial targeting signals, and immunohistochemistry indicated mitochondrial distribution. Western blots of Brassica oleracea cv. Botrytis (cauliflower) mitochondrial extracts were positive for H3, when the primary antibody was against the conserved C-terminus. MS/MS (tandem mass spectrometry) analyses confirmed the Western blot data. Interestingly, Western blots of the same mitochondrial extracts were almost completely negative for H3 when the primary antibodies were highly specific for the N-terminal tail region of H3, suggesting that these antibodies are blocked by a modification of the tail of the H3 that occurs predominantly in the mitochondria, but not in the nucleus. Modifications of the tail of core H3 are known to help control nuclear genes. Future studies of the possible functions of mitochondrial H3 could lead to a greater understanding of the ability of a cell to synchronize nuclear and mitochondrial gene expression.

BACKGROUND: Adherence to pharmacotherapy for heart failure is poor among older adults in part because of high prescription drug costs. We examined the impact of improvements in drug coverage under Medicare Part D on utilization of, and adherence to, medications for heart failure in older adults.

METHODS: We used a quasi-experimental approach to analyze pharmacy claims for 6,950 individuals aged >or=65 years with heart failure enrolled in a Medicare managed care organization 2 years before and after Part D's implementation. We compared prescription fill patterns among individuals who moved from limited (quarterly benefits caps of USD 150 or USD 350) or no drug coverage to Part D in 2006 with those who had generous employer-sponsored coverage throughout the study period.

RESULTS: Individuals who previously lacked drug coverage filled approximately 6 more heart failure prescriptions annually after Part D (adjusted ratio of prescription counts = 1.36, 95% CI 1.29-1.44, P < .0001 relative to the comparison group). Those previously lacking drug coverage were more likely to fill prescriptions for an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker plus a beta-blocker after Part D (adjusted ratio of odds ratios = 1.73, 95% CI 1.42-2.10, P < .0001) and more likely to be adherent to such pharmacotherapy (adjusted ratio of odds ratios = 2.95, 95% CI 1.85-4.69, P < .0001) relative to the comparison group.

CONCLUSIONS: Medicare Part D was associated with improved access to medications and adherence to pharmacotherapy in older adults with heart failure.