Publications

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.

OBJECTIVES: To examine variation in outpatient prescription use and spending for hyperlipidemia and diabetes mellitus in the Veterans Affairs Healthcare System (VA) and its association with quality measures for these conditions.

STUDY DESIGN: Cross-sectional.

METHODS: We compared outpatient prescription use, spending, and quality of care across 135 VA medical centers (VAMCs) in fiscal year 2008, including 2.3 million patients dispensed lipid-lowering medications and 981,031 patients dispensed diabetes medications. At each facility, we calculated VAMC-level cost per patient for these medications, the proportion of patients taking brand-name drugs, and Healthcare Effectiveness Data and Information Set (HEDIS) scores for hyperlipidemia (low-density lipoprotein cholesterol level <100 mg/dL) and for diabetes (glycosylated hemoglobin level >9% or not measured).

RESULTS: The median cost per patient for lipid-lowering agents in fiscal year 2008 was $49.60 and varied from $39.68 in the least expensive quartile of VAMCs to $69.57 in the most expensive quartile (P < .001). For diabetes agents, the median cost per patient was $158.34 and varied from $123.34 in the least expensive quartile to $198.31 in the most expensive quartile (P < .001). The proportion of patients dispensed brand-name oral drugs among these classes in the most expensive quartile of VAMCs was twice that in the least expensive quartile (P < .001). There was no correlation between VAMC-level prescription spending and performance on HEDIS measures for lipid-lowering drugs (r = 0.12 and r = 0.07) or for diabetes agents (r = -0.10).

CONCLUSIONS: Despite the existence of a closely managed formulary, significant variation in prescription spending and use of brand-name drugs exists in the VA. Although we could not explicitly risk-adjust, there appears to be no relationship between prescription spending and quality of care.

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.

OBJECTIVES: To examine variation in outpatient prescription use and spending for hyperlipidemia and diabetes mellitus in the Veterans Affairs Healthcare System (VA) and its association with quality measures for these conditions.

STUDY DESIGN: Cross-sectional.

METHODS: We compared outpatient prescription use, spending, and quality of care across 135 VA medical centers (VAMCs) in fiscal year 2008, including 2.3 million patients dispensed lipid-lowering medications and 981,031 patients dispensed diabetes medications. At each facility, we calculated VAMC-level cost per patient for these medications, the proportion of patients taking brand-name drugs, and Healthcare Effectiveness Data and Information Set (HEDIS) scores for hyperlipidemia (low-density lipoprotein cholesterol level <100 mg/dL) and for diabetes (glycosylated hemoglobin level >9% or not measured).

RESULTS: The median cost per patient for lipid-lowering agents in fiscal year 2008 was $49.60 and varied from $39.68 in the least expensive quartile of VAMCs to $69.57 in the most expensive quartile (P < .001). For diabetes agents, the median cost per patient was $158.34 and varied from $123.34 in the least expensive quartile to $198.31 in the most expensive quartile (P < .001). The proportion of patients dispensed brand-name oral drugs among these classes in the most expensive quartile of VAMCs was twice that in the least expensive quartile (P < .001). There was no correlation between VAMC-level prescription spending and performance on HEDIS measures for lipid-lowering drugs (r = 0.12 and r = 0.07) or for diabetes agents (r = -0.10).

CONCLUSIONS: Despite the existence of a closely managed formulary, significant variation in prescription spending and use of brand-name drugs exists in the VA. Although we could not explicitly risk-adjust, there appears to be no relationship between prescription spending and quality of care.

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.

alpha-Particles are suitable to treat cancer micrometastases because of their short range and very high linear energy transfer. alpha-Particle emitter (213)Bi-based radioimmunotherapy has shown efficacy in a variety of metastatic animal cancer models, such as breast, ovarian, and prostate cancers. Its clinical implementation, however, is challenging due to the limited supply of (225)Ac, high technical requirement to prepare radioimmunoconjugate with very short half-life (T(1/2) = 45.6 min) on site, and prohibitive cost. In this study, we investigated the efficacy of the alpha-particle emitter (225)Ac, parent of (213)Bi, in a mouse model of breast cancer metastases. A single administration of (225)Ac (400 nCi)-labeled anti-rat HER-2/neu monoclonal antibody (7.16.4) completely eradicated breast cancer lung micrometastases in approximately 67% of HER-2/neu transgenic mice and led to long-term survival of these mice for up to 1 year. Treatment with (225)Ac-7.16.4 is significantly more effective than (213)Bi-7.16.4 (120 microCi; median survival, 61 days; P = 0.001) and (90)Y-7.16.4 (120 microCi; median survival, 50 days; P < 0.001) as well as untreated control (median survival, 41 days; P < 0.0001). Dosimetric analysis showed that (225)Ac-treated metastases received a total dose of 9.6 Gy, significantly higher than 2.0 Gy from (213)Bi and 2.4 Gy from (90)Y. Biodistribution studies revealed that (225)Ac daughters, (221)Fr and (213)Bi, accumulated in kidneys and probably contributed to the long-term renal toxicity observed in surviving mice. These data suggest (225)Ac-labeled anti-HER-2/neu monoclonal antibody could significantly prolong survival in HER-2/neu-positive metastatic breast cancer patients.

The expanding clinical challenge of respiratory tract infections due to resistant bacteria necessitates the development of new forms of therapy. The development of a compound composed of silver coupled to a methylated caffeine carrier (silver carbene complex 1 [SCC1]) that demonstrated in vitro efficacy against bacteria, including drug-resistant organisms, isolated from patients with respiratory tract infections was described previously. The findings of current in vitro studies now suggest that bactericidal concentrations of SCC1 are not toxic to airway epithelial cells in primary culture. Thus, it was hypothesized that SCC1 could be administered by the aerosolized route to concentrate delivery to the lung while minimizing systemic toxicity. In vivo, aerosolized SCC1 delivered to mice resulted in mild aversion behavior, but it was otherwise well tolerated and did not cause lung inflammation following administration over a 5-day period. The therapeutic efficacy of SCC1 compared to that of water was shown in a 3-day prophylaxis protocol, in which mice infected with a clinical strain of Pseudomonas aeruginosa had increased survival, decreased amounts of bacteria in the lung, and a lower prevalence of bacteremia. Similarly, by using an airway infection model in which bacteria were impacted in the airways by agarose beads, the administration of SCC1 was significantly superior to water in decreasing the lung bacterial burden and the levels of bacteremia and markers of airway inflammation. These observations indicate that aerosolized SCC1, a novel antimicrobial agent, warrants further study as a potential therapy for bacterial respiratory tract infections.

OBJECTIVE: To examine racial differences in medication use by older long-stay Veterans Affairs Nursing Home Care Unit (NHCU) patients.

DESIGN: Longitudinal study.

SETTINGS: 133 Veterans Affairs NHCUs.

PARTICIPANTS: Three thousand four hundred eighty veterans 65 years of age or older admitted between January 1, 2004, and June 30, 2005, for 90 days or more.

MAIN OUTCOMES MEASURES: Prevalence of those taking nine or more medications (i.e., polypharmacy) and medications from specific therapeutic medication classes. Racial differences were determined using 0.05 level chi-squared tests.

RESULTS: The sample consisted of 14.3% who were black. Blacks compared with whites (all comparisons P < 0.05 except where noted) were younger (13.6% vs. 17.4%, older than 85 years of age), had less depression (22.24 vs. 29.79%), less allergies (9.82% vs. 20.36%), and a similar rate of moderate-to severe pain (22.65% vs. 24.05; P = 0.49). The percent of polypharmacy was similar by race (blacks 74.35% vs. whites 71.18%; P = 0.62), as was the prevalence of medication class use with the exceptions that blacks were less likely than whites to take central nervous system (CNS) medications (75.75% vs. 80.14%; P = 0.02) and antihistamines (13.03% vs. 16.8%; P = 0.04). Specifically, blacks were less likely than whites to receive a selective serotonin-reuptake inhibitor (SSRI) antidepressant (20.84% vs. 27.17%; P < 0.01) or a second-generation antihistamine (3.41% vs. 6.51%; P < 0.01), but more likely than whites to receive opioids (14.63% vs. 11.27%; P = 0.03).

CONCLUSION: There appears to be racial differences in the overall use of antihistamines and CNS medications and some of their subclasses.

OBJECTIVE: The objective of the study was to identify patient and provider factors associated with prescribing antibiotics for outpatients with acute respiratory tract infections of likely nonbacterial etiology.

METHODS: We identified outpatients who were diagnosed in the emergency department with nonspecific upper respiratory tract infections (URIs) and acute bronchitis at the VA Pittsburgh Healthcare System from June 15, 2003, to June 14, 2004, and the Philadelphia VA Medical Center from November 30, 2003, to March 31, 2004. Stepwise logistic regression was used to identify factors independently associated with antibiotic prescribing.

RESULTS: Overall, 26% of the 667 eligible patients with URIs and/or acute bronchitis received antibiotics. Antibiotics were prescribed significantly more frequently for acute bronchitis at one site (97% vs 65%, P < .001). Using multivariable analysis, the following factors were independently associated with antibiotic prescribing (odds ratio, 95% confidence interval): presence of 1 or more comorbidities (2.1, 1.2-3.5), fever (2.5, 1.4-4.4), purulent sputum (2.5, 1.5-4.4), shortness of breath (2.8, 1.4-5.4), altered breath sounds (4.6, 2.4-8.6), diagnosis of acute bronchitis (15.9, 8.0-31.8), provider age > or = 30 years (2.6, 1.1-6.3), and noninternal medicine specialty (2.7, 1.2-6.0).

CONCLUSIONS: Antibiotic use was high and varied substantially for URIs and acute bronchitis. Specific signs and symptoms, a diagnosis of acute bronchitis, and provider age and specialty were associated with antibiotic prescribing. Interventions to decrease inappropriate prescribing should address the perceived utility of antibiotics in acute bronchitis and the accuracy of signs and symptoms in diagnosing a bacterial respiratory infection.

OBJECTIVES: To establish consensus oral dosing guidelines for primarily renally cleared medications prescribed for older adults.

DESIGN: Literature search followed by a two-round modified Delphi survey.

SETTING: A nationally representative survey of experts in geriatric clinical pharmacy.

PARTICIPANTS: Eleven geriatric clinical pharmacists.

MEASUREMENTS: After a comprehensive literature search and review by an investigative group of six physicians (2 general internal medicine, 2 nephrology, 2 geriatrics), 43 dosing recommendations for 30 medications at various levels of renal function were created. The expert panel rated its agreement with each of these 43 dosing recommendations using a 5-point Likert scale (1=strongly disagree to 5=strongly agree). Recommendation-specific means and 95% confidence intervals were estimated. Consensus was defined as a lower 95% confidence limit of greater than 4.0 for the recommendation-specific mean score.

RESULTS: The response rate was 81.8% (9/11) for the first round. All respondents who completed the first round also completed the second round. The expert panel reached consensus on 26 recommendations involving 18 (60%) medications. For 10 medications (chlorpropamide, colchicine, cotrimoxazole, glyburide, meperidine, nitrofurantoin, probenecid, propoxyphene, spironolactone, and triamterene), the consensus recommendation was not to use the medication in older adults below a specified level of renal function (e.g., creatinine clearance <30 mL/min). For the remaining eight medications (acyclovir, amantadine, ciprofloxacin, gabapentin, memantine, ranitidine, rimantadine, and valacyclovir), specific recommendations for dose reduction or interval extension were made.

CONCLUSION: An expert panel of geriatric clinical pharmacists was able to reach consensus agreement on a number of oral medications that are primarily renally cleared.