State prescription drug monitoring programs and fatal drug overdoses.

OBJECTIVES: To examine the impact of prescription drug monitoring programs (PDMPs) on drug overdose deaths. STUDY DESIGN: We used variation in the timing of state PDMP legislation and implementation to estimate the impact of these programs on drug overdose mortality rates across all drug categories from 1999 to 2014 and separately for each category from 1999 to 2010. Data used include US all-jurisdiction mortality data, estimated population data, and sociodemographic data from the CDC and the US Census Bureau. METHODS: Multivariate regression models were applied to state panel data, including state and year fixed effects and state-specific linear time trends. Preprogram tests were used to assess the common trends assumption underlying our empirical approach. RESULTS: The implementation of PDMPs was not associated with reductions in overall drug overdose or prescription opioid overdose mortality rates relative to expected rates in the absence of PDMPs. For most categories, PDMPs were associated with increased mortality rates, but the associations were statistically insignificant. In a subsample analysis of states with PDMPs in operation for 5 or more years, the programs were found to be associated with significantly higher mortality rates in legal narcotics, illicit drugs, and other and unspecified drugs. CONCLUSIONS: PDMPs were not associated with reductions in drug overdose mortality rates and may be related to increased mortality from illicit drugs and other, unspecified drugs. More comprehensive and prevention-oriented approaches may be needed to effectively reduce drug overdose deaths and avoid fatal overdoses from other drugs used as substitutes for prescription opioids.

Cumulative Advantage, Cumulative Disadvantage, and Evolving Patterns of Late-Life Inequality.

Purpose of the Study: Earlier studies have identified a pattern of cumulative advantage leading to increased within-cohort economic inequality over the life course, but there is a need to better understand how levels of inequality by age have changed in the evolving economic environment of recent decades. We utilized Survey of Income and Program Participation (SIPP) data to compare economic inequality across age groups for 2010 versus 1983-1984. Design and Methods: We examined changing age profiles of inequality using a summary measure of economic resources taking into account income, annuitized value of wealth, and household size. We adjusted for survey underreporting of some income and asset types, based on National Income Accounts and other independent estimates of national aggregates. We examined inequality by age with Gini coefficients. Results: Late-life (65+) inequality increased between the 2 periods, with Gini coefficients remaining higher than during the working years, but with a less steep age difference in inequality in 2010 than in 1983-1984. Inequality increased sharply within each cohort, particularly steeply in Depression-era, war-baby, and leading-edge baby boom cohorts. The top quintile of elderly received increasing shares of most income sources. Implications: Increasing inequality among older people, and especially in cohorts approaching late life, presages upcoming financial challenges for elderly persons in the lower part of the income distribution. Implications of this increasingly high-inequality late-life environment need to be carefully evaluated as changes are considered in Social Security and other safety-net institutions, which moderate impacts of economic forces that drive increasingly disparate late-life economic outcomes.

Evaluation of a novel series of fluorine-18-labeled imidazobenzodiazepines as potential new positron emission tomography radioligands for the GABAA receptor.

INTRODUCTION: [(11)C]Flumazenil has been used to study the GABAA receptor in many preclinical and clinical studies, but the short half-life of carbon-11 means that this molecule is restricted to use by investigators with access to on-site cyclotron and radiosynthesis facilities. The radiosynthesis of [(18)F]flumazenil has been evaluated by several groups, but the radiochemical yield can be low and inconsistent. We previously reported a series of fluorine-18-labeled imidazobenzodiazepine-based ligands for the GABAA receptor, which had significantly improved radiosynthesis yields. Here we report the in vivo evaluation and comparison of the distribution, metabolism and specificity of the novel ligands in comparison with [(18)F]flumazenil. METHODS: In vivo biodistribution studies, at time points up to 90min post-injection, were performed in naïve rats to compare the performance of the novel compounds with particular attention paid to regional brain uptake and clearance. In vivo metabolism studies were carried out to determine the percentage of parent compound remaining in the plasma and brain at selected time points. Blocking studies were carried out, using pre-treatment of the test animals with either bretazenil or unlabeled fluorine-19 test compound, to determine the levels of specific and non-specific binding in selected brain regions. RESULTS: Two of the 12 new compounds were rejected due to poor biodistribution showing significant bone uptake. Some of the compounds showed insufficient whole brain uptake or limited evidence of differential binding to GABAA-rich brain regions to warrant further investigation. Four of the compounds were selected for in vivo metabolism and blocking studies. Overall, the studies indicated that two compounds 3 and 5 showed comparable or improved performance compared with [(18)F]flumazenil, with respect to distribution, metabolic profile and specific binding. CONCLUSIONS: These studies have demonstrated that compounds based on [(18)F]flumazenil, but with alterations to allow improved radiosynthesis, can be prepared which have ideal properties and warrant further evaluation as PET agents for the GABAA receptor. In particular, compounds 3 and 5 show very promising profiles with specific binding and in vivo stability comparable to flumazenil.

Exploration of the structure-activity relationship of a novel tetracyclic class of TSPO ligands-potential novel positron emitting tomography imaging agents.

A series of novel TSPO ligands based on the tetracyclic class of translocator protein (TSPO) ligands first described by Okubo et al. was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands.

The development of potential new fluorine-18 labelled radiotracers for imaging the GABA(A) receptor.

Positron emission tomography (PET) using the tracer [(11)C]Flumazenil has shown changes in the distribution and expression of the GABA(A) receptor in a range of neurological conditions and injury states. We aim to develop a fluorine-18 labelled PET agent with comparable properties to [(11)C]Flumazenil. In this study we make a direct comparison between the currently known fluorine-18 labelled GABA(A) radiotracers and novel imidazobenzodiazepine ligands. A focussed library of novel compound was designed and synthesised where the fluorine containing moiety and the position of attachment is varied. The in vitro affinity of twenty-two compounds for the GABA(A) receptor was measured. Compounds containing a fluoroalkyl amide or a longer chain ester group were eliminated due to low potency. The fluorine-18 radiochemistry of one compound from each structural type was assessed to confirm that an automated radiosynthesis in good yield was feasible. Eleven of the novel compounds assessed appeared suitable for in vivo assessment as PET tracers.

Exploration of the structure-activity relationship of the diaryl anilide class of ligands for translocator protein--potential novel positron emitting tomography imaging agents.

A series of novel ligands based on the diaryl anilide (DAA) class of translocator protein (TSPO) ligands was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands and will be evaluated further as potential clinical imaging agents.

[¹8F]GE-180: a novel fluorine-18 labelled PET tracer for imaging Translocator protein 18 kDa (TSPO).

A series of tricyclic compounds have been synthesised and evaluated in vitro for affinity against Translocator protein 18 kDa (TSPO) and for preferred imaging properties. The most promising of the compounds were radiolabelled and evaluated in vivo to determine biodistribution and specificity for high expressing TSPO regions. Metabolite profiling in brain and plasma was also investigated. Evaluation in an autoradiography model of neuroinflammation was also carried out for the best compound, 12a ([(18)F]GE-180).

Agency characteristics and changes in home health quality after Home Health Compare.

OBJECTIVE: This study examines the association between home health agency characteristics and quality improvement in home health care after Home Health Compare (HHC), a public-reporting initiative in the Medicare program. METHOD: We examined the changes in seven quality measures reported in HHC from 2003 to 2007. We used a linear regression model to examine whether quality changes over time differed by agency characteristics. RESULTS: We found improvements in quality after HHC in the indicators that measure patients' ability to independently manage daily activities; however, the use of emergent care did not change, and hospitalization rates increased during the study period. Agencies with low quality at baseline, not-for-profit or hospital-based agencies, and agencies with longer Medicare tenure showed greater improvement for some quality measures than their counterparts. DISCUSSION: There was large variation in the degree of quality improvement after HHC by quality indicators and by agency characteristics.

Meeting the need for personal care among the elderly: does Medicaid home care spending matter?

OBJECTIVE: To determine whether Medicaid home care spending reduces the proportion of the disabled elderly population who do not get help with personal care. DATA SOURCES: Data on Medicaid home care spending per poor elderly person in each state is merged with data from the Medicare Current Beneficiary Survey for 1992, 1996, and 2000. The sample (n=6,067) includes elderly persons living in the community who have at least one limitation in activities of daily living (ADLs). STUDY DESIGN: Using a repeated cross-section analysis, the probability of not getting help with an ADL is estimated as a function of Medicaid home care spending, individual income, interactions between income and spending, and a set of individual characteristics. Because Medicaid home care spending is targeted at the low-income population, it is not expected to affect the population with higher incomes. We exploit this difference by using higher-income groups as comparison groups to assess whether unobserved state characteristics bias the estimates. PRINCIPAL FINDINGS: Among the low-income disabled elderly, the probability of not receiving help with an ADL limitation is about 10 percentage points lower in states in the top quartile of per capita Medicaid home care spending than in other states. No such association is observed in higher-income groups. These results are robust to a set of sensitivity analyses of the methods. CONCLUSION: These findings should reassure state and federal policymakers considering expanding Medicaid home care programs that they do deliver services to low-income people with long-term care needs and reduce the percent of those who are not getting help.

Estimating the effects of prescription drug coverage for Medicare beneficiaries.

OBJECTIVE: To identify the effect of insurance coverage on prescription utilization by Medicare beneficiaries. DATA SOURCES/STUDY SETTING: Secondary data from the 1999 Medicare Current Beneficiary Survey (MCBS) Cost and Use files, a nationally representative survey of Medicare enrollees. STUDY DESIGN: The paper uses a cross-sectional design with (1) a standard regression framework to estimate the impact of prescription coverage on utilization controlling for potential selection bias with covariate control based on the Diagnostic Cost Group/Hierarchical Condition Category (DCG/HCC) risk adjuster, and (2) a multistage residual inclusion method using instrumental variables to control for selection bias and identify the insurance coverage effect. DATA COLLECTION/EXTRACTION METHODS: Data were extracted from the 1999 MCBS. Study inclusion criteria are community-dwelling MCBS respondents with full-year Medicare enrollment and supplemental medical insurance with or without full-year drug benefits. The final sample totaled 5,270 Medicare beneficiaries. PRINCIPAL FINDINGS: Both the model using the DCG/HCC risk adjuster and the model using the residual inclusion method produced similar results. The estimated price elasticity of demand for prescription drugs for the Medicare beneficiaries in our sample was -0.54. CONCLUSIONS: Our results confirm that selection into prescription coverage is predictable based on observable health. Our results further confirm prior estimates of price sensitivity of prescription drug demand for Medicare beneficiaries, though our estimate is slightly above prior results.

The caregiver stress process and health outcomes.

OBJECTIVE: The authors examine the impact of two caregiving stressors, care receivers' behavior problems (an objective stressor) and caregivers' feelings of overload (a subjective stressor), on three dimensions of caregiver health. METHOD: The participants were 234 primary caregivers of elderly relatives with dementia living in the community who completed a comprehensive interview about their current care situation, including stressors and health. RESULTS: Higher levels of both objective and subjective stressors were associated with all three dimensions of caregiver health: poorer self-reported health, more negative health behaviors, and greater use of health care services. The association between objective stressors and health was mediated by caregivers' feelings of overload. CONCLUSIONS: These findings demonstrate caregivers' vulnerability to the effects of stressors across three dimensions of health and also underscore the importance of subjective appraisals of stress.

Coverage and use of prescription drugs in nursing homes: implications for the medicare modernization act.

BACKGROUND: The Medicare Modernization Act will affect drug coverage for most nursing home residents in the United States. Understanding the impact of the MMA requires knowledge of the process by which drugs are prescribed to residents and the effect of coverage on medication use. OBJECTIVES: We sought to characterize sources of drug coverage for Medicare beneficiaries residing in nursing facilities and to provide empirical estimates of the relationship between coverage and use. RESEARCH DESIGN: We used bivariate and multivariate analyses to assess the relationship between coverage and drug use in a sample of nursing home residents drawn from the 2001 Medicare Current Beneficiary Survey augmented with monthly institutional drug administration data. SUBJECTS: A total of 789 residents with a mean nursing home stay of 8.7 months in 2001 were studied. MEASURES: We measured the proportions of residents with drug coverage from Medicaid, other sources, or none at all, and mean number of unique prescription drugs administered per resident per month by source of coverage. RESULTS: We found that 20% of the sample had no drug coverage, 56% had drug coverage under Medicaid, 9% had coverage from other sources, and for 15% drug coverage status could not be determined. There were no statistically significant differences in drug utilization by drug coverage status. CONCLUSIONS: When drug coverage becomes a Medicare benefit in 2006, it is unlikely to spur additional medication use among nursing home residents but may redirect utilization as a result of health plan formulary restrictions.

The relationship between quality of care and costs in nursing homes.

The purpose of this study was to evaluate the impact of quality of care on costs in nursing homes. The sample consisted of 749 nursing homes in 5 states in 1996. Nursing home cost functions were estimated using weighted 2-stage least-squares regression analysis. Costs are measured as the facility's total patient care costs. Two outcome measures are used as quality indicators: pressure ulcers worsening and mood decline. Nonmonotonic relationships are observed between quality and costs for nursing homes in the sample. However, the pattern of the relationship is different depending on the quality indicator. For pressure ulcers, the authors observe an inverted U-shaped curve with increasing costs at the lower range of quality but decreasing costs associated with higher quality after a threshold. The opposite pattern is observed for mood decline, with a relatively flat curve at the lower range of quality but increasing costs after a threshold.

Life on the edge: patterns of formal and informal help to older adults in the United States and Sweden.

OBJECTIVE: Our objective in this study was to compare assistance received by individuals in the United States and Sweden with characteristics associated with low, moderate, or high 1-year placement risk in the United States. METHODS: We used longitudinal nationally representative data from 4,579 participants aged 75 years and older in the 1992 and 1993 waves of the Medicare Current Beneficiary Survey (MCBS) and cross-sectional data from 1,379 individuals aged 75 years and older in the Swedish Aging at Home (AH) national survey for comparative purposes. We developed a logistic regression equation using U.S. data to identify individuals with 3 levels (low, moderate, or high) of predicted 1-year institutional placement risk. Groups with the same characteristics were identified in the Swedish sample and compared on formal and informal assistance received. RESULTS: Formal service utilization was higher in Swedish sample, whereas informal service use is lower overall. Individuals with characteristics associated with high placement risk received more formal and less informal assistance in Sweden relative to the United States. DISCUSSION: Differences suggest formal services supplement informal support in the United States and that formal and informal services are complementary in Sweden.

Riding the rollercoaster: the ups and downs in out-of-pocket spending under the standard Medicare drug benefit.

This study projects how much Medicare beneficiaries who sign up for the standard Part D drug benefit in 2006 will pay in quarterly out-of-pocket payments through 2008. In the first year we estimate that about 38 percent of enrollees will hit the benefit's no-coverage zone, known as the "doughnut hole," and that 14 percent will exceed the catastrophic threshold. Because drug spending is highly persistent over time, beneficiaries who experience the biggest gaps in coverage are likely to do so year after year, with potentially serious financial consequences.

The quality of antipsychotic drug prescribing in nursing homes.

BACKGROUND: The prescribing of antipsychotic drugs has been increasing in nursing homes (NHs) since the availability of second-generation antipsychotic agents, also known as the atypicals, but there is little information on the appropriateness of such prescribing. METHODS: A retrospective analysis using the nationally representative data set of the Medicare Current Beneficiary Survey merged to Minimum Data Sets assessments, medication administration records, and Medicare claims. We identified a sample of 2.5 million Medicare beneficiaries in NHs during 2000-2001 (unweighted n = 1096) to assess prevalence of antipsychotic use, rates of adherence to NH prescribing guidelines, and changes in behavioral symptoms. RESULTS: Approximately 693 000 (unweighted n = 302), or 27.6%, of all Medicare beneficiaries in NHs received at least 1 prescription for antipsychotics during the study period: 20.3% received atypicals only; 3.7%, conventionals only; and 3.6%, both atypicals and conventionals. Less than half (41.8%) of treated residents received antipsychotic therapy in accordance with NH prescribing guidelines. One (23.4%) in 4 patients had no appropriate indication, 17.2% had daily doses exceeding recommended levels, and 17.6% had both inappropriate indications and high dosing. Patients receiving antipsychotic therapy within guidelines were no more likely to achieve stability or improvement in behavioral symptoms than were those taking antipsychotics outside the guidelines. CONCLUSIONS: This study detected the highest level of antipsychotic use in NHs in over a decade. Most atypicals were prescribed outside the prescribing guidelines and for doses and indications without strong clinical evidence. Failure to detect positive relationships between behavioral symptoms and antipsychotic therapy raises questions about the appropriateness of prescribing.

Spouses of persons with dementia: their healthcare problems, utilization, and costs.

Spouses of persons with dementia (PWD) often experience poor health outcomes related to the experience of living with the afflicted spouse. Using the Anderson and Aday Healthcare Utilization Model, we conducted a retrospective review of an administrative database from a private healthcare insurer to compare health problems that precipitate utilization, patterns of utilization, and costs of care of spouses of PWD (n = 979) to those of spouses of persons without dementia (n = 979). Spouses of PWD were treated for more anxiety disorders (OR = 2.97; 95% CI = 1.63-5.44), falls (OR = 7.72; 95% CI = 2.73-21.84), rheumatologic diseases (OR = 2.5; 95% CI = 1.24-5.06), and diabetes with no complications (OR = 1.53; 95% CI = 1.06-2.22), but less pneumonia (OR =.55; 95%; CI =.35-.88) than comparison spouses. Spouses of PWD had a higher number of emergency room (ER) visits (p =.01). There were no differences in costs between the groups. The findings can be used to develop interventions for spouses of PWD.

Doughnut holes and price controls.

In 2003 citizens of Canada, the United Kingdom, and France paid an average of 34-59 percent of what Americans paid for a similar market basket of pharmaceuticals. If the Medicare program were to pay comparable prices for pharmaceuticals, it would be possible to eliminate the "doughnut hole" in its prescription drug benefit and keep Medicare drug spending within the overall limits established by Congress. This provides Congress with a clear choice: reduce the level of cost sharing and improve beneficiaries' access to pharmaceuticals, or allow the pharmaceutical industry to use the higher prices to fund research and development and to engage in other activities.

The economies of scale for nursing home care.

Using a modified hybrid short-term operating cost function and a national sample of nursing homes in 1994, the authors examined the scale economies of nursing home care. The results show that scale economies exist for Medicare postacute care, with an elasticity of -0.15 and an optimal scale of around 4,000 patient days annually. However, more than 68 percent of nursing homes in the analytic sample produced Medicare days at a level below the optimal scale. The financial pressures resulting from the implementation of a prospective payment system for Medicare skilled nursing facilities may further reduce the quantity of Medicare days served by nursing homes. In addition, the results show that chain-owned nursing homes do not have lower short-term operating costs than do independent facilities. This indicates that the rationale behind recent increasing horizontal integration among nursing homes may not be seeking greater cost efficiency but some other consideration.