Cost and Utilization of Behavioral Health Medications Associated with Rescission of an Exemption for Prior Authorization for Severe and Persistent Mental Illness in the Vermont Medicaid Program

BACKGROUND: In recent years, many state Medicaid programs have implemented preferred drug lists (PDL) to control pharmaceutical costs by generating supplemental rebate revenues and directing providers to the most cost-effective treatments. Two states, Michigan and Vermont, sought approval from the Centers for Medicare and Medicaid Services for supplemental rebates for their Medicaid fee-for-service programs in 2002. Behavioral health medications were largely excluded from PDLs and other managed care initiatives implemented by state Medicaid programs because of significant opposition to any impact on this vulnerable population. In November 2001, the Vermont Medicaid program implemented the Vermont Health Access Pharmacy Benefit Management Program, a PDL designed to promote cost-effective use of medications. Despite the potential cost savings resulting from implementation of a PDL, behavioral health providers and advocates in the state of Vermont opposed the implementation of the managed care initiative for beneficiaries with severe mental illness, and after January of 2002, Vermont\u27s program was changed to exempt beneficiaries meeting the severe and persistent mental illness (SPMI) criteria from prior authorization (PA) for behavioral health medications not on the Medicaid PDL. The SPMI exemption was phased out by June 30, 2006. OBJECTIVES: To determine the effects of the rescission of the PA exemption on utilization and costs of 3 classes of behavioral health medications (antidepressants, antipsychotics, and anxiolytics/sedatives). Secondary analyses were conducted to assess the association between rescission of the PA exemption and 2 quality measures that might be associated with pharmacy management policy: (a) behavioral health hospitalizations and (b) high-dose prescribing of antipsychotics, defined as dosing that exceeded the manufacturer-recommended maximum dose by 25%. METHODS: This was a retrospective analysis of pharmacy claims for beneficiaries of the Office of Vermont Health Access Medicaid Program for dates of service from July 1, 2005, through December 31, 2007. The 12-month PA exemption period for 3 categories of drugs (antidepressants, antipsychotics, and anxiolytics/sedatives) was July 1, 2005, through June 30, 2006; and the post-PA exemption period was the 12 months from January 1, 2007, through December 31, 2007, following rescission of the SPMI exemption. Costs in this analysis were defined as the amount paid by Medicaid, excluding federal drug rebates paid by drug manufacturers and supplemental rebates associated with the PDL program. Costs were adjusted for inflation using the Consumer Price Index for medical costs. Frequencies were used to identify trends between medication classes and time periods. Medical claims from the 2 time periods were used to assess inpatient hospitalization trends. Descriptive statistics, Pearson chi-square tests (for categorical data), and t-tests (for continuous data) were used to assess the 2 study cohorts. RESULTS: 17.8% (n=22,130) of 124,169 eligible beneficiaries in the PA exemption period had 1 or more pharmacy claims in the 3 classes of medications exempt from PA versus 19.2% (n=23,717) of 123,499 eligible beneficiaries in the post-PA exemption period. Utilization of behavioral medications per member per month (PMPM) increased by 14.3% from 0.14 claims PMPM in the PA exemption period to 0.16 claims PMPM in the post-PA exemption period, similar to the 14.1% increase in the utilization of nonbehavioral medications (from 0.64 to 0.73 claims PMPM). Utilization changed little between the PA exemption period and the post-PA exemption period for the 3 individual classes of behavioral health drugs, 0.08 claims PMPM versus 0.09 claims PMPM for antidepressants and 0.03 for both study periods for both antipsychotics and anxiolytics/sedative hypnotics. PMPM costs for the 3 drug classes exempt from PA increased by 2.1% from $12.76 to$13.03, compared with a 12.2% increase from $42.58 PMPM to$47.79 PMPM for nonbehavioral health medications. The small 2.1% increase in PMPM costs for the 3 formerly PA-exempt drug classes was attributable in part to a 12.9% reduction in average cost per pharmacy claim, from $94.05 to$81.92, including a 24.8% reduction in the average cost per antidepressant claim, from $65.59 to$49.33. For the subgroup of beneficiaries taking atypical antipsychotic medications, the percentage with high-dose prescriptions decreased from 3.1% to 2.2%. Mental health inpatient hospitalizations also decreased from 0.6% of beneficiaries in the PA exemption period to 0.4% in the post-PA exemption period. CONCLUSIONS: In a Medicaid population excluding Medicare dual-eligible beneficiaries, the rescission of a PA exemption for 3 major classes of behavioral health medications in a PDL was not associated with decreased utilization of formerly PA-exempt behavioral health medications. The increase in PMPM spending for the formerly PA-exempt behavioral health medications was small compared with the increase in PMPM cost for nonbehavioral health medications, and there were fewer beneficiaries with hospitalization for mental health reasons in the period after rescission of the PA exemption

Large-Scale Integration of Nanoelectromechanical Systems for Gas Sensing Applications

We have developed arrays of nanomechanical systems (NEMS) by large-scale integration, comprising thousands of individual nanoresonators with densities of up to 6 million NEMS per square centimeter. The individual NEMS devices are electrically coupled using a combined series-parallel configuration that is extremely robust with respect to lithographical defects and mechanical or electrostatic-discharge damage. Given the large number of connected nanoresonators, the arrays are able to handle extremely high input powers (>1 W per array, corresponding to <1 mW per nanoresonator) without excessive heating or deterioration of resonance response. We demonstrate the utility of integrated NEMS arrays as high-performance chemical vapor sensors, detecting a part-per-billion concentration of a chemical warfare simulant within only a 2 s exposure period

Environmental and climate finance in a new world: How past environmental aid allocation impacts future climate aid

In this paper we update previous work that categorizes foreign aid projects in terms of their likely impact on the natural environment. We then document trends in the global distribution of environmental aid over time and show that environmental aid has increasingly focussed on global environmental issues (especially climate change), rather than local issues in recipient countries. Somewhat surprisingly, we also find that environmental aid is increasingly allocated through bilateral aid agencies rather than through the increasing number of multilateral channels created for this purpose. After providing these descriptive statistics and demonstrating trends, we offer a tentative explanation for this puzzling pattern. We argue that each individual aid project represents a negotiation between donor and recipient. This additional level of bargaining significantly conditions the costs and benefits of multilateralism for donors, especially as recipients have multiple outside options for obtaining development finance. Reflecting the growing political salience of global environmental threats, donors are providing increasing levels of environmental aid, and especially climate finance. However, at the same time, donors are increasingly failing to co-ordinate their allocation of climate finance (and other environmental aid) within multilateral institutions. At a practical level, this raises the question whether the effect of increasing levels of funding will be undercut by decreasing co-ordination and efficiency

Multi-Armed Bandits for Correlated Markovian Environments with Smoothed Reward Feedback

We study a multi-armed bandit problem in a dynamic environment where arm rewards evolve in a correlated fashion according to a Markov chain. Different than much of the work on related problems, in our formulation a learning algorithm does not have access to either a priori information or observations of the state of the Markov chain and only observes smoothed reward feedback following time intervals we refer to as epochs. We demonstrate that existing methods such as UCB and $\varepsilon$-greedy can suffer linear regret in such an environment. Employing mixing-time bounds on Markov chains, we develop algorithms called EpochUCB and EpochGreedy that draw inspiration from the aforementioned methods, yet which admit sublinear regret guarantees for the problem formulation. Our proposed algorithms proceed in epochs in which an arm is played repeatedly for a number of iterations that grows linearly as a function of the number of times an arm has been played in the past. We analyze these algorithms under two types of smoothed reward feedback at the end of each epoch: a reward that is the discount-average of the discounted rewards within an epoch, and a reward that is the time-average of the rewards within an epoch.Comment: Significant revision of prior version including deeper discussion of related work, gap-independent regret bounds, and regret bounds for discounted reward

HCI as a means to prosociality in the economy

HCI research often involves intervening in the economic lives of people, but researchers only rarely give explicit consideration to what actually constitutes prosociality in the economy. Much has been said previously regarding sustainability but this has largely focused on environmental rather than interpersonal relations. This paper provides an analysis of how prosocial HCI has been discussed and continues to be defined as a research field. Based on a corpus of published works, we describe a variety of genres of work relating to prosocial HCI. Key intellectual differences are explored, including the epistemological and ethical positions involved in designing for prosocial outcomes as well as how HCI researchers posit economic decision-making. Finally, emerging issues and opportunities for further debate and collaboration are discussed in turn

Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: A randomized, double-blind, placebo-controlled study

AbstractObjectives. This study examined the of metoprolol on left ventricular performance, efficiency, neurohormonal activation and myocardial respiratory quotient in patients with dilated cardiomyopathy.Background.The mechanism by which beta-adrenergie blockade improves ejection fraction in patients with dilated cardiomyopathy remains an enigma. Thus, we undertook an extensive hemodynamic evaluation of this mechanism. In addition, because animal models have shown that catecholamine exposure may increase relative fatty acid utilization, we hypothesized that antagonism of sympathetic stimulation may result in increased carbohydrate utilization.Methods. This was a randomized, double-blind, prospective trial in which 24 men with nonischemic dilated cardiomyopathy underwent cardiac catheterization before and after 3 months of therapy with metoprolol (n = 15) or placebo (n = 9) in addition to standard therapy. Pressure-volume relations were examined using a micromanometer catheter and digital ventriculography.Results. At baseline, the placebo-treated patients had somewhat more advanced left ventricular dysfunction. Ejection fraction and left ventricular performance improved only in the metoprolol-treated patients. Stroke and minute work increased without an increase in myocardial oxgen consumption, suggesting increased myocardial efficiency. Further increases in ejection fraction were seen between 3 and 6 months in the metoprolol group. The placebo group had a significant increase in ejection fraction only after crossover to metoprolol. A significant relation the change in coronary sinus norepinephrine and myocardial respiratory quotient was seen, suggesting a possible effect of adrenergic deactivation on substrate utilization.Conclusions. These data demonstrate that in patients with cardiomyopthy, metoprolol treatment improves myocardial performance and energetics, and favorably alters substrate utilization. Beta-adrenergic blocking agents, such as metoprolol, are hemodynamically and energetically beneficial in the treatment of myocardial failure

Plasminogen activation triggers transthyretin amyloidogenesis in vitro

Systemic amyloidosis is a usually fatal disease caused by extracellular accumulation of abnormal protein fibers, amyloid fibrils, derived by misfolding and aggregation of soluble globular plasma protein precursors. Both WT and genetic variants of the normal plasma protein transthyretin (TTR) form amyloid, but neither the misfolding leading to fibrillogenesis nor the anatomical localization of TTR amyloid deposition are understood. We have previously shown that, under physiological conditions, trypsin cleaves human TTR in a mechano-enzymatic mechanism that generates abundant amyloid fibrils in vitro. In sharp contrast, the widely used in vitro model of denaturation and aggregation of TTR by prolonged exposure to pH 4.0 yields almost no clearly defined amyloid fibrils. However, the exclusive duodenal location of trypsin means that this enzyme cannot contribute to systemic extracellular TTR amyloid deposition in vivo. Here, we therefore conducted a bioinformatics search for systemically active tryptic proteases with appropriate tissue distribution, which unexpectedly identified plasmin as the leading candidate. We confirmed that plasmin, just as trypsin, selectively cleaves human TTR between residues 48 and 49 under physiological conditions in vitro. Truncated and full-length protomers are then released from the native homotetramer and rapidly aggregate into abundant fibrils indistinguishable from ex vivo TTR amyloid. Our findings suggest that physiological fibrinolysis is likely to play a critical role in TTR amyloid formation in vivo. Identification of this surprising intersection between two hitherto unrelated pathways opens new avenues for elucidating the mechanisms of TTR amyloidosis, for seeking susceptibility risk factors, and for therapeutic innovation

A specific nanobody prevents amyloidogenesis of D76N β2-microglobulin in vitro and modifies its tissue distribution in vivo

Systemic amyloidosis is caused by misfolding and aggregation of globular proteins in vivo for which effective treatments are urgently needed. Inhibition of protein self-aggregation represents an attractive therapeutic strategy. Studies on the amyloidogenic variant of β2-microglobulin, D76N, causing hereditary systemic amyloidosis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant conditions. Here we compare the potency of two previously described inhibitors of wild type β2-microglobulin fibrillogenesis, doxycycline and single domain antibodies (nanobodies). The β2-microglobulin -binding nanobody, Nb24, more potently inhibits D76N β2-microglobulin fibrillogenesis than doxycycline with complete abrogation of fibril formation. In β2-microglobulin knock out mice, the D76N β2-microglobulin/ Nb24 pre-formed complex, is cleared from the circulation at the same rate as the uncomplexed protein; however, the analysis of tissue distribution reveals that the interaction with the antibody reduces the concentration of the variant protein in the heart but does not modify the tissue distribution of wild type β2-microglobulin. These findings strongly support the potential therapeutic use of this antibody in the treatment of systemic amyloidosis

Angiolymphoid hyperplasia with eosinophilia: efficacy of isotretinoin?

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign but potentially disfiguring vascular lesion. It is usually characterized by dermal and subcutaneous nodules, primarily in the head and neck region. Spontaneous regression is common, but persistent or recurrent lesions may require treatment. Several treatments have been reported but surgery is the most efficient one. METHODS AND RESULTS: We report a 32-year-old man presenting with multiple nodules on the cheeks, preauricular region and the scalp and who received treatment with isotretinoin (0.5 mg/kg/day) for 1 year with complete resolution of one of his scalp nodules. The rest of the lesions remained stable and were treated with surgical excision without recurrence. CONCLUSION: Isotretinoin may play a role in the treatment of ALHE due to its antiangiogenic properties via a reduction of vascular endothelial growth factor (VEGF) production by keratinocytes