A primer on copay accumulators, copay maximizers, and alternative funding programs.

Insurer or self-insured employer's plans are increasingly using copay accumulator, copay maximizer, and alternative funding programs (AFPs) to reduce plan spending on high-priced prescriptions. These programs differ in their structure and impact on patient affordability but typically decrease the insurer or self-insured employer's financial responsibility for high-priced drugs and increase the complexity of specialty medication access for patients. The aim of this primer is to describe the structure of copay accumulator, copay maximizer, and AFPs to improve understanding of these cost-shifting strategies and help clinicians and patients navigate medication access and affordability issues to minimize treatment delays or non-initiation.

Discovery of Potent Glycosidases Enables Quantification of Smoke-Derived Phenolic Glycosides through Enzymatic Hydrolysis.

When grapes are exposed to wildfire smoke, certain smoke-related volatile phenols (VPs) can be absorbed into the fruit, where they can be then converted into volatile-phenol (VP) glycosides through glycosylation. These volatile-phenol glycosides can be particularly problematic from a winemaking standpoint as they can be hydrolyzed, releasing volatile phenols, which can contribute to smoke-related off-flavors. Current methods for quantitating these volatile-phenol glycosides present several challenges, including the requirement of expensive capital equipment, limited accuracy due to the molecular complexity of the glycosides, and the utilization of harsh reagents. To address these challenges, we proposed an enzymatic hydrolysis method enabled by a tailored enzyme cocktail of novel glycosidases discovered through genome mining, and the generated VPs from VP glycosides can be quantitated by gas chromatography-mass spectrometry (GC-MS). The enzyme cocktails displayed high activities and a broad substrate scope when using commercially available VP glycosides as the substrates for testing. When evaluated in an industrially relevant matrix of Cabernet Sauvignon wine and grapes, this enzymatic cocktail consistently achieved a comparable efficacy of acid hydrolysis. The proposed method offers a simple, safe, and affordable option for smoke taint analysis.

Development and implementation of a laboratory monitoring dashboard to reduce treatment gaps in inflammatory bowel disease.

PURPOSE: Patients receiving biologic therapy for inflammatory bowel disease (IBD) require routine laboratory monitoring to ensure the safety and efficacy of therapy. The purpose of this quality improvement project was to evaluate the implementation of a dashboard to prevent treatment gaps by prospectively identifying patients with IBD and outdated laboratory results receiving biologics. METHODS: We performed a pre/post analysis of dashboard implementation to assess the number of patients with overdue laboratory work resulting in treatment gaps. The dashboard combined data from the electronic health record (EHR) and pharmacy claims database to identify patients on a biologic with laboratory tests (white blood cell count, liver transaminases, C-reactive protein, and erythrocyte sedimentation rate) completed 5 or more months ago and/or a tuberculosis screen completed 11 or more months ago. After implementation, specialty pharmacists reviewed the dashboard and communicated via EHR if a new prescription and laboratory tests were needed. Messages were sent 4 weeks in advance of the next refill-eligible date. Mixed methods were used for analysis of qualitative data, including surveys, and quantitative data, assessing treatment gap length. RESULTS: A total of 40 patients who had outdated laboratory values and required a new prescription (15 before dashboard implementation and 25 after implementation) were included in the analysis. The frequency of a treatment gap decreased from 80% (n = 12) in the preimplementation phase to 32% (n = 8) in the postimplementation phase. The median gap length was shorter after dashboard implementation, decreasing from 21 days (range, 3-97 days) to 11 days (range, 2-23 days). CONCLUSION: Utilization of a quality measures dashboard decreased treatment gaps in patients with IBD receiving biologic therapy. Integrated specialty pharmacists are uniquely positioned to monitor adherence to laboratory monitoring parameters for patients on biologics.

Relationship between chest compression rates and outcomes from cardiac arrest.

BACKGROUND: Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions per minute. Animal and human studies have reported that blood flow is greatest with chest compression rates near 120/min, but few have reported rates used during out-of-hospital (OOH) cardiopulmonary resuscitation or the relationship between rate and outcome. The purpose of this study was to describe chest compression rates used by emergency medical services providers to resuscitate patients with OOH cardiac arrest and to determine the relationship between chest compression rate and outcome. METHODS AND RESULTS: Included were patients aged ≥ 20 years with OOH cardiac arrest treated by emergency medical services providers participating in the Resuscitation Outcomes Consortium. Data were abstracted from monitor-defibrillator recordings during cardiopulmonary resuscitation. Multiple logistic regression analysis assessed the association between chest compression rate and outcome. From December 2005 to May 2007, 3098 patients with OOH cardiac arrest were included in this study. Mean age was 67 ± 16 years, and 8.6% survived to hospital discharge. Mean compression rate was 112 ± 19/min. A curvilinear association between chest compression rate and return of spontaneous circulation was found in cubic spline models after multivariable adjustment (P=0.012). Return of spontaneous circulation rates peaked at a compression rate of ≈ 125/min and then declined. Chest compression rate was not significantly associated with survival to hospital discharge in multivariable categorical or cubic spline models. CONCLUSIONS: Chest compression rate was associated with return of spontaneous circulation but not with survival to hospital discharge in OOH cardiac arrest.

Gaussian Basis Set and Planewave Relativistic Spin-Orbit Methods in NWChem.

Relativistic spin-orbit density functional theory (DFT) methods have been implemented in the molecular Gaussian DFT and pseudopotential planewave DFT modules of the NWChem electronic-structure program. The Gaussian basis set implementation is based upon the zeroth-order regular approximation (ZORA) while the planewave implementation uses spin-orbit pseudopotentials that are directly generated from the atomic Dirac-Kohn-Sham wave functions or atomic ZORA-Kohn-Sham wave functions. Compared to solving the full Dirac equation these methods are computationally efficient but robust enough for a realistic description of relativistic effects such as spin-orbit splitting, molecular orbital hybridization, and core effects. Both methods have been applied to a variety of small molecules, including I2, IF, HI, Br2, Bi2, AuH, and Au2, using various exchange-correlation functionals. Our results are in good agreement with experiment and previously reported calculations.

Equatorial and apical solvent shells of the UO2 2+ ion.

First principles molecular dynamics simulations of the hydration shells surrounding UO(2)(2+) ions are reported for temperatures near 300 K. Most of the simulations were done with 64 solvating water molecules (22 ps). Simulations with 122 water molecules (9 ps) were also carried out. The hydration structure predicted from the simulations was found to agree with very well-known results from x-ray data. The average U=O bond length was found to be 1.77 A. The first hydration shell contained five trigonally coordinated water molecules that were equatorially oriented about the O-U-O axis with the hydrogen atoms oriented away from the uranium atom. The five waters in the first shell were located at an average distance of 2.44 A (2.46 A, 122 water simulation). The second hydration shell was composed of distinct equatorial and apical regions resulting in a peak in the U-O radial distribution function at 4.59 A. The equatorial second shell contained ten water molecules hydrogen bonded to the five first shell molecules. Above and below the UO(2)(2+) ion, the water molecules were found to be significantly less structured. In these apical regions, water molecules were found to sporadically hydrogen bond to the oxygen atoms of the UO(2)(2+), oriented in such a way as to have their protons pointed toward the cation. While the number of apical waters varied greatly, an average of five to six waters was found in this region. Many water transfers into and out of the equatorial and apical second solvation shells were observed to occur on a picosecond time scale via dissociative mechanisms. Beyond these shells, the bonding pattern substantially returned to the tetrahedral structure of bulk water.

A momentum-conserving Franck-Condon approximation: theory and application to the photodissociation of Li2+ in an intense laser field.

A new, computationally efficient approximation to calculating matrix elements between vibrational-electronic states that does not assume stationary nuclei is introduced. The approach emphasizes the importance of the conservation of nuclear momenta. The calculated quantities can be used wherever equivalent quantities from standard Franck-Condon treatments can be used. The new method is illustrated by a time-dependent perturbation theory description of the photodissociation of the Li(2) (+) molecular cation in an intense laser field (I=0.9x10(12) W/cm(2)), which was previously identified in a detailed study of the electronic structure [Khait et al., J. Chem. Phys. 122, 094111 (2005)] as likely to have unusual sensitivity to the initial vibrational state in dynamics. The current study confirms this speculation and shows this to be a specific instance of a situation in which nuclear dynamics during an electronic optical transition cannot be ignored.

Achieving a high-performance health care system with universal access: what the United States can learn from other countries.

This position paper concerns improving health care in the United States. Unlike previous highly focused policy papers by the American College of Physicians, this article takes a comprehensive approach to improving access, quality, and efficiency of care. The first part describes health care in the United States. The second compares it with health care in other countries. The concluding section proposes lessons that the United States can learn from these countries and recommendations for achieving a high-performance health care system in the United States. The articles are based on a position paper developed by the American College of Physicians' Health and Public Policy Committee. This policy paper (not included in this article) also provides a detailed analysis of health care systems in 12 other industrialized countries. Although we can learn much from other health systems, the College recognizes that our political and social culture, demographics, and form of government will shape any solution for the United States. This caution notwithstanding, we have identified several approaches that have worked well for countries like ours and could probably be adapted to the unique circumstances in the United States.