Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus

Candis M Morello1,21Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 2School of Pharmacy, University of California San Francisco, Veterans Affairs San Diego Healthcare System, San Diego, CA, USAIntroduction: The goal of insulin therapy in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) is to match as closely as possible normal physiologic insulin secretion to control fasting and postprandial plasma glucose. Modifications of the insulin molecule have resulted in two long-acting insulin analogs (glargine and detemir) and three rapid-acting insulins (aspart, lispro, and glulisine) with improved pharmacokinetic/pharmacodynamic (PK/PD) profiles. These agents can be used together in basal-bolus therapy to more closely mimic physiologic insulin secretion patterns.Methods: This study reviews effects of the multiple demographic and clinical parameters in the insulin analogs glargine, detemir, lispro, aspart, and glulisine in patients with T2DM. A search was conducted on PubMed for each major topic considered (effects of injection site, age, race/ethnicity, obesity, renal or hepatic dysfunction, pregnancy, exercise, drug interactions) using the topic words and name of each type of insulin analog. Information was also obtained from the prescribing information for each insulin analog.Results: The PK/PD profiles for insulin analogs may be influenced by many variables including age, weight, and hepatic and renal function. However, these variables do not have equivalent effects on all long-acting or rapid-acting insulin analogs.Conclusion: Rapid-acting and long-acting insulin analogs represent major advances in treatment for patients with T2DM who require insulin therapy. However, there are potentially important PK and PD differences between the two long-acting agents and among the three rapid-acting insulin analogs, which should be considered when designing treatment regimens for special patient groups.Keywords: insulin analogs, type 2 diabetes mellitus, pharmacodynamics, pharmacokinetic

Implementing a COVID 19 Policy for Telehealth

The proposed DNP Project explored the implementation of a COVID-19 telehealth policy to clarify evidence-based practice, promote use of safe medications, and reduce hospitalizations. Providers were recruited from a telehealth organization, educated on current guidelines, and given a pocket card for reference and re-enforcement of training. Data was collected to examine guideline utilization, confidence in treating COVID-19, and efficacy of pocket card. COVID-19 patients also received follow up calls to determine if hospitalization was required post treatment. Chart audits were then completed to review compliance with guidelines. The results indicated both objective and clinical improvement in provider confidence treating COVID-19. Implications for future practice include the ability to use the framework of the project to build other policies based on evidence-based practice. Ultimately, the project can further improve telehealth by disseminating the policy through journals, online training and social media

Rescattering effects in B_{u,d,s}(bar) to D P, D(bar) P decays

We study quasi-elastic rescattering effects in B_{u,d,s}(bar) to DP, D(bar)P decays, where P is a light pseudoscalar. The updated measurements of B_{u,d}(bar) to DP decays are used to extract the effective Wilson coefficients a^{eff}_1 ~ 0.90, a^{eff}_2 ~ 0.23, three strong phases delta ~ 53 degree, theta ~ 18 degree, sigma ~ -88 degree, and the mixing angle tau ~ 9 degree. This information is used to predict rates of nineteen B_{s}(bar) to DP and B_{u,d,s}(bar) to D(bar)P decay modes, including modes of interests in the gamma/phi_3 program. Many decay rates are found to be enhanced. In particular, the B_s(bar) to D0 K0 rate is predicted to be 8\times 10^{-4}, which could be measured soon. The rescattering effects on the corresponding B_{u,d,s}(bar) to D(bar)P, DP amplitude ratios r_B, r_{B_s}, and the relative strong phases delta_B, delta_{B_s} are studied. Although the decay rates are enhanced in most cases, r_{B,B_s} values are similar to factorization expectation.Comment: 16 page

Charmless b-hadrons decays at CDF

We present CDF results on the branching fractions and time-integrated direct CP asymmetries for Bd, Bs and Lb decay modes into pairs of charmless charged hadrons (pions, kaons and protons). The data-set for these measurements amounts to 1fb^{-1} of pbar-p collisions at a center of mass energy 1.96TeV. We report on the first observation of the Bs->Kpi, Lb-ppi and Lb->pK decay modes and on the measurement of their branching fractions and direct CP asymmetries.Comment: 4 pages, 1 figure, 2 tables, proceedings of ICHEP200

Review of operational aspects of initial experiments utilizing the U.S. MLS

An exercise to support the Federal Aviation Administration in demonstrating the U.S. candidate for an international microwave landing system (MLS) was conducted by NASA. During this demonstration the MLS was utilized to provide the TCV Boeing 737 research airplane with guidance for automatic control during transition from conventional RNAV to MLS RNAV in curved, descending flight; flare; touchdown; and roll-out. Flight profiles, system configuration, displays, and operating procedures used in the demonstration are described, and preliminary results of flight data analysis are discussed. Recent experiences with manually controlled flight in the NAFEC MLS environment are also discussed. The demonstration shows that in automatic three-dimensional flight, the volumetric signal coverage of the MLS can be exploited to enable a commercial carrier class airplane to perform complex curved, descending paths with precision turns into short final approaches terminating in landing and roll-out, even when subjected to strong and gusty tail and cross wind components and severe wind shear

3D-melting features of the irreversibility line in overdoped Bi2_2Sr2_2CuO6_6 at ultra-low temperature and high magnetic field

We have measured the irreversible magnetization of an overdoped Bi$_2$Sr$_2$CuO$_6$ single crystal up to B=28 T and down to T=60 mK, and extracted the irreversibility line $B_{\rm irr}(T)$: the data can be interpreted in the whole temperature range as a 3D-anisotropic vortex lattice melting line with Lindemann number $c_{\rm L}=0.13$. We also briefly discuss the applicability of alternative models such as 2D- and quantum melting, and the connection with magnetoresistance experiments.Comment: M2S-HTSC-VI Conference paper (2 pages, 1 figure), using Elsevier style espcrc2.st

A new approach to analysing HST spatial scans: the transmission spectrum of HD 209458 b

The Wide Field Camera 3 (WFC3) on Hubble Space Telescope (HST) is currently one of the most widely used instruments for observing exoplanetary atmospheres, especially with the use of the spatial scanning technique. An increasing number of exoplanets have been studied using this technique as it enables the observation of bright targets without saturating the sensitive detectors. In this work we present a new pipeline for analyzing the data obtained with the spatial scanning technique, starting from the raw data provided by the instrument. In addition to commonly used correction techniques, we take into account the geometric distortions of the instrument, whose impact may become important when combined to the scanning process. Our approach can improve the photometric precision for existing data and also push further the limits of the spatial scanning technique, as it allows the analysis of even longer spatial scans. As an application of our method and pipeline, we present the results from a reanalysis of the spatially scanned transit spectrum of HD 209458 b. We calculate the transit depth per wavelength channel with an average relative uncertainty of 40 ppm. We interpret the final spectrum with T-Rex, our fully Bayesian spectral retrieval code, which confirms the presence of water vapor and clouds in the atmosphere of HD 209458 b. The narrow wavelength range limits our ability to disentangle the degeneracies between the fitted atmospheric parameters. Additional data over a broader spectral range are needed to address this issue.Comment: 13 pages, 15 figures, 7 tables, Accepted for publication in Ap