Low-Temperature Kinetic Isotope Effects in CH3OH + H → CH2OH + H2 Shed Light on the Deuteration of Methanol in Space.

We calculated reaction rate constants including atom tunneling for the hydrogen abstraction reaction CH3OH + H → CH2OH + H2 with the instanton method. The potential energy was fitted by a neural network that was trained to UCCSD(T)-F12/VTZ-F12 data. Bimolecular gas-phase rate constants were calculated using microcanonic instanton theory. All H/D isotope patterns on the CH3 group and the incoming H atom are studied. Unimolecular reaction rate constants, representing the reaction on a surface, down to 30 K, are presented for all isotope patterns. At 30 K, they range from 4100 for the replacement of the abstracted H by D to ∼8 for the replacement of the abstracting H to ∼2 to 6 for secondary KIEs. The 12C/13C kinetic isotope effect is 1.08 at 30 K, while the 16O/18O kinetic isotope effect is extremely small. A simple kinetic surface model using these data predicts high abundances of the deuterated forms of methanol.

Undetectable Vancomycin Concentrations Utilizing a Particle Enhanced Turbidimetric Inhibition Immunoassay in a Patient with an Elevated IgM Level.

BACKGROUND: A case of undetectable vancomycin concentrations with the use of a particle enhanced turbidimetric inhibition immunoassay is reported. METHODS: A 73-year-old woman with B-cell lymphoma, chronic neutropenia with myelodysplastic syndrome and elevated IgM levels displayed repeated undetectable vancomycin concentrations, despite appropriate empiric vancomycin dosing. The vancomycin concentrations were processed utilizing a particle enhanced turbidimetric inhibition immunoassay (PETINIA). Patients with high concentrations of paraproteins in their serum may have interference with the PETINIA. This may include patients with plasma cell dyscrasias and lymphoreticular malignancies associated with abnormal immunoglobulin synthesis. RESULTS: Repeated undetectable vancomycin drug concentrations prompted us to send a serum sample to an outside facility to utilize another standardized assay, enzyme multiplied immunoassay (EMIT), which resulted in a detectable vancomycin serum concentration. The patient's undetectable vancomycin drug concentrations with the PETINIA may have been due to abnormal immunoglobulin synthesis interference with the assay. A limited number of case reports have been published demonstrating undetectable or unexpectedly elevated vancomycin concentrations due to monoclonal immunoglobulin interference in patients with immunological disorders. CONCLUSIONS: A 73-year-old woman with B-cell lymphoma, chronic neutropenia with myelodysplastic syndrome and elevated IgM levels may have had interference with a PETINIA resulting in undetectable vancomycin concentrations.

Averaging techniques for reaction barriers in QM/MM simulations.

Herein, we test and compare different techniques to obtain averaged reaction barriers from quantum mechanics/molecular mechanics (QM/MM) simulations based on snapshots taken from molecular dynamics. Reasonable values can be obtained from a fairly small sample of well-chosen snapshots if an exponential averaging, also called Boltzmann averaging, is used. Snapshots with geometries close to the expected transition state are to be picked preferentially. Exponential averaging, arithmetic averaging, and simply taking the minimum barrier are compared to free-energy calculations from umbrella sampling. Three reactions within a protein in a water environment are used as test cases.

Safety of Levalbuterol Compared to Albuterol in Patients With a Tachyarrhythmia.

Objective: To determine the safety of levalbuterol versus albuterol in patients with a tachyarrhythmia. Data Sources: A PubMed search was conducted using the MeSH search terms levalbuterol, albuterol, and tachyarrhythmia. Bibliographies of relevant articles were reviewed for additional citations. Study Selection and Data Extraction: Search results were limited to humans and randomized controlled trials. Those studies that excluded patients with predetermined tachyarrhythmias were excluded from this review. Trials that failed to compare levalbuterol and albuterol outcomes were excluded. Data Synthesis: Beta-2 receptor agonists are the mainstay of treatment in patients with respiratory disease, such as asthma or chronic obstructive pulmonary disease. Racemic albuterol has been linked to poor outcomes due to the fact that it contains both the S-isomer and the R-isomer. Levalbuterol, the "pure" R-isomer, has been thought to decrease cardiac side effects since it only contains the therapeutic component of the racemic mixture. Patients with tachyarrhythmias are at an increased probability to experience harmful, if not fatal, cardiac side effects from these drugs. Limitations of current studies include a lack of data in patient populations with baseline tachyarrhythmias. Conclusions: Tachyarrhythmias put a patient at increased risk of poor outcomes, including death. Evidence for using either racemic albuterol or levalbuterol for respiratory disease management in these patients is lacking and insufficient. Randomized controlled trials show that in intensive care unit patient populations there is no clear advantage to using levalbuterol over albuterol; however, this did not hold true in pediatric populations. No clinical trials exist that look at a direct comparison of these 2 agents in patients with underlying tachyarrhythmias. Further research into the most efficacious and safe ß-2 receptor agonists in this specialized patient population should be conducted to help reduce potential harmful outcomes.

Evaluation of the Efficacy and Safety of an eGlycemic Management System in a Community Hospital Setting.

BACKGROUND: Glucommander is an eGlycemic management system (eGMS) for intravenous (IV) and subcutaneous (SQ) insulin therapy in hospitalized patients. The purpose of this study was to evaluate the efficacy and safety of Glucommander compared to previously utilized nomograms in the community hospital setting. METHODS: This study was a retrospective, single-center cohort study comparing measures of efficacy and safety of IV and SQ insulin therapy via eGMS versus nomogram-driven IV insulin therapy followed by provider-ordered basal-bolus SQ insulin. The primary efficacy endpoint was percent of blood glucose (BG) readings per patient in target glycemic range. Safety objectives were percent of hyperglycemic events, hypoglycemic events, and severe hypoglycemic events after achieving target blood glucose range, and mean number of each event per patient. RESULTS: The percentage of BG readings in range was significantly higher for eGMS patients (n = 110) than comparison cohort patients (n = 108, 84.6% vs 76.8%, P < .001). Hyperglycemic events occurred for significantly fewer patients in the eGMS cohort relative to the comparison cohort (81.8% vs 92.6%, P = .03). Overall, there was no significant difference between cohorts in rate of hypoglycemic events, but hypoglycemic events while on IV insulin occurred in a significantly higher percentage of eGMS cohort patients than comparison cohort patients (30.9% vs 15.7%, P < .01). There were no significant differences in incidence of severe hypoglycemic events. CONCLUSIONS: Our study found that Glucommander maintained a higher percentage of BG readings in target BG range per patient compared to previously utilized nomograms. This result was driven by an improvement in hyperglycemia, but not hypoglycemia.

Evaluation of a vancomycin dosing nomogram in obese patients weighing at least 100 kilograms.

BACKGROUND: There remains variability in both practice and evidence related to optimal initial empiric dosing strategies for vancomycin. OBJECTIVE: Our primary objective was to describe the percentage of obese patients receiving vancomycin doses consistent with nomogram recommendations achieving targeted initial steady-state serum vancomycin concentrations. Secondary objectives were to describe the primary endpoint in subgroups based on patient weight and estimated creatinine clearance, to describe the rate of supratherapeutic vancomycin accumulation following an initial therapeutic trough concentration, and to describe the rate of vancomycin-related adverse events. METHODS: This single-center, IRB-approved, retrospective cohort included adult patients ≥ 100 kilograms total body weight with a body mass index (BMI) >30 kilograms/m2 who received a stable nomogram-based vancomycin regimen and had at least one steady-state vancomycin trough concentration. Data collected included vancomycin regimens and concentrations, vancomycin indication, serum creatinine, and vancomycin-related adverse events. Patients were divided into two cohorts by goal trough concentration: 10-15 mcg/mL and 15-20 mcg/mL. RESULTS: Of 325 patients screened, 85 were included. Goal steady-state concentrations were reached in 42/85 (49.4%) of total patients. CONCLUSIONS: Achievement of initial steady-state vancomycin serum concentrations in the present study (approximately 50%) was consistent with the use of published vancomycin dosing nomograms.

Assessing the Impact of an Order Panel Utilizing Weight-Based Insulin and Standardized Monitoring of Blood Glucose for Patients With Hyperkalemia.

Intravenous insulin with glucose is used in urgent treatment for hyperkalemia but has a significant risk of hypoglycemia. The authors developed an order panel within the electronic health record system that utilizes weight-based insulin dosing and standardized blood glucose monitoring to reduce hypoglycemia. As initial evaluation of this protocol, the authors retrospectively compared potassium and blood glucose lowering in patients treated with the weight-based (0.1 units/kg) insulin order panel (n = 195) with those given insulin based on provider judgment (n = 69). Serum potassium lowering did not differ between groups and there was no relationship between dose of insulin and amount of potassium lowering. There was a difference in hypoglycemia rates between groups ( P = .049), with fewer severe hypoglycemic events in the panel (2.56%) than in the non-panel group (10.14%). These data suggest weight-based insulin dosing is equally effective for lowering serum potassium and may lower risk of severe hypoglycemia.

Embracing a Nurse-Driven Alcohol Withdrawal Protocol Through Quality Improvement.

BACKGROUND: Alcohol withdrawal can lead to severe complications including seizures, delirium tremens, and death if not treated appropriately. Nurses are critical to the safety and outcomes of these patients. OBJECTIVE: The objective of this retrospective study was to determine if nursing education on a community hospital's alcohol withdrawal protocol led to improved nursing compliance. METHODS: This is a quality improvement project involving a two-part retrospective review-an initial needs assessment followed by nursing education and a subsequent posteducation retrospective review. The initial needs assessment included 65 patients. The subsequent posteducation group included 50 patients. RESULTS: Nursing compliance of 1-hour assessments increased after the educational intervention; however, there was no statistically significant difference in 6-hour assessment or medication administration protocol compliance between preeducation and posteducation groups. CONCLUSION: Nursing education is a good place to start in improving compliance with an alcohol withdrawal protocol, but physicians need to be included to increase standardization within the institution. Future study should look at the effectiveness of different assessment frequency intervals and its impact on patient-centered outcomes.

Evaluation of a vancomycin dosing nomogram in obese patients weighing at least 100 kilograms

Background: There remains variability in both practice and evidence related to optimal initial empiric dosing strategies for vancomycin. Objective: Our primary objective was to describe the percentage of obese patients receiving vancomycin doses consistent with nomogram recommendations achieving targeted initial steady-state serum vancomycin concentrations. Secondary objectives were to describe the primary endpoint in subgroups based on patient weight and estimated creatinine clearance, to describe the rate of supratherapeutic vancomycin accumulation following an initial therapeutic trough concentration, and to describe the rate of vancomycin-related adverse events. Methods: This single-center, IRB-approved, retrospective cohort included adult patients ≥ 100 kilograms total body weight with a body mass index (BMI) >30 kilograms/m2 who received a stable nomogram-based vancomycin regimen and had at least one steady-state vancomycin trough concentration. Data collected included vancomycin regimens and concentrations, vancomycin indication, serum creatinine, and vancomycin-related adverse events. Patients were divided into two cohorts by goal trough concentration: 10-15 mcg/mL and 15-20 mcg/mL. Results: Of 325 patients screened, 85 were included. Goal steady-state concentrations were reached in 42/85 (49.4%) of total patients. Conclusions: Achievement of initial steady-state vancomycin serum concentrations in the present study (approximately 50%) was consistent with the use of published vancomycin dosing nomograms

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