Benefits of dapagliflozin in chronic kidney disease for US commercial payers: A cost-offset analysis.

Background: One in 7 adults have chronic kidney disease (CKD), which is associated with high morbidity and mortality and substantial health care costs, especially in more advanced disease. Our data from a US commercial payer show rising per-member-per-year costs for renal and cardiac complications associated with CKD.

Objective: To predict the clinical and economic impact of treatment with or without dapagliflozin from the perspective of a US commercial payer using a cost-offset model (COM).

Decreasing formalin concentration improves quality of DNA extracted from formalin-fixed paraffin-embedded tissue specimens without compromising tissue morphology or immunohistochemical staining.

Genomic technologies are increasingly used clinically for both diagnosis and guiding cancer therapy. However, formalin fixation can compromise DNA quality. This study aimed to optimise tissue fixation using normal colon, liver and uterus (n=8 each) by varying neutral buffered formalin (NBF) concentration (1%-5% w/v) and fixation time (24-48 hours).

Carbon dioxide-catalyzed peroxynitrite reactivity - The resilience of the radical mechanism after two decades of research.

Peroxynitrite, ONOO, formed in tissues that are simultaneously generating NO and O, is widely regarded as a major contributor to oxidative stress. Many of the reactions involved are catalyzed by CO via formation of an unstable adduct, ONOOC(O)O, that undergoes O-O bond homolysis to produce NO and CO radicals, whose yields are equal at about 0.33 with respect to the ONOO reactant.

Oxidative Release of Copper from Pharmacologic Copper Bis(thiosemicarbazonato) Compounds.

Intracellular delivery of therapeutic or analytic copper from copper bis-thiosemicabazonato complexes is generally described in terms of mechanisms involving one-electron reduction to the Cu(I) analogue by endogenous reductants, thereby rendering the metal ion labile and less strongly coordinating to the bis-thiosemicarbazone (btsc) ligand. However, electrochemical and spectroscopic studies described herein indicate that one-electron oxidation of Cu(btsc) and ZnATSM (btsc = diacetyl-bis(4-methylthiosemicarbazonato)) complexes occurs within the range of physiological oxidants, leading to the likelihood that unrecognized oxidative pathways for copper release also exist. Oxidations of Cu(btsc) by HO catalyzed by either myeloperoxidase or horseradish peroxidase, by HOCl and taurine chloramine (which are chlorinating agents generated primarily in activated neutrophils from MPO-catalyzed reactions), and by peroxynitrite species (ONOOH, ONOOCO) that can form under certain conditions of oxidative stress are demonstrated.

Outcomes of Geriatric Trauma Patients on Preinjury Anticoagulation: A Multicenter Study.

Outpatient anticoagulation in the geriatric trauma patient is a challenging clinical problem. The aim of this study is to determine clinical outcomes associated with class of preinjury anticoagulants (PA) used by this population. This is a multicenter retrospective cohort study among four Level II trauma centers.

Benchmarking statewide trauma mortality using Agency for Healthcare Research and Quality's patient safety indicators.

Background: Improving clinical outcomes of trauma patients is a challenging problem at a statewide level, particularly if data from the state's registry are not publicly available. Promotion of optimal care throughout the state is not possible unless clinical benchmarks are available for comparison. Using publicly available administrative data from the State Department of Health and the Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs), we sought to create a statewide method for benchmarking trauma mortality and at the same time also identifying a pattern of unique complications that have an independent influence on mortality.

Mechanistic Insight into Peroxydisulfate Reactivity: Oxidation of the cis,cis-[Ru(bpy)2(OH2)]2O(4+) "Blue Dimer".

One-electron oxidation of the μ-oxo dimer (cis,cis-[Ru(III)(bpy)2(OH2)]2O(4+), {3,3}) to {3,4} by S2O8(2-) can be described by three concurrent reaction pathways corresponding to the three protic forms of {3,3}. Free energy correlations of the rate constants, transient species dynamics determined by pulse radiolysis, and medium and temperature dependencies of the alkaline pathway all suggest that the rate-determining step in these reactions is a strongly nonadiabatic dissociative electron transfer within a precursor ion pair leading to the {3,4}|SO4(2-)|SO4(•-) ion triple. As deduced from the SO4(•-) scavenging experiments with 2-propanol, the SO4(•-) radical then either oxidizes {3,4} to {4,4} within the ion triple, effecting a net two-electron oxidation of {3,3}, or escapes in solution with ∼25% probability to react with additional {3,3} and {3,4}, that is, effecting sequential one-electron oxidations.

Imidazole catalyzes chlorination by unreactive primary chloramines.

Hypochlorous acid and simple chloramines (RNHCl) are stable biologically derived chlorinating agents. In general, the chlorination potential of HOCl is much greater than that of RNHCl, allowing it to oxidize or chlorinate a much wider variety of reaction partners. However, in this study we demonstrate by kinetic analysis that the reactivity of RNHCl can be dramatically promoted by imidazole and histidyl model compounds via intermediary formation of the corresponding imidazole chloramines.

Geriatric outcomes for trauma patients in the state of Florida after the advent of a large trauma network.

Background: Florida State has one of the largest geriatric populations in the United States. However, recent data show that up to the year 2010, geriatric trauma patients were least served by designated trauma centers (TCs). One existing TC and five provisional Level 2 TCs were combined to create a large-scale trauma network (TN).

Electron paramagnetic resonance analysis of a transient species formed during water oxidation catalyzed by the complex ion [(bpy)2Ru(OH2)]2O(4+).

The ruthenium "blue dimer" [(bpy)2Ru(OH2)]2O(4+)--the first well-defined molecular complex able to catalyze water oxidation at low overpotentials--has been the subject of numerous experimental and computational studies. However, elements of the reaction mechanism remain controversial. Of particular interest is the nature of the O-O bond-forming step.

Anomalous reactivity of ceric nitrate in ruthenium "blue dimer"-catalyzed water oxidation.

At high concentrations, nitrate ion alters the dynamics of ruthenium "blue dimer"-catalyzed water oxidation by Ce(IV) such that the oxidation rate is enhanced and a unique reaction intermediate accumulates. This intermediate is characterized by distinct EPR, optical, and resonance Raman (RR) spectra, with the appearance in the latter of a new oxygen isotope-sensitive band. Both Ce(IV) and nitrate are required to generate this intermediate, which suggests ceric-nitrate complexes as the causative agents.

Cyclic transmembrane charge transport mediated by low-potential pyrylium ions.

We have investigated the capacity of a series of N-dialkylaminophenyl-substituted pyrylium and thiopyrylium ions to act as photosensitizers and redox mediators between reactants separated by bilayer membranes. These studies were prompted by earlier results indicating that simple trimethy- and triphenyl-substituted analogues could promote efficient photosensitized transmembrane redox between vectorially organized reactants by an electroneutral e(-)/OH(-) antiport mechanism. Unlike the dyes used in the earlier studies, the ions investigated herein absorb strongly throughout the visible absorption region and are therefore potentially useful in solar photoconversion processes.

Prospective evaluation of daily performance metrics to reduce emergency department length of stay for surgical consults.

Background: As part of a quality improvement initiative to reduce Emergency Department (ED) length of stay (LOS) for surgical consult patients, we e-mailed performance metrics to key stakeholders on a daily basis. ED and Surgery leadership used these daily metrics to identify and remedy contributing factors for increased ED LOS in patients who received surgical consults.

Objective: To evaluate whether a quality improvement process driven by a daily performance metric e-mail would be associated with a change in ED LOS for surgical consult patients.

What really happens in the neutrophil phagosome?

Current viewpoints concerning the bactericidal mechanisms of neutrophils are reviewed from a perspective that emphasizes challenges presented by the inability to duplicate ex vivo the intracellular milieu. Among the challenges considered are the influences of confinement upon substrate availability and reaction dynamics, direct and indirect synergistic interactions between individual toxins, and bacterial responses to stressors. Approaches to gauging relative contributions of various oxidative and nonoxidative toxins within neutrophils using bacteria and bacterial mimics as intrinsic probes are also discussed.

The determination of occupational exposure to polycyclic aromatic hydrocarbons by the analysis of 1-hydroxypyrene in urine using a simple automated online column switching device and high-performance liquid chromatography.

An analytical method using a liquid chromatograph combined with a simple online column switching sample pre-treatment system was developed for the determination of 1-hydroxypyrene (1-HP) in urine. This compound is the metabolite of pyrene and is used to assess the exposure of workers to polycyclic aromatic hydrocarbons (PAHs). After enzymatic hydrolysis, a urine sample was directly injected into a high-performance liquid chromatograph (HPLC) where it automatically underwent a sample cleanup using a column switching device.

Determination of quartz in bulk materials from workplace environments using X-ray diffractometry and the absorption diffraction method.

A method is described for the determination of crystalline quartz in bulk materials from workplace environments as part of occupational hygiene investigations using X-ray powder diffractometry. The absorption-diffraction model was used for quantification with mass absorption coefficients for samples being experimentally determined using an absorption cell placed in front of the diffracted beam anti-scatter slit. The method was found to be reliable for samples containing from 0.

Perspectives on intraoperative teaching: divergence and convergence between learner and teacher.

Objective: While current emphases on operative teaching focus on "virtual" education, residents and faculty engage most intimately in the operating room. The utilization of intraoperative teaching techniques, drawn from adult education principles, is understudied.

Design: A survey with both quantitative and qualitative elements was administered to surgical residents and their faculty.

"Covalent hydration" reactions in model monomeric Ru 2,2'-bipyridine complexes: thermodynamic favorability as a function of metal oxidation and overall spin states.

Density functional theory (DFT) has been used to investigate the plausibility of water addition to the simple mononuclear ruthenium complexes, [(NH(3))(3)(bpy)Ru═O](2+/3+) and [(NH(3))(3)(bpy)RuOH](3+), in which the OH fragment adds to the 2,2'-bipyridine (bpy) ligand. Activation of bpy toward water addition has frequently been postulated within the literature, although there exists little definitive experimental evidence for this type of "covalent hydration". In this study, we examine the energetic dependence of the reaction upon metal oxidation state, overall spin state of the complex, as well as selectivity for various positions on the bipyridine ring.

Mathematical modeling to define optimum operating room staffing for pediatric patients in trauma centers.

Background: Adult trauma centers (TCs) in the United States may be verified with an on-call operating room team if the performance improvement program shows no adverse outcome. Using queuing and simulation methodology, this study attempts to add a volume guideline for injured children.

Methods: Data from 63 verified TCs identified demographic factors including specific information regarding the first pediatric trauma-related operation done between 11 pm and 7 am each month for 1 year.

Management of the most severely injured spleen: a multicenter study of the Research Consortium of New England Centers for Trauma (ReCONECT).

Objective: To determine the rate and predictors of failure of nonoperative management (NOM) in grade IV and V blunt splenic injuries (BSI).

Design: Retrospective case series.

Setting: Fourteen trauma centers in New England.

Comparative study of HOCl-inflicted damage to bacterial DNA ex vivo and within cells.

The prospects for using bacterial DNA as an intrinsic probe for HOCl and secondary oxidants/chlorinating agents associated with it has been evaluated using both in vitro and in vivo studies. Single-strand and double-strand breaks occurred in bare plasmid DNA that had been exposed to high levels of HOCl, although these reactions were very inefficient compared to polynucleotide chain cleavage caused by the OH.-generating reagent, peroxynitrite.

Pathways of water oxidation catalyzed by ruthenium "blue dimers" characterized by 18O-isotopic labeling.

Earlier (18)O-H(2)O labeling studies had indicated that two concurrent pathways may exist for water oxidation catalyzed by [Ru(bpy)(2)(OH(2))](2)O(4+), a mu-oxo bridged diruthenium complex known colloquially as the "blue dimer". Specifically, the distribution of O(2) isotopomers obtained following its generation by the catalytically active form, [Ru(bpy)(2)(O)](2)(4+), suggested pathways in which either (1) one O atom was obtained from the terminally coordinated oxo atom and the second from the solvent or (2) both O atoms were obtained from the solvent. Plausible mechanisms have been advanced for the former pathway, but the second is enigmatic.

Blunt pancreatoduodenal injury: a multicenter study of the Research Consortium of New England Centers for Trauma (ReCONECT).

Objectives: To evaluate the safety of nonoperative management (NOM), to examine the diagnostic sensitivity of computed tomography (CT), and to identify missed diagnoses and related outcomes in patients with blunt pancreatoduodenal injury (BPDI).

Design: Retrospective multicenter study.

Setting: Eleven New England trauma centers (7 academic and 4 nonacademic).