Use of a Wedge Scheme to Describe Intermolecular Proton-Coupled Electron Transfer through the H‑bond Complex Formed Between a Phenylenediamine-Based Urea and 1,8-Naphthyridine

Recently we introduced the “wedge scheme” as a convenient means to include H-bonded intermediates in an overall proton-coupled electron transfer (PCET) mechanism by showing that it can nicely explain the unusual solvent- and concentration-dependent voltammetry of a phenylenediamine-based urea, U­(H)­H. This compound undergoes an apparent 1 e^– reversible oxidation in CH₂Cl₂ that actually corresponds to 2 e^– oxidation of half of the ureas to the quinoidal cation accompanied by transfer of a H⁺ and deactivation of the other half of the ureas. The reversibility of the process is due to the second electron transfer and proton transfer proceeding through a H-bond complex between the oxidized urea and the dimethylamino group on another urea. In this study the effect of adding 1,8-naphthyridine, naph, which H-bonds to the U­(H)H in its reduced state, is examined using cyclic voltammetry. Addition of naph causes both an increase in the current of the reversible U­(H)H cyclic voltammetric wave as well as the appearance of a new oxidation peak at slightly more positive potentials that gradually merges with the main wave as the naph concentration increases. This behavior can be explained by a transition from a U­(H)­H–U­(H)­H wedge scheme to a U­(H)­H–naph wedge, with the new second oxidation peak being due to the oxidation of the UHH⁺–naph H-bond complex. This complex is harder to oxidize than the UHH⁺–UHH complex due to weaker H-bonding of naph to U­(H)­H²⁺. Overall this study demonstrates the utility of the wedge scheme in explaining complex PCET reactions in which multiple types of H-bonding intermediates are involved

Hospitalization Costs for Patients Undergoing Orthopedic Surgery Treated With Intravenous Acetaminophen (IV-APAP) Plus Other IV Analgesics or IV Opioid Monotherapy for Postoperative Pain

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-016-0449-8"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p

Comparative analysis of length of stay, hospitalization costs, opioid use, and discharge status among spine surgery patients with postoperative pain management including intravenous versus oral acetaminophen

<p><b>Background:</b> Recovery from spine surgery is oriented toward restoring functional health outcomes while reducing resource use. Optimal pain management is a key to reaching these objectives. We compared outcomes of spine surgery patients who received standard pain management including intravenous (IV) acetaminophen (APAP) vs. oral APAP.</p> <p><b>Methods:</b> We performed a retrospective analysis of the Premier database (January 2012 to September 2015) comparing spine surgery patients who received pain management with IV APAP to those who received oral APAP, with no exclusions based on additional pain management. We performed multivariable logistic regression for the discharge and all cause 30-day readmission to the same hospital outcomes and instrumental variable regressions using the quarterly rate of IV APAP use for all hospitalizations by hospital as the instrument in two-stage least squares regressions for length of stay (LOS), hospitalization costs, and average daily morphine equivalent dose (MED) outcomes. Models adjusted for age, gender, race, admission type, 3M All Patient Refined Diagnosis Related Group severity of illness and risk of mortality, hospital size, and indicators for whether the hospital was an academic center and whether it was urban or rural.</p> <p><b>Results:</b> We identified 112,586 spine surgery patients with 51,835 (46%) having received IV APAP. Subjects averaged 57 and 59 years of age respectively in the IV APAP and oral APAP cohorts and were predominantly non-Hispanic Caucasians and female. In our adjusted models, IV APAP was associated with 0.68 days shorter LOS (95% CI: −0.76 to −0.59, <i>p</i> < .0001), $1175 lower hospitalization costs (95$1611 to −$739, <i>p</i> < .0001), 13 mg lower average daily MED (95% CI: −14 mg to −12 mg, <i>p</i> < .0001), 34% lower risk of discharge to a skilled nursing facility (95% CI: 0.63 to 0.69, <i>p</i> < .0001), and 13% less risk of 30-day readmission (95% CI: 0.73 to 1.03).</p> <p><b>Conclusions:</b> Compared to oral APAP, managing post-spine-surgery pain with IV APAP is associated with less resource use, lower costs, lower doses of opioids, and improved discharge status.</p

Electrochemical Evidence for Intermolecular Proton-Coupled Electron Transfer through a Hydrogen Bond Complex in a <i>p</i>‑Phenylenediamine-Based Urea. Introduction of the “Wedge Scheme” as a Useful Means To Describe Reactions of This Type

The electrochemistry of several <i>p</i>-phenylenediamine derivatives, in which one of the amino groups is part of an urea functional group, has been investigated in methylene chloride and acetonitrile. The ureas are abbreviated U­(R)­R′, where R′ indicates the substituent on the N that is part of the phenylenediamine redox couple and R indicates the substituent on the other urea N. Cyclic voltammetry and UV–vis spectroelectrochemical studies indicate that U­(Me)H and U­(H)H undergo an apparent 1e^– oxidation that actually corresponds to 2e^– oxidation of half the ureas to a quinoidal-diimine cation, U­(R)⁺. This is accompanied by proton transfer to the other half of the ureas to make the electroinactive cation HU­(R)­H⁺. This explains the observed irreversibility of the oxidation of U­(Me)H in both solvents and U­(H)­H in acetonitrile. However, the oxidation of U­(H)H in methylene chloride is reversible at higher concentrations and slower scan rates. Several lines of evidence suggest that the most likely reason for this is the accessibility of a H-bond complex between U­(H)⁺ and HU­(H)­H⁺ in methylene chloride. Reduction of the H-bond complex occurs at a less negative potential than that of U­(H)⁺, leading to reversible behavior. This conclusion is strongly supported by the appearance of a more negative reduction peak at lower concentrations and faster scan rates, conditions in which the H-bond complex is less favored. The overall reaction mechanism is conveniently described by a “wedge scheme”, which is a more general version of the square scheme typically used to describe redox processes in which proton transfer accompanies electron transfer

Analysis of predictors of opioid-free analgesia for management of acute post-surgical pain in the United States

<p><b>Objectives:</b> Utilization of opioid-free analgesia (OFA) for post-surgical pain is a growing trend to counter the risks of opioid abuse and opioid-related adverse drug events (ORADEs). However, utilization patterns of OFA have not been examined. In this study, we investigated the utilization patterns and predictors of OFA in a surgical population in the United States.</p> <p><b>Methods:</b> Analysis of the Cerner Health Facts database (January 2011 to December 2015) was conducted to describe hospital and patient characteristics associated with OFA. Baseline characteristics, such as age, gender, race, discharge status, year of admission and chronic comorbidities at index admission were collected. Hospital characteristics and payer type at index admission were collected as reported in the electronic health record database. Descriptive statistics and logistic regression were used to identify statistically significant predictors of OFA on patient and institutional levels.</p> <p><b>Results:</b> The study identified 10,219 patients, from 187 hospitals, who received post-surgical OFA and 255,196 patients who received post-surgical opioids. OFA rates varied considerably by hospital. Patients more likely to receive OFA were older (OR = 1.06, 95% CI [1.03, 1.10]; <i>p</i> < .001), or had neurological disorders (OR = 1.24, 95% CI [1.10, 1.39]; <i>p</i> < .001), diabetes (OR = 1.20, 95% CI [1.08, 1.33]; <i>p</i> = .001) or psychosis (OR = 1.18, 95% CI [1.01, 1.37]; <i>p</i> = .030). Patients with obesity and depression were less likely to receive OFA (OR = 0.80, 95% CI [0.67, 0.95]; <i>p</i> = .010 OR = 0.85, 95% CI [0.73, 0.98]; <i>p</i> = .030, respectively).</p> <p><b>Conclusions:</b> Use of post-surgical OFA was limited overall and was not favored in some patient groups prone to ORADEs, indicating missed opportunities to reduce opioid use and ORADE incidence. A substantial proportion of OFA patients was contributed by a few hospitals with especially high rates of OFA, suggesting that hospital policies, institutional structure and cross-functional departmental commitment to reducing opioid use may play a large role in the implementation of OFA.</p