Role of MCD and Mössbauer Spectroscopy in the Explanation of the Properties of a Highly Soluble (µ-Oxo)bis[tetra(tert-butyl)(phthalocyaninato)iron(III)] Complex, Its Pyridine Adduct, and Redox Forms Oxidized under Anaerobic Conditions in Non-Coordinating Solvents.

Solid-state Mössbauer spectra of a highly soluble (µ-oxo)bis[tetra(tert-butyl)(phthalocyaninato)iron(III)] complex 1 ((PctBuFe)2O) consist of two doublets that represent bent geometry in µ-oxo(1) (1a, ΔEQ = 0.43 mm/s, T = 10 K) and linear geometry in µ-oxo(2) (1b, ΔEQ = 1.40 mm/s, T = 10 K) isomers with the ratio between two isomers depending on the purification method. Both isomers were found to be diamagnetic and transform entirely to the 1a isomer in solution. The room- and low-temperature magnetic circular dichroism (MCD) spectra of 1a µ-oxo(1) show one Faraday A- and one B-term between 670 and 720 nm, which correlate with the 690 nm band and 709 nm shoulder observed in the UV-vis spectrum of this compound. UV-vis and MCD spectra of 1a are almost independent of the temperature. Both 1a and 1b are diamagnetic between room temperature and 4 K. Electrochemical experiments show up to three oxidations and up to four reduction processes in 1a. Its oxidation under spectroelectrochemical or chemical (in the absence of oxygen-containing oxidants) conditions in non-coordinating solvents results in the formation of broad NIR bands around 1195 nm (first oxidation) and 1264 nm (second oxidation). The MCD spectra of the redox-active species show a Faraday B-term signal with negative amplitude in this region and are very different from those in the monomeric PctBu(1-)FeIIIX2 complexes 5X (X = Cl- or CF3CO2-). The pyridine adduct of 1a ((PyPctBuFe)2O; 2Py) is paramagnetic (µB = 2.19, g = 2.11, and J = -6.1 cm-1) and has a major peak at 627 nm of its UV-vis spectrum, which is associated with a MCD pseudo A-term. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations, along with the exciton coupling theory, were used to explain the unusually red-shifted intense transitions in 1a as well as the H-aggregate-like spectra of the pyridine adduct 2Py.

Novel Monitoring and Dose Adjustment of Argatroban, a Direct Thrombin Inhibitor, to Maintain Therapeutic Anticoagulation in a Patient With Antiphospholipid Antibody Syndrome, Heparin-Induced Thrombocytopenia, and COVID-19 Pneumonia.

In patients who require systemic anticoagulation, a reliable monitoring method is required to ensure anticoagulation is maintained within the correct therapeutic window and patients are treated appropriately. When titrating direct thrombin inhibitors (DTIs), dilute thrombin time (dTT) measurements have been demonstrated to be more reliable and accurate than activated partial thromboplastin time (aPTT) measurements and thus often the preferred DTI assessment. However, a clinical need arises when both dTT measurements are not readily available and aPTT measurements are unreliable. CASE SUMMARY: A 57-year-old woman with a history of antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and multiple prior deep venous thromboses and pulmonary emboli was admitted with COVID-19 pneumonia and intubated due to hypoxic respiratory failure. Argatroban was initiated in place of her home medication warfarin. However, the patient had a prolonged aPTT value at baseline and overnight dTT assay measurements were limited at our institution. A multidisciplinary team of hematology and pharmacy clinicians created a modified patient-specific aPTT target range and argatroban dosing was titrated accordingly. Subsequent aPTT values in the modified target range corresponded to therapeutic dTT values, indicating therapeutic anticoagulation was successfully achieved and maintained. Patient blood samples were additionally evaluated retrospectively using an investigational novel point-of-care test that detected and quantified the argatroban anticoagulant effect. CONCLUSIONS: Therapeutic anticoagulation with a DTI in a patient with unreliable aPTT measurements can be achieved with use of a modified patient-specific aPTT target range. Early validation of an investigational rapid testing alternative for DTI monitoring is promising.

Economic Evaluation of a Pharmacist-Led 5-Day Therapeutic Hold of IV Levothyroxine at an Academic Medical Center.

Objective: Providers often admit patients with active outpatient prescriptions for levothyroxine. During an inpatient admission, providers may instruct critically ill patients to take nothing by mouth, or nil per os (NPO). Thus, they may prescribe the intravenous (IV) formulation of levothyroxine during this period. However, levothyroxine possesses a prolonged half-life of up to 7 days; therefore, immediate transition to IV levothyroxine may not be clinically necessary in the acute NPO setting. Intravenous levothyroxine is significantly more expensive than equivalent oral doses and may prove to be a financial burden for an institution. By understanding the pharmacokinetic properties of levothyroxine, we implemented a cost-saving initiative involving a 5-day therapeutic hold of IV levothyroxine. Methods: This was a retrospective evaluation in 2 intensive care units (ICU): a 20-bed surgical/trauma ICU and an 18-bed mixed medical/surgical ICU. Patient data, utilization data, and documented pharmacist interventions were collected for 6 months prior to implementation of the 5-day IV levothyroxine therapeutic hold and for 6 months post-implementation. All patients prescribed IV levothyroxine during these timeframes were included. Results: During the 6-month pre-implementation phase, 674 doses (691 vials) of IV levothyroxine for 77 unique patients were dispensed from the 2 ICUs. During the 6-month post-implementation phase, 168 doses (188 vials) of IV levothyroxine were dispensed for 44 unique patients. Of the 44 patients (48 orders) who still received IV levothyroxine, 22.9% of orders were deemed clinically necessary by the pharmacist and were not recommended to be held under the protocol, 64.6% were due to the verifying pharmacist being unaware of the protocol, 8.3% of orders were due to protocol non-compliance, and 4.2% were verified after the 5-day hold was complete as the patient remained NPO. This pharmacy-led initiative resulted in a 75% decrease in usage post-implementation and an estimated annualized savings of $80,000. Conclusion: A pharmacy-led initiative comprised of a 5-day therapeutic hold of IV levothyroxine was feasible and led to a 75% reduction in usage and cost over a 6-month period in 2 ICU's. Future steps include additional staff education for improved protocol adherence and expanding the protocol institution-wide for an even greater cost-savings potential.

A low dose heparinized saline protocol is associated with improved duration of arterial line patency in critically ill COVID-19 patients.

PURPOSE: Critically ill patients with Coronavirus Disease 2019 (COVID-19) have high rates of line thrombosis. Our objective was to examine the safety and efficacy of a low dose heparinized saline (LDHS) arterial line (a-line) patency protocol in this population. MATERIALS AND METHODS: In this observational cohort study, patients ≥18 years with COVID-19 admitted to an ICU at one institution from March 20-May 25, 2020 were divided into two cohorts. Pre-LDHS patients had an episode of a-line thrombosis between March 20-April 19. Post-LDHS patients had an episode of a-line thrombosis between April 20-May 25 and received an LDHS solution (10 units/h) through their a-line pressure bag. RESULTS: Forty-one patients (pre-LDHS) and 30 patients (post-LDHS) were identified. Baseline characteristics were similar between groups, including age (61 versus 54 years; p = 0.24), median Sequential Organ Failure Assessment score (6 versus 7; p = 0.67) and systemic anticoagulation (47% versus 32%; p = 0.32). Median duration of a-line patency was significantly longer in post-LDHS versus pre-LDHS patients (8.5 versus 2.9 days; p < 0.001). The incidence of bleeding complications was similar between cohorts (13% vs. 10%; p = 0.71). CONCLUSIONS: A LDHS protocol was associated with a clinically significant improvement in a-line patency duration in COVID-19 patients, without increased bleeding risk.

Safety and Effectiveness of Intravenous Chlorpromazine for Agitation in Critically Ill Patients.

BACKGROUND: Agitation is common in the intensive care unit (ICU). Although antipsychotics are frequently used as first-line therapy, chlorpromazine has fallen out of favor due to risk of cardiovascular complications and severe hypotension. Although chlorpromazine is used anecdotally, there is a lack of data regarding its safety and effectiveness. The objective of this study was to investigate the use of intravenous (IV) chlorpromazine for agitation in the ICU setting. METHODS: A retrospective review was performed at a tertiary care academic medical center. Patients were included if they received IV chlorpromazine in the ICU for agitation, infused at a rate of 1 mg/min. Primary end points were change in systolic blood pressure (SBP), heart rate (HR), and mean arterial pressure (MAP) within 4 hours of administration. Secondary end points included change in vasopressor and adjunct sedative medication requirements, achievement of Richmond-Agitation Sedation Scale (RASS) 0 to -1, and incidence of cardiac arrhythmias. RESULTS: A total of 39 patients encompassing 107 IV chlorpromazine administrations were included. The median dose was 25 mg. Median vital signs prior to infusion were SBP 129 mm Hg, HR 90 beats/minute, and MAP 88 mm Hg. Over the subsequent 4 hours, SBP and HR did not change significantly (P = .83 and P = .10, respectively). Mean arterial pressure decreased from a median of 88 to 83 mm Hg (P = .04). There were no significant changes in vasopressor requirements, adjunct sedative medication requirements, or achievement of RASS goal. No patients developed symptomatic cardiac arrhythmias. CONCLUSION: In our small retrospective study, the use of IV chlorpromazine at routine doses did not result in clinically significant hemodynamic changes when infused at a rate of 1 mg/min. Intravenous chlorpromazine may be considered as a potential treatment option for agitation in ICU patients with appropriate monitoring.

Iron(II) coordination complexes with panchromatic absorption and nanosecond charge-transfer excited state lifetimes.

Replacing current benchmark rare-element photosensitizers with ones based on abundant and low-cost metals such as iron would help facilitate the large-scale implementation of solar energy conversion. To do so, the ability to extend the lifetimes of photogenerated excited states of iron complexes is critical. Here, we present a sensitizer design in which iron(II) centres are supported by frameworks containing benzannulated phenanthridine and quinoline heterocycles paired with amido donors. These complexes exhibit panchromatic absorption and nanosecond charge-transfer excited state lifetimes, enabled by the combination of vacant, energetically accessible heterocycle-based acceptor orbitals and occupied molecular orbitals destabilized by strong mixing between amido nitrogen atoms and iron. This finding shows how ligand design can extend metal-to-ligand charge-transfer-type excited state lifetimes of iron(II) complexes into the nanosecond regime and expand the range of potential applications for iron-based photosensitizers.

Prospective evaluation of a continuous infusion vancomycin dosing nomogram in critically ill patients undergoing continuous venovenous haemofiltration.

OBJECTIVES: The most optimal method of attaining therapeutic vancomycin concentrations during continuous venovenous haemofiltration (CVVH) remains unclear. Studies have shown continuous infusion vancomycin (CIV) achieves target concentrations more rapidly and consistently when compared with intermittent infusion. Positive correlations between CVVH intensity and vancomycin clearance (CLvanc) have been noted. This study is the first to evaluate a CIV regimen in patients undergoing CVVH that incorporates weight-based CVVH intensity (mL/kg/h) into the dosing nomogram. METHODS: This was a prospective, observational study of patients undergoing CVVH and receiving CIV based on the nomogram. The primary outcome was achievement of a therapeutic vancomycin concentration (15-25 mg/L) at 24 h. Secondary outcomes included the achievement of therapeutic concentrations at 48 and 72 h. RESULTS: The nomogram was analysed in 52 critically ill adults. Vancomycin concentrations were therapeutic in 43/52 patients (82.7%) at 24 h. Of the nine patients who were not therapeutic at 24 h, seven were supratherapeutic and two were subtherapeutic. The mean (SD) concentration was 20.1 (4.2) mg/L at 24 h, 20.7 (3.7) mg/L at 48 h and 21.9 (3.5) mg/L at 72 h. Patients with CVVH intensity >20 mL/kg/h experienced higher CLvanc at 24 h compared with patients with CVVH intensity <20 mL/kg/h (3.1 versus 2.6 L/h; P = 0.013). CONCLUSIONS: By incorporating CVVH intensity into the CIV dosing nomogram, the majority of patients achieved therapeutic concentrations at 24 h and maintained them within range at 48 and 72 h. Additional studies are required to validate this nomogram before widespread implementation may be considered.

Direct Synthesis of an Unprecedented Stable Radical of Nickel(II) 3,5-Bis(dimedonyl)azadiisoindomethene with Strong and Narrow Near-Infrared Absorption at λ ∼ 1000 nm.

An unprecedented stable neutral radical nickel(II) complex of 3,5-bis(dimedonyl)azadiisoindomethene (1) was prepared by the direct reaction between 1,3-diiminoisoindoline and dimedone. A new radical complex 1 has an intense and narrow absorption at 1008 nm and can be reduced to a less stable anionic [1]- with a typical aza(dibenzo)boron dipyrromethene (aza-BODIPY) UV-vis spectrum. Complex 1, along with two other colored condensation reaction products 2 and 3, was characterized by spectroscopy and X-ray crystallography, while the paramagnetic nature of 1 was probed by EPR and SQUID methods. Complex 1 forms dimers in the solid state with short (∼3.16 Å) Ni---Ni contacts. Redox data on 1 are indicative of a reversible reduction process in this complex; its magnetism suggests a S = 1/2 state with the spin density delocalized over the aza-BODIPY core. The experimental data 1 and [1]- were correlated with the density functional theory (DFT) and time-dependent DFT calculations.

Impact of a Multidisciplinary Bundle on Time to Antibiotic Administration in Septic SICU Patients.

PURPOSE: The goal of this study was to investigate barriers to timely antibiotic administration in septic surgical intensive care unit (SICU) patients and examine the impact of a multidisciplinary bundle on the time from prescription to antibiotic administration. METHODS: This was a pre- and postintervention study that consisted of 3 phases: (1) preintervention phase, retrospective evaluation of data, (2) intervention implementation, and (3) a postintervention phase. A nurse survey was conducted to identify barriers to rapid antibiotic administration during phase 1. Based on this survey, multidisciplinary interventions included adding antibiotics to the automatic dispensing cabinet, educating monthly staff, and providing an antibiotic dosing table to all prescribers, which is attached to the computer workstations. Our multidisciplinary team consisted of the ICU medical directors, nurse managers, nurses, a critical care fellow, and ICU pharmacists. RESULTS: The percentage of antibiotics that were received within 60 minutes was 26.3% in the pregroup versus 84.0% in the postgroup ( P < .001). The mean total prescriber to patient time was 110 minutes in the pregroup versus 58.4 minutes in the postgroup ( P < .001). CONCLUSION: We achieved a higher rate of timely antibiotic administration among septic SICU patients by implementing process changes based on barriers identified by the nurses.

Injuries in elite and recreational snowboarders.

BACKGROUND: The relatively young sport of snowboarding exhibits high injury rates. The current efforts to characterise the injury pattern of snowboarders focus largely on the general snowboard population and upper extremity injuries, the most common injury site in snowboarders as a whole. METHODS: In an effort to describe the current published information available on snowboarding injuries in the elite-level population, a literature search was performed and the articles related to snowboarding injuries were analysed. Additionally, the literature pertaining to biomechanical analyses of injury and injury prevention was included. RESULTS: Studies rarely stratify the snowboarders by skill level, a classification which has a profound effect on the riding activities of snowboarders and the resultant injury patterns. Elite-level snowboarders are often injured when performing difficult manoeuvres at high velocities and with amplified levels of force to the lower limbs. Consequently, elite-level snowboarders suffer from injuries that are of higher severity and have decidedly greater lower extremity injury rates. Conversely, injuries to the upper extremities are decreased in the elite snowboarders. Furthermore, little has been published regarding the biomechanical analyses and injury prevention for the protection of the lower extremities in snowboarding. CONCLUSIONS: Snowboarding continues to evolve as a sport. This includes a steady progression in the degree of difficulty of the manoeuvres conducted by athletes and an increase in the number of snowboarders attempting such manoeuvres. The injury patterns across the skill levels are markedly different, and it is imperative that the research directed towards understanding the disparate lower extremity injury pattern of elite-level snowboarders is increased.

Heterogeneity of tibial plateau cartilage in response to a physiological compressive strain rate.

Knowledge of the extent to which tibial plateau cartilage displays non-uniform mechanical topography under physiologically relevant loading conditions is critical to evaluating the role of biomechanics in knee osteoarthritis. Cartilage explants from 21 tibial plateau sites of eight non-osteoarthritic female cadaveric knees (age: 41-54; BMI: 14-20) were tested in unconfined compression at 100% strain/s. The elastic tangent modulus at 10% strain (E(10%) ) was calculated for each site and averaged over four geographic regions: not covered by meniscus (I); covered by meniscus-anterior (II); covered by meniscus-exterior (III); and covered by meniscus-posterior (IV). A repeated-measures mixed model analysis of variance was used to test for effects of plateau, region, and their interaction on E(10%) . Effect sizes were calculated for each region pair. E(10%) was significantly different (p<0.05) for all regional comparisons, except I-II and III-IV. The regional pattern of variation was consistent across individuals. Moderate to strong effect sizes were evident for regional comparisons other than I-II on the lateral side and III-IV on both sides. Healthy tibial cartilage exhibits significant mechanical heterogeneity that manifests in a common regional pattern across individuals. These findings provide a foundation for evaluating the biomechanical mechanisms of knee osteoarthritis.