Publications

A family of 17 iron(III) aminobis(phenolate) complexes possessing different phenolate substituents, coordination geometries, and donor arrangements were used as catalysts for the reaction of carbon dioxide (CO2) with epoxides. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of the iron complexes with a bis(triphenylphosphine)iminium chloride cocatalyst in negative mode revealed the formation of six-coordinate iron "ate" species. Under low catalyst loadings (0.025 mol % Fe and 0.1 mol % chloride cocatalyst), all complexes showed good-to-excellent activity for converting propylene oxide to propylene carbonate under 20 bar of CO2. The most active complex possessed electron-withdrawing dichlorophenolate groups and for a 2 h reaction time gave a turnover frequency of 1240 h-1. Epichlorohydrin, styrene oxide, phenyl glycidyl ether, and allyl glycidyl ether could also be transformed to their respective cyclic carbonates with good-to-excellent conversions. Selectivity for polycarbonate formation was observed using cyclohexene oxide, where the best activity was displayed by trigonal-bipyramidal iron(III) complexes having electron-rich phenolate groups and sterically unencumbering tertiary amino donors. Those containing bulky tertiary amino ligands or those with square-pyramidal geometries around iron showed no activity for polycarbonate formation. While the overall conversions declined with decreasing CO2 pressure, CO2 incorporation remained high, giving a completely alternating copolymer. The difference in the optimum catalyst reactivity for cyclic carbonate versus polycarbonate formation is particularly noteworthy; that is, electron-withdrawing-group-containing phenolates give the most active catalysts for propylene carbonate formation, whereas catalysts with electron-donating-group-containing phenolates are the most active for polycyclohexene carbonate formation. This study demonstrates that the highly modifiable aminophenolate ligands can be tailored to yield iron complexes for both CO2/epoxide coupling and ring-opening copolymerization activity.

IMPORTANCE: Transient elevations of blood pressure (BP) are common in hospitalized older adults and frequently lead practitioners to prescribe more intensive antihypertensive regimens at hospital discharge than the patients were using before hospitalization.

OBJECTIVE: To investigate the association between intensification of antihypertensive regimens at hospital discharge and clinical outcomes after discharge.

DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, patients 65 years and older with hypertension who were hospitalized in Veterans Health Administration national health system facilities from January 1, 2011, to December 31, 2013, for common noncardiac conditions were studied. Data analysis was performed from October 1, 2018, to March 10, 2019.

EXPOSURES: Discharge with antihypertensive intensification, defined as receiving a prescription at hospital discharge for a new or higher-dose antihypertensive than was being used before hospitalization. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not receive antihypertensive intensifications at hospital discharge.

MAIN OUTCOMES AND MEASURES: The primary outcomes of hospital readmission, serious adverse events, and cardiovascular events were assessed by competing risk analysis. The secondary outcome was the change in systolic BP within 1 year of hospital discharge.

RESULTS: The propensity-matched cohort included 4056 hospitalized older adults with hypertension (mean [SD] age, 77 [8] years; 3961 men [97.7%]), equally split between those who did vs did not receive antihypertensive intensifications at hospital discharge. Groups were well matched on all baseline covariates (all standardized mean differences <0.1). Within 30 days, patients receiving intensifications had a higher risk of readmission (hazard ratio [HR], 1.23; 95% CI, 1.07-1.42; number needed to harm [NNH], 27; 95% CI, 16-76) and serious adverse events (HR, 1.41; 95% CI, 1.06-1.88; NNH, 63; 95% CI, 34-370). At 1 year, no differences were found in cardiovascular events (HR, 1.18; 95% CI, 0.99-1.40) or change in systolic BP among those who did vs did not receive intensifications (mean BP, 134.7 vs 134.4; difference-in-differences estimate, 0.6 mm Hg; 95% CI, -2.4 to 3.7 mm Hg).

CONCLUSIONS AND RELEVANCE: Among older adults hospitalized for noncardiac conditions, prescription of intensified antihypertensives at discharge was not associated with reduced cardiac events or improved BP control within 1 year but was associated with an increased risk of readmission and serious adverse events within 30 days.

The objective of the study was to (1) characterize and compare the chemical composition at the surface, subsurface and in the bulk of thin plastic films used for portosystemic shunt attenuation in their native state and after plasma exposure. (2) Assess the presence, concentration and location of irritant compounds (e.g dicetyl phosphate) within the films. Attenuated Total Reflectance Infrared Spectroscopy (ATR-IR), X-ray Photoelectron Spectroscopy (XPS) and dynamic Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) were used to analyze thirteen thin plastic films. Sample thickness was visualized and measured using Scanning Electron Microscopy (SEM). Sample thicknesses were compared using a one-way ANOVA. XPS reported low phosphorous concentrations (surrogate marker of dicetyl phosphate) between 0.01 and 0.19% wt at the sample surfaces (top 10 nm). There were significant differences between film thicknesses (P < .001) observed by SEM. The ATR-IR and ToF-SIMS identified four distinct surface and bulk chemical profiles: 1) Cellophane, 2) Polypropylene, 3) Modified Cellophane, and 4) Unique. Following plasma immersion for 6 weeks, samples showed little change in film thickness or chemical composition. This study confirmed that films used to attenuate portosystemic shunts were commonly not pure cellophane, with significant variations in surface and bulk chemistry. Suspected irritant compounds were not readily identifiable in significant proportions. Pronounced variability existed in both the thickness and chemical composition of these films (surface vs. bulk). The present findings lead to a legitimate question about the reproducibility of shunt occlusion when using thin plastic films from different origins.

BACKGROUND: Patients with spinal cord injury (SCI) have a high risk for multidrug-resistant organisms, including carbapenem-resistant Enterobacteriaceae (CRE). Accurate and easily applied definitions are critical to identify CRE. This study describes CRE and associated characteristics in veterans with SCI per Centers for Disease Control and Prevention (CDC) and Department of Veterans Affairs (VA) definitions.

METHODS: A retrospective cohort of veterans with SCI and more than 1 culture with Escherichia coli, Klebsiella spp and/or Enterobacter spp between 2012 and 2013 was examined. Antibiotic susceptibility criteria of pre-2015 (CDC1) and post-2015 (CDC2) CDC definitions and pre-2017 (VA1) and post-2017 (VA2) VA definitions were used to identify CRE. CRE prevalence and characteristics are described for isolates meeting each definition, and agreement was assessed with the Cohen kappa.

RESULTS: We reviewed 21,514 isolates cultured from 6,974 veterans; 423 isolates met any CRE definition. Although agreement among definitions was high (kappa = 0.82-0.93), definitions including ertapenem resistance led to higher CRE prevalence (VA1 = 1.7% and CDC2 = 1.9% vs VA2 = 1.4% and CDC1 = 1.5%). Forty-four of 142 VA facilities had more than 1 CRE case defined by VA2; 10 facilities accounted for 60% of CRE cases. Almost all CRE was isolated from high-complexity, urban facilities, and the South had the highest proportion of CRE.

CONCLUSIONS: Varying federal definitions give different CRE frequencies in a high-risk population. Definitions including ertapenem resistance resulted in higher CRE prevalence but may overemphasize noncarbapenemase isolates. Thus, both federal definitions now highlight the importance of carbapenemase testing.

Laboratory identification of carbapenem-resistant Enterobacteriaceae (CRE) is a key step in controlling its spread. Our survey showed that most Veterans Affairs laboratories follow VA guidelines for initial CRE identification, whereas 55.0% use PCR to confirm carbapenemase production. Most respondents were knowledgeable about CRE guidelines. Barriers included staffing, training, and financial resources.

BACKGROUND: Most antibiotic use in the United States occurs in the outpatient setting, and 10% of these prescriptions are generated by dentists. The development of comprehensive antibiotic stewardship programs (ASPs) in the dental setting is nascent, and therefore we describe the implementation of a dental ASP.

METHODS: A collaborative team of dentist, pharmacist, and physician leaders conducted a baseline needs assessment and literature evaluation to identify opportunities to improve antibiotic prescribing by dentists within Illinois' largest oral health care provider for Medicaid recipients. A multimodal intervention was implemented that included patient and provider education, clinical guideline development, and an assessment of the antibiotic prescribing rate per urgent care visit before and after the educational interventions.

RESULTS: We identified multiple needs, including standardization of antibiotic prescribing practices for patients with acute oral infections in the urgent care clinics. A 72.9% decrease in antibiotic prescribing was observed in urgent care visits after implementation of our multimodal intervention (preintervention urgent care prescribing rate, 8.5% [24/283]; postintervention, 2.3% [8/352]; P < .001).

CONCLUSIONS: We report the successful implementation of a dental ASP that is concordant with the Centers for Disease Control and Prevention Core Elements of Antibiotic Stewardship in the Outpatient Setting. Our approach may be adapted to other dental practices to improve antibiotic prescribing.

CONTEXT: Screening for asymptomatic bacteriuria (ASB) before non-urologic surgery is common but of unclear benefit. Our aim was to describe pre-operative ASB screening and post-operative outcomes in patients with neurogenic bladder due to spinal cord injury (SCI).

METHODS: This was a descriptive retrospective cohort study of adults with SCI undergoing neurosurgical spine or orthopedic lower limb surgery from 10/1/2012-9/30/2014 at Veterans Affairs (VA) medical centers. National VA datasets and medical record review was used to describe frequency of pre-operative ASB screening, presence of ASB, and association with post-operative surgical site infection, urinary tract infection, and hospital readmission.

RESULTS: 175 patients were included. Although over half of patients had pre-operative ASB screening, only 30.8% actually had pre-operative ASB. 15.2% of patients screened were treated for ASB with antibiotics before surgery. Post-operative urinary tract infection (UTI) or surgical site infection (SSI) occurred in 10 (5.7%) patients, and 20 patients (11.4%) were readmitted within 30 days. Neither ASB screening nor the presence of pre-operative ASB were associated with these post-op outcomes (p > 0.2 for all).

CONCLUSION: Pre-operative ASB screening is common in patients with SCI undergoing elective spine and lower limb surgery, although ASB occurs in less than 1/3rd of cases. There were no associations between pre-operative ASB and outcomes. Further studies evaluating the clinical benefit of this practice in patients with SCI should be performed.

CONTEXT/OBJECTIVE: To evaluate the impact of long-term nitrofurantoin for UTI prophylaxis in veterans with SCI.

DESIGN: Matched pairs study.

SETTING: Veterans cared for at VA facilities from 10/1/2012-9/30/2013.

PARTICIPANTS: Veterans.

INTERVENTIONS: n/a.

OUTCOMES MEASURES: UTI, positive urine cultures, resistant cultures.

METHODS: Cases receiving long-term nitrofurantoin (≥90 days supply) were matched to controls by facility. Controls were patients who did not receive long-term nitrofurantoin with a history of ≥3 positive urine cultures and at least one diagnosis of UTI or asymptomatic bacteriuria in the previous year.

RESULTS: 122 SCI cases were identified and matched to 196 controls. After adjusting for differences in baseline demographic characteristics, UTIs were less frequent in cases (OR = 0.60 [95% CI 0.44-0.72]). Cases had a greater mean number of days between positive urine cultures as compared to controls (<0.0001). Cases were more likely to have isolates resistant to nitrofurantoin (P ≤ 0.0001); however, the frequency of multi-drug resistant organisms isolated from the urine was not significantly different.

CONCLUSIONS: Long-term prescription of nitrofurantoin may reduce UTIs in veterans with SCI and there is no evidence that it promotes multi-drug resistance. Future prospective studies should be conducted prior to incorporating routine use of long-term nitrofurantoin into clinical care.

IMPORTANCE: Antibiotics are recommended before certain dental procedures in patients with select comorbidities to prevent serious distant site infections.

OBJECTIVE: To assess the appropriateness of antibiotic prophylaxis before dental procedures using Truven, a national integrated health claims database.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study. Dental visits from 2011 to 2015 were linked to medical and prescription claims from 2009 to 2015. The dates of analysis were August 2018 to January 2019. Participants were US patients with commercial dental insurance without a hospitalization or extraoral infection 14 days before antibiotic prophylaxis (defined as a prescription with ≤2 days' supply dispensed within 7 days before a dental visit).

EXPOSURES: Presence or absence of cardiac diagnoses and dental procedures that manipulated the gingiva or tooth periapex.

MAIN OUTCOMES AND MEASURES: Appropriate antibiotic prophylaxis was defined as a prescription dispensed before a dental visit with a procedure that manipulated the gingiva or tooth periapex in patients with an appropriate cardiac diagnosis. To assess associations between patient or dental visit characteristics and appropriate antibiotic prophylaxis, multivariable logistic regression was used. A priori hypothesis tests were performed with an α level of .05.

RESULTS: From 2011 to 2015, antibiotic prophylaxis was prescribed for 168 420 dental visits for 91 438 patients (median age, 63 years; interquartile range, 55-72 years; 57.2% female). Overall, these 168 420 dental visits were associated with 287 029 dental procedure codes (range, 1-14 per visit). Most dental visits were classified as diagnostic (70.2%) and/or preventive (58.8%). In 90.7% of dental visits, a procedure was performed that would necessitate antibiotic prophylaxis in high-risk cardiac patients. Prevalent comorbidities include prosthetic joint devices (42.5%) and cardiac conditions at the highest risk of adverse outcome from infective endocarditis (20.9%). Per guidelines, 80.9% of antibiotic prophylaxis prescriptions before dental visits were unnecessary. Clindamycin was more likely to be unnecessary relative to amoxicillin (odds ratio [OR], 1.10; 95% CI, 1.05-1.15). Prosthetic joint devices (OR, 2.31; 95% CI, 2.22-2.41), tooth implant procedures (OR, 1.66; 95% CI, 1.45-1.89), female sex (OR, 1.21; 95% CI, 1.17-1.25), and visits occurring in the western United States (OR, 1.15; 95% CI, 1.06-1.25) were associated with unnecessary antibiotic prophylaxis.

CONCLUSION AND RELEVANCE: More than 80% of antibiotics prescribed for infection prophylaxis before dental visits were unnecessary. Implementation of antimicrobial stewardship in dental practices is an opportunity to improve antibiotic prescribing for infection prophylaxis.

IMPORTANCE: The United States consumes most of the opioids worldwide despite representing a small portion of the world's population. Dentists are one of the most frequent US prescribers of opioids despite data suggesting that nonopioid analgesics are similarly effective for oral pain. While oral health and dentist use are generally similar between the United States and England, it is unclear how opioid prescribing by dentists varies between the 2 countries.

OBJECTIVE: To compare opioid prescribing by dentists in the United States and England.

DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of prescriptions for opioids dispensed from outpatient pharmacies and health care settings between January 1 and December 31, 2016, by dentists in the United States and England. Data were analyzed from October 2018 to January 2019.

EXPOSURES: Opioids prescribed by dentists.

MAIN OUTCOMES AND MEASURES: Proportion and prescribing rates of opioid prescriptions.

RESULTS: In 2016, the proportion of prescriptions written by US dentists that were for opioids was 37 times greater than the proportion written by English dentists. In all, 22.3% of US dental prescriptions were opioids (11.4 million prescriptions) compared with 0.6% of English dental prescriptions (28 082 prescriptions) (difference, 21.7%; 95% CI, 13.8%-32.1%; P < .001). Dentists in the United States also had a higher number of opioid prescriptions per 1000 population (35.4 per 1000 US population [95% CI, 25.2-48.7 per 1000 population] vs 0.5 per 1000 England population [95% CI, 0.03-3.7 per 1000 population]) and number of opioid prescriptions per dentist (58.2 prescriptions per dentist [95% CI, 44.9-75.0 prescriptions per dentist] vs 1.2 prescriptions per dentist [95% CI, 0.2-5.6 prescriptions per dentist]). While the codeine derivative dihydrocodeine was the sole opioid prescribed by English dentists, US dentists prescribed a range of opioids containing hydrocodone (62.3%), codeine (23.2%), oxycodone (9.1%), and tramadol (4.8%). Dentists in the United States also prescribed long-acting opioids (0.06% of opioids prescribed by US dentists [6425 prescriptions]). Long-acting opioids were not prescribed by English dentists.

CONCLUSIONS AND RELEVANCE: This study found that in 2016, dentists in the United States prescribed opioids with significantly greater frequency than their English counterparts. Opioids with a high potential for abuse, such as oxycodone, were frequently prescribed by US dentists but not prescribed in England. These results illustrate how 1 source of opioids differs substantially in the United States vs England. To reduce dental opioid prescribing in the United States, dentists could adopt measures similar to those used in England, including national guidelines for treating dental pain that emphasize prescribing opioids conservatively.