Safety and efficacy of IV theophylline for regadenoson-associated side effect reversal.

BACKGROUND: Aminophylline injection has been on an intermittent nation-wide shortage due to manufacturing delays leaving a need for an alternative reversal agent for regadenoson-associated side effects. Intravenous theophylline should be a logical acceptable pharmacological alternative; however, data regarding its safety and efficacy as a reversal agent are lacking. METHODS: Utilizing electronic medical records at the University of Colorado hospital, we identified patients ≥ 18 years of age who had a pharmacologic stress test using regadenoson during periods of aminophylline shortage (3/1/2013 to 5/31/2013 and 4/1/2018 to 8/30/2018) in which theophylline was used as an alternative antidote for side effect reversal. Intravenous theophylline was prepared by the inpatient pharmacy to a concentration of 0.8 mg/mL in a total volume of 100 mL D5W. Specific side effects and side effect resolution were evaluated. RESULTS: Of the 122 patients evaluated, theophylline was administered in doses ranging from 40 to 75 mg with the majority receiving 40 mg. Complete resolution of regadenoson side effects occurred in 98 patients with 12 experiencing partial resolution and 1 without resolution. No adverse effects or events were reported. CONCLUSION: Due to limited availability of aminophylline, theophylline may be a safe and effective alternative to reverse regadenoson-associated side effects.

Association of intraprocedural blood pressure and end tidal carbon dioxide with outcome after acute stroke intervention.

BACKGROUND: General anesthesia (GA) for acute stroke interventions may be associated with inferior functional outcomes. Our goal was to identify physiologic parameters that mediate this association. METHODS: Consecutive patients treated at our institution between August 2007 and December 2010 were identified from a prospective database. Clinical data were then extracted by retrospective chart review. Variables significantly associated with outcome in univariate analysis were also examined in multivariate analysis, controlling for well-established prespecified predictors of functional outcome. RESULTS: Of the 106 patients identified, 20 were excluded (17 due to the absence of 90-day mRS and 3 due to insufficient anesthetic records). Blood pressure (BP) decreased significantly after induction of GA, but there was no association between BP and outcome. End tidal carbon dioxide values (ETCO2) at 60 and 90 min, however, were significantly associated with outcomes in both univariate and multivariate analyses. Mean ETCO2 in patients with favorable outcomes (modified Rankin Scale (mRS) 0-3) was higher than in those with unfavorable outcomes (mRS 4-6): 35.2 mmHg versus 32.2 (p = 0.03) at 60 min and 34.9 versus 31.9 (p = 0.04) at 90 min. The adjusted odds ratios for poor outcomes for each 1 mmHg decrease in ETCO2 were the same: 0.76 (95 % CI 0.65-0.92; p = 0.004) at 60 min and 0.76 (95 % CI 0.61-0.93; p = 0.01) at 90 min. CONCLUSIONS: While BP decreased significantly in patients undergoing GA for acute stroke intervention, it did not correlate with patient outcome. Decreases in ETCO2 at 30 and 60 min, however, were associated with 90-day mRS.

Myocardial Injury and Altered Gene Expression Associated With SARS-CoV-2 Infection or mRNA Vaccination.

SARS CoV-2 enters host cells via its Spike protein moiety binding to the essential cardiac enzyme angiotensin-converting enzyme (ACE) 2, followed by internalization. COVID-19 mRNA vaccines are RNA sequences that are translated into Spike protein, which follows the same ACE2-binding route as the intact virion. In model systems, isolated Spike protein can produce cell damage and altered gene expression, and myocardial injury or myocarditis can occur during COVID-19 or after mRNA vaccination. We investigated 7 COVID-19 and 6 post-mRNA vaccination patients with myocardial injury and found nearly identical alterations in gene expression that would predispose to inflammation, coagulopathy, and myocardial dysfunction.

Comparative analysis of ferumoxytol and gadoteridol enhancement using T1- and T2-weighted MRI in neuroimaging.

OBJECTIVE: Ferumoxytol, an ultrasmall superparamagnetic iron oxide particle, has been suggested as a potential alternative MRI contrast agent in patients with renal failure. We compared ferumoxytol to gadoteridol enhancement on T1- and T2-weighted MRI in CNS disorders to explore its diagnostic utility. SUBJECTS AND METHODS: Data were collected from three protocols in 70 adults who underwent alternate-day gadoteridol- and ferumoxytol-enhanced MRI using identical parameters. Two neuroradiologists measured lesion-enhancing size and intensity on contrast-enhanced T1-weighted images in consensus. T2-weighted images were evaluated for the presence of contrast-enhanced hypointensity. Mixed model repeated measures analysis of variance determined differences between T1-weighted enhancement size and intensity for individual protocols and group. RESULTS: After exclusions, 49 MRI studies in 29 men and 20 women (mean age, 51 years) were assessed. T1-weighted estimated enhancing sizes were different between agents (p = 0.0456) as a group; however, no differences were observed with untreated gliomas (n = 17) in two protocols (p = 1.0 and p = 0.99, respectively). Differences in T1-weighted enhancement intensity between agents were significant for the group overall (p = 0.0006); however, three-way interactions were not significant (p = 0.1233). T2-weighted images were assessed for contrast-enhanced hypointensity, observed in 26 of 49 (53%) ferumoxytol and zero of 49 (0%) gadoteridol scans. CONCLUSION: Ferumoxytol may be a useful MRI contrast agent in patients who are unable to receive gadolinium-based contrast agents. Greater experience with a wider variety of disorders is necessary to understand differences in enhancement with ferumoxytol compared with gadolinium-based contrast agents, given their different mechanisms of action.

Acute Myocardial Infarction Cohorts Defined by International Classification of Diseases, Tenth Revision Versus Diagnosis-Related Groups: Analysis of Diagnostic Agreement and Quality Measures in an Integrated Health System.

BACKGROUND: Among Medicare value-based payment programs for acute myocardial infarction (AMI), the Hospital Readmissions Reduction Program uses International Classification of Diseases, Tenth Revision (ICD-10) codes to identify the program denominator, while the Bundled Payments for Care Improvement Advanced program uses diagnosis-related groups (DRGs). The extent to which these programs target similar patients, whether they target the intended population (type 1 myocardial infarction), and whether outcomes are comparable between cohorts is not known. METHODS: In a retrospective study of 2176 patients hospitalized in an integrated health system, a cohort of patients assigned a principal ICD-10 diagnosis of AMI and a cohort of patients assigned an AMI DRG were compared according to patient-level agreement and outcomes such as mortality and readmission. RESULTS: One thousand nine hundred thirty-five patients were included in the ICD-10 cohort compared with 662 patients in the DRG cohort. Only 421 patients were included in both AMI cohorts (19.3% agreement). DRG cohort patients were older (70 versus 65 years, P<0.001), more often female (48% versus 30%, P<0.001), and had higher rates of heart failure (52% versus 33%, P<0.001) and kidney disease (42% versus 25%, P<0.001). Comparing outcomes, the DRG cohort had significantly higher unadjusted rates of 30-day mortality (6.6% versus 2.5%, P<0.001), 1-year mortality (21% versus 8%, P<0.001), and 90-day readmission (26% versus 19%, P=0.006) than the ICD-10 cohort. Two observations help explain these differences: 61% of ICD-10 cohort patients were assigned procedural DRGs for revascularization instead of an AMI DRG, and type 1 myocardial infarction patients made up a smaller proportion of the DRG cohort (34%) than the ICD-10 cohort (78%). CONCLUSIONS: The method used to identify denominators for value-based payment programs has important implications for the patient characteristics and outcomes of the populations. As national and local quality initiatives mature, an emphasis on ICD-10 codes to define AMI cohorts would better represent type 1 myocardial infarction patients.

Integrated Critical Care Curriculum for the Third-Year Internal Medicine Clerkship.

Introduction: A majority of residents provide care for critically ill patients, yet only a minority of medical schools require ICU rotations. Therefore, many medical students enter residency without prior ICU experience. The third-year internal medicine (IM) clerkship at our institution's Veterans Affairs Medical Center (VAMC) provided an opportunity for medical students to rotate through an open ICU as part of their inpatient ward rotation. Prior to March 2019, no structured critical care curriculum existed within the IM clerkship to prepare students for this experience. Methods: We created a seven-session ICU curriculum integrated within the VAMC IM clerkship addressing core critical care topics and skills including bedside presentations, shock, and respiratory failure. IM residents facilitated the curriculum's case-based, small-group discussions. We assessed curricular efficacy and impact with a pre- and posttest and end-of-curriculum survey. Results: Forty-one students participated in the curriculum from March to November 2019. As a result, students agreed that their overall clerkship experience improved (73% strongly agree, 24% agree). Students also reported increased comfort in their ability to participate in the management of critically ill patients (44% strongly agree, 51% agree). Objectively, student performance on a 15-question pre- and posttest improved from a precurricular average of 7.5 (50%) questions correct to a postcurricular average of 10.7 (71%) questions correct (p <.0001; CI 2.2-4.4). Discussion: Following implementation of our ICU curriculum, medical student attitudes regarding overall IM clerkship experience, self-perceived confidence in critically ill patient management, and medical knowledge all improved.

Gainful employment reduces stigma toward people recovering from schizophrenia.

Stigma impedes the social integration of persons recovering from psychiatric disability, especially those with criminal histories. Little is known about factors that lessen this stigma. Four hundred and four adults listened to one of four vignettes describing a 25-year-old male with schizophrenia and responded to a standard set of items measuring social distance. The individual who was gainfully employed (vs. unemployed), or who had a prior misdemeanor (vs. felony) criminal offense, elicited significantly less stigma. Employment may destigmatize a person coping with both psychiatric disability and a criminal record. Mental health services should encourage paid employment and other paths to community integration.

Investigating molecular recognition and biological function at interfaces using piscidins, antimicrobial peptides from fish.

We studied amidated and non-amidated piscidins 1 and 3, amphipathic cationic antimicrobial peptides from fish, to characterize functional and structural similarities and differences between these peptides and better understand the structural motifs involved in biological activity and functional diversity among amidated and non-amidated isoforms. Antimicrobial and hemolytic assays were carried out to assess their potency and toxicity, respectively. Site-specific high-resolution solid-state NMR orientational restraints were obtained from (15)N-labeled amidated and non-amidated piscidins 1 and 3 in the presence of hydrated oriented lipid bilayers. Solid-state NMR and circular dichroism results indicate that the peptides are alpha-helical and oriented parallel to the membrane surface. This orientation was expected since peptide-lipid interactions are enhanced at the water-bilayer interface for amphipathic cationic antimicrobial peptides. (15)N solid-state NMR performed on oriented samples demonstrate that piscidin experiences fast, large amplitude backbone motions around an axis parallel to the bilayer normal. Under the conditions tested here, piscidin 1 was confirmed to be more antimicrobially potent than piscidin 3 and antimicrobial activity was not affected by amidation. In light of functional and structural similarities between piscidins 1 and 3, we propose that their topology and fast dynamics are related to their mechanism of action.

Program evaluation from an ecological perspective: supported employment services for persons with serious psychiatric disabilities.

Results of large-scale program evaluations supplement other kinds of evidence regarding interventions for psychiatric disabilities. This paper describes an ongoing 11-year effort to evaluate supported employment services provided to persons with serious psychiatric disabilities by community mental health centers in one Midwestern state. Using an ecological perspective, the evaluation emphasizes multiple kinds of products and the careful development and maintenance of stakeholder relationships. Data from over 4600 individuals in supported employment programs demonstrate that services are effective and efficient, that these employees and employers are satisfied, and that stable employment may sharply reduce the overall costs of mental health care.