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Although there have been several case reports and simulation models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission associated with air travel, there are limited data to guide testing strategy to minimize the risk of SARS-CoV-2 exposure and transmission onboard commercial aircraft. Among 9853 passengers with a negative SARS-CoV-2 polymerase chain reaction test performed within 72 hours of departure from December 2020 through May 2021, five (0.05%) passengers with active SARS-CoV-2 infection were identified with rapid antigen tests and confirmed with rapid molecular test performed before and after an international flight from the United States to Italy. This translates to a case detection rate of 1 per 1970 travelers during a time of high prevalence of active infection in the United States. A negative molecular test for SARS-CoV-2 within 72 hours of international airline departure results in a low probability of active infection identified on antigen testing during commercial airline flight.

In March 2020, our institution developed an interdisciplinary predictive analytics task force to provide coronavirus disease 2019 (COVID-19) hospital census forecasting to help clinical leaders understand the potential impacts on hospital operations. As the situation unfolded into a pandemic, our task force provided predictive insights through a structured set of visualizations and key messages that have helped the practice to anticipate and react to changing operational needs and opportunities. The framework shared here for the deployment of a COVID-19 predictive analytics task force could be adapted for effective implementation at other institutions to provide evidence-based messaging for operational decision-making. For hospitals without such a structure, immediate consideration may be warranted in light of the devastating COVID-19 third-wave which has arrived for winter 2020-2021.

Background Reactive balance recovery evokes a negative peak of cortical electroencephalography (EEG) activity (N1) that is simultaneous to brainstem-mediated automatic balance-correcting muscle activity. This study follows up on an observation from a previous study, in which N1 responses were larger in individuals who seemed to have greater difficulty responding to support-surface perturbations. Research Question We hypothesized that people engage more cortical activity when balance recovery is more challenging. We predicted that people with lower balance ability would exhibit larger cortical N1 responses during balance perturbations. Methods In 20 healthy young adults (11 female, ages 19–38) we measured the amplitude of the cortical N1 response evoked by 48 backward translational support-surface perturbations of unpredictable timing and amplitude. Perturbations included a Small (8 cm) perturbation that was identical across participants, as well as Medium (13−15 cm) and Large (18−22 cm) perturbations scaled to participant height to control for height-related differences in perturbation difficulty. To assess individual differences in balance ability, we measured the distance traversed on a narrow (0.5-inch wide) 12-foot beam across 6 trials. We tested whether the cortical N1 response amplitude was correlated to balance ability across participants. Results Cortical N1 amplitudes in response to standing balance perturbations (54 ± 18 μV) were inversely correlated to the distance traveled in the difficult beam-walking task (R2 = 0.20, p = 0.029). Further, there was a significant interaction between performance on the beam-walking task and the effect of perturbation magnitude on the cortical N1 response amplitude, whereby individuals who performed worse on the beam-walking task had greater increases in N1 amplitudes with increases in perturbation magnitude. Significance Cortical N1 response amplitudes may reflect greater cortical involvement in balance recovery when challenged. This increased cortical involvement may reflect cognitive processes such as greater perceived threat or attention to balance, which have the potential to influence subsequent motor control.

Characterizing the cellular heterogeneity of human ureter tissues using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics provides a detailed atlas of cell types, signaling networks, and potential cell-cell cross talk underlying developmental and regenerative pathways. We describe an optimized protocol for generating, cryopreserving, and thawing single-cell suspensions from ureter tissues isolated post-cystectomy for scRNA-seq. In addition, we describe an optimized protocol for cryopreserving human ureter tissues for 10x Genomics Visium spatial gene expression platform. For complete details on the use and execution of this protocol, please refer to Fink et al. (2022).

Tissue engineering offers a promising treatment strategy for ureteral strictures, but its success requires an in-depth understanding of the architecture, cellular heterogeneity, and signaling pathways underlying tissue regeneration. Here, we define and spatially map cell populations within the human ureter using single-cell RNA sequencing, spatial gene expression, and immunofluorescence approaches. We focus on the stromal and urothelial cell populations to enumerate the distinct cell types composing the human ureter and infer potential cell-cell communication networks underpinning the bi-directional crosstalk between these compartments. Furthermore, we analyze and experimentally validate the importance of the sonic hedgehog (SHH) signaling pathway in adult progenitor cell maintenance. The SHH-expressing basal cells support organoid generation in vitro and accurately predict the differentiation trajectory from basal progenitor cells to terminally differentiated umbrella cells. Our results highlight the essential processes involved in adult ureter tissue homeostasis and provide a blueprint for guiding ureter tissue engineering.

E2F1 is a transcription factor classically known to regulate G0/G1 to S phase progression in the cell cycle. In addition, E2F1 also regulates a wide range of apoptotic genes and thus has been well studied in the context of neuronal death and neurodegenerative diseases. However, its function and regulation in the mature central nervous system are not well understood. Alternative splicing is a well-conserved post-transcriptional mechanism common in cells of the CNS and is necessary to generate diverse functional modifications to RNA or protein products from genes. Heretofore, physiologically significant alternatively spliced E2F1 transcripts have not been reported. In the present study, we report the identification of two novel alternatively spliced E2F1 transcripts: E2F1b, an E2F1 transcript retaining intron 5, and E2F1c, an E2F1 transcript excluding exon 6. These alternatively spliced transcripts are observed in the brain and neural cell types including neurons, astrocytes, and undifferentiated oligodendrocytes. The expression of these E2F1 transcripts is distinct during maturation of primary hippocampal neuroglial cells. Pharmacologically-induced global translation inhibition with cycloheximide, anisomycin or thapsigargin lead to significantly reduced expression of E2F1a, E2F1b and E2F1c. Conversely, increasing neuronal activity by elevating the concentration of potassium chloride selectively increased the expression of E2F1b. Furthermore, experiments expressing these variants in vitro show the transcripts can be translated to generate a protein product. Taken together, our data suggest that the alternatively spliced E2F1 transcript behave differently than the E2F1a transcript, and our results provide a foundation for future investigation of the function of E2F1 splice variants in the CNS.

Objective To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. Methods We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. Results A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19–directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. Conclusion Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

BACKGROUND: Individuals with Parkinson’s disease (PD) are at increased risk for falls, which lead to substantial morbidity and mortality. Understanding the motor and non-motor impairments associated with falls in PD is critical to informing prevention strategies. In addition to motor symptoms, individuals with PD exhibit non-motor deficits, including impaired set shifting, an aspect of executive function related to cognitive flexibility that can be measured quickly with the Trailmaking Test. RESEARCH QUESTION: To determine whether impaired set shifting is associated with fall history in people with and without PD. METHODS: We examined associations between set shifting, PD status, and fall history (≥1 falls in the previous 6 months) in data from PD patients (n=65) with and without freezing of gait (FOG) and community-dwelling neurologically-normal older adults (NON-PD) (n=73) who had participated in our rehabilitation studies. RESULTS: Impaired set shifting was associated with previous falls after controlling for age, sex, overall cognitive function, PD status, FOG, and PD disease duration (OR=1.29 [1.03–1.60]; P=0.02). Consistent with literature, PD and FOG were also independently associated with increased fall prevalence (PD OR=4.15 [95% CI 1.65–10.44], P

Oral anticoagulation (OAC) with warfarin is underused for atrial fibrillation (AF). The availability of direct oral anticoagulants (DOACs) may improve overall OAC rates in AF patients, but a large-scale evaluation of their effects has not been conducted.This study assessed the effect of DOAC availability on overall OAC rates for nonvalvular AF.Between April 1, 2008 and September 30, 2014, we identified 655,000 patients with nonvalvular AF and a CHAOverall OAC rates increased from 52.4% to 60.7% among eligible AF patients (p for trend 0.01). Warfarin use decreased from 52.4% to 34.8% (p for trend 0.01), and DOAC use increased from 0% to 25.8% (p for trend 0.01). An increasing CHAIntroduction of DOACs in routine practice was associated with improved rates of overall OAC use for AF, but significant gaps remain. In addition, there is significant practice-level variation in OAC and DOAC use.

Simulating realistic musculoskeletal dynamics is critical to understanding neural control of muscle activity evoked in sensorimotor feedback responses that have inherent neural transmission delays. Thus, the initial mechanical response of muscles to perturbations in the absence of any change in muscle activity determines which corrective neural responses are required to stabilize body posture. Muscle short-range stiffness, a history-dependent property of muscle that causes a rapid and transient rise in muscle force upon stretch, likely affects musculoskeletal dynamics in the initial mechanical response to perturbations. Here we identified the contributions of short-range stiffness to joint torques and angles in the initial mechanical response to support surface translations using dynamic simulation, respectively. We developed a dynamic model of muscle short-range stiffness to augment a Hill-type muscle model. Our simulations show that short-range stiffness can provide stability against external perturbations during the neuromechanical response delay. Assuming constant muscle activation during the initial mechanical response, including muscle short-range stiffness was necessary to account for the rapid rise in experimental sagittal plane knee and hip joint torques that occurs simultaneously with very small changes in joint angles and reduced root mean square errors between simulated and experimental torques by 56% and 47%, respectively. Moreover, forward simulations lacking short-range stiffness produced unreasonably large joint angle changes during the initial response. Using muscle models accounting for short-range stiffness along with other aspects of history-dependent muscle dynamics may be important to advance our ability to simulate inherently unstable human movements based on principles of neural control and biomechanics.

Jonathan L. Halperin, MD, FACC, FAHA, Chair Glenn N. Levine, MD, FACC, FAHA, Chair-Elect Jeffrey L. Anderson, MD, FACC, FAHA, Immediate Past Chair [∗∗][1] Nancy M. Albert, PhD, RN, FAHA[∗∗][1] Sana M. Al-Khatib, MD, MHS, FACC, FAHA Kim K. Birtcher, PharmD, MS, AACC Biykem Bozkurt, MD

Paul A. Heidenreich, MD, MS, FACC, FAHA, Chair Nancy M. Albert, PhD, CCNS, CCRN, CCA, FAHA Paul S. Chan, MD, MSc, FACC Lesley H. Curtis, PhD T. Bruce Ferguson, Jr., MD, FACC, FAHA Gregg C. Fonarow, MD, FACC, FAHA P. Michael Ho, MD, PhD, FACC, FAHA Sean O’Brien, PhD Andrea M. Russo, MD

Dysregulation of DNA methylation and mRNA alternative cleavage and polyadenylation (APA) are both prevalent in cancer and have been studied as independent processes. We discovered a DNA methylation-regulated APA mechanism when we compared genome-wide DNA methylation and polyadenylation site usage between DNA methylation-competent and DNA methylation-deficient cells. Here, we show that removal of DNA methylation enables CTCF binding and recruitment of the cohesin complex, which, in turn, form chromatin loops that promote proximal polyadenylation site usage. In this DNA demethylated context, either deletion of the CTCF binding site or depletion of RAD21 cohesin complex protein can recover distal polyadenylation site usage. Using data from The Cancer Genome Atlas, we authenticated the relationship between DNA methylation and mRNA polyadenylation isoform expression in vivo. This DNA methylation-regulated APA mechanism demonstrates how aberrant DNA methylation impacts transcriptome diversity and highlights the potential sequelae of global DNA methylation inhibition as a cancer treatment.

Although it is possible to produce the same movement using an infinite number of different muscle activation patterns owing to musculoskeletal redundancy, the degree to which observed variations in muscle activity can deviate from optimal solutions computed from biomechanical models is not known. Here, we examined the range of biomechanically permitted activation levels in individual muscles during human walking using a detailed musculoskeletal model and experimentally-measured kinetics and kinematics. Feasible muscle activation ranges define the minimum and maximum possible level of each muscle's activation that satisfy inverse dynamics joint torques assuming that all other muscles can vary their activation as needed. During walking, 73% of the muscles had feasible muscle activation ranges that were greater than 95% of the total muscle activation range over more than 95% of the gait cycle, indicating that, individually, most muscles could be fully active or fully inactive while still satisfying inverse dynamics joint torques. Moreover, the shapes of the feasible muscle activation ranges did not resemble previously-reported muscle activation patterns nor optimal solutions, i.e. static optimization and computed muscle control, that are based on the same biomechanical constraints. Our results demonstrate that joint torque requirements from standard inverse dynamics calculations are insufficient to define the activation of individual muscles during walking in healthy individuals. Identifying feasible muscle activation ranges may be an effective way to evaluate the impact of additional biomechanical and/or neural constraints on possible versus actual muscle activity in both normal and impaired movements.

Neuromechanical principles define the properties and problems that shape neural solutions for movement. Although the theoretical and experimental evidence is debated, we present arguments for consistent structures in motor patterns, i.e., motor modules, that are neuromechanical solutions for movement particular to an individual and shaped by evolutionary, developmental, and learning processes. As a consequence, motor modules may be useful in assessing sensorimotor deficits specific to an individual and define targets for the rational development of novel rehabilitation therapies that enhance neural plasticity and sculpt motor recovery. We propose that motor module organization is disrupted and may be improved by therapy in spinal cord injury, stroke, and Parkinson’s disease. Recent studies provide insights into the yet-unknown underlying neural mechanisms of motor modules, motor impairment, and motor learning and may lead to better understanding of the causal nature of modularity and its underlying neural substrates.

The ability to quantify differences in walking balance proficiency is critical to curbing the rising health and financial costs of falls. Current laboratory-based approaches typically focus on successful recovery of balance while clinical instruments often pose little difficulty for all but the most impaired patients. Rarely do they test motor behaviors of sufficient difficulty to evoke failures in balance control limiting their ability to quantify balance proficiency. Our objective was to test whether a simple beam-walking task could quantify differences in walking balance proficiency across a range of sensorimotor abilities. Ten experts, ten novices, and five individuals with transtibial limb loss performed six walking trials across three different width beams. Walking balance proficiency was quantified as the ratio of distance walked to total possible distance. Balance proficiency was not significantly different between cohorts on the wide-beam, but clear differences between cohorts on the mid and narrow-beams were identified. Experts walked a greater distance than novices on the mid-beam (average of 3.63±0.04m verus 2.70±0.21m out of 3.66m; p=0.009), and novices walked further than amputees (1.52±0.20m; p=0.03). Amputees were unable to walk on the narrow-beam, while experts walked further (3.07±0.14m) than novices (1.55±0.26m; p=0.0005). A simple beam-walking task and an easily collected measure of distance traveled detected differences in walking balance proficiency across sensorimotor abilities. This approach provides a means to safely study and evaluate successes and failures in walking balance in the clinic or lab. It may prove useful in identifying mechanisms underlying falls versus fall recoveries.

Incomplete spinal cord injury (iSCI) disrupts motor control and limits the ability to coordinate muscles for overground walking. Inappropriate muscle activity has been proposed as a source of clinically observed walking deficits after iSCI. We hypothesized that persons with iSCI exhibit lower locomotor complexity compared to able-body (AB) controls as reflected by fewer motor modules, as well as, altered module composition and activation.Eight persons with iSCI and eight age-matched AB controls walked overground at prescribed cadences. Electromyograms of fourteen single leg muscles were recorded. Non-negative matrix factorization was used to identify the composition and activation of motor modules, which represent groups of consistently co-activated muscles that accounted for 90% of variability in muscle activity.Motor module number, composition, and activation were significantly altered in persons with iSCI as compared to AB controls during overground walking at self-selected cadences. However, there was no significant difference in module number between persons with iSCI and AB controls when cadence and assistive device were matched.Muscle coordination during overground walking is impaired after chronic iSCI.Our results are indicative of neuromuscular constraints on muscle coordination after iSCI. Altered muscle coordination contributes to person-specific gait deficits during overground walking.

Henry H. Ting, MD, MBA, FACC, Chair Eric R. Bates, MD, FACC John E. Brush, Jr, MD, FACC Megan Coylewright, MD Joseph P. Drozda, Jr, MD, FACC Robert A. Harrington, MD, FACC Steven G. Lloyd, MD, PhD, FACC Frederick A. Masoudi, MD, MSPH, FACC Rick A. Nishimura, MD, MACC Sara K. Pasquali, MD

A B S T R A C T The Nintendo Wii Balance Board (WBB) is increasingly used as an inexpensive force plate for assessment of postural control; however, no documentation of force and COP accuracy and reliability is publicly available. Therefore, we performed a standard measurement uncertainty analysis on 3 lightly and 6 heavily used WBBs to provide future users with information about the repeatability and accuracy of the WBB force and COP measurements. Across WBBs, we found the total uncertainty of force measurements to be within � 9.1 N, and of COP location within � 4.1 mm. However, repeatability of a single measurement within a board was better (4.5 N, 1.5 mm), suggesting that the WBB is best used for relative measures using the same device, rather than absolute measurement across devices. Internally stored calibration values were comparable to those determined experimentally. Further, heavy wear did not significantly degrade performance. In combination with prior evaluation of WBB performance and published standards for measuring human balance, our study provides necessary information to evaluate the use of the WBB for analysis of human balance control. We suggest the WBB may be useful for low-resolution measurements, but should not be considered as a replacement for laboratory-grade force plates.

The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can

Ultrasound-guided regional anesthesia (UGRA) has increased in popularity over the past 5 years. This interest is reflected by the plethora of publications devoted to technique development, as well as randomized and controlled trials. Despite the excitement around ultrasonography, skeptics argue that there is a lack of evidence-based medicine to support the unequivocal adoption of UGRA as a "standard of care." This article summarizes and critically assesses current data comparing traditional approaches to localizing nerves with those that use ultrasound guidance. In addition, the potential benefits of UGRA that go beyond current information available from comparative studies are explored.

Objectives We sought to determine the circadian, weekly, and seasonal variation of coronary stent thrombosis.Background Other adverse cardiovascular events such as acute myocardial infarction are known to have higher incidences during the early morning hours, Mondays, and winter months.Methods The Mayo Clinic Percutaneous Coronary Intervention Registry was searched for patients admitted to our center who underwent repeat percutaneous coronary intervention in a previously stented coronary artery segment. Stent thrombosis was confirmed by angiographic review, and date and time of symptom onset were obtained from medical records.Results We identified 124 patients with definite stent thrombosis and known date and time of symptom onset. In these patients, onset of stent thrombosis was significantly associated with time of day (p = 0.006), with a peak incidence around 7:00 AM. When patients were subdivided into early stent thrombosis (0 to 30 days; n = 49), late stent thrombosis (31 to 360 days; n = 30), and very late stent thrombosis (> 360 days; n = 45), only early stent thrombosis remained significantly associated with time of day (p = 0.030). No association with the day of the week was found (p = 0.509); however, onset of stent thrombosis did follow a significant seasonal pattern, with higher occurrences in the summer (p = 0.036).Conclusions Coronary stent thrombosis occurs more often in the early morning hours. Early stent thrombosis follows a circadian rhythm with a peak at 7:00 AM. This pattern was not significant in late and very late stent thrombosis. Occurrences throughout the week were equally distributed, but stent thrombosis was more likely to occur in the summer months. (J Am Coll Cardiol Intv 2011;4: 183-90) (C) 2011 by the American College of Cardiology Foundation

We hypothesized that the use of a patient decision aid (PDA) to facilitate a patient-centered discussion would increase patient knowledge. The aim of this study was to explore the feasibility of use of a chronic total occlusion (CTO) PDA in patients with coronary artery disease. We also discuss the

OBJECTIVE To compare outcomes of percutaneous coronary interventions (PCIs) at 2 community hospitals without on-site surgery (Franciscan Skemp Healthcare and Immanuel St. Joseph's Hospital) with a center with on-site surgery (Saint Marys Hospital). PATIENTS AND METHODS Using a matched case-control design, we studied 1842 elective and 667 nonelective PCI procedures (myocardial infarction [MI]/cardiogenic shock) performed from January 1, 1999, through December 31, 2007. The quality assurance protocol included operator volume and training, application of a risk-adjustment model, transport protocol, and database participation. We compared in-hospital mortality and/or emergent coronary artery bypass surgery after PCI at Franciscan Skemp Healthcare and Immanuel St. Joseph's Hospital, which do not have on-site surgery, with Saint Marys Hospital, a medical center with the capability to perform coronary artery bypass grafting on site. RESULTS Of 22 baseline variables, significant imbalances between matched groups were present in only 3 (hyperlipidemia, history of MI, American College of Cardiology/American Heart Association B2/C type lesion) in the elective group and 2 (Canadian Cardiovascular Society class III/IV angina, multivessel disease) in the nonelective group. The primary end point occurred in 0.3%, 0.1%, and 0.6% of patients undergoing elective PCI ( P =.07) and 3.3%, 3.3%, and 3.7% of patients undergoing nonelective PCI ( P =.65) at Immanuel St. Joseph's Hospital, Franciscan Skemp Healthcare, and Saint Marys Hospital, respectively. The in-hospital mortality rate at Immanuel St. Joseph's Hospital and Franciscan Skemp Healthcare was comparable to that at Saint Marys Hospital for both elective (0.3%, 0.1%, 0.4%; P =.24) and nonelective PCI (2.6%, 2.4%, 3.1%; P =.49). No patient undergoing elective PCI required transfer for emergency cardiac surgery. Of the 21 transfers, 20 (95%) were in the setting of MI and cardiogenic shock or left main/3-vessel disease; 18 patients (86%) survived to discharge. CONCLUSION Optimal outcomes with PCI have been observed at community hospitals without on-site cardiac surgical programs with application of a prospective, standardized quality assurance protocol.

OBJECTIVES To determine the frequency of urgent coronary angiography in patients with acute pericarditis and to examine clinical characteristics associated with coronary angiography. PATIENTS AND METHODS This is a retrospective analysis of all incident cases of acute viral or idiopathic pericarditis evaluated at Mayo Clinic's site in Rochester, MN, between January 1, 2000, and December 31, 2006. The main outcome measures were use of urgent coronary angiography and rate of concomitant coronary artery disease in patients with pericarditis. RESULTS There were 238 patients with a final diagnosis of acute pericarditis (mean age, 47.7±17.9 years; 157 [66.0%] were male). On the initial electrocardiogram, 146 patients (61.3%) had ST-segment elevation, and 92 (38.7%) had no ST-segment elevation. Coronary angiography was performed in 40 patients (16.8% of all patients); the frequency was 5-fold higher among those with ST-segment elevation (24.7% vs 4.3%; P P =.05). Characteristics associated with a higher likelihood of coronary angiography included typical anginal chest pain, ST-segment elevation, previous percutaneous coronary intervention, elevated troponin T values, diaphoresis, and male sex. Coronary angiography revealed concomitant mild to moderate coronary artery disease in 14 (35.0%) of the 40 patients who underwent this procedure. CONCLUSION Urgent coronary angiography is commonly performed in patients with acute pericarditis, particularly those with ST-segment elevation, typical myocardial infarction symptoms, and elevated troponin T values. Coronary artery disease was present angiographically in one-third of patients undergoing the procedure. Although patients with ST-segment elevation myocardial infarction must receive prompt reperfusion, clinicians must also consider the diagnosis of pericarditis to avoid unneeded coronary angiography.

Background Because of the expense of drug-eluting stents (DES) and associated adjuvant therapy, nonclinical, socioeconomic factors may be associated with DES use in clinical practice. Methods Data on 112,588 patients from the National Cardiovascular Data CathPCI Registry (NCDR) between 2004 and 2005 with “on-label” indications for DES were analyzed. Insurance status was categorized as No Insurance, Governmental, and Private Insurance. Hierarchical multivariable logistic regression analyses were used to evaluate the association between insurance status and DES use, after adjusting for patient and procedural characteristics. Results Drug-eluting stent use was >96% during the study period, with utilization significantly associated with insurance status. Compared with patients with Private Insurance, patients with No Insurance (odds ratio 0.44, 95% confidence interval 0.37-0.53) and Government Insurance (odds ratio 0.73, 95% confidence interval 0.67-0.80) were significantly less likely to receive a DES than a bare metal stent. Repeat analysis of patients Conclusions Despite the high penetration of DES, significant associations between insurance status and DES utilization were identified. This indicates that disparities in health care based on socioeconomic factors extend to DES utilization and highlights the need to address such disparities as novel therapies emerge.

Background Although the efficacy of platelet glycoprotein IIb/IIIa inhibitors (GPIIb/IIIa) in reducing complication rates during percutaneous coronary intervention (PCI) is well established, comparative studies assessing currently approved agents as administered in current practice are limited. We studied the clinical and length of stay (LOS) outcomes of patients undergoing PCI who received either abciximab or eptifibatide. Methods All patients undergoing elective, urgent, or emergency PCI at Mayo Clinic Rochester between November 17, 2000 and August 31, 2004 who received either abciximab or eptifibatide were included. Clinical, angiographic, and follow-up data were prospectively recorded in the Mayo Clinic PCI Registry; administrative data recorded LOS. We used logistic and Cox proportional hazard models to estimate the risk of adverse events and generalized linear modeling to predict LOS. Propensity score and standard risk adjustments were used to account for baseline differences. Results A total of 2123 PCI patients received eptifibatide and 951 received abciximab. The adjusted odds ratio for in-hospital death and myocardial infarction (MI) with eptifibatide was 0.80 (95% CI 0.56–1.14, P = 0.21) versus abciximab. Adjusted hazard ratios for death and MI and for death, MI, or target vessel revascularization during a median follow-up of 24.6 months were 0.84 (95% CI 0.68–1.02, P = 0.08) and 0.95 (95% CI 0.81–1.11, P = 0.53), respectively. Adjusted postprocedural LOS was similar at 3.4 days. Conclusion This large observational study found no evidence of a clinical or LOS advantage to physician choice of either abciximab or eptifibatide during PCI in contemporary practice.

We studied the relationship between longer delays from symptom onset to hospital presentation and the use of any reperfusion therapy, door-to-balloon time, and door-to-drug time.Cohort study of patients with ST-elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction from January 1, 1995 to December 31, 2004. Delay in hospital presentation was categorized into 1-hour intervals asor =1 hour,1-2 hours,2-3 hours, etc, up to11-12 hours. The study analyzed 3 groups: 440,398 patients for the association between delay and use of any reperfusion therapy; 67,207 patients for the association between delay and door-to-balloon time; 183,441 patients for the association between delay and door-to-drug time.In adjusted analyses, patients with longer delays between symptom onset and hospital presentation were less likely to receive any reperfusion therapy, had longer door-to-balloon times, and had longer door-to-needle times (all P.0001 for linear trend). For patients presentingor =1 hour,1-2 hours,2-3 hours,9-10 hours,10-11 hours, and11-12 hours after symptom onset, the use of any reperfusion therapy were 77%, 77%, 73%, 53%, 50%, and 46%, respectively. Door-to-balloon times were 99, 101, 106, 123, 125, and 123 minutes, respectively, and door-to-drug times were 33, 34, 36, 46, 44, and 47 minutes, respectively.Longer delays from symptom onset to hospital presentation were associated with reduced likelihood of receiving primary reperfusion therapy, and even among those treated, late presenters had significantly longer door-to-balloon and door-to-drug times.

Objectives The purpose of this study was to evaluate secular trends and factors associated with major femoral bleeding after percutaneous coronary intervention (PCI) in routine clinical practice during the past decade and to assess the impact of these complications on outcomes including mortality. Background Significant changes in patient demographic data, adjunctive pharmacotherapy, and access site management have occurred during the coronary stent era. Trends in major vascular complications after PCI during this time have not been well characterized. Methods Consecutive patients who underwent transfemoral PCI from 1994 to 2005 at the Mayo Clinic (n = 17,901) were studied. Patients were divided into 3 groups: Group 1 (1994 to 1995, n = 2,441); Group 2 (1996 to 1999, n = 6,207); and Group 3 (2000 to 2005, n = 9,253). Results The incidence of major femoral bleeding complications decreased (from 8.4% to 5.3% to 3.5%; p l 0.001). Reductions in sheath size, intensity and duration of anticoagulation with heparin, and procedure time were observed (p l 0.001), and multivariate analysis confirmed each as an independent predictor of complications (p l 0.001). Adverse outcomes of major femoral bleeding included prolonged hospital stay (mean 4.5 vs. 2.7 days; p l 0.0001) and increased requirement for blood transfusion (39% vs. 4.7%; p l 0.0001). Major femoral bleeding and blood transfusion were both associated with decreased long-term survival, driven by a significant increase in 30-day mortality (p l 0.001 for both). Conclusions We noted a marked decline in the incidence of major femoral bleeding after PCI over the past decade. Mortality associated with these bleeding complications and with blood transfusion remains a significant issue.

Objectives We sought to describe the rationale and methods for Door-to-Balloon (D2B): An Alliance for Quality, an international effort organized by the American College of Cardiology in partnership with the American Heart Association and 37 other organizations to rapidly translate research about how best to achieve outstanding D2B times for patients with ST-segment elevation myocardial infarction (STEMI) into practice. Background The D2B time, the time between hospital arrival and primary percutaneous coronary intervention for patients with STEMI, is strongly associated with the likelihood of survival, yet the majority of patients are not treated within the guideline-recommended time of ≤90 min. Recent research has revealed key and underused strategies that are associated with achieving faster D2B times. Methods The D2B Alliance has enrolled approximately 1,000 hospitals. Its goal is to achieve a D2B time of ≤90 min for at least 75% of non-transferred patients. The key strategies chosen by the D2B Alliance include having the emergency medicine physician activate the catheterization laboratory with a single call, having the team prepared within 20 to 30 min of the call; rapid data feedback; a team-based approach; and administrative support. The use of a pre-hospital electrocardiogram by emergency medical services personnel to activate the catheterization laboratory was also noted as an additional optional strategy. The project has many approaches to promote participation and adoption of effective strategies. An evaluation component is also described. Conclusions The design of the D2B: An Alliance for Quality, a novel campaign to improve D2B time, is described.

Drug-eluting stents (DESs) are used in >80% of percutaneous coronary intervention (PCI) procedures; however, up to 2/3 are used for off-label indications. Factors associated with DES use in patients with ST-elevation myocardial infarction (STEMI) are not known in contemporary clinical practice. We analyzed temporal trends, geographic patterns, and sociodemographic factors associated with off-label use of DESs in patients undergoing primary PCI for STEMI from July 2004 to March 2006 in the National Cardiovascular Data Registry (NCDR). The main outcome of this study was receipt of any DES, and the candidate independent variables were sociodemographic, hospital, clinical, and procedural variables. We also analyzed temporal trends and geographic patterns for use of DESs. A total of 30,235 patients with STEMI underwent primary PCI with use of DESs (84%) or bare metal stents (16%). Adoption of DESs was rapid but varied widely as a function of geographic location. After adjusting for clinical and procedural variables, older age was associated with lower use (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.91 to 0.98), whereas white race (OR 1.14, 95% CI 1.03 to 1.27), commercial insurance (OR 1.22, 95% CI 1.11 to 1.34), and the west census region (OR 1.37, 95% CI 1.04 to 1.81) were associated with higher use of DESs. In conclusion, adoption of DESs was rapid in patients with STEMI, but geographic location and sociodemographic and hospital factors were associated with the use DESs.

Objectives We implemented the Mayo Clinic ST-segment elevation myocardial infarction (STEMI) protocol and evaluated the timeliness of reperfusion therapy during off hours versus regular hours. Background Patients with STEMI who present during off hours have longer door-to-balloon times and door-to-needle times. Methods The Mayo STEMI protocol was implemented in May 2004 to optimize timeliness of reperfusion therapy for STEMI patients presenting to Saint Marys Hospital, a tertiary facility with on-site percutaneous coronary intervention (PCI), and for those presenting to 28 regional hospitals located up to 150 miles away from Saint Marys Hospital. We compared door-to-balloon times and door-to-needle times for 597 consecutive patients who presented during off hours (weekdays from 5 pm to 7 am and any time on weekends or holidays) versus regular hours (weekdays from 7 am to 5 pm). In 2003, prior to implementing the protocol, median door-to-balloon time at Saint Marys Hospital was 85 min during regular hours and 98 min during off hours. Results Among 258 patients who presented to Saint Marys Hospital, median door-to-balloon time was 65 min during regular hours versus 74 min during off hours (p = 0.085). Among 105 patients transferred from regional hospitals for primary PCI, median door-to-balloon time was 118 min during regular hours versus 114 min during off hours (p = 0.15). Among 131 patients treated with fibrinolytic therapy at regional hospitals, median door-to-needle time was 21 min during regular hours versus 26 min during off hours (p = 0.067). Conclusions The Mayo Clinic STEMI protocol demonstrates the rapid times that can be achieved through coordinated systems of care for STEMI patients presenting during off hours and regular hours.

Use of ultrasound guidance for regional anesthesia has grown in popularity recently. Advocates claim many benefits, including higher success rates, a decrease in block performance time, a decrease in onset time, a higher quality block, the ability to use less local anesthetic, and a longer duration of block. Many also believe that the ability to visualize critical structures decreases the rate of complications. This article reviews the current evidence for these claimed benefits. In addition, discussion of how clinical practice patterns are affected and how ultrasound can add to the knowledge base of regional anesthesia practice is presented.

OBJECTIVE To compare outcomes among patients receiving eptifibatide or abciximab during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) with ST elevation or new left bundle branch block. PATIENTS AND METHODS From January 1999 through January 2004, 576 patients underwent primary PCI and received adjunctive glycoprotein IIb/IIIa receptor antagonists. Propensity scores were used to adjust for baseline differences between groups. Logistic regression and Cox proportional hazards were used to model the association between choice of glycoprotein IIb/IIIa receptor antagonist and adverse events. RESULTS Abciximab was given to 327 patients (57%) and eptifibatide to 249 (43%). Observed rates of in-hospital death or MI did not differ between groups (eptifibatide, 6%; abciximab, 5%; P=.95). This result persisted with adjustment for various patient characteristics (adjusted odds ratio, 1.03; 95% confidence interval, 0.40-2.65; P=.95). Kaplan-Meier estimated rates of death, MI, or target vessel revascularization at 1-year follow-up were 20.9% with eptifibatide and 22.3% with abciximab. The adjusted hazard ratio for the composite end point during a median follow-up of 12 months was 1.36 (95% confidence interval, 0.89-2.07; P=.16). CONCLUSION In this observational analysis, outcomes were similar with use of either abciximab or eptifibatide among patients undergoing primary PCI for acute MI. Additional comparative research is warranted to confirm these results.

During postural responses to perturbations, horizontal plane forces generated by the cat hindlimb are stereotypically directed either towards or away from the animal's center of mass, independent of perturbation direction. We used a static, three-dimensional musculoskeletal model of the hindlimb to investigate possible biomechanical determinants of this "force constraint strategy." We hypothesized that directions in which the hindlimb can produce large forces are preferentially used in postural control. We computed feasible force sets (FFSs) based on hindlimb configurations of three cats during postural equilibrium tasks and compared them to horizontal plane postural force directions. The grand mean FFS was bimodal, with maxima near the posterior-anterior axis (-86+/-8 degrees and 71+/-4 degrees ), and minima near the medial-lateral axis (177+/-8 degrees and 8+/-8 degrees ). Experimental postural force directions clustered near both maxima; there were no medial postural forces near the absolute minimum. However, the medians of the anterior and posterior postural force direction histograms in the right hindlimb were rotated counter-clockwise from the FFS maxima (p

OBJECTIVE To study the safety of a protocol that allows ambulation 1 hour after diagnostic cardiac catheterization with a transfemoral approach using a 5F catheter system. PATIENTS AND METHODS A total of 1005 consecutive patients (1009 procedures) undergoing outpatient diagnostic cardiac catheterization with a transfemoral approach using a 5F catheter system at the Mayo Clinic in Rochester, Minn, were included in this study from January 1, 2004, to August 31, 2005. All patients underwent standard manual compression to achieve hemostasis and were ambulated after 1 hour of bed rest. RESULTS The mean age of the patients was 64.5 years, and 62% were male. Minor vascular complications occurred in 33 procedures (3.3%), including 14 hematomas (1.4%) less than 4 cm and 19 cases of rebleeding (1.9%) that required repeated manual compression. Only 1 patient (0.1%) had a hematoma greater than 4 cm. No patient had a major complication, such as surgical repair, red blood cell transfusion, retroperitoneal bleeding, formation of an arteriovenous fistula or pseudoaneurysm, arterial occlusion, or an infection. CONCLUSIONS Ambulation 1 hour after diagnostic cardiac catheterization with a transfemoral approach using a 5F catheter system is safe and associated with low rates of vascular complications. This strategy may improve patient comfort, reduce resource utilization, and be preferable to use of vascular closure devices.

Objectives We sought to compare clinical outcomes of elective percutaneous coronary intervention (PCI) and primary PCI for ST-segment elevation myocardial infarction (STEMI) at a community hospital without onsite cardiac surgery to those at a tertiary center with onsite cardiac surgery. Background Disagreement exists about whether hospitals with cardiac catheterization laboratories, but without onsite cardiac surgery, should develop PCI programs. Primary PCI for STEMI at hospitals without onsite cardiac surgery have achieved satisfactory outcomes; however, elective PCI outcomes are not well defined. Methods A total of 1,007 elective PCI and primary PCI procedures performed from March 1999 to August 2005 at the Immanuel St. Joseph’s Hospital–Mayo Health System (ISJ) in Mankato, Minnesota, were matched one-to-one with those performed at St. Mary’s Hospital (SMH) in Rochester, Minnesota. Strict protocols were followed for case selection and PCI program requirements. Clinical outcomes (in-hospital procedural success, death, any myocardial infarction, Q-wave myocardial infarction, and emergency coronary artery bypass surgery) and follow-up survival were compared between groups. Results Among 722 elective PCIs, procedural success was 97% at ISJ compared with 95% at SMH (p = 0.046). Among 285 primary PCIs for STEMI, procedural success was 93% at ISJ and 96% at SMH (p = 0.085). No patients at ISJ undergoing PCI required emergent transfer for cardiac surgery. Survival at two years’ follow-up by treatment location was similar for patients with elective PCI and primary PCI. Conclusions Similar clinical outcomes for elective PCI and primary PCI were achieved at a community hospital without onsite cardiac surgery compared with those at a tertiary center with onsite cardiac surgery using a prospective, rigorous protocol for case selection and PCI program requirements.

Objective To compare the safety and efficacy of percutaneous coronary intervention (PCI) for acute myocardial infarction performed at a hospital without cardiac surgical capability with PCI performed for acute myocardial infarction at a center with on-site surgery. Patients and Methods We included patients with acute myocardial infarction in whom PCI was performed from March 1, 2000, through May 31, 2002, at a community hospital (Immanuel St Joseph's) without on-site surgery. The procedural success, in-hospital adverse cardiac events, and 6-month follow-up were compared with those of PCI performed for acute myocardial infarction in matched controls from January 1, 2000, through February 28, 2002, at a center with cardiac surgery (Saint Marys Hospital). Results One hundred sixty patients (and 160 matched controls) underwent PCI for acute myocardial infarction. The procedural success rate was high and similar for the 2 groups (96% vs 95%; P =.79). In-hospital mortality, Q-wave myocardial infarction, and target vessel revascularization were low and similar for the 2 groups. No patient was referred for emergency coronary artery bypass graft surgery for failed PCI. Six-month survival from all-cause mortality was 96% for the Immanuel St Joseph's group and 94% for the Saint Marys Hospital group ( P =.92). Subgroup analysis of patients with primary PCI for ST-segment elevation acute myocardial infarction revealed high procedural success and low and similar rates of major cardiac adverse events in the 2 groups. Conclusion This study shows that PCI for acute myocardial infarction can be performed safely and effectively in a community hospital without on-site cardiac surgery.