The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation.

The Fontan Udenafil Exercise Longitudinal (FUEL) trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with Fontan physiology. However, it is not known how the initiation of phosphodiesterase 5 inhibitor therapy affects heart rate and blood pressure in this population. These data may help inform patient selection and monitoring after the initiation of udenafil therapy. The purpose of this study is to evaluate the effects of udenafil on vital signs in the cohort of patients enrolled in the FUEL trial. This international, multicenter, randomized, double-blind, placebo-controlled trial of udenafil included adolescents with single ventricle congenital heart disease who had undergone Fontan palliation. Changes in vital signs (heart rate [HR], systolic [SBP] and diastolic blood pressure [DBP]) were compared both to subject baseline and between the treatment and the placebo groups. Additional exploratory analyses were performed to evaluate changes in vital signs for prespecified subpopulations believed to be most sensitive to udenafil initiation. Baseline characteristics were similar between the treatment and placebo cohorts (n = 200 for each). The groups demonstrated a decrease in HR, SBP, and DBP 2 hours after drug/placebo administration, except SBP in the placebo group. There was an increase in SBP from baseline to after 6-min walk test in the treatment and placebo groups, and the treatment group showed an increase in HR (87.4 ± 15.0 to 93.1 ± 19.4 beats/min, p <0.01) after exercise. When comparing changes from baseline to the 26-week study visit, small decreases in both SBP (-1.9 ± 12.3 mm Hg, p = 0.03) and DBP (-3.0 ± 9.6 mm Hg, p <0.01) were seen in the treatment group. There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration.

Congenital Pulmonic Valve Dysfunction Treated With SAPIEN 3 Transcatheter Heart Valve (from the COMPASSION S3 Trial).

Significant pulmonary regurgitation (PR) and pulmonary stenosis are common after surgical repair of some congenital heart defects. This prospective, single-arm, multicenter trial enrolled patients who underwent transcatheter heart valve (THV) implantation with a SAPIEN 3 valve to treat dysfunctional right ventricular outflow tract (RVOT) conduits or pulmonic surgical valves (≥ moderate PR and/or mean RVOT gradient ≥35 mm Hg). The primary end point was a nonhierarchical composite of THV dysfunction at 1 year comprising RVOT reintervention, ≥ moderate total PR, and mean RVOT gradient >40 mm Hg. A performance goal of <25% of upper confidence interval (CI) was prespecified for the primary end point, using a 95% exact binomial CI. Patients (n = 58) were enrolled between July 5, 2016 and July 17, 2018, with mean age of 32 years. Prestenting was performed in 53.4%. At discharge, the device success was 98.1% (single valve without explant, < moderate PR, gradient <35 mm Hg). At 30 days, there were no major adjudicated adverse clinical events. At 1 year, the primary end point composite was 4.3% (95% CI 0.5 to 14.5). The composite components were 0% (0 of 56) RVOT reintervention, 2.1% (1 of 47) ≥ moderate PR, and 2.1% (1 of 48) mean RVOT gradient >40 mm Hg. No mortality, endocarditis, thrombosis, or stent fracture were reported at 1 year. In conclusion, the SAPIEN 3 THV was safe and effective in patients with dysfunctional RVOT conduits or previously implanted valves in the pulmonic position to 1 year. Clinical trial registration: NCT02744677; https://clinicaltrials.gov/ct2/show/NCT02744677.

Variability in radiation dose and image quality: A comparison across fluoroscopy-system vendors, generations of equipment and institutions.

OBJECTIVES: To evaluate differences in radiation dose and image quality across institutions, fluoroscope vendors and generations of fluoroscopes for pediatric cardiac catheterization. BACKGROUND: Increased recognition of the potentially harmful effects of ionizing radiation has spurred technological advances in fluoroscopes, as well as increased focus on optimizing fluoroscope performance. There is currently little understanding of variability in the dose-image quality relationship across institutions, fluoroscope vendor and/or generation of equipment. METHODS: We evaluated latest generation fluoroscopes from Phillips, Siemens, GE, and Toshiba, and an older generation Phillips fluoroscope (release date 2003) at three different institutions. Radiation dose was measured using an anthropomorphic dose-assessment phantom with effective dose in mSv estimated from Monte Carlo simulations. Image quality phantom images were scored on a 12-point scale by three blinded reviewers. RESULTS: Fluoroscope effective doses ranged from 0.04 to 0.14 mSv/1,000 pulses for fluoroscopy with associated composite image quality scores ranging from 8.0 ± 0.6 to 10.4 ± 1.3. For cineangiography, effective doses ranged from 0.17 to 0.57 mSv/1,000 frames with image quality scores ranging from 10.1 ± 0.3 to 11.1 ± 0.3. There was modest correlation between effective dose and image quality (r = 0.67, P = 0.006). The older generation fluoroscope delivered consistently higher doses than the newer generation systems (2.3- to 3.5-fold higher for fluoroscopy; 1.1- to 3.4-fold higher for cineangiography) without appreciable differences in image quality. CONCLUSION: Technological advances have markedly improved fluoroscope performance. Comparing latest generation systems across vendors and institutions, we found variability in the dose-IQ relationship and speculate that this reflects both equipment and institutional optimization practices.

Nutrition and health in amphibian husbandry.

Amphibian biology is intricate, and there are many inter-related factors that need to be understood before establishing successful Conservation Breeding Programs (CBPs). Nutritional needs of amphibians are highly integrated with disease and their husbandry needs, and the diversity of developmental stages, natural habitats, and feeding strategies result in many different recommendations for proper care and feeding. This review identifies several areas where there is substantial room for improvement in maintaining healthy ex situ amphibian populations specifically in the areas of obtaining and utilizing natural history data for both amphibians and their dietary items, achieving more appropriate environmental parameters, understanding stress and hormone production, and promoting better physical and population health. Using a scientific or research framework to answer questions about disease, nutrition, husbandry, genetics, and endocrinology of ex situ amphibians will improve specialists' understanding of the needs of these species. In general, there is a lack of baseline data and comparative information for most basic aspects of amphibian biology as well as standardized laboratory approaches. Instituting a formalized research approach in multiple scientific disciplines will be beneficial not only to the management of current ex situ populations, but also in moving forward with future conservation and reintroduction projects. This overview of gaps in knowledge concerning ex situ amphibian care should serve as a foundation for much needed future research in these areas.

Vitamin A values of wild-caught Cuban tree frogs (Osteopilus septentrionalis) and marine toads (Rhinella marina) in whole body, liver, and serum.

Recent issues surrounding captive amphibians are often nutritionally related problems, such as hypovitaminosis A. Although supplementation of frogs with vitamin A is a topic of investigation, the underlying issue is understanding vitamin A metabolism in amphibian species. To develop a range of "normal" vitamin A concentrations for captive amphibians, baseline vitamin A concentrations must be established in wild amphibian species. In this study, two species, Cuban tree frogs (Osteopilus septentrionalis; n = 59) and marine toads (Rhinella marina; n = 20) were collected from the wild as part of an invasive species control program at Zoo Miami, Miami, Florida. Serum, liver, and whole body samples were analyzed for vitamin A content. The Cuban tree frogs showed higher concentrations on average of vitamin A in serum (82.8 ppb), liver (248.3 IU/g), and whole body (5474.7 IU/kg) samples compared with marine toads (60.1 ppb; 105.3 IU/g; 940.7 IU/kg, respectively), but differences were not significant (P = 0.22). What can be considered "normal" values of vitamin A concentrations across different amphibian species requires further investigation. Although all amphibians collected in this study appeared healthy, a larger sample size of animals, with known health histories and diets, may provide stronger evidence of normal expectations.

Improving overtriage of aeromedical transport in trauma: a regional process improvement initiative.

BACKGROUND: Aeromedical transport (AMT) is an effective but costly means of rescuing critically injured patients. Although studies have shown that it improves survival to hospital discharge compared with ground transportation, an efficient threshold or universal criteria for this mode of transport remains to be established. Herein, we examined the effect of implementing a Trauma Advisory Committee (TAC) initiative focused on reducing AMT overtriage (OT) rates. METHODS: TAC outreach coordinators implemented a process improvement (PI) initiative and collected data prospectively from January 2007 to December 2011. OT was defined as patients who were airlifted from scene and later discharged from the emergency department. Serving as liaisons to surrounding counties, TAC outreach coordinators conducted quarterly PI meetings with local emergency medical service agencies. Patients were grouped into those who were airlifted from TAC counties versus counties outside TAC's jurisdiction (non-TAC). Standard statistical methods were used. RESULTS: From 2007 to 2011, 3,349 patients were airlifted from 30 counties, 1,427 (43%) from TAC counties and 1,922 (57%) from non-TAC counties. The OT rates from TAC counties declined compared with non-TAC counties each year and reached statistical significance in 2008 (17% vs. 23%, p < 0.05), 2009 (11% vs. 17%m p < 0.05), and 2011 (6% vs. 12%, p < 0.05). The reduction in OT continued over the study duration, with improvement in TAC counties compared with previous years. CONCLUSION: Implementation of a regional TAC PI initiative focused on OT issues led to a more efficient use of AMT. LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.

Full-scale regional exercises: closing the gaps in disaster preparedness.

BACKGROUND: Man-made (9/11) and natural (Hurricane Katrina) disasters have enlightened the medical community regarding the importance of disaster preparedness. In response to Joint Commission requirements, medical centers should have established protocols in place to respond to such events. We examined a full-scale regional exercise (FSRE) to identify gaps in logistics and operations during a simulated mass casualty incident. METHODS: A multiagency, multijurisdictional, multidisciplinary exercise (FSRE) included 16 area hospitals and one American College of Surgeons-verified Level I trauma center (TC). The scenario simulated a train derailment and chemical spill 20 miles from the TC using 281 moulaged volunteers. Third-party contracted evaluators assessed each hospital in five areas: communications, command structure, decontamination, staffing, and patient tracking. Further analysis examined logistic and operational deficiencies. RESULTS: None of the 16 hospitals were compliant in all five areas. Mean hospital compliance was 1.9 (± 0.9 SD) areas. One hospital, unable to participate because of an air conditioner outage, was deemed 0% compliant. The most common deficiency was communications (15 of 16 hospitals [94%]; State Medical Asset Resource Tracking Tool system deficiencies, lack of working knowledge of Voice Interoperability Plan for Emergency Responders radio system) followed by deficient decontamination in 12 (75%). Other deficiencies included inadequate staffing based on predetermined protocols in 10 hospitals (63%), suboptimal command structure in 9 (56%), and patient tracking deficiencies in 5 (31%). An additional 11 operational and 5 logistic failures were identified. The TC showed an appropriate command structure but was deficient in four of five categories, with understaffing and a decontamination leak into the emergency department, which required diversion of 70 patients. CONCLUSION: Communication remains a significant gap in the mass casualty scenario 10 years after 9/11. Our findings demonstrate that tabletop exercises are inadequate to expose operational and logistic gaps in disaster response. FSREs should be routinely performed to adequately prepare for catastrophic events.

Mycobacterium kansasii infection in a bontebok (Damaliscus pygaragus dorcas) herd: diagnostic challenges in differentiating from the Mycobacterium tuberculosis complex.

Two adult female bontebok (Damaliscus pygarus dorcas) were euthanized because of signs of pneumonia and weakness (case 1), and a nonresponsive lameness with draining fistula (case 2). Necropsy findings were similar in both cases and consisted of disseminated granulomatous lesions in the liver, kidneys, spleen, lungs, pleural surfaces, and multiple lymph nodes. Mycobacterium kansasii was isolated from both cases after multiple attempts on a variety of samples by two laboratories. The remaining four animals in the herd were tested for antibody responses using the Chembio ElephantTB STAT-PAK, DPP VetTB kits, and multi-antigen print immunoassay (MAPIA), for immune reaction using the intradermal tuberculin test, and by tracheal wash cultures, and thoracic radiographs. Banked serum samples collected in 2005 and obtained from the original institution, revealed 1/9 (11.11%) seropositive animals using the three immunoassays. Retesting the current herd in 2008 showed 2/6 (33.33%) seropositive animals by the three tests, with MAPIA demonstrating antibody reactivity to MPB83 and MPB70 proteins. Inconsistent intradermal tuberculin test results, cross-reactivity in serologic assays designed for tuberculosis detection, difficulty in obtaining definitive identification by culture, and inability to identify a source of infection created challenges in distinguishing the atypical mycobacteriosis due to M. kansasii from the initially suspected tuberculous infection in this herd. Owing to regulatory considerations, differences in host-to-host transmission, and source of infection between Mycobacterium tuberculosis complex and nontuberculous mycobacteria, correct diagnosis is crucial for management of these diseases in wildlife species.