Incidence of supraventricular tachycardia after inhaled short-acting beta agonist treatment in children.

INTRODUCTION: Albuterol can trigger supraventricular tachycardia (SVT). The clinical characteristics, incidence, and risk factors of SVT after inhaled SABA treatment in children are currently unknown. Through review of regional care delivery, we will describe cases of SVT during asthma treatment in hospital-based settings, define the incidence of SVT in our population, and evaluate risk factors of SABA-induced SVT. METHODS: We identified hospital-based care episodes of children 0-18 years old between 2006 and 2015 recorded in the Intermountain Healthcare EDW with either 1) diagnosis codes for both asthma and SVT or 2) both SABA and adenosine listed as billed medications. Controls were matched with cases by age and sex to determine risk factors for SVT after SABA using conditional logistic regression. RESULTS: Of 93 care episodes meeting criteria, we found 7 cases of SVT after SABA treatment in 6 patients over 10 years. In our population, the incidence of SVT is 3.9 per 10,000 episodes of SABA treatment, and 5.1 per 10,000 children with asthma receiving hospital-based asthma care. Two episodes of SVT followed treatment with only levalbuterol, three after only albuterol, and two after both albuterol and levalbuterol treatment. Five cases of SVT were converted to sinus rhythm with adenosine, one converted with synchronized electrical cardioversion, and one resolved spontaneously. No cases of SVT led to death. No examined variables were associated with SABA-induced SVT. CONCLUSIONS: SVT is rare during hospital-based treatment for acute asthma using inhaled SABAs and has low morbidity and mortality.

Identification of Pediatric Patients With Celiac Disease Based on Serology and a Classification and Regression Tree Analysis.

BACKGROUND & AIMS: Celiac disease is detected using serology and endoscopy analyses. We used multiple statistical analyses of a geographically isolated population in the United States to determine whether a single serum screening can identify individuals with celiac disease. METHODS: We performed a retrospective study of 3555 pediatric patients (18 years old or younger) in the intermountain West region of the United States from January 1, 2008, through September 30, 2013. All patients had undergone serologic analyses for celiac disease, including measurement of antibodies to tissue transglutaminase (TTG) and/or deamidated gliadin peptide (DGP), and had duodenal biopsies collected within the following year. Modified Marsh criteria were used to identify patients with celiac disease. We developed models to identify patients with celiac disease using logistic regression and classification and regression tree (CART) analysis. RESULTS: Single use of a test for serum level of IgA against TTG identified patients with celiac disease with 90% sensitivity, 90% specificity, a 61% positive predictive value (PPV), a 90% negative predictive value, and an area under the receiver operating characteristic curve value of 0.91; these values were higher than those obtained from assays for IgA against DGP or IgG against TTG plus DGP. Not including the test for DGP antibody caused only 0.18% of celiac disease cases to be missed. Level of TTG IgA 7-fold the upper limit of normal (ULN) identified patients with celiac disease with a 96% PPV and 100% specificity. Using CART analysis, we found a level of TTG IgA 3.2-fold the ULN and higher to most accurately identify patients with celiac disease (PPV, 89%). Multivariable CART analysis showed that a level of TTG IgA 2.5-fold the ULN and higher was sufficient to identify celiac disease in patients with type 1 diabetes (PPV, 88%). Serum level of IgA against TTG in patients with versus those without trisomy 21 did not affect diagnosis predictability in CART analysis. CONCLUSIONS: In a population-based study, we found that serum level of IgA against TTG can identify patients with celiac disease with PPVs of about 90%. Predictive values increase greatly when levels are markedly above the ULN or when the assay is used in combination with other variables. Measurement of IgG against TTG or DGP does not increase the accuracy of detection of celiac disease based against TTG IgA levels. There is a low risk of false-positive results from serologic analysis in patients with type I diabetes or persistent increases in antibody against TTG on repeat testing.

The relationship between performance on the Infectious Diseases In-Training and Certification Examinations.

BACKGROUND: The Infectious Diseases Society of America In-Training Examination (IDSA ITE) is a feedback tool used to help fellows track their knowledge acquisition during fellowship training. We determined whether the scores on the IDSA ITE and from other major medical knowledge assessments predict performance on the American Board of Internal Medicine (ABIM) Infectious Disease Certification Examination. METHODS: The sample was 1021 second-year fellows who took the IDSA ITE and ABIM Infectious Disease Certification Examination from 2008 to 2012. Multiple regression analysis was used to determine if ABIM Infectious Disease Certification Examination scores were predicted by IDSA ITE scores, prior United States Medical Licensing Examination (USMLE) scores, ABIM Internal Medicine Certification Examination scores, fellowship director ratings of medical knowledge, and demographic variables. Logistic regression was used to evaluate if these same assessments predicted a passing outcome on the certification examination. RESULTS: IDSA ITE scores were the strongest predictor of ABIM Infectious Disease Certification Examination scores (ß = .319), followed by prior ABIM Internal Medicine Certification Examination scores (ß = .258), USMLE Step 1 scores (ß = .202), USMLE Step 3 scores (ß = .130), and fellowship directors' medical knowledge ratings (ß = .063). IDSA ITE scores were also a significant predictor of passing the Infectious Disease Certification Examination (odds ratio, 1.017 [95% confidence interval, 1.013-1.021]). CONCLUSIONS: The significant relationship between the IDSA ITE score and performance on the ABIM Infectious Disease Certification Examination supports the use of the ITE as a valid feedback tool in fellowship training.

Myocardial, smooth muscle, nephron, and collecting duct gene targeting reveals the organ sites of endothelin A receptor antagonist fluid retention.

Endothelin-1 binding to endothelin A receptors (ETA) elicits profibrogenic, proinflammatory, and proliferative effects that can promote a wide variety of diseases. Although ETA antagonists are approved for the treatment of pulmonary hypertension, their clinical utility in several other diseases has been limited by fluid retention. ETA blocker-induced fluid retention could be due to inhibition of ETA activation in the heart, vasculature, and/or kidney; consequently, the current study was designed to define which of these sites are involved. Mice were generated with absence of ETA specifically in cardiomyocytes (heart), smooth muscle, the nephron, the collecting duct, or no deletion (control). Administration of the ETA antagonist ambrisentan or atrasentan for 2 weeks caused fluid retention in control mice on a high-salt diet as assessed by increases in body weight, total body water, and extracellular fluid volume (using impedance plethysmography), as well as decreases in hematocrit (hemodilution). Mice with heart ETA knockout retained fluid in a similar manner as controls when treated with ambrisentan or atrasentan. Mice with smooth muscle ETA knockout had substantially reduced fluid retention in response to either ETA antagonist. Mice with nephron or collecting duct ETA disruption were completely prevented from ETA blocker-induced fluid retention. Taken together, these findings suggest that ETA antagonist-induced fluid retention is due to a direct effect of this class of drug on the collecting duct, is partially related to the vascular action of the drugs, and is not due to alterations in cardiac function.

Disruption of the endothelin A receptor in the nephron causes mild fluid volume expansion.

BACKGROUND: Endothelin, via endothelin A receptors (ETA), exerts multiple pathologic effects that contribute to disease pathogenesis throughout the body. ETA antagonists ameliorate many experimental diseases and have been extensively utilized in clinical trials. The utility of ETA blockers has been greatly limited, however, by fluid retention, sometimes leading to heart failure or death. To begin to examine this issue, the effect of genetic disruption of ETA in the nephron on blood pressure and salt handling was determined. METHODS: Mice were generated with doxycycline-inducible nephron-specific ETA deletion using Pax8-rtTA and LC-1 transgenes on the background of homozygous loxP-flanked ETA alleles. Arterial pressure, Na metabolism and measures of body fluid volume status (hematocrit and impedance plethysmography) were assessed. RESULTS: Absence of nephron ETA did not alter arterial pressure whether mice were ingesting a normal or high Na diet. Nephron ETA disruption did not detectably affect 24 hr Na excretion or urine volume regardless of Na intake. However, mice with nephron ETA knockout that were fed a high Na diet had mild fluid retention as evidenced by an increase in body weight and a fall in hematocrit. CONCLUSIONS: Genetic deletion of nephron ETA causes very modest fluid retention that does not alter arterial pressure. Nephron ETA, under normal conditions, likely do not play a major role in regulation of Na excretion or systemic hemodynamics.

Differential Item Functioning Analysis of United States Medical Licensing Examination Step 1 Items.

PURPOSE: Previous studies have examined and identified demographic group score differences on United States Medical Licensing Examination (USMLE) Step examinations. It is necessary to explore potential etiologies of such differences to ensure fairness of examination use. Although score differences are largely explained by preceding academic variables, one potential concern is that item-level bias may be associated with remaining group score differences. The purpose of this 2019-2020 study was to statistically identify and qualitatively review USMLE Step 1 exam questions (items) using differential item functioning (DIF) methodology. METHOD: Logistic regression DIF was used to identify and classify the effect size of DIF on Step 1 items meeting minimum sample size criteria. After using DIF to flag items statistically, subject matter expert (SME) review was used to identify potential reasons why items may have performed differently between racial and gender groups, including characteristics such as content, format, wording, context, or stimulus materials. USMLE SMEs reviewed items to identify the group difference they believed was present, if any; articulate a rationale behind the group difference; and determine whether that rationale would be considered construct relevant or construct irrelevant. RESULTS: All identified DIF rationales were relevant to the constructs being assessed and therefore did not reflect item bias. Where SME-generated rationales aligned with statistical differences (flags), they favored self-identified women on items tagged to women's health content categories and were judged to be construct relevant. CONCLUSIONS: This study did not find evidence to support the hypothesis that group-level performance differences beyond those explained by prior academic performance variables are driven by item-level bias. Health professions examination programs have an obligation to assess for group differences, and when present, investigate to what extent, if any, measurement bias plays a role.

Traumatic stress disorders following first-trimester spontaneous abortion.

Provide counsel and support to women after a spontaneous abortion. Research indicates that many women will talk with their physician about their emotional distress and that physicians provide good information after the spontaneous abortion. Evaluate women for acute stress disorder (ASD) after a spontaneous abortion. Research found that women reporting physical, emotional, or sexual abuse are more likely to experience ASD. Patients should be assessed for post-traumatic stress disorder in follow-up visits 1 month after the initial visit. Research has found that up to 25% of women meet criteria for PTSD 1 month post the spontaneous abortion and 7% met criteria at 4 months. Physicians should refer women who are experiencing traumatic stress to a behavioral health professional.

Hyperbaric oxygen inhibits ischemia-reperfusion-induced neutrophil CD18 polarization by a nitric oxide mechanism.

BACKGROUND: Hyperbaric oxygen decreases ischemia-reperfusion-induced neutrophil/intercellular adhesion molecule-1 adhesion by blocking CD18 polarization. The purpose of this study was to evaluate whether this hyperbaric oxygen effect is nitric oxide dependent and to determine whether nitric oxide synthase is required. METHODS: A gracilis muscle flap was raised in nine groups of male Wistar rats. Global ischemic injury was induced by clamping the gracilis muscle pedicle artery and vein for 4 hours. The hyperbaric oxygen treatment consisted of 100% oxygen at 2.5 atm absolute during the last 90 minutes of ischemia. Groups were repeated with and without various nitric oxide synthase inhibitors and carboxy-2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (C-PTIO), a nitric oxide scavenger. Normal neutrophils were exposed to activated plasma on intercellular adhesion molecule-1-coated coverslips (percentage adherent) and labeled with fluorescein isothiocyanate/antirat-CD11b for confocal microscopy (percentage polarized). The percentage of adherent and polarized cells was reported as mean + or - SEM. Statistical analysis was by analysis of variance. A value of p < or = 0.05 was considered significant. RESULTS: C-PTIO-treated ischemia-reperfusion/hyperbaric oxygen plasma showed a significant increase in the percentage polarization of CD18 compared with ischemia-reperfusion/hyperbaric oxygen-untreated plasma from 4.1 + or - 2.5 percent to 33.7 + or - 7.7 percent (p < or = 0.05). The nitric oxide scavenger C-PTIO also increased the percentage of adherent cells from 1.6 + or - 0.4 percent to 20.3 + or - 5.9 percent (p < or = 0.05). Administration of N-nitro-L-arginine methyl ester and other nitric oxide synthase inhibitors before hyperbaric oxygen treatment restored neutrophil adhesion and CD18 polarization to ischemia-reperfusion control values, significantly greater than ischemia-reperfusion/hyperbaric oxygen alone. CONCLUSION: These results suggest that the hyperbaric oxygen reduction of ischemia-reperfusion-induced neutrophil polarization of CD18 and adherence to intercellular adhesion molecule-1 is mediated through a nitric oxide mechanism that requires nitric oxide synthase.

Effects of large-scale Amazon forest degradation on climate and air quality through fluxes of carbon dioxide, water, energy, mineral dust and isoprene.

Loss of large areas of Amazonian forest, through either direct human impact or climate change, could exert a number of influences on the regional and global climates. In the Met Office Hadley Centre coupled climate-carbon cycle model, a severe drying of this region initiates forest loss that exerts a number of feedbacks on global and regional climates, which magnify the drying and the forest degradation. This paper provides an overview of the multiple feedback process in the Hadley Centre model and discusses the implications of the results for the case of direct human-induced deforestation. It also examines additional potential effects of forest loss through changes in the emissions of mineral dust and biogenic volatile organic compounds. The implications of ecosystem-climate feedbacks for climate change mitigation and adaptation policies are also discussed.