Design and implementation of the hospital airway resuscitation trial.

Guidelines for the management of in-hospital cardiac arrest resuscitation are often drawn from evidence generated in out-of-hospital cardiac arrest populations and applied to the in-hospital setting. Approach to airway management during resuscitation is one example of this phenomenon, with the recommendation to place either a supraglottic airway or endotracheal tube when performing advanced airway management during in-hospital cardiac arrest based mainly in clinical trials conducted in the out-of-hospital setting. The Hospital Airway Resuscitation Trial (HART) is a pragmatic cluster-randomized superiority trial comparing a strategy of first choice supraglottic airway to a strategy of first choice endotracheal intubation during resuscitation from in-hospital cardiac arrest. The design includes a number of innovative elements such as a highly pragmatic design drawing from electronic health records and a novel primary outcome measure for cardiac arrest trials-alive-and-ventilator free days. Many of the topics explored in the design of HART have wide relevance to other trials in in-hospital cardiac arrest populations.

Use of clinical phenotypes to characterize emergency department patients administered intravenous opioids for acute pain.

OBJECTIVE: Individual experience with opioids is highly variable. Some patients with acute pain do not experience pain relief with opioids, and many report no euphoria or dysphoric reactions. In this study, we describe the clinical phenotypes of patients who receive intravenous opioids. METHODS: This was an emergency department-based study in which we enrolled patients who received an intravenous opioid. We collected 0 to 10 pain scores prior to opioid administration and 15 minutes after. We also used 0 to 10 instruments to determine how high and how much euphoria the patient felt after receipt of the opioid. Using a cutoff point of ≥50% improvement in pain and the median score on the high and euphoria scales, we assigned each participant to one of the following clinical phenotypes: pain relief with feeling high or euphoria, pain relief without feeling high or euphoria, inadequate relief with feeling high or euphoria, and inadequate relief without feeling high or euphoria. RESULTS: A total of 713 patients were enrolled, 409 (57%) of whom reported not feeling high, and 465 (65%) reported no feeling of euphoria. Median percent improvement in pain was 37.5% (interquartile range, 12.5%-60.0%). One hundred seventy-eight participants (25%) were classified as experiencing pain relief with euphoria or feeling high, 190 (27%) experienced inadequate relief with euphoria or feeling high, 101 (14%) experienced pain relief without euphoria or feeling high, and 244 (34%) reported inadequate relief without euphoria or feeling high. CONCLUSION: Among patients who receive intravenous opioids in the emergency department, the experiences of pain relief and euphoria are highly variable. For many, pain relief is independent of feeling high.

Oxycodone induced euphoria in ED patients with acute musculoskeletal pain. A secondary analysis of data from a randomized trial.

OBJECTIVES: Some opioid-naïve patients with acute musculoskeletal pain who are treated with opioids develop persistent opioid use. The impact of opioid-induced euphoria on this transition to persistent use has not been explored. We determined whether opioid-induced euphoria could be measured as a phenomenon distinct from relief of pain. METHODS: Patients with acute pain were randomized to receive oxycodone/acetaminophen (Oxy) or acetaminophen (APAP). We measured pain using a 0-10 verbal scale. To assess euphoria, participants provided a 0-10 response to each of these: 1) How good did the medication make you feel?; 2) How high did the medication make you feel?; 3) How blissful did the medication make you feel? We analyzed these data using successive multivariable linear regression models, in which each of these items was the dependent variable, and improvement in pain and medication were the independent variables, while controlling for age and sex. RESULTS: 75 were randomized to Oxy, 76 to APAP. Mean "how good" scores were 6.3 (SD 3.3) in the Oxy group and 4.8 (3.3) in the APAP group. Mean "how high" scores were 3.8 (3.7) in the Oxy group and 2.0 (3.0) in the APAP group. Mean "how blissful" scores were 4.9 (3.7) in the Oxy group and 3.1 (3.4) in the APAP group. After controlling for improvement in pain, age, and sex, the between-group difference in "how good" was 1.0 (95%CI: -0.1, 2.0), "how high" 1.5 (95% CI 0.4, 2.6), and "how blissful" 1.5 (95%CI: 0.4, 2.7). DISCUSSION: "How high" and "how blissful" but not "how good" were associated with opioid use after controlling for improvement in pain.

Epidemic gasoline exposures following Hurricane Sandy.

INTRODUCTION: Major adverse climatic events (MACEs) in heavily-populated areas can inflict severe damage to infrastructure, disrupting essential municipal and commercial services. Compromised health care delivery systems and limited utilities such as electricity, heating, potable water, sanitation, and housing, place populations in disaster areas at risk of toxic exposures. Hurricane Sandy made landfall on October 29, 2012 and caused severe infrastructure damage in heavily-populated areas. The prolonged electrical outage and damage to oil refineries caused a gasoline shortage and rationing unseen in the USA since the 1970s. This study explored gasoline exposures and clinical outcomes in the aftermath of Hurricane Sandy. METHODS: Prospectively collected, regional poison control center (PCC) data regarding gasoline exposure cases from October 29, 2012 (hurricane landfall) through November 28, 2012 were reviewed and compared to the previous four years. The trends of gasoline exposures, exposure type, severity of clinical outcome, and hospital referral rates were assessed. RESULTS: Two-hundred and eighty-three gasoline exposures were identified, representing an 18 to 283-fold increase over the previous four years. The leading exposure route was siphoning (53.4%). Men comprised 83.0% of exposures; 91.9% were older than 20 years of age. Of 273 home-based calls, 88.7% were managed on site. Asymptomatic exposures occurred in 61.5% of the cases. However, minor and moderate toxic effects occurred in 12.4% and 3.5% of cases, respectively. Gastrointestinal (24.4%) and pulmonary (8.4%) symptoms predominated. No major outcomes or deaths were reported. CONCLUSIONS: Hurricane Sandy significantly increased gasoline exposures. While the majority of exposures were managed at home with minimum clinical toxicity, some patients experienced more severe symptoms. Disaster plans should incorporate public health messaging and regional PCCs for public health promotion and toxicological surveillance.

Heterogeneity of genetic modifiers ensures normal cardiac development.

BACKGROUND: Mutations of the transcription factor Nkx2-5 cause pleiotropic heart defects with incomplete penetrance. This variability suggests that additional factors can affect or prevent the mutant phenotype. We assess here the role of genetic modifiers and their interactions. METHODS AND RESULTS: Heterozygous Nkx2-5 knockout mice in the inbred strain background C57Bl/6 frequently have atrial and ventricular septal defects. The incidences are substantially reduced in the Nkx2-5(+/-) progeny of first-generation (F1) outcrosses to the strains FVB/N or A/J. Defects recur in the second generation (F2) of the F1 X F1 intercross or backcrosses to the parental strains. Analysis of >3000 Nkx2-5(+/-) hearts from 5 F2 crosses demonstrates the profound influence of genetic modifiers on disease presentation. On the basis of their incidences and coincidences, anatomically distinct malformations have shared and unique modifiers. All 3 strains carry susceptibility alleles at different loci for atrial and ventricular septal defects. Relative to the other 2 strains, A/J carries polymorphisms that confer greater susceptibility to atrial septal defect and atrioventricular septal defects and C57Bl/6 to muscular ventricular septal defects. Segregation analyses reveal that > or = 2 loci influence membranous ventricular septal defect susceptibility, whereas > or = loci and at least 1 epistatic interaction affect muscular ventricular and atrial septal defects. CONCLUSIONS: Alleles of modifier genes can either buffer perturbations on cardiac development or direct the manifestation of a defect. In a genetically heterogeneous population, the predominant effect of modifier genes is health. (Circulation. 2010;121:1313-1321.)