Efficacy and tolerability of oral morphine versus oxycodone/acetaminophen for analgesia in the emergency department.

OBJECTIVE: Oxycodone/acetaminophen is one of the most commonly prescribed medications for pain management in the emergency department (ED) despite its high abuse liability. Our objective was to determine whether oral immediate-release morphine is as effective and well tolerated as oral oxycodone/acetaminophen for pain relief in stable ED patients. DESIGN: This is a prospective comparative study in which stable adult patients with acute painful conditions who had either oral morphine (15 or 30 mg) or oxycodone/acetaminophen (5/325 mg or 10/650 mg) ordered for them at the discretion of a triage physician were recruited. SETTING: This study took place in an urban, academic ED from 2016 to 2019. PARTICIPANTS: Seventy-three percent of the subjects were between the ages of 18 and 59, 57 percent were female, and 85 percent were African American. Most presented with abdominal, extremity, or back pain. Patient characteristics were similar between treatment groups. INTERVENTIONS: Of the 364 enrolled patients, 182 were given oral morphine and 182 were given oxycodone/acetaminophen at the discretion of the triage provider. They were asked to rate their pain score prior to receiving analgesia and at 60 and 90 minutes after administration. MAIN OUTCOME MEASURES: We examined pain scores, adverse effects, overall satisfaction, willingness to accept the same treatment again, and the need for additional analgesia. RESULTS: There was no difference in satisfaction reported by patients who received morphine versus oxycodone/acetaminophen: 15.9 percent vs 16.5 percent were very satisfied, 31.9 percent vs 26.4 percent were somewhat satisfied, and 23.6 percent vs 22.5 percent were not satisfied, p = 0.56. Secondary outcomes also showed no significant difference: net change in pain score -2 vs -2 at 60 and 90 minutes, p = 0.91 and p = 0.72, respectively; adverse effects 20.9 percent vs 19.2 percent, p = 0.69; need for further analgesia 9.3 percent vs 7.1 percent, p = 0.44; willingness to accept analgesic again 73.1 percent vs 78.6 percent, p = 0.22. CONCLUSIONS: Oral morphine is a feasible alternative to oxycodone/acetaminophen for analgesia in the ED.

High sensitivity troponin - Six hours is the magic number.

BACKGROUND: High sensitivity troponin assays have become widespread for emergency department evaluation of acute chest pain. We assessed if a high sensitivity troponin under the 99th percentile upper reference limit drawn at 6 h or greater from symptom onset could safely rule out acute coronary syndrome in patients who did not meet the rapid rule-out strategy. METHODS: We conducted a multicenter retrospective study examining emergency department patients with chest pain who did not meet rapid-rule out criteria and were admitted for further evaluation. Among these admitted patients, we assessed the rate of clinically relevant adverse cardiac events (death, cardiac or respiratory arrest, STEMI, or life-threatening arrhythmia) and NSTEMI in patients with high sensitivity troponin less than the 99th percentile value obtained after at least 6 h of chest pain. RESULTS: Out of 1187 patients admitted, we found 30 clinically relevant adverse cardiac events, all of which occurred in patients admitted for another compelling reason or ischemic ECG. 36 patients had an NSTEMI, of which 33 were identified with high sensitivity troponin greater than 99th percentile upper reference limit within 6 h of chest pain onset. This left 0 clinically relevant adverse cardiac events and 3 NSTEMI among the 429 patients with high sensitivity troponin less than the 99th percentile at 6 h and nonischemic ECG and no other compelling reason for admission. CONCLUSION: This study assessed patients with chest pain with high sensitivity troponin values between 3 ng/L and the 99th percentile upper reference limit after 6 h of chest pain and found that they have a low rate of clinically relevant adverse cardiac events and NSTEMI.

Extracellular Release of Mitochondrial DNA: Triggered by Cigarette Smoke and Detected in COPD.

Cigarette smoke (CS) is the most common risk factor for chronic obstructive pulmonary disease (COPD). The present study aimed to elucidate whether mtDNA is released upon CS exposure and is detected in the plasma of former smokers affected by COPD as a possible consequence of airway damage. We measured cell-free mtDNA (cf-mtDNA) and nuclear DNA (cf-nDNA) in COPD patient plasma and mouse serum with CS-induced emphysema. The plasma of patients with COPD and serum of mice with CS-induced emphysema showed increased cf-mtDNA levels. In cell culture, exposure to a sublethal dose of CSE decreased mitochondrial membrane potential, increased oxidative stress, dysregulated mitochondrial dynamics, and triggered mtDNA release in extracellular vesicles (EVs). Mitochondrial DNA release into EVs occurred concomitantly with increased expression of markers that associate with DNA damage responses, including DNase III, DNA-sensing receptors (cGAS and NLRP3), proinflammatory cytokines (IL-1ß, IL-6, IL-8, IL-18, and CXCL2), and markers of senescence (p16 and p21); the majority of the responses are also triggered by cytosolic DNA delivery in vitro. Exposure to a lethal CSE dose preferentially induced mtDNA and nDNA release in the cell debris. Collectively, the results of this study associate markers of mitochondrial stress, inflammation, and senescence with mtDNA release induced by CSE exposure. Because high cf-mtDNA is detected in the plasma of COPD patients and serum of mice with emphysema, our findings support the future study of cf-mtDNA as a marker of mitochondrial stress in response to CS exposure and COPD pathology.