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Importance: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.Objective: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock.Design, Setting, and Participants: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019.Interventions: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102).Main Outcomes and Measures: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses.Results: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively).Conclusions and Relevance: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock.Trial Registration: ClinicalTrials.gov Identifier: NCT03389555. [ABSTRACT FROM AUTHOR]

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 mmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels (P = .30). There was no difference in presurgical basal (1.0 mL/min/ mg [95% confidence interval [CI]: -0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: -4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05). [ABSTRACT FROM AUTHOR]

This JAMA Insights Clinical Update discusses the newer treatment option of extracorporeal cardiopulmonary resuscitation, particularly for patients with cardiac arrest who are not responsive to initial treatment. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to describe patient characteristics, event characteristics, and outcomes for patients with in-hospital cardiac arrest in Denmark.Methods: Data was obtained from DANARREST. DANARREST is a nationwide registry that covers all in-hospital cardiac arrests in Denmark with a clinical indication for cardiopulmonary resuscitation (i.e. without a prior "do-not-resuscitate" order).Results: A total of 4069 adult in-hospital cardiac arrests were registered between January 1st, 2017 and December 31st, 2018. The median age was 74 years (quartiles: 65, 81) and 37% were female. 71% had a non-shockable rhythm and the presumed etiology was primarily non-cardiac (57%). A total of 2180 patients (53.8%) achieved ROSC, with an additional 36 patients (0.9%) receiving extracorporeal cardiopulmonary resuscitation. At 30-days 1124 patients (27.8%) were alive. Of cardiac arrests from 2017, 404 patients (20.0%) survived to 1 year after the cardiac arrest. The incidence of adult in-hospital cardiac arrest in Denmark was estimated at 1.8 per 1000 admissions or 0.6 per 1000 in-patient days.Conclusion: In-hospital cardiac arrest occurs in at least 2000 patients each year in Denmark with a 30-day survival of approximately 28%. The establishment of a national registry for in-hospital cardiac arrest in Denmark will allow for quality improvement and research projects. [ABSTRACT FROM AUTHOR]

Background: Despite a consistent association with improved outcomes, public automated external defibrillators (AEDs) are rarely used in out-of-hospital cardiac arrest. One of the barriers towards increased use might be cost-effectiveness.Methods: We compared the cost-effectiveness of public AEDs to no AEDs for out-of-hospital cardiac arrest in the United States over a life-time horizon. The analysis assumed a societal perspective and results are presented as costs per quality-adjusted life year (QALY). Model inputs were based on reviews of the literature. For the base case, we modelled an annual cardiac arrest incidence per AED of 20%. A probabilistic sensitivity analysis was conducted to account for joint parameter uncertainty.Results: The no AED strategy resulted in 1.63 QALYs at a cost of $28,964. The AED strategy yielded an additional 0.26 QALYs for an incremental increase in cost of $13,793 per individual. The AED strategy yielded an incremental cost-effectiveness ratio of $53,797 per QALY gained. The yearly incidence of cardiac arrests occurring in the presence of an AED had minimal effect on the incremental cost-effectiveness ratio except at very low incidences. In several sensitivity analyses across a plausible range of health care and societal estimates, the AED strategy remained cost-effective. In the probabilistic sensitivity analysis, the AED strategy was cost-effective in 43%, 85%, and 91% of the scenarios at a willingness-to-pay threshold of $50,000, $100,000, and $150,000 per QALY gained, respectively.Conclusion: Public AEDs are a cost-effective public health intervention in the United States. These findings support widespread dissemination of public AEDs. [ABSTRACT FROM AUTHOR]

Aim of database: The aim of DANARREST is to collect data on processes of care and outcomes for patients with in-hospital cardiac arrest in Denmark, and thereby facilitate and monitor quality and quality improvement initiatives. Study population: In-hospital cardiac arrest patients with a clinical indication for cardiopulmonary resuscitation in Denmark. Main variables: DANARREST includes a number of descriptive variables as well as seven quality of care indicators; four related to processes of care and three related to clinical outcomes. The four process measures are related to whether the cardiac arrest was witnessed, whether the cardiac arrest was ECG-monitored, the timing of cardiopulmonary resuscitation, and the timing of the first rhythm analysis. The three outcomes measures include return of spontaneous circulation, 30-day survival, and 1-year survival. Database status: DANARREST started in 2013, and the coverage has increased steadily since. As of 2017, 95% of relevant hospitals are reporting data with an estimated coverage rate of approximately 80%. Conclusion: DANARREST is a relatively new national registry of in-hospital cardiac arrests in Denmark, with a high coverage rate. The registry provides an opportunity to monitor and improve quality of care for patients with in-hospital cardiac arrest. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this investigation was to determine if acute influenza infection is associated with depletion of CoQ10 compared to healthy controls and to determine any associations between CoQ10 levels and illness severity and inflammatory biomarkers. Patients and Methods: We analyzed serum CoQ10 concentrations of patients with acute influenza enrolled in a randomized clinical trial prior to study drug administration. Patients were enrolled at a single urban tertiary care center over 3 influenza seasons (December 27, 2013 to March 31, 2016). Wilcoxon rank sum test was used to compare CoQ10 levels between influenza patients and healthy controls. Correlations with inflammatory biomarkers and severity of illness were assessed using Spearman correlation coefficient. Results: We analyzed CoQ10 levels from 50 patients with influenza and 29 controls. Overall, patients with acute influenza had lower levels of CoQ10 (.53 μg/mL, IQR.37‐.75 vs.72, IQR.58‐.90, P = .004). Significantly more patients in the influenza group had low CoQ10 levels (<.5 μg/mL) compared to controls (48% vs 7%, P < .001). Among influenza patients, there were significant but weak correlations between CoQ10 levels and IL‐2 (r = −.30, P = .04), TNF‐alpha (r = −.35, P = .01) and VEGF (r = .38, P = .007), but no correlation with IL‐6, IL‐10, VCAM or influenza severity of illness score (all P > .05). Conclusions: We found that CoQ10 levels were significantly lower in patients with acute influenza infection and that these levels had significant although weak correlations with several inflammatory biomarkers. [ABSTRACT FROM AUTHOR]

The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC. The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin. The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference −48 ug/kg [95CI% −140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs. Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo. [ABSTRACT FROM AUTHOR]

Absolute vs. relative effects - implications for subgroup analyses If a treatment has an effect and the control-group outcome differs according to the subgroup characteristic, conclusions about subgroup differences will depend on the scale of the effect measure used. There was substantial heterogeneity in the effect measure used for subgroup analyses: 17 trials (61%) assessed subgroup differences on a relative scale, nine trials (32%) assessed subgroup differences on an absolute scale, one trial (4%) reported both scales, and one trial (4%) did not report the scale. [Extracted from the article]

This Guide to Statistics and Methods provides an overview of the use of adjustment for baseline characteristics in the analysis of randomized clinical trials and emphasizes several important considerations. [ABSTRACT FROM AUTHOR]