Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Graphs with equal domination and 2-distance domination numbers

Let G = (V,E) be a graph. The distance between two vertices u and v in a connected graph G is the length of the shortest (u-v) path in G. A set D ⊆ V(G) is a dominating set if every vertex of G is at distance at most 1 from an element of D. The domination number of G is the minimum cardinality of a dominating set of G. A set D ⊆ V(G) is a 2-distance dominating set if every vertex of G is at distance at most 2 from an element of D. The 2-distance domination number of G is the minimum cardinality of a 2-distance dominating set of G. We characterize all trees and all unicyclic graphs with equal domination and 2-distance domination numbers

Polynomial Algorithm for Minimal (1,2)-Dominating Set in Networks

Dominating sets find application in a variety of networks. A subset of nodes D is a (1,2)-dominating set in a graph G=(V,E) if every node not in D is adjacent to a node in D and is also at most a distance of 2 to another node from D. In networks, (1,2)-dominating sets have a higher fault tolerance and provide a higher reliability of services in case of failure. However, finding such the smallest set is NP-hard. In this paper, we propose a polynomial time algorithm finding a minimal (1,2)-dominating set, Minimal_12_Set. We test the proposed algorithm in network models such as trees, geometric random graphs, random graphs and cubic graphs, and we show that the sets of nodes returned by the Minimal_12_Set are in general smaller than sets consisting of nodes chosen randomly

Weakly connected domination subdivision numbers

A set D of vertices in a graph G = (V,E) is a weakly connected dominating set of G if D is dominating in G and the subgraph weakly induced by D is connected. The weakly connected domination number of G is the minimum cardinality of a weakly connected dominating set of G. The weakly connected domination subdivision number of a connected graph G is the minimum number of edges that must be subdivided (where each egde can be subdivided at most once) in order to increase the weakly connected domination number. We study the weakly connected domination subdivision numbers of some families of graphs

On domination multisubdivision number of unicyclic graphs

The paper continues the interesting study of the domination subdivision number and the domination multisubdivision number. On the basis of the constructive characterization of the trees with the domination subdivision number equal to 3 given in [H. Aram, S.M. Sheikholeslami, O. Favaron, Domination subdivision number of trees, Discrete Math. 309 (2009), 622-628], we constructively characterize all connected unicyclic graphs with the domination multisubdivision number equal to 3. We end with further questions and open problems

Trees with equal restrained domination and total restrained domination numbers

For a graph G = (V,E), a set D ⊆ V(G) is a total restrained dominating set if it is a dominating set and both ⟨D⟩ and ⟨V(G)-D⟩ do not have isolated vertices. The cardinality of a minimum total restrained dominating set in G is the total restrained domination number. A set D ⊆ V(G) is a restrained dominating set if it is a dominating set and ⟨V(G)-D⟩ does not contain an isolated vertex. The cardinality of a minimum restrained dominating set in G is the restrained domination number. We characterize all trees for which total restrained and restrained domination numbers are equal

Application of Doubly Connected Dominating Sets to Safe Rectangular Smart Grids

Smart grids, together with the Internet of Things, are considered to be the future of the electric energy world. This is possible through a two-way communication between nodes of the grids and computer processing. It is necessary that the communication is easy and safe, and the distance between a point of demand and supply is short, to reduce the electricity loss. All these requirements should be met at the lowest possible cost. In this paper, we study a two-dimensional rectangular grid graph which is considered to be a model of a smart grid; nodes of the graph represent points and devices of the smart grid, while links represent possible ways of communication and energy transfer. We consider the problem of choosing the lowest possible number of locations (nodes, points) of the grid which could serve as energy sources (or a source of different resources) to other nodes in such a way that we ensure reduction in electricity loss and provide safe communication and resistance to failures and increases in energy demand.Therefore, we study minimum doubly connected dominating sets in grid graphs. We show that the proposed solutions are the best possible in terms of the number of source points for the case of narrow grid graphs and we give upper and lower bounds for the case of wide grid graphs

Application of Doubly Connected Dominating Sets to Safe Rectangular Smart Grids

Smart grids, together with the Internet of Things, are considered to be the future of the electric energy world. This is possible through a two-way communication between nodes of the grids and computer processing. It is necessary that the communication is easy and safe, and the distance between a point of demand and supply is short, to reduce the electricity loss. All these requirements should be met at the lowest possible cost. In this paper, we study a two-dimensional rectangular grid graph which is considered to be a model of a smart grid; nodes of the graph represent points and devices of the smart grid, while links represent possible ways of communication and energy transfer. We consider the problem of choosing the lowest possible number of locations (nodes, points) of the grid which could serve as energy sources (or a source of different resources) to other nodes in such a way that we ensure reduction in electricity loss and provide safe communication and resistance to failures and increases in energy demand.Therefore, we study minimum doubly connected dominating sets in grid graphs. We show that the proposed solutions are the best possible in terms of the number of source points for the case of narrow grid graphs and we give upper and lower bounds for the case of wide grid graphs