Scoping Review of Wounds in Hospitalized Adults with COVID-19 Over the First Three Years of the Pandemic.

OBJECTIVE: To synthesize the literature on skin failure and pressure injuries among hospitalized patients with COVID-19. DATA SOURCES: An electronic literature search using relevant keywords and controlled vocabulary was conducted in March 2023 on MEDLINE/PubMed, Embase, and CINAHL. Manual citation searches of included articles and grey literature, including the Wound, Ostomy, and Continence Nurses Society website were performed. Articles published in English between 2020 and April 2023 were considered. STUDY SELECTION: Articles were included if they reported on COVID-19 positive hospitalized adults with wounds that were not present upon admission. A total of 31 articles met these criteria. DATA EXTRACTION: Covidence was used to extract the data and was reviewed by multiple team members. DATA SYNTHESIS: Of the 31 studies, 27 reported new onset skin lesions during hospitalization. Wounds were classified as pressure injuries, skin failure, livedo racemosea and/or, retiform purpura, and associated with microvascular thrombosisthrombotic vasculopathy. Most pressure injuries were associated with prone position and affected patients often had multiple comorbidities including hypertension, diabetes mellitus, end-stage renal disease, heart disease, and COPD. Four articles highlighted an increased risk of new onset wounds, and three emphasized the importance of distinguishing deep tissue pressure injuries from ischemic-related lesions in patients with COVID-19. CONCLUSIONS: The evidence suggests an increased risk of ischemic lesions and pressure injuries (PI) in patients with COVID-19 infection. This phenomenon may have inflated the numbers of PI during the pandemic and adversely affected nursing quality measures in acute care environments.

A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study.

AIMS: Pharmacodynamic (PD) studies comparing prasugrel and ticagrelor have reached inconsistent findings. Therefore, a comprehensive investigation comparing the PD effects of prasugrel vs. ticagrelor after switching from clopidogrel therapy, exploring both loading dose (LD) and maintenance dose (MD) regimens represented the aim of this study. METHODS AND RESULTS: Patients (n = 110) with coronary artery disease were randomized to prasugrel (60 mg LD/10 mg MD q.d.) or ticagrelor (180 mg LD/90 mg MD b.i.d) therapy for 1 week. Pharmacodynamic assessments were conducted using three assays (vasodilator-stimulated phosphoprotein, VerifyNow P2Y12, and light transmittance aggregometry, LTA) at baseline, 30 min, 2, 24 h, and 1 week. The impact of initiating ticagrelor MD 12 vs. 24 h after LD administration was also assessed. Switching clopidogrel-treated patients to an LD of prasugrel or ticagrelor was associated with a reduction in platelet reactivity at 30 min and was sustained at all time points up to 1 week with the MD (P < 0.001 for all assays). Platelet reactivity was similar with prasugrel and ticagrelor with all assays at 30 min, 2 h, and 1 week (P > 0.05 for all time points), with the exception of LTA at 30 min (lower with prasugrel; P = 0.003). At 24 h, platelet reactivity was lower among patients initiating ticagrelor MD after 12 vs. 24 h post-LD. Rates of high platelet reactivity (HPR) were markedly reduced and similar between groups. CONCLUSION: Prasugrel and ticagrelor exert similar levels of P2Y12 inhibition achieving more potent PD effects and reduced HPR rates compared with clopidogrel which are reached promptly following LD and sustained with MD. CLINICALTRIALSGOV IDENTIFIER: NCT01852175.

Impact of Escalating Loading Dose Regimens of Ticagrelor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results of a Prospective Randomized Pharmacokinetic and Pharmacodynamic Investigation.

OBJECTIVES: The goal of this study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of escalating ticagrelor loading dose (LD) regimens in primary percutaneous coronary intervention (PPCI). BACKGROUND: Patients with ST-segment elevation myocardial infarction undergoing PPCI frequently have suboptimal platelet inhibition in the early hours after ticagrelor LD. The use of high ticagrelor LD regimens has been hypothesized to optimize platelet inhibition in PPCI. METHODS: This was a prospective, randomized study of escalating ticagrelor LD regimens (180 mg, 270 mg, or 360 mg) in PPCI (N = 52). PK/PD analyses were performed before and 30 min, 1, 2, 4, 8, and 24 h post-LD. PK assessments included exposure to ticagrelor and its metabolite (AR-C124910XX). PD assessments included P2Y12 reaction units (PRU) measured by VerifyNow P2Y12 and platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein (VASP). RESULTS: Platelet reactivity was elevated during the first 2 h post-LD. There were no differences in PRU between groups during the study time course (p = 0.179). There were no significant differences in PRU levels across groups at all time points, except at 1 h (p = 0.017) where platelet reactivity was lowest with a 270-mg LD. No differences were found between the 180-mg and 360-mg groups (primary endpoint; p > 0.999). High on-treatment platelet reactivity rates were not different across groups, except at 1 hour (p = 0.038). Parallel PD findings were observed with VASP-PRI. PK analysis showed a delay in ticagrelor absorption and generation of AR-C124910XX, irrespective of dose. Although morphine was associated with a delay in ticagrelor PK/PD, it was not an independent predictor of high on-treatment platelet reactivity. CONCLUSIONS: ST-segment elevation myocardial infarction patients undergoing PPCI frequently exhibit impaired response to ticagrelor in the early hours after drug administration, which cannot be overcome by increasing LD regimens. These PD findings are largely attributed to an impaired PK profile, indicating a delay in drug absorption compared with that reported in stable clinical settings. (High Ticagrelor Loading Dose in STEMI; NCT01898442).

Pharmacodynamic Effects of Ticagrelor Dosing Regimens in Patients on Maintenance Ticagrelor Therapy: Results From a Prospective, Randomized, Double-Blind Investigation.

OBJECTIVES: The aim of this study was to assess the impact of ticagrelor dosing regimens on pharmacodynamic (PD) profiles in patients on maintenance ticagrelor therapy. BACKGROUND: Many patients on maintenance P2Y12-inhibiting therapies may require coronary revascularization procedures, raising a common clinical question with regard to the dosing regimen of the P2Y12-inhibiting agent to be used. To date, investigations assessing dosing regimens of P2Y12 receptor inhibitors in patients on maintenance therapy have been only assessed with thienopyridines, but not with ticagrelor. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study assessing the PD effects of 2 dosing regimens of ticagrelor in patients on standard aspirin and ticagrelor maintenance therapy. A total of 60 patients were randomized to either 90 mg (maintenance dose [MD] group) or 180 mg (loading dose [LD] group) dose of ticagrelor. PD assessments were conducted at 3 time points (baseline, 1 h and 4 h). PD assessments were defined according to the platelet reactivity index (PRI) (vasodilator-stimulated phosphoprotein phosphorylation assay), P2Y12 reaction unit (VerifyNow P2Y12 assay) and adenosine diphosphate-induced platelet aggregation by light transmittance aggregometry. RESULTS: There were no differences in baseline levels of platelet reactivity with all assays. Intergroup comparisons by means of repeated-measures analysis adjusted for baseline PRI values showed that the LD group had significantly lower PRI levels compared with the MD group during the overall study time course (p = 0.031). Consistent findings were found for P2Y12 reaction unit (p = 0.026) and light transmittance aggregometry (p = 0.004). Intragroup comparisons showed that a more prompt and sustained platelet inhibitory effect was achieved more consistently with an LD regimen compared with a MD regimen. CONCLUSIONS: In patients on maintenance ticagrelor therapy, a 180-mg LD regimen of ticagrelor is associated with more potent and prompt platelet inhibition compared with a 90-mg MD. (Impact of Ticagrelor Re-Load Pharmacodynamic Profiles; NCT01731041).