American journal of therapeutics最新文献

Background: In pediatric critical care, vasoactive/inotropic support is widely used in patients with heart failure, but it remains controversial because the influence of multiple medications and the interplay between their inotropic and vasoactive effects on a given patient are hard to predict. Robust evidence supporting their use and quantifying their effects in this group of patients is scarce.

Study question: The aim of this study was to characterize the effect of vasoactive medications on various cardiovascular parameters in pediatric patient with decreased ejection fraction.

Study design: Clinical-data based physiologic simulator study.

Measure and outcomes: We used a physics-based computer simulator for quantifying the response of cardiovascular parameters to the administration of various types of vasoactive/inotropic medications in pediatric patients with decreased ejection fraction. The simulator allowed us to study the impact of increasing medication dosage and the simultaneous administration of some vasoactive agents. Correlation and linear regression analyses yielded the quantified effects on the vasoactive/inotropic support.

Results: Cardiac output and systemic venous saturation significantly increased with the administration of dobutamine and milrinone in isolation, and combination of milrinone with dobutamine, dopamine, or epinephrine. Both parameters decreased with the administration of epinephrine and norepinephrine in isolation. No significant change in these hemodynamic parameters was observed with the administration of dopamine in isolation.

Conclusions: Milrinone and dobutamine were the only vasoactive medications that, when used in isolation, improved systemic oxygen delivery. Milrinone in combination with dobutamine, dopamine, or epinephrine also increased systemic oxygen delivery. The induced increment on afterload can negatively affect systemic oxygen delivery.

Background: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC).

Study question: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC?

Data sources: MEDLINE, Embase, Scopus, and Cochrane databases.

Study design: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis.

Results: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66-2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39-2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34-2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53-2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60-2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11-2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86-1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86-0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36-0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)].

Conclusion: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.