Retrospective evaluation of antithrombin III supplementation in neonates and infants receiving enoxaparin for treatment of thrombosis.

BACKGROUND: Thromboembolic events are occurring at increasing rates in neonates and infants. At Children's Mercy Hospitals and Clinics, antithrombin III (AT3) concentrates are often used in combination with enoxaparin to supplement physiologically low AT3 levels. Theoretically, AT3 enhances the anticoagulant activity of enoxaparin and results in decreased time to therapeutic anti-Xa levels. No data exist on use of AT3 for this indication. PROCEDURE: This retrospective study compared time to therapeutic anti-Xa levels in patients <1 year of age receiving enoxaparin with AT3 (Group 1) and without AT3 (Group 2) for treatment of thrombosis. Primary objective was to compare time to therapeutic anti-Xa levels (0.5-1 U/ml) between groups. Secondary objectives included comparison of the initial and therapeutic dose of enoxaparin, enoxaparin dose changes, AT3 supplementation, and level monitoring. Bleeding events and cost were also evaluated. Statistical tests included Schuirmann's two one-sided tests for equivalence and general linear models/logistic regression for independent effects of age, critical illness, and timing of AT3. RESULTS: Mean time to therapeutic anti-Xa levels were not equivalent between Groups 1 and 2 (80.7 vs. 65.2 hours; P = 0.28). Initial enoxaparin dose and number of dose changes were equivalent. Group 1 required higher doses of enoxaparin to achieve therapeutic anti-Xa levels. Age, critical illness, and timing of AT3 had no effect on time to therapeutic anti-Xa levels. Bleeding events were not equivalent between Groups 1 and 2 (14.3% vs. 3.9%; P = 0.55). CONCLUSION: Supplementation with AT3 did not decrease time to therapeutic anti-Xa levels, added significant cost, and was associated with increased bleeding events.

Systematic review of the effect of metabolic syndrome on outcomes due to acute respiratory distress syndrome: a protocol.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening condition commonly seen in the intensive care unit. COVID-19 has dramatically increased the incidence of ARDS-with this rise in cases comes the ability to detect predisposing factors perhaps not recognised before, such as metabolic syndrome (MetS) and its associated conditions (hypertension, obesity, dyslipidaemia and type 2 diabetes mellitus). In this systematic review, we seek to describe the complex relationship between MetS, its associated conditions and ARDS (including COVID-19 ARDS). METHODS AND ANALYSIS: A systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL and Web of Science will be conducted. The population of interest is adults with ARDS and MetS (as defined according to the study author recognising that MetS definitions vary) or any MetS-associated condition. The control group will be adult patients with ARDS without MetS or any individual MetS-associated condition. We will search studies published in English, with a date restriction from the year 2000 to June 2023 and employ the search phrases 'metabolic syndrome', 'acute respiratory distress syndrome' and related terms. Search terms including 'dyslipidaemia', 'hypertension', 'diabetes mellitus' and 'obesity' will also be utilised. Outcomes of interest will include mortality (in-hospital, ICU, 28-day, 60-day and 90-day), days requiring mechanical ventilation and hospital and/or ICU length of stay. Study bias will be assessed using the NIH Bias Scale. ETHICS AND DISSEMINATION: Ethical approval is not required because this study includes previously published and publicly accessible data. Findings from this review will be disseminated via publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023405816.

Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes - A systematic review and meta-analysis.

AIMS: The effect of Glucagon-like peptide 1 receptor agonists (GLP1 RA) on diabetic retinopathy (DR) remains controversial. Previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders, therefore may have generated misleading results. The study aimed to examine the effect of GLP1RA on DR in type 2 diabetes (T2DM) in RCTs with or without CV benefits and distinguish the effect by major confounders. METHODS: We conducted electronic searches of multiple databases and a manual search using references lists. We included 13 RCTs examining the effect of GLP1 RA on health outcomes/adverse events including DR or DR complications in T2DM. We performed a random-effects model meta-analysis. RESULTS: GLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23, 95 % CI 1.05-1.44). The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2, 1.00-1.43), using placebo as a comparator (1.22, 1.05-1.42). In subgroups with patients who had T2DM ≥10 years (1.19, 0.99-1.42) or with subjects enrolled from multiple countries (1.2, 0.99-1.46), the association appeared to be evident but did not reach statistical significance. CONCLUSIONS: GLP1 RA including liraglutide, semaglutide, and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits. Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted.