Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in extremely preterm infants: a clinical practice guideline incorporating family values and preferences.

ImportanceProphylactic cyclo-oxygenase inhibitors (COX-Is) such as indomethacin, ibuprofen and acetaminophen may prevent morbidity and mortality in extremely preterm infants (born ≤28 weeks' gestation). However, there is controversy around which COX-I, if any, is the most effective and safest, which has resulted in considerable variability in clinical practice. Our objective was to develop rigorous and transparent clinical practice guideline recommendations for the prophylactic use of COX-I drugs for the prevention of mortality and morbidity in extremely preterm infants. The Grading of Recommendations Assessment, Development and Evaluation evidence-to-decision framework for multiple comparisons was used to develop the guideline recommendations. A 12-member panel, including 5 experienced neonatal care providers, 2 methods experts, 1 pharmacist, 2 parents of former extremely preterm infants and 2 adults born extremely preterm, was convened. A rating of the most important clinical outcomes was established a priori. Evidence from a Cochrane network meta-analysis and a cross-sectional mixed-methods study exploring family values and preferences were used as the primary sources of evidence. The panel recommended that prophylaxis with intravenous indomethacin may be considered in extremely preterm infants (conditional recommendation, moderate certainty in estimate of effects). Shared decision making with parents was encouraged to evaluate their values and preferences prior to therapy. The panel recommended against routine use of ibuprofen prophylaxis in this gestational age group (conditional recommendation, low certainty in the estimate of effects). The panel strongly recommended against use of prophylactic acetaminophen (strong recommendation, very low certainty in estimate of effects) until further research evidence is available.

Lipid Profiles from Dried Blood Spots Reveal Lipidomic Signatures of Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is associated with perinatal brain injury, which may lead to disability or death. As the brain is a lipid-rich organ, various lipid species can be significantly impacted by HIE and these correlate with specific changes to the lipidomic profile in the circulation. Objective: To investigate the peripheral blood lipidomic signature in dried blood spots (DBS) from newborns with HIE. Using univariate analysis, multivariate analysis and sPLS-DA modelling, we show that newborns with moderate-severe HIE (n = 46) who underwent therapeutic hypothermia (TH) displayed a robust peripheral blood lipidomic signature comprising 29 lipid species in four lipid classes; namely phosphatidylcholine (PC), lysophosphatidylcholine (LPC), triglyceride (TG) and sphingomyelin (SM) when compared with newborns with mild HIE (n = 18). In sPLS-DA modelling, the three most discriminant lipid species were TG 50:3, TG 54:5, and PC 36:5. We report a reduction in plasma TG and SM and an increase in plasma PC and LPC species during the course of TH in newborns with moderate-severe HIE, compared to a single specimen from newborns with mild HIE. These findings may guide the research in nutrition-based intervention strategies after HIE in synergy with TH to enhance neuroprotection.

Steady-state [Formula: see text] above MLSS: evidence that critical speed better represents maximal metabolic steady state in well-trained runners.

The metabolic boundary separating the heavy-intensity and severe-intensity exercise domains is of scientific and practical interest but there is controversy concerning whether the maximal lactate steady state (MLSS) or critical power (synonymous with critical speed, CS) better represents this boundary. We measured the running speeds at MLSS and CS and investigated their ability to discriminate speeds at which [Formula: see text] was stable over time from speeds at which a steady-state [Formula: see text] could not be established. Ten well-trained male distance runners completed 9-12 constant-speed treadmill tests, including 3-5 runs of up to 30-min duration for the assessment of MLSS and at least 4 runs performed to the limit of tolerance for assessment of CS. The running speeds at CS and MLSS were significantly different (16.4 ± 1.3 vs. 15.2 ± 0.9 km/h, respectively; P < 0.001). Blood lactate concentration was higher and increased with time at a speed 0.5 km/h higher than MLSS compared to MLSS (P < 0.01); however, pulmonary [Formula: see text] did not change significantly between 10 and 30 min at either MLSS or MLSS + 0.5 km/h. In contrast, [Formula: see text] increased significantly over time and reached [Formula: see text] at end-exercise at a speed ~ 0.4 km/h above CS (P < 0.05) but remained stable at a speed ~ 0.5 km/h below CS. The stability of [Formula: see text] at a speed exceeding MLSS suggests that MLSS underestimates the maximal metabolic steady state. These results indicate that CS more closely represents the maximal metabolic steady state when the latter is appropriately defined according to the ability to stabilise pulmonary [Formula: see text].