Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia
During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.
KEY FINDINGS: During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.
BACKGROUND: Objective of this study is to determine cerebral glucose concentration and its relationship with glucose infusion rate (GIR) and blood glucose concentration in neonatal encephalopathy during therapeutic hypothermia (TH).
DETAILS: This was an observational study in which cerebral glucose during TH was quantified by magnetic resonance (MR) spectroscopy and compared with mean blood glucose at the time of scan. Clinical data (gestational age, birth weight, GIR, sedative use) that could affect glucose use were collected. The severity and pattern of brain injury on MR imaging were scored by a neuroradiologist. Student t test, Pearson correlation, repeated measures ANOVA, and multiple regression analysis were performed. Three-hundred-sixty blood glucose values and 402 MR spectra from 54 infants (30 female infants; mean gestational age 38.6 ± 1.9 weeks) were analyzed. In total, 41 infants had normal-mild and 13 had moderate-severe injury. Median GIR and blood glucose during TH were 6.0 mg/kg/min (IQR 5-7) and 90 mg/dL (IQR 80-102), respectively. GIR did not correlate with blood or cerebral glucose. Cerebral glucose was significantly greater during than after TH (65.9 ± 22.9 vs 60.0 ± 25.2 mg/dL, P < .01), and there was a significant correlation between blood glucose and cerebral glucose during TH (basal ganglia: r = 0.42, thalamus: r = 0.42, cortical gray matter: r = 0.39, white matter: r = 0.39, all P < .01). There was no significant difference in cerebral glucose concentration in relation to injury severity or pattern.
Our Most Popular Resources
Copyright © Elsevier Inc. All rights reserved.
Source: Tetarbe, M., Wisnowski, J. L., Geyer, E., et al. (2023). Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia. J Pediatr.. Published: October, 2023. DOI: 10.1016/j.jpeds.2023.113560.
Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts
Early initiation of a 5-day oral ensitrelvir regimen within 72 hours after symptom onset in an index patient significantly reduced the risk of developing Covid-19 among household contacts while maintaining a safety profile comparable to placebo. Clinical benefit was observed across major patient subgroups, including individuals at increased risk for severe disease, and treatment was associated with reduced household transmission. These findings support ensitrelvir as an effective postexposure prophylactic option for household contacts and suggest potential utility in other high-risk exposure settings where rapid outbreak control is needed.
KEY FINDINGS: Early initiation of a 5-day oral ensitrelvir regimen within 72 hours after symptom onset in an index patient significantly reduced the risk of developing Covid-19 among household contacts while maintaining a safety profile comparable to placebo. Clinical benefit was observed across major patient subgroups, including individuals at increased risk for severe disease, and treatment was associated with reduced household transmission. These findings support ensitrelvir as an effective postexposure prophylactic option for household contacts and suggest potential utility in other high-risk exposure settings where rapid outbreak control is needed.
BACKGROUND: Household transmission remains a major contributor to the spread of SARS-CoV-2, particularly among individuals at increased risk for severe Covid-19. Although vaccination and prior infection have reduced disease severity, waning immunity and emerging variants continue to sustain transmission. Previous trials evaluating oral antiviral agents for postexposure prophylaxis in household contacts have not demonstrated significant protection, highlighting the need for effective preventive therapies. This phase 3 trial evaluated whether oral ensitrelvir, a SARS-CoV-2 3C-like protease inhibitor, could prevent Covid-19 among household contacts exposed to an infected index patient.
DETAILS: This phase 3, double-blind, randomized, placebo-controlled trial was conducted between June 2023 and mid-September 2024 across the United States, Argentina, Japan, South Africa, and Vietnam. Eligible household contacts were 12 years of age or older, had a negative SARS-CoV-2 test at enrollment, and were randomized within 72 hours after symptom onset in the index patient. Participants received either ensitrelvir 375 mg on day 1 followed by 125 mg once daily on days 2-5 or matching placebo. The primary endpoint was laboratory-confirmed Covid-19 by day 10 in the modified intention-to-treat population, defined as RT-PCR positivity accompanied by at least one prespecified Covid-19 symptom lasting 48 hours or longer. Secondary endpoints included laboratory-confirmed SARS-CoV-2 infection regardless of symptoms, subgroup analyses, and safety outcomes. Overall, 2,387 household contacts were randomized, including 1,030 participants in the ensitrelvir group and 1,011 in the placebo group within the modified intention-to-treat population. The mean participant age was 42.4 years, 71.1% were enrolled within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. By day 10, laboratory-confirmed Covid-19 occurred in 2.9% of participants receiving ensitrelvir compared with 9.0% receiving placebo, corresponding to a risk ratio of 0.33 (95% CI, 0.22-0.49; P<0.001) and an approximate 67% relative risk reduction in the modified intention-to-treat population. In the intention-to-treat population, Covid-19 developed in 4.4% and 10.2% of participants, respectively (risk ratio, 0.43; 95% CI, 0.32-0.59; P<0.001). Laboratory-confirmed SARS-CoV-2 infection irrespective of symptoms was also lower with ensitrelvir (14.0% vs. 21.5%; risk ratio, 0.66; 95% CI, 0.55-0.79). Subgroup analyses demonstrated generally consistent efficacy across age groups and participants with risk factors for severe disease. Among participants with risk factors, Covid-19 developed in 2.4% of the ensitrelvir group compared with 9.9% of the placebo group. Ensitrelvir was also associated with a 34% relative reduction in household SARS-CoV-2 transmission. Adverse events occurred at similar frequencies in the ensitrelvir and placebo groups (15.1% vs. 15.5%), with serious adverse events reported in 0.2% of participants in each group. No Covid-19-related hospitalizations or deaths occurred. Transient reductions in high-density lipoprotein concentrations were observed with ensitrelvir but returned toward baseline by day 15 and were not associated with clinical events.
Our Most Popular Resources
Pharmacogenomic-Informed Antidepressant Prescribing in Australian Primary Care
In this pragmatic double-blind randomized controlled trial conducted in Australian primary care, pharmacogenomic-informed antidepressant prescribing did not improve depressive symptoms compared with prescribing guided by national therapeutic guidelines. Clinical outcomes, medication tolerability, adherence, and quality of life were similar between groups, while cost-effectiveness analyses did not support routine implementation of pharmacogenomic testing in this setting. These findings suggest that broad pharmacogenomic-guided antidepressant prescribing in general practice does not provide additional clinical benefit over guideline-based management, although targeted evaluation in carefully selected patient populations may warrant further investigation.
Summary
Findings from the PRESIDE Double-Blind Randomized Controlled Trial
[Posted 7/Jul/2026]
AUDIENCE: Family Medicine, Psychiatry
KEY FINDINGS: In this pragmatic double-blind randomized controlled trial conducted in Australian primary care, pharmacogenomic-informed antidepressant prescribing did not improve depressive symptoms compared with prescribing guided by national therapeutic guidelines. Clinical outcomes, medication tolerability, adherence, and quality of life were similar between groups, while cost-effectiveness analyses did not support routine implementation of pharmacogenomic testing in this setting. These findings suggest that broad pharmacogenomic-guided antidepressant prescribing in general practice does not provide additional clinical benefit over guideline-based management, although targeted evaluation in carefully selected patient populations may warrant further investigation.
BACKGROUND: Pharmacogenomic testing has been proposed as a strategy to individualize antidepressant selection by identifying CYP2D6 and CYP2C19 variants that influence drug metabolism. Although previous studies have suggested potential clinical benefits, evidence from pragmatic primary care settings remains limited. The Pharmacogenomic-Informed Antidepressant Prescribing for Moderate-to-Severe Depressive Symptoms in Australian General Practice (PRESIDE) trial evaluated whether pharmacogenomic-guided prescribing improves depression outcomes compared with guideline-based prescribing in routine general practice.
DETAILS: PRESIDE was a multicenter, double-blind, randomized controlled trial conducted in Australian general practice between May 26, 2021, and September 28, 2023. Of 5185 patients approached, 552 were randomized, and 550 participants (275 per group) were included in the intention-to-treat analysis. Participants with moderate-to-severe depressive symptoms were assigned in a 1:1 ratio to receive antidepressant prescribing recommendations based either on pharmacogenomic testing combined with Australian Therapeutic Guidelines or on Australian Therapeutic Guidelines alone. Pharmacogenomic reports incorporated CYP2D6 and CYP2C19 metabolizer phenotypes derived from saliva-based genotyping. The primary endpoint was change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 12 weeks after the prescribing report was received. Secondary outcomes included remission, treatment response, antidepressant-related adverse effects, medication adherence, prescribing congruence, quality of life, and cost-effectiveness. A total of 479 participants (87%) completed the primary 12-week outcome assessment. Depressive symptoms improved over time in both groups. At 12 weeks, the adjusted between-group difference in PHQ-9 change was 0.90 (95% CI, 0.06-1.75; standardized mean difference 0.23 [95% CI, 0.02-0.45]; p=0.036), indicating a small but greater improvement in depressive symptoms in the guideline-based control group. No significant between-group differences were observed at 4, 8, or 26 weeks. Remission at 12 weeks occurred in 11% of participants receiving pharmacogenomic-guided prescribing compared with 18% in the control group, corresponding to an adjusted difference of -7.22% (95% CI, -13.25 to -1.19) and an odds ratio of 0.530 (95% CI, 0.311-0.903; p=0.020). Treatment response rates did not differ significantly between groups (29% vs 32%; OR 0.874; 95% CI, 0.581-1.315; p=0.518). Approximately two-thirds of participants had an actionable CYP2D6 or CYP2C19 phenotype, yet subgroup analyses demonstrated no differential treatment benefit based on genotype. Antidepressant adherence, side-effect burden, health-related quality of life, and health-care utilization were comparable between groups. Economic analyses indicated that pharmacogenomic-guided prescribing was more costly and less effective than standard guideline-based care, although differences in costs and quality-adjusted life years were not statistically significant. No grade 2-5 adverse events occurred, and only one grade 1 adverse event related to an administrative reporting error was documented.
Our Most Popular Resources
Source: Saya, S., Chondros, P., Abela, A., et al. Pharmacogenomic-informed antidepressant prescribing for moderate-to-severe depressive symptoms in Australian general practice (PRESIDE): a double-blind, randomised controlled trial. The Lancet Primary Care. 2026; Published: June 25, 2026. DOI: 10.1016/j.lanprc.2026.100158
Is Cyanoacrylate Fixation Safe for Neonatal IV Access? A Quality Improvement Evaluation of Cyanoacrylate Adhesive Securement for Short Peripheral Catheters
Cyanoacrylate fixation can support proactive vascular access care, offering a safe and feasible option to prevent complications rather than reacting to them after they occur. No adverse local effects were observed with cyanoacrylate adhesive, suggesting compatibility with neonatal skin and alignment with the Right Patient, Right Device, and Right Care principles within the 7 Rights of Neonatal Vascular Access.
KEY FINDINGS: This quality improvement evaluation suggests that medical-grade cyanoacrylate adhesive is a feasible and well-tolerated option for securing neonatal short peripheral catheters in routine clinical practice. Use of the adhesive was not associated with local skin injury, bleeding, or dressing displacement and did not increase application time. Although catheter dwell time was numerically longer and clinician-rated ease of use was favorable with cyanoacrylate fixation, no statistically significant differences were observed compared with conventional securement. Because infection-related outcomes were not assessed and the study was non-randomized with a limited sample size, larger prospective multicenter studies are needed to determine clinical effectiveness, infection outcomes, cost-effectiveness, and long-term safety.
BACKGROUND: Maintaining reliable peripheral intravenous (IV) access in neonates remains challenging because short peripheral catheters (SPCs) frequently fail due to infiltration, dislodgement, or occlusion, resulting in repeated cannulation and increased procedural burden. Conventional fixation methods may provide inadequate catheter stability, particularly in preterm infants with fragile skin. Medical-grade cyanoacrylate adhesive has been proposed as an adjunct to improve catheter securement, but evidence regarding its safety and feasibility in neonatal populations is limited. This quality improvement evaluation compared cyanoacrylate adhesive securement with conventional fixation for neonatal SPCs during routine clinical care.
DETAILS: This single-center quality improvement evaluation was conducted in the neonatal intensive care unit of University Hospital Lozenetz, Bulgaria, between March and August 2025. A total of 67 short peripheral catheter insertions were assessed, including 34 secured using conventional methods and 33 secured with medical-grade cyanoacrylate adhesive. The primary outcome was short-term safety, defined by the absence of bleeding, skin injury, or dressing displacement. Secondary outcomes included catheter dwell time, unplanned catheter removal, dressing application time, and clinician-rated ease of securement. Catheter and patient characteristics were prospectively documented during routine clinical practice, and outcomes were compared using non-parametric statistical analyses. Infection-related outcomes were not evaluated. Median dressing application time was identical in both groups at 5 minutes (p = 0.295). Median catheter dwell time was modestly longer with cyanoacrylate fixation (68.1 hours [IQR 46.3-101.7]) compared with conventional securement (64.0 hours [IQR 41.6-88.3]), although this difference was not statistically significant (p = 0.259). Overall, 76.1% of catheters underwent unplanned removal, with similar rates between the cyanoacrylate and conventional groups (78.8% vs 73.5%; p = 0.776). Infiltration or extravasation accounted for 70.1% of catheter removals, whereas phlebitis (1.5%), occlusion (3.0%), and accidental removal (1.5%) occurred infrequently. Clinician acceptance was favorable, with 83.6% of catheter securements rated as easy or very easy, and a greater proportion of "very easy" ratings was observed with cyanoacrylate fixation (21.2% vs 8.8%), although the difference was not statistically significant (p = 0.400). Importantly, no bleeding, skin injury, or dressing displacement was observed in either study group during the evaluation period.
Our Most Popular Resources
Copyright © Neonatal Nurses Association. Published by Elsevier Ltd. All rights reserved.
Source:XBoyadzhiev, S., Hoogendijk, E. O., van Rens, M., et al. Is cyanoacrylate fixation safe for neonatal IV access? A quality improvement evaluation of cyanoacrylate adhesive securement for short peripheral catheters. Journal of Neonatal Nursing. 2026; 32(3): 101796. Published: June, 2026. DOI: 10.1016/j.jnn.2026.101796.
Maternal RSV Vaccination, Infant Nirsevimab, or Both
Maternal RSV vaccination and infant nirsevimab immunization, administered either alone or sequentially, were safe and provided high RSV-A and -B nAb titers in infants that persisted through 3 months after delivery. While most infants will not need to receive both products to be protected, our results suggest that maternal RSV vaccination and infant nirsevimab immunization may be safely sequentially administered.
KEY FINDINGS: Maternal RSVpreF vaccine and infant nirsevimab administration, either alone or in combination, were safe and provided high RSV nAb titers in infants through interim follow-up.
BACKGROUND: Although both maternal respiratory syncytial virus (RSV) prefusion F vaccination (RSVpreF) and infant nirsevimab immunization have been approved for the prevention of RSV lower respiratory tract infections, the 2 have not been evaluated in a single study, and their sequential administration has not been studied systematically.
DETAILS: Authors performed a prospective, randomized, open-label, phase 4 study at 8 US sites of mother-infant pairs randomized 1:1:1:1 during pregnancy: maternal RSVpreF vaccine alone, maternal RSVpreF vaccine/infant nirsevimab at birth, maternal RSVpreF vaccine/infant nirsevimab at 3 months, or infant nirsevimab alone at birth. We are following the mother-infant pairs for 12 months to ascertain safety, infant tolerability, and the magnitude and durability of RSV-A and -B neutralizing antibodies (nAbs). Authors report interim data from September 19, 2024, to May 15, 2025, including 4-month infant follow-up. In total, 181 mothers were enrolled. Both products alone and in combination were safe. No related serious adverse events were observed in mothers or infants. Nirsevimab was well tolerated, and all local and systemic reactogenicity was mild to moderate in severity. RSVpreF vaccination boosted maternal RSV-A nAb titers 17.35-fold at the time of delivery, and titers were durable through 3 months postdelivery. The geometric mean transfer ratio of RSV-A nAbs was higher than 1.3 and similar across groups. RSV nAbs were highly elevated in infants at 6 weeks and 3 months, irrespective of group, with modest differences in waning.
Our Most Popular Resources
Copyright © American Academy of Pediatrics. All rights reserved.
Source: Rostad, C. A., Mary Healy, C., Nayak, J. L., et al. Maternal RSV Vaccination, Infant Nirsevimab, or Both: Interim Analysis of a Randomized Trial. Pediatrics. 2026; 157(6): e2025075223. Published: June, 2026. DOI: 10.1542/peds.2025-075223
FDA Approves First Single-Dose Generic Treatment for Influenza
FDA approved the first generic single-dose baloxavir marboxil tablet for influenza in patients aged 5 years and above, ahead of the 20262027 flu season. Approved for both acute uncomplicated influenza treatment (within 48 hours of symptom onset) and post-exposure prophylaxis, this milestone may improve access, affordability, and ease of antiviral use in clinical practice.
KEY FINDINGS:
- FDA approved the first generic form of baloxavir marboxil tablets.
- Approved for patients aged 5 years and older.
- Indications include acute uncomplicated influenza treatment and post-exposure prophylaxis.
- Treatment eligibility requires symptom duration of no more than 48 hours.
- Contraindicated in patients with hypersensitivity to baloxavir marboxil or formulation ingredients.
- Common adverse effects: diarrhea, bronchitis, nausea, sinusitis, and headache.
- In the U.S., nine out of 10 prescriptions filled are for generic drugs.
- Approval granted to Norwich Pharmaceuticals, Inc.
BACKGROUND: The U.S. Food and Drug Administration (FDA) announced approval of the first generic version of baloxavir marboxil tablets, previously marketed as Xofluza. This approval introduces the first single-dose generic option for both treatment and post-exposure prophylaxis of influenza. The approval was issued ahead of the 2026–2027 influenza season with the objective of expanding access to generic medications and supporting public health preparedness.
DETAILS: Generic baloxavir marboxil tablets are approved for use in patients aged 5 years and older. Indications include treatment of acute uncomplicated influenza in individuals who have experienced symptoms for no more than 48 hours and who are either otherwise healthy or at elevated risk for influenza-related complications. The medication is also approved for post-exposure prophylaxis following contact with an infected individual.
Our Most Popular Resources
The drug is contraindicated in patients with known hypersensitivity to baloxavir marboxil or any formulation components. Safety considerations include warnings regarding increased incidence of treatment-emergent resistance in patients younger than 5 years of age.
Common adverse effects reported include diarrhea, bronchitis, nausea, sinusitis, and headache.
FDA approval of generic baloxavir marboxil provides an additional therapeutic option for influenza management through a single-dose regimen. Increased availability of generic alternatives may support broader patient access and affordability while maintaining treatment availability before the upcoming flu season.
Copyright © Skyscape Editorial Team. All rights reserved.
Source: News Release: FDA Approves First Single-Dose Generic Treatment for Influenza.. FDA. Published: June 17, 2026.
Specialty: