Geeta K. Swamy

Maternal-infant immunity against influenza is improved through vaccination during pregnancy. We conducted an in-depth analysis of antibody (Ab) responses in sera from pregnant and non-pregnant women immunized with an unadjuvanted inactivated influenza A (H1N1) monovalent vaccine during the 2009 pandemic (NCT00992719). Pregnant women received either the standard 15 µg dose or the increased 30 µg dose, while non-pregnant women received the 15 µg dose. Ab specific for influenza hemagglutinin (HA), HA stalk, and neuraminidase (NA), as well as canonical functions of hemagglutination inhibition (HAI), microneutralization, and neuraminidase inhibition, was examined at baseline, 21 days post-vaccination, at delivery, and in cord blood. Ab subclasses, Fc receptor binding, and Fc-mediated immune functions, including cellular cytotoxicity, phagocytosis, and complement deposition, were also assessed. The vaccine was well tolerated and highly immunogenic in recipients; most participants had a ≥4-fold increase in Ab titers post-vaccination for HAI (HAI > 70%) and HA-specific IgG (IgG > 50%). Pregnant women who received the 15 µg dose had lower vaccine responses, as measured by NA-specific IgG, Fc receptor binding, and cell-mediated activity, compared with the other groups. Immunization of pregnant women with the 30 µg dose resulted in more robust humoral immunity, including a larger number of HA Ab features reaching 4-fold increases compared to the other groups, a more durable antiviral function, and increased NA-specific Ab features that were transferred to the infant as compared to pregnant women who received the standard 15 µg dose. Increasing the antigen content of seasonal vaccines could enhance immunity against influenza in mothers and infants and warrants further study. IMPORTANCE: Pregnant women and infants are at-risk groups for influenza infection. Vaccination is recommended during pregnancy to stimulate adaptive immunity and protect both the mother and infant early in life. We characterized the immune responses of pregnant and non-pregnant women to an unadjuvanted inactivated 2009 pandemic influenza A (H1N1). Pregnant women immunized with the 15 µg standard seasonal influenza vaccine dose developed lower NA-specific responses compared to non-pregnant women immunized with the same vaccine dose. Vaccination of pregnant women with a 30 µg dose resulted in more robust and durable post-vaccination responses, particularly longer-lasting functional antibodies and NA-specific antibodies in maternal and cord blood. A deeper analysis of antibody responses beyond the traditional hemagglutination inhibition (HAI) assay suggests that a higher-dose influenza vaccine, already recommended for the elderly, could be beneficial for pregnant women and warrants further investigation. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT00992719 .

Authorship remains the primary currency of academic credit and a cornerstone of research integrity, yet current practices often fail to reflect the collaborative and interdisciplinary nature of modern science and questionable authorship practices persist. We argue that addressing these shortcomings is a collective responsibility shared by researchers, journals, research funders, scholarly societies, and research institutions. We examined authorship guidelines issued by journals and research institutions and found that their recommendations to researchers are highly variable. We propose that fostering a responsible authorship culture requires a shared, principle-based framework grounded in transparency, credit, and accountability. These three interconnected principles highlight when authorship practices are questionable and offer a framework for constructive reflection on the meaning of authorship. We outline practical ways research leaders can embed these principles into everyday practice by initiating early, inclusive, and fair authorship discussions and ensuring transparent description of contributions. Research institutions have a unique opportunity to inculcate good practices and lead this culture change with harmonized guidance, education, fair conflict resolution, and reform of researcher assessment. Anchoring authorship in transparency, credit, and accountability will strengthen the credibility of individual research, the fairness of recognition systems, and, ultimately, the trustworthiness of science itself.

In this study, a single hepatitis C virus (HCV) RNA at 2–6 months was sensitive and specific (86.7% and 95% confidence interval [CI], 62.1%–96.3% and 100% and 95% CI, 98.8%–100%, respectively) in identifying perinatal transmission of HCV. No cases of perinatal infection requiring treatment were missed.

INTRODUCTION: Black birthing people are at increased risk for cesarean delivery (CD) and gestational hypertension (gHTN), compared to their White counterparts. In the ARRIVE trial, labor induction at 39 weeks decreased CD and gHTN in low-risk nulliparous patients. Our aim was to determine whether racial differences in labor induction, CD or gHTN changed after ARRIVE and the COVID-19 pandemic. METHODS: We conducted an IRB-approved, retrospective cohort study using publicly available birth certificate data from three time periods: pre-ARRIVE (January 1, 2015 to August 31, 2018), post-ARRIVE (September 1, 2018 to February 29, 2020), and post-COVID (March 1, 2020 to December 31, 2020). All non-Hispanic Black (NHB) or White (NHW) nulliparous patients with a singleton gestation who delivered at more than 39 weeks of gestation with no documented high-risk conditions were included. Odds of labor induction, gHTN, and CD were compared by time period and race and ethnicity using an interrupted time series analysis adjusted for seasonality and covariates. RESULTS: There were 471,351 NHB and 2,265,018 NHW birth records included in the analysis. Post ARRIVE, the rate of labor induction increased among NHB and NHW birthing people. Non-Hispanic Black patients were less likely to be induced than their White counterparts before and after the publication of ARRIVE and COVID-19. In the adjusted ITS analysis, the odds of induction of labor (IOL) were lower while the odds of gestational hypertension and cesarean birth were higher for NHB compared to NHW in all three time periods. CONCLUSION: It is plausible that the racial difference in 39-week IOL may contribute to racial disparities in gestational hypertension and cesarean delivery. The results of the ARRIVE trial suggest that ensuring equitable access to IOL in the 39^th week may be one strategy to reduce obstetric racial disparities.

Background and Objective Piperacillin/tazobactam is one of the most frequently used antimicrobials in older adults. Using an opportunistic study design, we evaluated the pharmacokinetics of piperacillin/tazobactam as a probe drug to evaluate changes in antibacterial drug exposure and dosing requirements, including in older adults. Methods A total of 121 adult patients were included. The population pharmacokinetic models that best characterized the observed plasma concentrations of piperacillin and tazobactam were one-compartment structural models with zero-order input and linear elimination. Results Among all potential covariates, estimated creatinine clearance had the most substantial impact on the elimination clearance for both piperacillin and tazobactam. After accounting for renal function and body size, there was no remaining impact of frailty on the pharmacokinetics of piperacillin and tazobactam. Monte Carlo simulations indicated that renal function had a greater impact on the therapeutic target attainment than age, although these covariates were highly correlated. Frailty, using the Canadian Study of Health and Aging Clinical Frailty Scale, was assessed in 60 patients who were ≥ 65 years of age. Conclusions The simulations suggested that adults ≤ 50 years of age infected with organisms with higher minimum inhibitory concentrations may benefit from continuous piperacillin/tazobactam infusions (12 g/day of piperacillin component) or extended infusions of 4 g every 8 hours. However, for a target of 50% fT + minimum inhibitory concentration, dosing based on renal function is generally preferable to dosing by age, and simulations suggested that patients with creatinine clearance ≥ 120 mL/min may benefit from infusions of 4 g every 8 hours for organisms with higher minimum inhibitory concentrations.

Botulism is a rare, life-threatening paralytic disease caused by botulinum neurotoxin (BoNT). Available treatments including an equine antitoxin and human immune globulin are given postexposure and challenging to produce and administer.

Objective Botulism is a rare, life-threatening paralytic disease caused by Clostridium botulinum neurotoxin (BoNT). Available treatments including an equine antitoxin and human immune globulin are given post-exposure and challenging to produce and administer. NTM-1632 is an equimolar mixture of 3 human IgG monoclonal antibodies, B1, B2, and B3, targeting BoNT serotype B (BoNT/B). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1632. Methods This double-blind, single-center, placebo-controlled dose escalation study, randomized 3 cohorts of healthy volunteers to receive a single intravenous dose of NTM-1632 (0.033, 0.165, or 0.330 mg/kg) or saline placebo. Safety monitoring included physical examinations, clinical laboratory studies, and vital signs. Blood sampling was performed at pre-specified time points for PK and immunogenicity analyses. Results Twenty-four subjects received study product (18 NTM-1632; 6 placebo), and no deaths or serious adverse events were reported. Adverse events in the NTM-1632 groups were generally mild and similar in frequency and severity to the placebo group, and no safety signal was identified. NTM-1632 has a favorable PK profile with a half-life >20 days for the 0.330 mg/kg dose and an approximately linear relationship with respect to maximum concentration and area under the concentration-time curve (AUC_0→t). NTM-1632 demonstrated low immunogenicity with only a few treatment-emergent anti-drug antibody responses in the low and middle dosing groups and none at the highest dose. Interpretation NTM-1632 is well-tolerated at the administered doses. The favorable safety, PK, and immunogenicity profile of NTM-1632 supports further clinical development as a treatment for BoNT/B intoxication and post-exposure prophylaxis.

Objective In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically (72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18). Conclusion In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure. Key Points ^* Additional members of this network are listed in [ Supplementary Material ] (available in the online version). Received: 08 October 2020 Accepted: 16 March 2021 Article published online: 27 May 2021 © 2021. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA