ABSTRACT
BACKGROUND: The COVID-19 pandemic dramatically altered the psychosocial environment of pregnant women and new mothers. In addition, prenatal infection is a known risk factor for altered fetal development. Here we examine joint effects of maternal psychosocial stress and COVID-19 infection during pregnancy on infant attention at 6 months postpartum. METHOD: One-hundred and sixty-seven pregnant mothers and infants (40% non-White; n = 71 females) were recruited in New York City (n = 50 COVID+, n = 117 COVID-). Infants' attentional processing was assessed at 6 months, and socioemotional function and neurodevelopmental risk were evaluated at 12 months. RESULTS: Maternal psychosocial stress and COVID-19 infection during pregnancy jointly predicted infant attention at 6 months. In mothers reporting positive COVID-19 infection, higher prenatal psychosocial stress was associated with lower infant attention at 6 months. Exploratory analyses indicated that infant attention in turn predicted socioemotional function and neurodevelopmental risk at 12 months. CONCLUSIONS: These data suggest that maternal psychosocial stress and COVID-19 infection during pregnancy may have joint effects on infant attention at 6 months. This work adds to a growing literature on the effects of the COVID-19 pandemic on infant development, and may point to maternal psychosocial stress as an important target for intervention. IMPACT: This study found that elevated maternal psychosocial stress and COVID-19 infection during pregnancy jointly predicted lower infant attention scores at 6 months, which is a known marker of risk for neurodevelopmental disorder. In turn, infant attention predicted socioemotional function and risk for neurodevelopmental disorder at 12 months. These data suggest that maternal psychosocial stress may modulate the effects of gestational infection on neurodevelopment and highlight malleable targets for intervention.
ABSTRACT
Objectives: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. Methods: An online survey was sent to all infection consultants in NHS acute hospitals in England. Results: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. Conclusions: The 'subscription-type' model was viewed favourably by infection consultants in England.
ABSTRACT
The intestinal lymphatic system plays an important role in the pathophysiology of multiple diseases including lymphomas, cancer metastasis, autoimmune diseases, and human immunodeficiency virus (HIV) infection. It is thus an important compartment for delivery of drugs in order to treat diseases associated with the lymphatic system. Lipophilic prodrug approaches have been used in the past to take advantage of the intestinal lymphatic transport processes to deliver drugs to the intestinal lymphatics. Most of the approaches previously adopted were based on very bulky prodrug moieties such as those mimicking triglycerides (TG). We now report a study in which a lipophilic prodrug approach was used to efficiently deliver bexarotene (BEX) and retinoic acid (RA) to the intestinal lymphatic system using activated ester prodrugs. A range of carboxylic ester prodrugs of BEX were designed and synthesised and all of the esters showed improved association with chylomicrons, which indicated an improved potential for delivery to the intestinal lymphatic system. The conversion rate of the prodrugs to BEX was the main determinant in delivery of BEX to the intestinal lymphatics, and activated ester prodrugs were prepared to enhance the conversion rate. As a result, an 4-(hydroxymethyl)-1,3-dioxol-2-one ester prodrug of BEX was able to increase the exposure of the mesenteric lymph nodes (MLNs) to BEX 17-fold compared to when BEX itself was administered. The activated ester prodrug approach was also applied to another drug, RA, where the exposure of the MLNs was increased 2.4-fold through the application of a similar cyclic activated prodrug. Synergism between BEX and RA was also demonstrated in vitro by cell growth inhibition assays using lymphoma cell lines. In conclusion, the activated ester prodrug approach results in efficient delivery of drugs to the intestinal lymphatic system, which could benefit patients affected by a large number of pathological conditions.
