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Patients on dialysis are at high risk for severe COVID-19 and associated morbidity and mortality. We examined the humoral response to SARS-CoV-2 mRNA vaccine BNT162b2 in a maintenance dialysis population.
Single-center cohort study.
Setting and participants:
Adult maintenance dialysis patients at 3 outpatient dialysis units of a large academic center.
Participants were vaccinated with 2 doses of BNT162b2, 3 weeks apart. We assessed anti–SARS-CoV-2 spike antibodies (anti-S) ∼4–7 weeks after the second dose and evaluated risk factors associated with insufficient response. Definitions of antibody response are as follows: nonresponse (anti-S level, <50 AU/mL), low response (anti-S level, 50–839 AU/mL), and sufficient response (anti-S level, ≥840 AU/mL).
Among the 173 participants who received 2 vaccine doses, the median age was 60 years (range, 28–88), 53.2% were men, 85% were of Black race, 86% were on in-center hemodialysis and 14% were on peritoneal dialysis. Also, 7 participants (4%) had no response, 27 (15.6%) had a low response, and 139 (80.3%) had a sufficient antibody response. In multivariable analysis, factors significantly associated with insufficient antibody response included end-stage renal disease comorbidity index score ≥5 and absence of prior hepatitis B vaccination response.
Although most of our study participants seroconverted after 2 doses of BNT162b2, 20% of our cohort did not achieve sufficient humoral response. Our findings demonstrate the urgent need for a more effective vaccine strategy in this high-risk patient population and highlight the importance of ongoing preventative measures until protective immunity is achieved.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in neonatal intensive care units (NICU) that confers significant morbidity and mortality.
Improving our understanding of MRSA transmission dynamics, especially among high-risk patients, is an infection prevention priority.
We investigated a cluster of clinical MRSA cases in the NICU using a combination of epidemiologic review and whole-genome sequencing (WGS) of isolates from clinical and surveillance cultures obtained from patients and healthcare personnel (HCP).
Phylogenetic analysis identified 2 genetically distinct phylogenetic clades and revealed multiple silent-transmission events between HCP and infants. The predominant outbreak strain harbored multiple virulence factors. Epidemiologic investigation and genomic analysis identified a HCP colonized with the dominant MRSA outbreak strain who cared for most NICU patients who were infected or colonized with the same strain, including 1 NICU patient with severe infection 7 months before the described outbreak. These results guided implementation of infection prevention interventions that prevented further transmission events.
Silent transmission of MRSA between HCP and NICU patients likely contributed to a NICU outbreak involving a virulent MRSA strain. WGS enabled data-driven decision making to inform implementation of infection control policies that mitigated the outbreak. Prospective WGS coupled with epidemiologic analysis can be used to detect transmission events and prompt early implementation of control strategies.
From 2014 to 2020, we compiled radiocarbon ages from the lower 48 states, creating a database of more than 100,000 archaeological, geological, and paleontological ages that will be freely available to researchers through the Canadian Archaeological Radiocarbon Database. Here, we discuss the process used to compile ages, general characteristics of the database, and lessons learned from this exercise in “big data” compilation.
The aim of this study was to investigate the performance of key hospital units associated with emergency care of both routine emergency and pandemic (COVID-19) patients under capacity enhancing strategies.
This investigation was conducted using whole-hospital, resource-constrained, patient-based, stochastic, discrete-event, simulation models of a generic 200-bed urban U.S. tertiary hospital serving routine emergency and COVID-19 patients. Systematically designed numerical experiments were conducted to provide generalizable insights into how hospital functionality may be affected by the care of COVID-19 pandemic patients along specially designated care paths, under changing pandemic situations, from getting ready to turning all of its resources to pandemic care.
Several insights are presented. For example, each day of reduction in average ICU length of stay increases intensive care unit patient throughput by up to 24% for high COVID-19 daily patient arrival levels. The potential of 5 specific interventions and 2 critical shifts in care strategies to significantly increase hospital capacity is also described.
These estimates enable hospitals to repurpose space, modify operations, implement crisis standards of care, collaborate with other health care facilities, or request external support, thereby increasing the likelihood that arriving patients will find an open staffed bed when 1 is needed.
Philosophical arguments must be understood in relation to the historical contexts in which they were produced. This yields the recognition that the distinction between early modern “philosophy” and “science” is an anachronistic imposition—the philosophical foundation of modernity and the Scientific Revolution are facets of the same transformations. However, the “contextualist turn” presents methodological difficulties arising from the opposition of philosophical analysis and historical narrative. This introduction presents two strategies for resolving these tensions in the study of the period. First, examination of how authors identified with peers and opposed themselves to foes generates a fine-grained understanding of early modern disciplines, without anachronistic impositions. Second, shifts in disciplinary boundaries can be used as entry points into the networks of influences that ramified across the intellectual landscape, yielding narratives that are sensitive to a wide range of textual and contextual factors. Together, awareness of disciplinary boundaries and their “inflection points” offers an updated methodology for the investigation of the early modern period. Anachronistic grand narratives of early modern philosophy and of the Scientific Revolution will be superseded by more modest but much more sophisticated accounts of the multiplication and reorganization of intellectual disciplines.
Sidereus Nuncius was a seminal text of the Scientific Revolution. It reported celestial observations whose implications upended the geocentric cosmology few had ever doubted. But Galileo’s treatise also combined topics and methodologies that traditionally had been assigned separately to mixed mathematics and natural philosophy. Whereas the bounds between these disciplines had been weakened by earlier controversies, particularly about the regressus method and about the certainty of mathematics (i.e., the Quaestio de Certitudine), Sidereus Nuncius broke them down altogether, to the delight and dismay of readers. Galileo’s application of mathematical methods—empiricism and quantification—to natural philosophy framed the ensuing discussions, such that even those who disagreed with his conclusions responded on those grounds. Thus, the book was pivotal in the process of disciplinary admixture that reorganized the study of nature into modern science.
To evaluate the impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in severe Ebstein anomaly and tricuspid valve dysplasia.
Thirty-four fetuses with Ebstein anomaly/tricuspid valve dysplasia were referred from 2013 to 2019 for fetal echocardiography and clinical management. Nineteen fetuses with Ebstein anomaly/tricuspid valve dysplasia and 30 controls underwent cardiovascular magnetic resonance to quantify the fetal blood flow and to calculate cerebral oxygen delivery (cDO2) and consumption (cVO2). The 3D steady-state free precession acquisition was used to measure fetal brain volume. Surgical outcome, brain MRI, and neurodevelopmental follow-up were reviewed.
Twenty-six fetuses were live born (76%) and survival (65%) at a mean follow-up of 4 years. Nine fetuses had a brain MRI before discharge, and all had clinically silent injuries and volume loss. At 18 months, five single-ventricle patients had a neurodevelopmental delay in cognition and language (mean percentile: 11th), with gross-motor skills more affected than fine-motor skills (mean percentiles: 4th and 34th). Fetuses with Ebstein anomaly/tricuspid valve dysplasia had smaller brains, lower combined ventricular output, ascending aorta, superior caval vien and umbilical vein flows, lower oxygen saturation in ascending aorta and superior caval vien, lower cDO2 and cVO2 (p < 0.05). Superior caval vien/combined ventricular output and descending aorta/combined ventricular output ratios were lower in fetuses with circular shunt (p < 0.05). Fetuses requiring the Starnes procedure tended to have smaller brains, lower combined ventricular output, superior caval vien, descending aorta, and umbilical vein flows.
All patients with Ebstein anomaly/tricuspid valve dysplasia are at high risk of neurodevelopmental delay and warrant follow-up. Fetal cardiovascular magnetic resonance revealed impaired brain growth with diminished cerebral blood flow and cDO2, the extenting dependent on the severity of the haemodynamic compromise.
The early modern era produced the Scientific Revolution, which originated our present understanding of the natural world. Concurrently, philosophers established the conceptual foundations of modernity. This rich and comprehensive volume surveys and illuminates the numerous and complicated interconnections between philosophical and scientific thought as both were radically transformed from the late sixteenth to the mid-eighteenth century. The chapters explore reciprocal influences between philosophy and physics, astronomy, mathematics, medicine, and other disciplines, and show how thinkers responded to an immense range of intellectual, material, and institutional influences. The volume offers a unique perspicuity, viewing the entire landscape of early modern philosophy and science, and also marks an epoch in contemporary scholarship, surveying recent contributions and suggesting future investigations for the next generation of scholars and students.
Praziquantel (PZQ) remains the only drug of choice for the treatment of schistosomiasis, caused by parasitic flatworms. The widespread use of PZQ in schistosomiasis endemic areas for about four decades raises concerns about the emergence of resistance of Schistosoma spp. to PZQ under drug selection pressure. This reinforces the urgency in finding alternative therapeutic options that could replace or complement PZQ. We explored the potential of medicinal plants commonly used by indigenes in Kenya for the treatment of various ailments including malaria, pneumonia, and diarrhoea for their antischistosomal properties. Employing the Soxhlet extraction method with different solvents, seven medicinal plants Artemisia annua, Ajuga remota, Bredilia micranta, Cordia africana, Physalis peruviana, Prunus africana and Senna didymobotrya were extracted. Qualitative phytochemical screening was performed to determine the presence of various phytochemicals in the plant extracts. Extracts were tested against Schistosoma mansoni newly transformed schistosomula (NTS) and adult worms and the schistosomicidal activity was determined by using the adenosine triphosphate quantitation assay. Phytochemical analysis of the extracts showed different classes of compounds such as alkaloids, tannins, terpenes, etc., in plant extracts active against S. mansoni worms. Seven extracts out of 22 resulted in <20% viability against NTS in 24 h at 100 μg/ml. Five of the extracts with inhibitory activity against NTS showed >69.7% and ≥72.4% reduction in viability against adult worms after exposure for 24 and 48 h, respectively. This study provides encouraging preliminary evidence that extracts of Kenyan medicinal plants deserve further study as potential alternative therapeutics that may form the basis for the development of the new treatments for schistosomiasis.