Degradation of endothelial glycocalyx in Tanzanian children with falciparum malaria.

A layer of glycocalyx covers the vascular endothelium serving important protective and homeostatic functions. The objective of this study was to determine if breakdown of the endothelial glycocalyx (eGC) occurs during malaria infection in children. Measures of eGC integrity, endothelial activation, and microvascular reactivity were prospectively evaluated in 146 children: 44 with moderately severe malaria (MSM), 42 with severe malaria (SM), and 60 healthy controls (HC). Biochemical measures of eGC integrity included plasma syndecan-1 and total urinary glycosaminoglycans (GAG). Side-stream dark field imaging was used to quantitatively assess integrity of eGC. Plasma angiopoietin-2 (Ang-2) was measured as a marker of endothelial activation and also as a possible mediator of eGC breakdown. Our results show that urinary GAG, syndecan-1, and Ang-2 were elevated in patients with MSM and SM compared with HC. Syndecan-1 and GAG levels correlated significantly with each other and with plasma Ang-2. The eGC breakdown products also inversely correlated significantly with hemoglobin and platelet count. In the MSM group, imaging results provided further evidence for eGC degradation. Although not correlated with markers of eGC degradation, vascular function (assessed by non-invasive near infrared spectroscopy [NIRS]) demonstrated reduced microvascular reactivity, particularly affecting the SM group. Our findings provide further evidence for breakdown of eGC in falciparum malaria that may contribute to endothelial activation and adhesion of parasitized red blood cells, with reduced nitric oxide formation, and vascular dysfunction.

Improving Patient Experience and Treatment Adherence in the Adult, Outpatient Hemodialysis Population.

BACKGROUND: The commonly employed medication reconciliation process leaves room for mismanagement of medications in the complex end-stage renal disease patient population. PURPOSE: The purpose of this quality improvement project was to implement and evaluate a multidisciplinary education and feedback intervention designed to improve self-management for adults with end-stage renal disease. METHODS: A pre-post, same subject repeated measures design was used to evaluate the intervention. Laboratory values, vital signs, interdialytic weight gains, dialysis attendance, and questionnaires were used to assess regimen adherence. RESULTS: We observed improvements in patient outcomes including laboratory values, vital signs, and interdialytic weight gains. Significant improvements in process outcomes were also seen, including accuracy of medication lists, dialysis attendance, and use of remote pharmacy services. CONCLUSIONS: A comprehensive medication review, with concurrent pharmacist access, represents a time-effective approach to improved self-management and end-stage renal disease outcomes.

Transitioning your course to online: High-yield modifications for success.

INTRODUCTION: Faculty everywhere are struggling to transition their on-campus courses to an online format due to the COVID-19 pandemic. We transitioned our graduate pathophysiology and clinical pharmacology courses for advanced practice providers from the classroom to completely online several years ago. These are content heavy courses with relatively high enrollment. PERSPECTIVE: Since transitioning we have identified challenges and gathered extensive student feedback that has guided substantial refinement of these courses. In this article we highlight how our approaches to online teaching focus on four basic pillars: organization, course content delivery, communication, and assessment. IMPLICATIONS: Examples of high-yield improvements that enhance learning are provided.

Vascular Dysfunction in Malaria: Understanding the Role of the Endothelial Glycocalyx.

Malaria caused by Plasmodium falciparum results in over 400,000 deaths annually, predominantly affecting African children. In addition, non-falciparum species including vivax and knowlesi cause significant morbidity and mortality. Vascular dysfunction is a key feature in malaria pathogenesis leading to impaired blood perfusion, vascular obstruction, and tissue hypoxia. Contributing factors include adhesion of infected RBC to endothelium, endothelial activation, and reduced nitric oxide formation. Endothelial glycocalyx (eGC) protects the vasculature by maintaining vessel integrity and regulating cellular adhesion and nitric oxide signaling pathways. Breakdown of eGC is known to occur in infectious diseases such as bacterial sepsis and dengue and is associated with adverse outcomes. Emerging studies using biochemical markers and in vivo imaging suggest that eGC breakdown occurs during Plasmodium infection and is associated with markers of malaria disease severity, endothelial activation, and vascular function. In this review, we describe characteristics of eGC breakdown in malaria and discuss how these relate to vascular dysfunction and adverse outcomes. Further understanding of this process may lead to adjunctive therapy to preserve or restore damaged eGC and reduce microvascular dysfunction and the morbidity/mortality of malaria.

Surface Contamination With Antineoplastic Drugs on Two Inpatient Oncology Units.

OBJECTIVES: To measure surface contamination with antineoplastic drugs on inpatient oncology units and to characterize nursing staff personal protective equipment (PPE) use and factors that predict this use. SAMPLE & SETTING: A descriptive pilot study of two inpatient oncology units at Duke University Hospital in Durham, North Carolina, administering etoposide and cyclophosphamide. METHODS & VARIABLES: Surfaces in four patient rooms and select shared areas were swabbed with methanol, acetonitrile, and water. Samples were analyzed by liquid chromatography tandem mass spectrometry. Nursing staff (N = 27) answered questions about their demographics, PPE use, and factors that influence PPE use via online survey. RESULTS: Contamination with cyclophosphamide and etoposide was detectable and quantifiable in 61% and 31% of surfaces tested, respectively. Nursing staff reported suboptimal use of PPE when administering, disposing, and handling excreta of patients. Workplace safety climate was predictive of PPE use. IMPLICATIONS FOR NURSING: The potential for contamination with antineoplastic drugs in inpatient oncology units presents exposure risks for healthcare workers, patients, family members, and visitors. Future research and interventions to limit exposure and increase routine surface sampling should focus on those areas of greatest contamination, including toilet seats, a prominent finding from the current study.

Student evaluations of teaching (SET): Guidelines for their use.

Student evaluations of teaching (SET) provide a structured way of collecting feedback from students about the course and teacher's effectiveness. We reviewed literature describing use of SET across a broad range of disciplines in undergraduate and graduate education to provide guidelines for faculty in using SET in a nursing or other health professions program. On SET tools, students typically rate their satisfaction with a course and perceptions about the quality of the teaching. It is important to evaluate SET tools prior to their use including pilot testing tools with students because studies show students may not interpret items or questions on a SET tool as faculty intended. Common uses of the evaluation data from SET include improvement of courses and teaching, and for personnel decisions.

Monocyte polarization in children with falciparum malaria: relationship to nitric oxide insufficiency and disease severity.

We earlier established that nitric oxide (NO) is protective against severe malaria and that arginine and NO levels are reduced in malaria patients. We now show that an M2-like blood monocyte phenotype is significantly associated with hypoargininemia, NO insufficiency, and disease severity in Tanzanian children with falciparum malaria. Compared to control children (n = 106), children with moderately severe (n = 77) and severe falciparum malaria (n = 129) had significantly higher mononuclear cell arginase 1 mRNA, protein, and enzyme activity; lower NOS2 mRNA; lower plasma arginine; and higher plasma IL-10, IL-13, and IL-4. In addition, monocyte CD206 and CD163 and plasma soluble CD163 were elevated. Multivariate logistic regression analysis revealed a significant correlation of risk of severe malaria with both plasma IL-10 and soluble CD163 levels. Monocyte M2 skewing likely contributes to NO bioinsufficiency in falciparum malaria in children. Treatments that reverse the M2 polarization may have potential as adjunctive treatment for malaria.