Multidisciplinary First-Line Healthcare Leaders' Roles and Experiences During the COVID-19 Pandemic in Ontario Canada.

BACKGROUND: Throughout the COVID-19 pandemic, first-line healthcare leaders across the healthcare system played crucial roles leading, motivating, and supporting staff. PURPOSE: This study aims to describe multidisciplinary first-line healthcare leaders' experiences during the COVID-19 pandemic in Ontario, Canada using transformational and crisis leadership theory. METHODS: A descriptive two-phase (quantitative & qualitative) design was conducted in the spring of 2021. Phase 1 employed an online survey sent via email to first-line leaders from various sectors who were members of healthcare professional associations in Ontario. Participants included nurse managers, professional practice leaders (e.g., occupational and physiotherapists), advanced practice nurses, and clinical educators. In Phase 2, a subset (n = 19) of the Phase 1 participants were interviewed to gain a deeper understanding of these leaders' experiences including role impact and support available. Semistructured individual interviews were conducted and recorded via Zoom©. Inductive and deductive analysis approaches identified key themes. This paper reports the qualitative findings from Phase 2. RESULTS: Leaders' behaviors were representative of the key dimensions of transformational and complexity leadership theories. Recommendations for leading during a crisis included: engaging in self-care activities to manage the personal impact of the crisis; teamwork and collaborative leadership; and support from fellow first-line leaders and senior leaders. Findings can inform healthcare leadership education programs designed to manage future crises for both academic and practice settings. CONCLUSION: Descriptions of first-line healthcare leaders' roles and experiences during multiple waves of the COVID-19 pandemic validated their important contributions within various health sectors.

Career Pathway Strategies That Reduce Barriers for Nontraditional Nursing Students.

Everyone recognizes the current nursing scarcity, but not everyone recognizes the need for a diverse nursing workforce to adequately serve patients whose social determinants of health include racism, racial bias, and reduced access to care. This article explores how building innovative partnerships between health-care providers and nursing institutions to advance the incumbent workforce can increase capacity and reduce staff burnout. Such partnerships can drive a culture of employee engagement through the development of career pathways while reducing barriers for nontraditional nursing students in advancing their credentials. This article reports on a strategy to address the nursing shortage and to increase the diversity of the nursing workforce through a licensed vocational nurse-to-registered nurse partnership between a school of nursing and a Federally Qualified Health Center.

Antimicrobial susceptibility of Salmonella and Escherichia coli from equids sampled in the NAHMS 2015-16 equine study and association of management factors with resistance.

Several studies have investigated antimicrobial resistance (AMR) in Salmonella spp. and Escherichia coli isolated from hospitalized horses, but studies conducted on community-based populations of equids are limited. The factors associated with AMR in these bacteria in the general horse population are not well understood. The primary objective of our study was to estimate the prevalence of Salmonella and describe antimicrobial susceptibility of Salmonella and E. coli from equids across the United States. The second objective was to identify associations between health management and biosecurity practices and AMR. Fecal samples submitted from 1357 equids on 199 operations were tested for Salmonella, identifying 27 positive samples with 29 isolates belonging to 18 serotypes. Fecal sample and operation-level prevalence of Salmonella was 2.0% (27/1357) and 7.0% (14/199), respectively. Most (25/29) isolates were pan-susceptible while four isolates exhibited resistance, three of which were multidrug resistant. Of the 721 samples cultured for E. coli, 85% (613/721) were positive. Eighty-six percent of the E. coli isolates recovered were pan-susceptible (529/612). Ten isolates were intermediate to one antimicrobial drug and susceptible to all others. Seventy-three E. coli isolates (11.9%, SE=1.3) were resistant to one or more antimicrobials, corresponding to a 33.0% (64/194) operation-level prevalence. Resistance to sulfonamide drugs was most common with 63 isolates (10.3%) resistant to sulfisoxazole, 57 of which (9.3%) were resistant to trimethoprim-sulfamethoxazole. MDR in E. coli was rare (1.8%, SE=0.5). Univariate and multivariable regression were used to evaluate associations between health management and biosecurity questionnaire items and AMR in E. coli. The outcome modeled was resistance to any of the 14 tested antimicrobials. Depending on the operation type, operations with greater than 20 resident equids were significantly associated with resistance. In addition, performance operations were significantly associated with resistance when compared to farm/ranch operations. Operations with feed containers that prevent fecal contamination and those that had treated any equids for illness or injury were associated with a lower AMR. The study results suggest that equids in the general population appear to pose low risk of shedding antimicrobial resistant strains of Salmonella and E. coli, and therefore low transmission potential to other equids, animals, humans, or the environment. However, it is prudent to practice good hand hygiene to prevent spread of Salmonella as well as AMR, and to protect both animal and human health. Despite study limitations, potential management factors that may influence prevalence and prevent spread of AMR shed by equids were identified.

Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation.

Quantitative pharmacology brings important advantages in the design and conduct of pediatric clinical trials. Herein, we demonstrate the application of a model-based approach to select doses and pharmacokinetic sampling scenarios for the clinical evaluation of a novel oral suspension of spironolactone in pediatric patients with edema. A population pharmacokinetic model was developed and qualified for spironolactone and its metabolite, canrenone, using data from adults and bridged to pediatrics (2 to <17 years old) using allometric scaling. The model was then used via simulation to explore different dosing and sampling scenarios. Doses of 0.5 and 1.5 mg/kg led to target exposures (i.e., similar to 25 and 100 mg of the reference product in adults) in all the reference pediatric ages (i.e., 2, 6, 12 and 17 years). Additionally, two different sampling scenarios were delineated to accommodate patients into sparse sampling schemes informative to characterize drug pharmacokinetics while minimizing phlebotomy and burden to participating children.

Antimicrobial resistant gene prevalence in soils due to animal manure deposition and long-term pasture management.

The persistence of antimicrobial resistant (AMR) genes in the soil-environment is a concern, yet practices that mitigate AMR are poorly understood, especially in grasslands. Animal manures are widely deposited on grasslands, which are the largest agricultural land-use in the United States. These nutrient-rich manures may contain AMR genes. The aim of this study was to enumerate AMR genes in grassland soils following 14-years of poultry litter and cattle manure deposition and evaluate if best management practices (rotationally grazed with a riparian (RBR) area and a fenced riparian buffer strip (RBS), which excluded cattle grazing and poultry litter applications) relative to standard pasture management (continuously grazed (CG) and hayed (H)) minimize the presence and amount of AMR genes. Quantitative PCR (Q-PCR) was performed to enumerate four AMR genes (ermB, sulI, intlI, and blactx-m-32 ) in soil, cattle manure, and poultry litter environments. Six soil samples were additionally subjected to metagenomic sequencing and resistance genes were identified from assembled sequences. Following 14-years of continuous management, ermB, sulI, and intlI genes in soil were greatest (P < 0.05) in samples collected under long-term continuous grazing (relative to conservation best management practices), under suggesting overgrazing and continuous cattle manure deposition may increase AMR gene presence. In general, AMR gene prevalence increased downslope, suggesting potential lateral movement and accumulation based on landscape position. Poultry litter had lower abundance of AMR genes (ermB, sulI, and intlI) relative to cattle manure. Long-term applications of poultry litter increased the abundance of sulI and intlI genes in soil (P < 0.05). Similarly, metagenomic shotgun sequencing revealed a greater total number of AMR genes under long-term CG, while fewer AMR genes were found in H (no cattle manure) and RBS (no animal manure or poultry litter). Results indicate long-term conservation pasture management practices (e.g., RBS and RBR) and select animal manure (poultry litter inputs) may minimize the presence and abundance of AMR genes in grassland soils.

Soil bacterial biodiversity is driven by long-term pasture management, poultry litter, and cattle manure inputs.

Soil microorganisms are important for maintaining soil health, decomposing organic matter, and recycling nutrients in pasture systems. However, the impact of long-term conservation pasture management on soil microbial communities remains unclear. Therefore, soil microbiome responses to conservation pasture management is an important component of soil health, especially in the largest agricultural land-use in the US. The aim of this study was to identify soil microbiome community differences following 13-years of pasture management (hayed (no cattle), continuously grazed, rotationally grazed with a fenced, un-grazed and unfertilized buffer strip, and a control (no poultry litter or cattle manure inputs)). Since 2004, all pastures (excluding the control) received annual poultry litter at a rate of 5.6 Mg ha-1. Soil samples were collected at a 0-15 cm depth from 2016-2017 either pre or post poultry litter applications, and bacterial communities were characterized using Illumina 16S rRNA gene amplicon sequencing. Overall, pasture management influenced soil microbial community structure, and effects were different by year (P < 0.05). Soils receiving no poultry litter or cattle manure had the lowest richness (Chao). Continuously grazed systems had greater (P < 0.05) soil community richness, which corresponded with greater soil pH and nutrients. Consequently, continuously grazed systems may increase soil diversity, owing to continuous nutrient-rich manure deposition; however, this management strategy may adversely affect aboveground plant communities and water quality. These results suggest conservation pasture management (e.g., rotationally grazed systems) may not improve microbial diversity, albeit, buffer strips were reduced nutrients and bacterial movement as evident by low diversity and fertility in these areas compared to areas with manure or poultry litter inputs. Overall, animal inputs (litter or manure) increased soil microbiome diversity and may be a mechanism for improved soil health.

Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti-Helicobacter pylori IgG antibodies.

BACKGROUND: Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection. METHODS: A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old. RESULTS: We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered. CONCLUSIONS: Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity.

Metabolomic profiling of asthma: diagnostic utility of urine nuclear magnetic resonance spectroscopy.

BACKGROUND: The ability to diagnose and monitor asthma on the basis of noninvasive measurements of airway cellular dysfunction is difficult in the typical clinical setting. OBJECTIVE: Metabolomics is the study of molecules created by cellular metabolic pathways. We hypothesized that the metabolic activity of children with asthma would differ from healthy children without asthma. Furthermore, children having an asthma exacerbation would be different compared with children with stable asthma in outpatient clinics. Finally, we hypothesized that (1)H-nuclear magnetic resonance (NMR) would measure such differences using urine samples, one of the least invasive forms of biofluid sampling. METHODS: Children (135 total, ages 4-16 years) were enrolled, having met the criteria of healthy controls (C), stable asthma in the outpatient clinic (AO), or unstable asthma in the emergency department (AED). Partial least squares discriminant analysis was performed on the NMR data to create models of separation (70 metabolites were measured/urine sample). Some NMR data were withheld from modeling to be run blindly to determine possible diagnostic accuracy. RESULTS: On the basis of the model of AO versus C, 31 of 33 AO samples were correctly diagnosed with asthma (94% accuracy). Only 1 of 20 C samples was incorrectly labeled as asthma (5% misclassification). On the basis of the AO versus AED model, 31 of the 33 AO samples were correctly diagnosed as outpatient asthma (94% accurate). CONCLUSION: This is the first report suggesting that (1)H-NMR analysis of human urine samples has the potential to be a useful clinical tool for physicians treating asthma.

B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody.

The pan B-cell surface antigen CD19 is an attractive target for therapeutic monoclonal antibody (mAb) approaches. We have generated a new afucosylated anti-human (hu)CD19 mAb, MEDI-551, with increased affinity to human FcγRIIIA and mouse FcγRIV and enhanced antibody-dependent cellular cytotoxicity (ADCC). During in vitro ADCC assays with B-cell lines, MEDI-551 is effective at much lower mAb concentrations than the fucosylated parental mAb anti-CD19-2. Furthermore, the afucosylated CD19 mAb MEDI-551 depleted B cells from normal donor peripheral blood mononuclear cell samples in an autologous ADCC assay, as well as blood and tissue B cells in human CD19/CD20 double transgenic (Tg) mice at lower concentrations than that of the positive control mAb rituximab. In huCD19/CD20 Tg mice, both macrophage-mediated phagocytosis and complement-dependent cytotoxicity contribute to depletion with rituximab; MEDI-551 did not require complement for maximal B-cell depletion. Furthermore, extended B-cell depletion from the blood and spleen was achieved with MEDI-551, which is probably explained by bone marrow B-cell depletion in huCD19/CD20 Tg mice relative to the control mAb rituximab. In summary, MEDI-551 has potent B-cell-depleting activity in vitro and in vivo and may be a promising new approach for the treatment of B-cell malignancies and autoimmune diseases.

Antibody-dependent cell-mediated cytotoxicity effector-enhanced EphA2 agonist monoclonal antibody demonstrates potent activity against human tumors.

EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vitro and in vivo antibody-dependent cell-mediated cytotoxicity (ADCC) activity of EphA2 effector-enhanced agonist monoclonal antibodies was evaluated. With tumor cell lines and healthy human peripheral blood monocytes, the EphA2 antibodies demonstrated approximately 80% tumor cell killing. In a dose-dependent manner, natural killer (NK) cells were required for the in vitro ADCC activity and became activated as demonstrated by the induction of cell surface expression of CD107a. To assess the role of NK cells on antitumor efficacy in vivo, the EphA2 antibodies were evaluated in xenograft models in severe compromised immunodeficient (SCID) mice (which have functional NK cells and monocytes) and SCID nonobese diabetic (NOD) mice (which largely lack functional NK cells and monocytes). Dosing of EphA2 antibody in the SCID murine tumor model resulted in a 6.2-fold reduction in tumor volume, whereas the SCID/nonobese diabetic model showed a 1.6-fold reduction over the isotype controls. Together, these results demonstrate that the anti-EphA2 monoclonal antibodies may function through at least two mechanisms of action: EphA2 receptor activation and ADCC-mediated activity. These novel EphA2 monoclonal antibodies provide additional means by which host effector mechanisms can be activated for selective destruction of EphA2-expressing tumor cells.

Cancer screening practices and attitudes: comparison of low-income women in three ethnic groups.

OBJECTIVE: Based on the Health Belief Model, this study investigates differences among ethnically diverse, low-income women in the USA to inform better outreach strategies to encourage participation in the Centers for Disease Control & Prevention (CDC)- sponsored breast and cervical cancer early detection program. DESIGN: Program-eligible, low-income, Hispanic, Vietnamese and Cambodian American women who were over the age of 40 volunteered to be interviewed in their first language for the study. A total of 78 women completed the interviews. RESULTS: All three samples of women were more likely to perceive barriers to having a mammogram performed compared to the non-minority normative group. Hispanic and Vietnamese women were more similar in their health beliefs and behaviors than Vietnamese and Cambodian women. CONCLUSION: This study supports other research on the barriers and health belief differences found among ethnic minority women in the USA. Further, these findings suggest that it is not advisable to collapse ethnic groups into general categories such as 'Asian' when planning cancer control strategies, as differences were found by country of origin.