Intervention-Induced Changes in Balance and Task-Dependent Neural Activity in Adults with Acquired Brain Injury: A Pilot Randomized Control Trial.

Advances in neuroimaging technology, like functional near-infrared spectroscopy (fNIRS), support the evaluation of task-dependent brain activity during functional tasks, like balance, in healthy and clinical populations. To date, there have been no studies examining how interventions, like yoga, impact task-dependent brain activity in adults with chronic acquired brain injury (ABI). This pilot study compared eight weeks of group yoga (active) to group exercise (control) on balance and task-dependent neural activity outcomes. Twenty-three participants were randomized to yoga (n = 13) or exercise groups (n = 10). Neuroimaging and balance performance data were collected simultaneously using a force plate and mobile fNIRS device before and after interventions. Linear mixed-effects models were used to evaluate the effect of time, time x group interactions, and simple (i.e., within-group) effects. Regardless of group, all participants had significant balance improvements after the interventions. Additionally, regardless of group, there were significant changes in task-dependent neural activity, as well as distinct changes in neural activity within each group. In summary, using advances in sensor technology, we were able to demonstrate preliminary evidence of intervention-induced changes in balance and neural activity in adults with ABI. These preliminary results may provide an important foundation for future neurorehabilitation studies that leverage neuroimaging methods, like fNIRS.

Comparison of Infinium MethylationEPIC v2.0 to v1.0 for human population epigenetics: considerations for addressing EPIC version differences in DNA methylation-based tools.

Background: The recently launched DNA methylation profiling platform, Illumina MethylationEPIC BeadChip Infinium microarray v2.0 (EPICv2), is highly correlated with measurements obtained from its predecessor MethylationEPIC BeadChip Infinium microarray v1.0 (EPICv1). However, the concordance between the two versions in the context of DNA methylation-based tools, including cell type deconvolution algorithms, epigenetic clocks, and inflammation and lifestyle biomarkers has not yet been investigated. Findings: We profiled DNA methylation on both EPIC versions using matched venous blood samples from individuals spanning early to late adulthood across three cohorts. On combining the DNA methylomes of the cohorts, we observed that samples primarily clustered by the EPIC version they were measured on. Within each cohort, when we calculated cell type proportions, epigenetic age acceleration (EAA), rate of aging estimates, and biomarker scores for the matched samples on each version, we noted significant differences between EPICv1 and EPICv2 in the majority of these estimates. These differences were not significant, however, when estimates were adjusted for EPIC version or when EAAs were calculated separately for each EPIC version. Conclusions: Our findings indicate that EPIC version differences predominantly explain DNA methylation variation and influence estimates of DNA methylation-based tools, and therefore we recommend caution when combining cohorts run on different versions. We demonstrate the importance of calculating DNA methylation-based estimates separately for each EPIC version or accounting for EPIC version either as a covariate in statistical models or by using version correction algorithms.

Cold versus hot snare endoscopic mucosal resection for large (≥15 mm) flat non-pedunculated colorectal polyps: a randomised controlled trial.

BACKGROUND AND AIMS: Conventional hot snare endoscopic mucosal resection (H-EMR) is effective for the management of large (≥20 mm) non-pedunculated colon polyps (LNPCPs) however, electrocautery-related complications may incur significant morbidity. With a superior safety profile, cold snare EMR (C-EMR) of LNPCPs is an attractive alternative however evidence is lacking. We conducted a randomised trial to compare the efficacy and safety of C-EMR to H-EMR. METHODS: Flat, 15-50 mm adenomatous LNPCPs were prospectively enrolled and randomly assigned to C-EMR or H-EMR with margin thermal ablation at a single tertiary centre. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at 6 months surveillance colonoscopy. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success. RESULTS: 177 LNPCPs in 177 patients were randomised to C-EMR arm (n=87) or H-EMR (n=90). Treatment groups were equivalent for technical success 86/87 (98.9%) C-EMR versus H-EMR 90/90 (100%); p=0.31. Recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; relative risk (RR) 16.6, 95% CI 2.24 to 122; p<0.001).Delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB was significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); RR 6.77, 95% CI 0.85 to 53.9; p=0.034). CONCLUSION: Compared with H-EMR, C-EMR for flat, adenomatous LNPCPs, demonstrates superior safety with equivalent technical success. However, endoscopic recurrence is significantly greater for cold snare resection and is currently a limitation of the technique. TRIAL REGISTRATION NUMBER: NCT04138030.

Outcomes of Micropulse Transscleral Cyclophotocoagulation in Uveitic Glaucoma.

PURPOSE: To report a case series of patients with uveitic glaucoma who were treated with micropulse transscleral cyclophotocoagulation (mpCPC). METHODS: This retrospective case series consists of patients from the University of Colorado Sue Anschutz-Rodgers Eye Center from 2015 to 2020 who were diagnosed with uveitic glaucoma. Information collected includes demographic data, type of uveitis, glaucoma severity, and prior glaucoma surgeries. Pre- and postoperative best corrected visual acuity, intraocular pressure (IOP), glaucoma medications, degree of inflammation, and uveitis therapies were included up to 36 months postoperatively. Surgical success was defined as an IOP reduction of 30% with achievement of IOP goal using the same number of glaucoma medications or less at 6 months or 1 year. Uveitis success was defined as the absence of persistent anterior uveitis at 3 months. RESULTS: Six patients and seven eyes with uveitic glaucoma underwent mpCPC. Types of uveitis included idiopathic anterior uveitis, HLA-B27-associated anterior uveitis, varicella zoster virus anterior uveitis, juvenile idiopathic arthritis-associated chronic anterior uveitis, lichen planus-associated intermediate uveitis, and sarcoidosis-associated panuveitis. Two of six eyes (33.3%) at 6 months and three of five eyes (60%) at 1 year achieved surgical success. Around 6 months postoperatively, two out of seven eyes (28.6%) required Ahmed glaucoma valve placement (n = 1) or repeat mpCPC (n = 1). One eye (14.3%) required phacoemulsification with goniotomy followed by an Ahmed glaucoma valve 18 months after mpCPC. There were no cases of persistent anterior uveitis, hypotony, or phthisis after mpCPC in this cohort. CONCLUSIONS: Micropulse transscleral cyclophotocoagulation may safely reduce intraocular pressure in some patients with uveitic glaucoma without exacerbation of intraocular inflammation. Multiple treatments may be required to achieve longer-term success.

Development of neural circuits for social motion perception in schooling fish.

The collective behavior of animal groups emerges from the interactions among individuals. These social interactions produce the coordinated movements of bird flocks and fish schools, but little is known about their developmental emergence and neurobiological foundations. By characterizing the visually based schooling behavior of the micro glassfish Danionella cerebrum, we found that social development progresses sequentially, with animals first acquiring the ability to aggregate, followed by postural alignment with social partners. This social maturation was accompanied by the development of neural populations in the midbrain that were preferentially driven by visual stimuli that resemble the shape and movements of schooling fish. Furthermore, social isolation over the course of development impaired both schooling behavior and the neural encoding of social motion in adults. This work demonstrates that neural populations selective for the form and motion of conspecifics emerge with the experience-dependent development of collective movement.

Lipid-lowering optimisation for secondary prevention vascular and diabetic foot patients in a pharmacist-led clinic.

Patients attending vascular or diabetic foot clinics commonly have atherosclerotic disease, are at increased risk of cardiovascular disease (CVD), merit high-intensity lipid-modifying therapy to maintain secondary prevention targets and are often sub optimally treated in primary care. We set out to assess the impact of a pharmacist led lipid optimisation clinic in these patients in an area with high levels of social deprivation. METHODS: We performed a clinical cohort study to assess the effectiveness of a pharmacist led clinic to optimise lipid lowering therapy by optimising of statin therapy and commencing additional lipid lowering therapy if applicable with monitoring of blood lipid profiles. RESULTS: Of the 216 patients (166 (77%) on statins) triaged by the pharmacist, 175 (81%) had non-HDL cholesterol levels above the target value of 97 mg/dL (2.5 mmol/L) with a mean non-HDL cholesterol level of 135.73 mg/dL (3.51 mmol/L). Pre optimisation by the prescribing clinical pharmacist 41/216 (19%) patients were at target with a mean non-HDL cholesterol of 135.5 mg/dL improving to 92/137 (67%) patients achieving the target non-HDL cholesterol level with a mean post optimisation non-HDL cholesterol of 94.35 mg/dL (2.44 mmol/L), odds ratio for being at target 8.67 [95% CI 5.30-14.20]. The calculated LDL cholesterol levels (Friedewald) demonstrated a mean reduction of 35.19 [95% CI 29.23-41.38] mg/dL (0.91 [95% CI 0.76-1.07] mmol/l). Proportion on high intensity statin increased from 65 out of 166 (39%) to 129 of 170 (76%) at follow up O.R. 4.89 [3.06-7.82], equivalent to an NNT = 3. CONCLUSIONS: A pharmacist led service in undertreated and clinically challenging vascular and diabetic foot patients in an area of high social deprivation produced significant improvements in utilization of high intensity statin and other lipid lowering therapies and attainment of lipid goals.

Rethinking the Esterquats: Synthesis, Stability, Ecotoxicity and Applications of Esterquats Incorporating Analogs of Betaine or Choline as the Cation in Their Structure.

Esterquats constitute a unique group of quaternary ammonium salts (QASs) that contain an ester bond in the structure of the cation. Despite the numerous advantages of this class of compounds, only two mini-reviews discuss the subject of esterquats: the first one (2007) briefly summarizes their types, synthesis, and structural elements required for a beneficial environmental profile and only briefly covers their applications whereas the second one only reviews the stability of selected betaine-type esterquats in aqueous solutions. The rationale for writing this review is to critically reevaluate the relevant literature and provide others with a "state-of-the-art" snapshot of choline-type esterquats and betaine-type esterquats. Hence, the first part of this survey thoroughly summarizes the most important scientific reports demonstrating effective synthesis routes leading to the formation of both types of esterquats. In the second section, the susceptibility of esterquats to hydrolysis is explained, and the influence of various factors, such as the pH, the degree of salinity, or the temperature of the solution, was subjected to thorough analysis that includes quantitative components. The next two sections refer to various aspects associated with the ecotoxicity of esterquats. Consequently, their biodegradation and toxic effects on microorganisms are extensively analyzed as crucial factors that can affect their commercialization. Then, the reported applications of esterquats are briefly discussed, including the functionalization of macromolecules, such as cotton fabric as well as their successful utilization on a commercial scale. The last section demonstrates the most essential conclusions and reported drawbacks that allow us to elucidate future recommendations regarding the development of these promising chemicals.

Structuring medication signeturs as a language regression task: comparison of zero- and few-shot GPT with fine-tuned models.

Importance: Electronic health record textual sources such as medication signeturs (sigs) contain valuable information that is not always available in structured form. Commonly processed through manual annotation, this repetitive and time-consuming task could be fully automated using large language models (LLMs). While most sigs include simple instructions, some include complex patterns. Objectives: We aimed to compare the performance of GPT-3.5 and GPT-4 with smaller fine-tuned models (ClinicalBERT, BlueBERT) in extracting the average daily dose of 2 immunomodulating medications with frequent complex sigs: hydroxychloroquine, and prednisone. Methods: Using manually annotated sigs as the gold standard, we compared the performance of these models in 702 hydroxychloroquine and 22 104 prednisone prescriptions. Results: GPT-4 vastly outperformed all other models for this task at any level of in-context learning. With 100 in-context examples, the model correctly annotates 94% of hydroxychloroquine and 95% of prednisone sigs to within 1 significant digit. Error analysis conducted by 2 additional manual annotators on annotator-model disagreements suggests that the vast majority of disagreements are model errors. Many model errors relate to ambiguous sigs on which there was also frequent annotator disagreement. Discussion: Paired with minimal manual annotation, GPT-4 achieved excellent performance for language regression of complex medication sigs and vastly outperforms GPT-3.5, ClinicalBERT, and BlueBERT. However, the number of in-context examples needed to reach maximum performance was similar to GPT-3.5. Conclusion: LLMs show great potential to rapidly extract structured data from sigs in no-code fashion for clinical and research applications.

HEX17(Neumifil): An intranasal respiratory biotherapeutic with broad-acting antiviral activity.

Broad-acting antiviral strategies to prevent respiratory tract infections are urgently required. Emerging or re-emerging viral diseases caused by new or genetic variants of viruses such as influenza viruses (IFVs), respiratory syncytial viruses (RSVs), human rhinoviruses (HRVs), parainfluenza viruses (PIVs) or coronaviruses (CoVs), pose a severe threat to human health, particularly in the very young or old, or in those with pre-existing respiratory conditions such as asthma or chronic obstructive pulmonary disease (COPD). Although vaccines remain a key component in controlling and preventing viral infections, they are unable to provide broad-spectrum protection against recurring seasonal infections or newly emerging threats. HEX17 (aka Neumifil), is a first-in-class protein-based antiviral prophylactic for respiratory viral infections. HEX17 consists of a hexavalent carbohydrate-binding module (CBM) with high affinity to sialic acids, which are typically present on terminating branches of glycans on viral cellular receptors. This allows HEX17 to block virus engagement of host receptors and inhibit infection of a wide range of viral pathogens and their variants with reduced risk of antiviral resistance. As described herein, HEX17 has demonstrated broad-spectrum efficacy against respiratory viral pathogens including IFV, RSV, CoV and HRV in multiple in vivo and in vitro studies. In addition, HEX17 can be easily administered via an intranasal spray and is currently undergoing clinical trials.

Single-cell RNA-sequencing of human eosinophils in allergic inflammation in the esophagus.

BACKGROUND: Eosinophils are elusive cells involved in allergic inflammation. Single-cell RNA-sequencing (scRNA-seq) is an emerging approach to deeply characterize cellular properties, heterogeneity, and functionality. OBJECTIVES: We sought to comprehensively characterize the transcriptome and biological functions of human eosinophils at a site of severe allergic inflammation in the esophagus (ie, eosinophilic esophagitis [EoE]). METHODS: We employed a gravity-based scRNA-seq methodology to sequence blood eosinophils from patients with EoE and control individuals compared to a reanalyzed public scRNA-seq dataset of human esophageal eosinophils of EoE patients. We used flow cytometry, immunostaining, and a stimulation assay to verify mRNA findings. RESULTS: In total, scRNA-seq was obtained from 586 eosinophils (188 from blood [n = 6 individuals] and 398 from esophagus [n = 6 individuals]). The esophageal eosinophils were composed of a population of activated eosinophils (enriched in 659 genes compared with peripheral blood-associated eosinophils) and a small population of eosinophils resembling peripheral blood eosinophils (enriched in 62 genes compared with esophageal eosinophils). Esophageal eosinophils expressed genes involved in sensing and responding to diverse stimuli, most notably IFN-γ, IL-10, histamine and leukotrienes, and succinate. Esophageal eosinophils were most distinguished from other esophageal populations by gene expression of the receptors CCR3, HRH4, SUCNR1, and VSTM1; transcription factors CEBPE, OLIG1, and OLIG2; protease PRSS33; and the hallmark eosinophil gene CLC. A web of bidirectional eosinophil interactions with other esophageal populations was derived. Comparing esophageal eosinophils and mast cells revealed that esophageal eosinophils expressed genes involved in DNAX-activation protein-12 (also known as TYROBP) interactions, IgG receptor-triggered events, immunoregulation, and IL-10 signaling. CONCLUSIONS: In EoE, esophageal eosinophils exist as 2 populations, a minority population resembling blood eosinophils and the other population characterized by high de novo transcription of diverse sensing receptors and inflammatory mediators readying them to potentially intersect with diverse cell types.

Genotypic and phenotypic characterization of Enterococcus faecalis isolates from periprosthetic joint infections.

Over 2.5 million prosthetic joint implantation surgeries occur annually in the United States. Periprosthetic joint infections (PJIs), though occurring in only 1-2% of patients receiving replacement joints, are challenging to diagnose and treat and are associated with significant morbidity. The Gram-positive bacterium Enterococcus faecalis, which can be highly antibiotic-resistant and is a robust biofilm producer on indwelling medical devices, accounts for 2-11% of PJIs. E. faecalis PJIs are understudied compared to those caused by other pathogens, such as Staphylococcus aureus. This motivates the need to generate a comprehensive understanding of E. faecalis PJIs to guide future treatments for these infections. To address this, we describe a panel of E. faecalis strains isolated from the surface of prosthetic joints in a cohort of individuals treated at the Mayo Clinic in Rochester, MN. Here, we present the first complete genome assemblage of E. faecalis PJI isolates. Comparative genomics shows differences in genome size, virulence factors, antimicrobial resistance genes, plasmids, and prophages, underscoring the genetic diversity of these strains. These isolates have strain-specific differences in in vitro biofilm biomass, biofilm burden, and biofilm morphology. We measured robust changes in biofilm architecture and aggregation for all isolates when grown in simulated synovial fluid (SSF). Finally, we evaluated the antibiotic efficacy of these isolates and found strain-specific changes across all strains when grown in SSF. Results of this study highlight the existence of genetic and phenotypic heterogeneity among E. faecalis PJI isolates which will provide valuable insight and resources for future E. faecalis PJI research. IMPORTANCE: Periprosthetic joint infections (PJIs) affect ~1-2% of those who undergo joint replacement surgery. Enterococcus faecalis is a Gram-positive opportunistic pathogen that causes ~10% of PJIs in the United States each year, but our understanding of how and why E. faecalis causes PJIs is limited. E. faecalis infections are typically biofilm-associated and can be difficult to clear with antibiotic therapy. Here, we provide complete genomes for four E. faecalis PJI isolates from the Mayo Clinic. These isolates have strain-specific differences in biofilm formation, aggregation, and antibiotic susceptibility in simulated synovial fluid. These results provide important insight into the genomic and phenotypic features of E. faecalis isolates from PJI.

Low Vitamin D Concentration Is Associated with Increased Depression Risk in Adults 20-44 Years Old, an NHANES 2007-2018 Data Analysis with a Focus on Perinatal and Breastfeeding Status.

The objective was to investigate associations of serum vitamin D concentration with depressive symptoms and assess the impact that vitamin D concentration has on the occurrence of depressive symptoms in 20-44-year-old pregnant women, postpartum women, non-pp women (non-pregnant/postpartum women), and men, including a separate subgroup analysis of postpartum breastfeeding and non-breastfeeding women. The study populations were selected from the 2007-2018 NHANES public data. Subjective interview data and objective laboratory data including depressive symptoms, serum vitamin D concentration, nutrient intake, and demographic information were utilized. Two diet patterns were created using principal component analysis, and a Bayesian multinomial model was fit to predict the depression outcomes for each subpopulation. The estimates for the log vitamin D slope parameter were negative for all cohorts; as vitamin D increased, the probability of having no depression increased, while the probability of depression decreased. The pregnant cohort had the steepest vitamin D slope, followed by postpartum women, then non-pp women and men. Higher vitamin D concentration had more impact on decreasing depression risk in pregnant and postpartum women compared to non-pp women and men. Among postpartum women, higher vitamin D concentration had a greater influence on decreasing breastfeeding women's depression risk than non-breastfeeding women.

Design of Chitin Cell Culture Matrices for 3D Tissue Engineering: The Importance of Chitin Types, Solvents, Cross-Linkers, and Fabrication Techniques.

This review focuses on factors and the fabrication techniques affecting the microarchitecture of tissue engineering scaffolds from the second most abundant biopolymer, chitin. It emphasizes the unique potentiality of this polymer in tissue engineering (TE) applications and highlights the variables important to achieve tailored scaffold properties. First, we describe aspects of scaffolds' design, and the complex interplay between chitin types, solvent systems, additives, and fabrication techniques to incorporate porosity, with regard to best practices. In the following section, we provide examples of scaffolds' use, with a focus on in vitro cell studies. Finally, an analysis of their biodegradability is presented. Our review emphasizes the potentiality of chitin and the pressing need for further research to overcome existing challenges and fully harness its capabilities in tissue engineering.

Understanding collective behavior through neurobiology.

A variety of organisms exhibit collective movement, including schooling fish and flocking birds, where coordinated behavior emerges from the interactions between group members. Despite the prevalence of collective movement in nature, little is known about the neural mechanisms producing each individual's behavior within the group. Here we discuss how a neurobiological approach can enrich our understanding of collective behavior by determining the mechanisms by which individuals interact. We provide examples of sensory systems for social communication during collective movement, highlight recent discoveries about neural systems for detecting the position and actions of social partners, and discuss opportunities for future research. Understanding the neurobiology of collective behavior can provide insight into how nervous systems function in a dynamic social world.

One health in the Philippines: A review and situational analysis.

The Philippines faces a complex and interconnected web of human, animal, and environmental health issues, including zoonotic and reverse zoonotic diseases, antimicrobial resistance, food insecurity and contamination, and threats from environmental degradation. This paper examines these issues, existing interventions, and their implementation challenges. The overall framework used to analyze the level of operationalization of the One Health approach is the Multi-sectoral One Health Coordination Framework developed by the World Health Organization, Food and Agriculture Organization, and the World Organization for Animal Health. A two-step process was conducted: literature review, followed by consultations with government and non-government stakeholders across national, subnational, and local levels. There has been significant progress in laying the foundation for collaboration between the human, animal, and environmental sectors. These are demonstrated by the presence of structures and systems, including inter-agency task forces, emergency response plans and mechanisms, and a network for health human resources. However, these are eclipsed by challenges, including the limited governance mechanisms within inter-agency committees, fragmented risk assessment and surveillance, untapped opportunities for joint investigation and response, insufficient resources for capacity-building, and absence of comprehensive risk communication and community engagement initiatives. These challenges highlight the importance of promoting multi-sectoral governance and ensuring resource allocation and sharing. Joint activities across risk assessment, surveillance, investigation, and response are critical in ensuring a proactive and holistic approach to addressing threats. A well-capacitated interdisciplinary workforce, not only capable of managing these hazards but also empowering communities to protect themselves, is necessary in ensuring innovation and collaboration on health risks at the human-animal-environment interface. In light of the multifaceted challenges faced by the Philippines, the One Health approach emerges as a vital strategy. By addressing governance issues, enhancing coordination, and bolstering resource allocation, the country can better protect the health and well-being of its people, animals, and ecosystems.

Arginine impacts aggregation, biofilm formation, and antibiotic susceptibility in Enterococcus faecalis.

Enterococcus faecalis is a commensal bacterium in the gastrointestinal tract (GIT) of humans and other organisms. E. faecalis also causes infections in root canals, wounds, the urinary tract, and on heart valves. E. faecalis metabolizes arginine through the arginine deiminase (ADI) pathway, which converts arginine to ornithine and releases ATP, ammonia, and CO2. E. faecalis arginine metabolism also affects virulence of other pathogens during co-culture. E. faecalis may encounter elevated levels of arginine in the GIT or the oral cavity, where arginine is used as a dental therapeutic. Little is known about how E. faecalis responds to growth in arginine in the absence of other bacteria. To address this, we used RNAseq and additional assays to measure growth, gene expression, and biofilm formation in E. faecalis OG1RF grown in arginine. We demonstrate that arginine decreases E. faecalis biofilm production and causes widespread differential expression of genes related to metabolism, quorum sensing, and polysaccharide synthesis. Growth in arginine also increases aggregation of E. faecalis and promotes decreased susceptibility to the antibiotics ampicillin and ceftriaxone. This work provides a platform for understanding of how the presence of arginine in biological niches affects E. faecalis physiology and virulence of surrounding microbes.

Limited English proficiency, cardiovascular risk factors, cardiovascular disease, and in-hospital COVID-19 outcomes.

OBJECTIVES: Cardiovascular risk factors and history of cardiovascular disease are associated with greater morbidity and mortality in patients hospitalized with COVID-19. Limited English proficiency (LEP) has also been associated with worse outcomes in this setting, including requiring intensive care unit (ICU) level of care and in-hospital death. Whether non-English-language preference (NELP) modifies the association between cardiovascular risk factors or disease and outcomes in patients hospitalized with COVID-19 is unknown. STUDY DESIGN: Retrospective cohort study of adult patients admitted to a large New England health system between March 1 and December 31, 2020, who tested positive for COVID-19. NELP was defined as having a preferred language that was not English noted in the electronic health record. METHODS: Cardiovascular risk factors, history of cardiovascular disease, and NELP were related to the primary composite clinical outcome-death or ICU admission-using multivariable binary logistic regression adjusted for demographic and clinical characteristics. Interaction terms for NELP and model covariates were evaluated. RESULTS: Of 3582 patients hospitalized with COVID-19, 1024 (28.6%) had NELP; 812 (79.3%) of the patients with NELP received interpreter services. Death or ICU admission occurred in 794 (22.2%) of the hospitalized patients. NELP was not significantly associated with the primary composite outcome in unadjusted or adjusted analyses. In the adjusted analyses, only male gender, coronary artery disease, pulmonary circulatory disease, and liver disease significantly predicted the primary outcome. NELP did not modify the effect of these associations. CONCLUSIONS: NELP was not significantly associated with odds of death or ICU admission, nor did it modify the association between cardiovascular risk factors or history of cardiovascular disease and this composite outcome. Because most patients with NELP received interpreter services, these findings may support the role of such services in ensuring equitable outcomes.

Association of Vitamin A and D Deficiencies with Infectious Outcomes in Children Undergoing Intensive Induction Therapy for Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the association between deficiency of vitamin A or D at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and subsequent infectious complications during induction therapy. STUDY DESIGN: We conducted an institutional review board-approved, retrospective cohort study of children with newly diagnosed ALL from 2007 to 2017 at St. Jude Children's Research Hospital. We measured vitamin D, vitamin D binding protein, retinol binding protein as a surrogate for vitamin A, and immunoglobulin isotypes in serum obtained at ALL diagnosis, and we assessed the association between vitamin deficiencies or levels and infection-related complications during the 6-week induction phase using Cox regression models. RESULTS: Among 378 evaluable participants, vitamin A and D deficiencies were common (43% and 17%, respectively). Vitamin D deficiency was associated with higher risks of febrile neutropenia (adjusted hazard ratio [aHR], 1.7; P = .0072), clinically documented infection (aHR, 1.73; P = .025), and likely bacterial infection (aHR, 1.86; P = .008). Conversely, vitamin A deficiency was associated solely with a lower risk of sepsis (aHR, 0.19; P = .027). CONCLUSIONS: In this retrospective study, vitamin D deficiency was associated with an increased risk of common infection-related complications during induction therapy for ALL. Additional studies are warranted to evaluate whether vitamin D supplementation could mitigate this effect.

Life and Disability Insurance for People with or at Risk of HIV: Aligning Policy with Evidence.

Antiretroviral medications have substantially improved life expectancy for people with HIV. These medications are also highly effective in preventing HIV acquisition in people who do not have HIV, a strategy known as HIV preexposure prophylaxis (PrEP). Despite these advances, some life and disability insurers continue to deny or limit coverage for people with HIV, and some have even refused to cover people who are using PrEP to protect themselves. These policies unfairly deny people with HIV, PrEP users, and their families the peace of mind and financial protection that can come with life and disability insurance coverage. This article summarizes the current evidence on HIV treatment and prevention, arguing that underwriting decisions by life and disability insurers should not be made based on HIV status or use of PrEP.