Follow‐Up Survey on Functionality of Nutrition Documentation and Ordering Nutrition Therapy in Currently Available Electronic Health Record Systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141915/1/ncp0401.pd

A Call to Action for Optimizing the Electronic Health Record in the Parenteral Nutrition Workflow

Parenteral nutrition (PN) is a complex therapeutic modality provided to neonates, children, and adults for various indications. Surveys have shown that current electronic health record (EHR) systems are in need of functionality enhancement for safe and optimal delivery of PN. This is a consensus statement from the American Society for Parenteral and Enteral Nutrition, the Academy of Nutrition and Dietetics, and the American Society of Health‐System Pharmacists outlining some of the key challenges to prescribing, order review/verification, compounding, and administration of PN using EHRs today and is a call to action for clinicians and vendors to optimize their EHRs regarding the PN build and workflow.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146340/1/ncp10095.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146340/2/ncp10095_am.pd

A Call to Action for Optimizing the Electronic Health Record in the Parenteral Nutrition Workflow: Executive Summary

Parenteral nutrition (PN) is a complex therapeutic modality provided to neonates, children, and adults for various indications. Surveys have shown that current electronic health record (EHR) systems are in need of functionality enhancement for safe and optimal delivery of PN. This is a consensus statement from the American Society for Parenteral and Enteral Nutrition, the Academy of Nutrition and Dietetics, and the American Society of Health‐System Pharmacists outlining some of the key challenges to prescribing, order review/verification, compounding, and administration of PN using EHRs today and is a call to action for clinicians and vendors to optimize their EHRs regarding the PN build and workflow.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146349/1/ncp10202.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146349/2/ncp10202_am.pd

RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients

Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). ROR gamma t, the key Thelperl7 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and gamma delta-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular ROR gamma t(+)T-be(lo)PLZF(-) iNKT and gamma delta-hi T cell subsets in healthy peripheral blood. ROR gamma t(+) iNKT and gamma delta-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and gamma delta-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, ROR gamma t inhibition blocked gamma delta 17 and iNKT17 cell function while selectively sparing IL-22(+) subsets. Overall, our findings highlight a unique diversity of human ROR gamma t(+) T cells and underscore the potential of ROR gamma t antagonism to modulate aberrant type 17 responses

Actionable, Pathogenic Incidental Findings in 1,000 Participants’ Exomes

The incorporation of genomics into medicine is stimulating interest on the return of incidental findings (IFs) from exome and genome sequencing. However, no large-scale study has yet estimated the number of expected actionable findings per individual; therefore, we classified actionable pathogenic single-nucleotide variants in 500 European- and 500 African-descent participants randomly selected from the National Heart, Lung, and Blood Institute Exome Sequencing Project. The 1,000 individuals were screened for variants in 114 genes selected by an expert panel for their association with medically actionable genetic conditions possibly undiagnosed in adults. Among the 1,000 participants, 585 instances of 239 unique variants were identified as disease causing in the Human Gene Mutation Database (HGMD). The primary literature supporting the variants’ pathogenicity was reviewed. Of the identified IFs, only 16 unique autosomal-dominant variants in 17 individuals were assessed to be pathogenic or likely pathogenic, and one participant had two pathogenic variants for an autosomal-recessive disease. Furthermore, one pathogenic and four likely pathogenic variants not listed as disease causing in HGMD were identified. These data can provide an estimate of the frequency (∼3.4% for European descent and ∼1.2% for African descent) of the high-penetrance actionable pathogenic or likely pathogenic variants in adults. The 23 participants with pathogenic or likely pathogenic variants were disproportionately of European (17) versus African (6) descent. The process of classifying these variants underscores the need for a more comprehensive and diverse centralized resource to provide curated information on pathogenicity for clinical use to minimize health disparities in genomic medicine

mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron

Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors 18 months after the diagnosis of the first COVID-19 case in the United States in January 2020. The average time between production to infusion of IG products was 8 months, which resulted in poor neutralization of the variant strain circulating at the time of infusion. Despite limited neutralizing activity, IG prophylaxis with clinically relevant dosing protected susceptible K18-hACE2-transgenic mice against clinical disease, lung infection, and lung inflammation caused by the XBB.1.5 Omicron variant. Moreover, following IG prophylaxis, levels of XBB.1.5 infection in the lung were higher in FcγR-KO mice than in WT mice. Thus, IG replacement products with poor neutralizing activity against evolving SARS-CoV-2 variants likely confer protection to patients with immune deficiency disorders through Fc effector function mechanisms

Associations between self-reported pest treatments and pesticide concentrations in carpet dust

BACKGROUND: Recent meta-analyses demonstrate an association between self-reported residential pesticide use and childhood leukemia risk. Self-reports may suffer from recall bias and provide information only on broad pesticide categories. We compared parental self-reported home and garden pest treatments to pesticides measured in carpet dust. METHODS: Parents of 277 children with leukemia and 306 controls in Northern and Central California (2001–2007) were asked about insect and weed treatments during the previous year. Carpet dust samples were analyzed for 47 pesticides. We present results for the 7 insecticides (carbaryl, propoxur, chlorpyrifos, diazinon, cyfluthrin, cypermethrin, permethrin), 5 herbicides (2,4-dichlorophenoxyacetic acid [2,4-D], chlorthal, dicamba, mecoprop, simazine), and 1 synergist (piperonyl butoxide) that were present in home and garden products during the study period and were detected in ≥25% of carpet dust samples. We constructed linear regression models for the relative change in pesticide concentrations associated with self-reported treatment of pest types in cases and controls separately and combined, adjusting for demographics, housing characteristics, and nearby agricultural pesticide applications. RESULTS: Several self-reported treatments were associated with pesticide concentrations in dust. For example, households with flea/tick treatments had 2.3 (95% Confidence Interval [CI]: 1.4, 3.7) times higher permethrin concentrations than households not reporting this treatment. Households reporting treatment for ants/cockroaches had 2.5 (95% CI: 1.5, 4.2) times higher cypermethrin levels than households not reporting this treatment. Weed treatment by a household member was associated with 1.9 (1.4, 2.6), 2.2 (1.6, 3.1), and 2.8 (2.1, 3.7) times higher dust concentrations of dicamba, mecoprop, and 2,4-D, respectively. Weed treatments by professional applicators were null/inversely associated with herbicide concentrations in dust. Associations were generally similar between cases and controls and were consistent with pesticide active ingredients in these products during the study time period. CONCLUSIONS: Consistency between self-reported pest treatments, concentrations in dust, and pesticides in products lends credibility to the exposure assessment methods and suggests that differential recall by case–control status is minimal. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-015-0015-x) contains supplementary material, which is available to authorized users