Methods to Increase Reliability in Quality Improvement Projects.

Although many quality improvement initiatives in health care see early and laudable success, 1 of the greatest challenges is sustaining the gains and avoiding the natural tendency of systems to revert to their original state, function, and outcomes. Reliability science describes a mathematical and systematic framework for understanding the level of reliability of interventions, and therefore the anticipated success and failure rate of both the steps of a process and the cumulative process overall. Successful utilization of this framework, along with the mindful organizing principles of high-reliability organizations, will facilitate ongoing and long-lasting improvement in outcomes. In this article, we describe practical methods to increase the reliability of interventions toward achieving and sustaining improvement goals.

A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

Quantitative 23Na magnetic resonance imaging in the abdomen at 3 T.

OBJECTIVES: To assess the feasibility of sodium-23 MRI for performing quantitative and non-invasive measurements of total sodium concentration (TSC) and relaxation in a variety of abdominal organs. MATERIALS AND METHODS: Proton and sodium imaging of the abdomen was performed in 19 healthy volunteers using a 3D cones sequence and a sodium-tuned 4-rung transmit/receive body coil on a clinical 3 T system. The effects of B1 non-uniformity on TSC measurements were corrected using the double-angle method. The long-component of 23Na T2* relaxation time was measured using a series of variable echo-times. RESULTS: The mean and standard deviation of TSC and long-component 23Na T2* values were calculated across the healthy volunteer group in the kidneys, cerebrospinal fluid (CSF), liver, gallbladder, spleen, aorta, and inferior vena cava. DISCUSSION: Mean TSC values in the kidneys, liver, and spleen were similar to those reported using 23Na-MRI previously in the literature. Measurements in the CSF and gallbladder were lower, potentially due to the reduced spatial resolution achievable in a clinically acceptable scan time. Mean long-component 23Na T2* values were consistent with previous reports from the kidneys and CSF. Intra-population standard error was larger in smaller, fluid-filled structures due to fluid motion and partial volume effects.

Sleep-Disordered Breathing and Associated Comorbidities among Preschool-Aged Children with Down Syndrome.

Children with Down syndrome (DS) are at high risk of sleep-disordered breathing (SDB). The American Academy of Pediatrics recommends a polysomnogram (PSG) in children with DS prior to the age of 4. This retrospective study examined the frequency of SDB, gas exchange abnormalities, co-morbidities, and surgical management in children with DS aged 2-4 years old at Seattle Children's Hospital from 2015-2021. A total of 153 children underwent PSG, with 75 meeting the inclusion criteria. The mean age was 3.03 years (SD 0.805), 56% were male, and 54.7% were Caucasian. Comorbidities included (n, %): cardiac (43, 57.3%), dysphagia or aspiration (24, 32.0%), prematurity (17, 22.7%), pulmonary (16, 21.3%), immune dysfunction (2, 2.7%), and hypothyroidism (23, 30.7%). PSG parameter data collected included (mean, SD): obstructive AHI (7.9, 9.4) and central AHI (2.4, 2.4). In total, 94.7% met the criteria for pediatric OSA, 9.5% met the criteria for central apnea, and 9.5% met the criteria for hypoventilation. Only one child met the criteria for hypoxemia. Overall, 60% had surgical intervention, with 88.9% of these being adenotonsillectomy. There was no statistically significant difference in the frequency of OSA at different ages. Children aged 2-4 years with DS have a high frequency of OSA. The most commonly encountered co-morbidities were cardiac and swallowing dysfunction. Among those with OSA, more than half underwent surgical intervention, with improvements in their obstructive apnea hypopnea index, total apnea hypopnea index, oxygen saturation nadir, oxygen desaturation index, total arousal index, and total sleep duration. This highlights the importance of early diagnosis and appropriate treatment. Our study also suggests that adenotonsillar hypertrophy is still a large contributor to upper airway obstruction in this age group.

Polysomnographically Defined Restless Sleep Disorder and Periodic Limb Movements during Sleep in Children Born Prematurely.

INTRODUCTION: Children born prematurely (<37 weeks' gestation) are at increased risk of perinatal complications, comorbidities, and iron deficiency. Iron deficiency is associated with restless legs syndrome and periodic limb movement disorder. In this study, we assessed the prevalence of restless sleep disorder (RSD) and elevated periodic limb movements during sleep (PLMS) in children born prematurely who underwent polysomnography. METHODS: A retrospective chart review of sleep studies was conducted in children aged 1-18 years (median age 4 years) with a history of premature birth. Children with genetic syndrome, airway surgery, or tracheostomy were excluded. Three groups were compared: children with PLMS index >5, children with RSD, and children with neither elevated PLMS index nor RSD. RESULTS: During the study, 2577 sleep studies were reviewed. Ninety-two studies fit our criteria and were included in the analysis. The median age at birth was 31 weeks, and the interquartile range (IQR) was 27-34 weeks. A total of 32 (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring. After polysomnography, 18% were found to have a PLMS index >5/h, and 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters among the children with RSD, PLMS, and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p = 0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5) or the non-RSD/non-PLMS (median 2.0, IQR 0.8-4.5) groups. CONCLUSIONS: There was an elevated frequency of RSD and elevated PLMS in our cohort of children born prematurely. Children born prematurely are at higher risk of iron deficiency which can be a contributor factor to sleep -related movement disorders. These results add new knowledge regarding the prevalence of RSD and PLMS in these children.

Challenges and Opportunities in Big Data Science to Address Health Inequities and Focus the HIV Response.

PURPOSE OF REVIEW: Big Data Science can be used to pragmatically guide the allocation of resources within the context of national HIV programs and inform priorities for intervention. In this review, we discuss the importance of grounding Big Data Science in the principles of equity and social justice to optimize the efficiency and effectiveness of the global HIV response. RECENT FINDINGS: Social, ethical, and legal considerations of Big Data Science have been identified in the context of HIV research. However, efforts to mitigate these challenges have been limited. Consequences include disciplinary silos within the field of HIV, a lack of meaningful engagement and ownership with and by communities, and potential misinterpretation or misappropriation of analyses that could further exacerbate health inequities. Big Data Science can support the HIV response by helping to identify gaps in previously undiscovered or understudied pathways to HIV acquisition and onward transmission, including the consequences for health outcomes and associated comorbidities. However, in the absence of a guiding framework for equity, alongside meaningful collaboration with communities through balanced partnerships, a reliance on big data could continue to reinforce inequities within and across marginalized populations.

Ionic Liquid-Based Silane for SiO2 Nanoparticles: A Versatile Coupling Agent for Dental Resins.

The current longevity of dental resins intraorally is limited by susceptibility to acidic attacks from bacterial metabolic byproducts and vulnerability to enzymatic or hydrolytic degradation. Here, we demonstrate synthesizing an ionic liquid-based antibiofilm silane effective against Streptococcus mutans, a major caries pathogen. Furthermore, we incorporate this silane into dental resins, creating antibiofilm- and degradation-resistant materials applicable across resin types. FTIR, UV-vis, and NMR spectroscopy confirmed the synthesis of the expected ionic liquid-based silane. The characterization of SiO2 after the silanization indicated the presence of the silane and how it interacted with the oxide. All groups achieved a degree of conversion similar to that found for commercial resin composites immediately and after two months of storage in water. The minimum of 2.5 wt % of silane led to lower softening in solvent than the control group (GCTRL) (p < 0.05). While the flexural strength indicated a lower value from 1 wt % of silane compared to GCTRL (p < 0.05), the ultimate tensile strength did not indicate differences among groups (p > 0.05). There was no difference within groups between the immediate and long-term tests of flexural strength (p > 0.05) or ultimate tensile strength (p > 0.05). The addition of at least 5 wt % of silane reduced the viability of S. mutans compared to GCTRL (p < 0.05). The fluorescence microscopy analysis suggested that the higher the silane concentration, the higher the amount of bacteria with membrane defects. There was no difference among groups in the cytotoxicity test (p > 0.05). Therefore, the developed dental resins displayed biocompatibility, proper degree of conversion, improved resistance against softening in solvent, and stability after 6 months of storage in water. This material could be further developed to produce polymeric antimicrobial layers for different surfaces, supporting various potential avenues in developing novel biomaterials with enhanced therapeutic characteristics using ionic liquid-based materials.

NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.

DORAVIR: a French national survey of people with HIV-1 treated with an antiretroviral regimen including doravirine.

BACKGROUND: Doravirine is the latest NNRTI to be approved for the treatment of HIV-1 and has a different resistance profile from first-generation NNRTIs. Our aim was to investigate the virological efficacy of antiretroviral treatment including doravirine in people living with HIV-1 (PLWHIV), the factors associated with virological failure (VF) and those associated with the emergence of reverse transcriptase (RT) mutations in the case of VF. METHODS: A retrospective national survey of PLWHIV who were either naive or experienced on antiretroviral treatment including doravirine was conducted. VF was defined as two consecutive plasma viral loads (VLs) of ≥50 copies/mL or one VL of ≥200 copies/mL. Genotypic resistance tests were interpreted using the Stanford (v9.4.1) and ANRS (v33) algorithms. RESULTS: Of the 589 PLWHIV treated with a doravirine-containing regimen, 8.5% were naive and 91.5% had prior antiretroviral experience; 56.9% were infected with HIV-1 B subtype. Overall, 88.3% and 85.1% of participants were virologically controlled at Month (M)3 and M6 of doravirine treatment, respectively. In multivariable analysis, CRF02_AG subtype, higher zenith plasma HIV-1 RNA VL, doravirine initiation in the context of failure and baseline V179D mutation presence were associated with VF. Among 88 PLWHIV who experienced virological failure at M6, 15.9% had a median of 2 (IQR 1-3) HIV RT mutations. In multivariable analysis, the only factor associated with the occurrence of mutations was a genotypic sensitivity score that was not fully sensitive. CONCLUSIONS: This study is one of the largest to characterize the virological efficacy of doravirine-containing regimens in clinical practice and to identify factors associated with VF or emergence of resistance mutations that should be considered in clinical management.

Introducing Isotòpia: A stable isotope database for Classical Antiquity.

We present Isotòpia, an open-access database compiling over 36,000 stable isotope measurements (δ13C, δ15N, δ18O, δ34S, 87Sr/86Sr, 206Pb/204Pb, 207Pb/204Pb, 208Pb/204Pb, 207Pb/206Pb, and 208Pb/206Pb) on human, animal, and plant bioarchaeological remains dating to Classical Antiquity (approximately 800 BCE - 500 CE). These were recovered from different European regions, particularly from the Mediterranean. Isotòpia provides a comprehensive characterisation of the isotopic data, encompassing various historical, archaeological, biological, and environmental variables. Isotòpia is a resource for meta-analytical research of past human activities and paleoenvironments. The database highlights data gaps in isotopic classical archaeology, such as the limited number of isotopic measurements available for plants and animals, limited number of studies on spatial mobility, and spatial heterogeneity of isotopic research. As such, we emphasise the necessity to address and fill these gaps in order to unlock the reuse potential of this database.

Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole.

PURPOSE: ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes. METHODS: MA.27 (ClinicalTrials.gov identifier: NCT00066573) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤-1; (-1, 0]; (0, 1]; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance P < .05. RESULTS: Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS (P < .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated (P = .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS (P = .001) in models with ER. CONCLUSION: Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤-1.

Histotaphonomic analysis of bone bioerosion reveals a regional framework of diverse deathways in the Neolithic of Southeast Italy.

The wide diversity of Neolithic funerary practices is increasingly recognised. In Southeast Italy, recent studies have drawn attention to the co-existence of multiple ways of treating the dead within single sites and across the region. In this study, we address how such diverse deathways form a regional framework of ritual practice through histotaphonomic analysis of bone bioerosion. Samples were obtained from articulated, semi-articulated and disarticulated remains from four sites in Apulia which each presented different modes of treatment and disposal of the dead. Bone thin sections were analysed by light microscopy to characterise microstructural preservation through features including bacterial bioerosion, staining, inclusions, and Wedl tunnelling. We investigate the early post-mortem histories of individuals whose remains ended up in various states of dis/articulation and diverse depositional contexts. Disarticulated remains frequently displayed arrested or extensive bacterial bioerosion, which was also found in articulated and semi-articulated skeletons. Additionally, remains deposited in similar contexts, as well as articulated and disarticulated remains deposited together in the same context, often showed different histotaphonomic characteristics, suggesting diverse early post-mortem trajectories. As a result, we argue that Neolithic deathways in southeastern Italy incorporated a high level of diversity in the early post-mortem treatment of the body. A framework for funerary practices emerges, whereby disarticulated remains probably originated from bodies which had been buried previously and subjected to varying extents of shelter, exposure to invertebrates, and duration of burial. However, we acknowledge the ongoing research into the origins of bacterial bioerosion and the problem of equifinality, which leaves open the possibility for further scenarios of early post-mortem treatment.

Novel strategy of S. mutans gcrR gene over-expression plus antibacterial dimethylaminohexadecyl methacrylate suppresses biofilm acids and reduces dental caries in rats.

OBJECTIVE: Streptococcus mutans (S. mutans) is a major contributor to dental caries, with its ability to synthesize extracellular polysaccharides (EPS) and biofilms. The gcrR gene is a regulator of EPS synthesis and biofilm formation. The objectives of this study were to investigate a novel strategy of combining gcrR gene over-expression with dimethylaminohexadecyl methacrylate (DMAHDM), and to determine their in vivo efficacy in reducing caries in rats for the first time. METHODS: Two types of S. mutans were tested: Parent S. mutans; and gcrR gene over-expressed S. mutans (gcrR OE S. mutans). Bacterial minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were measured with DMAHDM and chlorhexidine (CHX). Biofilm biomass, polysaccharide, lactic acid production, live/dead staining, colony-forming units (CFUs), and metabolic activity (MTT) were evaluated. A Sprague-Dawley rat model was used with parent S. mutans and gcrR OE S. mutans colonization to determine caries-inhibition in vivo. RESULTS: Drug-susceptibility of gcrR OE S. mutans to DMAHDM or CHX was 2-fold higher than that of parent S. mutans. DMAHDM reduced biofilm CFU by 3-4 logs. Importantly, the combined gcrR OE S. mutans+ DMAHDM dual strategy reduced biofilm CFU by 5 logs. In the rat model, the parent S. mutans group had a higher cariogenicity in dentinal (Dm) and extensive dentinal (Dx) regions. The DMAHDM + gcrR OE group reduced the Dm and Dx caries to only 20 % and 0 %, those of parent S. mutans + PBS control group (p < 0.05). The total caries severity of gcrR OE + DMAHDM group was decreased to 51 % that of parent S. mutans control (p < 0.05). SIGNIFICANCE: The strategy of combining S. mutans gcrR over-expression with antibacterial monomer reducing biofilm acids by 97 %, and reduced in vivo total caries in rats by 48 %. The gcrR over-expression + DMAHDM strategy is promising for a wide range of dental applications to inhibit caries and protect tooth structures.

Integrated spatial and multimodal single-cell transcriptomics reveal patient-dependent cell heterogeneity in splenic marginal zone lymphoma.

Biological hallmarks of splenic marginal zone lymphoma (SMZL) remain poorly described. Herein, we performed in-depth SMZL characterization through multimodal single-cell analyses of paired blood/spleen samples. The 3'-single-cell RNA-sequencing, Cellular Indexing of Transcriptomes and Epitopes by sequencing, and 5'-V(D)J single-cell RNA-sequencing datasets were integrated to characterize SMZL transcriptome profiles, including B-cell receptor and T-cell receptor repertoires. Hyperexpanded B-cell clones in the spleen were at a memory-like stage, whereas recirculating tumor B-cells in blood encompassed multiple differentiation stages, indicating an unexpected desynchronization of the B-cell maturation program in SMZL cells. Spatial transcriptomics showed the enrichment of T-effector and T-follicular helper (TFH) signatures in the nodular subtype of SMZL. This latter also exhibited gene-based cell-cell interactions suggestive of dynamic crosstalk between TFH and cancer cells in transcriptomics, further substantiated by using imaging mass cytometry. Our findings provide a comprehensive high-resolution description of SMZL biological hallmarks and characterize, for the first time in situ, inter- and intra-patient heterogeneity at both transcriptomic and protein levels. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVES: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. METHODS: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions. RESULTS: 1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states. CONCLUSIONS: Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

Caregiver and Child Mental Health During 3 Years of the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) lockdowns (stay-at-home orders) had significant mental health consequences in 2020 to 2021 for caregivers and children. Little is known about "postlockdown" periods in 2022 to 2023. We investigated the mental health experiences of Australian families throughout the 3 years of the COVID-19 pandemic (2020-2023), by demographic characteristics and lockdown length. METHODS: A total N = 12 408 caregivers (N = 20 339 children, aged 0-17 years) completed Australia's only representative, repeated, cross-sectional, National Child Health Poll across 6 waves (June 2020-April 2023). Caregivers reported mental health for themselves (Kessler-6, poor versus not) and each child (self-rated mental health, poor/fair versus good/very good/excellent), and perceived impacts of the pandemic on own/child mental health (negative versus none/positive). Binary logistic models were fitted to predict marginal probabilities of each mental health measure by state/territory group (proxy for lockdown length), over time, adjusted for potential demographic confounders. RESULTS: Poor caregiver Kessler-6 was similar between genders but more common for sole caregivers, and those with a home language other than English and lower education. Poor/fair child self-rated mental health was similar between genders and increased with child age. Perceived negative impacts were more common for females and socially advantaged caregivers. Overall, negative mental health experiences increased with lockdown length, peaking with the height of lockdown in July 2021, before declining. CONCLUSIONS: Negative mental health experiences of Australian caregivers and children decreased during postlockdown periods of 2022-2023; however, social gradients persisted. These data can inform more precise mental health policies that enable better use of limited mental health infrastructure.

Special Issue "Recent Process Design and Development Strategies for Dental Materials".

The field of dental materials is rapidly evolving, and this Special Issue of the International Journal of Molecular Sciences offers a comprehensive examination of the latest advancements in process design and development strategies [...].

Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures.

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.

Increasing the Use of Enteral Antibiotics in Hospitalized Children With Uncomplicated Infections.

BACKGROUND: Route of administration is an important component of antimicrobial stewardship. Early transition from intravenous to enteral antibiotics in hospitalized children is associated with fewer catheter-related adverse events, as well as decreased costs and length of stay. Our aim was to increase the percentage of enteral antibiotic doses for hospital medicine patients with uncomplicated common bacterial infections (community-acquired pneumonia, skin and soft tissue infection, urinary tract infection, neck infection) from 50% to 80% in 6 months. METHODS: We formed a multidisciplinary team to evaluate key drivers and design plan-do-study-act cycles. Interventions included provider education, structured discussion at existing team huddles, and pocket-sized printed information. Our primary measure was the percentage of antibiotic doses given enterally to patients receiving other enteral medications. Secondary measures included antibiotic cost, number of peripheral intravenous catheters, length of stay, and 7-day readmission. We used statistical process control charts to track our measures. RESULTS: Over a 6-month baseline period and 12 months of improvement work, we observed 3183 antibiotic doses (888 in the baseline period, 2295 doses during improvement work). We observed an increase in the percentage of antibiotic doses given enterally per week for eligible patients from 50% to 67%. We observed decreased antibiotic costs and fewer peripheral intravenous catheters per encounter after the interventions. There was no change in length of stay or readmissions. CONCLUSIONS: We observed increased enteral antibiotic doses for children hospitalized with common bacterial infections. Interventions targeting culture change and communication were associated with sustained improvement.