FAB1C, a phosphatidylinositol 3-phosphate 5-kinase, interacts with PIN-FORMEDs and modulates their lytic trafficking in Arabidopsis.

PIN-FORMEDs (PINs) are auxin efflux carriers that asymmetrically target the plasma membrane (PM) and are critical for forming local auxin gradients and auxin responses. While the cytoplasmic hydrophilic loop domain of PIN (PIN-HL) is known to include some molecular cues (e.g., phosphorylation) for the modulation of PIN's intracellular trafficking and activity, the complexity of auxin responses suggests that additional regulatory modules may operate in the PIN-HL domain. Here, we have identified and characterized a PIN-HL-interacting protein (PIP) called FORMATION OF APLOID AND BINUCLEATE CELL 1C (FAB1C), a phosphatidylinositol-3-phosphate 5-kinase, which modulates PIN's lytic trafficking. FAB1C directly interacts with PIN-HL and is required for the polarity establishment and vacuolar trafficking of PINs. Unphosphorylated forms of PIN2 interact more readily with FAB1C and are more susceptible to vacuolar lytic trafficking compared to phosphorylated forms. FAB1C also affected lateral root formation by modulating the abundance of periclinally localized PIN1 and auxin maximum in the growing lateral root primordium. These findings suggest that a membrane-lipid modifier can target the cargo-including vesicle by directly interacting with the cargo and modulate its trafficking depending on the cargo's phosphorylation status.

Calcium-dependent protein kinase 29 modulates PIN-FORMED polarity and Arabidopsis development via its own phosphorylation code.

PIN-FORMED (PIN)-mediated polar auxin transport (PAT) is involved in key developmental processes in plants. Various internal and external cues influence plant development via the modulation of intracellular PIN polarity and, thus, the direction of PAT, but the mechanisms underlying these processes remain largely unknown. PIN proteins harbor a hydrophilic loop (HL) that has important regulatory functions; here, we used the HL as bait in protein pulldown screening for modulators of intracellular PIN trafficking in Arabidopsis thaliana. Calcium-dependent protein kinase 29 (CPK29), a Ca2+-dependent protein kinase, was identified and shown to phosphorylate specific target residues on the PIN-HL that were not phosphorylated by other kinases. Furthermore, loss of CPK29 or mutations of the phospho-target residues in PIN-HLs significantly compromised intracellular PIN trafficking and polarity, causing defects in PIN-mediated auxin redistribution and biological processes such as lateral root formation, root twisting, hypocotyl gravitropism, phyllotaxis, and reproductive development. These findings indicate that CPK29 directly interprets Ca2+ signals from internal and external triggers, resulting in the modulation of PIN trafficking and auxin responses.

Reducing Overuse of 3-Day Repeat Type and Screen Testing across an 11-Hospital Safety Net System.

BACKGROUND: According to the American Association of Blood Banks, a Type and Screen (T&S) is valid for up to three calendar days. Beyond a limited number of clinical indications such as a transfusion reaction, repeat T&S testing within 3 days is not warranted. Inappropriate repeat T&S testing is a costly medical waste and can lead to patient harm. OBJECTIVE: To reduce inappropriate duplicate T&S testing across a large, multihospital setting. SETTING: The largest urban safety net health system in the USA, with 11 acute care hospitals. INTERVENTIONS: Our first intervention involved adding the time elapsed since the last T&S order into the order and the process instructions that described when a T&S was indicated. The second intervention was a best practice advisory that triggered when T&S was ordered before the expiration of an active T&S. MAIN MEASURES: The primary outcome measure was the number of duplicate inpatient T&S per 1000 patient days. KEY RESULTS: Across all hospitals, the weekly average rate of duplicate T&S ordering decreased from 8.42 to 7.37 per 1000 patient days (12.5% reduction, p < 0.001) after the first intervention and to 4.32 per 1000 patient days (48.7% reduction, p < 0.001) after the second intervention. Using linear regression to compare pre-intervention to post-intervention 1, the level difference was - 2.46 (9.17 to 6.70, p < 0.001) and slope difference was 0.0001 (0.0282 to 0.0283, p = 1). For post-intervention 1 to post-intervention 2, the level difference was - 3.49 (8.06 to 4.58, p < 0.001) and slope difference was - 0.0428 (0.0283 to - 0.0145, p < 0.05). CONCLUSIONS: Our intervention successfully reduced duplicate T&S testing using a two-pronged electronic health record intervention. The success of this low effort intervention across a diverse health system provides a framework for similar interventions in various clinical settings.

Evaluation of bovine coronavirus in Korean native calves challenged through different inoculation routes.

Bovine coronavirus (BCoV) is a pneumoenteric virus that can infect the digestive and respiratory tracts of cattle, resulting in economic losses. Despite its significance, information regarding BCoV pathogenesis is limited. Hence, we investigated clinical signs, patterns of viral shedding, changes in antibody abundance, and cytokine/chemokine production in calves inoculated with BCoV via intranasal and oral. Six clinically healthy Korean native calves (< 30 days old), initially negative for BCoV, were divided into intranasal and oral groups and monitored for 15 days post-infection (dpi). BCoV-infected calves exhibited clinical signs such as nasal discharge and diarrhea, starting at 3 dpi and recovering by 12 dpi, with nasal discharge being the most common symptoms. Viral RNA was detected in nasal and fecal samples from all infected calves. Nasal shedding occurred before fecal shedding regardless of the inoculation route; however, fecal shedding persisted longer. Although the number of partitions was very few, viral RNA was identified in the blood of two calves in the oral group at 7 dpi and 9 dpi using digital RT-PCR analysis. The effectiveness of maternal antibodies in preventing viral replication and shedding appeared limited. Our results showed interleukin (IL)-8 as the most common and highly induced chemokine. During BCoV infection, the levels of IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1ß were significantly affected, suggesting that these emerge as potential and reliable biomarkers for predicting BCoV infection. This study underscores the importance of BCoV as a major pathogen causing diarrhea and respiratory disease.

Preliminary report of Mycoplasma Wenoynii and Candidatus Mycoplasma haemobos infection in Korean native cattle.

BACKGROUND: Hemotropic mycoplasmas or hemoplasmas are bacteria that attach to the erythrocyte surface and cause bovine hemoplasmosis. Two species, Mycoplasma wenyonii and Candidatus Mycoplasma haemobos, have been identified and shown to be distributed worldwide. However, there is currently no information available on hemoplasmas in cattle in the Republic of Korea. The aim of this study was to investigate the presence of hemoplasmas in Korean native cattle and to evaluate the association between hemoplasma infection and anemia. METHODS: One farm was selected, at which blood samples were collected from 104 Korean native cattle [grazing cattle (n = 89) and housed cattle (n = 15)]. Hemoplasmas were detected via polymerase chain reaction analysis and complete blood counts were also performed. RESULTS: The overall prevalence of hemoplasmas was 34% (35/104); 20.2% (21/104) for M. wenyonii, 3.8% (4/104) for C. M. haemobos, and 9.6% (10/104) for co-infection. Candidatus Mycoplasma haemobos was detected only in grazing cattle. Of red blood cell (RBC) parameters, C. M. haemobos-infected cattle had lower RBC and hematocrit, and higher mean cell volume than hemoplasma-negative cattle, although none of these differences were statistically significant. This is the first study to report the occurrence of M. wenyonii and C. M. haemobos. Mycoplasma wenyonii is more prevalent than C. M. haemobos in Korean native cattle. The results did not show an association between hemoplasma infection and anemia. CONCLUSIONS: Considering the infection rate of hemoplasmas shown in this study, further studies, such as on the pathogenicity and clinical significance of hemoplasmas are necessary.

The DME demethylase regulates sporophyte gene expression, cell proliferation, differentiation, and meristem resurrection.

The flowering plant life cycle consists of alternating haploid (gametophyte) and diploid (sporophyte) generations, where the sporophytic generation begins with fertilization of haploid gametes. In Arabidopsis, genome-wide DNA demethylation is required for normal development, catalyzed by the DEMETER (DME) DNA demethylase in the gamete companion cells of male and female gametophytes. In the sporophyte, postembryonic growth and development are largely dependent on the activity of numerous stem cell niches, or meristems. Analyzing Arabidopsis plants homozygous for a loss-of-function dme-2 allele, we show that DME influences many aspects of sporophytic growth and development. dme-2 mutants exhibited delayed seed germination, variable root hair growth, aberrant cellular proliferation and differentiation followed by enhanced de novo shoot formation, dysregulation of root quiescence and stomatal precursor cells, and inflorescence meristem (IM) resurrection. We also show that sporophytic DME activity exerts a profound effect on the transcriptome of developing Arabidopsis plants, including discrete groups of regulatory genes that are misregulated in dme-2 mutant tissues, allowing us to potentially link phenotypes to changes in specific gene expression pathways. These results show that DME plays a key role in sporophytic development and suggest that DME-mediated active DNA demethylation may be involved in the maintenance of stem cell activities during the sporophytic life cycle in Arabidopsis.

Effect of nanobubbles on powder morphology in the spray drying process.

This study investigated the influence of gas-injected nanobubbles on the morphology of particles during spray drying under various experimental conditions. The nanoparticle tracking system was used to measure the generation, size, and concentration of nanobubbles. Experiments were conducted at different temperatures (160°C-260°C) and feed rates (0.2-0.26 g/s) to examine the effect of nanobubbles on spray drying and present diverse results. The deionized (DI) water with generated nanobubbles had a particle concentration of 1.8 × 108 particles/mL and a mean particle size of 242.6 nm, which was ∼3.31 × 107 particles/mL higher untreated DI water. The maltodextrin solution containing nanobubbles also showed a significant increase in particle generation, with a concentration of 1.62 × 109 particles/mL. The viscosity of the maltodextrin solution containing nanobubbles decreased by ∼18%, from 9.3 mPa·s to 7.5 mPa·s. Overall, the size of the generated particles was similar regardless of nanobubble treatment, but there was a tendency for particle size to increase under specific temperature (260°C) and feed flow rate (0.32 g/s) conditions. Furthermore, it was observed that the Hausner ratio significantly varied with increasing temperature and feed flow rate, and these results were explained through scanning electron microscopy images. These findings confirm that the gas nanobubbles mixed in the feed can exert diverse effects on the spray drying system and powder characteristics depending on the operating conditions. This study suggests that nanobubbles can contribute to a more efficient process in spray drying and can influence the morphological characteristics of particles depending on the spray drying conditions.

Sinonasal seromucinous hamartoma: a single institution case series combined with a narrative review of the literature.

PURPOSE: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs). METHODS: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature. RESULTS: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996). CONCLUSION: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia.

Mycoproteins and their health-promoting properties: Fusarium species and beyond.

Filamentous fungal mycoproteins have gained increasing attention as sustainable alternatives to animal and plant-based proteins. This comprehensive review summarizes the nutritional characteristics, toxicological aspects, and health-promoting effects of mycoproteins, focusing on those derived from filamentous fungi, notably Fusarium venenatum. Mycoproteins are characterized by their high protein content, and they have a superior essential amino acid profile compared to soybeans indicating excellent protein quality and benefits for human nutrition. Additionally, mycoproteins offer enhanced digestibility, further highlighting their suitability as a protein source. Furthermore, mycoproteins are rich in dietary fibers, which have been associated with health benefits, including protection against metabolic diseases. Moreover, their fatty acids profile, with significant proportions of polyunsaturated fatty acids and absence of cholesterol, distinguishes them from animal-derived proteins. In conclusion, the future of mycoproteins as a health-promoting protein alternative and the development of functional foods relies on several key aspects. These include improving the acceptance of mycoproteins, conducting further research into their mechanisms of action, addressing consumer preferences and perceptions, and ensuring safety and regulatory compliance. To fully unlock the potential of mycoproteins and meet the evolving needs of a health-conscious society, continuous interdisciplinary research, collaboration among stakeholders, and proactive engagement with consumers will be vital.

H2A.X promotes endosperm-specific DNA methylation in Arabidopsis thaliana.

BACKGROUND: H2A.X is an H2A variant histone in eukaryotes, unique for its ability to respond to DNA damage, initiating the DNA repair pathway. H2A.X replacement within the histone octamer is mediated by the FAcilitates Chromatin Transactions (FACT) complex, a key chromatin remodeler. FACT is required for DEMETER (DME)-mediated DNA demethylation at certain loci in Arabidopsis thaliana female gametophytes during reproduction. Here, we sought to investigate whether H2A.X is involved in DME- and FACT-mediated DNA demethylation during reproduction. RESULTS: H2A.X is encoded by two genes in Arabidopsis genome, HTA3 and HTA5. We generated h2a.x double mutants, which displayed a normal growth profile, whereby flowering time, seed development, and root tip organization, S-phase progression and proliferation were all normal. However, h2a.x mutants were more sensitive to genotoxic stress, consistent with previous reports. H2A.X fused to Green Fluorescent Protein (GFP) under the H2A.X promoter was highly expressed especially in newly developing Arabidopsis tissues, including in male and female gametophytes, where DME is also expressed. We examined DNA methylation in h2a.x developing seeds and seedlings using whole genome bisulfite sequencing, and found that CG DNA methylation is decreased genome-wide in h2a.x mutant endosperm. Hypomethylation was most striking in transposon bodies, and occurred on both parental alleles in the developing endosperm, but not the embryo or seedling. h2a.x-mediated hypomethylated sites overlapped DME targets, but also included other loci, predominately located in heterochromatic transposons and intergenic DNA. CONCLUSIONS: Our genome-wide methylation analyses suggest that H2A.X could function in preventing access of the DME demethylase to non-canonical sites. Overall, our data suggest that H2A.X is required to maintain DNA methylation homeostasis in the unique chromatin environment of the Arabidopsis endosperm.

Flexible Metasurface for Microwave-Infrared Compatible Camouflage via Particle Swarm Optimization Algorithm.

Metamaterials have the powerful ability to freely control multiband electromagnetic (EM) waves through elaborately designed "artificial atoms" and are hence in the limelight in various fields. Typically, camouflage materials manipulate wave-matter interactions to achieve the desired optical properties, in particular, various techniques are used for multiband camouflage materials in both infrared (IR) and microwave (MW) ranges to overcome the scale difference between these bands. However, in the context of components required for microwave communications, simultaneous control of IR emission and MW transmission is required, which is challenging owing to differences in the wave-matter interactions in these two bands. Herein, the state-of-the-art concept of flexible compatible camouflage metasurface (FCCM) is demonstrated, which can manipulate IR signatures while maintaining MW selective transmission simultaneously. For achieving maximum IR tunability and MW selective transmission, it is performed optimization using the particle swarm optimization (PSO) algorithm. Consequently, the FCCM exhibits compatible camouflage performance with both IR signature reduction and MW selective transmission is demonstrated, with 77.7% IR tunability and 93.8% transmission achieved for a flat FCCM. Furthermore, the FCCM reached the 89.8% IR signature reduction effect even in curved situations.

Artificial Intelligence-Powered Hematoxylin and Eosin Analyzer Reveals Distinct Immunologic and Mutational Profiles among Immune Phenotypes in Non-Small-Cell Lung Cancer.

The tumor microenvironment can be classified into three immune phenotypes: inflamed, immune excluded, and immune-desert. Immunotherapy efficacy has been shown to vary by phenotype; yet, the mechanisms are poorly understood and demand further investigation. This study unveils the mechanisms using an artificial intelligence-powered software called Lunit SCOPE. Artificial intelligence was used to classify 965 samples of non-small-cell lung carcinoma from The Cancer Genome Atlas into the three immune phenotypes. The immune and mutational profiles that shape each phenotype using xCell, gene set enrichment analysis with RNA-sequencing data, and cBioportal were described. In the inflamed subtype, which showed higher cytolytic score, the enriched pathways were generally associated with immune response and immune-related cell types were highly expressed. In the immune excluded subtype, enriched glycolysis, fatty acid, and cholesterol metabolism pathways were observed. The KRAS mutation, BRAF mutation, and MET splicing variant were mostly observed in the inflamed subtype. The two prominent mutations found in the immune excluded subtype were EGFR and PIK3CA mutations. This study is the first to report the distinct immunologic and mutational landscapes of immune phenotypes, and demonstrates the biological relevance of the classification. In light of these findings, the study offers insights into potential treatment options tailored to each immune phenotype.

Risk of various cancers in adults with abdominal aortic aneurysms.

BACKGROUND: The cause of death for patients with an abdominal aortic aneurysm (AAA) can be related to the AAA itself. However, cancer-related mortality could also be a contributing factor. In the present study, we examined the hypothesis that an association exists between AAAs and certain cancers. METHODS: Information from 2009 to 2015 was extracted from the Korean National Health Insurance Service database. We included 14,920 participants with a new diagnosis of an AAA. Propensity score matching by age and sex with disease-free patients was used to select the control group of 44,760 participants. The primary end point of the present study was a new diagnosis of various cancers. RESULTS: The hazard ratio (HR) for cancer incidence was higher in the AAA group than in the control group for hepatoma, pancreatic cancer, and lung cancer (HR, 1.376, 1.429, and 1.394, respectively). In the case of leukemia, the HR for cancer occurrence was not significantly higher in the AAA group than in the control group. However, when stratified by surgery, the HR was significantly higher for the surgical group (HR, 3.355), especially for endovascular aneurysm repair (HR, 3.864). CONCLUSIONS: We found that AAAs are associated with an increased risk of cancer, in particular, hepatoma, pancreatic cancer, and lung cancer, even after adjusting for several comorbidities. Thus, continued follow-up is necessary for patients with an AAA to permit the early detection of the signs and symptoms of cancer.

Generalized optical signal-to-noise ratio monitoring using a convolutional neural network for digital coherent receivers.

In this Letter, we propose a generalized optical signal-to-noise ratio (GOSNR) monitoring scheme using a convolutional neural network trained on constellation density features acquired from a back-to-back setup and demonstrate accurate GOSNR estimations for links having different nonlinearities. The experiments were carried over dense wavelength division multiplexing links configured on 32-Gbaud polarization division multiplexed 16-quadrature amplitude modulation (QAM) and demonstrated that the GOSNRs are estimated within 0.1 dB mean absolute error with maximum estimation errors below 0.5 dB on metro class links. The proposed technique does not require any information about the noise floor in the conventional spectrum-based means and therefore is readily deployable for real-time monitoring.

IL-4 drastically decreases deuterosomal and multiciliated cells via alteration in progenitor cell differentiation.

BACKGROUND: Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. METHODS: We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. RESULTS: We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+ -ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation. CONCLUSION: The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.

Student High Value Care Initiative: a Longitudinal Model for Student-Led Implementation and Scholarship.

BACKGROUND: Educating medical trainees to practice high value care is a critical component to improving quality of care and should be introduced at the beginning of medical education. AIM: To create a successful educational model that provides medical students and junior faculty with experiential learning in quality improvement and mentorship opportunities, and produce effective quality initiatives. SETTING: A tertiary medical center affiliated with a medical school in New York City. PARTICIPANTS: First year medical students, junior faculty in hospital medicine, and a senior faculty course director. PROGRAM DESCRIPTION: The Student High Value Care initiative is a longitudinal initiative comprised of six core elements: (1) project development, (2) value improvement curriculum, (3) mentorship, (4), Institutional support, (5) scholarship, and (6) student leadership. PROGRAM EVALUATION: During the first 3 years, 68 medical students and ten junior faculty participated in 10 quality improvement projects. Nine projects were successful in their measured outcomes, with statistically significant improvements. Nine had an abstract accepted to a regional or national meeting, and seven produced publications in peer-reviewed literature. DISCUSSION: In the first 3 years of the initiative, we successfully engaged medical students and junior faculty to create and support the implementation of successful quality improvement initiatives. Since that time, the program continues to offer meaningful mentorship and scholarship opportunities.

Reducing 25-Hydroxyvitamin D Testing in a Large, Urban Safety Net System.

BACKGROUND: 25-Hydroxyvitamin D testing is increasing despite national guidelines and Choosing Wisely recommendations against routine screening. Overuse can lead to misdiagnosis and unnecessary downstream testing and treatment. Repeat testing within 3 months is a unique area of overuse. OBJECTIVE: To reduce 25-hydroxyvitamin D testing in a large safety net system comprising 11 hospitals and 70 ambulatory centers. DESIGN: This was a quality improvement initiative with a quasi-experimental interrupted time series design with segmented regression. PARTICIPANTS: All patients in the inpatient and outpatient settings with at least one order for 25-hydroxyvitamin D were included in the analysis. INTERVENTIONS: An electronic health record clinical decision support tool was designed for inpatient and outpatient orders and involved two components: a mandatory prompt requiring appropriate indications and a best practice advisory (BPA) focused on repeat testing within 3 months. MAIN MEASURES: The pre-intervention period (6/17/2020-6/13/2021) was compared to the post-intervention period (6/14/2021-8/28/2022) for total 25-hydroxyvitamin D testing, as well as 3-month repeat testing. Hospital and clinic variation in testing was assessed. Additionally, best practice advisory action rates were analyzed, separated by clinician type and specialty. KEY RESULTS: There were 44% and 46% reductions in inpatient and outpatient orders, respectively (p < 0.001). Inpatient and outpatient 3-month repeat testing decreased by 61% and 48%, respectively (p < 0.001). The best practice advisory true accept rate was 13%. CONCLUSION: This initiative successfully reduced 25-hydroxyvitamin D testing through the use of mandatory appropriate indications and a best practice advisory focusing on a unique area of overuse: the repeat testing within a 3-month interval. There was wide variation among hospitals and clinics and variation among clinician types and specialties regarding actions to the best practice advisory.

Reducing low-value ED coags across 11 hospitals in a safety net setting.

BACKGROUND: Prothrombin/international normalized ratio and activated partial thromboplastin time (PT/INR and aPTT) are frequently ordered in emergency departments (EDs), but rarely affect management. They offer limited utility outside of select indications. Several quality improvement initiatives have shown reduction in ED use of PT/INR and aPTT using multifaceted interventions in well-resourced settings. Successful reduction of these low-value tests has not yet been shown using a single intervention across a large hospital system in a safety net setting. This study aims to determine if an intervention of two BPAs is associated with a reduction in PT/INR and aPTT usage across a large safety net system. METHODS: This initiative was set at a large safety net system in the United States with 11 acute care hospitals. Two Best Practice Advisories (BPAs) discouraging inappropriate PT/INR and aPTT use were implemented from March 16, 2022-August 30, 2022. Order rate per 100 ED patients during the pre-intervention period was compared to the post-intervention period on both the system and individual hospital level. Complete blood count (CBC) testing served as a control, and packed red blood cell transfusions served as a balancing measure. An interrupted time series regression analysis was performed to capture immediate and temporal changes in ordering for all tests in the pre and post-intervention periods. RESULTS: PT/INR tests exhibited an absolute decline of 4.11 tests per 100 ED encounters (95% confidence interval -5.17 to -3.05; relative reduction of 18.9%). aPTT tests exhibited absolute decline of 4.03 tests per 100 ED encounters (95% CI -5.10 to -2.97; relative reduction of 19.8%). The control measure, CBC, did not significantly change (-0.43, 95% CI -2.83 to 1.96). Individual hospitals showed variable response, with absolute reductions from 2.02 to 9.6 tests per 100 ED encounters for PT/INR (relative reduction 12.1%-30.5%) and 2.07 to 10.04 for aPTT (relative reduction 12.1%-31.4%). Regression analysis showed that the intervention caused an immediate 25.7% decline in PT/INR and 24.7% decline in aPTT tests compared to the control measure. The slope differences (rate of order increase pre vs post intervention) did not significantly decline compared to the control. CONCLUSIONS: This BPA intervention reduced PT/INR and aPTT use across 11 EDs in a large, urban, safety net system. Further study is needed in implementation to other non-safety net settings.

Reducing daily dosing in opioid prescriptions in 11 safety net emergency departments.

BACKGROUND: The United States continues to face a significant issue with opioid misuse, overprescribing, dependency, and overdose. Electronic health record (EHR) interventions have shown to be an effective tool to modify opioid prescribing behaviors. This quality improvement project describes an EHR intervention to reduce daily dosing in opioid prescriptions in 11 emergency departments (ED) across the largest safety net health system in the US. MEASURES: The primary outcome measure was the rates of oxycodone-acetaminophen 5-325 mg prescriptions exceeding 50 morphine milligram equivalents per day (MMED) pre- vs. post-intervention; and stratified by individual hospitals and provider type. INTERVENTION: The defaults for dose and frequency were uniformly changed to 'every 6 hours as needed' and '1 tablet', respectively, across 11 EDs. OUTCOMES: The percentage of prescriptions greater than or equal to 50 MMED decreased from 46.0% (1624 of 3530 prescriptions) to 1.6% (52 of 3165 prescriptions) (96.4% relative reduction; p < 0.001). All 11 hospitals had a significant reduction in prescriptions exceeding 50 MMED. Nurse practitioners had the highest relative reduction of prescriptions exceeding 50 MMED at 100% (p < 0.001), and the attendings/fellows had the lowest relative reduction at 95.6% (p < 0.001). CONCLUSIONS/LESSONS LEARNED: Default nudges are a simple yet powerful intervention that can strongly influence opioid prescribing patterns.

Nationwide-incidence and trends of fibromyalgia in South Korea: a population-based study.

Reports of the incidence of fibromyalgia (FM) in Asia are uncommon. Therefore, this study used nationwide representative data to investigate the age- and sex-specific incidence and annual trends of FM in South Korea. This nationwide population-based study used data from the Korean National Health Claims Database. From 2012 to 2021, patients with FM diagnosed according to the ACR 2010 criteria from the entire Korean population aged 20-70 years were included in the enrolment database. Age- and sex-specific cumulative and annual incidences were analyzed and incident cases from 2014 to 2021 were included, considering the 2-year washout period. Among the total cohort of 42 million in the entire Korean population, 270,160 had FM during the study period. The incidence in the general population aged 20-70 years was 751.25 (95% confidence interval [CI] 751.10-751.40) per 100,000 persons (men: 95% CI 608.45-608.98; women: 95% CI 898.02-898.69). The incidence of FM increased with advancing age, peaking at 50-54 years both in men and women. The annual incidence was 88.07 (95% CI 88.02-88.13) in 2014; it increased from 2014 to 2019 and peaked in 2019 (109.20; 95% CI 101.65-101.76). The incidence of FM in South Korea was about twice the global average, with a gradual increase over the study period. These detailed estimates can help with proper planning within the healthcare system.