Characterizing emergency department and inpatient health care utilization after seizure-related hospitalization: A retrospective cohort study.

OBJECTIVE: Seizure care is a significant driver of health care costs in both emergency department (ED) and inpatient settings, but the majority of studies have focused on inpatient admissions as the only metric of health care utilization. This study aims to better characterize ED and inpatient encounters among patients with seizure to inform care and policy. METHODS: Using statewide administrative data from the Healthcare Cost and Utilization Project State Inpatient Databases and State Emergency Department Databases from Florida and New York, we identified patients with a seizure-related index hospitalization between January 1, 2016, and December 31, 2018. Among this cohort, we examined the incidence and characteristics of subsequent acute care visits in the ED and inpatient settings for 365 days after initial hospital discharge. RESULTS: A total of 54 456 patients had an eligible seizure-related hospitalization. Patients were 49% female, predominantly White (64%) and non-Hispanic (84%), and used a public primary payer (68%). There were 36 838 (68%) patients with at least one acute care visit in the year following discharge. Overall, patients had a median of 2 (interquartile [IQR] = 1-5) subsequent acute care visits and the median time to first acute care visit was 53 days (IQR = 15-138). Of the 154 369 subsequent acute care visits, 97 399 (63%) were ED-only visits, 56 970 (37%) were readmissions, and 37 176 (24%) were seizure-related. There were 18 786 patients (35%) with four or more acute care visits over 365 days of follow-up. Patients with four or more visits contributed 84% of acute care visits and 78% of costs after initial hospitalization. SIGNIFICANCE: The majority of patients hospitalized for seizure return to the ED or hospital at least once in the year after discharge. A small portion of patients account for the majority of ED and inpatient visits as well as health care costs associated with this population, identifying a subgroup of patients who may benefit from improved inpatient and outpatient management.

Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability.

Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2nes) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4+CD8+ T-cell stage from which tumors initiate. Premalignant CD4+CD8+ T cells show persistent catenations during chromosome segregation, triggering DNA damage in diploid daughter cells and elevated ploidy. Genome sequencing revealed that Caph2 single-mutant tumors are near diploid but carry deletions spanning tumor suppressor genes, whereas P53 inactivation allowed Caph2 mutant cells with whole-chromosome gains and structural rearrangements to form highly aggressive disease. Together, our data challenge the view that mitotic chromosome formation is an invariant process during development and provide evidence that defective mitotic chromosome structure can promote tumorigenesis.

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis.

Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.

Heterochromatin delays CRISPR-Cas9 mutagenesis but does not influence the outcome of mutagenic DNA repair.

Genome editing occurs in the context of chromatin, which is heterogeneous in structure and function across the genome. Chromatin heterogeneity is thought to affect genome editing efficiency, but this has been challenging to quantify due to the presence of confounding variables. Here, we develop a method that exploits the allele-specific chromatin status of imprinted genes in order to address this problem in cycling mouse embryonic stem cells (mESCs). Because maternal and paternal alleles of imprinted genes have identical DNA sequence and are situated in the same nucleus, allele-specific differences in the frequency and spectrum of mutations induced by CRISPR-Cas9 can be unequivocally attributed to epigenetic mechanisms. We found that heterochromatin can impede mutagenesis, but to a degree that depends on other key experimental parameters. Mutagenesis was impeded by up to 7-fold when Cas9 exposure was brief and when intracellular Cas9 expression was low. In contrast, the outcome of mutagenic DNA repair was unaffected by chromatin state, with similar efficiencies of homology-directed repair (HDR) and deletion spectra on maternal and paternal chromosomes. Combined, our data show that heterochromatin imposes a permeable barrier that influences the kinetics, but not the endpoint, of CRISPR-Cas9 genome editing and suggest that therapeutic applications involving low-level Cas9 exposure will be particularly affected by chromatin status.

Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip.

Long noncoding RNAs (lncRNAs) have been implicated in various biological functions including the regulation of gene expression, however, the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them. Moreover, little is known about the upstream regulation of lncRNAs. Here we show that the short isoform (p52) of a transcriptional co-activator-PC4 and SF2 interacting protein (Psip1), which is known to be involved in linking transcription to RNA processing, specifically regulates the expression of the lncRNA Hottip-located at the 5' end of the Hoxa locus. Using both knockdown and knockout approaches we show that Hottip expression is required for activation of the 5' Hoxa genes (Hoxa13 and Hoxa10/11) and for retaining Mll1 at the 5' end of Hoxa. Moreover, we demonstrate that artificially inducing Hottip expression is sufficient to activate the 5' Hoxa genes and that Hottip RNA binds to the 5' end of Hoxa. By engineering premature transcription termination, we show that it is the Hottip lncRNA molecule itself, not just Hottip transcription that is required to maintains active expression of posterior Hox genes. Our data show a direct role for a lncRNA molecule in regulating the expression of developmentally-regulated mRNA genes in cis.

Evolution by duplication: paleopolyploidy events in plants reconstructed by deciphering the evolutionary history of VOZ transcription factors.

BACKGROUND: Facilitated by the rapid progress of sequencing technology, comparative genomic studies in plants have unveiled recurrent whole genome duplication (i.e. polyploidization) events throughout plant evolution. The evolutionary past of plant genes should be analyzed in a background of recurrent polyploidy events in distinctive plant lineages. The Vascular Plant One Zinc-finger (VOZ) gene family encode transcription factors associated with a number of important traits including control of flowering time and photoperiodic pathways, but the evolutionary trajectory of this gene family remains uncharacterized. RESULTS: In this study, we deciphered the evolutionary history of the VOZ gene family by analyses of 107 VOZ genes in 46 plant genomes using integrated methods: phylogenic reconstruction, Ks-based age estimation and genomic synteny comparisons. By scrutinizing the VOZ gene family phylogeny the core eudicot γ event was well circumscribed, and relics of the precommelinid τ duplication event were detected by incorporating genes from oil palm and banana. The more recent T and ρ polyploidy events, closely coincident with the species diversification in Solanaceae and Poaceae, respectively, were also identified. Other important polyploidy events captured included the "salicoid" event in poplar and willow, the "early legume" and "soybean specific" events in soybean, as well as the recent polyploidy event in Physcomitrella patens. Although a small transcription factor gene family, the evolutionary history of VOZ genes provided an outstanding record of polyploidy events in plants. The evolutionary past of VOZ gene family demonstrated a close correlation with critical plant polyploidy events which generated species diversification and provided answer to Darwin's "abominable mystery". CONCLUSIONS: We deciphered the evolutionary history of VOZ transcription factor family in plants and ancestral polyploidy events in plants were recapitulated simultaneously. This analysis allowed for the generation of an idealized plant gene tree demonstrating distinctive retention and fractionation patterns following polyploidy events.

Identification, Classification, and Functional Analysis of AP2/ERF Family Genes in the Desert Moss Bryum argenteum.

Bryum argenteum is a desert moss which shows tolerance to the desert environment and is emerging as a good plant material for identification of stress-related genes. AP2/ERF transcription factor family plays important roles in plant responses to biotic and abiotic stresses. AP2/ERF genes have been identified and extensively studied in many plants, while they are rarely studied in moss. In the present study, we identified 83 AP2/ERF genes based on the comprehensive dehydrationrehydration transcriptomic atlas of B. argenteum. BaAP2/ERF genes can be classified into five families, including 11 AP2s, 43 DREBs, 26 ERFs, 1 RAV, and 2 Soloists. RNA-seq data showed that 83 BaAP2/ERFs exhibited elevated transcript abundances during dehydration⁻rehydration process. We used RT-qPCR to validate the expression profiles of 12 representative BaAP2/ERFs and confirmed the expression trends using RNA-seq data. Eight out of 12 BaAP2/ERFs demonstrated transactivation activities. Seven BaAP2/ERFs enhanced salt and osmotic stress tolerances of yeast. This is the first study to provide detailed information on the identification, classification, and functional analysis of the AP2/ERFs in B. argenteum. This study will lay the foundation for the further functional analysis of these genes in plants, as well as provide greater insights into the molecular mechanisms of abiotic stress tolerance of B. argenteum.

Condensin and cohesin complexity: the expanding repertoire of functions.

Condensin and cohesin complexes act in diverse nuclear processes in addition to their widely known roles in chromosome compaction and sister chromatid cohesion. Recent work has elucidated the contribution of condensin and cohesin to interphase genome organization, control of gene expression, metazoan development and meiosis. Despite these wide-ranging functions, several themes have come to light: both complexes establish higher-order chromosome structure by inhibiting or promoting interactions between distant genomic regions, both complexes influence the chromosomal association of other proteins, and both complexes achieve functional specialization by swapping homologous subunits. Emerging data are expanding the range of processes in which condensin and cohesin are known to participate and are enhancing our knowledge of how chromosome architecture is regulated to influence numerous cellular functions.

De novo transcriptome characterization and gene expression profiling of the desiccation tolerant moss Bryum argenteum following rehydration.

BACKGROUND: The desiccation-tolerant moss Bryum argenteum is an important component of the Biological Soil Crusts (BSCs) found in the Gurbantunggut desert. Desiccation tolerance is defined as the ability to revive from the air dried state. To elucidate the molecular mechanisms related to desiccation tolerance, we employed RNA-Seq and digital gene expression (DGE) technologies to study the genome-wide expression profiles of the dehydration and rehydration processes in this important desert plant. RESULTS: We applied a two-step approach to investigate the gene expression profile upon rehydration in the moss Bryum argenteum using Illumina HiSeq2000 sequencing platform. First, a total of 57,247 transcript assembly contigs (TACs) were obtained from 54.79 million reads by de novo assembly, with an average length of 863 bp and N50 of 1,372 bp. Among the reconstructed TACs, 36,916 (64.5%) revealed similarity with existing protein sequences in the public databases. 23,509 and 21,607 TACs were assigned GO and KEGG annotation information, respectively. Second, samples were taken from 3 hydration stages: desiccated (Dry), rehydrated 2 h (R2) and rehydrated 24 h (R24), and DEG libraries were constructed for Differentially Expressed Genes (DEGs) discovery. 4,081 and 6,709 DEGs were identified in R2 and R24, compared with Dry, respectively. Compared to the desiccated sample, up-regulated genes after two hours of hydration are primarily related to stress responses. GO function enrichment network, EKGG metabolic pathway and MapMan analysis supports the idea of the rapid recovery of photosynthesis after 24 h of rehydration. We identified 770 transcription factors (TFs) which were classified into 50 TF families. 142 TF transcripts were up-regulated upon rehydration including 23 members of the ERF family. CONCLUSIONS: In this study, we constructed a pioneering, high-quality reference transcriptome in B. argenteum and generated three DGE libraries to elucidate the changes of gene expression upon rehydration. Expression profiles consistent with the rapid recovery of photosynthesis (at R2) and the re-establishment of a positive carbon balance following rehydration (at R24) were observed. Our study will extend our knowledge of bryophyte transcriptomes and provide further insight into the molecular mechanisms related to rehydration and desiccation-tolerance.

EsDREB2B, a novel truncated DREB2-type transcription factor in the desert legume Eremosparton songoricum, enhances tolerance to multiple abiotic stresses in yeast and transgenic tobacco.

BACKGROUND: Dehydration-Responsive Element-Binding Protein2 (DREB2) is a transcriptional factor which regulates the expression of several stress-inducible genes. DREB2-type proteins are particularly important in plant responses to drought, salt and heat. DREB2 genes have been identified and characterized in a variety of plants, and DREB2 genes are promising candidate genes for the improvement of stress tolerance in plants. However, little is known about these genes in plants adapted to water-limiting environments. RESULTS: In this study, we describe the characterization of EsDREB2B, a novel DREB2B gene identified from the desert plant Eremosparton songoricum. Phylogenetic analysis and motif prediction indicate that EsDREB2B encodes a truncated DREB2 polypeptide that belongs to a legume-specific DREB2 group. In E. songoricum, EsDREB2B transcript accumulation was induced by a variety of abiotic stresses, including drought, salinity, cold, heat, heavy metal, mechanical wounding, oxidative stress and exogenous abscisic acid (ABA) treatment. Consistent with the predicted role as a transcription factor, EsDREB2B was targeted to the nucleus of onion epidermal cells and exhibited transactivation activity of a GAL4-containing reporter gene in yeast. In transgenic yeast, overexpression of EsDREB2B increased tolerance to multiple abiotic stresses. Our findings indicate that EsDREB2B can enhance stress tolerance in other plant species. Heterologous expression of EsDREB2B in tobacco showed improved tolerance to multiple abiotic stresses, and the transgenic plants exhibited no reduction in foliar growth. We observed that EsDREB2B is a functional DREB2-orthologue able to influence the physiological and biochemical response of transgenic tobacco to stress. CONCLUSIONS: Based upon these findings, EsDREB2B encodes an abiotic stress-inducible, transcription factor which confers abiotic stress-tolerance in yeast and transgenic tobacco.

Epigenetic control of alternative mRNA processing at the imprinted Herc3/Nap1l5 locus.

Alternative polyadenylation increases transcriptome diversity by generating multiple transcript isoforms from a single gene. It is thought that this process can be subject to epigenetic regulation, but few specific examples of this have been reported. We previously showed that the Mcts2/H13 locus is subject to genomic imprinting and that alternative polyadenylation of H13 transcripts occurs in an allele-specific manner, regulated by epigenetic mechanisms. Here, we demonstrate that allele-specific polyadenylation occurs at another imprinted locus with similar features. Nap1l5 is a retrogene expressed from the paternally inherited allele, is situated within an intron of a 'host' gene Herc3, and overlaps a CpG island that is differentially methylated between the parental alleles. In mouse brain, internal Herc3 polyadenylation sites upstream of Nap1l5 are used on the paternally derived chromosome, from which Nap1l5 is expressed, whereas a downstream site is used more frequently on the maternally derived chromosome. Ablating DNA methylation on the maternal allele at the Nap1l5 promoter increases the use of an internal Herc3 polyadenylation site and alters exon splicing. These changes demonstrate the influence of epigenetic mechanisms in regulating Herc3 alternative mRNA processing. Internal Herc3 polyadenylation correlates with expression levels of Nap1l5, suggesting a possible role for transcriptional interference. Similar mechanisms may regulate alternative polyadenylation elsewhere in the genome.

Degron tagging for rapid protein degradation in mice.

Degron tagging allows proteins of interest to be rapidly degraded, in a reversible and tuneable manner, in response to a chemical stimulus. This provides numerous opportunities for understanding disease mechanisms, modelling therapeutic interventions and constructing synthetic gene networks. In recent years, many laboratories have applied degron tagging successfully in cultured mammalian cells, spurred by rapid advances in the fields of genome editing and targeted protein degradation. In this At a Glance article, we focus on recent efforts to apply degron tagging in mouse models, discussing the distinct set of challenges and opportunities posed by the in vivo environment.

Differences in Cardiovascular Health at the Intersection of Race, Ethnicity, and Sexual Identity.

Importance: An understanding of the intersectional effect of sexual identity, race, and ethnicity on disparities in cardiovascular health (CVH) has been limited. Objective: To evaluate differences in CVH at the intersection of race, ethnicity, and sexual identity using the American Heart Association's Life's Essential 8 measure. Design, Setting, and Participants: This cross-sectional study was conducted from July 27 to September 6, 2023, using National Health and Nutrition Examination Survey data from 2007 to 2016. Participants were noninstitutionalized, nonpregnant adults (aged 18-59 years) without cardiovascular disease or stroke. Exposures: Self-reported sexual identity, categorized as heterosexual or sexual minority (SM; lesbian, gay, bisexual, or "something else"), and self-reported race and ethnicity, categorized as non-Hispanic Black (hereafter, Black), Hispanic, non-Hispanic White (hereafter, White), and other (Asian, multiracial, or any other race and ethnicity). Main Outcome and Measures: The primary outcome was overall CVH score, which is the unweighted mean of 8 CVH metrics, assessed from questionnaire, dietary, and physical examination data. Regression models stratified by sex, race, and ethnicity were developed for the overall CVH score and individual CVH metrics, adjusting for age, survey year, and socioeconomic status (SES) factors. Results: The sample included 12 180 adults (mean [SD] age, 39.6 [11.7] years; 6147 [50.5%] male, 2464 [20.2%] Black, 3288 [27.0%] Hispanic, 5122 [42.1%] White, and 1306 [10.7%] other race and ethnicity). After adjusting for age, survey year, and SES, Black (ß, -3.2; 95% CI, -5.8 to -0.6), Hispanic (ß, -5.9; 95% CI, -10.3 to -1.5), and White (ß, -3.3; 95% CI, -6.2 to -0.4) SM female adults had lower overall CVH scores compared with their heterosexual counterparts. There were no statistically significant differences for female adults of other race and ethnicity (ß, -2.8; 95% CI, -9.3 to 3.7) and for SM male adults of any race and ethnicity compared with their heterosexual counterparts (Black: ß, 2.2 [95% CI, -1.2 to 5.7]; Hispanic: ß, -0.9 [95% CI, -6.3 to 4.6]; White: ß, 1.5 [95% CI, -2.2 to 5.2]; other race and ethnicity: ß, -2.2 [95% CI, -8.2 to 3.8]). Conclusions and Relevance: In this cross-sectional study, CVH differed across race and ethnicity categories in SM females, suggesting that different communities within the larger SM population require tailored interventions to improve CVH. Longitudinal studies are needed to identify the causes of CVH disparities, particularly in Black and Hispanic SM females and inclusive of other racial and ethnic identities.

Evaluating the feasibility of prehospital point-of-care EEG: The prehospital implementation of rapid EEG (PHIRE) study.

Background: Point-of-care electroencephalography (EEG) devices can be rapidly applied and do not require specialized technologists, creating new opportunities to use EEG during prehospital care. We evaluated the feasibility of point-of-care EEG during ambulance transport for 911 calls. Methods: This mixed-methods study was conducted between May 28, 2022 and October 28, 2023. Emergency Medical Services (EMS) clinicians identified eligible individuals, provided emergent treatment, applied EEG, and obtained an EEG recording during ambulance transport. Eligible patients were aged 6 years or older and evaluated for seizure, stroke, or altered mental status. EMS clinicians completed a survey and a brief phone interview following every enrollment. Two epileptologists reviewed EEG recordings for interpretability and artifact. Results: There were 34 prehospital encounters in which EEG was applied. Patients had a mean age of 69 years, and 15 (44%) were female. EEG recordings had a median duration of 10 min 30 s. It took EMS clinicians an average of 2.5 min to apply the device and begin EEG recording. There were 14 (47%) recordings where clinicians achieved a high-quality connection for all 10 electrodes and 32 (94%) recordings that were sufficient in quality to interpret. There were 24 (71%) recordings with six or more channels free of artifact for 5 min or more. All clinicians agreed or strongly agreed that the device was easy to use. Conclusion: Among real-world prehospital encounters for patients with neurologic symptoms, point-of-care EEG was rapidly applied and yielded EEG recordings that could be used for clinical interpretation, demonstrating the feasibility of point-of-care EEG in future prehospital care.

Aldehyde dehydrogenase (ALDH) superfamily in plants: gene nomenclature and comparative genomics.

In recent years, there has been a significant increase in the number of completely sequenced plant genomes. The comparison of fully sequenced genomes allows for identification of new gene family members, as well as comprehensive analysis of gene family evolution. The aldehyde dehydrogenase (ALDH) gene superfamily comprises a group of enzymes involved in the NAD(+)- or NADP(+)-dependent conversion of various aldehydes to their corresponding carboxylic acids. ALDH enzymes are involved in processing many aldehydes that serve as biogenic intermediates in a wide range of metabolic pathways. In addition, many of these enzymes function as 'aldehyde scavengers' by removing reactive aldehydes generated during the oxidative degradation of lipid membranes, also known as lipid peroxidation. Plants and animals share many ALDH families, and many genes are highly conserved between these two evolutionarily distinct groups. Conversely, both plants and animals also contain unique ALDH genes and families. Herein we carried out genome-wide identification of ALDH genes in a number of plant species-including Arabidopsis thaliana (thale crest), Chlamydomonas reinhardtii (unicellular algae), Oryza sativa (rice), Physcomitrella patens (moss), Vitis vinifera (grapevine) and Zea mays (maize). These data were then combined with previous analysis of Populus trichocarpa (poplar tree), Selaginella moellindorffii (gemmiferous spikemoss), Sorghum bicolor (sorghum) and Volvox carteri (colonial algae) for a comprehensive evolutionary comparison of the plant ALDH superfamily. As a result, newly identified genes can be more easily analyzed and gene names can be assigned according to current nomenclature guidelines; our goal is to clarify previously confusing and conflicting names and classifications that might confound results and prevent accurate comparisons between studies.

Human imprinted retrogenes exhibit non-canonical imprint chromatin signatures and reside in non-imprinted host genes.

Imprinted retrotransposed genes share a common genomic organization including a promoter-associated differentially methylated region (DMR) and a position within the intron of a multi-exonic 'host' gene. In the mouse, at least one transcript of the host gene is also subject to genomic imprinting. Human retrogene orthologues are imprinted and we reveal that human host genes are not imprinted. This coincides with genomic rearrangements that occurred during primate evolution, which increase the separation between the retrogene DMRs and the host genes. To address the mechanisms governing imprinted retrogene expression, histone modifications were assayed at the DMRs. For the mouse retrogenes, the active mark H3K4me2 was associated with the unmethylated paternal allele, while the methylated maternal allele was enriched in repressive marks including H3K9me3 and H4K20me3. Two human retrogenes showed monoallelic enrichment of active, but not of repressive marks suggesting a partial uncoupling of the relationship between DNA methylation and repressive histone methylation, possibly due to the smaller size and lower CpG density of these DMRs. Finally, we show that the genes immediately flanking the host genes in mouse and human are biallelically expressed in a range of tissues, suggesting that these loci are distinct from large imprinted clusters.

US practice adoption of patient-engagement strategies and spending for adults with diabetes and cardiovascular disease.

Patient-engagement strategies are being encouraged by payers and governments, but with limited evidence about whether practice adoption of these strategies impacts utilization and spending. We examine the association of physician practice adoption of patient-engagement strategies (low vs moderate vs high) with potentially preventable utilization and total spending for patients with type 2 diabetes and/or cardiovascular disease using US physician practice survey (n = 2086) and Medicare fee-for-service (n = 736 269) data. In adjusted analyses, there were no differences in potentially preventable utilization associated with practice adoption of patient-engagement strategies. Compared with patients attributed to practices with moderate adoption, patients attributed to practices with high adoption had higher total spending ($26 364 vs $25 991; P < .05) driven by spending for long-term services and supports, including home health agency, long-term care, skilled nursing facilities, and hospice payments. In contrast, patients attributed to practices with low adoption had higher total spending ($26 481 vs $25 991; P < .01) driven by spending for tests and acute care and clinical access spending. The results highlight that stakeholders that encourage the use of patient-engagement strategies should not necessarily expect reduced spending.

Improving the engagement of patients with type 2 diabetes and cardiovascular disease (CVD) in their own health and health care can enhance self-management skills and self-efficacy for behavior change, potentially reducing treatment burden. It remains unclear, however, whether US physician practices with more extensive adoption of patient-engagement strategies, including shared decision making, motivational interviewing, and shared medical appointments, have lower potentially preventable utilization and total spending for adults with type 2 diabetes and/or CVD. In a national study of US physician practices and Medicare beneficiaries, we find that practice adoption of patient-engagement strategies is associated with total spending in a nonlinear fashion. Compared with practices with moderate adoption of patient-engagement strategies, practices with high adoption had higher total spending ($25 991 vs $26 364; P < .05) driven by spending for long-term services and supports, while practices with low adoption had higher total spending ($25 991 vs $26 481; P < .01) driven by tests, acute care, and clinical access spending. The results highlight that key stakeholders encouraging the use of patient-engagement strategies should not necessarily expect reduced spending.

Hospital EEG Capability and Associations With Interhospital Transfer in Status Epilepticus.

Background and Objectives: EEG is widely recommended for status epilepticus (SE) management. However, EEG access and use across the United States is poorly characterized. We aimed to evaluate changes in inpatient EEG access over time and whether availability of EEG is associated with interhospital transfers for patients hospitalized with SE. Methods: We performed a cross-sectional study using data available in the National Inpatient Sample data set from 2012 to 2018. We identified hospitals that used continuous or routine EEG during at least 1 seizure-related hospitalization in a given year using ICD-9 and ICD-10 procedure codes and defined these hospitals as EEG capable. We examined annual change in the proportion of hospitals that were EEG capable during the study period, compared characteristics of hospitals that were EEG capable with those that were not, and fit multivariable logistic regression models to determine whether hospital EEG capability was associated with likelihood of interhospital transfer. Results: Among 4,550 hospitals in 2018, 1,241 (27.3%) were EEG capable. Of these, 1,188 hospitals (95.7%) were in urban settings. From 2012 to 2018, the proportion of hospitals that were EEG capable increased in urban settings (30.5%-41.1%, Mann-Kendall [M-K] test p < 0.001) and decreased in rural settings (4.0%-3.2%, M-K p = 0.026). Among 130,580 patients hospitalized with SE, 80,725 (61.8%) presented directly to an EEG-capable hospital. However, EEG use during hospitalization varied from 8% to 98%. Initial admission to a hospital without EEG capability was associated with 22% increased likelihood of interhospital transfer (adjusted RR 1.22, [95% CI, 1.09-1.37]; p < 0.01). Among those hospitalized at an EEG-capable hospital, patients admitted to hospitals in the lowest quintile of EEG volume were more than 2 times more likely to undergo interhospital transfer (adjusted RR 2.22, [95% CI 1.65-2.93]; p < 0.001). Discussion: A minority of hospitals are EEG capable yet care for most patients with SE. Inpatient EEG use, however, varies widely among EEG-capable hospitals, and lack of inpatient EEG access is associated with interhospital transfer. Given the high incidence and cost of SE, there is a need to better understand the importance and use of EEG in this patient population to further organize inpatient epilepsy systems of care to optimize outcomes.

Care Ecosystem Collaborative Model and Health Care Costs in Medicare Beneficiaries With Dementia: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Collaborative dementia care programs are effective in addressing the needs of patients with dementia and their caregivers. However, attempts to consider effects on health care spending have been limited, leaving a critical gap in the conversation around value-based dementia care. Objective: To determine the effect of participation in collaborative dementia care on total Medicare reimbursement costs compared with usual care. Design, Setting, and Participants: This was a prespecified secondary analysis of the Care Ecosystem trial, a 12-month, single-blind, parallel-group randomized clinical trial conducted from March 2015 to March 2018 at 2 academic medical centers in California and Nebraska. Participants were patients with dementia who were living in the community, aged 45 years or older, and had a primary caregiver and Medicare fee-for-service coverage for the duration of the trial. Intervention: Telehealth dementia care program that entailed assignment to an unlicensed dementia care guide who provided caregiver support, standardized education, and connection to licensed dementia care specialists. Main Outcomes and Measures: Primary outcome was the sum of all Medicare claim payments during study enrollment, excluding Part D (drugs). Results: Of the 780 patients in the Care Ecosystem trial, 460 (59.0%) were eligible for and included in this analysis. Patients had a median (IQR) age of 78 (72-84) years, and 256 (55.7%) identified as female. Participation in collaborative dementia care reduced the total cost of care by $3290 from 1 to 6 months postenrollment (95% CI, -$6149 to -$431; P = .02) and by $3027 from 7 to 12 months postenrollment (95% CI, -$5899 to -$154; P = .04), corresponding overall to a mean monthly cost reduction of $526 across 12 months. An evaluation of baseline predictors of greater cost reduction identified trends for recent emergency department visit (-$5944; 95% CI, -$10 336 to -$1553; interaction P = .07) and caregiver depression (-$6556; 95% CI, -$11 059 to -$2052; interaction P = .05). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial among Medicare beneficiaries with dementia, the Care Ecosystem model was associated with lower total cost of care compared with usual care. Collaborative dementia care programs are a cost-effective, high-value model for dementia care. Trial Registration: ClinicalTrials.gov Identifier: NCT02213458.