Findings of a national dataset analysis on the visits of homeless patients to US emergency departments during 2005-2015.

OBJECTIVES: To our knowledge, there has been limited description of emergency department (ED) visits involving homeless patients over the last decade. Our study aims to analyze US national survey data to elucidate the differences between homeless and non-homeless patients' ED visits in terms of patient demographics, resource utilization, and diagnoses received. STUDY DESIGN: This was a retrospective study using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2005 until 2015. METHODS: Patient visits were classified as homeless or non-homeless based on survey data; appropriate statistical analyses were subsequently performed to compare these groups in terms of patient demographics, geography, payment method, resource utilization/diagnostic service use, as well as both psychiatric and non-psychiatric diagnoses received in the ED. RESULTS: NHAMCS data from 2005 to 2015 were aggregated. In total, 303,326 patient visits were included, which represent an estimated 1.30 billion ED visits over this period. Of these, 2750 encounters were by homeless people, representing 8,781,925 ED visits. Compared with non-homeless visits, homeless patients were disproportionately male, black, non-Hispanic, and seen in large metropolitan areas or the Western/Southern US. Homeless visits were more likely to be related to an injury (47.5% vs. 33.8%), related to an assault (4.2% vs. 1.3%), or self-inflicted (4.8% vs 0.84%). Homeless patients were also more likely to have been seen in the same ED within 72 h (7.3% vs. 3.9%) compared with non-homeless patients (3.9%, 95% confidence interval [CI]: 3.5-4.4) and were seen an average of 5.7 times (95% CI: 4.7-6.8) in the same ED over the preceding 12 months, with non-homeless patients seen an average of 3.2 times (95% CI: 3.1-3.4). Homeless patients were more likely to be admitted to the hospital (14.9% vs. 11.2%) and, when admitted, spent an average of 6.3 days in the hospital (95% CI: 5.6-7.1) compared with non-homeless patients at 5.2 (95% CI: 5.1-5.3). In total, 28.4% of homeless patients received a psychiatric diagnosis (95% CI: 25.8-31.2) compared with 5.4% for non-homeless patients (95% CI: 5.2-5.7, P < 0.001). In reference to non-homeless visits, homeless visits showed increased odds of alcohol-related diagnoses (odds ratio [OR]: 17.3, 95% CI: 10.1-29.8, P < 0.001) and substance abuse diagnoses (OR: 8.4, 95% CI: 7.2-9.8, P < 0.001). Homeless visits also exhibited greatly increased odds of diagnosis of schizophrenia (OR: 16.6, 95% CI: 12.6-22.5, P < 0.001) and personality disorders (OR: 15.4, 95% CI: 6.4-36.9, P < 0.001). CONCLUSIONS: Less than one in 100 US ED visits in 2005-2015 were made by homeless patients. Compared with the non-homeless, homeless patients had greatly increased rates of ED care for alcohol-related, substance abuse-related, and mental health-related problems, particularly schizophrenia and personality disorders. Homeless patients were also more likely to be seen in the ED within the past 72 h or the past 12 months. Homeless patients were more likely to be admitted to the hospital and, when admitted, exhibited longer stay times.

The variation in quality and content of patient-focused health information on the Internet for otitis media.

BACKGROUND: When symptoms of otitis media appear, parents and patients often access the Internet for health information. We study the content and quality of health information in parent-patient-focused websites for otitis media. METHODS: We searched the 3 search engines (Google, Yahoo, and Bing) using "otitis media" and "middle ear infection" then reviewed the top 30 hits for each search. We included sites that were focused on providing patient-patient information about otitis media. A variety of instruments were used to assess website content and quality. RESULTS: In 35 included websites, there was considerable variation in content, with the average site having 11 out of 15 informational items potentially useful to parents and patients on otitis media (range 4-15). Across included websites, the mean DISCERN score was 47 out of 80 (low to medium quality), 16 (46%) were HONcode certified, and 8 (23%) fulfilled all the JAMA benchmark criteria. The average website was written at a 9th/10th-grade reading level. CONCLUSION: The content and quality of health information for otitis media in parent-and-patient-focused websites is highly variable. Although easy-to-read, high-quality websites with complete content are available, the average website sites is difficult to read without a high school education and is difficult to use. Consideration should be given to adopting a standard approach for presenting disease-specific information to parents and patients.

Data systems for the Linac coherent light source.

The data systems for X-ray free-electron laser (FEL) experiments at the Linac coherent light source (LCLS) are described. These systems are designed to acquire and to reliably transport shot-by-shot data at a peak throughput of 5 GB/s to the offline data storage where experimental data and the relevant metadata are archived and made available for user analysis. The analysis and monitoring implementation (AMI) and Photon Science ANAlysis (psana) software packages are described. Psana is open source and freely available.

Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.

We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. Mean follow-up was 690 days in the transplantation group and 758 days in the conventional-dose chemotherapy group. Subjects in the transplantation group were hospitalized for more days (28.6 vs 17.8, P=0.0041) and incurred higher costs (US dollars 84055 vs US dollars 28169) than subjects receiving conventional-dose chemotherapy, with a mean difference of US dollars 55886 (95% CI, US dollars 47298-US dollars 63666). Sensitivity analyses resulted in cost differences between the treatment groups from US dollars 36528 to US dollars 75531. High-dose chemotherapy plus stem-cell transplantation resulted in substantial additional morbidity and costs at no improvement in survival. Neither the survival results nor the economic findings support the use of this procedure outside of the clinical trial setting.

CrkRS: a novel conserved Cdc2-related protein kinase that colocalises with SC35 speckles.

We have isolated and characterised a novel human protein kinase, Cdc2-related kinase with an arginine/serine-rich (RS) domain (CrkRS), that is most closely related to the cyclin-dependent kinase (CDK) family. CrkRS is a 1490 amino acid protein, the largest CDK-related kinase so far isolated. The protein kinase domain of CrkRS is 89% identical to the 46 kDa CHED protein kinase, but outside the kinase domains the two proteins are completely unrelated. CrkRS has extensive proline-rich regions that match the consensus for SH3 and WW domain binding sites, and an RS domain that is predominantly found in splicing factors. CrkRS is ubiquitously expressed in tissues, and maps to a single genetic locus. There are closely related protein kinases in both the Drosophila and Caenorhabditis elegans genomes. Consistent with the presence of an RS domain, anti-CrkRS antibodies stain nuclei in a speckled pattern, overlapping with spliceosome components and the hyperphosphorylated form of RNA polymerase II. Like RNA polymerase II, CrkRS is a constitutive MPM-2 antigen throughout the cell cycle. Anti-CrkRS immunoprecipitates phosphorylate the C-terminal domain of RNA polymerase II in vitro. Thus CrkRS may be a novel, conserved link between the transcription and splicing machinery.

Web alert: Cell-to-cell contact and extracellular matrix.

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Cell Biology.

Stability, chromatin association and functional activity of mammalian pre-replication complex proteins during the cell cycle.

We have examined the behavior of pre-replication complex (pre-RC) proteins in relation to key cell cycle transitions in Chinese Hamster Ovary (CHO) cells. ORC1, ORC4 and Cdc6 were stable (T1/2 >2 h) and associated with a chromatin-containing fraction throughout the cell cycle. Green fluorescent protein-tagged ORC1 associated with chromatin throughout mitosis in living cells and co-localized with ORC4 in metaphase spreads. Association of Mcm proteins with chromatin took place during telophase, approximately 30 min after the destruction of geminin and cyclins A and B, and was coincident with the licensing of chromatin to replicate in geminin-supplemented Xenopus egg extracts. Neither Mcm recruitment nor licensing required protein synthesis throughout mitosis. Moreover, licensing could be uncoupled from origin specification in geminin-supplemented extracts; site-specific initiation within the dihydrofolate reductase locus required nuclei from cells that had passed through the origin decision point (ODP). These results demonstrate that mammalian pre-RC assembly takes place during telophase, mediated by post-translational modifications of pre-existing proteins, and is not sufficient to select specific origin sites. A subsequent, as yet undefined, step selects which pre-RCs will function as replication origins.

Differential localization of HDAC4 orchestrates muscle differentiation.

The class II histone deacetylases HDAC4 and HDAC5 interact specifically with the myogenic MEF2 transcription factor and repress its activity. Here we show that HDAC4 is cytoplasmic during myoblast differentiation, but relocates to the nucleus once fusion has occurred. Inappropriate nuclear entry of HDAC4 following overexpression suppresses the myogenic programme as well as MEF2-dependent transcription. Activation of the Ca(2+)/calmodulin signalling pathway via constitutively active CaMKIV prevents nuclear entry of HDAC4 and HDAC4-mediated inhibition of differentiation. Consistent with a role of phosphorylation in HDAC4 cytoplasmic localisation, HDAC4 binds to 14-3-3 proteins in a phosphorylation-dependent manner. Together these data establish a role for HDAC4 in muscle differentiation. Recently, HDAC5 has also been implicated in muscle differentiation. However, despite the functional similarities of HDAC4 and HDAC5, their intracellular localisations are opposed, suggesting a distinct role for these enzymes during muscle differentiation.

Membrane permeability. Membranes and sorting. Web alert.

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Cell Biology.

Use of Green Fluorescent Protein in mouse embryos.

Green Fluorescent Protein (GFP) has rapidly been established as a versatile and powerful cell marker in many organisms. Initial problems in using it in mammalian cells were solved by introducing mutations to increase its solubility at higher temperatures, such that GFP has now been used as a reporter in both gene expression and cell lineage studies, and to localize proteins within mammalian cells. GFP has two unique advantages: (i) the protein becomes fluorescent in an autocatalytic reaction, so that it can be introduced into any cell type simply as a cDNA or mRNA, or as protein; (ii) it is "bright" enough to be visualized in living cells under conditions that do not cause photodamage to the cells. In this article we outline the ways in which we have used GFP mRNA and cDNA in our studies of mouse cell lineages, and to characterize the behavior of proteins within the embryos.

Cyclin A is destroyed in prometaphase and can delay chromosome alignment and anaphase.

Mitosis is controlled by the specific and timely degradation of key regulatory proteins, notably the mitotic cyclins that bind and activate the cyclin-dependent kinases (Cdks). In animal cells, cyclin A is always degraded before cyclin B, but the exact timing and the mechanism underlying this are not known. Here we use live cell imaging to show that cyclin A begins to be degraded just after nuclear envelope breakdown. This degradation requires the 26S proteasome, but is not affected by the spindle checkpoint. Neither deletion of its destruction box nor disrupting Cdk binding prevents cyclin A proteolysis, but Cdk binding is necessary for degradation at the correct time. We also show that increasing the levels of cyclin A delays chromosome alignment and sister chromatid segregation. This delay depends on the proteolysis of cyclin A and is not caused by a lag in the bipolar attachment of chromosomes to the mitotic spindle, nor is it mediated via the spindle checkpoint. Thus, proteolysis that is not under the control of the spindle checkpoint is required for chromosome alignment and anaphase.

The localization of human cyclins B1 and B2 determines CDK1 substrate specificity and neither enzyme requires MEK to disassemble the Golgi apparatus.

In this paper, we show that substrate specificity is primarily conferred on human mitotic cyclin-dependent kinases (CDKs) by their subcellular localization. The difference in localization of the B-type cyclin-CDKs underlies the ability of cyclin B1-CDK1 to cause chromosome condensation, reorganization of the microtubules, and disassembly of the nuclear lamina and of the Golgi apparatus, while it restricts cyclin B2-CDK1 to disassembly of the Golgi apparatus. We identify the region of cyclin B2 responsible for its localization and show that this will direct cyclin B1 to the Golgi apparatus and confer upon it the more limited properties of cyclin B2. Equally, directing cyclin B2 to the cytoplasm with the NH(2) terminus of cyclin B1 confers the broader properties of cyclin B1. Furthermore, we show that the disassembly of the Golgi apparatus initiated by either mitotic cyclin-CDK complex does not require mitogen-activated protein kinase kinase (MEK) activity.

Re-staging mitosis: a contemporary view of mitotic progression.

The process of cell division, or mitosis, has fascinated biologists since its discovery in the late 1870s. Progress through mitosis is traditionally divided into stages that were defined over 100 years ago from analyses of fixed material from higher plants and animals. However, this terminology often leads to ambiguity, especially when comparing different systems. We therefore suggest that mitosis can be re-staged to reflect more accurately the molecular pathways that underlie key transitions.

Assays for CDK activity and DNA replication in the cell cycle.

This unit describes two assays for different stages of the cell cycle in tissue culture cells. One is a biochemical measurement that assays the protein kinase activity of different cyclin-dependent kinase complexes that are present in late G1 phase, S phase, G2 phase, or mitosis. The other assay uses immunofluorescence to detect DNA replication by the incorporation of nucleotide analogs into DNA. These assays are useful in analyzing the stage and degree of synchrony of the cell cycle and changes in the basic cell cycle machinery.

Web alert

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Cell Biology.