Interprofessional 30-day readmission review novel curriculum

ABSTRACT

Planning and coordination among health-care professionals decrease readmission rates, yet workers have few opportunities to learn interprofessionally to improve transitions of care. An interprofessional readmission review curriculum engaged medical residents, pharmacy residents, nurse practitioner students, early-career nurses, and social work students in a critical analysis of readmissions. Learners (N = 98) participated in a 2 h, collaborative learning session to review health records from a patient readmitted within 30 days of discharge and determine plausible root causes for readmissions. A 5-item post-session survey completed by 83 (85%) evaluated knowledge and perceived competencies in transitions of care before and after participation. Significant improvements (p < .001) occurred in ratings for all five items. Two open-ended questions captured learners’ perceptions of understanding and appreciating the roles of other disciplines in the discharge process and importance of interprofessional communication. Several themes emerged including understanding gaps in the discharge process, improving interprofessional collaboration and communication, and paying more attention to discharge documentation. This innovative program helped build essential skills to ensure safe discharges by introducing learners to interprofessional perspectives in analyzing root causes for readmissions, strategies to improve discharge planning, and the value of team-based care.     

Alterations in endogenous osteogenic protein-1 with degeneration of human articular cartilage.

A synchronized balance between synthesis and breakdown of extracellular matrix (ECM) molecules in normal articular cartilage is disturbed in osteoarthritis (OA). The focus of our study is the anabolic factor, osteogenic protein-1 (OP-1) that is expressed in articular cartilage and is able to induce the synthesis of ECM components. The major aim was to investigate both qualitatively and quantitatively endogenous OP-1 in normal, degenerative, and OA cartilage. Normal and degenerative cartilage was obtained at autopsies from femoral condyles of human organ donors with no documented history of joint disease; OA cartilage was obtained from patients undergoing joint arthroplasty. Appearance of donor cartilage was evaluated by Collins scale, where normal cartilage is assigned grades 0-1, and degenerated cartilage is assigned grades 2-4. OP-1 mRNA expression was assessed by RT-PCR; OP-1 protein (pro- and active forms) was qualitatively analyzed by Western blotting and quantified by OP-1 ELISA. The highest levels of OP-1 expression (mRNA and protein) were detected in normal cartilage of grade 0. The concentration of OP-1 protein was about 50 ng per gram cartilage dry weight. With the progression of cartilage degeneration (increased Collins grades and OA) OP-1 protein was down-regulated up to 9-fold. These changes affected primarily the active form of OP-1. OP-1 message also declined in cartilages with the increase of degenerative changes. In conclusion, an overall decrease in endogenous OP-1 in degenerated and OA tissue suggests that OP-1 could be one of the factors responsible for normal homeostasis and matrix integrity in cartilage.     

Optimizing Ligand Efficiency of Selective Androgen Receptor Modulators (SARMs)

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Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein–Barr virus IgG antibody titers

Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) IgG antibody titers. This study investigated whether antibody titers against HHV‐6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients. An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV‐6 IgG ≥1:320, EBV viral capsid antigen (VCA) IgG ≥1:640, and EBV early antigen (EA) IgG ≥1:160. Patients self‐rated physical and cognitive functioning as a percentage of their functioning prior to illness. Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning. Thirty‐two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively. Baseline antibody titers showed no significant association with response. After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001). Longer treatment was associated with improved response (P = 0.0002). No significant difference was found between responders and non‐responders among other variables analyzed. Valganciclovir treatment, independent of the baseline antibody titers, was associated with self‐rated improvement in physical and cognitive functioning for CFS patients who had positive HHV‐6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response. J. Med. Virol. 84:1967–1974, 2012. © 2012 Wiley Periodicals, Inc.     

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV‐6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double‐blind, placebo‐controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI‐20) and Fatigue Severity Scale (FSS) scores, self‐reported cognitive function, and physician‐determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI‐20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI‐20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1‐profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 85:2101–2109, 2013. © 2013 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.     

Use of shotgun proteomics for the identification, confirmation, and correction of C. elegans gene annotations

We describe a general mass spectrometry-based approach for gene annotation of any organism and demonstrate its effectiveness using the nematode Caenorhabditis elegans. We detected 6779 C. elegans proteins (67,047 peptides), including 384 that, although annotated in WormBase WS150, lacked cDNA or other prior experimental support. We also identified 429 new coding sequences that were unannotated in WS150. Nearly half (192/429) of the new coding sequences were confirmed with RT-PCR data. Thirty-three (~8%) of the new coding sequences had been predicted to be pseudogenes, 151 (~35%) reveal apparent errors in gene models, and 245 (57%) appear to be novel genes. In addition, we verified 6010 exon–exon splice junctions within existing WormBase gene models. Our work confirms that mass spectrometry is a powerful experimental tool for annotating sequenced genomes. In addition, the collection of identified peptides should facilitate future proteomics experiments targeted at specific proteins of interest.     

Efficient modification of the APRT gene by FLP/FRT site-specific targeting

The FLP/FRT site-specific recombination system was established and characterized at the APRT gene in CHO cells. Targeting frequencies with FLP-stimulation were about 1 to 5×10^–5, which were 6–22-fold above gene targeting frequencies in the absence of FLP. Fifty two APRT⁺ cell lines were analyzed by Southern blotting: 56% were FLP-targeted integrants; 33% were APRT target convertants; 11% gave undefined patterns. In separate experiments we first enriched for integrants by screening for two additional markers carried on the targeting vector; 18 of 19 (95%) of the resulting cell lines were integrants. Intrachromosomal site-specific recombination was tested by reexposing integrants to FLP. Intrachromosomal popouts were stimulated over 200-fold, while homologous recombination in an adjacent interval was unchanged. The utility of this system was demonstrated by one-step FLP targeting to generate chromosomal substrates for homologous recombination, and by a two-step, FLP-and-run procedure to construct a chromosomal substrate for illegitimate recombination.     

Composition of Caenorhabditis elegans extracellular vesicles suggests roles in metabolism,immunity, and aging

The nematode Caenorhabditis elegans has been instrumental in the identification of evolutionarily conserved mechanisms of aging. C. elegans also has recently been found to have evolutionarily conserved extracellular vesicle (EV) signaling pathways. We have been developing tools that allow for the detailed study of EV biology in C. elegans. Here we apply our recently published method for high specificity purification of EVs from C. elegans to carry out target-independent proteomic and RNA analysis of nematode EVs. We identify diverse coding and non-coding RNA and protein cargo types commonly found in human EVs. The EV cargo spectrum is distinct from whole worms, suggesting that protein and RNA cargos are actively recruited to EVs. Gene ontology analysis revealed C. elegans EVs are enriched for extracellular-associated and signaling proteins, and network analysis indicates enrichment for metabolic, immune, and basement membrane associated proteins. Tissue enrichment and gene expression analysis suggests the secreted EV proteins are likely to be derived from intestine, muscle, and excretory tissue. An unbiased comparison of the EV proteins with a large database of C. elegans genome-wide microarray data showed significant overlap with gene sets that are associated with aging and immunity. Taken together our data suggest C. elegans could be a promising in vivo model for studying the genetics and physiology of EVs in a variety of contexts including aging, metabolism, and immune response.